TW202428348A - Reagent delivery system with fluidic device and sensor - Google Patents

Abstract

Systems and devices for reagent delivery are described. In one example, a disclosed fluidic device comprises: a plurality of first inlet ports; a first common channel; a plurality of first valves each associated with one first inlet port; a plurality of second inlet ports; a second common channel; a plurality of second valves each associated with one second inlet port; a plurality of outlet ports; a third common channel; a plurality of third valves each associated with one outlet ports; a first shutoff valve fluidically coupled between the first and the third common channels; and a second shutoff valve fluidically coupled between the second and the third common channels. Each first or second valve is fluidically coupled between a first or second inlet port and the first or second common channel. Each third valve is fluidically coupled between an outlet port and the third common channel.

Description

Reagent delivery system with fluid device and sensor

The present invention relates generally to fluid reagent delivery, and more particularly, the present invention relates to systems, devices and methods for delivering fluid reagents with sensors for fill control.

Microfluidics is considered a set of technologies that enable manipulation of small amounts of fluids in chemical biology, chemical synthesis, and lab-on-a-chip devices. The challenge in getting a small amount of fluid from point A to point B is to minimize the working volume and dead volume, which will reduce reagent usage and cross-contamination. We are very interested in moving fluids in cross-sectional areas of about 10 µm ² to 1000 µm ² and volumes of about 1 µL to 1000 µL. But in the slightly larger range of cross-sectional areas of 0.1 mm ² to 10 mm ² and reagent volumes of 1 mL to 100 mL, distribution manifold technology is rare.

Mechanical motion is used in some larger scale delivery applications. Mechanical pipettes are easy to implement but suffer from low velocities, atmospheric contamination, and the large volumes required for fluid connections. Smaller scale microfluidic devices have been developed to jet/ink print small droplets onto a substrate surface. This approach can achieve high resolution and small reaction droplets but is not suitable for a closed reaction chamber. Microfluidic valve/manifold systems with zero dead volume have been developed on a smaller scale. Valves and manifolds must be tightly integrated and therefore lack application flexibility and expansion space.

Syringe pumps are often the primary instrument used to deliver small amounts of liquid to the desired location. However, they are limited in terms of volume capacity, chemical compatibility, pressure fluctuations, and vibrations. Efforts to expand their capabilities involve pumping media from outlets, sealing reservoirs with permeable membranes, and optimizing operating conditions. Pressure-driven flow is an alternative to limiting dynamic forces, is pulse-free, and has a faster response time. The disadvantage is that additional components are required to adjust the dosing volume.

The exemplary embodiments disclosed herein are intended to solve problems associated with one or more of the problems existing in the prior art and to provide additional features that will become readily apparent by reference to the following detailed description in conjunction with the accompanying drawings. According to various embodiments, exemplary systems, methods, devices, and computer program products are disclosed herein. However, it should be understood that these embodiments are provided for illustration only and not limitation, and a person of ordinary skill in the art who reads the present invention will understand that various modifications may be made to the disclosed embodiments within the scope of the present invention.

In one embodiment, a fluid device is disclosed. The fluid device includes: a plurality of first inlet ports; a first common channel; a plurality of first valves, each associated with one of the plurality of first inlet ports; a plurality of second inlet ports; a second common channel; a plurality of second valves, each associated with one of the plurality of second inlet ports; a plurality of outlet ports; a third common channel; a plurality of third valves, each associated with one of the plurality of outlet ports; a first shut-off valve, whose fluid is coupled between the first common channel and the third common channel; and a second shut-off valve, whose fluid is coupled between the second common channel and the third common channel. Each first valve is fluidly coupled between an associated first inlet port and the first common channel. Each second valve is fluidly coupled between an associated second inlet port and the second common channel. Each third valve is fluidly coupled between an associated outlet port and the third common passage.

In another embodiment, a reagent delivery system is disclosed. The reagent delivery system includes: a plurality of first reagent containers, each containing a first liquid reagent selected from a first group; a plurality of second reagent containers, each containing a second liquid reagent selected from a second group; a fluid device, which includes a plurality of first inlet ports, a plurality of second inlet ports, and a plurality of outlet ports; and a plurality of chambers, each including a first chamber port and a second chamber port. Each of the plurality of first reagent containers is fluidly coupled to one of the plurality of first inlet ports. Each of the plurality of second reagent containers is fluidly coupled to one of the plurality of second inlet ports. The first chamber port of each chamber is fluidly coupled to one of the plurality of outlet ports.

In yet another embodiment, a non-transitory computer-readable medium having stored thereon computer-executable instructions useful for executing a disclosed method performed by a disclosed apparatus or system in some embodiments is disclosed.

Priority Claim and Cross-Reference This application claims the rights of U.S. Provisional Application No. 63/409,251 filed on September 23, 2022, which is expressly incorporated herein by reference in its entirety.

Various exemplary embodiments of the present invention are described below with reference to the accompanying drawings to enable one of ordinary skill to make and use the present invention. One of ordinary skill will understand after reading the present invention that various changes or modifications may be made to the examples described herein without departing from the scope of the present invention. Therefore, the present invention is not limited to the exemplary embodiments and applications described and illustrated herein. In addition, the specific order or hierarchy of steps in the methods disclosed herein are merely exemplary methods. Based on design preferences, the specific order or hierarchy of steps of the disclosed methods or procedures may be reconfigured within the scope of the present invention. Therefore, one of ordinary skill in the art should understand that the methods and techniques disclosed herein present various steps or actions in a sample order, and the present invention is not limited to the specific order or level presented unless otherwise explicitly stated.

This description of exemplary embodiments is intended to be read in conjunction with the appended drawings, which are to be considered part of the entire written description. In the description, relative terms such as "lower", "upper", "horizontal", "vertical", "above", "below", "upward", "downward", "top", and "bottom" and derivatives thereof (e.g., "horizontally", "downwardly", "upwardly", etc.) should be interpreted as referring to the orientation shown in the drawings in the subsequent description or discussion. Such relative terms are for convenience of description and do not require that the equipment be constructed or operated in a particular orientation. Terms related to attachment, coupling, and the like (such as "connect", "coupled", and "interconnected") refer to a relationship in which structures are fixed or attached to each other directly or indirectly through intervening structures as well as both removable or rigid attachments or relationships, unless expressly described otherwise.

For the purpose of the following description, it should be understood that the embodiments described below may present alternative variations and embodiments. It should also be understood that the specific items, compositions and/or procedures described herein are exemplary and should not be considered as limiting.

In the present invention, the singular forms "a", "an" and "the" include plural references, and reference to a particular numerical value includes at least that particular value unless the context clearly indicates otherwise. When a value is expressed as an approximation by using the antecedent "about", it is understood that the particular value forms another embodiment. As used herein, "about X" (where X is a numerical value) preferably refers to the value ±10% (inclusive). For example, the phrase "about 8" preferably refers to a value of 7.2 to 8.8 (inclusive). The term "substantially the same" will be understood to allow a variation such as ±10% or 5%.

The present invention provides a reagent dispensing system that utilizes available valves and integrates them into a modular manifold. Actuation of the corresponding valve will allow a selected reagent to flow from its corresponding inlet to a selected outlet. In some embodiments, the reagents that can flow through the reagent dispensing system are separated into two groups: a dry group and a wet group. A reagent in the dry group is substantially anhydrous or does not contain water, while a reagent in the wet group may contain water. A reagent in the dry group may also be referred to as anhydrous and may include a moisture content of less than 100 pm by weight. In some embodiments, a "dry" reagent includes a moisture content of less than 10 ppm. A reagent in the wet group may include water exceeding 0.1% by weight of the reagent. In some embodiments, water is a solvent for a reagent in the wet group. In some embodiments, the reagent is used to synthesize a biochemical substance such as DNA, RNA and peptide, and the reaction is performed in a microfluidic device such as a microarray synthesis chip. For example, a suitable example of a reagent in the dry group may include (but is not limited to) an imide, an activator and an inert gas. A suitable example of a reagent in the wet group may include (but is not limited to) an oxidant (OX), a Cap A solution (Cap A), a Cap B solution (Cap B) and an electrochemical reaction medium (Echem). Cap A and Cap B are a first and a second end-capping reagent for DNA synthesis. Separation further reduces cross contamination between dry and wet reagent groups and is implemented by built-in shut-off valves which significantly reduce the internal volume of the fluid manifold.

In some embodiments, the fluid system is isolated from the atmosphere and protected from contamination by it while being driven by a pressurized inert gas. A pressure-driven reagent delivery system can utilize an inert gas to prevent atmospheric contamination. The pressurized inert gas can push a desired reagent through a delivery manifold into a target chamber. The target chamber is filled when atmospheric pressure is reached at its chamber outlet. The process stops when a bubble sensor positioned at the chamber outlet detects the transition from gas to liquid. In some embodiments, the bubble sensor can be an ultrasonic bubble sensor that can monitor fluid flow in a non-invasive manner. In certain non-continuous applications, a reagent delivery system is required to fill and drain a fixed volume chamber. Therefore, using a bubble sensor on the chamber outlet will indicate whether the liquid meniscus has passed through the chamber to indicate a full chamber when no additional bubbles are present.

In some embodiments, a pressure sensor is positioned on the pressurized gas side to monitor pressure so that a consistent and stable pressure differential can be achieved for flow and software control.

FIG. 1A shows an exemplary perspective view of a fluid manipulation device 100 according to some embodiments of the present invention. The fluid manipulation device described herein also refers to a fluid device or a fluid delivery device, and is a fluid device for delivering one or more different fluids or chemicals. In some embodiments, the fluid device is a microfluidic device. The term "manipulation" can be understood to cover the delivery of different chemicals with precise control, such as using the same device structure to deliver dry and wet chemicals while keeping them separated and free of any contamination. Such a device can have a suitable size, such as millimeters or centimeters. Such a device can be an independent integral device or its components can be located in a panel or block. The device can be used to move and deliver a fluid in a suitable cross-sectional area (e.g., in some embodiments, in a range from 0.1 square millimeters to 10 square millimeters). As shown in FIG. 1A , an exemplary fluid manipulation device 100 includes a plastic base 101 and a plurality of valves 102. In this example, the plastic base 101 includes five blocks, which form three sections: a first input section 110, a second input section 120, and an output section 130. The five blocks 105-1, 105-2, 105-3, 105-4, 105-5 ( FIG. 1B ) are connected and integrated together along a straight line using fasteners 104 located on both sides of the fluid manipulation device 100. The numbers of valves and ports described herein are for illustration only and may be any suitable number.

FIG. 1B shows another exemplary perspective view of a fluid manipulation device 100 according to some embodiments of the present invention. The perspective view in FIG. 1B shows the bottom of the fluid manipulation device 100. As shown in FIG. 1B, there are multiple ports on the bottom of the fluid manipulation device 100. In this example, the first input section 110 of the fluid manipulation device 100 has one of seven first inlet ports 111 suitable for a first number, and the second input section 120 of the fluid manipulation device 100 has one of ten second inlet ports 121 suitable for a second number. In addition, the output section 130 of the fluid manipulation device 100 has six outlet ports 131. The valve 102 is integrated into different sections of the plastic base 101 and includes a plurality of first valves 102-1, a plurality of second valves 102-2, a plurality of third valves 102-3, a first shut-off valve 102-4 and a second shut-off valve 102-5.

As shown in FIG1B , the first input section 110 of the fluid manipulation device 100 is formed of two integrated plastic blocks: one plastic block 105-1 having five inlet ports and another plastic block 105-2 having two inlet ports. The second input section 120 of the fluid manipulation device 100 is formed of two integrated plastic blocks: one plastic block 105-4 having five inlet ports and another plastic block 105-5 also having five inlet ports. The output section 130 of the first input section 110 is formed of a single piece of plastic block 105-3 including six outlet ports.

As shown in Figures 1A and 1B, each inlet and outlet port is associated with a corresponding valve 102 that is integrated into the plastic base 101 and placed on the top of the port. Each first valve 102-1 is associated with one of the first inlet ports 111 in the first input section 110; each second valve 102-2 is associated with one of the second inlet ports 121 in the second input section 120; and each third valve 102-3 is associated with one of the outlet ports 131 in the output section 130. The term "associated with..." used herein will also be understood as "coupled with..." or "corresponding to...". The term "coupled" refers to being directly or indirectly connected to each other. In this example, there are a total of 23 ports and a total of 25 valves. This is because there are two special valves: a first shut-off valve 102-4 disposed in the first input section 110 and closer to (or adjacent to) the output section 130 than all other valves in the first input section 110, and a second shut-off valve 102-5 disposed in the second input section 120 and closer to (adjacent to) the output section 130 than all other valves in the second input section 120. For each of the two shut-off valves 102-4, 102-5, there is no associated port on the bottom of the first input section 110.

In some embodiments, 25 valves 102 in the fluid manipulation device 100 are arranged in a row, wherein every two adjacent valves are arranged close to each other and the spacing therebetween is negligible. Along the Y direction, a distance between every two adjacent first inlet ports 111 is a first distance; a distance between every two adjacent second inlet ports 121 is a second distance; and a distance between every two adjacent outlet ports 131 is a third distance. In some embodiments, all the first distances, the second distances, and the third distances are the same as each other and are substantially the same as a width of each valve 102 along the Y axis. This compact design of the fluid manipulation device 100 can reduce the internal volume of the fluid manipulation device 100. As shown in Figures 1A to 1B, the X direction and the Y direction are respectively along the longitudinal direction and the width direction of the device, and the Z direction is along the height direction of the device. The three directions are orthogonal to each other.

