KR102515270B1 - Apparatus for analyzing cell characteristics using bio-chip - Google Patents

Abstract

The present invention relates to an apparatus for analyzing a cell using a biochip, the apparatus comprising: the biochip including a sample chamber configured to accommodate a sample, a hydrodynamic coupling region connected to the sample chamber and a sheath solution supply channel and configured to mix the sample discharged from the sample chamber with the sheath solution supplied through the sheath solution supply channel, and a biochip outlet channel configured to discharge the mixed sample and sheath solution from the hydrodynamic coupling region; one or more laser light sources configured to irradiate laser light from a side of the biochip toward at least one of the sample channel, the coupling region, and the biochip outlet channel; and one or more photosensors configured to capture scattered light generated by at least one of the sample channel, the hydrodynamic coupling region, and the biochip outlet channel by irradiation of the laser light. According to the present invention, the apparatus can have a structure optimized to enable cell analysis.

Description

Cell analysis device using a biochip {APPARATUS FOR ANALYZING CELL CHARACTERISTICS USING BIO-CHIP}

The present disclosure relates to a cell analysis device using a biochip, and more specifically, to a cell analysis device using a biochip configured to efficiently perform cell counting, cell characterization, and the like.

In general, a bio-chip is a chip that arranges biomaterials such as DNA, proteins, and cells in an array or other various forms on a substrate such as plastic or glass, and checks the presence or absence of substances that bind or react with them. it means. Recently, as various immunodiagnostic or molecular diagnostic techniques have been proposed due to the rapid development of biotechnology, it has become important to simultaneously process various types of cell, genetic information, or protein information. Biochip-related technologies are developing rapidly.

On the other hand, a flow cytometer quickly measures each particle or cell when a particle or cell in a fluid state passes through a certain sensing point, and measures the size of the cell, the degree of composition inside the cell, and the recognition of cell function. It is a device that can simultaneously measure various characteristics of cells and, in some cases, select and sort specific cells. In general, a flow cytometer has a feature of measuring and analyzing cells of a cell population to be measured one by one. In order to detect particles or cells in a fluid state using a flow cytometer, labeling of a fluorescent dye such as an antibody labeled with fluorescence having a certain wavelength is required. In addition, as a method of detecting fluorescence, an LED or laser light source is used. For example, when a light source having a specific wavelength is irradiated to a cell displaying fluorescence, light of a level lower in energy than that of the light source may be generated from the cell. For example, when irradiated with 488 nm blue light, 520 nm green light is generated from FITC-labeled cells.

A conventional flow cytometer has a complex optical system or cell feature detection and analysis parts, such as a laser or LED emitter of various wavelengths, a light receiver that measures forward scattering after irradiating light to cells, and a light receiver of various wavelengths that measures side scatter. Since it uses, a lot of cost and effort are required to manufacture and maintain the analyzer. Therefore, the flow cytometer is burdensome for small companies or research institutes to perform biotechnology-related work or research activities using the existing flow cytometer.

Embodiments disclosed herein provide a cell analysis device using a biochip configured to efficiently perform cell counting, cell characterization, and the like. In particular, some of the embodiments of the present disclosure provide a cell analysis device using a biochip capable of precise cell analysis using side scattering and forward scattering generated by light irradiated on a cell sample to be measured.

The present disclosure may be implemented in a variety of ways, including apparatus and methods.

A cell analysis device using a biochip according to an embodiment of the present disclosure, comprising: a sample chamber configured to receive a sample, cells connected to the sample chamber and a cis fluid supply channel, and cells and cis fluid coming out of a channel (flow path) connected to the sample chamber A biochip including a hydrodynamic binding region configured to mix cis fluid supplied through a supply channel (flow path), and a biochip outlet configured to discharge the sample and cis fluid mixed in the coupling region, and a sample chamber from a side of the biochip , the hydrodynamic coupling region, and at least one of the sample chamber, the hydrodynamic coupling region, and the biochip exit channel by irradiation of one or more laser light sources and the laser beam irradiating the laser light toward at least one of the biochip exit channel, which is generated from at least one of the It includes one or more photosensors that capture scattered light.

According to one embodiment, the biochip further includes a cis fluid chamber connected to the cis fluid supply channel and configured to receive cis fluid.

According to an embodiment, an LED light source radiating light toward an upper surface of the bio-chip and an image sensor disposed on a lower surface of the bio-chip are further included.

