Optical device

Abstract

The invention provides an optical device. The optical device includes a substrate, a first light sensor, a waveguide, and a nanowell array. The first light sensor is arranged on the substrate, and the waveguide is arranged on the first light sensor. The waveguide is in contact with the first light sensor or is separated from the first light sensor by a color filter array in contact with the waveguide and the first light sensor. The nanowell array is disposed on the waveguide, and the optical device does not have a multilayer film filter.

Description

Technical Field

[0001] The present invention relates to an optical device, and more particularly to an optical device for third generations sequencing (TGS). Background Art

[0002] Third-generation sequencing (TGS), also known as long-read sequencing, has a 10- to 1,000-fold increase in read length for a single sample area compared to next-generation sequencing (NGS) that relies on short-read methods, and has a fast processing speed and an accuracy of up to 99.9%. The technology behind third-generation sequencing (TGS) involves the use of single-molecule real-time (SMRT) sequencing, which uses single molecules to produce photoluminescence by binding fluorescently labeled nucleotides to anchored polymerases. Due to the weak emission of single molecules, an optical density filter with an OD greater than 6 is required to eliminate interference from the excitation light. The filter is typically an interference-type multilayer filter with a thickness of 10 μm, located on a complementary metal oxide semiconductor (CMOS)-based deoxyribonucleic acid (DNA) sequencing chip. In order to make whole-genome sequencing more cost-effective and faster, it is necessary to develop an image system with a small pixel size with high resolution. However, current technology relies on ultra-thick multi-layer filters to filter the excitation light and pass the fluorescence signal to achieve a high signal-to-noise ratio, which limits the miniaturization of imaging systems, causes cross-talk between signals, and increases sequencing costs. Summary of the invention

[0003] An object of the present invention is to provide an optical device to solve at least one of the above problems.

[0004] The present invention discloses a method for creating a miniaturized third generation sequencing (TGS) complementary metal oxide semiconductor (CMOS) chip without relying on optical density (OD) filters. The method eliminates the need for expensive manufacturing costs and can still have a sufficient signal-to-noise ratio at a reduced pixel size.

[0005] According to one embodiment of the present invention, an optical device is provided. The optical device includes a substrate, a first light sensor, a waveguide, and a nano-well array. The first light sensor is disposed on the substrate. The waveguide is disposed on the first light sensor. The waveguide is in contact with the first light sensor or is separated from the first light sensor by a color filter array in contact with the waveguide and the first light sensor. The nano-well array is disposed on the waveguide.

[0006] In some embodiments, the substrate includes a complementary metal oxide semiconductor (CMOS) readout circuit array.

[0007] In some embodiments, the waveguide transmits long wavelength light with a wavelength of 800nm ​​to 1,600nm. In some embodiments, the nanowell array is loaded with fluorescently labeled nucleotides to convert the long wavelength light into short wavelength light with a wavelength of 400nm to 800nm. In some embodiments, the first photosensor includes a first photoactive layer having a first energy gap, the first energy gap being less than the photon energy of the short wavelength light and greater than the photon energy of the long wavelength light. In some embodiments, the first energy gap of the first photoactive layer is in the range of 1.5eV to 2.5eV. In some embodiments, the first photoactive layer includes an organic semiconductor, an inorganic semiconductor, or a perovskite semiconductor. In some embodiments, the first photoactive layer absorbs the short wavelength light. In some embodiments, the pixel size of the optical device is less than 10μm, such as 10μm, 3μm, or 1μm.

[0008] In some embodiments, the optical device further includes a second photosensor, including a second photoactive layer having a second energy gap, disposed between the substrate and the first photosensor. In some embodiments, the first energy gap of the first photoactive layer is greater than the second energy gap of the second photoactive layer. In some embodiments, the optical device further includes a third photosensor, including a third photoactive layer having a third energy gap, disposed between the substrate and the second photosensor. In some embodiments, the second energy gap of the second photoactive layer is greater than the third energy gap of the third photoactive layer. In some embodiments, the optical device further includes a fourth photosensor, including a fourth photoactive layer having a fourth energy gap, disposed between the substrate and the third photosensor. In some embodiments, the third energy gap of the third photoactive layer is greater than the fourth energy gap of the fourth photoactive layer. In some embodiments, the first photoactive layer absorbs short-wavelength light mainly in the range of 400nm to 550nm, the second photoactive layer absorbs short-wavelength light mainly in the range of 530nm to 650nm, the third photoactive layer absorbs short-wavelength light mainly in the range of 580nm to 700nm, and the fourth photoactive layer absorbs short-wavelength light mainly in the range of 620nm to 750nm. In some embodiments, the pixel size of the optical device is less than 20μm, such as 20μm, 15μm, 8μm, 4μm or 2μm.

[0009] In some embodiments, the waveguide transmits short-wavelength light with a wavelength of 300nm to 500nm. In some embodiments, the nanowell array is loaded with a polymerase to sequentially connect the single-stranded DNA sequence of the template with complementary fluorescent-labeled nucleotides to synthesize double-stranded DNA. The short-wavelength light excites the fluorescence labeled by each connected nucleotide and is converted into long-wavelength light with a wavelength of 500nm to 800nm. The converted long-wavelength light will be determined by the different fluorescent molecules labeled on different nucleotides (A, T, G, C). In some embodiments, the first light sensor includes a first photoactive layer with a first energy gap, a second photoactive layer with a second energy gap, a third photoactive layer with a third energy gap, and a fourth photoactive layer with a fourth energy gap, which are arranged in a mosaic form on a horizontal plane. In some embodiments, the first energy gap, the second energy gap, the third energy gap and the fourth energy gap are different. In some embodiments, the thickness of the first photoactive layer, the second photoactive layer, the third photoactive layer and the fourth photoactive layer is greater than 2μm. In some embodiments, the first photoactive layer absorbs long wavelength light with a wavelength of 550 nm, the second photoactive layer absorbs long wavelength light with a wavelength of 650 nm, the third photoactive layer absorbs long wavelength light with a wavelength of 700 nm, and the fourth photoactive layer absorbs long wavelength light with a wavelength of 750 nm.

[0010] In some embodiments, the first photosensor includes a first photoactive layer having a first energy gap, and the thickness of the first photoactive layer is greater than 2 μm. In some embodiments, the optical device further includes a second photosensor including a second photoactive layer having a second energy gap, disposed between the substrate and the first photosensor. In some embodiments, the first energy gap of the first photoactive layer is greater than the second energy gap of the second photoactive layer. In some embodiments, the optical device further includes a third photosensor including a third photoactive layer having a third energy gap, disposed between the substrate and the second photosensor. In some embodiments, the second energy gap of the second photoactive layer is greater than the third energy gap of the third photoactive layer. In some embodiments, the optical device further includes a fourth photosensor including a fourth photoactive layer having a fourth energy gap, disposed between the substrate and the third photosensor. In some embodiments, the third energy gap of the third photoactive layer is greater than the fourth energy gap of the fourth photoactive layer. In some embodiments, the first photoactive layer absorbs long wavelength light with a wavelength of 550nm, the second photoactive layer absorbs long wavelength light with a wavelength of 530nm to 650nm, the third photoactive layer absorbs long wavelength light with a wavelength of 580nm to 700nm, and the fourth photoactive layer absorbs long wavelength light with a wavelength of 620nm to 750nm.

