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WO2019088445A1 - Immune cell diagnostic chip - Google Patents

Immune cell diagnostic chip Download PDF

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Publication number
WO2019088445A1
WO2019088445A1 PCT/KR2018/010975 KR2018010975W WO2019088445A1 WO 2019088445 A1 WO2019088445 A1 WO 2019088445A1 KR 2018010975 W KR2018010975 W KR 2018010975W WO 2019088445 A1 WO2019088445 A1 WO 2019088445A1
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WIPO (PCT)
Prior art keywords
immune
immune cell
immune cells
substance
unit
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Ceased
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PCT/KR2018/010975
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French (fr)
Korean (ko)
Inventor
양성
김한별
최종찬
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Gwangju Institute of Science and Technology
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Gwangju Institute of Science and Technology
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Publication of WO2019088445A1 publication Critical patent/WO2019088445A1/en
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/505—Cells of the immune system involving T-cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/554—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being a biological cell or cell fragment, e.g. bacteria, yeast cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances

Definitions

  • the present invention relates to an immune cell diagnostic chip for producing immune cells for enhancing the immune function of cancer patients by analyzing antigen responses of the immune cells based on immune cells of cancer patients.
  • Nanobiochip is a nanotechnology integrated with biochip. Nano-biochip technology combines nanotechnology (NT) and biotechnology (BT) to produce a variety of genes (DNA, RNA), proteins, cells and various metabolites on a chip By sensing directly with various sensors and various preprocessing functions, it is possible to diagnose diseases faster and more accurately, thereby contributing to the eradication of human diseases and quality improvement of healthy life.
  • This nano-biochip has advantages such as small size, low price, high performance, high integration, low power, relatively small amount of sample, fast reaction time and analysis time compared to micro-biochip. And is rapidly growing, expecting to make innovative changes in various fields such as life sciences, medicine, pharmacy, and clinical.
  • the present inventors have sought to develop a method of overcoming cancer by improving immune function in cancer patients.
  • an immune cell was collected from the cancer patient's body, and a chip was detected that detects immune cells effectively acting on the cancer of the cancer patient based on the collected immune cells.
  • a chip was detected that detects immune cells effectively acting on the cancer of the cancer patient based on the collected immune cells.
  • an immune cell diagnostic chip for analyzing an antigenic reaction of an immune cell based on immune cells of a cancer patient to enhance the immune function of the cancer patient
  • a method for producing immune cells comprising: a substrate; and a plurality of immune cell analysis units arranged on the substrate, wherein the immune cell analysis unit comprises: a capturing unit capturing the immune cells; And a detection unit for detecting the immunologically active substance.
  • the capturing unit may include an immobilization unit for immobilizing the immune cells to capture the immune cells.
  • the fixing unit may include a first fixing pin and a second fixing pin spaced apart from the first fixing pin.
  • the immune cells may be trapped between the first fixing pin and the second fixing pin.
  • the immune cells and the antigen are located in the capturing portion, and the interaction between the immune cells and the antigen can be performed.
  • the immunoactive substance is secreted by the interaction, and the immunoactive substance can move to the detection unit.
  • the detection unit can detect each of the plurality of substances.
  • the detection unit may include at least one protein marker that recognizes the immunoactive substance.
  • the detection unit may detect each of the plurality of substances by matching with any one of at least one protein included in the protein label.
  • the immunocyte analysis unit may include a plurality of detection units, wherein each of the plurality of detection units may be located adjacent to the capturing unit.
  • each of the plurality of detection units detects the immunoactive substance at a time interval, detects the immunoactive substance from any one of the plurality of detection units, and detects the immunoactive substance from another one of the plurality of detection units after a predetermined time interval
  • the secreted immunologically active substance can be detected.
  • the substance supply unit is configured to dissolve the immune cells and to immobilize a substance for amplifying the amount of remaining genes in the dissolved immune cells, To the analysis unit.
  • an immune cell diagnostic chip for producing an immune cell for enhancing the immune function of the cancer patient by analyzing the antigen response of the immune cell based on the immune cell of the cancer patient.
  • FIG. 1 is a plan view of an immune cell diagnostic chip according to an embodiment of the present invention.
  • FIG 2 shows an immunocyte analysis unit included in an immune cell diagnostic chip.
  • 3 is an exemplary illustration of the protein label of the detection unit included in the immune cell analysis unit.
  • FIG. 4 illustrates a detection process of the detection unit.
  • FIG. 5 shows dissolution of immune cells to analyze cell composition.
  • Figure 6 shows amplification of the amount of gene in dissolved immune cells and analysis of the base sequence.
  • Figure 7 shows the steps of capturing and analyzing immune cells in accordance with the present invention.
  • FIG. 1 is a plan view of an immune cell diagnostic chip according to an embodiment of the present invention
  • FIG. 2 is an immunocyte analysis unit included in an immune cell diagnostic chip
  • FIG. ≪ / RTI &gt is an immunocyte analysis unit included in an immune cell diagnostic chip
  • the immune cell diagnostic chip 10 of the present invention analyzes the antigenic reaction of the immune cells on the basis of the immune cells of a cancer patient to prepare an anti-cancer immune cell for enhancing the immune function of the cancer patient It is used in the method to do.
  • the immune cell diagnostic chip 10 may include a substrate 20, and a plurality of immune cell analysis units 100 arranged on the substrate 20.
  • the substrate 20 may be made of, for example, glass.
  • the immune cells collected from the cancer patient are captured and distributed in each of the immune cell analysis units 100 arranged on the substrate 20.
  • a plurality of immune cell analysis units 100 arranged on a substrate 20 of an immune cell diagnostic chip 10 includes a capturing unit 110 for capturing immune cells, And a detection unit 120 for detecting the secreted immunoactive substance.
  • a plurality of conductive patterns 101 of the immune cell analysis unit 100 can be formed.
  • the conductive pattern 101 may function as an electrode in the immune cell analysis unit 100.
  • the immunoactive substance secreted from the T-cell or the T-cell by the conductive pattern 101 can move to the neighboring conductive pattern 101.
  • the conductive pattern 101 is formed of a conductive material, and a magnet or a polymer pattern may be added.
  • the conductive pattern may be formed by a known patterning technique, such as a patterning method using a mask, or an inkjet printing technique.
  • the capturing unit 110 captures immune cells (T-cells) and immobilizes immune cells (T-cells) on the substrate 20.
  • the capturing unit 110 is included in each of the plurality of immune cell analysis units 100.