According to an embodiment, a pin hole disposed between the bio chip and the LED light source and configured to limit a light irradiation range is further included.

According to an embodiment, one or more light-receiving elements for detecting side-scattered light generated on the upper surface of the biochip by one or more laser light sources are further included.

According to one embodiment, the image sensor detects side-scattered light or fluorescence generated on the lower surface of the biochip by one or more laser light sources, or detects a dark field image or fluorescence generated on the lower surface of the biochip by light irradiated from an LED light source. configured to detect brightfield or absorption images.

A cell analysis method using a biochip according to another embodiment of the present disclosure, comprising: a sample chamber configured to accommodate a sample, a cis fluid chamber configured to accommodate a cis fluid, and connected to the sample chamber and the cis fluid chamber, the sample chamber and the cis fluid Prepare a biochip including a channel (flow path) moving from the chamber, a hydrodynamic binding area configured to mix the cis fluid, and a biochip outlet configured to discharge the sample and cis fluid mixed in the hydrodynamic coupling area irradiating a laser light from the side surface of the biochip toward at least one of the sample chamber, the hydrodynamic coupling area, and the exit channel of the biochip by means of one or more laser light sources; and by one or more photo sensors, one or more laser beams. and photographing scattered light generated from at least one of the sample chamber, the hydrodynamic coupling region, and the exit channel of the biochip by irradiation of a light source.

According to various embodiments of the present disclosure, a cell analysis device has a structure optimized to enable cell analysis using a biochip having a relatively simple configuration and function and a cell detection sensor.

According to various embodiments of the present disclosure, a cell analysis device using a biochip selectively or comprehensively analyzes various characteristics of a cell sample by using forward scattering and side scattering generated by light irradiation on the cell sample to be analyzed. can do.

According to various embodiments of the present disclosure, fluorescence emission through a laser light source can be efficiently detected by using an image sensor and an optical sensor closely disposed on a biochip without installing a complicated optical system in a cell analysis device. .

Effects of the present disclosure are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description below.

1 is a diagram showing an example of a cell analysis device using a biochip according to an embodiment of the present disclosure.
2 is a diagram illustrating a cell analysis device for capturing and analyzing images of cells by an LED light source according to an embodiment of the present disclosure.
3 is a diagram illustrating a cell analysis device for detecting side scatter generated from cells by laser light according to an embodiment of the present disclosure.
4 shows a spectrum of fluorescence excited or scattered from cells stained with various fluorescent dyes or fluorescent substances in the biochip when laser light is irradiated toward the biochip installed in the cell analysis device according to an embodiment of the present disclosure. it is a drawing
5 is a diagram illustrating a cell analysis method using a biochip according to an embodiment of the present disclosure.

Hereinafter, specific details for the implementation of the present disclosure will be described in detail with reference to the accompanying drawings. However, in the following description, if there is a risk of unnecessarily obscuring the gist of the present disclosure, detailed descriptions of well-known functions or configurations will be omitted.

In the accompanying drawings, identical or corresponding elements are given the same reference numerals. In addition, in the description of the following embodiments, overlapping descriptions of the same or corresponding components may be omitted. However, omission of a description of a component does not intend that such component is not included in any embodiment.

Advantages and features of the disclosed embodiments, and methods of achieving them, will become apparent with reference to the following embodiments in conjunction with the accompanying drawings. However, the present disclosure is not limited to the embodiments disclosed below and may be implemented in various different forms, only the present embodiments make the present disclosure complete, and those of ordinary skill in the art to which the present disclosure belongs It is provided only to fully inform the person of the scope of the invention.

Terms used in the present disclosure will be briefly described, and the disclosed embodiments will be described in detail. The terms used in this specification have been selected from general terms that are currently widely used as much as possible while considering the functions in the present disclosure, but they may vary according to the intention of a person skilled in the related field, a precedent, or the emergence of new technology. In addition, in a specific case, there is also a term arbitrarily selected by the applicant, and in this case, the meaning will be described in detail in the description of the invention. Therefore, the terms used in the present disclosure should be defined based on the meaning of the terms and the general content of the present disclosure, not simply the names of the terms.

Expressions in the singular number in this specification include plural expressions unless the context clearly dictates that they are singular. Also, plural expressions include singular expressions unless the context clearly specifies that they are plural. When it is said that a certain part "includes" a certain component throughout the specification, it means that it may further include other components without excluding other components unless otherwise stated.

