Biomolecule imaging sensor and method for detecting biomolecules using the same

Abstract

The present application provides a biomolecule imaging sensor and a method for detecting biomolecules using the same. The biomolecule imaging sensor comprises: an image sensing component comprising a plurality of unit pixels arranged in an array on a substrate, each of the unit pixels comprising at least one photoelectric conversion component that generates electrons upon receiving an incident light, wherein a surface of the image sensing component that receives the incident light is defined as a light receiving surface; and a plurality of detection molecules disposed above the light receiving surface to bind to a biomolecule to be detected.

Description

TECHNICAL FIELD

[0001] The present application relates to a biomolecule imaging sensor and its use for detecting biomolecules, in particular, a biomolecule imaging sensor with detection molecules disposed on the surface of a pixel assembly receiving light and its use for detecting biomolecules. BACKGROUND

[0002] Enzyme-Linked Immunosorbent Assay (ELISA) or Enzyme-linked immunoassay (EIA) is a so-called specific antigen-antibody reaction test that uses the specific binding characteristics between antigens and antibodies to detect the molecules to be detected in the sample, and uses enzymes to perform color reactions, which can show whether specific antigens or antibodies exist, and can be used for quantitative analysis by the depth of color, thereby achieving the purpose of detection and screening.

[0003] Biochip is a micro device that uses biological materials that can produce specific biochemical reactions with the biomolecules to be detected on a substrate and can be quantitatively detected by a highly sensitive detection system. Biochip has the ability of fast, accurate, and low-cost biological analysis and testing, and in molecular biology, biochip is basically a small-sized carrier plate that can perform hundreds or thousands of biochemical reactions at the same time.

[0004] However, after the operation process of traditional biochemical detection such as tissue section, large and expensive equipment is needed to receive optical or electronic signals to detect the status of biochemical molecular reactions, such as observation with a microscope and image capture with an additional camera device for further analysis, which requires a certain amount of time and manual operation. On the other hand, traditional biochip needs to be equipped with other expensive and large image capture systems or devices to detect and capture the luminescence image of the biochip after the biochemical detection process to perform subsequent analysis. Furthermore, traditional ELISA uses an ELISA reader to detect the absorption light in each well of a microplate after the operation of an ELISA kit to make quantitative analysis.

[0005] With the increasing popularity of the concept of POCT (Point of Care Testing), which is a simple and short-time analysis of personalized health detection, in order to overcome the need for large equipment and complex biochemical detection processes in traditional biomolecule detection methods, more sensitive and simple testing equipment and methods are needed. SUMMARY

[0006] Therefore, one of the purposes of the present application is to provide a biomolecule image sensor, comprising: an image sensing component, comprising a plurality of unit pixels arranged in an array on a substrate, and each of the plurality of unit pixels comprises at least one photoelectric conversion component, which generates electrons after receiving an incident light, wherein the surface of the image sensing component receiving the incident light is defined as a light receiving surface; and a plurality of detection molecules arranged above the light receiving surface to bind a to-be-detected biomolecule.

[0007] According to a preferred embodiment of the present application, the biomolecule image sensor further comprises at least one readout circuit coupled to the plurality of unit pixels, and the readout circuit generates a voltage signal according to the number of electrons.

[0008] According to a preferred embodiment of the present application, the plurality of detection molecules can be arranged corresponding to the plurality of unit pixels.

[0009] According to a preferred embodiment of the present application, a binding layer for arranging the plurality of detection molecules above the light receiving surface can be further included between the light receiving surface and the plurality of detection molecules.

[0010] According to a preferred embodiment of the present application, a medium layer for attaching the binding layer above the light receiving surface can be further included between the light receiving surface and the binding layer.

[0011] According to a preferred embodiment of the present application, the binding layer can be formed as a plurality of island structures arranged in an array, and each of the plurality of island structures can be arranged corresponding to a single unit pixel.

[0012] According to a preferred embodiment of the present application, the plurality of island structures can be formed above the light receiving surface by a lithography etching or an imprinting process.

[0013] According to a preferred embodiment of the present application, the binding layer can further comprise a plurality of light blocking layers, and the plurality of light blocking layers can be arranged above the light receiving surface and corresponding to the spaces between the plurality of unit pixels, and the width of the plurality of light blocking layers can be greater than the width of the spaces between the plurality of unit pixels.

[0014] According to a preferred embodiment of the present application, the height of the plurality of light blocking layers can be the same as or different from the height of the medium layer as a whole.