In some embodiments, the fluid manipulation device 100 has a length of about 20 cm along the Y direction, a width of about 2 cm to 3 cm along the X direction, and a height of about 5 cm along the Z direction.

As shown in FIG. 1A and FIG. 1B , all valves including the first valve 102-1, the second valve 102-2, the third valve 102-3, the first shut-off valve 102-4, and the second shut-off valve 102-5 are arranged in parallel and on a same first side (i.e., the top side) of the fluid manipulation device 100. All ports including the first inlet port 111, the second inlet port 121, and the outlet port 131 are arranged on a same second side (i.e., the bottom side) of the fluid manipulation device 100. In some embodiments, the outlet port 131 may be located on an opposite side of a side where the first inlet port 111 and the second inlet port 121 are located. Therefore, the third valve 102-3 may be located on an opposite side of a side where the other valves are located.

As shown in Figure 1B, the first inlet port 111 in the first input section 110 and the second inlet port 121 in the second input section 120 are all aligned and arranged along a straight line in the Y direction. In addition, the outlet ports 131 in the output section 130 are all aligned and arranged along another straight line in the Y direction. This will be better shown in Figure 2A.

FIG. 2A illustrates an exemplary cross-sectional bottom view 200-1 of a fluid manipulation device (e.g., the fluid manipulation device 100 in FIG. 1A and FIG. 1B ) according to some embodiments of the present invention. In some embodiments, the cross-sectional bottom view 200-1 can be obtained by cutting the fluid manipulation device 100 in FIG. 1A along plane PP' and looking from bottom to top along the Z direction. FIG. 2B illustrates an exemplary cross-sectional side view 200-2 of a fluid manipulation device (e.g., the fluid manipulation device 100 in FIG. 1A and FIG. 1B ) according to some embodiments of the present invention. In some embodiments, the cross-sectional side view 200-2 can be obtained by cutting the fluid manipulation device 100 along the line AA' shown in Figure 2A and looking from the side of the fluid manipulation device 100 along the -X direction (i.e., looking down in Figure 2A), without cutting the bottom of the fluid manipulation device 100. Figure 2C shows another exemplary cross-sectional side view 200-3 of a fluid manipulation device (e.g., the fluid manipulation device 100 in Figures 1A and 1B) according to some embodiments of the present invention. In some embodiments, the cross-sectional side view 200-3 can be obtained by cutting the fluid manipulation device 100 along the line BB' shown in Figure 2A and looking from the side of the fluid manipulation device 100 along the -X direction (i.e., looking down in Figure 2A), without cutting the bottom of the fluid manipulation device 100. In some embodiments, the cross-sectional bottom view 200-1 can also be obtained by cutting the fluid manipulation device 100 along the line CC' in Figure 2B or Figure 2C and looking from the bottom to the top along the Z direction, without cutting the side of the fluid manipulation device 100.

As shown in FIG. 2A , the first input section 110 may include a first common channel 212 extending horizontally along the Y direction; and the second input section 120 may include a second common channel 222 extending horizontally along the Y direction. In addition, the output section 130 may also include a third common channel 232 extending horizontally along the Y direction. The term "a common channel" used herein should be understood to cover a channel belonging to or shared by two or more ports or valves.

As shown in FIG. 2A and FIG. 2C , the first input section 110 includes a plurality of first inlet channels 211 each corresponding to and connected to one of the first inlet ports 111. Each first inlet channel 211 extends vertically along the Z direction in the fluid manipulation device 100 and is fluidically coupled between a corresponding first inlet port 111 and an associated first valve 102-1 disposed directly above the first inlet channel 211 along the Z direction. Each first valve 102-1 is fluidically coupled between an associated first inlet port 111 and the first common channel 212 through the corresponding first inlet channel 211. In some embodiments, each first inlet port 111 is configured to receive a wet liquid reagent containing water. When a first valve 102-1 is opened, it allows the wet liquid reagent to flow from the corresponding first inlet port 111 directly below the first valve 102-1 in the Z direction through the corresponding first inlet channel 211 directly above the first inlet port 111 and directly below the first valve 102-1 in the Z direction to the first common channel 212, for example due to a pressure difference driven by a pressurized inert gas. As shown in Figures 2A to 2C, the first common channel 212 is shared by all first inlet ports in the first input section 110.

As shown in FIG. 2A and FIG. 2C , the second input section 120 includes a plurality of second inlet channels 221 each corresponding to and connected to one of the second inlet ports 121. Each second inlet channel 221 extends vertically along the Z direction in the fluid manipulation device 100 and is fluidically coupled between a corresponding second inlet port 121 and an associated second valve 102-2 disposed directly above the second inlet channel 221 along the Z direction. Each second valve 102-2 is fluidically coupled between an associated second inlet port 121 and the second common channel 222 through the corresponding second inlet channel 221. In some embodiments, each second inlet port 121 is configured to receive a dry liquid reagent. When a second valve 102-2 is opened, it allows the dry liquid reagent to flow from the corresponding second inlet port 121 directly below the second valve 102-2 in the Z direction through the corresponding second inlet channel 221 directly above the second inlet port 121 and directly below the second valve 102-2 in the Z direction to the second common channel 222, for example due to a pressure difference driven by a pressurized inert gas. As shown in Figures 2A to 2C, the second common channel 222 is shared by all second inlet ports in the second input section 120. For convenience of description, the first input section 110 and the second input section 120 are used for wet reagents and dry reagents, respectively. However, this does not limit the scope of use of these two sections. The two sections 110 and 120 can be used for reagents of different properties, which cannot be mixed during the transport phase and before being transported to a reaction chamber. For example, the first input section 110 and the second input section 120 are used for dry reagents and wet reagents, respectively.

As shown in FIG. 2A and FIG. 2B , the output section 130 includes a plurality of outlet channels 231 each corresponding to and connected to one of the outlet ports 131. Each outlet channel 231 extends vertically along the Z direction in the fluid manipulation device 100 and is fluidically coupled between a corresponding outlet port 131 and an associated third valve 102-3 disposed directly above the outlet channel 231 along the Z direction. Each third valve 102-3 is fluidically coupled between an associated outlet port 131 and the third common channel 232 through the corresponding outlet channel 231. When a third valve 102-3 is opened, it allows a liquid reagent to flow from the third common channel 232 through the corresponding outlet channel 231 directly below the third valve 102-3 in the Z direction to the corresponding outlet port 131 directly below the outlet channel 231 in the Z direction, for example due to a pressure difference driven by a pressurized inert gas. As shown in Figures 2A to 2C, the third common channel 232 is shared by all outlet ports in the output section 130.

As shown in FIGS. 2A to 2C , although the first common passage 212 is a single continuous and straight tube extending through the two blocks 105-1, 105-2 ( FIG. 1B ) in the first input section 110, the two blocks 105-1, 105-2 in the first input section 110 are connected and integrated using fasteners 104 and flange seals 204. Although the second common passage 222 is a single continuous and straight tube extending through the two blocks 105-4, 105-5 ( FIG. 1B ) in the second input section 120, the two blocks 105-4, 105-5 in the second input section 120 are connected and integrated using fasteners 104 and flange seals 204. Similarly, the first input section 110 is connected and integrated to the output section 130 using fasteners 104 and flange seals 204 ; and the second input section 120 is also connected and integrated to the output section 130 using fasteners 104 and flange seals 204 .

In some embodiments, all channels including the first inlet channel 211, the second inlet channel 221, the third inlet channel 231, the first common channel 212, the second common channel 222, and the third common channel 232 have the same cross-sectional area (e.g., a cross-sectional area between 0.1 square millimeters and 10 square millimeters) and the same inner diameter. In some embodiments, the liquid flowing in each of the first inlet channel 211, the second inlet channel 221, the third inlet channel 231, the first common channel 212, the second common channel 222, and the third common channel 232 is isolated from the atmosphere and driven by a pressurized inert gas.

The first shut-off valve 102-4 is fluidically coupled between the first common channel 212 and the third common channel 232. When the first shut-off valve 102-4 is opened, it allows a wet fluid reagent to flow from the first common channel 212 to the third common channel 232. The second shut-off valve 102-5 is fluidically coupled between the second common channel 222 and the third common channel 232. When the second shut-off valve 102-5 is opened, it allows a dry fluid reagent to flow from the second common channel 222 to the third common channel 232.

In some embodiments, the wet liquid is selected from the wet group consisting of an oxidant (OX), Cap A, Cap B, and an electrochemical reaction medium (Echem); and the dry liquid is selected from the dry group consisting of an imide, an activator, and an inert gas.

As shown in FIGS. 2A to 2C , the first inlet port 111, the first inlet channel 211, the first common channel 212, the first valve 102-1 and the first shut-off valve 102-4 are integrated in the first input section 110 of the fluid manipulation device 100; the second inlet port 121, the second inlet channel 221, the second common channel 222, the second valve 102-2 and the second shut-off valve 102-5 are integrated in the second input section 120 of the fluid manipulation device 100; the outlet port 131, the outlet channel 231, the third common channel 232 and the third valve 102-3 are integrated in the output section 130 of the fluid manipulation device 100. The output section 130 is physically coupled between the first input section 110 and the second input section 120. The first input section 110 and the second input section 120 are separated from each other. In some embodiments, the device 100 shown in Figures 1A to 1B and Figures 2A to 2C further includes a controller (not shown) configured to be connected to a control panel of a computer, such as a control panel, by wire or wireless, or a controller configured to a control panel or a computer.

As shown in FIG2A , the first common channel 212, the second common channel 222, and all the outlet channels 231 (and therefore all the outlet ports 131) are all aligned along the straight line AA'; while the third common channel 232, all the first inlet channels 211, and all the second inlet channels 221 (and therefore all the first inlet ports 111, and all the second inlet ports 121) are all aligned along the straight line BB'. The offset between the straight line AA' and the straight line BB' corresponds to one of the first ports and the second port connection described in FIG3B .

In some embodiments, all valves 102 including a plurality of first valves 102-1, a plurality of second valves 102-2, a plurality of third valves 102-3, a first shut-off valve 102-4, and a second shut-off valve 102-5 have the same structure and the same aperture. Each valve can be implemented as any valve that is chemically compatible with the reagent of interest and has sufficient dynamic response to fluid reagent delivery.

FIG. 3A shows an exemplary perspective view of an exemplary valve in a fluid manipulation device 100 according to some embodiments of the present invention. FIG. 3B shows an exemplary side and cross-sectional view of the valve shown in FIG. 3A according to some embodiments of the present invention. In some embodiments, the valve shown in FIG. 3A and FIG. 3B can serve as any of the valves 102 in FIG. 1-2.

As shown in FIG. 3A , the valve 102 includes a valve body 310 , a coil housing 320 on the valve body 310 , and a connector 330 on the coil housing 320 . The valve body 310 may include some plastic material with high chemical resistance. The coil housing 320 may include a coil and/or some circuit structure to generate magnetic force. The connector 330 may include pins for connecting the valve 102 to a control panel using a wire or other connection method. In some embodiments, the control panel may be connected to all valves 102 of the fluid manipulation device 100 and also to a control computer. Thus, the operation of the fluid manipulation device 100 may be controlled based on a firmware or software running on the control computer.

In some embodiments, the side view and cross-sectional view in FIG. 3B can be obtained by cutting the valve body 310 of the valve 102 in FIG. 3A along plane Q in the Z direction and looking from the side of the valve 102 along the -Y direction. As shown in FIG. 3B, the valve body 310 includes a first port 301 including a vertical channel, a second port 302 including an inclined channel, and a movable diaphragm 305 disposed above both the first port 301 and the second port 302. The valve body 310 also includes a metal weight 306 on the movable diaphragm 305. In some embodiments, each valve 102 is integrated to the plastic base 101 using flange seals 304 and some fasteners located on both sides of the valve 102 along the X direction.

Depending on the implementation, either the first port 301 or the second port 302 may be an input port, while the other may therefore be an output port. In the example shown in FIGS. 2A to 2C , all first ports 301 of the valves 102 are aligned along line BB′ in FIG. 2A ; and all second ports 302 of the valves 102 are aligned along line AA′ in FIG. 2A . Thus, in the first input section 110 , a first port 301 of each first valve 102-1 is an input port of the first valve 102-1 because the first port 301 is directly connected or integrated to a first inlet channel 211 of a corresponding first inlet port 111 (e.g., using fasteners and flange seals). Therefore, a second port 302 of each first valve 102 - 1 in the first input section 110 is an output port of the first valve 102 - 1 because the second port 302 is fluidly connected or integrated to the first common channel 212 in the first input section 110 .

Similarly, in the second input section 120, a first port 301 of each second valve 102-2 is an input port of the second valve 102-2 because the first port 301 is directly connected or integrated to a second inlet passage 221 of a corresponding second inlet port 121 (e.g., using fasteners and flange seals). Therefore, a second port 302 of each second valve 102-2 in the second input section 120 is an output port of the second valve 102-2 because the second port 302 is fluidly connected or integrated to the second common passage 222 in the second input section 120.

In the output section 130, a first port 301 of each third valve 102-3 is an input port of the third valve 102-3 because the first port 301 is fluidly connected or integrated to the third common channel 232 in the output section 130. Therefore, a second port 302 of each third valve 102-3 in the output section 130 is an output port of the third valve 102-3 because the second port 302 is directly connected or integrated to an output channel 231 of a corresponding output port 131 (e.g., using fasteners and flange seals).