  • the immune cells (T-cells) are supplied from one side of the substrate 20, and the details thereof are beyond the scope of the present invention, and a detailed description thereof will be omitted.
  • the capturing unit 110 may include fixing units 111 and 112 for fixing immune cells (T-cells) to capture immune cells (T-cells) supplied from one side of the substrate.
  • the fixing parts 111 and 112 may be formed of a material such as a polymer material, a magnet material, or an optical structure.
  • the fixing parts 111 and 112 may include a first fixing pin 111 and a second fixing pin 112 to effectively capture the immune cells (T-cell).
  • the second fixing pin 112 and the first fixing pin 111 are spaced apart from each other.
  • the distance between the first fixing pin 111 and the second fixing pin 112 is the widest at the portion where the T-cell is introduced.
  • the distance between the first fixing pin 111 and the first fixing pin 111 increases as the distance from the inflow portion increases.
  • the second fixing pin 112 is narrowed.
  • the immune cells (T-cell) can be more effectively captured in the capturing part 110.
  • the immune cells (T-cell) are trapped between the first fixing pin 111 and the second fixing pin 112, and the distance between the first fixing pin 111 and the second fixing pin 112 is larger than the inflow width
  • the trapped immune cells (T-cell) can not pass between the first fixing pin 111 and the second fixing pin 112 and can be fixed on the capturing unit 110 have.
  • an antigen reacting with the immune cell is supplied to the capturing unit.
  • the antigen is a cancer antigen (neo antigen), which reacts with the receptor (TCR) of immune cells (T-cells). That is, the interaction between the T-cell receptor and the antigen can result in the interaction between the T-cell and the antigen.
  • TCR tumor receptor
  • the immunoactive substance secreted from the capture unit 110 by the T-cell moves to the detection unit 120.
  • At least one protein label 121 capable of recognizing an immunoactive substance is located in the detection unit 120 (see FIGS. 3 and 4).
  • the protein label 121 may include an antibody which is activated by an immunoactive substance.
  • the protein label 121 may include a plurality of proteins so that the detection unit 120 can detect each of the plurality of substances.
  • Each of the plurality of different substances is a substance capable of activating an antibody and can be matched with any one of a plurality of proteins contained in the protein label 121.
  • the immune cell analysis unit 100 may include a plurality of detection units 120 located adjacent to the capturing unit 110.
  • the immunoactive substance can be detected by the detection unit 120 at intervals of time. That is, at any one of the detecting units 120, the secreted immunoactive substance is detected at 0H (time). Thereafter, water is re-supplied to the capturing unit 110 to secrete the secreted secretions from the immune cells.
  • the solution contained an immunologically active substance.
  • the solution containing the newly generated immunoactive substance is transferred to the other detection unit 120 to detect the immunoactive substance after 6H. In this way, the immunologically active substance after 12H, 18H, 24H is detected. That is, the plurality of detection units 120 detect the immunoactive substance with a gap of time.
  • the above-mentioned time gap is exemplary only, and the present invention is not limited thereto.
  • an immune cell when an immune cell is bound to an antigen, it can be determined whether the immunologically active substance most effective for immunization is secreted. In other words, based on the antigen that the researcher can control, you can see which immune cells in the body react with the specific antigen. Based on these results, it is possible to design immune cells that are effective against cancers of cancer patients.
  • a plurality of substance supply units 300 may be positioned around the immune cell analysis unit 100 arranged on the substrate 20.
  • the substance supply unit 300 may supply the immune cell analysis unit 100 with, for example, an antigen (neo antigen), a washing solution, an antibody for detection, an immune cell lysate, a primer, a reverse transcriptase and the like.
  • the composition of the immune cells is analyzed by dissolving the immune cells.
  • the composition of the analyzed immune cells can be used to analyze antibodies that specifically react to specific antigens, and based on the analyzed data, the most effective antibodies can be tailored to cancer patients.
  • the amount of the gene remaining in the dissolved immune cells is amplified.
  • a known initiator and reverse transcriptase amplify the small amount of gene and analyze the base sequence.
  • immune cells necessary for cancer patients can be designed.
  • Immune cells are collected from the cancer patient's body. At this time, various kinds of immune cells can be collected. For example, dozens to thousands of species can be harvested.
  • each of the plurality of collected immune cells is fixed to each of a plurality of immune cell analysis units 100 included in the immunocellular diagnostic chip 10 described above. That is, each of the immune cell analysis units 100 can capture each of a plurality of collected immune cells (S10).
  • the immune cells and the antigen are reacted. More specifically, more than 20 kinds of antigens whose structures and characteristics have been identified are reacted with immune cells. At this time, the immune cells and antigens will react to each other. If it is a reaction, the immune cell will secrete an immunologically active substance. On the other hand, identification of immune cells including an antigen-bound receptor (TCR) is performed. Thereby, immune cells binding to a specific antigen can be identified (S20).
  • TCR antigen-bound receptor
  • the immunologically active substance secreted by the immune cell is detected, and when the immune cell is bound to an antigen, it can be known which secretes the immunologically active substance. Thereby, the characteristics of the antibody that specifically reacts with a specific antigen can be confirmed (S30).
  • composition of the immune cells is analyzed (S40).
  • the composition of the analyzed immune cells can be used to analyze antibodies that specifically react to specific antigens, and based on the analyzed data, the most effective antibodies can be tailored to cancer patients.
  • the amount of the gene remaining in the dissolved immune cells is amplified.
  • a small amount of the gene is amplified and the base sequence is analyzed (S50).
  • S50 base sequence
  • the present invention provides a method for detecting multiple immune cells from a cancer patient and simultaneously reacting multiple collected immune cells with the antigen to detect immune cells specifically reacting with a specific antigen, By designing the immune cells by manipulation, there is an effect of drastically improving the chemotherapy of cancer patients.
  • the number of immune cells reacting with an antigen, the kind and amount of each secreted protein in the immune cells, and the gene base sequence information of the immune cells can be seen at once, among many kinds of immune cells have.

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Abstract

The present invention provides an immune cell diagnostic chip for producing immune cells for enhancing the immune function of a cancer patient by analyzing antigen responses of immune cells on the basis of the immune cells of the cancer patient. An immune cell diagnostic chip of the present invention comprises a substrate and a plurality of immune cell analysis units arranged on the substrate, wherein the immune cell analysis units may comprise a capture unit for capturing the immune cells and a detection unit for detecting an immunoactive material secreted by the immune cells.