[0015] According to a preferred embodiment of the present application, the incident light can be light emitted by a fluorescent label or a chemiluminescent label of the to-be-detected biomolecule.

[0016] Another object of the present application is to provide a method for detecting a biomolecule using the biomolecule image sensor as described above, comprising: combining a biomolecule to be detected in a sample to be detected with the plurality of detection molecules; allowing the plurality of unit pixels to detect an incident light, wherein the incident light comprises light emitted by a fluorescent label or a chemiluminescent label of the biomolecule to be detected; generating electrons by the photoelectric conversion component from the incident light received by each of the plurality of unit pixels; generating a voltage signal by the plurality of readout circuits according to the number of electrons; and analyzing the presence and / or concentration of the biomolecule to be detected according to the voltage signal.

[0017] The present application is completely innovative to invent a novel image sensor for detecting a biomolecule in a semiconductor process method without additional large equipment, but can directly detect whether a specific molecule exists in a sample to be detected and can be used to quantify the concentration, etc. with a coin smaller image sensor.

[0018] On the other hand, compared with the traditional biochip, the present application does not require additional image capturing systems or equipment, that is, the biomolecule image sensor of the present application itself includes the functions of biological or chemical analysis and image capturing and interpretation, that is, the detection process can be directly operated on the biomolecule image sensor of the present application, and the corresponding detection results can be obtained in real time.

[0019] On the other hand, compared with the traditional biochip, the present application does not require additional image capturing systems or equipment, that is, the biomolecule image sensor of the present application itself includes the functions of biological or chemical analysis and image capturing and interpretation, that is, the detection process can be directly operated on the biomolecule image sensor of the present application, and the corresponding detection results can be obtained in real time.

[0020] In addition, in the biomolecule image sensor of the present application, the detection molecules are arranged above the light receiving surface, so that the photoelectric conversion component of the unit pixel in the image sensing component can be very close to the incident light emitted by the biomolecule to be detected. Therefore, the photoelectric conversion component can receive incident light with weak intensity, thereby improving the detection sensitivity of the biomolecule image sensor of the present application.

[0021] Furthermore, since the light blocking layers are formed between the binding layer and each unit pixel in the biomolecule image sensor of the present application, the photoelectric conversion component can determine whether the incident light is indeed from the luminescent or fluorescent marker on the biomolecule to be detected, and by adjusting the arrangement of the light blocking layers, the single incident light can be received by only a single unit pixel, and the mutual interference between the unit pixels can be effectively reduced.

[0022] In order to enable those skilled in the art to understand the purpose, features and effects of the present application, the present application is described in detail below by means of specific embodiments, and in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 A cross-sectional view of a biomolecule image sensor according to an embodiment of the present application;

[0024] Figure 2 A cross-sectional view of a biomolecule image sensor according to another embodiment of the present application, further comprising a binding layer;

[0025] Figure 3 A cross-sectional view of a biomolecule image sensor according to yet another embodiment of the present application, wherein the binding layer forms an island structure;

[0026] Figure 4 A cross-sectional view of a biomolecule image sensor according to yet another embodiment of the present application, wherein the binding layer further comprises light blocking layers;

[0027] Figure 5 A cross-sectional view of a biomolecule image sensor according to yet another embodiment of the present application, wherein the binding layer forms an island structure and comprises light blocking layers;

[0028] Figure 6A A flow chart of a method for detecting a biomolecule to be detected by a biomolecule image sensor according to an embodiment of the present application;

[0029] Figure 6B A flow chart of a method for detecting a biomolecule to be detected by a biomolecule image sensor according to yet another embodiment of the present application.

[0030] BRIEF DESCRIPTION OF DRAWINGS

[0031] 100, 100A, 100B, 100C, 100D: biomolecule image sensor;

[0032] 10: image sensing component;

[0033] 11: unit pixel;

[0034] 21: detection molecule;

[0035] 30: bonding layer;

[0036] 31: light blocking layer;

[0037] 40: medium layer;

[0038] S11 to S162: steps. DETAILED DESCRIPTION

[0039] Embodiments of the present application will be further described with reference to the drawings, in which the following examples are presented by way of illustration and are not intended to limit the scope of the application. Any person skilled in the art, without departing from the spirit and scope of the present application, can make some changes and modifications, and therefore the scope of protection of the present application shall be subject to the scope defined by the appended claims.