Specifically, a first port 301 of the first shut-off valve 102-4 (FIG. 2B to FIG. 2C) is an output port of the first shut-off valve 102-4 because the first port 301 is fluidly connected or integrated to the third common channel 232. Therefore, a second port 302 of the first shut-off valve 102-4 is an input port of the first shut-off valve 102-4 because the second port 302 is fluidly connected or integrated to the first common channel 212.

Similarly, a first port 301 of the second shut-off valve 102-5 is an output port of the second shut-off valve 102-5 because the first port 301 is fluidly connected or integrated to the third common channel 232. Therefore, a second port 302 of the second shut-off valve 102-5 is an input port of the second shut-off valve 102-5 because the second port 302 is fluidly connected or integrated to the second common channel 222.

3B shows a closed state of the valve 102, wherein a pressure generated by the weight of the coil in the coil housing 320 and/or the metal weight 306 itself is applied to the movable diaphragm 305. Therefore, the movable diaphragm 305 is pushed downward to cover the first port 301 and the second port 302, so that the first port 301 and the second port 302 are not fluidly coupled to each other. That is, a liquid in the input port of the first port 301 and the second port 302 cannot flow into the output port of the first port 301 and the second port 302.

When the valve 102 is switched to an open state (e.g., based on a control signal sent by the control computer through the control panel), no pressure is applied to the metal counterweight 306 (or there is a suction force that lifts the metal counterweight 306). Then, the fluid in the input port will give pressure from the bottom of the movable diaphragm 305 to push the movable diaphragm 305 and the metal counterweight 306 upward, so that the fluid can flow from the input port to the output port.

In one example, one of the first valves 102-1 allows a wet liquid to flow from an associated first inlet port 111 through a corresponding first inlet channel 211, through the first valve 102-1, to the first common channel 212 when opened. The first shut-off valve 102-4 allows the wet liquid to flow from the first common channel 212 through the first shut-off valve 102-4 to the third common channel 232 when opened. Then, one of the third valves 102-3 allows the wet liquid to flow from the third common channel 232, through the third valve 102-3, through a corresponding outlet channel 231, to an associated outlet port 131 when opened. The wet liquid will then be delivered to a target chamber connected to the associated outlet port 131.

In another example, one of the second valves 102-2 allows a dry liquid to flow from an associated second inlet port 121 through a corresponding second inlet channel 221, through the second valve 102-2, to the second common channel 222 when opened. The second shut-off valve 102-5 allows a wet liquid to flow from the second common channel 222 through the second shut-off valve 102-5 to the third common channel 232 when opened. Then, one of the third valves 102-3 allows a dry liquid to flow from the third common channel 232 through the third valve 102-3, through a corresponding outlet channel 231, to an associated outlet port 131 when opened. The dry liquid will then be delivered to a target chamber connected to the associated outlet port 131.

In some embodiments, the cross-sectional area of the fluid flow path is kept uniform within the range of manufacturing capabilities. Specifically, the inner diameters of all inlet/outlet channels 211, 221, 231, the inner diameters of all common channels 212, 222, 232, the orifice diameters of all valves 102, and the interconnecting orifice diameters of the fluid manipulation device 100 are all closely matched. Therefore, the fluid path will hardly expand or contract suddenly to cause changes in pressure and flow rate.

In some embodiments, the fluid manipulation device 100 has an internal reagent volume between 1 milliliter (mL) and 100 mL, wherein the cross-sectional area of the channel in the fluid manipulation device 100 is between 0.1 square millimeters (mm ² ) and 10 mm ^2. A channel in the fluid manipulation device 100 (e.g., the first common channel 212, the second common channel 222, or the third common channel 232) can be formed by digging holes from two opposite sides of a plastic block. The channel will not collapse during digging. The holes from both sides (e.g., having a diameter of 1 mm) need to be aligned with each other.

It will not work simply by downsizing a device used for larger scale fluid dispensing. Because a fluid device with a larger internal volume (e.g., 1 L to 100 L) does not have to worry about small amounts (e.g., 100 mL) of waste reagent or waste during dispensing. Using the same design as a larger scale fluid device (e.g., connecting metal tubing with 3/8 and 1/2 inch inner diameters, such as by connectors or welding) will produce a large and unacceptable percentage of waste reagent, such as 100 mL of waste reagent for every 300 mL of reagent delivered. Additionally, for one of the dimensions of the fluid manipulation device 100 (1 mL to 100 mL internal volume and 0.1 mm ² to 10 mm ² ), it is very difficult, if not impossible, to connect or weld side metal channels together in close proximity (eg, 7.5 mm between two adjacent side channels).

Nor will it work simply by increasing the dimensions of a device used for a smaller scale fluid distribution. A fluid device with a smaller dimension has channels with an inner diameter of 10 μm to 100 μm, where the channels are connected by pouring PDMS silicone into a mold (e.g., 4-5 inches). But pouring PDMS silicone into a mold with a larger dimension (e.g., >10 inches) is very difficult (if not impossible) because a channel constructed in this manner with a larger size may easily collapse.

In some embodiments, each valve has an aperture of 0.7 mm to 1 mm (e.g., 0.8 mm) and has a station width of about 7 mm to 8 mm (e.g., 7.2 mm), which is the minimum allowable station-to-station (center-to-center) spacing. The flange interface of the fluid manipulation device 100 can be designed according to manufacturer recommendations.

In some embodiments, a simple implementation of a common channel connecting all the outputs of these valves 102 would be about 166 mm long resulting in an aspect ratio (channel length: channel inner diameter) of about 150:1 to 200:1. It is not possible to drill very accurately with this dimension without the channel collapsing. It can be determined that the maximum drilling depth for a 1.0 mm hole is 40 mm for the required accuracy. Therefore, the fluid manipulation device 100 includes five blocks: a 3-station block and a 5-station block forming the first input section 110; a 5-station block and a 6-station block forming the second input section 120; and a 6-station block forming the output section 130.

Every two adjacent manifold blocks are sealed with an O-ring having high temperature resistance and strong chemical resistance. In some embodiments, each O-ring has an inner diameter of about 1 mm (e.g., 1.07 mm). In some embodiments, there is no additional retaining structure in the O-ring to allow the O-ring to form a long channel with almost no change in cross-section. In some embodiments, the operating compression of the O-ring is about 24%.

Two shut-off valves 102-4, 102-5 are integrated into the fluid manipulation device 100 to separate the inputs and prevent reagents from one group from contaminating the other group. For example, when a wet reagent flows toward the outlet, it will not flow through the dry side shut-off valve, and therefore will not contaminate the dry reagent inlet. In addition, the above-mentioned integration of the shut-off valve into the fluid manipulation device 100 can greatly reduce the internal volume of the fluid manipulation device 100, while keeping the percentage of invalid reagents very low.

The embodiment shown in Figures 1 to 3 uses at least 23 valve stations. In other embodiments, the number of blocks can be easily increased. For example, 2 blocks in the first input section 110 and the second input section 120 can be easily expanded to 3 or more blocks. In some embodiments, due to the manufacturing limitations described, the number of stations per block is at most 6 stations.

Generally speaking, the fluid manipulation device 100 can be used as a reagent distribution manifold in any fluid distribution application having multiple inlets and multiple outlets, such as a bioreactor, chemical synthesis, or other microfluidic chip.

FIG. 4 shows a barebones diagram of a fluid manipulation manifold 400 according to some embodiments of the present invention. In some embodiments, the manifold 400 may have a structure like the fluid manipulation device 100 in FIG. 1A and FIG. 1B . As shown in FIG. 4 , the manifold 400 includes a wet side input section 410 configured to receive a wet fluid via an inlet port, an inlet valve 402-1, and a wet side common channel 412. The manifold 400 also includes a dry side input section 420 configured to receive a dry fluid via an inlet port, an inlet valve 402-2, and a dry side common channel 422. In addition, the manifold 400 also includes an output section 430, which is configured to receive a wet fluid from the wet side input section 410 through a shut-off valve 402-4, receive a dry fluid from the dry side input section 420 through a shut-off valve 402-5, and output each received fluid to a target chamber through an outlet common channel 432, an outlet valve 402-3, and a corresponding outlet. In some embodiments, the sections 410 and 420 in FIG. 4 correspond to the sections 110 and 120 in FIG. 1 to FIG. 3, respectively.

FIG4 also shows an exemplary fluid path when one inlet 421 in the dry side input section 420 is activated and one outlet 431 in the output section 430 is activated. In some embodiments, it is expected that all valves on the fluid path are open, while all other valves are closed. For example, with respect to the fluid path in FIG4 (marked with a bold line), the inlet valve 402-2, the shutoff valve 402-5, and the outlet valve 402-3 through which the fluid path passes are all open, while all other valves including the shutoff valve 402-4 are all closed.

Along the fluid path (marked with a thick line) in FIG. 4 , a dry fluid flows into the fluid manifold through the start-up inlet 421 to flow through the open inlet valve 402-2 to the dry-side common channel 422, then flows through the open shut-off valve 402-5 to the outlet common channel 432, and then flows through the open outlet valve 402-3 to the start-up outlet 431. The dry fluid can then flow to a target chamber through the start-up outlet 431. Because the shut-off valve 402-4 is closed, the dry fluid can only flow to the end of the outlet common channel 432 and cannot flow into the wet-side common channel 412.

FIG. 5 illustrates an example diagram of a reagent delivery system 500 including the fluid manifold 400 shown in FIG. 4 according to some embodiments of the present invention. The reagent delivery system 500 is a pressure-driven reagent delivery system that utilizes an inert gas to prevent atmospheric contamination. In some embodiments, a pressurized inert gas pushes a reagent through the fluid manifold 400 into a target chamber. The target chamber is completely filled when the chamber outlet reaches atmospheric pressure. The process is stopped when a bubble sensor positioned at the chamber outlet detects the transition from gas to liquid. A pressure sensor is positioned on the side of the pressurized gas to monitor the air pressure so that a consistent and stable pressure differential can be achieved for flow and software control.

As shown in FIG5 , the reagent delivery system 500 includes: a plurality of wet reagent containers 541, each containing a respective wet liquid reagent containing water; a plurality of dry reagent containers 542, each containing a respective dry liquid reagent containing no water or only a trace amount of water; an inert gas source 510, which is configured to provide a pressurized inert gas; and an inert gas manifold 520, which is coupled to the inert gas source 510. In this example, the inert gas is argon; the inert gas source 510 is an argon cylinder; and the inert gas manifold 520 is an argon manifold. Although in other examples, the pressurized inert gas may be any other inert gas (e.g., nitrogen, helium, etc.), the inert gas source 510 may be a source or container of any inert gas and the inert gas manifold 520 may be a manifold of inert gas provided by the inert gas source 510. The inert gas manifold 520 is configured to distribute the pressurized inert gas to a plurality of wet reagent containers 541 and a plurality of dry reagent containers 542.

As shown in FIG. 5 , the reagent delivery system 500 also includes a fluid manipulation manifold 400. In some embodiments, the fluid manipulation manifold 400 in FIG. 5 is a fluid device having a structure identical to that of the fluid manipulation device 100 described with respect to FIGS. 1 to 3 . For example, the fluid manipulation manifold 400 may include a plurality of first inlet ports, a plurality of second inlet ports, and a plurality of outlet ports. Each of the plurality of wet reagent containers 541 is fluidically coupled to one of the plurality of first inlet ports; and each of the plurality of dry reagent containers 542 is fluidically coupled to one of the plurality of second inlet ports. For example, the wet reagent containers in the wet reagent container 541 that respectively contain Cap A and Cap B are fluidically coupled to the first inlet ports 463, 464 of the fluid manipulation manifold 400, respectively. For example, a dry reagent container containing an activating agent (ACT) in the dry reagent container 542 is fluidly coupled to the second inlet port 453 of the fluid manipulation manifold 400 .

As shown in FIG. 5 , the reagent delivery system 500 also includes a plurality of bubble sensors 590 , 591 . . . 596 and a plurality of chambers: chamber 0, chamber 1 , chamber 2, chamber 3. Each chamber includes two chamber ports: a first chamber port and a second chamber port. The first chamber port of each chamber is fluidically coupled to one of the plurality of outlet ports of the manifold 400 ; and the second chamber port of each chamber is fluidically coupled to one of the plurality of bubble sensors 590 , 591 . . . 596 . For example, chamber 2 has a first chamber port 481 and a second chamber port 482 . While the first chamber port 481 is fluidically coupled to the outlet port 474 of the fluid manipulation manifold 400 , the second chamber port 482 is fluidically coupled to the bubble sensor 592 .

As shown in FIG. 5 , the inert gas manifold 520 has an inlet coupled to the inert gas source 510 via a first plastic tube 515; and the inert gas manifold 520 has a plurality of outlets. The reagent delivery system 500 also includes a plurality of pressure regulators PR0, PR1 ... PR5, each of which is fluidly coupled to one of the plurality of outlets of the inert gas manifold 520 via a second plastic tube. An inner diameter of the first plastic tube 515 is larger than an inner diameter of the second plastic tube. For example, the inert gas manifold 520 has an outlet 524 fluidly coupled to the pressure regulator PR4 via the second plastic tube 525, wherein an inner diameter of the first plastic tube 515 is larger than an inner diameter of the second plastic tube 525. In some embodiments, the inner diameter of the first plastic tube 515 is approximately 1/4 inch, and the inner diameter of each second plastic tube is approximately 1/8 inch.

