JP3634796B2 - Microdispenser and dispensing device for biochemical analysis - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a microdispenser for biochemical analysis. More particularly, it relates to a micro-dispenser with replaceable capillaries arranged in a high density array.
[0002]
[Background Art and Problems to be Solved by the Invention]
Reactions between biomolecules exhibit a very high degree of specificity. It is this specificity that provides live cells with the ability to perform thousands of chemical reactions simultaneously in the same container. In general, this specificity arises from a fit between two molecules having a very complex surface topology.
[0003]
Systems for medical diagnosis often include a series of tests, where each test includes a measurement of the binding of one mobile component to the corresponding fixed component. In order to provide an inexpensive test kit, systems that include a matrix of fixed spots have been proposed. Each spot contains a fixed component of a two component test. The liquid to be tested is basically brought into contact with the matrix.
[0004]
The matrix is basically constructed by dispensing a small amount of fixed component onto a substrate such as glass that has been chemically modified to bind to the fixed component. The amount of material at each spot is relatively small. However, the number of spots may be very large. Therefore, the production of such an analytical evaluation plate requires a reliable microdispenser that can arrange individual spots at predetermined positions with high accuracy.
[0005]
5 and 6 show a conventional dispenser disclosed in US Pat. No. 6,001,309. The device 10 has an outer housing 12 that surrounds the capillary assembly. The housing 12 has an opening 14 through which the capillary 16 extends. At the top of the housing is a gasket 20. In addition, the cover 22 used during cleaning and filling of the device 10 is shown. Within the cover 22 is a first conduit 24 for cleaning solvent additives when the system needs to be emptied or pressurized, a second conduit 28 for connection to a vacuum source, and gas pressure. A third conduit 32 is included for introducing the. The cover 22 is adjacent to a threaded tube 42 that functions to secure the capillary casing 50 in the housing 12. The threaded tube 42 has a conical receptacle 46 for receiving a sample. After cleaning, the cover 22 is removed to expose the conical receiving port 46, and the sample can be received using the receiving port. The conical receptacle 46 has a port 48 that fits into the capillary so that the sample can contact the capillary 16 and the sample can move over the entire length of the capillary 16 due to surface tension, filling the capillary. . The threaded casing 50 has a notch extending downwardly through the threaded casing 50 to receive the electrical wire 54 for driving the transducer 56. Piezoelectric transducer 56 is proximate to orifice 60. The wall of the capillary 16 is so thin that it can move as the transducer 56 expands and contracts.
[0006]
FIG. 7 is a schematic process diagram of a system for manufacturing an array according to US Pat. No. 6,001,309. In FIG. 7, the storage subsystem 300 is shown as an array of racks. Each integrated storage container in the rack includes an array of storage well plates 302. Master controller 304 controls this system. Under the signal of the computer, one or more plates 302 are transported from the storage area 300 to the next station 306. At station 306, robot arm 308 is under the control of subsystem controller 309. The robotic arm 308 using the micropipette tip 310 is one or more suitable injectors placed in the maintenance and filling station 314 under the control of the subsystem controller 315 from the plate 302 with a volume of several microliters of liquid. Move to 312. For reusable sprayers, the maintenance and filling station 314 has a maintenance cap 316. The holder 318 positions the injector 312 on the transfer bar 320 so that the injector 312 is moved to the test station 322 under the control of the subsystem controller 323. As the spray device 312 passes the test station, the spray device is then moved to the spray position 334 by the transfer bar 320 and placed above the substrate 336 by the transfer bar 320 and holder 318. The jet dispenser is now in a position to start jetting drops to create an array.