[0011] In the present invention, when long-wavelength light is used as a light source, combined with fluorescently labeled nucleotides located in the sample well that can convert long-wavelength light into short-wavelength light, and a wide bandgap semiconductor that is sensitive to short-wavelength light used in the photoactive layer, there is no need to add long-pass or short-pass filters, which can significantly reduce the module thickness, allow for smaller pixel sizes, and eliminate optical crosstalk problems. In addition, when short-wavelength light is used as a light source, combined with a thick photoactive layer, the thick photoactive layer can filter out short-wavelength light (i.e., noise), and at the same time, the photoactive layer improves the sensitivity of narrow-band light (i.e., signal) to achieve a high S / N ratio. The present invention provides a high-resolution, tiny pixel-size optical device for third-generation sequencing (TGS).

[0012] Embodiments are given in the following examples with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The present invention may be more fully understood by reading the following detailed description and examples and by referring to the accompanying drawings, in which:

[0014] Figure 1A A schematic cross-sectional view of an optical device according to an embodiment of the present invention;

[0015] Figure 1B is an enlarged cross-sectional schematic diagram showing some components in an optical device according to an embodiment of the present invention;

[0016] Figure 1C is an enlarged cross-sectional schematic diagram showing some components in an optical device according to an embodiment of the present invention;

[0017] Figure 1D According to one embodiment of the present invention, the absorption and reflection spectra of the light sensor are shown;

[0018] Figure 2A A schematic cross-sectional view of an optical device according to an embodiment of the present invention;

[0019] Figure 2B According to one embodiment of the present invention, the absorption and reflection spectra of the light sensor are shown;

[0020] Figure 3 A schematic cross-sectional view of an optical device according to an embodiment of the present invention;

[0021] Figure 4 A top view showing some components of an optical device according to an embodiment of the present invention;

[0022] Figure 5A-5D According to one embodiment of the present invention, the absorption and reflection spectra of the light sensor are shown;

[0023] Figure 6 A schematic cross-sectional view showing an optical device according to an embodiment of the present invention; and

[0024] Figure 7A-7B FIG. 1 is a diagram showing absorption and reflection spectra of a light sensor according to an embodiment of the present invention.

[0025] The reference numerals are as follows:

[0026] 10: Optical Devices

[0027] 12:Substrate

[0028] 14: Light sensor

[0029] 14a: First light sensor

[0030] 14b: Second light sensor

[0031] 14c: Third light sensor

[0032] 14d: Fourth light sensor

[0033] 16: Color filter array

[0034] 18: Waveguide

[0035] 20: Nanowell Array

[0036] 20':Nanowell

[0037] 22: Complementary Metal Oxide Semiconductor (CMOS) Readout Circuit Array

[0038] 24: Lower electrode

[0039] 26: Electron transport layer

[0040] 28, 28a, 28b, 28c, 28d: Photoactive layer

[0041] 28': Photoactive layer array

[0042] 30: Hole transport layer

[0043] 32: Upper electrode

[0044] 34: Encapsulation layer

[0045] 36,48: Long wavelength light

[0046] 38: Deoxyribonucleic acid (DNA)

[0047] 40: polymerase

[0048] 42: Fluorescently labeled nucleotides

[0049] 44,46: Short wavelength light

[0050] Ps: Pixel size

[0051] T: Thickness of the photoactive layer array

[0052] Ta: thickness of the first light sensor DETAILED DESCRIPTION

[0053] The optical device of the present invention is described in detail in the following description. In the following embodiments, for the purpose of explanation, many specific details and embodiments are set forth to provide a thorough understanding of the present disclosure. The specific elements and configurations described in the following embodiments are set forth to clearly describe the present disclosure. However, it will be apparent that the exemplary embodiments set forth herein are for illustrative purposes only, and the inventive concept can be embodied in various forms, without being limited to those exemplary embodiments. In addition, the drawings of different embodiments may use similar and / or corresponding numbers to represent similar and / or corresponding elements in order to clearly describe the present disclosure. However, the use of similar and / or corresponding numbers in the drawings of different embodiments does not imply any correlation between different embodiments. In addition, in this specification, for example, the expression "a first material layer disposed on / above a second material layer" may refer to direct contact between the first material layer and the second material layer, or it may refer to a non-contact state with one or more intermediate layers between the first material layer and the second material layer. In the above case, the first material layer may not be in direct contact with the second material layer.

[0054] In addition, in this specification, relative expressions are used. For example, "lower", "bottom", "upper" or "top" are used to describe the position of an element relative to another element. It should be understood that if the device is turned upside down, the "lower" element will become the "upper" element.

[0055] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as generally understood by one of ordinary skill in the art to which the invention belongs. It should be understood that in various cases, terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with the relative skill of the present disclosure and the background or context of the present disclosure, and should not be interpreted in an idealized or overly formal manner unless so defined.

[0056] In the description, relative terms such as "lower", "upper", "horizontal", "vertical", "below", "above", "top", "bottom", etc. should be understood as the orientation shown in the embodiment and related drawings. This relative terminology is for the convenience of description and does not mean that the device described needs to be manufactured or operated in a specific orientation. In addition, terms related to bonding and connection, such as "connection", "interconnection", etc., unless otherwise defined, can indicate that two structures are in direct contact, or can also indicate that two structures are not in direct contact, but there is another structure arranged between the two structures. In addition, terms related to bonding and connection can also include embodiments in which both structures are movable or both structures are fixed.

[0057] It should be understood that, although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, film layers, parts and / or sections, these elements, components, regions, film layers, parts and / or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, film layer, part or section from another element, component, region, film layer, part or section. Therefore, without departing from the teachings of the present disclosure, the first element, component, region, film layer, part or section discussed below may be referred to as the second element, component, region, film layer, part or section.

[0058] In the specification, the terms "about", "approximately" and "generally" generally indicate a range within plus or minus 20%, plus or minus 10%, plus or minus 5%, plus or minus 3%, plus or minus 2%, plus or minus 1%, or plus or minus 0.5% of a given value. The quantity given here is an approximate quantity, that is, in the absence of a specific description of "about", "approximately" and "generally", the meaning of "about", "approximately" and "generally" can still be implied.

[0059] The following description is the best mode of implementing the present invention. The purpose of this description is to illustrate the general principles of the present invention and should not be considered as limiting. The scope of the present invention shall be determined by the appended claims.

[0060] See also Figure 1A-Figure 1C According to one embodiment of the present invention, an optical device 10 is provided. Figure 1A A schematic cross-sectional view of the optical device 10 is shown. Figure 1B The enlarged cross-sectional diagram shows a part of the components (ie, the light sensor) in the optical device 10 . Figure 1C An enlarged cross-sectional schematic diagram showing a portion of components (ie, a well in the well array) in the optical device 10 .

[0061] like Figure 1AAs shown, the optical device 10 includes a substrate 12, a light sensor 14, a color filter array 16, a waveguide 18, and a nano-well array 20. The light sensor 14 is disposed on the substrate 12. The color filter array 16 is disposed on the light sensor 14. The waveguide 18 is disposed on the color filter array 16. The nano-well array 20 is disposed on the waveguide 18.

[0062] In some embodiments, the substrate 12 includes a silicon substrate, but the invention is not limited thereto. In some embodiments, the substrate 12 includes a complementary metal oxide semiconductor (CMOS) readout circuit array 22 .