In some embodiments, the reagent delivery system 500 includes: at least one dry-side manifold, which is fluidically coupled between at least one of the plurality of outlets of the inert gas manifold 520 and a plurality of dry reagent containers 542 via a third plastic tube; and at least one wet-side manifold, which is fluidically coupled between at least one of the plurality of outlets of the inert gas manifold 520 and a plurality of wet reagent containers 541 via a third plastic tube. In some embodiments, each third plastic tube has an inner diameter that is the same as the inner diameter of the second plastic tube. In the example shown in FIG. 5 , the reagent delivery system 500 includes: a first wet-side manifold 531, a second wet-side manifold 532, and a dry-side manifold 533. The dry-side manifold 533 is fluidly coupled between one of the plurality of outlets of the inert gas manifold 520 and all the dry reagent containers 542 via the third plastic tube 535 and the pressure regulator PRO. The dry-side manifold 533 is configured to receive the pressurized inert gas from the inert gas manifold 520 via the pressure regulator PRO and distribute the received pressurized inert gas to all the dry reagent containers 542 to push the dry reagents in the dry reagent containers 542 to the respective inlet ports of the manifold 400. In some embodiments, each third plastic tube 535 has an inner diameter of 1/8 inch, which is the same as the inner diameter of the second plastic tube 525.

Similarly, the first wet side manifold 531 is fluidly coupled between one of the plurality of outlets of the inert gas manifold 520 and two wet reagent containers containing Cap A and Cap B respectively through a third plastic tube. The second wet side manifold 532 is fluidly coupled between one of the plurality of outlets of the inert gas manifold 520 and three wet reagent containers containing Echem, OX and trichloroacetic acid deblocking (DB) respectively through a third plastic tube. Each of the first wet-side manifold 531 and the second wet-side manifold 532 is configured to receive pressurized inert gas from the inert gas manifold 520 and distribute the received pressurized inert gas to the corresponding wet reagent container 541 to push the wet reagent in the wet reagent container 541 to the respective inlet ports of the manifold 400 .

In some embodiments, each of the plurality of dry reagent containers 542 is fluidly coupled to a corresponding second inlet port of the manifold 400 via a fourth plastic tube; and each of the plurality of wet reagent containers 541 is fluidly coupled to a corresponding first inlet port of the manifold 400 via a fifth plastic tube. The fourth plastic tube has an inner diameter that is the same as the inner diameter of the fifth plastic tube. In one example, a dry reagent container ACT containing an activator is fluidly coupled to a corresponding second inlet port 453 of the manifold 400 via a fourth plastic tube 555. In another example, a wet reagent container Cap A containing Cap A is fluidly coupled to a corresponding first inlet port 463 of the manifold 400 via a fifth plastic tube 556. In some embodiments, the fourth plastic tube 555 and the fifth plastic tube 556 both have the same inner diameter of 1/8 inch. In other embodiments, the fourth plastic tube 555 and the fifth plastic tube 556 both have the same inner diameter of 1/16 inch. In other embodiments, the fourth plastic tube 555 and the fifth plastic tube 556 both have an inner diameter that changes from 1/8 inch at a portion near the reagent container to 1/16 inch at a portion near the corresponding inlet port of the manifold 400. In the example shown in FIG. 5 , the dry reagent container 542 also includes containers for accommodating imide X (X), universal linker (UL), imide T (T), imide C (C), imide G (G), and imide A (A), respectively.

For each of the wet reagent container 541 and the dry reagent container 542, a pressure of the inert gas can force the fluid reagent in the reagent container to flow to the manifold 400. The chamber outlet reaches atmospheric pressure during a filling process to generate the pressure difference required for flow. The flow rate can be determined by the pressure of the inert gas, the pressure at the chamber outlet of the target chamber (during a filling process) and the fluid resistance experienced by the fluid reagent when flowing through the tubes and channels in the reagent delivery system 500.

As shown in FIG5 , the reagent delivery system 500 also includes a plurality of dry flow sensors 553, each of which is coupled to a fourth plastic tube connecting a dry reagent container 542 and its corresponding second inlet port of the manifold 400, and is configured to monitor a flow rate of the respective dry liquid reagent flowing from the dry reagent container 542 to the corresponding second inlet port. For example, a dry flow sensor ACT' 553 is coupled to a fourth plastic tube 555 connecting a dry reagent container ACT 542 and its corresponding second inlet port 453 of the manifold 400. In some embodiments, the dry flow sensor ACT' 553 can be coupled to the fourth plastic tube 555 in a non-invasive manner and does not affect the flow of the fluid in the fourth plastic tube 555. Therefore, the dry flow sensor ACT' 553 can monitor the flow rate of the activating agent flowing from the dry reagent container ACT 542 to the corresponding second inlet port 453.

The reagent delivery system 500 also includes a plurality of wet flow sensors 551, 552, each of which is coupled to a fifth plastic tube connecting a wet reagent container 541 and its corresponding first inlet port of the manifold 400, and is configured to monitor a flow rate of the respective wet liquid reagent flowing from the wet reagent container 541 to the corresponding first inlet port. For example, a wet flow sensor CapA' 551 is coupled to a fifth plastic tube 556 connecting the wet reagent container CapA 541 and its corresponding first inlet port 463 of the manifold 400. In some embodiments, the wet flow sensor CapA' 551 can be coupled to the fifth plastic tube 556 in a non-invasive manner and does not affect the flow of the fluid in the fifth plastic tube 556. Thus, the wet flow sensor CapA' 551 can monitor the flow rate from the wet reagent container CapA 541 to the Cap A corresponding to the first inlet port 463. In some embodiments, all containers containing reagents that need to be mixed with another reagent should be coupled to a flow sensor via corresponding plastic tubes. Thus, one can monitor whether the mixing is according to a predetermined ratio, such as 1:1 or 50%:50%. For example, one of the imides can be mixed with an activator (ACT); Cap A and Cap B solutions can be mixed together. In some embodiments, due to volume and tube size constraints, the container of the universal connector (UL) is not coupled to any flow sensor.

In some embodiments, the outlet ports of the manifold 400 are arranged in a row on one side of the manifold 400. As shown in FIG5 , a first outlet port 471 arranged at one end of the row is directly coupled to a bubble sensor 595 without any chamber disposed therebetween; and a second outlet port 476 arranged at the other end of the row is directly coupled to a bubble sensor 596 without any chamber disposed therebetween. The bubble sensor 595 and the bubble sensor 596 are both configured to monitor the fluid flow in the outlet common channel 432 of the manifold 400. In one example, when the shut-off valve 402-5 is open and the shut-off valve 402-4 is closed, the bubble sensor 596 can indicate whether the outlet common channel 432 is filled with a dry fluid, wherein the outlet common channel 432 is full when no additional bubbles are present at the bubble sensor 596. In another example, when the shut-off valve 402-5 is closed and the shut-off valve 402-4 is open, the bubble sensor 595 can indicate whether the outlet common channel 432 is filled with a wet fluid, wherein the outlet common channel 432 is full when no additional bubbles are present at the bubble sensor 595.

5 , the reagent delivery system 500 also includes a first waste container 581 coupled to the bubble sensor 595 and a second waste container 582 coupled to the bubble sensor 596. The reagent flowing from the outlet port 471 to the bubble sensor 595 is considered as a waste and is collected by the first waste container 581. Similarly, the reagent flowing from the outlet port 476 to the bubble sensor 596 is considered as a waste and is collected by the second waste container 582. In some embodiments, the first waste container 581 and the second waste container 582 always have a pressure at atmospheric pressure.

5 , the reagent delivery system 500 also includes: a plurality of first two-way valves 560, 561, each coupled between one of the bubble sensors 590, 591 and the first waste container 581; and a plurality of second two-way valves 562, 563, each coupled between one of the bubble sensors 592, 593 and the second waste container 582. In addition, the reagent delivery system 500 also includes a plurality of first three-way valves 570, 571 and a plurality of second three-way valves 572, 573. The three-way valve 570 has a first end coupled to the two-way valve 560 and a second end switchable between the first waste container 581 and the pressure regulator PR5, which is fluidically coupled to one of the plurality of outlets of the inert gas manifold 520. The three-way valve 571 has a first end coupled to the two-way valve 561 and a second end switchable between the first waste container 581 and the pressure regulator PR5, which is fluidically coupled to one of the plurality of outlets of the inert gas manifold 520. The three-way valve 572 has a first end coupled to the two-way valve 562 and a second end switchable between the second waste container 582 and the pressure regulator PR5, and the pressure regulator PR5 is fluidly coupled to one of the plurality of outlets of the inert gas manifold 520. The three-way valve 573 has a first end coupled to the two-way valve 563 and a second end switchable between the second waste container 582 and the pressure regulator PR5, and the pressure regulator PR5 is fluidly coupled to one of the plurality of outlets of the inert gas manifold 520.

Each of the bubble sensors 590, 591, 592, 593 is configured to monitor the liquid fluid in a corresponding connected chamber and indicate when the connected chamber is full. The fluid flowing from the connected chamber to the corresponding bubble sensor is considered as a waste and is collected by the corresponding waste container. In one example, the bubble sensor 592 can indicate whether the liquid fluid fills chamber 2, wherein chamber 2 is completely filled with liquid fluid when there are no additional bubbles at the bubble sensor 592. The liquid fluid flowing from chamber 2 to the bubble sensor 592 is considered as a waste and is collected by the waste container 582 via the two-way valve 562 and the three-way valve 572.

As shown in FIG. 5 , the reagent delivery system 500 also includes a cleaning liquid container 543 that contains a cleaning liquid configured to clean the channels, valves, and ports of the manifold 400. The cleaning liquid container 543 is coupled between the pressure regulator PR2 and the second common channel 422 of the manifold 400. In the example shown in FIG. 5 , the cleaning liquid is acetonitrile (ACN). In other examples, the cleaning liquid in the cleaning liquid container 543 can be water, ethanol, methanol, acetone, hexane, benzene, and/or acetic acid. The cleaning liquid is a solvent or a solvent mixture. Acetonitrile (ACN) is an exemplary cleaning liquid described herein and in FIG. 5 to FIG. 10 .

As shown in FIG. 5 , the reagent delivery system 500 also includes: a two-way valve 565 coupled between the cleaning liquid container 543 and the second common channel 422 ; and a three-way valve 575 having a first end coupled to the two-way valve 565 and a second end switchable between the first waste container 581 and the cleaning liquid container 543 .

As shown in FIG. 5 , the reagent delivery system 500 also includes: a bubble sensor 594 coupled between the first common channel 412 and the second waste container 582 ; and a two-way valve 564 coupled between the bubble sensor 594 and the second waste container 582 .

In some embodiments, the reagent delivery system 500 also includes pressure sensors 585, 586, 587, 588. As shown in FIG. 5, a gas tube 526 is coupled between the pressure regulator PR1 and a second inlet port 450 located at one end of the manifold 400. The gas tube 526 is configured to transport pressurized inert gas from the pressure regulator PR1 to the second inlet port 450 to purge the manifold 400. In this example, the inert gas is argon, while in other examples, the inert gas can be nitrogen or helium. In some embodiments, a pressure sensor 587 is coupled to the gas tube 526 and is configured to monitor a pressure of the gas blown into the manifold 400.

As shown in FIG5 , the reagent delivery system 500 also includes an air pipe 528 coupled between the pressure regulator PR5 and each of the three-way valves 570, 571, 572, 573. The air pipe 528 is configured to transport the pressurized inert gas from the pressure regulator PR5 to at least one of the plurality of chambers (chambers 0 to 3) to purge at least one chamber. In some embodiments, a pressure sensor 588 is coupled to the air pipe 528 and is configured to monitor a pressure of the gas blown into at least one chamber.

In some embodiments, the pressure sensor 585 is directly coupled to one of the plurality of outlets of the inert gas manifold 520 without any pressure regulator disposed therebetween, and is configured to monitor a pressure of the gas blown out from the inert gas source 510 and/or the inert gas manifold 520. In some embodiments, the fourth pressure sensor 586 is coupled between the pressure regulator PR0 and the dry side manifold 533 fluidly coupled to the plurality of dry reagent containers 542, and is configured to monitor a pressure of the gas blown into the plurality of dry reagent containers 542.

In some embodiments, each of the plurality of pressure regulators 585, 586, 587, 588 is configured to use a program to control a pressure and/or air volume of the pressurized inert gas based on feedback information from at least one of the plurality of bubble sensors 590, 591 ... 596. In some embodiments, the pressure of the inert gas entering the reagent container 541, 542 is higher than atmospheric pressure, for example, 8 psi higher. In some embodiments, the feedback information is also used to control at least one valve in the reagent delivery system 500.

FIG. 6A illustrates an actuating fluid path during a first operation of a wash solution (e.g., ACN) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present invention. The bold line in FIG. 6A represents a fluid path through all regions that ACN will pass through during the first operation. Before the first operation, all valves in the reagent delivery system 500 are closed. At the beginning of the first operation, all valves on the fluid path in FIG. 6A are opened in a sequence from downstream to upstream of the fluid path. That is, an outlet valve 476-1 of an outlet port 476 in the control manifold 400 is opened first. Then, the shut-off valve 402-5 is opened to connect the dry side common channel 422 and the outlet common channel 432 with fluid. Next, the two-way valve 565 opens to allow ACN to flow into the dry side common channel 422. Here, it is assumed that the three-way valve 575 has been switched to the ACN container 543 before the first operation. In some embodiments, the three-way valve 575 may be switched to the ACN container 543 after the two-way valve 565 is opened to push the ACN into the dry side common channel 422.