In the present disclosure, an upper part of a figure may be referred to as a “top” or “upper side” of the configuration shown in the figure, and a lower part thereof may be referred to as a “lower” or “lower side”. In addition, the portion between the upper and lower portions or the upper and lower portions of the illustrated configuration in the drawings may be referred to as “side” or “side”. Relative terms such as “upper” and “upper” may be used to describe relationships between components shown in the drawings, and the present disclosure is not limited by such terms.

Reference to "A and/or B" herein means A, or B, or A and B.

1 is a diagram showing an example of a cell analysis device 100 using a biochip according to an embodiment of the present disclosure. The cell analysis device 100 may be a device for counting cells or analyzing cell characteristics using a biochip. As shown, the cell analysis device 100 includes a biochip 110 configured to accommodate a cell sample in a fluid state, and one or more laser light sources 122, 124, and 126 radiating laser light toward the biochip 110. ), and one or more photo sensors 132 , 134 , and 136 that capture scattered light generated by irradiation of laser light in the bio chip 110 . Here, the photosensors 132, 134, and 136 may include image sensors.

The biochip 110 may be a biochip configured to allow cells or biological particles in a fluid state to pass through one or more sensing points. In addition, the biochip 110 is a microchip including a configuration in which a sample chamber, a cis fluid chamber, etc. are connected through one or more microchannels to perform microfluidic control for cell analysis, or a biomaterial implemented using MEMS or BioMEMS technology. It may be a chip, but is not limited thereto.

As shown in FIG. 1, the biochip 110 accommodates a sample to be analyzed (eg, a biological material such as a cell or protein, or micro beads for simulating or mediating a biological material). A sample chamber 112, a hydrodynamic coupling region 114 connected to the sample chamber 112 and containing a sample mixed with sheath liquid, and a sample and sheath liquid discharged from the hydrodynamic coupling region 114 The biochip outlet channel 116 may be included. When a sample is introduced into the sample chamber 112 , the sample may be discharged to the hydrodynamic coupling region 114 along a channel connected to the sample chamber 112 by a constant pressure applied to the sample chamber 112 . The cis fluid is supplied from a cis fluid chamber or a cis fluid tank installed inside or outside the biochip 110 to the cis fluid inlet, and may be injected into the hydrodynamic coupling region 114 through a channel connected to the cis fluid inlet. . According to this configuration, each cell or sample discharged from the sample chamber 112 may be surrounded by cis fluid and discharged from the coupling region 114 . The sample and the cis fluid mixed in the binding area 114 may be discharged through the biochip outlet channel 116 .

The sample chamber 112 is a configuration for accommodating a sample and may have an overall substantially rectangular shape having a thickness smaller than that of the biochip 110, but is not limited thereto. In addition, one side of the sample chamber 112 may be connected to the sample inlet 113 through which a sample is supplied through a microchannel. A sample may be injected through the sample inlet 113 using a separate sample supply device such as a pipette. In addition, a first pump (not shown) may be connected to or mounted to the sample inlet 113 . The first pump may generate air pressure and supply it to the sample inlet 113 to induce the sample in the sample chamber 112 to be discharged or moved to the outside. Through this configuration, the sample supplied to the sample chamber 112 through the sample inlet 113 can be effectively discharged from the sample chamber 112 toward the hydrodynamic coupling region 114 by the first pump. For example, the first pump may be a micro-pump or a piezoelectric pump implemented using MEMS technology. In this way, when the first pump is implemented as a piezoelectric pump, a configuration capable of generating air pressure for the sample chamber 112 can be configured within the biochip 110 without being separately configured from the biochip 110 .

The cis fluid injection port 115 may include an opening for injecting cis fluid. When cis fluid is injected through the cis fluid injection port 115 , the corresponding cis fluid may be discharged to the hydrodynamic coupling region 114 through a microchannel (ie, a cis fluid supply channel). The cis fluid discharged to the hydrodynamic coupling region 114 as described above may be mixed with the sample discharged from the sample chamber 112 in the hydrodynamic coupling region 114 . That is, the cis fluid may be mixed with the samples in the coupling area 114 to cover each sample discharged from the sample chamber 112 . In addition, the sample and cis fluid mixed in the hydrodynamic coupling area 114 may be discharged to the outside of the biochip 110 through the biochip outlet channel 116 .

