KR102874554B1 - Flow cytometer for analyzing cell characteristics - Google Patents

Abstract

The present disclosure provides a flow cytometer for cell analysis. The flow cytometer comprises a sample chamber, at least a portion of which is formed in a streamlined shape to receive a sample through a sample inlet, a biochip including a hydrodynamic coupling region configured to mix a sample discharged from an outlet of the sample chamber and a sis fluid supplied through the sis fluid supply channel, and a biochip outlet channel configured to discharge a sample and a sis fluid mixed from the hydrodynamic coupling region to a biochip outlet, a light source irradiating LED light or laser light toward at least one of the biochip outlet channel or an adjacent portion of the biochip outlet, and an image sensor or a light sensor that photographs fluorescence or scattered light generated from at least one of the sample chamber, the hydrodynamic coupling region, the biochip outlet channel, or the adjacent portion of the biochip outlet.

Description

Flow cytometer for analyzing cell characters

The present disclosure relates to a flow cytometer for cell analysis, and more particularly, to a flow cytometer configured to efficiently perform cell characteristic analysis, etc.

In general, a biochip is a chip that arranges biological substances such as DNA, proteins, and cells in an array on a substrate made of plastic, crystal, or glass, and detects the presence or absence of substances that bind or react with them. With the recent rapid advancements in biotechnology, various immunodiagnostic and molecular diagnostic techniques have been proposed, making it crucial to simultaneously process large amounts of genetic or protein information. This need has led to rapid advancements in biochip-related technologies.

Biochips can be implemented as DNA chips, protein chips, or cell chips, for example, which only contain a chip with an array of biological materials. Alternatively, biochips can be implemented as lab-on-a-chip (LOC) chips, which are configured to automatically perform analysis within the chip via microfluidics after injecting a sample (or samples). Lab-on-a-chips can be implemented using BioMEMS technology, which enables the fabrication of structures on the order of micrometers based on semiconductor manufacturing technology. Furthermore, lab-on-a-chips can reduce the amount of sample required for analysis due to the miniaturization of the chip size, thereby reducing experimental costs.

However, existing biochips lack efficient methods for maintaining fluid flow through microfluidic control, and require extensive additional equipment for continuous liquid supply. Furthermore, biochip manufacturing requires complex manufacturing equipment, which can increase production costs.

Meanwhile, sample contamination in flow cytometers for cell analysis is a critical issue for experimental reliability. Conventional flow cytometers are inherently vulnerable to sample contamination. Specifically, when placing a sample in a vial or other container in the flow cytometer's sample holder, contamination can occur during the path where the syringe pump within the flow cytometer draws the sample from the vial into the cylinder and then fluidically transports it with the sheath solution. This necessitates the cumbersome task of cleaning the flow cytometer after each experiment.

Furthermore, conventional flow cytometers can be contaminated throughout the sample acquisition process, from transporting the sample to a cylinder using a syringe pump within the flow cytometer system, to sending the sample to the biochip's sample inlet via a flow tube. During the flow cytometry process, potentially contaminated components, such as the flow tubes connected to the sample, are discarded as consumables. This increases the cost of consumables.

The present disclosure provides a flow cytometer for cell analysis to solve the above problems.

The present disclosure can be implemented in various ways, including methods and devices (systems).

A flow cytometer according to one embodiment of the present disclosure may include a biochip including a sample chamber, at least a portion of which is formed in a streamlined shape to receive a sample through a sample inlet, a hydrodynamic coupling region connected to the sample chamber and a sis fluid supply channel, configured to mix a sample discharged from an outlet of the sample chamber and a sis fluid supplied through the sis fluid supply channel, and a biochip outlet channel configured to discharge a sample and a sis fluid mixed from the hydrodynamic coupling region to a biochip outlet, a light source irradiating LED light or laser light toward at least one of the biochip outlet channel or an adjacent portion of the biochip outlet, and an image sensor or a light sensor that photographs fluorescence or scattered light generated from at least one of the sample chamber, the hydrodynamic coupling region, the biochip outlet channel, or the adjacent portion of the biochip outlet.