During the first operation, ACN flows from the ACN container 543 through the three-way valve 575 and the two-way valve 565 into the dry side common channel 422, and then flows into the outlet common channel 432 through the shut-off valve 402-5. When the shut-off valve 402-4 is closed, ACN cannot flow into the wet side common channel 412. ACN will flow out of the manifold 400 through the outlet valve 476-1 and the outlet port 476 and be collected by the second waste container 582 as a waste. The bubble sensor 596 can monitor the state of the ACN flow and indicate whether the outlet common channel 432 is completely filled with ACN. One purpose of the first operation is to fill and/or wash the dry side common channel 422 and the outlet common channel 432 with ACN, for example in preparation for later filling and/or washing of a chamber.

At the end of the first operation, all valves on the fluid path in FIG. 6A are closed in a sequence from upstream to downstream of the fluid path. That is, the two-way valve 565 is first closed to stop the ACN from flowing into the dry side common channel 422. In some embodiments, the three-way valve 575 can remain as it is. In other embodiments, the three-way valve 575 can be switched from the ACN container 543 to the first waste container 581. Then, the shut-off valve 402-5 is closed to fluidly disconnect the dry side common channel 422 and the outlet common channel 432. Then, the outlet valve 476-1 of the control outlet port 476 is closed.

FIG. 6B illustrates an actuating fluid path during a second operation of a wash solution (e.g., ACN) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present invention. The bold line in FIG. 6B represents a fluid path through all regions that ACN will pass through during the second operation. In some embodiments, the second operation is performed immediately after the first operation. Before the second operation, all valves in the reagent delivery system 500 are closed. At the beginning of the second operation, all valves on the fluid path in FIG. 6B are opened in a sequence from downstream to upstream of the fluid path. That is, the two-way valve 562 is first opened to allow a fluid to flow from chamber 2 to the second waste container 582. Here, it is assumed that the three-way valve 572 has been switched to the second waste container 582 before the second operation. In some embodiments, the three-way valve 572 may be switched to the second waste container 582 before the two-way valve 562 is opened. Next, the outlet valve 474-1 of the outlet port 474 in the control manifold 400 is opened. Next, the shut-off valve 402-5 is opened to fluidly connect the dry side common channel 422 and the outlet common channel 432. Next, the two-way valve 565 is opened and the three-way valve 575 is switched to the ACN container 543 (if it has not been switched to the ACN container 543), as described above for the first operation.

During the second operation, ACN flows from the ACN container 543 through the three-way valve 575 and the two-way valve 565 into the dry side common channel 422, and then flows into the outlet common channel 432 through the shut-off valve 402-5. The ACN will then flow out of the manifold 400 through the outlet valve 474-1 and the outlet port 474, and flow into the chamber 2. Since the ACN has filled the outlet common channel 432 during the first operation, the chamber 2 can directly receive the ACN at the beginning of the second operation without receiving impurities or residues from the outlet common channel 432. The bubble sensor 592 can monitor the state of the ACN flowing into the chamber 2 and indicate whether the chamber 2 is completely filled with ACN. The ACN flowing out of chamber 2 (after chamber 2 is filled) flows through two-way valve 562 and three-way valve 572 and is collected as a waste by the second waste container 582. One purpose of the second operation is to fill and/or wash chamber 2 with ACN.

At the end of the second operation, all valves on the fluid path in FIG. 6B are closed in a sequence from upstream to downstream of the fluid path. That is, the two-way valve 565 is first closed to stop the ACN from flowing into the dry side common channel 422. In some embodiments, the three-way valve 575 can remain as it is. In other embodiments, the three-way valve 575 can be switched from the ACN container 543 to the first waste container 581. Then, the shut-off valve 402-5 is closed to fluidly disconnect the dry side common channel 422 and the outlet common channel 432. Then, the outlet valve 474-1 controlling the outlet port 474 is closed. The two-way valve 562 is then closed.

FIG. 7 illustrates an actuating fluid path during a flushing operation of a cleaning solution (e.g., CAN (acetonitrile)) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present invention. The bold line in FIG. 7 represents a fluid path of all regions that will be passed through during the flushing operation by ACN. Before the flushing operation, all valves in the reagent delivery system 500 are closed. When the flushing operation begins, all valves on the fluid path in FIG. 7 are opened in a sequence from downstream to upstream of the fluid path. That is, the two-way valve 564 is first opened to allow a fluid in the wet side common channel 412 to flow into the second waste container 582. Next, shutoff valve 402-4 opens to fluidly connect wet side common channel 412 and outlet common channel 432. Next, shutoff valve 402-5 opens to fluidly connect dry side common channel 422 and outlet common channel 432. Next, two-way valve 565 opens and three-way valve 575 switches to ACN container 543 (if not already switched to ACN container 543), as described above for the first operation.

During the flushing operation, ACN flows from the ACN container 543 through the three-way valve 575 and the two-way valve 565 into the dry side common channel 422, then flows into the outlet common channel 432 through the shut-off valve 402-5, and then flows into the wet side common channel 412 through the shut-off valve 402-4. The bubble sensor 594 can monitor the state of the ACN flow and indicate whether the wet side common channel 412 is completely filled with ACN. The extra ACN flowing out of the wet side common channel 412 is collected by the second waste container 582 as a waste. One purpose of the flushing operation is to clean the wet side common channel 412, the dry side common channel 422, and the outlet common channel 432 with ACN, for example, after fluid manipulation and transportation using the manifold 400.

At the end of the flushing operation, all valves on the fluid path in FIG. 7 are closed in a sequence from upstream to downstream of the fluid path. That is, the two-way valve 565 is first closed to stop the ACN from flowing into the dry side common channel 422. In some embodiments, the three-way valve 575 can remain as it is. In other embodiments, the three-way valve 575 can be switched from the ACN container 543 to the first waste container 581. Then, the shut-off valve 402-5 is closed to disconnect the dry side common channel 422 and the outlet common channel 432 with fluid. Then, the shut-off valve 402-4 is closed to disconnect the wet side common channel 412 and the outlet common channel 432 with fluid. Next, the two-way valve 564 is closed.

FIG8 illustrates an actuating fluid path during a purge operation of an inert gas (e.g., argon) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present invention. The bold line in FIG8 represents a fluid path through all areas that the argon will pass through during the purge operation. In some embodiments, the purge operation of the inert gas may be performed immediately after the purge operation of the washing liquid.

Before the cleaning operation, all valves in the reagent delivery system 500 are closed. When the cleaning operation starts, all valves on the fluid path in FIG. 8 are opened in a sequence from downstream to upstream of the fluid path. That is, the two-way valve 564 is first opened to allow a gas fluid in the wet side common channel 412 to flow or be blown into the second waste container 582. Then, the shut-off valve 402-4 is opened to connect the wet side common channel 412 and the outlet common channel 432 with the fluid. Then, the shut-off valve 402-5 is opened to connect the dry side common channel 422 and the outlet common channel 432 with the fluid. Next, an inlet valve 450 - 1 of the inlet port 450 in the control manifold 400 is opened to allow argon to flow into the dry-side common passage 422 .

During the cleaning operation, argon flows from the inert gas manifold 520, through the pressure regulator PR1, through the inlet valve 450-1 and the inlet port 450, into the dry side common channel 422, then through the shut-off valve 402-5 into the outlet common channel 432, and then through the shut-off valve 402-4 into the wet side common channel 412. The bubble sensor 594 can monitor the state of the argon flow and indicate whether the wet side common channel 412 is completely filled with argon. The extra argon flowing out of the wet side common channel 412 is collected by the second waste container 582 as a waste. One purpose of the cleaning operation is to clean the wet-side common channel 412 , the dry-side common channel 422 , and the outlet common channel 432 using argon or another inert gas, for example, after fluid manipulation at the manifold 400 and flushing the manifold 400 .

At the end of the cleaning operation, all valves on the fluid path in FIG8 are closed in a sequence from upstream to downstream of the fluid path. That is, the inlet valve 450-1 of the control inlet port 450 is first closed to stop the argon gas from flowing into the dry side common channel 422. Then, the shut-off valve 402-5 is closed to disconnect the dry side common channel 422 and the outlet common channel 432 with the fluid. Then, the shut-off valve 402-4 is closed to disconnect the wet side common channel 412 and the outlet common channel 432 with the fluid. Then, the two-way valve 564 is closed.

Fig. 9 A illustrates an actuating fluid path during the initial operation of a dry reagent (such as ACT) in a reagent delivery system (such as reagent delivery system 500) according to some embodiments of the present invention. ACT (which includes an activator) is an exemplary dry reagent for describing the operation that can be applied to each other dry reagent. The bold line in Fig. 9 A represents a fluid path of all regions that will be passed through during the initial operation by ACT. Before the initial operation, all valves in the reagent delivery system 500 are closed. When the initial operation begins, all valves on the fluid path in Fig. 9 A are opened in a sequence from the downstream of the fluid path to the upstream. That is, the outlet valve 476-1 of the outlet port 476 in the control manifold 400 is opened at first. Next, the shut-off valve 402-5 is opened to fluidly connect the dry common channel 422 and the outlet common channel 432. Next, the inlet valve 453-1 of the control inlet port 453 is opened to allow ACT to flow into the dry common channel 422. Here, the two-way valve 565 is closed, so that ACT cannot flow out of the dry common channel 422 from the left end of the manifold 400.

During the initial feed operation, ACT flows from the ACT container 542 through the inlet valve 453-1 and the inlet port 453 into the dry side common channel 422, and then flows into the outlet common channel 432 through the shut-off valve 402-5. When the shut-off valve 402-4 is closed, ACT cannot flow into the wet side common channel 412. ACT will flow out of the manifold 400 through the outlet valve 476-1 and the outlet port 476 and be collected by the second waste container 582 as a waste. The bubble sensor 596 can monitor the state of the ACT flow and indicate whether the outlet common channel 432 is completely filled with ACT. One purpose of the initial feed operation is to use ACT to fill the dry side common channel 422 and the outlet common channel 432, for example, to prepare to fill a chamber with ACT later.

At the end of the initial supply operation, all valves on the fluid path in FIG. 9A are closed in a sequence from upstream to downstream of the fluid path. That is, the inlet valve 453-1 of the control inlet port 453 is first closed to stop ACT from flowing into the dry side common channel 422. Then, the shut-off valve 402-5 is closed to fluidly disconnect the dry side common channel 422 and the outlet common channel 432. Then, the outlet valve 476-1 of the control outlet port 476 is closed.

FIG. 9B illustrates an actuating fluid path during an operation of filling a dry reagent (e.g., ACT) into a chamber in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present invention. The bold line in FIG. 9B represents a fluid path through all regions that will be passed through during the filling operation by ACT. In some embodiments, the filling operation in FIG. 9B is performed immediately after the initial feeding operation in FIG. 9A. Before the filling operation, all valves in the reagent delivery system 500 are closed. At the beginning of the filling operation, all valves on the fluid path in FIG. 9B are opened in a sequence from downstream to upstream of the fluid path. That is, the two-way valve 562 is first opened to allow a fluid to flow from chamber 2 to the second waste container 582. Here, it is assumed that the three-way valve 572 has been switched to the second waste container 582 before the filling operation. In some embodiments, the three-way valve 572 may be switched to the second waste container 582 before the two-way valve 562 is opened. Next, the outlet valve 474-1 of the outlet port 474 in the control manifold 400 is opened. Next, the shut-off valve 402-5 is opened to fluidly connect the dry common channel 422 and the outlet common channel 432. Next, the inlet valve 453-1 of the control inlet port 453 is opened to allow ACT to flow into the dry common channel 422.

During the filling operation, ACT flows from the ACT container 542 through the inlet valve 453-1 and the inlet port 453 into the dry side common channel 422, and then flows into the outlet common channel 432 through the shut-off valve 402-5. The ACT then flows out of the manifold 400 through the outlet valve 474-1 and the outlet port 474, and flows into the chamber 2, for example, for use in a DNA synthesizer, analysis, or other chemical reaction or biotechnology operation. Since the ACT has filled the outlet common channel 432 during the initial feeding operation, the chamber 2 can directly receive the ACT at the beginning of the filling operation without receiving impurities or residues from the outlet common channel 432. The bubble sensor 592 can monitor the state of the ACT flowing into the chamber 2 and indicate whether the chamber 2 is completely filled with ACT. ACT flowing out of chamber 2 (after chamber 2 is filled) flows through two-way valve 562 and three-way valve 572 and is collected as a waste by second waste container 582. During the filling operation, ACT flows into chamber 2 through port 481 and flows out of chamber 2 through port 482. One purpose of the filling operation is to transport ACT into chamber 2 for some biotechnology and/or chemical operation.

At the end of the filling operation, all valves on the fluid path in FIG. 9B are closed in a sequence from upstream to downstream of the fluid path. That is, the inlet valve 453-1 of the control inlet port 453 is first closed to stop the ACT from flowing into the dry side common channel 422. Then, the shut-off valve 402-5 is closed to fluidly disconnect the dry side common channel 422 and the outlet common channel 432. Then, the outlet valve 474-1 of the control outlet port 474 is closed. After that, the two-way valve 562 will be closed.