[0007]
FIG. 8 shows another conventional dispensing device disclosed in US Pat. No. 6,110,426. The dispensing device 110 generally includes a reagent dispenser 112 having a capillary channel 114 suitable for holding a quantity of reagent solution 116. This flow path is formed by a pair of members 112a and 112b that join at the tip region 118 at the lower end of the flow path. At the tip 118, the aqueous solution in the flow path forms a concave surface (meniscus) 120 as shown in FIG. When the dispenser is placed in this manner and the solenoid 122 is actuated to pull out the piston 124, the coupling member 126 moves so that the tip 118 rapidly moves toward and away from the surface of the substrate 130 and momentarily contacts the surface 131. Will come into contact. In practice, the tip 118 of the dispenser 112 is tapped against the substrate surface 131. The tapping motion of the tip 118 with respect to the surface 131 acts to break the liquid meniscus 120 in the tip channel 114 and causes the liquid at the tip 118 to contact the substrate surface 131. This in turn creates a flow of liquid into the capillary space between the tip 118 and the surface 131 and acts to cause the liquid to flow out of the dispenser flow path 114 as seen in FIG. FIG. 11 shows the flow of liquid from the tip 118 onto the substrate surface 131. FIG. 11 illustrates that liquid continues to flow from dispenser 112 onto substrate surface 131 until liquid beads 132 are formed.
[0008]
The dispenser must also operate without clogging for a large number of samples. In addition, the dispenser must be able to quickly replace the sample because each spot in the matrix requires a different fixed component.
[0009]
The dispenser disclosed in US Pat. No. 6,001,309 is reusable. For this reason, the dispenser must be cleaned and refilled, so the problem of cross-contamination easily occurs. Furthermore, due to maintenance time, the overall operation of such a system is cumbersome and inconvenient and further increases costs.
[0010]
Similarly, since the dispenser disclosed in US Pat. No. 6,110,426 is a contact type, the problem of cross-contamination easily occurs as well.
[0011]
To overcome the above disadvantages of dispensers, the present invention provides a microdispenser with replaceable capillaries arranged in a high density array.
[0012]
Another object of the present invention is to provide a microdispenser that can avoid the problem of cross-contamination.
[0013]
[Means for Solving the Problems]
The present invention provides a microdispenser for dispensing a predetermined amount of liquid under the control of a controller. The microdispenser includes a base and an array of tube assemblies. A pedestal having a plurality of holes is electrically connected to the controller. Tube assemblies pre-filled with a given liquid are removably placed in the holes and are individually electrically connected to the pedestal. The tube assembly delivers liquid through the pedestal and is replaceable.
[0014]
In a preferred embodiment, the pedestal is provided with at least one recess formed adjacent to each hole. Furthermore, the pedestal is provided with at least one first pad disposed in each of the holes. Each tube assembly includes a receptacle, a capillary tube and a printed chip head. The receptacle having the passage is provided with at least one protrusion corresponding to the recess in the base and at least one second pad corresponding to the first pad. The second pad abuts the first pad when the tube assembly is inserted into the hole in the pedestal. A capillary for receiving liquid is disposed in the receptacle at one end of the passage. A print chip head disposed in the receptacle at the other end of the passage is in contact with the second pad and communicates with the capillary tube.
[0015]
In addition, each tube assembly is marked with a code indicating the type of liquid contained therein. The pedestal is provided with a first detector for detecting the amount of liquid. Furthermore, each tube assembly is provided with a second detector for detecting the amount of liquid remaining in the capillary.
[0016]
It will be appreciated that the tube assembly may be a pulse pressure ink jet type, a bubble jet ink jet type or a slit jet ink jet type.
[0017]
Furthermore, the present invention provides a dispensing device for biochemical analysis including a controller and at least one microdispenser. A microdispenser for dispensing a predetermined amount of reagent to a substrate used in biochemical analysis is electrically connected to the controller. The microdispenser includes a base and an array of tube assemblies. A pedestal having a plurality of holes is electrically connected to the controller. Tube assemblies pre-filled with predetermined reagents are removably disposed in the holes and are individually electrically connected to the pedestal. Under control of the controller, the tube assembly delivers reagents through the pedestal when the pedestal faces the substrate. The tube assembly is replaceable.
[0018]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, a microdispenser of the present invention will be described in detail with reference to the accompanying drawings.