According to an embodiment, a cis fluid chamber and a second pump may be installed outside the biochip 110 . For example, the cis fluid chamber may be manufactured or provided separately from the biochip 110 and connected to the cis fluid inlet 115 from the outside of the biochip 110 through a channel or passage for supplying cis fluid. In another example, the cis fluid chamber may be formed inside the biochip 110 . In this case, the cis fluid chamber may be configured to have a substantially polygonal or circular shape with a thickness smaller than that of the biochip 110 . Also, a second pump may be connected to one side of the cis fluid chamber. The second pump may generate air pressure to supply the cis fluid in the cis fluid chamber to the cis fluid inlet 115 . For example, the second pump may be a micro pump or a piezoelectric pump implemented using MEMS technology. In this way, when the second pump is implemented using a piezoelectric pump, a configuration capable of generating air pressure for the cis liquid chamber can be configured within the biochip 110 without the need to be configured separately from the biochip 110 .

Additionally, an acoustic vibration element configured to generate acoustic vibration toward the hydrodynamic coupling area 114 may be further disposed. The acoustic vibration device may generate vibration or sound waves for inducing binding of the sample and the cis fluid. Samples and cis fluid supplied from each of the sample chamber 112 and the cis fluid chamber to the hydrodynamic coupling area 114 are effectively collided with each other and arranged repeatedly by acoustic vibration, passing through the biochip exit channel 116 one by one. can be discharged in a state of being wrapped in cis fluid and arranged in a line. For example, the acoustic vibration element may include a piezoelectric vibration element implemented using MEMS technology or an acoustic speaker. According to the above configuration, the sample and the cis fluid supplied to the hydrodynamic coupling region 114 collide and mix with each other by the acoustic vibration generated by the acoustic vibration element, and among them, the sample (or the cells in the sample) is the cis fluid They may be aligned in a line within the biochip and discharged through the biochip outlet channel 116 . The samples arranged in a row and discharged through the biochip outlet channel 116 may be detected for counting and characteristic analysis of the samples by a separately installed light source, photosensor, light receiving device, or image sensor.

The laser light sources 122, 124, and 126 include a first laser light source 122 for irradiating cross-sectional light toward the side of the sample chamber 112 and a laser light toward the side of the hydrodynamic coupling region 114. At least one of a second laser light source 124 for radiating laser light toward the side of the biochip exit channel 116 and a third laser light source 126 for radiating laser light. In FIG. 1 , the laser light sources 122 , 124 , and 126 are illustrated as including three light sources, but are not limited thereto. The laser light sources 122 , 124 , and 126 may include one or two light sources according to design requirements of the cell analysis device 100 .

The first laser light source 122 may radiate laser cross-sectional light having a predetermined cross-sectional shape (eg, an elongated rectangle) toward the side of the sample chamber 112 . The cross-sectional light may cause forward scattering when irradiated to the sample in the sample chamber 112 . Here, the sample may be a sample previously stained with a fluorescent material. In one embodiment, the first laser light source 122 may generate cross-sectional light having a wavelength of 488 nm.

The second laser light source 124 may radiate laser light toward the side of the hydrodynamic coupling region 114 or the side of the channel between the sample chamber 112 and the hydrodynamic coupling region 114 . The second laser light source 124 may irradiate laser light to the sample and the cis fluid existing in the hydrodynamic coupling region 114 to generate forward scattered light and side scattered light from at least one of the sample and the cis fluid. In one embodiment, the second laser light source 124 may be a point-shaped laser light having a wavelength of 488 nm or a single-sided laser beam. When using a single-sided laser beam as the second laser light source 124 (described below with reference to FIG. 2 ), fluorescence or a fluorescence-dyed sample can be easily detected by an image sensor.

The third laser light source 126 may radiate laser light toward the side of the biochip exit channel 116 . The third laser light source 126 may irradiate laser light toward the sample and the cis fluid moving in a line arrangement through the biochip exit channel 116 to generate forward scattered light and side scattered light from the sample. In addition, the third laser light source 126 may use a wavelength different from that of the second laser light source 124 in order to detect a fluorescent substance that is not detected by irradiation of the laser light of the second laser light source 124 . In one embodiment, the third laser light source 126 may be a point-shaped cross-sectional laser light having a wavelength of 638 nm.