[0063] See also Figure 1B , further providing a detailed structure of the photo sensor 14. In some embodiments, the photo sensor 14 includes a lower electrode 24, an electron transport layer (ETL) 26, a photoactive layer 28, a hole transport layer (HTL) 30, an upper electrode 32, and an encapsulation layer 34. The electron transport layer (ETL) 26 is disposed on the lower electrode 24. The photoactive layer 28 is disposed on the electron transport layer (ETL) 26. The hole transport layer (HTL) 30 is disposed on the photoactive layer 28. The upper electrode 32 is disposed on the hole transport layer (HTL) 30. The encapsulation layer 34 is disposed on the upper electrode 32. In some embodiments, the energy gap of the photoactive layer 28 is approximately in the range of 1.5 eV to 2.5 eV. In some embodiments, the material of the photoactive layer 28 includes an organic semiconductor, an inorganic semiconductor, or a perovskite semiconductor, for example, amorphous silicon (a-Si), Zu2ZnSnS4, CH3NH3PbCl3, CH3NH3PbBr3, CH3NH3PbI3, Rubrene mixture, UPSQ, P3HT, PBT-OTT, OC1C10-PPV, PCDTBT, PDPP5T, PDPP3T, PDPPSDTPS, PCBM, P70BM, C60, C70, ICBA, bis-PCBM, [6 0]IPB, N2200, Y6, Y7, COTIC-4Cl, 6TIC, ZY-4Cl, IEICO-4Cl, ITIC, ITIC-4F, ITIC-M, DTY6, BTP-eC9, ITIC-Th, o-IDTBR, ITIC-4Cl, COTIC-4Cl, 6TIC, IDT-2Br, COTIC-4F, ITIC-DM, ZY-4Cl, IEICO-4Cl, BTP-4Cl-12, N3, L8-BO-F, or L8-BO, but the present invention is not limited thereto.

[0064] In some embodiments, the waveguide 18 transmits long wavelength light 36. In some embodiments, the wavelength of the long wavelength light 36 is approximately in the range of 800 nm to 1,600 nm. In some embodiments, the long wavelength light 36 includes near infrared (NIR) light and short wave infrared (SWIR) light.

[0065] See also Figure 1C In some embodiments, the nanowell 20' in the nanowell array 20 is loaded with, for example, deoxyribonucleic acid (DNA) 38, polymerase 40, and fluorescently labeled nucleotides 42. In some embodiments, the fluorescently labeled nucleotides 42 include four different fluorescently labeled nucleotides, which are respectively used to identify the A base, T base, G base, and C base on the DNA 38. In some embodiments, the fluorescently labeled nucleotides 42 include, for example, (ErL)2F compounds (Er: erbium (rare earth element), L: F: fluorine), but the present invention is not limited thereto. In some embodiments, the fluorescently labeled nucleotide 42 converts the long wavelength light 36 into short wavelength light 44. In some embodiments, the wavelength of the short wavelength light 44 is approximately in the range of 400nm to 800nm. In some embodiments, the short wavelength light 44 includes visible light.

[0066] In some embodiments, in the optical device 10 , the pixel size Ps is approximately less than or equal to 10 μm.

[0067] See also Figure 1A-Figure 1CThe sensing mechanism of the optical device 10 is further described below. The waveguide 18 transmits the long wavelength light 36 (i.e., the excitation light) to the nanowell 20' in the nanowell array 20. In the nanowell 20', the polymerase 40 binds to the specific base (i.e., A, T, G or C) on the single strand of DNA 38 and the corresponding fluorescently labeled nucleotide 42. When the anchored polymerase grabs the fluorescently labeled complementary nucleotide 42 according to the base template on the single strand of DNA, the long wavelength light 36 is absorbed by the up conversion molecule and a specific short wavelength light 44 (i.e., the emission light) is emitted. The wavelength of the emission light depends on the fluorescent species labeled by the base of the single strand of DNA and the anchor nucleotide of its complementary strand. For example, the fluorescently labeled nucleotides anchored by base A mainly emit photons with wavelengths between 400-550nm, the fluorescently labeled nucleotides anchored by base T emit photons with wavelengths between 530-650nm, the fluorescently labeled nucleotides anchored by base G emit photons with wavelengths between 580-700nm, and the fluorescently labeled nucleotides anchored by base C emit photons with wavelengths between 620-750nm. The upconversion process involves combining low-energy photons to produce light of higher energy levels, which is called the Anti-Stokes luminescence process. This phenomenon is often observed in rare earth-doped phosphors and rare earth-based nanoparticles. Rare earth ions, such as Er, Tm, and Ho, have energy levels from the near infrared (NIR) to the visible light region, and exhibit long-lasting excited states due to Laporte forbidden electric dipole transitions. Multiple factors make multiple first-order absorption phenomena possible, resulting in the cumulative effect of upconversion (UC). The specific short-wavelength light 44 passes through the specific color filter in the color filter array 16. The light sensor 14 absorbs the specific short-wavelength light 44 and converts the optical signal of the specific short-wavelength light 44 into an electrical signal, and then transmits the electrical signal to the readout circuit (not shown) in the substrate 12 to identify the base sequence on the DNA 38.

[0068] Next, according to Figure 1D The absorption spectrum (curve 1) and reflection spectrum (curve 1') of the light sensor 14 further illustrate that the light sensor 14 can absorb short-wavelength light below 700nm, and has no sensitivity to light above 700nm, so as to achieve the purpose of eliminating noise. In some embodiments, the excitation light wavelength range transmitted by the waveguide 18 is approximately 800nm ​​to 1,600nm, for example, 840nm. Figure 1D, the absorption intensity of the photoactive layer 28 (i.e., P3HT:PCBM) for different wavelength bands is represented by curve 1. As can be seen from curve 1, the photoactive layer 28 has a strong absorption for short-wavelength emission light with a wavelength of about 400-700nm, for example, the absorption intensity is about 0.8 or higher. However, the photoactive layer 28 hardly absorbs long-wavelength emission light with a wavelength greater than 800nm. The absorption spectra of other material layers in the optical sensor 14 are also disclosed herein, for example, an indium tin oxide (ITO) material layer (represented by curve 2), a silver (Ag) material layer (represented by curve 3), an aluminum-doped zinc oxide (AZO) material layer (represented by curve 4), and a molybdenum oxide (MoO3) material layer (represented by curve 5). The above material layers and the photoactive layer 28 have very different absorption intensities in different wavelength bands. For example, it can be seen from curves 2 to 5 that multiple material layers (e.g., ITO, Ag, AZO, MoO3) hardly absorb short-wavelength emission light with a wavelength of approximately 400-800nm. In addition, the reflection intensity of the light sensor 14 for different wavelength bands is represented by curve 1'. As can be seen from curve 1', the light sensor 14 has a strong reflection for long-wavelength emission light with a wavelength greater than 700nm, for example, the reflection intensity is approximately 0.9 or greater. Therefore, the light sensor 14 having a photoactive layer 28 of a specific wide energy gap material can absorb short-wavelength light, but has no sensitivity to long-wavelength light above 800nm. In other words, because the energy gap of the photoactive layer 28 of the light sensor 14 is less than the photon energy of the short-wavelength light 44 but greater than the photon energy of the long-wavelength light 36, the photoactive layer 28 has sensitivity to the short-wavelength light 44 but has no sensitivity to the long-wavelength light 36. That is, the photoactive layer 28 does not absorb the long wavelength light 36 (in this case, noise), and a high S / N ratio is achieved.

[0069] See also Figure 2A According to one embodiment of the present invention, an optical device 10 is provided. Figure 2A A schematic cross-sectional view of the optical device 10 is shown.

[0070] like Figure 2A As shown, the optical device 10 includes a substrate 12, a first light sensor 14a, a second light sensor 14b, a third light sensor 14c, a fourth light sensor 14d, a waveguide 18, and a nano-well array 20. The fourth light sensor 14d is disposed on the substrate 12. The third light sensor 14c is disposed on the fourth light sensor 14d. The second light sensor 14b is disposed on the third light sensor 14c. The first light sensor 14a is disposed on the second light sensor 14b. The waveguide 18 is disposed on the first light sensor 14a. The nano-well array 20 is disposed on the waveguide 18.

[0071] In some embodiments, the substrate 12 includes a silicon substrate, but the invention is not limited thereto. In some embodiments, the substrate 12 includes a complementary metal oxide semiconductor (CMOS) readout circuit array 22 .