According to one embodiment of the present disclosure, the flow cytometer may further include a first pump connected to the sis fluid supply channel and injecting the sis fluid, and a second pump connected to the sample inlet and injecting the sis fluid for discharging a sample within the sample chamber.

According to one embodiment of the present disclosure, the pressure at which the second pump injects the sis fluid may be greater than the pressure at which the first pump injects the sis fluid.

According to one embodiment of the present disclosure, the pressure at which the second pump injects the sis fluid so that the sample is aligned in a row in the biochip outlet channel can be determined.

According to one embodiment of the present disclosure, the sample chamber may be configured in a streamlined manner in which the width of the internal space extending from the sample inlet gradually increases and then gradually decreases to approach the fluidic coupling region.

According to one embodiment of the present disclosure, an image sensor or an optical sensor can detect the number of samples or characteristics of samples in at least one of a sample chamber, a fluidic coupling region, a biochip outlet channel, or an area adjacent to a biochip outlet.

A cell analysis method using a flow cytometer according to one embodiment of the present disclosure may include the steps of preparing a sample in a sample chamber at least partially formed in a streamlined shape, inserting a biochip including the sample chamber into the flow cytometer, injecting a first cis solution through a cis solution supply channel by a first pump, injecting a second cis solution into the sample chamber through a sample inlet by a second pump, mixing a sample and the second cis solution discharged from the sample chamber with the first cis solution supplied through the cis solution supply channel by a hydrodynamic coupling region, discharging the mixed sample and cis solution in the hydrodynamic coupling region to a biochip outlet by a biochip outlet channel, irradiating LED light or laser light toward at least one of the biochip outlet channel or an adjacent portion of the biochip outlet by a light source, and photographing fluorescence or scattered light generated from at least one of the sample chamber, the hydrodynamic coupling region, the biochip outlet channel, or the adjacent portion of the biochip outlet by a light sensor or an image sensor.

According to one embodiment of the present disclosure, the method may further include a step of detecting a count of cells or a characteristic of cells in at least one of a sample chamber, a hydrodynamic coupling region, a biochip outlet channel, or an adjacent portion of a biochip outlet by an optical sensor or an image sensor.

According to one embodiment of the present disclosure, in the fluid dynamic coupling region, the samples discharged from the sample chamber can be aligned in a row depending on the amount or speed at which the second sis fluid is injected.

According to one embodiment of the present disclosure, the pressure at which the second pump injects the second sis fluid may be greater than the pressure at which the first pump injects the first sis fluid.

According to some embodiments of the present disclosure, a biochip for cell analysis can have a relatively simple structure that facilitates cell analysis. Furthermore, a sample chamber, at least partially formed in a streamlined shape, can facilitate smooth mixing of the sample and the sis fluid in a fluid-dynamic coupling region.

According to some embodiments of the present disclosure, a biochip for cell analysis may have an optimized structure for more precise cell analysis using fluorescence or scattered light generated by light irradiation of a cell sample as a target of analysis. Furthermore, by utilizing pressure, rather than air pressure, to inject the sis fluid into the sample chamber, quantitative control can be achieved so that the sample injected into the sample chamber is effectively mixed with the sis fluid in the hydrodynamic coupling region.

According to some embodiments of the present disclosure, a biochip includes a sample chamber therein, and a structure for moving the sample inside the sample chamber using a sis fluid enables complete separation of the flow cytometry system and the sample inside the biochip. Furthermore, since the sample is moved using a sis fluid transfer pump, a separate sample transfer pump may not be provided. Accordingly, since the sis fluid transfer pump is not contaminated, contamination of the sample can be prevented during the process of moving the sample inside the biochip using the sis fluid.

The effects of the present disclosure are not limited to the effects mentioned above, and other effects not mentioned can be clearly understood by a person having ordinary skill in the art to which the present disclosure belongs (referred to as “one skilled in the art”) from the description of the claims.