The photosensors 132 , 134 , and 136 may be components for sensing scattering of light generated by the laser light sources 122 , 124 , and 126 . The photo sensors 132, 134, and 136 may be implemented as a photodiode, a silicon photo multiplier (SiPM), a multi pixel photon counter (MPPC), an image sensor, a CMOS sensor, and the like.

The photo sensors 132 , 134 , and 136 may include a first photo sensor 132 for detecting forward scattered light generated by cross-sectional light irradiated onto the sample chamber 112 . In addition, the photo sensors 132, 134, and 136 detect the state of the sample in the channel between the sample chamber 112 and the hydrodynamic coupling region 114 or the combined state of the sample and the sheath solution in the hydrodynamic coupling region 114 Alternatively, a second photo sensor 134 may be included to detect forward scattering generated by the laser light irradiated onto the sample and/or the cis solution. The photo sensors 132, 134, and 136 are arranged in a row through the biochip exit channel 116 to sense the mixed sample and cis fluid discharged, or to detect the sample and/or the cis fluid generated by the laser beam irradiated onto the sample and/or the cis fluid. A third photo sensor 136 for detecting scattering may be included.

2 is a diagram illustrating a cell analysis device 200 for photographing and analyzing a cell image by an LED light source according to an embodiment of the present disclosure. As shown, the cell analysis device 200 adjusts the LED light source 220 for radiating light toward the upper surface of the biochip 210 and the coherence and illuminance of the light emitted from the LED light source 220. An image sensor 240 disposed on the lower surface of the biochip 210 to detect an image of a cell generated by light emitted from the pin hole 230 and the LED light source 220 towards the biochip 210. ) may be included. For example, the biochip 210 may include the same configuration as the biochip 110 shown in FIG. 1 .

The LED light source 220 may be positioned on the upper surface of the bio-chip 210 to irradiate LED light toward the bio-chip 210 . For example, the LED light source may be a UV (ultraviolet ray) light source, a light source generating visible light, or a light source generating infrared light. Light radiated from the LED light source 220 toward the biochip 210 generates a darkfield or brightfield image, a shadow image, or an absorption image of cells included in the biochip 210 or cells in a fluid state, or fluorescence. , forward scattered light and/or side scattered light. For example, a shadow image or forward scattered light may be detected by the image sensor 240 configured on the lower surface of the biochip 210 . Meanwhile, the side scattered light may be detected by one or more photo sensors as shown in FIG. 1 .

The pin hole 230 is located between the bio chip 210 and the LED light source 220, and may be configured to adjust coherence, illuminance, and range of light emitted from the LED light source 220. The hole of the pin hole 230 may be a minute hole having a size of nm to μm. For example, the pin hole 230 is used when capturing a dark field image, and may be separated from the LED light source 220 or moved to the side of the LED light source 220 when capturing a bright field image.

The image sensor 240 may be disposed close to the lower surface of the biochip 210 . For example, the image sensor 240 may be implemented as a complementary metal-oxide semiconductor (CMOS) image sensor or a charge coupled device (CCD) sensor. The image sensor 240 may detect a shadow image or scattered light of a cell generated by the LED light source 220 or side-scattered light generated by the laser light source shown in FIG. 1 .

2 illustrates that the LED light source 220 and the image sensor 240 are respectively disposed above and below the biochip 210 inside the cell analysis device 200, but is not limited thereto. One or more laser light sources as shown in FIG. 1 may be installed on one side of the biochip 210, and one or more photosensors may be installed on the other side of the biochip 210 facing the same.

FIG. 3 is a diagram illustrating a cell analysis device 300 for detecting side-scattered light generated from cells by laser light according to an embodiment of the present disclosure. As shown, the cell analysis device 300 is disposed on the upper side of the biochip 210 and detects side-scattered light generated from cells included in the biochip 210 by a laser light source at least one light receiving element ( 310, 320, 330) may be included. In this case, the laser light source may be disposed on the side surface of the bio-chip 210 to emit cross-section light or point-shaped laser light toward the side surface of the bio-chip 210 . One or more light-receiving elements 310, 320, and 330 are configured to detect side scattered light generated from the upper surface of the bio-chip 210 when a laser light source irradiates laser light toward the side of the bio-chip 210. It can be placed on the upper side of (210). For example, the biochip 210 may include the same configuration as the biochip 110 shown in FIG. 1 .