Description

면역세포 진단칩Immune cell diagnostic chip

본 발명은 암환자의 면역세포를 바탕으로, 상기 면역세포의 항원 반응을 분석하여 상기 암환자의 면역기능을 강화하기 위한 면역세포를 제조하기 위한 면역세포 진단칩에 관한 것이다.The present invention relates to an immune cell diagnostic chip for producing immune cells for enhancing the immune function of cancer patients by analyzing antigen responses of the immune cells based on immune cells of cancer patients.

나노바이오칩(nanobiochip)란 바이오칩에 나노기술이 접목된 것이다. 나노바이오칩 기술은 나노기술(NT)과 생명공학기술(BT)을 결합하여 극미량의 혈액이나 뇨, 타액 등과 같은 실질적인 생체시료로 여러 유전자(DNA, RNA), 단백질, 세포 및 다양한 대사물질을 칩 상에서 여러 센서와 다양한 전처리 기능으로 직접 감지하여, 보다 빠르고 정확한 질병 진단을 가능케 함으로써 인류의 질병퇴치와 건강한 삶의 질적 향상에 혁신적으로 기여할 수 있다. 이러한 나노바이오칩은 마이크로-바이오칩(micro-biochip)에 비해 상대적으로 초소형, 저가격, 고성능, 고집적, 저전력화는 물론 적은 시료의 양과 빠른 반응 시간과 분석시간이 가능하다는 장점을 가지고 이어 차세대 바이오칩으로 주목을 받고 있으며, 생명과학, 의학, 약학, 임상 등 다양한 분야에 혁신적인 변화를 일으킬 것으로 기대되어 빠르게 성장하고 있다.Nanobiochip is a nanotechnology integrated with biochip. Nano-biochip technology combines nanotechnology (NT) and biotechnology (BT) to produce a variety of genes (DNA, RNA), proteins, cells and various metabolites on a chip By sensing directly with various sensors and various preprocessing functions, it is possible to diagnose diseases faster and more accurately, thereby contributing to the eradication of human diseases and quality improvement of healthy life. This nano-biochip has advantages such as small size, low price, high performance, high integration, low power, relatively small amount of sample, fast reaction time and analysis time compared to micro-biochip. And is rapidly growing, expecting to make innovative changes in various fields such as life sciences, medicine, pharmacy, and clinical.

한편, 암의 치료를 위해서는 외과적 수술, 방사선 치료법, 항암제 치료법 및 면역 치료법 등이 있으나, 이러한 많은 치료법에도 불구하고 임상적 치료효능이 낮은 이유는 재발암의 발생 때문이다. 임상적 난제인 재발암의 주요 원인은 항암 치료에 대한 암세포의 내성 획득과 관련이 있으므로, 효과적인 암 치료를 위해서는 항암 치료법에 대한 암세포의 내성 극복에 대한 연구가 필요하다. 내성 극복에 대한 연구는 내성 관련 유전자 또는 분자축의 규명 및 규명된 유전자 또는 분자축을 이용하여 진단 및 표적화하는 암치료법이 연구되어야 한다.On the other hand, surgical treatment, radiation therapy, anticancer therapy, and immunotherapy are the treatment methods for cancer, but the reason for the low clinical efficacy is the occurrence of recurrent cancer. Since the primary cause of recurrent cancer, which is a clinical problem, is related to the acquisition of cancer cell resistance to chemotherapy, studies for overcoming cancer cell resistance to chemotherapy for effective cancer therapy are needed. Studies on overcoming tolerance should be based on the identification of tolerance-related genes or molecular axes and the treatment of cancer by diagnosing and targeting by using identified genes or molecular axes.

본 발명자는, 암환자의 면역기능 개선을 통해 암을 극복하는 방법을 개발하고자 노력하였다. 그 결과, 암환자의 신체에서 면역세포를 채취하고, 채취된 면역세포를 근거로 암환자의 암에 효과적으로 작용하는 면역세포를 검출하는 칩을 발명하였고, 이를 통해 암환자의 암에 대항할 수 있는 면역세포를 설계하는 방법을 해결하였다. The present inventors have sought to develop a method of overcoming cancer by improving immune function in cancer patients. As a result, an immune cell was collected from the cancer patient's body, and a chip was detected that detects immune cells effectively acting on the cancer of the cancer patient based on the collected immune cells. Thus, And solved the method of designing immune cells.

따라서 본 발명의 목적은 암환자의 신체에서 면역세포를 채취하고, 채취된 면역세포를 근거로 암환자의 암에 효과적으로 작용하는 면역세포를 검출하는 칩을 제공하는데 있다.Accordingly, it is an object of the present invention to provide a chip for detecting immune cells in a cancer patient's body and detecting immune cells effectively acting on cancer of a cancer patient based on the collected immune cells.

본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 보다 명확하게 된다.Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

상기 해결하려는 과제를 달성하기 위한 본 발명의 일 실시예에 따른 면역세포 진단칩은, 암환자의 면역세포를 바탕으로, 상기 면역세포의 항원 반응을 분석하여 상기 암환자의 면역기능을 강화하기 위한 면역세포를 제조하기 위한 것으로, 기판과, 상기 기판 상에 배열된 다수의 면역세포 분석유닛을 포함하되, 상기 면역세포 분석유닛은, 상기 면역세포를 포획하는 포획부와, 상기 면역세포가 분비하는 면역활성물질을 검출하는 검출부를 포함할 수 있다.According to an aspect of the present invention, there is provided an immune cell diagnostic chip for analyzing an antigenic reaction of an immune cell based on immune cells of a cancer patient to enhance the immune function of the cancer patient A method for producing immune cells, comprising: a substrate; and a plurality of immune cell analysis units arranged on the substrate, wherein the immune cell analysis unit comprises: a capturing unit capturing the immune cells; And a detection unit for detecting the immunologically active substance.

상기 포획부는 상기 면역세포를 포획하기 위해 상기 면역세포를 고정하는 고정부를 포함할 수 있다. The capturing unit may include an immobilization unit for immobilizing the immune cells to capture the immune cells.

상기 고정부는 제1 고정핀과 상기 제1 고정핀과 이격되어 위치하는 제2 고정핀을 포함할 수 있다.The fixing unit may include a first fixing pin and a second fixing pin spaced apart from the first fixing pin.

상기 면역세포는 상기 제1 고정핀과 상기 제2 고정핀 사이에 포획될 수 있다.The immune cells may be trapped between the first fixing pin and the second fixing pin.

상기 포획부에는 상기 면역세포와 상기 항원이 위치하여, 상기 면역세포와 상기 항원간의 상호 작용이 이루어질 수 있다.The immune cells and the antigen are located in the capturing portion, and the interaction between the immune cells and the antigen can be performed.