[0072] The detailed structure of each of the first photo sensor 14a, the second photo sensor 14b, the third photo sensor 14c, and the fourth photo sensor 14d includes a lower electrode, an electron transport layer (ETL), a photoactive layer, a hole transport layer (HTL), an upper electrode, and an encapsulation layer, which is similar to Figure 1B The structure of the photo sensor 14 is not described in detail here. In some embodiments, the energy gap of the photoactive layer in each of the first photo sensor 14a, the second photo sensor 14b, the third photo sensor 14c, and the fourth photo sensor 14d is approximately in the range of 1.5eV to 2.5eV. In some embodiments, the energy gap of the photoactive layer in the first photo sensor 14a is greater than the energy gap of the photoactive layer in the second photo sensor 14b, the energy gap of the photoactive layer in the second photo sensor 14b is greater than the energy gap of the photoactive layer in the third photo sensor 14c, and the energy gap of the photoactive layer in the third photo sensor 14c is greater than the energy gap of the photoactive layer in the fourth photo sensor 14d.

[0073] In some embodiments, the material of the photoactive layer in the first photo sensor 14a, the second photo sensor 14b, the third photo sensor 14c, and the fourth photo sensor 14d includes an organic semiconductor, an inorganic semiconductor, or a perovskite semiconductor, for example, amorphous silicon (a-Si), Zu2ZnSnS4, CH3NH3PbCl3, CH3NH3PbBr3, CH3NH3PbI3, Rubrene mixture, UPSQ, P3HT, PBT-OTT, OC1C10-PPV, PCDTBT, PDPP5T, PDPP3T, PDPPSDTPS, PCBM, P70BM, C60, C70, ICBA, bis-PCBM,

[60] IPB, N2200, Y6, Y7, COTIC-4Cl, 6TIC, ZY-4Cl, IEICO-4Cl, ITIC, ITIC-4F, ITIC-M, DTY6, BTP-eC9, ITIC-Th, o-IDTBR, ITIC-4Cl, COTIC-4Cl, 6TIC, IDT-2Br, COTIC-4F, ITIC-DM, ZY-4Cl, IEICO-4Cl, BTP-4Cl-12, N3, L8-BO-F, or L8-BO, but the present invention is not limited thereto. In some embodiments, the materials of the photoactive layers in the first light sensor 14a, the second light sensor 14b, the third light sensor 14c, and the fourth light sensor 14d are different. For example, the material of the photoactive layer in the first light sensor 14a absorbs light with a wavelength between about 400-550nm. The material of the photoactive layer in the second photosensor 14b absorbs light with a wavelength between about 530-650 nm. The material of the photoactive layer in the third photosensor 14c absorbs light with a wavelength between about 580-700 nm. The material of the photoactive layer in the fourth photosensor 14d absorbs light with a wavelength between about 620-750 nm.

[0074] In some embodiments, the waveguide 18 transmits long wavelength light 36. In some embodiments, the wavelength of the long wavelength light 36 is approximately in the range of 800 nm to 1,600 nm. In some embodiments, the long wavelength light 36 includes near infrared (NIR) light and short wave infrared (SWIR) light.

[0075] DNA 38, polymerase 40, and fluorescently labeled nucleotides 42 are loaded into nanowells 20' in the nanowell array 20, similar to Figure 1C The loading status shown will not be described in detail here.

[0076] In some embodiments, in the optical device 10 , the pixel size Ps is approximately less than or equal to 20 μm.

[0077] See also Figure 2A and Figure 1C , the sensing mechanism of the optical device 10 is further described below. The waveguide 18 transmits the long wavelength light 36 (i.e., the excitation light) to the nanowell 20' in the nanowell array 20. In the nanowell 20', the polymerase 40 binds to the specific base (i.e., A, T, G or C) on the DNA 38 and the corresponding fluorescently labeled nucleotide 42. The fluorescently labeled nucleotide 42 absorbs the long wavelength light 36 and emits a specific short wavelength light 44 (i.e., the emission light). For example, when the fluorescently labeled nucleotide 42 emits light with a wavelength of about 500nm, since the photon energy of the light source is less than the energy gap of the photoactive layer in the first light sensor 14a, the first light sensor 14a only absorbs the 500nm light and converts the optical signal into an electrical signal, and then transmits the electrical signal to the readout circuit (not shown) in the substrate 12 to identify the specific base on the DNA 38 corresponding to the light wavelength of 500nm. When the fluorescently labeled nucleotide 42 emits light with a wavelength of approximately 600 nm, since the photon energy of the light is less than the energy gap of the photoactive layer in the first light sensor 14 a but greater than the energy gap of the photoactive layer in the second light sensor 14 b, the light with a wavelength of approximately 600 nm will pass through the first light sensor 14 a, but the second light sensor 14 b will absorb the light with a wavelength of approximately 600 nm and convert the green light signal into an electrical signal, and then transmit the electrical signal to the readout circuit (not shown) in the substrate 12 to identify the specific base corresponding to the green light on the DNA 38. When the fluorescently labeled nucleotide 42 emits light with a wavelength of approximately 650 nm, since the photon energy of the light with a wavelength of approximately 650 nm is smaller than the energy gap of the photoactive layer in the first light sensor 14 a and the second light sensor 14 b but larger than the energy gap of the photoactive layer in the third light sensor 14 c, the light with a wavelength of approximately 650 nm will pass through the first light sensor 14 a and the second light sensor 14 b, but the third light sensor 14 c will absorb the orange light and convert the optical signal of the light with a wavelength of approximately 650 nm into an electrical signal, and then transmit the electrical signal to the readout circuit (not shown) in the substrate 12 to identify the specific base on the DNA 38 corresponding to the light with a wavelength of approximately 650 nm. When the fluorescently labeled nucleotide 42 emits light with a wavelength of approximately 700 nm, since the photon energy of the light with a wavelength of approximately 700 nm is smaller than the energy gap of the photoactive layer in the first light sensor 14 a, the second light sensor 14 b, and the third light sensor 14 c but larger than the energy gap of the photoactive layer in the fourth light sensor 14 d, the light with a wavelength of approximately 700 nm will pass through the first light sensor 14 a, the second light sensor 14 b, and the third light sensor 14 c, but the fourth light sensor 14 d will absorb the light with a wavelength of approximately 700 nm and convert the red light signal into an electrical signal, which is then transmitted to the readout circuit (not shown) in the substrate 12 to identify the specific base on the DNA 38 corresponding to the light with a wavelength of approximately 700 nm.

[0078] Next, according to Figure 2B The absorption spectrum and reflection spectrum of the light sensor further illustrate that the first light sensor 14a, the second light sensor 14b, the third light sensor 14c, and the fourth light sensor 14d can absorb short-wavelength light of different wavelength bands and filter out long-wavelength light (i.e., have narrow-band characteristics) to achieve the purpose of eliminating noise. In some embodiments, the wavelength range of the excitation light transmitted by the waveguide 18 is approximately 800nm ​​to 1,600nm, for example, 980nm. The photoactive layer can be composed of Rubrene mixture, UPSQ, P3HT, PBT-OTT, OC1C10-PPV, PCDTBT, PDPP5T, PDPP3T, PDPPSDTPS, PCBM, P70BM, C60, C70, ICBA, bis-PCBM,

[60] IPB, N2200, Y6, Y7, COTIC-4Cl, 6TIC, ZY-4Cl, IEICO-4Cl, ITIC, ITIC-4F, ITIC-M, DTY6, BTP-eC9, ITIC-Th, o-IDTBR, ITIC-4Cl, COTIC-4Cl, 6TIC, IDT-2Br, COTIC-4F, ITIC-DM, ZY-4Cl, IEICO-4Cl, BTP-4Cl-12, N3, L8-BO-F, or L8-BO. Figure 2B , the absorption intensity of the photoactive layer (i.e., UPSQ) of the first photosensor 14a in different wavelength bands is represented by Curve 1. The absorption intensity of the photoactive layer (i.e., PBT-OTT:PCBM) of the second photosensor 14b in different wavelength bands is represented by Curve 2. The absorption intensity of the photoactive layer (i.e., OC1C10-PPV:PCBM) of the third photosensor 14c in different wavelength bands is represented by Curve 3. The absorption intensity of the photoactive layer (i.e., PTB7-Th:PCBM) of the fourth photosensor 14d in different wavelength bands is represented by Curve 4.