The image sensor 240 may be disposed close to the lower surface of the biochip 210 . For example, the image sensor 240 may be implemented as a CMOS image sensor. The image sensor 240 may detect a shadow image of a cell generated by an LED light source or side-scattered light of a cell generated by a laser light source.

Although FIG. 3 shows three light receiving elements 310, 320, and 330, it is not limited thereto and may be configured to include any number of light receiving elements. For example, the light-receiving elements 310, 320, and 330 use an optical sensor such as a photomultiplier (PMT), a multi-pixel photon counter (MPPC), or a silicon photo multiplier (SiPM) having high sensing performance, and an image sensor. Samples can be observed more precisely.

In addition, although FIG. 3 shows that the light receiving elements 310, 320, and 330 and the image sensor 240 are respectively disposed on the upper and lower sides of the biochip 210 inside the cell analysis device 300, it is limited thereto. it is not going to be One or more laser light sources as shown in FIG. 1 may be installed on one side of the biochip 210, and one or more photosensors may be installed on the other side of the biochip 210 facing the same.

4 is a spectrum of fluorescence excited or scattered from cells stained with various fluorescent dyes or fluorescent substances in the biochip when laser light is irradiated toward the biochip installed in the cell analysis device according to an embodiment of the present disclosure (400 ) is a drawing showing.

As shown, cells stained with various fluorescent dyes may have different fluorescence detected as they are irradiated with laser light of different wavelengths. For example, when cells stained with FITC (S410) are irradiated with a laser light having a wavelength of 488 nm (blue light), fluorescence of a wavelength of 520 nm (green light) is excited and generated. In addition, cells stained with PerCP or PerCPCy5.5 (S420) are excited by both 88 nm laser light and 638 nm laser light, and red fluorescence is generated. In addition, when the cells stained with DAPI (S430) are irradiated with a 355nm UV laser or a 365nm LED light source instead of a 488nm wavelength laser light, fluorescence around 450nm, which is blue light, is excited and generated.

For example, when cells stained with various fluorescent dyes included in the biochip 110 are irradiated with the laser light sources 122, 124, and 126 described with reference to FIG. 1, the graph S410 shows a wavelength of 488 nm. It can represent the intensity or spectrum distribution of fluorescence generated by the first laser light source 122, which is a cross-sectional laser light source having . The detection result of fluorescence generated from the cells stained with FITC (S410) as described above can be used to count the number of cells with a hemocytometer or to extract cell characteristics. Meanwhile, the graph S420 may represent intensity or spectrum distribution of fluorescence generated by the laser light sources 122, 124, and 126 having a wavelength of 488 nm or 638 nm. In addition, the graph S430 may represent intensity or spectrum distribution of fluorescence generated by the laser light sources 122 , 124 , and 126 having a wavelength of 355 nm or 365 nm.

5 is a diagram illustrating a cell analysis method 500 using a biochip according to an embodiment of the present disclosure. The cell analysis method 500 using a biochip may begin with preparing a biochip including a sample chamber, a hydrodynamic coupling region, and a biochip outlet channel (S510). When a sample is injected into the biochip, it is discharged into the sample chamber, and then the sample and the cis fluid may be mixed in a hydrodynamic coupling area. The mixed or combined sample and cis fluid may be discharged through the biochip outlet channel.

Next, laser light may be radiated from the side of the biochip toward at least one of the sample chamber, the hydrodynamic coupling region, and the biochip exit channel by a laser light source (S520). In one embodiment, referring to FIG. 1 , the first laser light source may radiate laser light toward the sample chamber. Laser light irradiated to the sample chamber is cross-sectional light, and the number of cells in the sample can be counted. The sample can then be discharged into the hydrodynamic binding area and combined with the cis fluid in the hydrodynamic binding area. The second laser light source may radiate laser light toward the hydrodynamic coupling area. Light irradiated to the hydrodynamic coupling region may cause side scattering and forward scattering. Then, the combined sample and cis fluid can be discharged through the biochip outlet channel. The third laser light source may radiate laser light toward the exit channel of the biochip. Light irradiated to the exit channel of the biochip may cause side scattering and forward scattering.