상기 면역세포와 상기 항원 간에 상호작용이 일어나는 경우, 상기 상호작용에 의해 상기 면역활성물질이 분비되고, 상기 면역활성물질은 상기 검출부로 이동할 수 있다.When the interaction between the immune cells and the antigen occurs, the immunoactive substance is secreted by the interaction, and the immunoactive substance can move to the detection unit.

상기 면역활성물질이 서로 다른 복수의 물질을 포함하는 경우, 상기 검출부는 상기 복수의 물질 각각을 검출할 수 있다.When the immunoactive substance includes a plurality of different substances, the detection unit can detect each of the plurality of substances.

상기 검출부는 상기 면역활성물질을 인지하는 적어도 하나의 단백질 표지를 포함할 수 있다. The detection unit may include at least one protein marker that recognizes the immunoactive substance.

상기 면역활성물질이 서로 다른 복수의 물질을 포함하는 경우, 상기 검출부는 상기 단백질 표지에 포함된 적어도 하나의 단백질 중 어느 하나의 단백질과 매칭되어 상기 복수의 물질 각각을 검출할 수 있다.When the immunoactive substance includes a plurality of different substances, the detection unit may detect each of the plurality of substances by matching with any one of at least one protein included in the protein label.

상기 면역세포 분석유닛은 상기 검출부를 복수개 포함하되, 상기 복수개의 검출부 각각은 상기 포획부와 이웃하여 위치할 수 있다.The immunocyte analysis unit may include a plurality of detection units, wherein each of the plurality of detection units may be located adjacent to the capturing unit.

상기 복수개의 검출부 각각은, 시간 간격을 두고 상기 면역활성물질을 검출하되, 상기 복수개의 검출부 중 어느 하나에서 상기 면역활성물질을 검출하고, 소정의 시간 간격 이후에 상기 복수개의 검출부 중 다른 하나에서 새로이 분비된 상기 면역활성물질을 검출할 수 있다.Wherein each of the plurality of detection units detects the immunoactive substance at a time interval, detects the immunoactive substance from any one of the plurality of detection units, and detects the immunoactive substance from another one of the plurality of detection units after a predetermined time interval The secreted immunologically active substance can be detected.

상기 면역세포 분석유닛의 주변에 위치하는 다수의 물질 공급부를 더 포함하되, 상기 물질 공급부는, 상기 면역세포를 용해시키고, 용해된 면역세포 내 잔존하는 유전자의 양을 증폭시키기 위한 물질을 상기 면역세포 분석유닛에 공급할 수 있다.Further comprising a plurality of substance supply units located in the periphery of the immune cell analysis unit, wherein the substance supply unit is configured to dissolve the immune cells and to immobilize a substance for amplifying the amount of remaining genes in the dissolved immune cells, To the analysis unit.

본 발명에 의할 경우, 암환자의 면역세포를 바탕으로, 상기 면역세포의 항원 반응을 분석하여 상기 암환자의 면역기능을 강화하기 위한 면역세포를 제조하기 위한 면역세포 진단칩이 제공된다.According to the present invention, there is provided an immune cell diagnostic chip for producing an immune cell for enhancing the immune function of the cancer patient by analyzing the antigen response of the immune cell based on the immune cell of the cancer patient.

도 1은 본 발명의 실시예에 따른 면역세포 진단칩의 평면도이다.1 is a plan view of an immune cell diagnostic chip according to an embodiment of the present invention.

도 2는 면역세포 진단칩에 포함된 면역세포 분석유닛을 나타낸 것이다.2 shows an immunocyte analysis unit included in an immune cell diagnostic chip.

도 3은 면역세포 분석유닛에 포함된 검출부의 단백질 표지를 예시적으로 나타낸 것이다.3 is an exemplary illustration of the protein label of the detection unit included in the immune cell analysis unit.

도 4는 검출부의 검출 과정을 나타내기 위한 것이다.FIG. 4 illustrates a detection process of the detection unit. FIG.

도 5는 면역세포를 용해시켜 세포 조성을 분석하는 것을 나타낸 것이다.FIG. 5 shows dissolution of immune cells to analyze cell composition.

도 6은 용해된 면역세포 내의 유전자 양을 증폭시키고 염기서열을 분석하는 것을 나타낸 것이다.Figure 6 shows amplification of the amount of gene in dissolved immune cells and analysis of the base sequence.

도 7은 본 발명에 따라 면역세포를 포획 및 분석하는 단계를 나타낸 것이다.Figure 7 shows the steps of capturing and analyzing immune cells in accordance with the present invention.

본 발명의 이점 및 특징, 그리고 그것들을 달성하는 방법은 첨부되는 도면과 함께 상세하게 후술되어 있는 실시예들을 참조하면 명확해질 것이다. 그러나 본 발명은 이하에서 개시되는 실시예들에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 것이며, 단지 본 실시예들은 본 발명의 개시가 완전하도록 하며, 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위해 제공되는 것이며, 본 발명은 청구항의 범주에 의해 정의될 뿐이다. 아래 첨부된 도면을 참조하여 본 발명의 실시를 위한 구체적인 내용을 상세히 설명한다. 도면에 관계없이 동일한 부재번호는 동일한 구성요소를 지칭하며, "및/또는"은 언급된 아이템들의 각각 및 하나 이상의 모든 조합을 포함한다.BRIEF DESCRIPTION OF THE DRAWINGS The advantages and features of the present invention and the manner of achieving them will become apparent with reference to the embodiments described in detail below with reference to the accompanying drawings. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Is provided to fully convey the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Reference will now be made in detail to the preferred embodiments of the present invention, examples of which are illustrated in the accompanying drawings. &Quot; and / or " include each and every combination of one or more of the mentioned items. ≪ RTI ID = 0.0 >

본 명세서에서 사용된 용어는 실시예들을 설명하기 위한 것이며 본 발명을 제한하고자 하는 것은 아니다. 본 명세서에서, 단수형은 문구에서 특별히 언급하지 않는 한 복수형도 포함한다. 명세서에서 사용되는 "포함한다(comprises)" 및/또는 "포함하는(comprising)"은 언급된 구성요소 외에 하나 이상의 다른 구성요소의 존재 또는 추가를 배제하지 않는다.The terminology used herein is for the purpose of illustrating embodiments and is not intended to be limiting of the present invention. In the present specification, the singular form includes plural forms unless otherwise specified in the specification. The terms " comprises " and / or " comprising " used in the specification do not exclude the presence or addition of one or more other elements in addition to the stated element.