[0079] The photoactive layer can be composed of Rubrene mixture, UPSQ, P3HT, PBT-OTT, OC1C10-PPV, PCDTBT, PDPP5T, PDPP3T, PDPPSDTPS, PCBM, P70BM, C60, C70, ICBA, bis-PCBM,

[60] IPB, N2200, Y6, Y7, COTIC-4Cl, 6TIC, ZY-4Cl, IEICO-4Cl, ITIC, ITIC-4F, ITIC-M, DTY6, BTP-eC9, ITIC-Th, o-IDTBR, ITIC-4Cl, COTIC-4Cl, 6TIC, IDT-2Br, COTIC-4F, ITIC-DM, ZY-4Cl, IEICO-4Cl, BTP-4Cl-12, N3, L8-BO-F, or L8-BO. As can be seen from Curve 1, the photoactive layer (i.e., UPSQ) of the first photosensor 14a has strong absorption for a specific short-wavelength emission light having a wavelength of about 400-550nm, for example, the absorption intensity is about 0.8 or higher. However, the photoactive layer of the first photosensor 14a hardly absorbs the emission light having a wavelength greater than 600nm. As can be seen from Curve 2, the photoactive layer (i.e., PBT-OTT:PCBM) of the second photosensor 14b has strong absorption for a specific short-wavelength emission light having a wavelength of about 530-650nm, for example, the absorption intensity is about 0.65 or higher. However, the photoactive layer of the second photosensor 14b hardly absorbs the emission light having a wavelength greater than 650nm. As can be seen from Curve 3, the photoactive layer (i.e., OC1C10-PPV:PCBM) of the third photosensor 14c has strong absorption for a specific short-wavelength emission light having a wavelength of about 580-700nm, for example, the absorption intensity is about 0.6 or higher. However, the photoactive layer of the third light sensor 14c hardly absorbs emission light with a wavelength greater than 700nm. As can be seen from Curve 4, the photoactive layer of the fourth light sensor 14d (i.e., PTB7-Th:PCBM) has strong absorption for a specific short-wavelength emission light with a wavelength of about 620-750nm, for example, the absorption intensity is about 0.8 or higher. However, the photoactive layer of the fourth light sensor 14d hardly absorbs emission light with a wavelength greater than 750nm. By corresponding the fluorescence band to the first to fourth light absorption layer bands, the fluorescence band can be identified, and then the type of nucleotide and the type of base on the DNA template can be estimated.

[0080] The absorption spectra of other material layers in the optical sensor are also disclosed herein, for example, the indium tin oxide (ITO) material layer (represented by curve 5), the intermediate layer (represented by curve 6), and the silver (Ag) material layer (represented by curve 7). The absorption intensities of the above material layers and the photoactive layer in different wavelength bands are greatly different. For example, it can be seen from curves 5 to 7 that multiple material layers (e.g., ITO, intermediate layer, Ag) hardly absorb short-wavelength emission light with a wavelength of about 400-800nm. In addition, the reflection intensity of the optical sensor for different wavelength bands is represented by curve 1'. It can be seen from curve 1' that the optical sensor has a strong reflection for long-wavelength emission light with a wavelength greater than 800nm, for example, the reflection intensity is about 0.9 or greater. Therefore, the first optical sensor 14a, the second optical sensor 14b, the third optical sensor 14c, and the fourth optical sensor 14d each having a photoactive layer of a specific wide bandgap material can absorb short-wavelength light of different wavelength bands respectively, but have no sensitivity to light with a wavelength greater than 800nm. In other words, since the energy gaps of the photoactive layers in the first photo sensor 14a, the second photo sensor 14b, the third photo sensor 14c, and the fourth photo sensor 14d are different (decreasing from top to bottom) and are greater than the photon energy of the long wavelength light 36, the photoactive layers in the first photo sensor 14a, the second photo sensor 14b, the third photo sensor 14c, and the fourth photo sensor 14d are sensitive to short wavelength light 44 of different wavelength bands, respectively, but not sensitive to the long wavelength light 36. In other words, the photoactive layers in the first photo sensor 14a, the second photo sensor 14b, the third photo sensor 14c, and the fourth photo sensor 14d do not absorb the long wavelength light 36 (which is noise in this case), and a high S / N ratio is achieved.

[0081] See also Figure 3 and Figure 4 According to one embodiment of the present invention, an optical device 10 is provided. Figure 3 A schematic cross-sectional view of the optical device 10 is shown. Figure 4 A top view of a portion of the components of optical device 10 (ie, the array of photoactive layers) is shown.

[0082] like Figure 3 As shown, the optical device 10 includes a substrate 12, a light sensor 14, a waveguide 18, and a nano-well array 20. The light sensor 14 is disposed on the substrate 12. The waveguide 18 is disposed on the light sensor 14. The nano-well array 20 is disposed on the waveguide 18.

[0083] In some embodiments, the substrate 12 includes a silicon substrate, but the invention is not limited thereto. In some embodiments, the substrate 12 includes a complementary metal oxide semiconductor (CMOS) readout circuit array 22 .

[0084] The detailed structure of the photo sensor 14 is further provided. In some embodiments, the photo sensor 14 includes a lower electrode 24, an electron transport layer (ETL) 26, a photoactive layer array 28', a hole transport layer (HTL) 30, an upper electrode 32, and an encapsulation layer 34. The electron transport layer (ETL) 26 is disposed on the lower electrode 24. The photoactive layer array 28' is disposed on the electron transport layer (ETL) 26. The hole transport layer (HTL) 30 is disposed on the photoactive layer array 28'. The upper electrode 32 is disposed on the hole transport layer (HTL) 30. The encapsulation layer 34 is disposed on the upper electrode 32.

[0085] like Figure 3 and Figure 4As shown, in some embodiments, the photoactive layer array 28' includes a plurality of photoactive layers (e.g., 28a, 28b, 28c, 28d) with different energy gaps, which are arranged in a mosaic form on a horizontal plane, for example, on an electron transport layer (ETL) 26. In some embodiments, the material of the photoactive layer (28a, 28b, 28c, 28d) includes an organic semiconductor, an inorganic semiconductor, or a perovskite semiconductor, for example, amorphous silicon (a-Si), Zu2ZnSnS4, CH3NH3PbCl3, CH3NH3PbBr3, CH3NH3PbI3, Rubrene mixture, UPSQ, P3HT, PBT-OTT, OC1C10-PPV, PCDTBT, PDPP5T, PDPP3T, PDPPSDTPS, PCBM, P70BM, C60, C70, ICBA, bis- PCBM,

[60] IPB, N2200, Y6, Y7, COTIC-4Cl, 6TIC, ZY-4Cl, IEICO-4Cl, ITIC, ITIC-4F, ITIC-M, DTY6, BTP-eC9, ITIC-Th, o-IDTBR, ITIC-4Cl, COTIC-4Cl, 6TIC, IDT-2Br, COTIC-4F, ITIC-DM, ZY-4Cl, IEICO-4Cl, BTP-4Cl-12, N3, L8-BO-F, or L8-BO, but the present invention is not limited thereto. In some embodiments, the materials of the photoactive layers (28a, 28b, 28c, 28d) are different. For example, the material of photoactive layer 28a has an absorption edge at a wavelength of about 550 nm, the material of photoactive layer 28b has an absorption edge at a wavelength of about 650 nm, the material of photoactive layer 28c has an absorption edge at a wavelength of about 700 nm, and the material of photoactive layer 28d has an absorption edge at a wavelength of about 750 nm. In some embodiments, the thickness T of photoactive layer array 28' is greater than about 2 μm. When the thickness of photoactive layer array 28' is greater than 2 μm, the optical response of the organic photo sensor becomes narrow-band and has sensitivity at the absorption band boundary, so no filter is required.