[0040] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the present application, unless otherwise defined, which are commonly understood by those skilled in the art. As used herein, the singular forms "a", "an" and "the" are intended to include plural forms unless the context clearly indicates otherwise. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0041] Similarly, it is to be understood that, when an element is referred to as being "on" or "above" another element, it can be directly on the other element or intervening elements can also be present. In contrast, the term "directly" means that no intervening element is present. It is to be further understood that, as used herein, the term "comprises" or "comprising" or "includes" or "including" means the presence of stated features, integers, steps, operations, components, and / or groups thereof, but not the exclusion of one or more other features, integers, steps, operations, components, and / or groups thereof.

[0042] According to the present application, the operation procedures and parameter conditions related to enzyme-linked immunosorbent assay (ELISA) are within the professional knowledge and routine technical scope of those skilled in the art.

[0043] According to the present application, the fluorescent molecules can be, but are not limited to, FITC, HEX, FAM, TAMRA, Cy3, Cy5, quantum dots, and the like.

[0044] Figures 1 to 5 Biomolecule image sensor according to different embodiments of the present application. As Figures 1 to 5As shown, the biomolecule imaging sensor of the present application comprises an image sensing component 10 and a plurality of detecting molecules 21, and can further comprise at least one readout circuit; wherein the image sensing component 10 can comprise a plurality of unit pixels 11 arranged in an array on a substrate; further, the plurality of detecting molecules 21 can be capable of binding to a to-be-detected biomolecule (not shown in the figure); for example, the plurality of detecting molecules can be a ligand, and the to-be-detected biomolecule can be a receptor thereof, or the plurality of detecting molecules can be a receptor, and the to-be-detected biomolecule can be a ligand thereof, and the interaction between such a receptor and a ligand can be an antigen-antibody, enzyme-substrate, DNA-RNA hybridization, etc.

[0045] More specifically, the image sensing component 10 in the biomolecule imaging sensor according to the present application can be a back-illuminated CMOS (complementary metal-oxide-semiconductor, CMOS) image sensor or a front-illuminated CMOS image sensor, however the present application is not limited thereto.

[0046] In embodiments of the present application, each of the plurality of unit pixels 11 can comprise at least one photoelectric conversion component, wherein the photoelectric conversion component can receive an incident light to generate electrons, and the photoelectric conversion component also has the ability to accumulate the above-mentioned electrons, however the present application is not limited thereto.

[0047] In addition, the photoelectric conversion component can be a component that generates and accumulates electrons corresponding to the incident light. For example, the photoelectric conversion component can be a photodiode, a phototransistor, a photo gate, a pinned photo diode (PPD), an avalanche photodiode (APD), a single-photon avalanche diode (SPAD), a photomultiplier tube (PMT), or any combination thereof.

[0048] In addition, the plurality of detecting molecules 21 can be molecules that have selective and / or specific binding ability to specific molecules; in preferred embodiments of the present application, the plurality of detecting molecules 21 can be, but are not limited to, antibodies or aptamers.

[0049] In an embodiment of the present application, the surface of the image sensing component 10 receiving incident light can be defined as a light receiving surface, and the plurality of detection molecules 21 can be disposed above the light receiving surface; wherein the light receiving surface has the characteristics of light transmittance and low extinction coefficient. In addition, a protective layer can be further formed at the light receiving surface, which is preferably composed of silicon dioxide (SiO2), and the protective layer can prevent external factors from damaging the plurality of unit pixels 11 or other components on the image sensing component 10, such as oxidation, dust prevention, scratch prevention, water vapor prevention, etc.

[0050] In a preferred embodiment of the present application, the plurality of detection molecules 21 can be disposed in correspondence with the plurality of unit pixels 11, especially the photoelectric conversion components therein, so that the photoelectric conversion components in the plurality of unit pixels 11 can emit light corresponding to the detection molecules 21 when receiving incident light to improve detection sensitivity, and also reduce mutual interference between each unit pixel 11.

[0051] In an embodiment of the present application, the plurality of readout circuits can be coupled to the plurality of unit pixels 11 and generate a voltage signal according to the number of electrons generated by the photoelectric conversion components after receiving incident light, as a signal read value.

[0052] In a preferred embodiment of the present application, referring to Figure 1 According to the image sensing component 10 in the biomolecular image sensor 100 of the present application, a CMOS image sensor obtained by semiconductor process can be used, and the surface thereof is oxidized after packaging to form a flat light-transmitting surface composed of silicon dioxide (SiO2), which is the protective layer at the light receiving surface for receiving incident light.