Embodiments of the present disclosure will be described below with reference to the accompanying drawings, wherein like reference numerals represent similar elements, but are not limited thereto.
FIG. 1 is a plan view showing an example of a biochip for cell analysis according to one embodiment of the present disclosure.
FIG. 2 is a perspective view showing an example of a biochip for cell analysis according to one embodiment of the present disclosure.
FIG. 3 is a diagram illustrating an example of a flow cytometer using a biochip for cell analysis according to one embodiment of the present disclosure.
FIG. 4 is a drawing showing an example of scattered light generated by a light source according to one embodiment of the present disclosure.
FIG. 5 is a flowchart illustrating an example of a cell analysis method according to one embodiment of the present disclosure.

Hereinafter, specific details for implementing the present disclosure will be described in detail with reference to the attached drawings. However, in the following description, specific descriptions of widely known functions or configurations will be omitted if they may unnecessarily obscure the gist of the present disclosure.

In the attached drawings, identical or corresponding components are assigned the same reference numerals. Furthermore, in the description of the embodiments below, duplicate descriptions of identical or corresponding components may be omitted. However, even if a description of a component is omitted, it is not intended that such component is not included in any embodiment.

The advantages and features of the disclosed embodiments, and the methods for achieving them, will become clearer with reference to the embodiments described below, along with the accompanying drawings. However, the present disclosure is not limited to the embodiments disclosed below and may be implemented in various different forms. These embodiments are provided solely to ensure the completeness of the disclosure and to fully inform those skilled in the art of the present disclosure of the scope of the invention.

The terms used in this disclosure will be briefly explained, followed by a detailed description of the disclosed embodiments. The terms used in this specification have been selected from widely used, current terms, taking into account the functions of the present disclosure. However, these terms may vary depending on the intentions of engineers working in the relevant field, precedents, the emergence of new technologies, etc. Furthermore, in certain cases, terms may be arbitrarily selected by the applicant, and in such cases, their meanings will be described in detail in the relevant description of the invention. Therefore, the terms used in this disclosure should not be defined simply as names of terms, but rather based on their meanings and the overall content of the present disclosure.

In this specification, singular expressions include plural expressions unless the context clearly dictates otherwise. Furthermore, plural expressions include singular expressions unless the context clearly dictates otherwise. Throughout the specification, when a part is said to "include" a component, this does not exclude other components, but rather implies that other components may be included, unless otherwise specifically stated.

In this disclosure, the upper portion of a drawing may be referred to as the "upper portion" or "upper side" of the configuration depicted in the drawing, and the lower portion thereof may be referred to as the "lower portion" or "lower side." Furthermore, the portion between the upper and lower portions of the configuration depicted in the drawing, or the portion excluding the upper and lower portions, may be referred to as the "side portion" or "side." Relative terms such as "upper portion" and "upper side" may be used to describe the relationship between the configurations depicted in the drawing, and the present disclosure is not limited by such terms.

In this specification, the description of “A and/or B” means A, or B, or A and B.

In the present disclosure, 'each of the plurality of As' or 'each of the plurality of As' may refer to each of all components included in the plurality of As, or may refer to each of some components included in the plurality of As.

FIG. 1 is a plan view showing an example of a biochip (100) for cell analysis according to one embodiment of the present disclosure, and FIG. 2 is a perspective view showing an example of a biochip (100) for cell analysis according to one embodiment of the present disclosure. The biochip (100) may be a biochip included in a flow cytometer (or cell analysis device) for performing cell counting, cell characteristic analysis, etc. In addition, the biochip (100) may be a microchip or a biochip implemented using MEMS or BioMEMS technology that includes a configuration in which a sample chamber, a sis fluid chamber, etc. are connected by one or more microchannels to perform microfluidic control for cell analysis, but is not limited thereto.