[0086] In some embodiments, the waveguide 18 transmits short wavelength light 46. In some embodiments, the wavelength of the short wavelength light 46 is approximately in the range of 300 nm to 500 nm. In some embodiments, the short wavelength light 46 includes, for example, light having a wavelength of 404 nm or 488 nm.

[0087] In some embodiments, the nanowell 20' in the nanowell array 20 is loaded with, for example, DNA 38 and a polymerase 40 for recognizing an A base, a T base, a G base, and a C base on the DNA 38. In some embodiments, the polymerase 40 converts the short wavelength light 46 into a long wavelength light 48. In some embodiments, the wavelength of the long wavelength light 48 is in the range of about 500 nm to 800 nm.

[0088] In some embodiments, in the optical device 10 , the pixel size Ps is approximately less than or equal to 10 μm.

[0089] See also Figure 3 , the sensing mechanism of the optical device 10 is further described below. The waveguide 18 transmits short-wavelength light 46 (i.e., excitation light) to the nanowell 20' in the nanowell array 20. In the nanowell 20', the polymerase 40 binds to a specific base (i.e., A, T, G, or C) on the DNA 38. The polymerase 40 absorbs the short-wavelength light 46 and emits a specific long-wavelength light 48 (i.e., emission light). The specific long-wavelength light 48 enters the optical sensor 14. For example, when the polymerase 40 emits light with a wavelength of approximately 550 nm, the photoactive layer 28a absorbs the light with a wavelength of approximately 550 nm and converts the optical signal into an electrical signal, which is then transmitted to a readout circuit (not shown) in the substrate 12 to identify a specific base on the DNA 38 corresponding to the optical wavelength of 550 nm. When the polymerase 40 emits light with a wavelength of about 650 nm, the photoactive layer 28b absorbs the light with a wavelength of about 650 nm and converts the green light signal into an electrical signal, which is then transmitted to the readout circuit (not shown) in the substrate 12 to identify the specific base corresponding to the light wavelength of 650 nm on the DNA 38. When the polymerase 40 emits light with a wavelength of about 700 nm, the photoactive layer 28c absorbs the orange light and converts the light signal of the light with a wavelength of about 700 nm into an electrical signal, which is then transmitted to the readout circuit (not shown) in the substrate 12 to identify the specific base corresponding to the light with a wavelength of about 700 nm on the DNA 38. When the polymerase 40 emits light with a wavelength of about 750 nm, the photoactive layer 28d absorbs the light with a wavelength of about 750 nm and converts the red light signal into an electrical signal, which is then transmitted to the readout circuit (not shown) in the substrate 12 to identify the specific base corresponding to the light with a wavelength of about 750 nm on the DNA 38.

[0090] Next, according to Figure 5A-5DThe absorption spectrum and reflection spectrum of the light sensor 14 further illustrate that the photoactive layers (28a, 28b, 28c, 28d) in the light sensor 14 can absorb long wavelength light of different wavelength bands and filter out short wavelength light (i.e., have narrowband characteristics) to achieve the purpose of eliminating noise. In some embodiments, the wavelength range of the excitation light transmitted by the waveguide 18 is 300nm to 500nm, for example, 404nm or 488nm. Figure 5A , the absorption intensity of the photoactive layer 28a (i.e., UPSQ) for different wavelength bands is represented by curve 1. As can be seen from curve 1, the photoactive layer 28a exhibits a strong and narrow absorption band at a wavelength of about 550nm (corresponding to blue light), for example, the absorption intensity is about 0.4. The absorption spectra of other material layers in the photosensor are also disclosed herein, for example, an indium tin oxide (ITO) material layer (represented by curve 2), an aluminum (Al) material layer (represented by curve 3), an aluminum-doped zinc oxide (AZO) material layer (represented by curve 4), and a molybdenum oxide (MoO3) material layer (represented by curve 5). The absorption intensities of the above material layers and the photoactive layer 28a in different wavelength bands are greatly different. For example, it can be seen from curves 2 to 5 that multiple material layers (e.g., ITO, Al, AZO, MoO3) have almost no absorption in the entire wavelength range.

[0091] exist Figure 5B , the absorption intensity of the photoactive layer 28b (i.e., PBT-OTT:PCBM) for different wavelength bands is represented by curve 1. As can be seen from curve 1, the photoactive layer 28b exhibits a strong and narrow absorption band at a wavelength of about 650nm (corresponding to green light), for example, the absorption intensity is about 0.35. The absorption spectra of other material layers in the photosensor are also disclosed herein, for example, an indium tin oxide (ITO) material layer (represented by curve 2), an aluminum (Al) material layer (represented by curve 3), an aluminum-doped zinc oxide (AZO) material layer (represented by curve 4), and a molybdenum oxide (MoO3) material layer (represented by curve 5). The absorption intensities of the above material layers and the photoactive layer 28b in different wavelength bands are greatly different. For example, it can be seen from curves 2 to 5 that multiple material layers (e.g., ITO, Al, AZO, MoO3) have almost no absorption in the full wavelength range.

[0092] exist Figure 5C, the absorption intensity of the photoactive layer 28c (i.e., OC1C10-PPV:PCBM) for different wavelength bands is represented by curve 1. As can be seen from curve 1, the photoactive layer 28c exhibits a strong and narrow absorption band at a wavelength of about 700nm (corresponding to orange light), for example, the absorption intensity is about 0.5. The absorption spectra of other material layers in the photosensor are also disclosed herein, for example, an indium tin oxide (ITO) material layer (represented by curve 2), an aluminum (Al) material layer (represented by curve 3), an aluminum-doped zinc oxide (AZO) material layer (represented by curve 4), and a molybdenum oxide (MoO3) material layer (represented by curve 5). The absorption intensities of the above material layers and the photoactive layer 28c in different wavelength bands are greatly different. For example, it can be seen from curves 2 to 5 that multiple material layers (e.g., ITO, Al, AZO, MoO3) have almost no absorption in the full wavelength range.

[0093] exist Figure 5D , the absorption intensity of the photoactive layer 28d (i.e., PTB7-Th:PCBM) for different wavelength bands is represented by curve 1. As can be seen from curve 1, the photoactive layer 28d exhibits a strong and narrow absorption band at a wavelength of about 750nm (corresponding to red light), for example, the absorption intensity is about 0.4. The absorption spectra of other material layers in the photosensor are also disclosed herein, for example, an indium tin oxide (ITO) material layer (represented by curve 2), an aluminum (Al) material layer (represented by curve 3), an aluminum-doped zinc oxide (AZO) material layer (represented by curve 4), and a molybdenum oxide (MoO3) material layer (represented by curve 5). The above-mentioned material layers and the photoactive layer 28d have very different absorption in different wavelength bands. For example, it can be seen from curves 2 to 5 that multiple material layers (e.g., ITO, Al, AZO, MoO3) have almost no absorption in the entire wavelength range.

[0094] Therefore, the photoactive layers (28a, 28b, 28c, 28d) can indeed absorb long-wavelength light of different wavelength bands and filter out short-wavelength light (that is, have narrow-band characteristics).