[0053] Then, a plurality of detection molecules 21 are directly fixed on the light receiving surface by chemical modification, for example, the oxygen atoms in the silicon dioxide on the light receiving surface are first surface-modified by a silane compound such as (3-aminopropyl) triethoxysilane (APTES) to make the surface have an amine group (NH2), so that the plurality of detection molecules 21 can be bonded with detection molecules 21 such as antibodies, receptor proteins, DNA, aptamers, or other chemical molecules, to directly fix the plurality of detection molecules 21 on the light receiving surface of the image sensing component 10.

[0054] More specifically, the carboxyl group on the antibody as the detection molecule 21 can be bonded with the amine group on the light receiving surface to be fixed on the light receiving surface by using the EDC / NHS reaction; or the glutaraldehyde can be used to connect the protein G with the amine group on the light receiving surface, since the protein G can bind with the Fc region of most antibodies, thus different specific antibodies as the detection molecule 21 can be flexibly replaced according to different biological molecules to be detected.

[0055] In another preferred embodiment of the present application, referring to Figure 2 In order to make the detection molecules 21 more easily arranged above the light receiving surface, in the biological molecule imaging sensor 100A of the present application, a bonding layer 30 can be further included between the light receiving surface and the detection molecules 21, and the detection molecules 21 are directly fixed on the bonding layer 30. In the embodiments of the present application, the bonding layer 30 can be composed of the following materials, however the present application is not limited thereto: silicon dioxide, polyimide (PI), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), polystyrene (PS), polydimethylsiloxane (PDMS), epoxy, and the like.

[0056] In addition, in order to make the bonding layer 30 more easily and firmly attached above the light receiving surface, a passivation layer 40 can be further included between the light receiving surface and the bonding layer 30. In the embodiments of the present application, the passivation layer 40 can be composed of the following materials, however the present application is not limited thereto: indium tin oxide (ITO), tin dioxide (SnO2), ZnSnO2 (ITO; wherein Zn and Sn can be other atoms), indium oxide (In2O3), silicon nitride, and the like; wherein the skilled in the art can select suitable materials to prepare the passivation layer 40 according to the material of the bonding layer 30.

[0057] In another preferred embodiment of the present application, referring to Figure 3In the biomolecule imaging sensor 100B of the present application, the binding layer 30 can be formed in a plurality of island structures arranged in an array, and each of the plurality of island structures can correspond to a unit pixel 11, preferably a light conversion component in the plurality of unit pixels 11. More specifically, the binding layer 30 can be formed in a plurality of island structures above the light receiving surface by using a semiconductor process, such as photolithography etching or imprinting process, and a dielectric layer 40 can be further included between the light receiving surface and the binding layer 30.

[0058] More specifically, since each of the plurality of island structures in the binding layer 30 directly corresponds to the plurality of unit pixels 11, the detection molecules 21 arranged above the binding layer 30 can be concentrated above the plurality of unit pixels 11, so that the photoelectric conversion components in the plurality of unit pixels 11 can more concentratedly receive incident light emitted by the detection molecules 21, such as luminescence or fluorescence incident light emitted by the biological molecules to be detected combined with the detection molecules 21, when receiving the incident light. Since the incident light is closer to the photoelectric conversion components, the photoelectric conversion components can receive the incident light even if the intensity of the incident light is weak, so that the sensitivity of detecting the specific biological molecules in the sample to be detected can be improved.

[0059] In another preferred embodiment of the present application, referring to Figure 4 In the biomolecule imaging sensor 100C of the present application, the binding layer 30 can further include a plurality of light blocking layers 31 arranged in an array above the light receiving surface and corresponding to spaces between the plurality of unit pixels 11, so as to reduce the mutual interference between the unit pixels 11. More specifically, in order to avoid a single incident light being received by two or more unit pixels 11, that is, a single incident light being received by only a single unit pixel 11, the plurality of light blocking layers 31 can be arranged in the binding layer 30 corresponding to the spaces between the unit pixels 11, so as to avoid the light receiving ranges of the unit pixels 11 interfering with each other. The plurality of light blocking layers 31 can be composed of light absorbing substances, more specifically, black photoresist, metal, or metal compounds, such as chromium trioxide (CrO3), but the present application is not limited thereto.