As illustrated, the biochip (100) may include a sample inlet (110) for injecting a sample to be analyzed (e.g., a biological material such as a cell or protein), a sample chamber (120) for receiving a sample injected through the sample inlet (110), a sis solution inlet (130) for injecting a sis solution, a sis solution channel (140) for supplying the sis solution injected through the sis solution inlet (130), and a fluidic coupling region (150) connected to the sample chamber (120) and the sis solution channel (140) and configured such that the sample discharged from the sample chamber (120) and the sis solution supplied through the sis solution channel (140) are mixed. Additionally, the biochip (100) may include a biochip outlet channel configured such that the sample and sis solution mixed from the fluidic coupling region (150) are discharged through a biochip outlet (170).

The sample chamber (120) is configured to accommodate a sample and may have a thickness smaller than the thickness of the biochip (100). In addition, at least a portion of the sample chamber (120) may be formed in a streamlined shape so that the sample and the sis solution are smoothly mixed in the fluidic coupling region (150). Specifically, the sample chamber (120) may be configured in a streamlined shape in which the width of the internal space extending from the sample inlet (110) gradually increases and then gradually decreases as it approaches the fluidic coupling region (150). Additionally, one side of the sample chamber (120) may be connected to the sample inlet (110) through which the sample is supplied via a microchannel. The sample may be injected through the sample inlet (110) using a separate sample supply device such as a pipette.

The sis liquid can be injected into the biochip (100) through the sis liquid supply channel. Here, the sis liquid supply channel can include a sis liquid inlet (130) and a sis liquid path (140). The sis liquid inlet (130) can include an opening for injecting the sis liquid. When the sis liquid is injected through the sis liquid inlet (130), the sis liquid can be discharged into the hydrodynamic coupling region (150) through the sis liquid path (140). The sis liquid discharged into the hydrodynamic coupling region (150) through the sis liquid path (140) in this way can be mixed with the sample discharged from the sample chamber (120) in the hydrodynamic coupling region (150).

The sample and the solution mixed in the fluid dynamic coupling region (150) can be discharged to the outside of the biochip (100) through the biochip outlet channel (160) and the biochip outlet (170). Here, the biochip outlet channel (160) can be configured so that at least a portion of the width of the biochip outlet channel (160) narrows in the direction in which the sample is discharged.

For example, after a sample and a sis liquid are mixed in a fluidic coupling region (150) connected to a biochip outlet channel (160), the mixed sample and sis liquid can flow through the biochip outlet channel (160). When the mixed sample and sis liquid are discharged through the biochip outlet channel (160), the samples surrounded by the sis liquid move dropwise while being aligned in a row, thereby enabling detection with higher precision or accuracy by a flow cytometer.

As illustrated, the biochip outlet channel (160) may be formed so that a portion connected to the hydrodynamic coupling region (150) is wide, and may include a tapered portion configured such that the width of a certain portion gradually narrows in the direction in which the sample is discharged. In addition, the biochip outlet channel (520) may be configured to have a constant width after the tapered portion. In this way, by configuring the width of at least a portion of the biochip outlet channel (520) to gradually narrow, the samples mixed with the sis fluid in the hydrodynamic coupling region (150) may be gradually arranged in a single line in the tapered portion of the biochip outlet channel (160), and then the state may be maintained constant after the tapered portion.

In one embodiment, the sis solution may be injected through the sample inlet (110). In this case, the sis solution injected through the sample inlet (110) may push the sample already injected into the sample chamber (120) toward the hydrodynamic coupling region (150). In the case of a biochip inserted into a conventional flow cytometer, a method is used in which a cell sample is injected through a sample supply channel using a pressurizing device such as a syringe pump, and at the same time, the sis solution is injected through a separate sis solution supply channel, thereby mixing and aligning the cell sample and the sis solution. However, in the case of the biochip of the present embodiment, since the sample is injected into the sample chamber (120) in advance and accommodated, a separate pressurizing process is required to discharge the sample accommodated in the sample chamber (120) through the hydrodynamic coupling region (150) and the biochip outlet channel (160). However, when air pressure is used in the separate pressurizing process, there is a problem in that quantitative injection of the sample is difficult due to air tension. In contrast, in the present embodiment, the sample can be quantitatively controlled through the sis liquid injected through the sample inlet (110) rather than through air pressure by pushing the sample already injected into the sample chamber (120) into the fluid dynamic coupling region (150). Accordingly, the samples discharged from the sample chamber (120) can be aligned in a row depending on the amount or speed at which the sis liquid injected through the sample inlet (110) is injected.