다른 정의가 없다면, 본 명세서에서 사용되는 모든 용어(기술 및 과학적 용어를 포함)는 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에게 공통적으로 이해될 수 있는 의미로 사용될 수 있을 것이다. 또 일반적으로 사용되는 사전에 정의되어 있는 용어들은 명백하게 특별히 정의되어 있지 않는 한 이상적으로 또는 과도하게 해석되지 않는다. Unless defined otherwise, all terms (including technical and scientific terms) used herein may be used in a sense commonly understood by one of ordinary skill in the art to which this invention belongs. Also, commonly used predefined terms are not ideally or excessively interpreted unless explicitly defined otherwise.

이하, 본 발명의 실시예에 따른 면역세포 진단칩을 설명한다. 도 1은 본 발명의 실시예에 따른 면역세포 진단칩의 평면도이고, 도 2는 면역세포 진단칩에 포함된 면역세포 분석유닛을 나타낸 것이고, 도 3은 면역세포 분석유닛에 포함된 검출부의 검출 단백질을 예시적으로 나타낸 것이다.Hereinafter, an immune cell diagnostic chip according to an embodiment of the present invention will be described. FIG. 1 is a plan view of an immune cell diagnostic chip according to an embodiment of the present invention, FIG. 2 is an immunocyte analysis unit included in an immune cell diagnostic chip, and FIG. ≪ / RTI >

먼저 도 1을 참조하면, 본 발명의 면역세포 진단칩(10)은 암환자의 면역세포를 바탕으로, 상기 면역세포의 항원 반응을 분석하여 암환자의 면역기능을 강화하기 위한 항암 면역세포를 제조하는 방법에 사용되는 것이다. 이를 위해, 면역세포 진단칩(10)은 기판(20), 상기 기판(20) 상에 배열된 다수의 면역세포 분석유닛(100)을 포함할 수 있다. 기판(20)은 예를 들어, 유리로 이루어질 수 있다.First, referring to FIG. 1, the immune cell diagnostic chip 10 of the present invention analyzes the antigenic reaction of the immune cells on the basis of the immune cells of a cancer patient to prepare an anti-cancer immune cell for enhancing the immune function of the cancer patient It is used in the method to do. To this end, the immune cell diagnostic chip 10 may include a substrate 20, and a plurality of immune cell analysis units 100 arranged on the substrate 20. [ The substrate 20 may be made of, for example, glass.

면역세포 진단칩(10) 상에는 암환자로부터 채취한 면역세포가 포획되어, 기판(20) 상에 배열된 면역세포 분석유닛(100) 각각에 분포하게 된다.On the immune cell diagnostic chip 10, the immune cells collected from the cancer patient are captured and distributed in each of the immune cell analysis units 100 arranged on the substrate 20.

도 1 및 도 2를 참조하면, 면역세포 진단칩(10)의 기판(20) 상에 배열된 다수의 면역세포 분석유닛(100)은 면역세포를 포획하는 포획부(110)와, 면역세포가 분비하는 면역활성물질을 검출하는 검출부(120)를 포함할 수 있다. 1 and 2, a plurality of immune cell analysis units 100 arranged on a substrate 20 of an immune cell diagnostic chip 10 includes a capturing unit 110 for capturing immune cells, And a detection unit 120 for detecting the secreted immunoactive substance.

한편, 면역세포 분석유닛(100)의 다수의 전도성 패턴(101)으로 이루어질 수 있다. 전도성 패턴(101)은 면역세포 분석유닛(100)에서 전극으로 기능할 수 있다. 전도성 패턴(101)에 의해 면역세포(T-cell)나 면역세포(T-cell)에서 분비된 면역활성물질이 이웃하는 전도성 패턴(101)으로 이동할 수 있다. 전도성 패턴(101)은 전도성 물질로 형성되며, 자석 또는 고분자 패턴이 부가될 수 있다. 또한 전도성 패턴은 공지의 패터닝 기술인 마스크를 이용한 패터닝 방법 또는 잉크젯 프린팅 기술 등으로 형성될 수 있다.On the other hand, a plurality of conductive patterns 101 of the immune cell analysis unit 100 can be formed. The conductive pattern 101 may function as an electrode in the immune cell analysis unit 100. The immunoactive substance secreted from the T-cell or the T-cell by the conductive pattern 101 can move to the neighboring conductive pattern 101. [ The conductive pattern 101 is formed of a conductive material, and a magnet or a polymer pattern may be added. The conductive pattern may be formed by a known patterning technique, such as a patterning method using a mask, or an inkjet printing technique.

계속해서, 포획부(110)는 면역세포(T-cell)를 포획하고, 기판(20) 상에 면역세포(T-cell)를 고정시킨다. 포획부(110)는 다수의 면역세포 분석유닛(100) 각각에 포함된다. 면역세포(T-cell)는 기판(20)의 일측에서 공급되며, 이에 대한 사항은 본 발명의 범위를 넘는 것으로 자세한 설명은 생략하기로 한다. Subsequently, the capturing unit 110 captures immune cells (T-cells) and immobilizes immune cells (T-cells) on the substrate 20. The capturing unit 110 is included in each of the plurality of immune cell analysis units 100. The immune cells (T-cells) are supplied from one side of the substrate 20, and the details thereof are beyond the scope of the present invention, and a detailed description thereof will be omitted.

포획부(110)는 기판의 일측에서 공급되는 면역세포(T-cell)를 포획하기 위해 면역세포(T-cell)를 고정하는 고정부(111, 112)를 포함할 수 있다. 고정부(111, 112)는 예를들어 고분자 물질, 자석 물질, 광학적 구조물 등의 물질로 형성될 수 있다. 고정부(111, 112)는 면역세포(T-cell)를 효과적으로 포획하기 위해 제1 고정핀(111)과 제2 고정핀(112)을 포함할 수 있다. 제2 고정핀(112)과 제1 고정핀(111)은 서로 이격되어 위치하고 있다. The capturing unit 110 may include fixing units 111 and 112 for fixing immune cells (T-cells) to capture immune cells (T-cells) supplied from one side of the substrate. The fixing parts 111 and 112 may be formed of a material such as a polymer material, a magnet material, or an optical structure. The fixing parts 111 and 112 may include a first fixing pin 111 and a second fixing pin 112 to effectively capture the immune cells (T-cell). The second fixing pin 112 and the first fixing pin 111 are spaced apart from each other.