FIG. 9C illustrates an actuating fluid path during a cleaning operation of a chamber filled with a dry reagent (e.g., ACT) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present invention. The bold line in FIG. 9C represents a fluid path through all regions that will be passed through during the cleaning operation by ACT. In some embodiments, the cleaning operation in FIG. 9C is performed immediately after the filling operation in FIG. 9B. Before the cleaning operation, all valves in the reagent delivery system 500 are closed. At the beginning of the cleaning operation, all valves on the fluid path in FIG. 9C are opened in a sequence from downstream to upstream of the fluid path. That is, the outlet valve 476-1 of the outlet port 476 in the control manifold 400 is opened first. Next, the outlet valve 474 - 1 of the outlet port 474 in the control manifold 400 is opened. Next, the two-way valve 562 is opened, and the three-way valve 572 is switched to the pressure regulator PR5 to receive pressurized inert gas from the inert gas manifold 520 .

During the cleaning operation, an inert gas (e.g., argon) flows from the inert gas manifold 520 through the pressure regulator PR5 through the three-way valve 572 and the two-way valve 562 into the chamber 2. The inert gas flows into the chamber 2 through the port 482, and pushes the ACT (or any other liquid) remaining in the chamber 2 out of the chamber 2 through the port 481. Thus, the ACT (and any other liquid) flows out of the chamber 2 through the port 481, flows into the outlet common channel 432 through the outlet valve 474-1 and the outlet port 474. The ACT (and any other liquid) will flow out of the manifold 400 through the outlet valve 476-1 and the outlet port 476 and be collected by the second waste container 582 as a waste. The bubble sensor 596 can monitor the state of the ACT flow and indicate whether there is any ACT left in the outlet common channel 432. Therefore, the flow direction of ACT in the purge operation is opposite to the flow direction of ACT in the fill operation. One purpose of the purge operation is to purge the chamber 2 with argon or another inert gas, for example, after the fluid is transported to the chamber 2 and operated in the chamber 2.

In some embodiments, chamber 2 (and each other chamber in reagent delivery system 500) has a shape like a window with a small thickness value, a fixed length value, and a large height value. In some embodiments, first chamber port 481 is located at the lower portion or bottom of the window, and second chamber port 482 is located at the upper portion or top of the window. Although a liquid reagent can easily enter chamber 2 through first chamber port 481 to push air or gas in chamber 2 upward during filling, it is preferred to allow inert gas to enter chamber 2 through second chamber port 482 to push liquid reagent in chamber 2 downward during cleaning procedures. Thus, a flow direction of the liquid reagent in chamber 2 (and every other chamber in the reagent delivery system 500) during the filling process is different from its flow direction during the cleaning process.

At the end of the cleaning operation, all valves on the fluid path in FIG. 9C are closed in a sequence from upstream to downstream of the fluid path. That is, the three-way valve 572 is first switched to the second waste container 582 to stop receiving pressurized inert gas from the inert gas manifold 520. Then, the two-way valve 562 is closed. Then, the outlet valve 474-1 of the outlet port 474 in the control manifold 400 is closed. Then, the outlet valve 476-1 of the outlet port 476 in the control manifold 400 is closed.

Figure 10A illustrates an actuating fluid path during the initial operation of a wet reagent (e.g., OX) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present invention. OX (which represents an oxidant) is an exemplary wet reagent for describing the operation that can be applied to each other wet reagent. The bold line in Figure 10A represents a fluid path of all regions that will be passed through during the initial operation by OX. Before the initial operation, all valves in the reagent delivery system 500 are closed. When the initial operation begins, all valves on the fluid path in Figure 10A are opened in a sequence from the downstream of the fluid path to the upstream. That is, the outlet valve 471-1 of the outlet port 471 in the control manifold 400 is opened first. Then, the shut-off valve 402-4 is opened to fluidly connect the wet side common channel 412 and the outlet common channel 432. Then, an inlet valve 462-1 of the control inlet port 462 is opened to allow OX to flow into the wet side common channel 412. Here, the two-way valve 564 is opened, so that OX cannot flow out of the wet side common channel 412 from the right end of the manifold 400.

During the initial feeding operation, OX flows from the OX container 541 through the inlet valve 462-1 and the inlet port 462 into the dry side common channel 422, and then flows into the outlet common channel 432 through the shut-off valve 402-4. When the shut-off valve 402-5 is closed, OX cannot flow into the dry side common channel 422. OX will flow out of the manifold 400 through the outlet valve 471-1 and the outlet port 471 and be collected by the first waste container 581 as a waste. The bubble sensor 595 can monitor the state of the OX flow and indicate whether the outlet common channel 432 is completely filled with OX. One purpose of the initial feeding operation is to use OX to fill the wet side common channel 412 and the outlet common channel 432, for example, to prepare to fill a chamber with OX later.

At the end of the initial supply operation, all valves on the fluid path in FIG. 10A are closed in a sequence from upstream to downstream of the fluid path. That is, the inlet valve 462-1 of the control inlet port 462 is first closed to stop OX from flowing into the wet side common channel 412. Then, the shut-off valve 402-4 is closed to fluidly disconnect the wet side common channel 412 and the outlet common channel 432. Then, the outlet valve 471-1 of the control outlet port 471 is closed.

FIG. 10B illustrates an actuating fluid path during an operation of filling a wet reagent (e.g., OX) into a chamber in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present invention. The bold line in FIG. 10B represents a fluid path through all regions that OX will pass through during the filling operation. In some embodiments, the filling operation in FIG. 10B is performed immediately after the initial feeding operation in FIG. 10A. Before the filling operation, all valves in the reagent delivery system 500 are closed. At the beginning of the filling operation, all valves on the fluid path in FIG. 10B are opened in a sequence from downstream to upstream of the fluid path. That is, the two-way valve 562 is first opened to allow a fluid to flow from the chamber 2 to the second waste container 582. Here, it is assumed that the three-way valve 572 has been switched to the second waste container 582 before the filling operation. In some embodiments, the three-way valve 572 may be switched to the second waste container 582 before the two-way valve 562 is opened. Then, the outlet valve 474-1 of the outlet port 474 in the control manifold 400 is opened. Then, the shut-off valve 402-4 is opened to fluidly connect the wet side common channel 412 and the outlet common channel 432. Then, the inlet valve 462-1 of the control inlet port 462 is opened to allow OX to flow into the wet side common channel 412.

During the filling operation, OX flows from the OX container 541 through the inlet valve 462-1 and the inlet port 462 into the wet side common channel 412, and then flows into the outlet common channel 432 through the shut-off valve 402-4. OX then flows out of the manifold 400 through the outlet valve 474-1 and the outlet port 474, and flows into the chamber 2, for example, for use in a DNA synthesizer, analysis or other chemical reaction or biotechnology operation. Since OX has filled the outlet common channel 432 during the initial feeding operation, the chamber 2 can directly receive OX at the beginning of the filling operation without receiving impurities or residues from the outlet common channel 432. The bubble sensor 592 can monitor the state of the OX flow in the chamber 2 and indicate whether the chamber 2 is completely filled with OX. OX flowing out of chamber 2 (after chamber 2 is filled) flows through two-way valve 562 and three-way valve 572 and is collected as a waste by second waste container 582. During the filling operation, OX flows into chamber 2 through port 481 and flows out of chamber 2 through port 482. One purpose of the filling operation is to transport OX into chamber 2 for some biotechnological and/or chemical operations.

At the end of the filling operation, all valves on the fluid path in FIG. 10B are closed in a sequence from upstream to downstream of the fluid path. That is, the inlet valve 462-1 controlling the inlet port 462 is first closed to stop the flow of OX into the wet side common channel 412. Then, the shut-off valve 402-4 is closed to fluidly disconnect the wet side common channel 412 and the outlet common channel 432. Then, the outlet valve 474-1 controlling the outlet port 474 is closed. After that, the two-way valve 562 is closed.

Figure 10C illustrates an actuating fluid path during a cleaning operation of a chamber filled with a wet reagent (e.g., OX) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present invention. The bold line in Figure 10C represents a fluid path through all areas that will pass through during the cleaning operation by OX. In some embodiments, the cleaning operation in Figure 10C is performed immediately after the filling operation in Figure 10B. Before the cleaning operation, all valves in the reagent delivery system 500 are closed. At the beginning of the cleaning operation, all valves on the fluid path in Figure 10C are opened in a sequence from downstream to upstream of the fluid path. That is, the outlet valve 471-1 of the outlet port 471 in the control manifold 400 is opened first. Next, the outlet valve 474 - 1 of the outlet port 474 in the control manifold 400 is opened. Next, the two-way valve 562 is opened, and the three-way valve 572 is switched to the pressure regulator PR5 to receive pressurized inert gas from the inert gas manifold 520 .

During the cleaning operation, an inert gas (e.g., argon) flows from the inert gas manifold 520 through the pressure regulator PR5 through the three-way valve 572 and the two-way valve 562 into the chamber 2. The inert gas flows into the chamber 2 through the port 482 and pushes the OX (and any other liquid) remaining in the chamber 2 out of the chamber 2 through the port 481. Thus, the OX (and any other liquid) flows out of the chamber 2 through the port 481, flows into the outlet common channel 432 through the outlet valve 474-1 and the outlet port 474. The OX (and any other liquid) will flow out of the manifold 400 through the outlet valve 471-1 and the outlet port 471 and be collected by the first waste container 581 as a waste. The bubble sensor 595 can monitor the state of the OX flow and indicate whether there is any OX left in the outlet common channel 432. Therefore, the flow direction of OX in the cleaning operation is opposite to the flow direction of OX in the filling operation. One purpose of the cleaning operation is to clean the chamber 2 with argon or another inert gas, for example, after the fluid is transported to the chamber 2 and operated in the chamber 2.

At the end of the cleaning operation, all valves on the fluid path in FIG. 10C are closed in a sequence from upstream to downstream of the fluid path. That is, the three-way valve 572 is first switched to the second waste container 582 to stop receiving pressurized inert gas from the inert gas manifold 520. Then, the two-way valve 562 is closed. Then, the outlet valve 474-1 of the outlet port 474 in the control manifold 400 is closed. Then, the outlet valve 471-1 of the outlet port 471 in the control manifold 400 is closed.

Each inlet and outlet of the manifold 400 can be activated individually. In some embodiments, two reagents in two reagent containers can be pushed into the manifold 400 through two respective inlet ports. For example, when the outlet port 474 and the two inlet ports 463, 464 are all opened at the same time, CapA and CapB in the wet reagent containers Cap A and Cap B can be transported to the chamber 2 together in equal amounts to mix with each other for some electrochemical reactions.

Referring to Figures 11A-11B, according to some embodiments, the manifold function of a fluid manipulation device is tested. The fluid manipulation device is the same as the fluid manipulation device described in Figures 1-3, except that the port at the bottom is used for gas outlet during testing. Similar to Figures 2B-2C, Figure 11A is an exemplary cross-sectional side view of the fluid manipulation device 100. Similar to Figure 2A, Figure 11B is an exemplary cross-sectional bottom view of the fluid manipulation device 100. Blocks are labeled "LH", "CTL", "CH", "CTR" and "RT" based on location and function. The codes "LH", "CTL", "CH", "CTR" and "RT" represent left hand, center left, chamber, center and right, respectively.

The test medium used is compressed air having a pressure in the range of 0.0827 MPa to 0.331 MPa (from 12 psi to 48 psi). The volume flow rate of the air used is in the range of 4 L/min to 40 L/min.

For an external leak test, all ports are pressurized and the valve is actuated to test the valve mounting seal, O-rings at the manifold connection points, and the flatness of the 10-32 sealing surface. For a seat leak test, the inlet port is pressurized and the valve is tested in the NC state (not actuated) to test the seat. During an external leak test, the valve is open. During a seat leak test, the valve is closed.

The duration of a leak test lasts for 10 seconds. The pass criterion for a leak test is a pressure drop less than 1/1000 of the inlet pressure.

For a functional flow test, a near inlet is pressurized and the valve is individually tested to ensure that the valve is operating correctly and that the flow path is not blocked. The flow rate of the air used is tested. These results indicate that the device can be used for reagents with good flow.

Perform the following four sets of tests.

1. The first set of tests was performed on the valves (V1 to V5) in the LH manifold shown in Figures 11A-11B.

1-1. External Leak Test: Inlet 1 (Fig. 11A) and outlet are pressurized. Five valves (LH: V1 to V5) are actuated (opened). The pressurized gas is then shut off. After the leak test duration has elapsed, the pressure drop is measured.

1-2. Valve Seat Leak Test: Inlet 1 (Fig. 11A) is pressurized. Five valves (LH: V1 to V5) are closed. The pressurized gas is then shut off. After the leak test duration has elapsed, the pressure drop is measured.

1-3. Functional flow test: Inlet 1 (Fig. 11A) is pressurized. Five valves (LH: V1 to V5) are tested individually. Once a steady flow is achieved, an individual flow rate is recorded.

2. A second set of tests was performed on the valves in the CTL manifold (CTL: V1 to V5) and one valve in the CH manifold shown in Figures 11A-11B. Valve No. 6 (CTL: V6) in the CTL manifold was actuated to test flow through the CH.

2-1. External Leak Test: Inlet 1 (Fig. 11A) and outlet (Fig. 11B) are pressurized. The first five valves in the CTL manifold and the first valve in the CH manifold (CTL: V1 to V5; CH: V1) are actuated (opened). The pressurized gas is then shut off. After the leak test duration has elapsed, the pressure drop is measured.

2-2. Valve Seat Leak Test: Inlet 1 (Fig. 11A) is pressurized. The first five valves in the CTL manifold and the first valve in the CH manifold (CTL: V1 to V5; CH: V1) are closed. The pressurized gas is then shut off. After the leak test duration has elapsed, the pressure drop is measured.