[0019]
1 and 2 show a microdispenser 200 disclosed in the present invention. Microdispenser 200 dispenses a predetermined amount of liquid under the control of a controller (not shown) and includes a base 210 and an array of tube assemblies 200. The pedestal 210 is electrically connected to the controller 400, and includes a plurality of holes 211, a plurality of recesses 212 formed adjacent to the holes 211, and a plurality of first pads 213 disposed in each of the holes 211. , And a plurality of third pads 214 arranged around the pedestal 210.
[0020]
Specifically, two recesses 212 are formed on both sides of each hole 211. Since the third pad 214 is electrically connected to the first pad 213 by a predetermined method, the controller 400 connects the tube assembly 220 inserted into the hole 211 of the base 210 to the third pad 214 and the first pad 213. Can be driven through.
[0021]
The tube assembly 220 prefilled with a predetermined liquid is detachably disposed in the hole 211 of the pedestal 210 and is electrically connected to the hole 210 via the first pad 213. Referring to FIG. 3, each of the tube assemblies 220 includes at least one protrusion 221 corresponding to the recess 212, two second pads 222 corresponding to the first pad 213, a receptacle 223, a capillary 224, and a printed chip. A head 225 is provided.
[0022]
Specifically, the protrusion 221 engages with the recess 212 of the pedestal 210. The second pad 222 contacts the first pad 213 when the tube assembly 220 is inserted into the hole 211 of the base 210. The receiving port 223 having the passage 2231 is provided with a protrusion 221 and a second pad 222. A capillary tube 224 for receiving liquid is disposed in the receiving port 223 at one end of the passage 2231. A print chip head 225 disposed in the receiving port 223 at the other end of the passage 2231 is adjacent to the second pad 222 and communicates with the capillary 224. Since the print chip head 225 is provided with a nozzle 2251 that communicates with the capillary tube 224, the liquid contained in the capillary tube 224 can be dispensed through the nozzle 2251. With this arrangement, the tube assembly 220 delivers liquid through the pedestal 210.
[0023]
It is noted that the liquid received in the capillary 224 is held by a frictional force between the surface properties of the capillary 224 and the surface tension of the reagent. In order to increase the frictional force, a gel-like or oily substance can be added to the filled end of the capillary 24 so that the reagent does not leak from the filled end of the capillary 24. Furthermore, gel or oily materials will not mix with the reagents.
[0024]
In addition, each tube assembly 220 is marked with a code 226 indicating the type of liquid contained therein. The pedestal 210 is provided with a first detector (not shown) for detecting the amount of liquid. Furthermore, each tube assembly 220 is provided with a second detector (not shown) for detecting the amount of liquid remaining in the tube.
[0025]
The tube assembly 220 may be a pulse pressure ink jet type, a bubble jet (registered trademark) ink jet type, or a slit jet ink jet type.
[0026]
The microdispenser of the present invention has the following advantages.
[0027]
1. By separating the protrusion 221 and the recess 212, the tube assembly 220 can be replaced after the liquid contained in the capillary 224 has flowed out. It is also noted that the tube assembly 220 can also be replaced for various requirements. Furthermore, a predetermined amount of tube assembly can be preset in a single setting. Thus, one set of tube assemblies can be replaced at a time.
[0028]
2. Since the liquid is prefilled in the tube assembly 220, the entire tube assembly 220 can be replaced directly if the liquid must be replaced.
[0029]
3. Because no cleaning and refilling is required, the microdispenser of the present invention can avoid the problem of cross-contamination.
[0030]
Referring to FIG. 4, a dispensing device 500 for biochemical analysis includes a controller 400 and at least one microdispenser 200. The controller 400 allows the dispensing device 500 to control one or more microdispensers 200 simultaneously. In biochemical analysis, the microdispenser 200 dispenses a predetermined amount of a predetermined reagent onto the substrate 410. Microdispenser 200 is electrically connected to controller 400 through electric wire 420. The tube assembly 220 is pre-filled with a predetermined reagent and delivers the reagent through the pedestal 210 when the pedestal faces the substrate 410.
[0031]
With the dispensing device 500 disclosed in the present invention, an analytical evaluation means or kit used in biochemical analysis can be conveniently manufactured with a high yield.