이때, 제1 고정핀(111)과 제2 고정핀(112)간의 이격 폭은 면역세포(T-cell)가 유입되는 부분에서 가장 넓고, 유입되는 부분에서 멀어질수록 제1 고정핀(111)과 제2 고정핀(112) 간의 이격 폭이 좁아진다. 이에 의해, 면역세포(T-cell)가 보다 효과적으로 포획부(110)에서 포획될 수 있다. 즉, 면역세포(T-cell)는 제1 고정핀(111)과 제2 고정핀(112) 사이에 포획되되, 제1 고정핀(111)과 제2 고정핀(112) 간의 이격 폭이 유입되는 부분에서 멀어질수록 좁아지므로, 포획된 면역세포(T-cell)는 제1 고정핀(111)과 제2 고정핀(112) 사이를 통과하지 못하고, 포획부(110) 상에 고정될 수 있다.The distance between the first fixing pin 111 and the second fixing pin 112 is the widest at the portion where the T-cell is introduced. The distance between the first fixing pin 111 and the first fixing pin 111 increases as the distance from the inflow portion increases. And the second fixing pin 112 is narrowed. Thereby, the immune cells (T-cell) can be more effectively captured in the capturing part 110. [ That is, the immune cells (T-cell) are trapped between the first fixing pin 111 and the second fixing pin 112, and the distance between the first fixing pin 111 and the second fixing pin 112 is larger than the inflow width The trapped immune cells (T-cell) can not pass between the first fixing pin 111 and the second fixing pin 112 and can be fixed on the capturing unit 110 have.

포획부(110)에 면역세포(T-cell)가 포획된 후, 면역세포(T-cell)와 반응하는 항원을 포획부에 공급한다. 항원은 암항원(neo antigen)으로써, 면역세포(T-cell)의 수용체(TCR)와 반응한다. 즉, 면역세포(T-cell)의 수용체와 항원간의 결합에 의해, 면역세포(T-cell)와 항원간의 상호작용이 이루어질 수 있다. 면역세포(T-cell)와 항원간의 상호작용에 의해, 면역세포(T-cell)는 면역활성물질을 분비한다.After an immune cell (T-cell) is captured in the capturing unit 110, an antigen reacting with the immune cell (T-cell) is supplied to the capturing unit. The antigen is a cancer antigen (neo antigen), which reacts with the receptor (TCR) of immune cells (T-cells). That is, the interaction between the T-cell receptor and the antigen can result in the interaction between the T-cell and the antigen. By interaction between T-cell and antigen, immune cells (T-cells) secrete immunologically active substances.

한편, 면역세포(T-cell)가 포획부(110)에서 분비한 면역활성물질은 검출부(120)로 이동한다. 검출부(120)에는 면역활성물질을 인지할 수 있는 적어도 하나 이상의 단백질 표지(121)가 위치한다(도 3 및 도 4 참조).On the other hand, the immunoactive substance secreted from the capture unit 110 by the T-cell moves to the detection unit 120. At least one protein label 121 capable of recognizing an immunoactive substance is located in the detection unit 120 (see FIGS. 3 and 4).

단백질 표지(121)는 면역활성물질에 의해 활성화되는 항체가 포함될 수 있다. 이때, 면역활성물질이 서로 다른 복수의 물질을 포함하는 경우, 검출부(120)가 복수의 물질 각각을 검출할 수 있도록, 단백질 표지(121)는 다수의 단백질을 포함할 수 있다. 서로 다른 복수의 물질 각각은 항체를 활성화시킬 수 있는 물질로써, 단백질 표지(121)에 포함된 다수의 단백질 중 어느 하나의 단백질과 매칭될 수 있다. The protein label 121 may include an antibody which is activated by an immunoactive substance. In this case, when the immunoactive substance includes a plurality of different substances, the protein label 121 may include a plurality of proteins so that the detection unit 120 can detect each of the plurality of substances. Each of the plurality of different substances is a substance capable of activating an antibody and can be matched with any one of a plurality of proteins contained in the protein label 121.

한편, 면역세포 분석유닛(100)은 포획부(110)와 이웃하여 위치하는 검출부(120)를 다수개 포함할 수 있다. 검출부(120)가 다수개 포함됨으로써, 면역활성물질은 시간 간격을 두고 검출부(120)에서 검출될 수 있다. 즉, 검출부(120)중 어느 하나에서, 분비된 면역활성물질을 0H(시간)에 검출한다. 그후, 포획부(110)에 수분을 재공급하여, 면역세포에서 분비된 분비물을 용액화한다. 용액 내에는 면역활성물질이 포함되어 있디. 새로이 생성된 면역활성물질을 포함하는 용액을 다른 검출부(120)로 이동시켜 6H 후의 면역활성물질을 검출한다. 이러한 방식으로, 12H, 18H, 24H 후의 면역활성물질을 검출한다. 즉, 다수의 검출부(120)에서 시간의 갭을 두고, 면역활성물질을 검출한다. 이상의 시간의 갭은 어디까지나 예시적인 것이며, 본 발명은 이에 제한되지 않는다.Meanwhile, the immune cell analysis unit 100 may include a plurality of detection units 120 located adjacent to the capturing unit 110. By including a plurality of detection units 120, the immunoactive substance can be detected by the detection unit 120 at intervals of time. That is, at any one of the detecting units 120, the secreted immunoactive substance is detected at 0H (time). Thereafter, water is re-supplied to the capturing unit 110 to secrete the secreted secretions from the immune cells. The solution contained an immunologically active substance. The solution containing the newly generated immunoactive substance is transferred to the other detection unit 120 to detect the immunoactive substance after 6H. In this way, the immunologically active substance after 12H, 18H, 24H is detected. That is, the plurality of detection units 120 detect the immunoactive substance with a gap of time. The above-mentioned time gap is exemplary only, and the present invention is not limited thereto.

이에 의해, 면역세포가 어떤 항원과 결합되었을 때, 가장 면역에 효과적인 면역활성물질을 분비하는지 알 수 있다. 즉, 연구자가 콘트롤 할 수 있는 항원을 바탕으로 인체내의 어떤 면역세포가 특정 항원과 반응하는지 알 수 있다. 이러한 결과를 바탕으로 암환자의 암질환에 효과적인 면역세포를 설계할 수 있다. As a result, when an immune cell is bound to an antigen, it can be determined whether the immunologically active substance most effective for immunization is secreted. In other words, based on the antigen that the researcher can control, you can see which immune cells in the body react with the specific antigen. Based on these results, it is possible to design immune cells that are effective against cancers of cancer patients.