2-3. Functional flow test: Inlet 1 (Fig. 11A) is pressurized. The first five valves in the CTL manifold and the first valve in the CH manifold (CTL: V1 to V5; CH: V1) are tested individually. Once a steady flow is achieved, an individual flow rate is recorded.

3. A third set of tests was performed on the second to sixth valves (CH: V2 to V6) in the CH manifold to CTR shown in Figures 11A-11B. The first valve in the CTR manifold (CTR: V1) was actuated to test flow through CH.

3-1. External Leak Test: Inlet 2 (Fig. 11A) and outlet are pressurized. The valve (CH: V2 to V6) is actuated (opened). The pressurized gas is then shut off. After the leak test duration has elapsed, the pressure drop is measured.

3-2. Valve Seat Leak Test: Inlet 2 (Fig. 11A) is pressurized. The valve (CH: V2 to V6) is closed. The pressurized gas is then shut off. After the leak test duration has elapsed, the pressure drop is measured.

3-2. Functional flow test: Inlet 2 (Fig. 11A) is pressurized. Valves (CH: V2-V6) are tested individually. Once a steady flow is achieved, an individual flow rate is tested.

4. The fourth set of tests is performed on two valves in the CTR manifold (CTR: V2 to V3) and five valves in the RT manifold (RT: V1 to V5):

4-1. External Leak Test: Inlet 2 (Fig. 11A) and outlet are pressurized. The valves (CTR: V2-V3; RT: V1-V5) are actuated (opened). The pressurized gas is then shut off. After the leak test duration has elapsed, the pressure drop is measured.

4-2. Valve Seat Leak Test: Inlet 2 is pressurized. The valve (CTR: V2-V3; RT: V1 to V5) is closed. The pressurized gas is then shut off. After the leak test duration has elapsed, the pressure drop is measured.

4-3. Functional flow test: Inlet 2 is pressurized. Valves (CTR: V2-V3; RT: V1-V5) are tested individually. Once a stable flow is achieved, an individual flow rate is recorded.

The test results are shown in Table 1. As shown in Table 1, all results including external leakage and valve seat leakage meet the pass criteria, where a pressure drop is less than 1/1000 of the inlet test pressure. The device including the valve and port has a good seal and no leakage is shown or the leakage is negligible. The functional flow test results also indicate that the device including the valve can operate correctly and the flow path is not blocked. The device and system provided in the present invention can be used for reagents with good flow.

Table 1 Test Set 1 LH Manifold Test pressure (bar) Function/flow rate (L/min) Test pressure (bar) / external leakage (mbar) Test pressure (bar)/valve leakage (mbar) LH V1 3.27 5.82 3.29/.85 3.29/.77 LH V2 3.26 5.71 LH V3 3.25 5.60 LH V4 3.25 5.67 LH V5 3.24 5.54 Test Group 2 CTL&CH Manifold Test pressure (bar) Function/flow rate (L/min) Test pressure (bar) / external leakage (mbar) Test pressure (bar)/valve leakage (mbar) CTL V1 3.24 5.75 3.29/.77 3.29/.79 CTL V2 3.26 5.61 CTL V3 3.24 5.60 CTL V4 3.24 5.59 CTL V5 3.24 5.50 CH V1 3.23 6.00 Test Group 3 CH&CTR Manifold Test pressure (bar) Function/flow rate (L/min) Test pressure (bar) / external leakage (mbar) Test pressure (bar)/valve leakage (mbar) CH V2 3.26 6.87 3.29/.74 3.28/.82 CH V3 3.24 6.70 CH V4 3.25 6.68 CH V5 3.26 6.65 V6 3.23 6.72 Test Group 4 CTR&RT Manifold Test pressure (bar) Function/flow rate (L/min) Test pressure (bar) / external leakage (mbar) Test pressure (bar)/valve leakage (mbar) CTR V2 3.27 7.32 3.29/.73 3.28/.79 CTR V3 3.24 7.29 RT V1 3.24 7.37 RT V2 3.23 7.29 RT V3 3.23 7.31 RT V4 3.26 7.41 RT V5 3.24 7.36 Average flow rate 6.41 Flow rate standard deviation 0.74

Although various embodiments of the present invention have been described above, it should be understood that they are provided for illustration only and not limitation. Similarly, various drawings may depict an exemplary architecture or configuration, which are provided to enable a person of ordinary skill to understand the exemplary features and functions of the present invention. However, a person of ordinary skill should understand that the present invention is not limited to the exemplary architecture or configuration depicted, but may be implemented using various alternative architectures and configurations. In addition, a person of ordinary skill should understand that one or more features of one embodiment may be combined with one or more features of another embodiment described herein. Therefore, the breadth and scope of the present invention should not be limited to any of the exemplary embodiments described above.

It should also be understood that any reference to an element using a symbol such as "first," "second," etc. herein generally does not limit the number or order of the elements. Rather, such symbols may be used herein as a shorthand way to distinguish between two or more elements or instances of an element. Thus, reference to a first and a second element does not mean that only two elements may be used or that the first element must precede the second element in some manner.

In addition, it should be understood by a person skilled in the art that information and signals may be represented using any of a variety of different technologies and techniques. For example, data, instructions, commands, information, signals, bits, and symbols referred to in the above description may be represented by voltage, current, electromagnetic waves, magnetic fields or magnetic particles, optical fields or optical particles, or any combination thereof.

A person of ordinary skill in the art should further understand that any of the various illustrative logic blocks, modules, processors, components, circuits, methods, and functions described in conjunction with the aspects disclosed herein may be implemented by electronic hardware (e.g., a digital implementation, an analog implementation, or a combination of the two), firmware, various forms of programs or design codes incorporating instructions (for convenience, which may be referred to herein as "software" or "software modules"), or any combination of such technologies.

To clearly illustrate this interchangeability of hardware, firmware, and software, various illustrative components, blocks, modules, circuits, and steps have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware, firmware, or software, or a combination of such technologies, depends on the particular application and the design constraints imposed on the overall system. Those skilled in the art may implement the described functionality in a variety of ways for each particular application, but such implementation decisions do not cause a departure from the scope of the present invention. According to various embodiments, a processor, device, component, circuit, structure, machine, module, etc. may be configured to perform one or more of the functions described herein. The terms "configured to" or "configured for" as used herein with respect to a specific operation or function refer to a processor, device, component, circuit, structure, machine, module, etc. that is physically constructed, programmed and/or configured to perform a specific operation or function.

In addition, it should be understood by those of ordinary skill in the art that the various illustrative logic blocks, modules, devices, components, and circuits described herein may be implemented in or performed by an integrated circuit (IC), which may include a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), or other programmable logic devices, or any combination thereof. The logic blocks, modules, and circuits may further include antennas and/or transceivers to communicate with various components within a network or within a device. A general purpose processor may be a microprocessor, but alternatively, the processor may be any learning processor, controller, or state machine. A processor may also be implemented as a combination of computing devices, such as a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other suitable configuration for performing the functions described herein.

If implemented in software, the functions may be stored as one or more instructions or code on a computer-readable medium. Thus, the steps of a method or algorithm disclosed herein may be implemented as software stored on a computer-readable medium. Computer-readable media include both computer storage media and communication media, including any media capable of transferring a computer program or code from one location to another. A storage medium may be any available media that can be accessed by a computer. By way of example and not limitation, such computer-readable media may include RAM, ROM, EEPROM, CD-ROM or other optical disk storage, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired program code in the form of instructions or data structures and that can be accessed by a computer.

In the present invention, as used herein, the term "module" refers to software, firmware, hardware, and any combination of such components for performing the associated functions described herein. In addition, for the purpose of discussion, various modules are described as discrete modules; however, a person of ordinary skill in the art will appreciate that two or more modules may be combined to form a single module that performs the associated functions according to the embodiments of the present invention.

In addition, memory or other storage and communication components may be used in embodiments of the present invention. It should be understood that, for clarity, the above description has been described with reference to different functional units and processors to describe embodiments of the present invention. However, it should be understood that any suitable allocation of functionality between different functional units, processing logic elements or domains may be used without detracting from the present invention. For example, functionality that is illustrated as being performed by a separate processing logic element or controller may be performed by the same processing logic element or controller. Therefore, reference to a specific functional unit is only a reference to a component that is suitable for providing the described functionality, rather than indicating a strict logical or physical structure or organization.

Those skilled in the art will readily appreciate various modifications of the embodiments described in the present invention, and the general principles defined herein may be applied to other embodiments without departing from the scope of the present invention. Therefore, the present invention is not intended to be limited to the embodiments shown herein, but is to be given the widest scope consistent with the novel features and principles disclosed herein, as described in the following patent application scope.

100: Fluid manipulator 101: Plastic base 102: Valve 102-1: First valve 102-2: Second valve 102-3: Third valve 102-4: First shut-off valve 102-5: Second shut-off valve 104: Fastener 105-1: Block 105-2: Block 105-3: Block 105-4: Block 105-5: Block 110: First input section 111: First inlet port 120: Second input section 121: Second inlet port 130: Output section 131: Outlet port 200-1: Cross-sectional bottom view 200-2: Cross-section side view 200-3: Cross-section side view 204: Flange seal 211: First inlet channel 212: First common channel 221: Second inlet channel 222: Second common channel 231: Outlet channel 232: Third common channel 301: First port 302: Second port 304: Flange seal 305: Removable diaphragm 306: Metal weight 310: Valve body 320: Coil housing 330: Connector 400: Fluid control manifold 402-1: Inlet valve 402-2: Inlet valve 402-3: Outlet valve 402-4: Shut-off valve 402-5: Shut-off valve 410: Wet side input section 412: Wet side common channel 420: Dry side input section 421: Inlet 422: Dry side common channel 430: Output section 431: Outlet 432: Outlet common channel 450: Second inlet port 450-1: Inlet valve 453: Second inlet port 453-1: Inlet valve 462: Inlet port 462-1: Inlet valve 463: First inlet port 464: First inlet port 471: First outlet port 471-1: Outlet valve 474: Outlet port 474-1: Outlet valve 476: Second outlet port 476-1: Outlet valve 481: First chamber port 482: Second chamber port 500: Reagent delivery system 510: Inert gas source 515: First plastic tube 520: Inert gas manifold 524: Outlet 525: Second plastic tube 526: Air tube 528: Air tube 531: First wet side manifold 532: Second wet side manifold 533: Dry side manifold 535: Third plastic tube 541: Wet reagent container 542: Dry reagent container 543: Cleaning liquid container 551: Wet flow sensor 552: Wet flow sensor 553: Dry flow sensor 555: Fourth plastic tube 556: Fifth plastic tube 560: First two-way valve 561: First two-way valve 562: Second two-way valve 563: Second two-way valve 564: Two-way valve 565: Two-way valve 570: First three-way valve 571: First three-way valve 572: Second three-way valve 573: Second three-way valve 575: Three-way valve 581: First waste container 582: Second waste container 585: Pressure sensor 586: Pressure sensor 587: Pressure sensor 588: Pressure sensor 590, 591…596: Bubble sensor PR0, PR1…PR5: Pressure regulator Q: Plane

Various exemplary embodiments of the present invention are described in detail below with reference to the following figures. The figures are for illustration only and depict only exemplary embodiments of the present invention to facilitate the reader's understanding of the present invention. Therefore, the figures should not be considered to limit the breadth, scope and applicability of the present invention. It should be noted that for clarity and ease of illustration, these figures are not necessarily drawn to scale.

Figure 1A shows an exemplary perspective view of an exemplary fluid manipulation device according to some embodiments of the present invention.

FIG. 1B shows another exemplary perspective view of the fluid manipulation device of FIG. 1A according to some embodiments of the present invention.

2A illustrates an exemplary cross-sectional bottom view of the fluid manipulation device of FIG. 1A according to some embodiments of the present invention.

Figure 2B shows an exemplary cross-sectional side view of the fluid manipulation device of Figure 1A according to some embodiments of the present invention.

2C illustrates another exemplary cross-sectional side view of the fluid manipulation device of FIG. 1A according to some embodiments of the present invention.

Figure 3A shows an exemplary perspective view of an exemplary valve in a fluid manipulation device according to some embodiments of the present invention.

3B illustrates an exemplary side and cross-sectional view of a valve in a fluid manipulation device shown in FIG. 3A according to some embodiments of the present invention.

FIG. 4 shows a quasi-system diagram of an exemplary fluid manipulation device according to some embodiments of the present invention.

FIG. 5 shows an exemplary diagram of an exemplary reagent delivery system according to some embodiments of the present invention.

FIG. 6A illustrates an actuating fluid path of a wash solution during a first operation period in the reagent delivery system of FIG. 5 according to some embodiments of the present invention.

FIG. 6B illustrates an actuating fluid path of a wash solution during a second operation period in the reagent delivery system of FIG. 5 according to some embodiments of the present invention.

FIG. 7 illustrates an actuating fluid path during a flushing operation of a wash solution in the reagent delivery system of FIG. 5 according to some embodiments of the present invention.

FIG. 8 illustrates an actuating fluid path during a purge operation of an inert gas in the reagent delivery system of FIG. 5 according to some embodiments of the present invention.

FIG. 9A illustrates an actuating fluid path during an initial dosing operation of a dry reagent in the reagent delivery system of FIG. 5 according to some embodiments of the present invention.

FIG. 9B illustrates an actuating fluid path during an operation of filling a dry reagent into a chamber in the reagent delivery system of FIG. 5 according to some embodiments of the present invention.