Although Fig. 1 shows a planar configuration as viewed from the top of the biochip (100), the side surface of the biochip (100) may be processed into a flat surface to prevent optical distortion. That is, in order to prevent optical distortion due to forward scattering by a light source as described below with reference to Fig. 3, the side surface of the biochip (100) may be subjected to a flat finishing or surface treatment process.

With this configuration, a biochip for cell analysis can have a relatively simple structure that facilitates cell analysis. Furthermore, by utilizing a pressurized process using a sis fluid and a sample chamber with at least a portion of a streamlined shape, the sample and sis fluid can be smoothly mixed in the fluid-mechanical bonding region.

FIG. 3 is a drawing showing an example of a flow cytometer (300) using a biochip (100) for cell analysis according to one embodiment of the present disclosure, and FIG. 4 is a drawing showing an example of scattered light (420, 430) generated by a light source (330) according to one embodiment of the present disclosure. As illustrated, the biochip (100) may include a first pump (310) connected to a sis solution inlet (130) to inject sis solution and induce fluid movement of the sis solution, and a second pump (320) connected to a sample inlet (110) to inject sis solution and induce movement of a sample within a sample chamber (120). In addition, the flow cytometer (300) may include a light source (330) that irradiates, for example, LED light or laser light toward the biochip (100) and a light sensor or image sensor (340) that photographs fluorescence or scattered light generated by irradiation of the LED light or laser light on the biochip (100). Meanwhile, the biochip (100) may include a sample chamber (120) that accommodates a sample, a hydrodynamic coupling region (150) that is connected to the sample chamber (120) and in which a sample mixed with a sis fluid exists, and a biochip outlet channel (160) through which the sample and the sis fluid are discharged from the hydrodynamic coupling region (150) to a biochip outlet (170).

The first pump (310) may be connected to the sis solution inlet (130). Here, the first pump (310) may be installed outside the biochip (100). In addition, the sis solution inlet (130) may be connected to one side of the first pump (310), and a sis solution chamber (not shown) may be connected to the other side of the first pump (310). The sis solution chamber may be manufactured or provided separately from the biochip (100) and may be connected through a channel or passage for supplying the sis solution from the outside of the biochip (100). The first pump (310) may generate air pressure to supply the sis solution in the sis solution chamber to the sis solution inlet (130). For example, the first pump (310) may be a micro pump or a piezoelectric pump implemented using MEMS technology, but is not limited thereto.

The second pump (320) may be connected to the sample inlet (110). Here, the second pump (320) may be installed outside the biochip (100). In addition, the sample inlet (110) may be connected to one side of the second pump (320), and a sis solution chamber may be connected to the other side of the second pump (320). In this case, the sis solution chambers connected to each of the first pump (310) and the second pump (320) may be different or the same. The second pump (320) may supply the sis solution to the sample inlet (110), thereby inducing the sample within the sample chamber (120) to be discharged or moved to the outside. Accordingly, the sample supplied to the sample chamber (120) through the sample inlet (110) can be effectively pushed out from the sample chamber (120) to the hydrodynamic coupling region (150) while being surrounded by the sis liquid supplied through the second pump (320). In addition, in the hydrodynamic coupling region (150), the sample mixed with the sis liquid discharged from the sample chamber (120) can be additionally mixed with the sis liquid entering the hydrodynamic coupling region (150) through the sis liquid path (140), thereby being aligned in a row while being discharged through the biochip outlet channel (160). For example, the second pump (320) may be a micro pump or a piezoelectric pump implemented using MEMS technology, but is not limited thereto.