[0032]
Although the invention has been shown and described in detail with reference to preferred embodiments, it will be readily appreciated by those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention. Will. It is intended that the claims be construed to include the disclosed aspects, alternative aspects previously discussed and all equivalents thereto.
[0033]
【The invention's effect】
ADVANTAGE OF THE INVENTION According to this invention, the microdispenser provided with the exchangeable capillary tube arrange | positioned with a high-density arrangement | sequence, and can avoid the problem of cross contamination can be provided.
[Brief description of the drawings]
FIG. 1 is a schematic perspective view showing an embodiment of a microdispenser of the present invention.
FIG. 2 is a schematic perspective view of the microdispenser of FIG. 1 as viewed from below.
3 is an exploded perspective view of the tube assembly of FIG. 1. FIG.
FIG. 4 is a schematic perspective view showing an embodiment of a dispensing apparatus for biochemical analysis of the present invention.
FIG. 5 is a schematic front view of a conventional dispenser.
6 is a cross-sectional view of the dispenser shown in FIG.
FIG. 7 is a schematic process diagram of a system for manufacturing a conventional array.
FIG. 8 is a side view of another conventional dispensing device.
FIG. 9 is a diagram showing a process of supplying a fixed volume of beads onto a hydrophobic surface using the dispenser of FIG. 8;
10 is a diagram showing a process of supplying a constant volume of beads onto a hydrophobic surface using the dispenser of FIG. 8; FIG.
11 is a diagram showing a process of supplying a constant volume of beads onto a hydrophobic surface using the dispenser of FIG. 8;

Claims (20)

A microdispenser for dispensing a predetermined amount of liquid under the control of a controller,
A pedestal having a plurality of holes and electrically connected to the controller;
An array of tube assemblies prefilled with a predetermined liquid, removably placed in the hole, individually electrically connected to the pedestal, and capable of delivering and exchanging liquid under the control of the controller; Consists of
Each of the tube assemblies includes
A receiving port having a passage;
A capillary for holding a liquid provided at one end of the passage in the receptacle; and a print chip head provided at the other end of the passage in the receptacle and communicating with the capillary. A microdispenser further provided. The pedestal is provided with at least one recess formed adjacent to each hole, and each of the receptacles of the tube assembly has at least one corresponding to the at least one recess for engaging the pedestal. The microdispenser according to claim 1, wherein one protrusion is provided. A microdispenser for dispensing a predetermined amount of liquid under the control of a controller,
A pedestal having a plurality of holes, electrically connected to the controller, and provided with at least one first pad individually disposed in each of the holes;
It consists of an array of tube assemblies that are pre-filled with a predetermined liquid, are removably placed in the holes, are individually electrically connected to the pedestal, and are capable of delivering and replacing liquid under the control of a controller. ,
Each of the tube assemblies includes
A receptacle provided with at least one second pad that has a passage and corresponds to the first pad when the tube assembly is inserted into the hole of the base;
A capillary for holding a liquid, provided at one end of the passage in the receptacle;
A microdispenser further provided with a print chip head provided at the other end of the passage in the receiving port, contacting the second pad, and communicating with the capillary. A microdispenser for dispensing a predetermined amount of liquid under the control of a controller,
A pedestal having a plurality of holes, electrically connected to the controller, each provided with at least a recess and at least one first pad;
It consists of an array of tube assemblies that are pre-filled with a predetermined liquid, are removably placed in the holes, are individually electrically connected to the pedestal, and are capable of delivering and replacing liquid under the control of a controller. ,
Each of the tube assemblies includes
At least one protrusion corresponding to the recess is formed for engaging the tube assembly and the pedestal, and the tube assembly corresponds to the first pad and the tube assembly corresponds to the hole of the pedestal. A receptacle provided with at least one second pad that comes into contact with the first pad when inserted into
A capillary for holding a liquid, provided at one end of the passage in the receptacle;