[0060] Furthermore, based on the relationship between the plurality of unit pixels 11, the size, spacing, and / or setting method of the plurality of light-blocking layers 31 can be adjusted. For example, the width of the plurality of light-blocking layers 31 can be greater than the width of the space between the plurality of unit pixels 11, that is, the plurality of light-blocking layers 31 can slightly cover part of the edges of the plurality of unit pixels 11, so that the setting of the plurality of light-blocking layers 31 allows the opening of the light-receiving range of each unit pixel 11 to be smaller than the plurality of unit pixels 11 themselves, and thus more effectively reduces the mutual interference between the unit pixels 11.

[0061] In another preferred embodiment of the present invention, see Figure 5 Based on such Figure 4 The biomolecular image sensor 100C of the present invention, in order to make the plurality of detection molecules 21 more concentrated and closer to the image sensing component 10, so that the light emitted by the biomolecules to be detected bound thereto is more easily received by the photoelectric conversion component in the unit pixel 11, in the biomolecular image sensor 100D of the present invention, the binding layer 30 can be formed into an island structure as described above using a semiconductor process such as photolithography, and further, the height of each island structure is greater than the height of each light-blocking layer 31, the top of each island structure extends to the top of each light-blocking layer 31, the island structures are independently arranged, and the surface area of ​​the top of each island structure is equal to the surface area of ​​each unit pixel 11.

[0062] The biomolecular imaging sensor according to the present invention is not limited to a specific application. In a preferred embodiment, the biomolecular imaging sensor according to the present invention is used for biological or chemical analysis, such as detecting the presence and / or concentration of a target biomolecule in a sample, i.e., the incident light can be emitted by a fluorescent label, reporter molecule label, or chemiluminescent label of the target biomolecule. More specifically, the target biomolecule detected by the biomolecular imaging sensor of the present invention can emit multiple incident lights, either cold light or fluorescence, through a luminescent reaction with other molecules during the biological or chemical analysis procedure. Furthermore, the target biomolecule can be a protein, peptide, antibody, nucleic acid, or an analogue thereof.

[0063] Furthermore, these biological or chemical analyses and luminescent reactions can be performed on the biomolecular image sensor of the present invention, and the presence and / or concentration of the target biomolecule can be directly detected using the image sensing component 10. For example, ELISA can be performed on the biomolecular image sensor of the present invention, so that the target biomolecule binds to the plurality of detection molecules 21 and undergoes a luminescent reaction to generate a chemical cold light, and the chemical cold light is the incident light received by the photoelectric conversion component in the unit pixel 11.

[0064] More specifically, seeFigure 6A and Figure 6B The method for detecting a biomolecule in a sample using the biomolecule image sensor of the present application can be as follows: the biomolecule in the sample is combined with the detection molecules 21 through ELISA biological or chemical analysis (step S11), and each unit pixel 11 detects an incident light (step S12), wherein the incident light includes the light emitted by the fluorescent or chemiluminescent label of the biomolecule, then the photoelectric conversion component generates an electron from the incident light received by each unit pixel 11 (step S13), and the readout circuit generates a voltage signal according to the electron (step S14), and the presence and / or concentration of the biomolecule is analyzed according to the voltage signal.

[0065] Alternatively, the biomolecule can be detected by a fluorescently labeled antibody or aptamer, and a specific wavelength of excitation light is irradiated to generate a radiation light, and the radiation light is the incident light received by the photoelectric conversion component of the unit pixel 11; wherein an antibody or aptamer labeled with different fluorescent molecules can be used as a detection molecule 21, so that multiple target biomolecules in the same sample can be detected; in addition, in order to use the antibody or aptamer containing multiple fluorescent labels, the CMOS image sensor RGB technology can be used.

[0066] When the biomolecule image sensor of the present application is used to detect the presence and / or concentration of the biomolecule, in addition to the analog colorimetric method, that is, the incident light received by each unit pixel 11 is used as a single signal reading value to determine whether the biomolecule exists (step S151), or the standard concentration curve is compared to obtain the concentration of the biomolecule (step S161); the digital method can also be used for quantification, that is, according to the set threshold value, the unit pixel 11 whose signal reading value exceeds the threshold value is defined as 1 (step S153), and the unit pixel 11 whose signal reading value does not exceed the threshold value is defined as 0 (step S154), and finally the total number of unit pixels 11 with a value of 1 is calculated and compared with the standard concentration curve (step S162), so as to more accurately obtain the concentration of the biomolecule.