In one embodiment, a first sis liquid may be injected into a sis liquid path (140) through a sis liquid inlet (130) by a first pump (310). In addition, a second sis liquid may be injected into a sample chamber (120) through a sample inlet (110) by a second pump (320). In this case, in the fluid dynamic coupling region (150), samples discharged from the sample chamber (120) may be aligned in a row depending on the amount or speed at which the second sis liquid is injected. In addition, the pressure at which the second pump (320) injects the second sis liquid may be greater than the pressure at which the first pump (310) injects the first sis liquid. In this way, due to the pressure difference generated by the second pump (320) and the first pump (310), the sample pushed into the fluid dynamic coupling region (150) by the second sis fluid can be mixed with the first sis fluid and discharged in a lined state within the biochip outlet channel (160).

The light source (330) can irradiate LED light or laser light toward at least one of the sample chamber (120), the hydrodynamic coupling region (150), the biochip outlet channel (160), or the adjacent portion of the biochip outlet (170). For example, the light source (330) can include a first light source for irradiating LED light or laser light toward the side of the sample chamber (120), a second light source for irradiating LED light or laser light toward the side of the hydrodynamic coupling region (150), a third light source for irradiating LED light or laser light toward the side of the biochip outlet channel (323), and a fourth light source for irradiating LED light or laser light toward the side of the adjacent portion of the biochip outlet (170). In FIG. 3, the third light source is illustrated as irradiating light toward the biochip outlet channel (323), but is not limited thereto. Additionally, the light source (330) may be further added or part of the light source may be removed depending on the design requirements of the flow cytometer (300).

The light source (330) can irradiate LED light or laser light toward at least one of the sample chamber (120), the hydrodynamic coupling region (150), the biochip outlet channel (160), or the adjacent portion of the biochip outlet (170) to generate fluorescence, forward scattered light, or side scattered light. In this case, the wavelength of the LED light or laser light irradiated by the light source (330) may vary depending on the target location. For example, when the light source (330) irradiates the LED light or laser light toward the biochip outlet channel (160), the wavelength of the LED light or laser light may be 355 nm, 488 nm, or 638 nm. As another example, when the light source (330) irradiates the LED light or laser light toward the hydrodynamic coupling region (150), the wavelength of the LED light or laser light may be 488 nm.

The light sensor or image sensor (340) can capture fluorescence or scattered light generated by the light source (330) in at least one of the sample chamber (120), the fluidic coupling region (150), the biochip outlet channel (160), or the adjacent portion of the biochip outlet (170). Here, the light sensor or image sensor can be implemented as a CMOS sensor, etc. Accordingly, the light sensor or image sensor (340) can detect the coefficient of the sample or the characteristics of the sample in at least one of the sample chamber (120), the fluidic coupling region (150), the biochip outlet channel (160), or the adjacent portion of the biochip outlet (170).

The light sensor or image sensor (340) may include a first image sensor for detecting fluorescence or scattered light generated by LED light or laser light irradiated onto the sample chamber (120). In addition, the light sensor or image sensor (340) may include a second image sensor for detecting a binding state of the sample and the sis liquid in the hydrodynamic bonding region (150) or for detecting fluorescence or scattered light generated by LED light or laser light irradiated onto the sample and the sis liquid. The light sensor or image sensor (340) may include a third image sensor for detecting a mixed sample and sis liquid that are arranged in a row and discharged through the biochip outlet channel (160) or for detecting fluorescence or scattered light generated by LED light or laser light irradiated onto the sample and the sis liquid. Additionally, the light sensor or image sensor (340) may include a fourth image sensor for detecting the mixed sample and sis fluid discharged adjacent to the biochip outlet (170), or for detecting fluorescence or scattered light generated by LED light or laser light irradiated on the sample and sis fluid.