A microdispenser further provided with a print chip head provided at the other end of the passage in the receiving port, contacting the second pad, and communicating with the capillary. The microdispenser according to claim 1 , wherein each of the tube assemblies is marked with a code indicating the type of liquid contained therein. The microdispenser according to claim 1 , wherein the pedestal is provided with a first detector for detecting the amount of liquid. The microdispenser according to claim 1 , wherein each tube assembly is provided with a second detector for detecting the amount of liquid remaining in the capillary tube. The microdispenser according to claim 1 , wherein the tube assembly is a pulse pressure ink jet type. The microdispenser according to claim 1 , wherein the tube assembly is a bubble jet (registered trademark) type ink jet type. The microdispenser according to claim 1 , wherein the tube assembly is of a slit jet type ink jet type. A dispensing device for biochemical analysis comprising a controller and at least one microdispenser electrically connected to the controller for dispensing a predetermined amount of a reagent to a substrate used in biochemical analysis, ,
The microdispenser has a plurality of holes and is electrically connected to the controller;
Pre-filled with a predetermined liquid, removably placed in the hole, individually electrically connected to the pedestal, and when the pedestal faces the substrate, the liquid can be sent and replaced under the control of the controller An array of tube assemblies,
Each of the tube assemblies includes
A receptacle having the above;
A capillary provided at one end of the passage in the receptacle for holding liquid;
A dispensing device further comprising: a print chip head provided at the other end of the passage in the receiving port and communicating with the capillary. The pedestal is provided with at least one recess formed adjacent to each hole, and each of the receptacles of the tube assembly has at least one corresponding to the at least one recess for engaging the pedestal. 12. The dispensing device according to claim 11, wherein one projection is provided. A dispensing device for biochemical analysis comprising a controller and at least one microdispenser electrically connected to the controller for dispensing a predetermined amount of a reagent to a substrate used in biochemical analysis, ,
The microdispenser has a plurality of holes, is electrically connected to a controller, and is provided with at least one first pad disposed individually in each of the holes;
It consists of an array of tube assemblies that are pre-filled with a predetermined liquid, are removably placed in the hole, are individually electrically connected to the pedestal, and are capable of delivering and replacing liquid under the control of the controller. ,
Each of the tube assemblies includes
A receptacle provided with at least one second pad that has a passage and corresponds to the first pad when the tube assembly is inserted into the hole of the base;
A capillary for holding a liquid, provided at one end of the passage in the receptacle;
A dispensing device, comprising: a print chip head provided at the other end of the passage in the receptacle, contacting the second pad, and communicating with the capillary. A dispensing device for biochemical analysis comprising a controller and at least one microdispenser electrically connected to the controller for dispensing a predetermined amount of a reagent to a substrate used in biochemical analysis, ,
A pedestal having a plurality of holes, electrically connected to the controller, each provided with at least a recess and at least one first pad;
From an array of tube assemblies that are pre-filled with a predetermined liquid, removably placed in the hole, individually electrically connected to the pedestal, and sent and exchanged under the control of the controller Become
Each of the tube assemblies includes
At least one protrusion corresponding to the recess is formed to engage the tube assembly and the pedestal, and the tube assembly corresponds to the first pad. A receptacle provided with a second pad that comes into contact with the first pad when inserted into
A capillary for holding a liquid, provided at one end of the passage in the receptacle;
A dispensing device further comprising a print chip head provided at the other end of the passage in the receiving port, contacting the second pad, and communicating with the capillary. 15. The dispensing device according to claim 11 , wherein each of the tube assemblies is marked with a code indicating the type of liquid contained therein. The dispensing device according to claim 11 , wherein the pedestal is provided with a first detector for detecting the amount of liquid. The dispensing device according to claim 11 , wherein each tube assembly is provided with a second detector for detecting the amount of liquid contained in the capillary tube. The dispensing device according to claim 11 , wherein the tube assembly is of a pulse pressure type ink jet type. The dispensing device according to claim 11 , wherein the tube assembly is a bubble jet (registered trademark) ink jet type. The dispensing device according to claim 11 , wherein the tube assembly is a slit jet type ink jet type.

Images