[0095] Since the thickness of the photoactive layer array 28' is relatively thick, for example, approximately greater than 2 μm, the photoactive layer array 28' can filter out the short-wavelength light 46. At the same time, the photoactive layers in the photoactive layer array 28' are also sensitive to narrow-band light. Therefore, the photoactive layer array 28' does not absorb the short-wavelength light 46 (in this case, noise), thereby achieving a high S / N ratio.

[0096] See also Figure 6 According to one embodiment of the present invention, an optical device 10 is provided. Figure 6 A schematic cross-sectional view of the optical device 10 is shown.

[0097] like Figure 6As shown, the optical device 10 includes a substrate 12, a first light sensor 14a, a second light sensor 14b, a third light sensor 14c, a fourth light sensor 14d, a waveguide 18, and a nano-well array 20. The fourth light sensor 14d is disposed on the substrate 12. The third light sensor 14c is disposed on the fourth light sensor 14d. The second light sensor 14b is disposed on the third light sensor 14c. The first light sensor 14a is disposed on the second light sensor 14b. The waveguide 18 is disposed on the first light sensor 14a. The nano-well array 20 is disposed on the waveguide 18.

[0098] In some embodiments, the substrate 12 includes a silicon substrate, but the invention is not limited thereto. In some embodiments, the substrate 12 includes a complementary metal oxide semiconductor (CMOS) readout circuit array 22 .

[0099] The detailed structure of each of the first photo sensor 14a, the second photo sensor 14b, the third photo sensor 14c, and the fourth photo sensor 14d includes a lower electrode, an electron transport layer (ETL), a photoactive layer, a hole transport layer (HTL), an upper electrode, and an encapsulation layer, which is similar to Figure 1B The structure of the optical sensor 14 is not described in detail here. In some embodiments, the bandgap of the photoactive layer in the first optical sensor 14a is greater than the bandgap of the photoactive layer in the second optical sensor 14b, the bandgap of the photoactive layer in the second optical sensor 14b is greater than the bandgap of the photoactive layer in the third optical sensor 14c, and the bandgap of the photoactive layer in the third optical sensor 14c is greater than the bandgap of the photoactive layer in the fourth optical sensor 14d.

[0100] In some embodiments, the material of the photoactive layer in the first photo sensor 14a, the second photo sensor 14b, the third photo sensor 14c, and the fourth photo sensor 14d includes an organic semiconductor, an inorganic semiconductor, or a perovskite semiconductor, for example, amorphous silicon (a-Si), Zu2ZnSnS4, CH3NH3PbCl3, CH3NH3PbBr3, CH3NH3PbI3, Rubrene mixture, UPSQ, P3HT, PBT-OTT, OC1C10-PPV, PCDTBT, PDPP5T, PDPP3T, PDPPSDTPS, PCBM, P70BM, C60, C70, ICBA, bis-PCBM,

[60] IPB, N2200, Y6, Y7, COTIC-4Cl, 6TIC, ZY-4Cl, IEICO-4Cl, ITIC, ITIC-4F, ITIC-M, DTY6, BTP-eC9, ITIC-Th, o-IDTBR, ITIC-4Cl, COTIC-4Cl, 6TIC, IDT-2Br, COTIC-4F, ITIC-DM, ZY-4Cl, IEICO-4Cl, BTP-4Cl-12, N3, L8-BO-F, or L8-BO, but the present invention is not limited thereto. In some embodiments, the materials of the photoactive layers in the first light sensor 14a, the second light sensor 14b, the third light sensor 14c, and the fourth light sensor 14d are different. For example, the material of the photoactive layer in the first light sensor 14a absorbs light with a wavelength of approximately 550nm. The material of the photoactive layer in the second photo sensor 14b absorbs light with a wavelength between about 530-650nm. The material of the photoactive layer in the third photo sensor 14c absorbs light with a wavelength between about 580-700nm. The material of the photoactive layer in the fourth photo sensor 14d absorbs light with a wavelength between about 620-750nm. Specifically, in some embodiments, the thickness Ta of the first photo sensor 14a at the top is about greater than 2μm.

[0101] In some embodiments, the waveguide 18 transmits short wavelength light 46. In some embodiments, the wavelength of the short wavelength light 46 is approximately in the range of 300 nm to 500 nm. In some embodiments, the short wavelength light 46 includes, for example, light having a wavelength of 404 nm or 488 nm.

[0102] In some embodiments, the nanowell 20' in the nanowell array 20 is loaded with, for example, DNA 38 and polymerase 40 for identifying A bases, T bases, G bases, and C bases on the DNA 38. In some embodiments, by sequentially grabbing fluorescently labeled complementary nucleotides according to the base sequence on the DNA 38, the fluorescent markers thereof are excited by the short-wavelength light 46 to emit long-wavelength light 48. It is briefly described hereinafter that the polymerase 40 converts the short-wavelength light 46 into the long-wavelength light 48. In some embodiments, the wavelength of the long-wavelength light 48 is in the range of about 500 nm to 800 nm.

[0103] In some embodiments, in the optical device 10 , the pixel size Ps is approximately less than or equal to 20 μm.

[0104] See also Figure 6, the sensing mechanism of the optical device 10 is further described below. The waveguide 18 transmits short-wavelength light 46 (i.e., excitation light) to the nanowell 20' in the nanowell array 20. In the nanowell 20', the polymerase 40 assists the specific base (i.e., A, T, G or C) on the DNA 38 to bind to the complementary nucleotide labeled with fluorescent light in the environment. The polymerase 40 absorbs the short-wavelength light 46 and emits a specific long-wavelength light 48 (i.e., emission light). For example, when the polymerase 40 emits light with a wavelength of about 500-550nm, since the photon energy of the light with a wavelength of about 500-550nm is greater than the energy gap of the photoactive layer in the first light sensor 14a, the first light sensor 14a absorbs the light with a wavelength of about 500-550nm and converts the blue light signal into an electrical signal, and then transmits the electrical signal to the readout circuit (not shown) in the substrate 12 to mainly identify the specific base on the DNA 38 corresponding to the blue light. When light with a wavelength between 550-600nm is emitted from the polymerase 40, since the photon energy of the light with a wavelength between 550-600nm is smaller than the energy gap of the photoactive layer in the first light sensor 14a but larger than the energy gap of the photoactive layer in the second light sensor 14b, the light with a wavelength between 550-600nm will pass through the first light sensor 14a, but the second light sensor 14b will absorb the light with a wavelength between 530-650nm and convert the green light signal into an electrical signal, which is then transmitted to the readout circuit (not shown) in the substrate 12 to mainly identify the specific base on the DNA 38 corresponding to the light with a wavelength between 550-600nm. When the polymerase 40 emits light with a wavelength between 600-650nm, since the photon energy of the light with a wavelength between 600-650nm is smaller than the first light sensor 14a, partially larger than the energy gap of the photoactive layer in the second light sensor 14b, and mainly larger than the energy gap of the photoactive layer in the third light sensor 14c, most of the light with a wavelength between 600-650nm will pass through the first light sensor 14a and the second light sensor 14b, but the third light sensor 14c will absorb the light with a wavelength between 580-700nm and convert the orange light signal into an electrical signal, and then transmit the electrical signal to the readout circuit (not shown) in the substrate 12 to mainly identify the specific base on the DNA 38 corresponding to the light with a wavelength between 600-650nm.When light with a wavelength between 650-750 nm is emitted from the polymerase 40, since most of the photon energies of the light with a wavelength between 650-750 nm are smaller than the energy gap of the photoactive layer in the first light sensor 14 a, the second light sensor 14 b, and the third light sensor 14 c but larger than the energy gap of the photoactive layer in the fourth light sensor 14 d, the light with a wavelength between 650-750 nm will pass through the first light sensor 14 a, the second light sensor 14 b, and the third light sensor 14 c, but the fourth light sensor 14 d will absorb the light with a wavelength between 620-750 nm and convert the optical signal of the light with a wavelength between 620-750 nm into an electrical signal, and then transmit the electrical signal to the readout circuit (not shown) in the substrate 12 to mainly identify the specific base on the DNA 38 corresponding to the light with a wavelength between 650-750 nm.