한편, 기판(20) 상에 배열된 면역세포 분석유닛(100)의 주변에는 다수의 물질 공급부(300)가 위치할 수 있다. 물질 공급부(300)는 예를 들어, 항원(neo antigen), 세척액, 검출용 항체, 면역세포 용해액, 개시제(primer), 역전사-효소 등을 면역세포 분석유닛(100)에 공급할 수 있다.On the other hand, a plurality of substance supply units 300 may be positioned around the immune cell analysis unit 100 arranged on the substrate 20. [ The substance supply unit 300 may supply the immune cell analysis unit 100 with, for example, an antigen (neo antigen), a washing solution, an antibody for detection, an immune cell lysate, a primer, a reverse transcriptase and the like.

계속해서, 도 5를 참조하면, 면역세포를 용해시켜 면역세포의 조성을 분석한다. 분석된 면역세포의 조성은 특정 항원에 특이적인 반응을 하는 항체를 분석할 수 있고, 분석된 자료를 바탕으로 암환자에게 가장 효과적인 항체를 맞춤형으로 설계할 수 있다.Next, referring to FIG. 5, the composition of the immune cells is analyzed by dissolving the immune cells. The composition of the analyzed immune cells can be used to analyze antibodies that specifically react to specific antigens, and based on the analyzed data, the most effective antibodies can be tailored to cancer patients.

계속해서, 도 6을 참조하면 용해된 면역세포 내에 잔존하는 유전자의 양을 증폭시킨다. 개시제와 역전사 효소등을 활용하여, 기존에 알려져 있는 방식으로, 소량 존재하는 유전자를 증폭시키고 염기서열을 분석한다. 이에 의해, 암환자에게 필요한 면역세포를 설계할 수 있다.Subsequently, referring to FIG. 6, the amount of the gene remaining in the dissolved immune cells is amplified. Using a known initiator and reverse transcriptase, amplify the small amount of gene and analyze the base sequence. Thus, immune cells necessary for cancer patients can be designed.

다음으로, 도 7을 참조하여, 본 발명의 실시예에 따른 면역세포 진단칩(10)을 이용한 면역세포 포획 및 분석 단계를 설명한다.Next, referring to FIG. 7, immune cell capturing and analysis steps using the immune cell diagnostic chip 10 according to the embodiment of the present invention will be described.

암환자의 신체로부터 면역세포(T-cell)를 채취한다. 이때, 면역세포는 다양한 종류가 채취될 수 있다. 예를들어 수십 종부터 수천 종까지 채취될 수 있다. Immune cells (T-cells) are collected from the cancer patient's body. At this time, various kinds of immune cells can be collected. For example, dozens to thousands of species can be harvested.

계속해서, 채취된 다수의 면역세포 각각을 상술한 면역세포 진단칩(10)에 포함된 다수의 면역세포 분석유닛(100) 각각에 고정시킨다. 즉, 면역세포 분석유닛(100) 각각은 채취된 다수의 면역세포 각각을 포획할 수 있다(S10). Subsequently, each of the plurality of collected immune cells is fixed to each of a plurality of immune cell analysis units 100 included in the immunocellular diagnostic chip 10 described above. That is, each of the immune cell analysis units 100 can capture each of a plurality of collected immune cells (S10).

계속해서 포획된 면역세포와 항원(neo antigen)을 반응시킨다. 보다구체적으로, 구조와 특성이 규명된 20여종 이상의 항원을 면역세포와 반응시킨다. 이때 면역세포와 항원이 반응하는 경우가 있을 것이고, 그렇지 않은 경우도 있을 것이다. 반응이 되는 경우라면, 면역세포는 면역활성물질을 분비할 것이다. 한편, 항원과 결합된 수용체(TCR)를 포함하는 면역세포를 식별(identification)하는 작업을 수행한다. 이에 의해, 특정 항원에 결합하는 면역세포가 식별될 수 있다(S20). Subsequently, the immune cells and the antigen (neo antigen) are reacted. More specifically, more than 20 kinds of antigens whose structures and characteristics have been identified are reacted with immune cells. At this time, the immune cells and antigens will react to each other. If it is a reaction, the immune cell will secrete an immunologically active substance. On the other hand, identification of immune cells including an antigen-bound receptor (TCR) is performed. Thereby, immune cells binding to a specific antigen can be identified (S20).

계속해서, 면역세포가 분비하는 면역활성물질을 검출하여, 면역세포가 어떤 항원과 결합되었을 때, 어떠한 면역활성물질을 분비하는지 알 수 있다. 이에 의해 특정 항원에 특이적으로 반응하는 항체의 특성을 확인할 수 있다(S30).Subsequently, the immunologically active substance secreted by the immune cell is detected, and when the immune cell is bound to an antigen, it can be known which secretes the immunologically active substance. Thereby, the characteristics of the antibody that specifically reacts with a specific antigen can be confirmed (S30).

계속해서, 면역세포를 용해시킨다(도 5참조). 용해 후, 면역세포의 조성을 분석한다(S40). 분석된 면역세포의 조성은 특정 항원에 특이적인 반응을 하는 항체를 분석할 수 있고, 분석된 자료를 바탕으로 암환자에게 가장 효과적인 항체를 맞춤형으로 설계할 수 있다.Subsequently, immune cells are dissolved (see Fig. 5). After dissolution, the composition of the immune cells is analyzed (S40). The composition of the analyzed immune cells can be used to analyze antibodies that specifically react to specific antigens, and based on the analyzed data, the most effective antibodies can be tailored to cancer patients.

계속해서, 용해된 면역세포 내에 잔존하는 유전자의 양을 증폭시킨다. 개시제와 역전사 효소등을 활용하여, 기존에 알려져 있는 방식으로, 소량 존재하는 유전자를 증폭시키고 염기서열을 분석한다(S50). 이에 의해, 암환자에게 필요한 면역세포를 설계할 수 있다.Subsequently, the amount of the gene remaining in the dissolved immune cells is amplified. Using a known initiator and reverse transcriptase, a small amount of the gene is amplified and the base sequence is analyzed (S50). Thus, immune cells necessary for cancer patients can be designed.

상술한 바와 같이, 본 발명은 암환자로부터 다수의 면역세포를 채취하고, 채취된 다수의 면역세포를 동시다발적으로 항원과 반응시켜, 특정 항원에 특이적으로 반응하는 면역세포를 검출하고, 유전자 조작에 의해 면역세포를 설계함으로써, 암환자의 항암치료를 획기적으로 개선할 수 있는 효과가 있다.As described above, the present invention provides a method for detecting multiple immune cells from a cancer patient and simultaneously reacting multiple collected immune cells with the antigen to detect immune cells specifically reacting with a specific antigen, By designing the immune cells by manipulation, there is an effect of drastically improving the chemotherapy of cancer patients.