Finally, scattered light generated from at least one of the sample chamber, the hydrodynamic coupling area, and the exit channel of the biochip may be captured by irradiation of a laser light source by the photo sensor (S530). Forward scattering generated from the sample in the sample chamber by the first laser light source may be detected by the first photo sensor. Next, forward scattering generated in the hydrodynamic coupling area by the second laser light source can be detected by the second photo sensor. In addition, the second photo sensor may detect a mixed state of the sample and the cis solution in the binding region. Finally, the forward scattering generated in the exit channel of the biochip by the third laser light source is detected by the third photo sensor, and the third photo sensor can detect sample characteristics such as arrangement state or flow of the samples in the exit channel of the biochip. there is.

The previous description of the present disclosure is provided to enable any person skilled in the art to make or use the present disclosure. Various modifications of this disclosure will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied in various modifications without departing from the spirit or scope of the disclosure. Thus, this disclosure is not intended to be limited to the examples set forth herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Although this subject matter has been described in language specific to structural features and/or methodological acts. It will be understood that subject matter defined in the appended claims is not necessarily limited to the specific features or acts described above. Rather, the specific features and acts described above are described as example forms of implementing the claims.

Although the present disclosure has been described in relation to some embodiments in this specification, various modifications and changes may be made without departing from the scope of the present disclosure that can be understood by those skilled in the art. Also, such modifications and variations are intended to fall within the scope of the claims appended hereto.

100: cell analysis device
110: bio chip
112: sample chamber
114: bonding area
116: biochip exit channel
122: first laser light source
124: second laser light source
126 Third laser light source
132: first photo sensor
134: second photo sensor
136: third photo sensor

Claims (7)

As a cell analysis device using a biochip,
A sample chamber configured to receive a sample, a hydrodynamic coupling region connected to the sample chamber and the cis fluid supply channel, configured to mix the sample discharged from the outlet of the sample chamber and the cis fluid supplied through the cis fluid supply channel a biochip including a biochip outlet channel configured to discharge the sample and the cis fluid mixed in the hydrodynamic coupling region;
at least one laser light source radiating laser light from a side surface of the biochip toward at least one of the sample chamber, the hydrodynamic coupling region, and the biochip outlet channel;
at least one photo sensor for photographing scattered light generated from at least one of the sample chamber, the hydrodynamic coupling region, and the exit channel of the biochip by irradiation of the laser light;
an LED light source radiating light toward an upper surface of the biochip;
an image sensor located on a lower surface of the biochip; and
A pin hole located between the biochip and the LED light source and configured to limit the irradiation range of the light
Including, cell analysis device.
According to claim 1,
The biochip,
a cis fluid chamber connected to the cis fluid supply channel and configured to receive cis fluid;
Further comprising a, cell analysis device.
delete delete According to claim 1,
One or more light-receiving elements sensing side-scattered light generated on the upper surface of the biochip by the one or more laser light sources
Further comprising a, cell analysis device.
According to claim 1,
The image sensor detects side-scattered light or fluorescence generated on the lower surface of the bio-chip by the one or more laser light sources, or dark-field image or light generated on the lower surface of the bio-chip by light emitted from the LED light source. A cell analysis device configured to detect a field of view or absorbance image.
As a cell analysis method using a biochip,
A sample chamber configured to receive a sample, a cis fluid chamber configured to receive a cis fluid, connected to the sample chamber and the cis fluid chamber, and configured to mix the sample and the cis fluid discharged from the sample chamber and the cis fluid chamber, respectively preparing a biochip including a hydrodynamic coupling region and a biochip outlet channel configured to discharge the sample and cis fluid mixed in the hydrodynamic coupling region;
irradiating a laser light from a side surface of the biochip toward at least one of the sample chamber, the hydrodynamic coupling region, and the biochip outlet channel by one or more laser light sources; and
photographing scattered light generated from at least one of the sample chamber, the hydrodynamic coupling region, and the exit channel of the biochip by irradiation of the at least one laser light source by one or more photo sensors;
irradiating light toward an upper surface of the bio-chip using an LED light source and a pin hole disposed between the bio-chip and the LED light source and configured to limit an irradiation range of the LED light source; and
Side-scattered light or fluorescence generated on the lower surface of the bio-chip by the one or more laser light sources is sensed by an image sensor located on the lower surface of the bio-chip, or light emitted from the LED light source is applied to the lower surface of the bio-chip. detecting the resulting darkfield image or brightfield or absorption image;
Including, cell analysis method.

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