9C illustrates an actuating fluid path during a cleaning operation of a chamber filled with a dry reagent in the reagent delivery system of FIG. 5 according to some embodiments of the present invention.

FIG. 10A illustrates an actuating fluid path during an initial dosing operation of a wet reagent in the reagent delivery system of FIG. 5 according to some embodiments of the present invention.

FIG. 10B illustrates an actuating fluid path during an operation of filling a wet reagent into a chamber in the reagent delivery system of FIG. 5 , according to some embodiments of the present invention.

10C illustrates an actuating fluid path during a cleaning operation of a chamber filled with a wet reagent in the reagent delivery system of FIG. 5 according to some embodiments of the present invention.

11A-11B illustrate a fluid manipulation device undergoing manifold functionality testing according to some embodiments. FIG. 11A is an exemplary cross-sectional side view of the fluid manipulation device, and FIG. 11B is an exemplary cross-sectional bottom view of the fluid manipulation device.

100: Fluid manipulation device

101: Plastic base

102: Valve

104: Fasteners

110: First input section

120: Second input section

130: Output section

Claims (44)

A fluid device, comprising: a plurality of first inlet ports; a first common channel; a plurality of first valves, each of which is associated with one of the plurality of first inlet ports, wherein each first valve fluid is coupled between an associated first inlet port and the first common channel; a plurality of second inlet ports; a second common channel; a plurality of second valves, each of which is associated with one of the plurality of second inlet ports, wherein each second valve fluid is coupled between an associated second inlet port and the second common channel; a plurality of outlet ports; a third common channel; a plurality of third valves, each of which is associated with one of the plurality of outlet ports, wherein each third valve fluid is coupled between an associated outlet port and the third common channel; a first shut-off valve, whose fluid is coupled between the first common channel and the third common channel; and A second shut-off valve, the fluid of which is coupled between the second common channel and the third common channel. A fluid device as claimed in claim 1, wherein: the plurality of first inlet ports, the first common channel, the plurality of first valves and the first shut-off valve are integrated in a first input section of the fluid device; the plurality of second inlet ports, the second common channel, the plurality of second valves and the second shut-off valve are integrated in a second input section of the fluid device; the plurality of outlet ports, the third common channel and the plurality of third valves are integrated in an outlet section of the fluid device; and the output section is physically coupled between the first input section and the second input section. A fluid device as claimed in claim 2, wherein: The first input section and the second input section are separated from each other. A fluid device as claimed in claim 1, wherein: All valves of the plurality of first valves, the plurality of second valves, the plurality of third valves, the first shut-off valve and the second shut-off valve are arranged in parallel and on a same first side of the fluid device. A fluid device as claimed in claim 4, wherein: All of the plurality of first inlet ports, the plurality of second inlet ports and the plurality of outlet ports are disposed on a same second side of the fluid device; and The second side is opposite to the first side. A fluid device as claimed in claim 1, wherein: each first inlet port is configured to receive a first liquid; and each second inlet port is configured to receive a second liquid. A fluid device as claimed in claim 6, wherein: the first liquid is selected from a first group consisting of an oxidant, a first blocking reagent (A), a second blocking reagent (B) and an electrochemical reaction medium; and the second liquid is selected from a second group consisting of an imide, an activator and an inert gas. A fluidic device as claimed in claim 7, wherein: The separation of the first group and one of the second groups minimizes cross contamination between the first group and the second group near the outlet ports. A fluid device as claimed in claim 6, wherein: the plurality of first inlet ports includes a first number of first inlet ports; and the plurality of second inlet ports includes a second number of second inlet ports. A fluid device as claimed in claim 9, wherein: the first amount is different from the second amount. A fluid device as claimed in claim 10, wherein: the first amount is less than the second amount. The fluid device of claim 1 further comprises: a plurality of first inlet channels, each corresponding to one of the plurality of first inlet ports, wherein each first inlet channel is vertically arranged in the fluid device in a longitudinal direction normal to the fluid device and the fluid is coupled between a corresponding first inlet port and an associated first valve; a plurality of second inlet channels, each corresponding to one of the plurality of second inlet ports, wherein each second inlet channel is vertically arranged in the fluid device and the fluid is coupled between a corresponding second inlet port and an associated second valve; and a plurality of outlet channels, each corresponding to one of the plurality of outlet ports, wherein each outlet channel is vertically arranged in the fluid device and the fluid is coupled between a corresponding outlet port and an associated third valve. A fluid device as claimed in claim 12, wherein: The first common channel, the second common channel and the third common channel are horizontally arranged in the fluid device along the longitudinal direction of the fluid device. A fluid device as claimed in claim 13, wherein: All of the plurality of first inlet channels, the plurality of second inlet channels, the plurality of third inlet channels, the first common channel, the second common channel and the third common channel have a same cross-sectional area and a same inner diameter. A fluid device as claimed in claim 14, wherein: All valves of the plurality of first valves, the plurality of second valves, the plurality of third valves, the first shut-off valve and the second shut-off valve have a same structure and a same orifice. A fluid device as claimed in claim 15, wherein: The liquid flowing in each of the plurality of first inlet channels, the plurality of second inlet channels, the plurality of third inlet channels, the first common channel, the second common channel and the third common channel is isolated from the atmosphere and driven by a pressurized inert gas. A fluid device as claimed in claim 15, wherein: the same cross-sectional area is between 0.1 square millimeters and 10 square millimeters; the fluid device has an internal volume between 1 milliliter and 100 milliliters; and the same inner diameter is substantially the same as the same pore diameter. A fluid device as claimed in claim 12, wherein: a first valve allows a first liquid to flow from an associated first inlet port, through a corresponding first inlet channel, through the first valve to the first common channel when opened; the first shut-off valve allows the first liquid to flow from the first common channel through the first shut-off valve to the third common channel when opened; and a third valve allows the first liquid to flow from the third common channel, through the third valve, through a corresponding outlet channel to an associated outlet port when opened. A fluid device as claimed in claim 12, wherein: a second valve allows a second liquid to flow from an associated second inlet port, through a corresponding second inlet channel, through the second valve to the second common channel when opened; the second shut-off valve allows the second liquid to flow from the second common channel through the second shut-off valve to the third common channel when opened; and a third valve allows the second liquid to flow from the third common channel, through the third valve, through a corresponding outlet channel to an associated outlet port when opened. A reagent delivery system, comprising: a plurality of first reagent containers, each containing a respective first liquid reagent selected from a first group; a plurality of second reagent containers, each containing a respective second liquid reagent selected from a second group; a fluid device, comprising a plurality of first inlet ports, a plurality of second inlet ports, and a plurality of outlet ports, wherein each of the plurality of first reagent containers is fluidly coupled to one of the plurality of first inlet ports, and each of the plurality of second reagent containers is fluidly coupled to one of the plurality of second inlet ports; and a plurality of chambers, each of which comprises a first chamber port and a second chamber port, wherein the first chamber port of each chamber is fluidly coupled to one of the plurality of outlet ports. The reagent delivery system of claim 20 further comprises: an inert gas source configured to provide a pressurized inert gas; an inert gas manifold coupled to the inert gas source and configured to distribute the pressurized inert gas to the plurality of first reagent containers and the plurality of second reagent containers; and a plurality of bubble sensors. A reagent delivery system as claimed in claim 21, wherein: the inert gas manifold has an inlet coupled to the inert gas source via a first plastic tube; and the inert gas manifold has a plurality of outlets. The reagent delivery system of claim 22 further comprises: A plurality of pressure regulators, each of which is fluidically coupled to one of the plurality of outlets of the inert gas manifold via a second plastic tube. The reagent delivery system of claim 23 further comprises: At least one first side manifold, which is fluidically coupled between at least one of the plurality of outlets of the inert gas manifold and the plurality of first reagent containers via a third plastic tube; and At least one second side manifold, which is fluidically coupled between at least one of the plurality of outlets of the inert gas manifold and the plurality of second reagent containers via a third plastic tube. A reagent delivery system as claimed in claim 24, wherein: the at least one second-side manifold comprises a manifold that is fluidically coupled to all of the plurality of second reagent containers; and the at least one first-side manifold comprises a first manifold that is fluidically coupled to three of the plurality of first reagent containers and a second manifold that is fluidically coupled to the other two of the plurality of first reagent containers. A reagent delivery system as claimed in claim 24, wherein: Each of the plurality of second reagent containers is fluidically coupled to a corresponding second inlet port of the fluid device via a fourth plastic tube; and Each of the plurality of first reagent containers is fluidically coupled to a corresponding first inlet port of the fluid device via a fifth plastic tube. The reagent delivery system of claim 26 further comprises: A plurality of second-side flow sensors, each of which is coupled to a fourth plastic tube connecting a second reagent container and its corresponding second inlet port, and is configured to monitor a flow rate of the respective second liquid reagent flowing from the second reagent container to the corresponding second inlet port. The reagent delivery system of claim 26 further comprises: A plurality of first-side flow sensors, each of which is coupled to a fifth plastic tube connecting a first reagent container and its corresponding first inlet port, and is configured to monitor a flow rate of the respective first liquid reagent flowing from the first reagent container to the corresponding first inlet port. A reagent delivery system as claimed in claim 23, wherein: The second chamber port of each chamber is fluidly coupled to one of the plurality of bubble sensors. A reagent delivery system as claimed in claim 29, wherein: the plurality of outlet ports are arranged in a row on one side of the fluid device; a first outlet port arranged at one end of the row is directly coupled to a first bubble sensor without any chamber disposed therebetween; and a second outlet port arranged at the other end of the row is directly coupled to a second bubble sensor without any chamber disposed therebetween. The reagent delivery system of claim 30 further comprises: a plurality of first three-way valves, each of which has a first end and a second end; and a plurality of second three-way valves, each of which has a first end and a second end. The reagent delivery system of claim 31 further comprises: a plurality of first two-way valves, each coupled between the second chamber port of one of the plurality of chambers and the first end of a respective first three-way valve; and a plurality of second two-way valves, each coupled between the second chamber port of one of the plurality of chambers and the first end of a respective second three-way valve. A reagent delivery system as claimed in claim 32, wherein: the second end of each first three-way valve is switchable between a first waste container and a pressure regulator, the pressure regulator being fluidly coupled to one of the plurality of outlets of the inert gas manifold; and the second end of each second three-way valve is switchable between a second waste container and the pressure regulator. A reagent delivery system as claimed in claim 33, wherein the fluid device further comprises: a first common channel; a plurality of first valves, each of which is associated with one of the plurality of first inlet ports, wherein each first valve fluid is coupled between an associated first inlet port and the first common channel; a second common channel; a plurality of second valves, each of which is associated with one of the plurality of second inlet ports, wherein each second valve fluid is coupled between an associated second inlet port and the second common channel; a third common channel; a plurality of third valves, each of which is associated with one of the plurality of outlet ports, wherein each third valve fluid is coupled between an associated outlet port and the third common channel; a first shut-off valve, whose fluid is coupled between the first common channel and the third common channel; and A second shut-off valve, the fluid of which is coupled between the second common channel and the third common channel. The reagent delivery system of claim 34 further comprises: A cleaning liquid container containing a cleaning liquid configured to clean the channels, valves and ports of the fluid device, wherein the cleaning liquid container is coupled between one of the plurality of pressure regulators and the second common channel. The reagent delivery system of claim 35 further comprises: a third two-way valve coupled between the cleaning liquid container and the second common channel; and a third three-way valve having a first end coupled to the third two-way valve and a second end switchable between the first waste container and the cleaning liquid container. The reagent delivery system of claim 36 further comprises: a third bubble sensor coupled between the first common channel and the second waste container; and a fourth two-way valve coupled between the third bubble sensor and the second waste container. The reagent delivery system of claim 37 further comprises: a first air pipe coupled between a first pressure regulator and a second inlet port located at one end of the fluid device and configured to transport the pressurized inert gas from the first pressure regulator to the second inlet port to purge the fluid device; and a first pressure sensor coupled to the first air pipe and configured to monitor a pressure of the gas blown into the fluid device. The reagent delivery system of claim 37 further comprises: a second air pipe coupled between a second pressure regulator and each of the first and second three-way valves, and configured to transport the pressurized inert gas from the second pressure regulator to at least one of the plurality of chambers to purge the at least one chamber; and a second pressure sensor coupled to the second air pipe and configured to monitor a pressure of the gas blown into the at least one chamber. The reagent delivery system of claim 37 further comprises: A third pressure sensor directly coupled to one of the plurality of outlets of the inert gas manifold without any pressure regulator disposed therebetween, and configured to monitor a pressure of the gas blown out from the inert gas manifold. The reagent delivery system of claim 37 further comprises: A fourth pressure sensor coupled between a third pressure regulator and a second side manifold fluidically coupled to the plurality of second reagent containers, and configured to monitor a pressure of the gas blown into the plurality of second reagent containers. A reagent delivery system as claimed in claim 23, wherein: Each of the plurality of bubble sensors is configured to monitor the state of a corresponding chamber to determine whether the corresponding chamber is completely filled with liquid; and Each of the plurality of pressure regulators is configured to control a pressure and/or air volume of the pressurized inert gas based on feedback information from at least one of the plurality of bubble sensors. A reagent delivery system as claimed in claim 42, wherein: The feedback information is also used to control at least one valve in the reagent delivery system. A reagent delivery system as claimed in claim 20, wherein: The pressurized inert gas comprises at least one of argon, nitrogen or helium.