[0067] Further, the conventional ELISA is to receive optical or electrical signals after a complicated biochemical detection operation process, and then use large and expensive equipment to detect the biochemical reaction. However, the present application is to use a semiconductor process to develop a novel image sensor for detecting the biological molecules, without the need of additional large equipment. Instead, the present application can use a coin-sized image sensor to directly detect whether the specific biological molecules exist in the sample and to quantify the concentration of the biological molecules.

[0068] In another aspect, compared with the conventional biochip, the present application does not need additional image capturing system or equipment. That is, the biological molecule image sensor of the present application itself includes the functions of biological or chemical analysis, image capturing and interpretation. That is, the detection process can be directly operated on the biological molecule image sensor of the present application, and the corresponding detection results can be obtained in real time.

[0069] In another aspect, compared with the conventional biochip, the present application does not need additional image capturing system or equipment. That is, the biological molecule image sensor of the present application itself includes the functions of biological or chemical analysis, image capturing and interpretation. That is, the detection process can be directly operated on the biological molecule image sensor of the present application, and the corresponding detection results can be obtained in real time.

[0070] In addition, in the biological molecule image sensor of the present application, the detection molecules are arranged above the light receiving surface, so that the photoelectric conversion components of the unit pixels in the image sensing component can be very close to the incident light emitted by the biological molecules to be detected. Therefore, the photoelectric conversion components can receive incident light with weak intensity, thereby improving the detection sensitivity of the biological molecule image sensor of the present application.

[0071] In addition, in the biological molecule image sensor of the present application, the detection molecules are arranged above the light receiving surface, so that the photoelectric conversion components of the unit pixels in the image sensing component can be very close to the incident light emitted by the biological molecules to be detected. Therefore, the photoelectric conversion components can receive incident light with weak intensity, thereby improving the detection sensitivity of the biological molecule image sensor of the present application.

[0072] The above described is the preferred embodiment of the present application, it should be pointed out that for the ordinary person in the art, without departing from the principles described in the present application can also be made several improvements and refinements, these improvements and refinements are also within the scope of the present application.

Claims

1. A biomolecule image sensor, characterized by, The image sensing device comprises: an image sensing component comprising a plurality of unit pixels arranged in an array on a substrate, each of the plurality of unit pixels comprising at least one photoelectric conversion component that generates electrons upon receiving an incident light, wherein a surface of the image sensing component that receives the incident light defines a light receiving surface; a medium layer disposed on the light receiving surface; a binding layer disposed on the medium layer to form a plurality of island structures arranged in an array, each of the plurality of island structures corresponding to a single unit pixel; a plurality of light blocking layers disposed on the medium layer and corresponding to spaces between the plurality of unit pixels; a plurality of detection molecules disposed on the binding layer to bind to a target biomolecule in a target sample; and at least one readout circuit coupled to the plurality of unit pixels, the readout circuit generating a voltage signal according to the number of electrons. Each of the island structures has a height greater than that of each of the light blocking layers, the top of each of the island structures extends to the top of each of the light blocking layers, the plurality of island structures are independently disposed from each other, and the top of each of the island structures has a surface area equal to that of each of the unit pixels. The plurality of unit pixels detect an incident light comprising light emitted by a fluorescent or chemiluminescent label of the target biomolecule, generate electrons from the incident light received by each of the plurality of unit pixels via the photoelectric conversion component, generate a voltage signal according to the number of electrons via the plurality of readout circuits, and analyze the presence and / or concentration of the target biomolecule according to the voltage signal. When detecting the presence and / or concentration of the plurality of target biomolecules, a quantitative analysis is performed via an analog colorimetric method or a digital method. The analog colorimetric method defines a single signal reading value for the incident light received by each of the plurality of unit pixels to determine whether the target biomolecule is present or to compare with a standard concentration curve to obtain the concentration of the target biomolecule. The digital method defines a unit pixel with a signal reading value exceeding a threshold value as 1 and a unit pixel without a signal reading value exceeding the threshold value as 0, calculates the total number of unit pixels with a signal reading value exceeding the threshold value, and compares with a standard concentration curve to more accurately obtain the concentration of the target biomolecule. The plurality of island structures are formed above the light receiving surface via a lithography etching or imprinting process.

2. The biomolecule image sensor according to claim 1, wherein The plurality of light blocking layers have a width greater than that of the spaces between the plurality of unit pixels.

3. The biomolecule image sensor according to claim 1, wherein The incident light is light emitted by a fluorescent or chemiluminescent label of the target biomolecule.

4. The biomolecule image sensor according to claim 1, wherein ​

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