In one embodiment, as illustrated in FIG. 4, a light sensor or an image sensor (e.g., a fourth image sensor) can detect fluorescence or scattered light (420, 430) generated by LED light or laser light irradiated on a mixed sample and sis liquid (410) discharged adjacent to a biochip outlet (170). Here, the mixed sample and sis liquid (410) may be in a form in which the sample located on the inside is surrounded by the sis liquid located on the outside. When LED light or laser light is irradiated on the mixed sample and sis liquid (410), forward scattered light (420), side scattered light (430), or fluorescence may be generated. Accordingly, based on the generated forward scattered light (420), side scattered light (430), or fluorescence, the coefficient of the sample or the characteristics of the sample can be detected and analyzed.

Although Fig. 3 shows a planar configuration as viewed from the top of a biochip (100) inserted into a flow cytometer (300), the side surface of the biochip (100) may be processed into a flat surface to prevent optical distortion. That is, in order to prevent optical distortion, etc., when irradiating LED light or laser light from a light source (330) or detecting fluorescence or scattered light generated by LED light or laser light by a light sensor or image sensor (340), the side surface of the biochip (100) may be subjected to a flat finishing treatment or surface treatment process (also known as a surface treatment process).

With this configuration, a biochip for cell analysis can have an optimized structure for more precise cell analysis using fluorescence or scattered light generated by light irradiation of the cell sample being analyzed. Furthermore, by utilizing pressure to inject the sis fluid into the sample chamber, rather than air pressure, quantitative control can be achieved to ensure that the sample injected into the sample chamber effectively mixes with the sis fluid in the hydrodynamic coupling region.

Furthermore, since the biochip includes a sample chamber within it and the structure of moving the sample within the sample chamber using a sis fluid enables complete separation of the flow cytometry system and the sample within the biochip. Furthermore, since the sample is moved using a sis fluid transfer pump, a separate sample transfer pump may not be required. Accordingly, since the sis fluid transfer pump is not contaminated, contamination of the sample can be prevented during the process of moving the sample within the biochip using a sis fluid.

FIG. 5 is a flowchart illustrating an example of a cell analysis method (500) according to one embodiment of the present disclosure. In one embodiment, the method (500) may begin by preparing a sample in a sample chamber, at least part of which is formed in a streamlined shape (S510). Thereafter, a biochip including the sample chamber may be inserted into a flow cytometer (or cell analysis device) (S520).

Thereafter, the first sis liquid can be injected into the sis liquid path through the sis liquid inlet by the first pump (S530). In addition, the second sis liquid can be injected into the sample chamber through the sample inlet by the second pump (S540). Thereafter, the sample and the second sis liquid discharged from the sample chamber and the first sis liquid supplied through the sis liquid path can be mixed by the hydrodynamic coupling region. In this case, the sample from the sample chamber can be aligned in a row in the hydrodynamic coupling region depending on the amount or speed at which the second sis liquid is injected (S550). Thereafter, the sample and sis liquid mixed in the hydrodynamic coupling region can be discharged to the biochip outlet by the biochip outlet channel (S560).

Thereafter, forward scattering or side scattering is generated by the light source, and thus, the flow cytometry and cell characteristics can be detected through the light sensor or the image sensor (S570). Specifically, the light source can irradiate LED light or laser light toward at least one of the biochip outlet channel or the adjacent portion of the biochip outlet. In addition, the light sensor or the image sensor can capture fluorescence or scattered light generated from at least one of the sample chamber, the hydrodynamic coupling region, the biochip outlet channel or the adjacent portion of the biochip outlet. Accordingly, the light sensor or the image sensor can detect the cell count or the cell characteristics in at least one of the biochip outlet channel or the adjacent portion of the biochip outlet.

While the present disclosure has been described in connection with certain embodiments herein, various modifications and variations may be made without departing from the scope of the present disclosure, which would be apparent to those skilled in the art. Furthermore, such modifications and variations are intended to fall within the scope of the claims appended to this specification.

The above preferred embodiments of the present invention are disclosed for the purpose of illustration, and those skilled in the art with ordinary knowledge of the present invention will be able to make various modifications, changes, and additions within the spirit and scope of the present invention, and such modifications, changes, and additions should be considered to fall within the scope of the patent claims.