또한, 본 발명에 의하면, 수 많은 종류의 면역세포 중에서 항원과 반응하는 면역세포의 수, 상기 면역세포에서 각각 분비하는 단백질 종류와 양, 상기 면역세포의 유전자 염기서열 정보를 한번에 볼 수 있는 효과가 있다.In addition, according to the present invention, the number of immune cells reacting with an antigen, the kind and amount of each secreted protein in the immune cells, and the gene base sequence information of the immune cells can be seen at once, among many kinds of immune cells have.

이상 본 발명의 실시예들을 설명하였으나, 본 발명은 상기 실시예들에 한정되는 것이 아니라 서로 다른 다양한 형태로 제조될 수 있으며, 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.While the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, It will be understood that the invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.

Claims (12)

암환자의 면역세포를 바탕으로, 상기 면역세포의 항원 반응을 분석하여 상기 암환자의 면역기능을 강화하기 위한 면역세포를 제조하기 위한 면역세포 진단칩에 있어서,1. An immune cell diagnostic chip for producing immune cells for enhancing immune function of cancer patients by analyzing antigen responses of the immune cells based on immune cells of cancer patients, 기판과,A substrate; 상기 기판 상에 배열된 다수의 면역세포 분석유닛을 포함하되,A plurality of immune cell analysis units arranged on the substrate, 상기 면역세포 분석유닛은,Said immune cell analysis unit comprising: 상기 면역세포를 포획하는 포획부와, A capturing unit capturing the immune cells; 상기 면역세포가 분비하는 면역활성물질을 검출하는 검출부를 포함하는 면역세포 진단칩.And a detection unit for detecting an immunologically active substance secreted by said immune cell. 제1 항에 있어서, The method according to claim 1, 상기 포획부는 상기 면역세포를 포획하기 위해 상기 면역세포를 고정하는 고정부를 포함하는 면역세포 진단칩.Wherein the capturing part comprises a fixing part for fixing the immune cell to capture the immune cell. 제2 항에 있어서, 3. The method of claim 2, 상기 고정부는 제1 고정핀과 상기 제1 고정핀과 이격되어 위치하는 제2 고정핀을 포함하는 면역세포 진단칩.Wherein the fixing portion includes a first fixing pin and a second fixing pin spaced apart from the first fixing pin. 제3 항에 있어서,The method of claim 3, 상기 면역세포는 상기 제1 고정핀과 상기 제2 고정핀 사이에 포획되는 면역세포 진단칩.Wherein the immune cell is captured between the first fixing pin and the second fixing pin. 제1 항에 있어서,The method according to claim 1, 상기 포획부에는 상기 면역세포와 상기 항원이 위치하여, 상기 면역세포와 상기 항원간의 상호 작용이 이루어지는 면역세포 진단칩.Wherein the immune cell and the antigen are located in the capturing part, and interaction between the immune cell and the antigen is carried out. 제5 항에 있어서,6. The method of claim 5, 상기 면역세포와 상기 항원 간에 상호작용이 일어나는 경우, When the interaction between the immune cells and the antigen occurs, 상기 상호작용에 의해 상기 면역활성물질이 분비되고, 상기 면역활성물질은 상기 검출부로 이동하는 면역세포 진단칩.Wherein the immunostimulatory substance is secreted by the interaction, and the immunostimulatory substance is transferred to the detection section. 제6 항에 있어서,The method according to claim 6, 상기 면역활성물질이 서로 다른 복수의 물질을 포함하는 경우, 상기 검출부는 상기 복수의 물질 각각을 검출하는 면역세포 진단칩.Wherein the detection unit detects each of the plurality of substances when the immunoactive substance comprises a plurality of different substances. 제7 항에 있어서,8. The method of claim 7, 상기 검출부는 상기 면역활성물질을 인지하는 적어도 하나의 단백질 표지를 포함하는 면역세포 진단칩.Wherein the detection portion comprises at least one protein label recognizing the immunoactive substance. 제8 항에 있어서,9. The method of claim 8, 상기 면역활성물질이 서로 다른 복수의 물질을 포함하는 경우, 상기 검출부는 상기 단백질 표지에 포함된 적어도 하나의 단백질 중 어느 하나의 단백질과 매칭되어 상기 복수의 물질 각각을 검출하는 면역세포 진단칩.Wherein the detection unit detects each of the plurality of substances by matching with any one of at least one protein included in the protein label when the immunoactive substance comprises a plurality of different substances. 제1 항에 있어서,The method according to claim 1, 상기 면역세포 분석유닛은 상기 검출부를 복수개 포함하되, 상기 복수개의 검출부 각각은 상기 포획부와 이웃하여 위치하는 면역세포 진단칩.Wherein the immune cell analysis unit includes a plurality of detection units, each of the plurality of detection units being located adjacent to the capturing unit. 제10 항에 있어서,11. The method of claim 10, 상기 복수개의 검출부 각각은, Wherein each of the plurality of detecting portions includes: 시간 간격을 두고 상기 면역활성물질을 검출하되,Detecting said immunologically active substance at intervals of time, 상기 복수개의 검출부 중 어느 하나에서 상기 면역활성물질을 검출하고, 소정의 시간 간격 이후에 상기 복수개의 검출부 중 다른 하나에서 새로이 분비된 상기 면역활성물질을 검출하는 면역세포 진단칩.Wherein the immunoactive substance is detected in any one of the plurality of detection units and the immunologically active substance newly secreted in another one of the plurality of detection units is detected after a predetermined time interval. 제1 항에 있어서,The method according to claim 1, 상기 면역세포 분석유닛의 주변에 위치하는 다수의 물질 공급부를 더 포함하되,Further comprising a plurality of substance supply units located in the periphery of the immune cell analysis unit, 상기 물질 공급부는,Wherein the material supply unit comprises: 상기 면역세포를 용해시키고, 용해된 면역세포 내 잔존하는 유전자의 양을 증폭시키기 위한 물질을 상기 면역세포 분석유닛에 공급하는 면역세포 진단칩.Wherein the immune cell analyzing unit supplies a substance for dissolving the immune cells and for amplifying the amount of the remaining genes in the immune cells dissolved.
PCT/KR2018/010975 2017-11-03 2018-09-18 Immune cell diagnostic chip Ceased WO2019088445A1 (en)

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