Anyone having ordinary skill in the art to which the present invention pertains can make various substitutions, modifications, and changes within the scope that does not depart from the technical spirit of the present invention, and therefore the present invention is not limited to the above-described embodiments and the attached drawings.

100: Biochip
110: Sample inlet
120: Sample chamber
130: Syringe injection port
140: Sisac Euro
150: Hydrodynamic coupling region
160: Biochip exit channel
170: Biochip Exit

Claims (10)

As a flow cytometer for cell analysis,
A biochip comprising a sample chamber at least partially formed in a streamlined shape to receive a sample through a sample inlet, a fluid dynamic coupling region connected to the sample chamber and a sis fluid supply channel, the fluid dynamic coupling region configured to combine the sample discharged from an outlet of the sample chamber and the sis fluid supplied through the sis fluid supply channel, and a biochip outlet channel configured to discharge the combined sample and sis fluid from the fluid dynamic coupling region to a biochip outlet;
A first pump connected to the above-mentioned sisal solution supply channel and injecting sisal solution;
A second pump connected to the sample inlet and injecting a sis fluid for discharging a sample within the sample chamber;
A light source that irradiates LED light or laser light toward at least one of the biochip outlet channel or an adjacent portion of the biochip outlet; and
An image sensor or optical sensor that captures fluorescence or scattered light generated from at least one of the sample chamber, the fluidic coupling region, the biochip outlet channel, or an adjacent portion of the biochip outlet.
Including,
A flow cytometer, wherein at least one of the pressure at which the second pump injects the sis liquid so that the samples are aligned in a row in the biochip outlet channel, the amount of the sis liquid to be injected, or the speed at which the sis liquid is injected is determined.
delete In the first paragraph,
A flow cytometer, wherein the pressure at which the second pump injects the sis liquid is different from the pressure at which the first pump injects the sis liquid.
delete In the first paragraph,
A flow cytometer, wherein the sample chamber is configured in a streamlined shape in which the width of the internal space extending from the sample inlet gradually increases and then gradually decreases so as to approach the fluidic coupling region.
In the first paragraph,
A flow cytometer, wherein the image sensor or optical sensor detects the number of samples or characteristics of samples in at least one of the sample chamber, the fluidic coupling region, the biochip outlet channel, or an adjacent portion of the biochip outlet.
A cell analysis method using a flow cytometer,
A step of preparing a sample in a sample chamber, at least part of which is formed in a streamlined shape;
A step of inserting a biochip including the sample chamber into a flow cytometer;
A step of injecting a first sis fluid through a sis fluid supply channel by a first pump;
A step of injecting a second sis liquid into the sample chamber through a sample inlet by a second pump;
A step in which a sample and a second sis fluid discharged from the sample chamber and a first sis fluid supplied through the sis fluid supply channel are combined by a fluid dynamic coupling region;
A step of discharging the sample and the sis fluid mixed in the fluid dynamic coupling region to the biochip outlet through the biochip outlet channel;
A step of irradiating LED light or laser light toward at least one of the biochip outlet channel or an adjacent portion of the biochip outlet by a light source; and
A step of photographing fluorescence or scattered light generated from at least one of the sample chamber, the fluidic coupling region, the biochip outlet channel, or an adjacent portion of the biochip outlet by a light sensor or an image sensor.
Including,
A cell analysis method, wherein, in the fluid dynamic coupling region, the samples discharged from the sample chamber are aligned in a row according to at least one of the pressure at which the second sis liquid is injected, the amount or speed at which the second sis liquid is injected.
In paragraph 7,
A step of detecting the count of cells or characteristics of cells in at least one of the sample chamber, the fluidic coupling region, the biochip outlet channel, or the adjacent portion of the biochip outlet by the light sensor or the image sensor.
A cell analysis method further comprising:
delete In paragraph 7,
A cell analysis method, wherein the pressure at which the second pump injects the second sis liquid is different from the pressure at which the first pump injects the first sis liquid.