[0105] Next, according to Fig. 7A and Figure 7B The absorption spectrum and reflection spectrum of the light sensor further illustrate that the first light sensor 14a, the second light sensor 14b, the third light sensor 14c, and the fourth light sensor 14d can absorb long wavelength light of different wavelength bands and filter out short wavelength light (i.e., have narrowband characteristics) to achieve the purpose of eliminating noise. In some embodiments, the wavelength range of the excitation light transmitted by the waveguide 18 is 300nm to 500nm, for example, 404nm or 488nm. Fig. 7A , the absorption intensity of the photoactive layer (i.e., UPSQ) of the first photosensor 14a for different wavelength bands is represented by curve 1. As can be seen from curve 1, the photoactive layer of the first photosensor 14a exhibits a strong and narrow absorption band at a wavelength of about 550nm (corresponding to blue light), for example, the absorption intensity is about 0.4. The absorption spectra of other material layers in the photosensor are also disclosed herein, for example, an indium tin oxide (ITO) material layer (represented by curve 2), an aluminum (Al) material layer (represented by curve 3), an aluminum-doped zinc oxide (AZO) material layer (represented by curve 4), and a molybdenum oxide (MoO3) material layer (represented by curve 5). The above material layers and the first photosensor 14a have very different absorption in different wavelength bands. For example, it can be seen from curves 2 to 5 that multiple material layers (e.g., ITO, Al, AZO, MoO3) have almost no absorption in the full wavelength range.

[0106] exist Figure 7B, the absorption intensity of the photoactive layer (i.e., PBT-OTT:PCBM) of the second photosensor 14b for different wavelengths is represented by Curve 2. The absorption intensity of the photoactive layer (i.e., OC1C10-PPV:PCBM) of the third photosensor 14c for different wavelengths is represented by Curve 3. The absorption intensity of the photoactive layer (i.e., PTB7-Th:PCBM) of the fourth photosensor 14d for different wavelengths is represented by Curve 4.

[0107] As can be seen from Curve 2, the photoactive layer (i.e., PBT-OTT:PCBM) of the second photosensor 14b has strong absorption for a specific long-wavelength emission light having a wavelength of about 530-650nm, for example, the absorption intensity is about 0.5 or higher. However, the photoactive layer of the second photosensor 14b hardly absorbs the emission light having a wavelength below 550nm. As can be seen from Curve 3, the photoactive layer (i.e., OC1C10-PPV:PCBM) of the third photosensor 14c has strong absorption for a specific long-wavelength emission light having a wavelength of about 580-700nm, for example, the absorption intensity is about 0.7 or higher. However, the photoactive layer of the third photosensor 14c hardly absorbs the emission light having a wavelength below 580nm. As can be seen from Curve 4, the photoactive layer (i.e., PTB7-Th:PCBM) of the fourth photosensor 14d has strong absorption for a specific long-wavelength emission light having a wavelength of about 620-750nm (which may correspond to red light), for example, the absorption intensity is about 0.8 or higher. However, the photoactive layer of the fourth photosensor 14d hardly absorbs emission light having a wavelength below 620nm.

[0108] The absorption spectra of other material layers in the optical sensor are also disclosed herein, for example, the indium tin oxide (ITO) material layer (represented by curve 5), the intermediate layer (represented by curve 6), and the silver (Ag) material layer (represented by curve 7). The absorption intensities of the above material layers and the photoactive layer in different wavelength bands are greatly different. For example, it can be seen from curves 5 to 7 that multiple material layers (e.g., ITO, intermediate layer, Ag) hardly absorb long-wavelength emission light with a wavelength of about 500-800nm. In addition, the reflection intensity of the optical sensor for different wavelength bands is represented by curve 1'. It can be seen from curve 1' that the optical sensor has a strong reflection for long-wavelength emission light with a wavelength greater than 800nm, for example, the reflection intensity is about 0.9 or greater. Therefore, the first optical sensor 14a, the second optical sensor 14b, the third optical sensor 14c, and the fourth optical sensor 14d can indeed absorb long-wavelength light of different wavelength bands respectively and filter out short-wavelength light (that is, have narrowband characteristics).

[0109] Since the thickness of the first light sensor 14a is relatively thick, for example, approximately greater than 2 μm, the first light sensor 14a can filter out the short-wavelength light 46. At the same time, the first light sensor 14a, the second light sensor 14b, the third light sensor 14c, and the fourth light sensor 14d are also sensitive to narrow-band light. Therefore, the first light sensor 14a, the second light sensor 14b, the third light sensor 14c, and the fourth light sensor 14d do not absorb the short-wavelength light 46 (in this case, noise), thereby achieving a high S / N ratio.

[0110] In the present invention, when long-wavelength light is used as a light source, combined with fluorescently labeled nucleotides located in the sample well that can convert long-wavelength light into short-wavelength light, and a wide bandgap semiconductor that is sensitive to short-wavelength light used in the photoactive layer, there is no need to add long-pass or short-pass filters, which can significantly reduce the module thickness, allow for smaller pixel sizes, and eliminate optical crosstalk problems. In addition, when short-wavelength light is used as a light source, combined with a thick photoactive layer, the thick photoactive layer can filter out short-wavelength light (i.e., noise), and at the same time, the photoactive layer improves the sensitivity of narrow-band light (i.e., signal) to achieve a high S / N ratio. The present invention provides a high-resolution, tiny pixel-size optical device for third-generation sequencing (TGS).

[0111] Although the embodiments of the present disclosure and their advantages have been disclosed as above, it should be understood that those skilled in the art to which the present disclosure belongs can make changes, substitutions and modifications without departing from the spirit and scope of the present disclosure. In addition, the scope of protection of the present disclosure is not limited to the processes, machines, manufactures, material compositions, devices, methods and steps in the specific embodiments described in the specification. Those skilled in the art to which the present disclosure belongs can understand from the contents of the embodiments of the present disclosure that the processes, machines, manufactures, material compositions, devices, methods and steps currently or developed in the future can be used according to the embodiments of the present disclosure as long as they can achieve substantially the same functions or obtain substantially the same results as in the embodiments described herein. Therefore, the scope of protection of the present disclosure includes the above-mentioned processes, machines, manufactures, material compositions, devices, methods and steps. In addition, the scope of protection of the present disclosure shall be defined as defined by the attached claims.

Claims

1. An optical device, comprising: substrate; A first light sensor is disposed on the substrate; a waveguide disposed on the first light sensor, wherein the waveguide is in contact with the first light sensor or is separated from the first light sensor by a color filter array in contact with the waveguide and the first light sensor; and The nanowell array is arranged on the waveguide.

2. The optical device of claim 1, wherein the substrate comprises a complementary metal oxide semiconductor readout circuit array, and the waveguide transmits short wavelength light with a wavelength of 300 nm to 500 nm.

3. The optical device of claim 1, wherein the waveguide transmits long-wavelength light having a wavelength of 800 nm to 1,600 nm, and the nanowell array is loaded with fluorescently labeled nucleotides to convert the long-wavelength light into short-wavelength light having a wavelength of 400 nm to 800 nm.

4. The optical device of claim 3, wherein the first photosensor comprises a first photoactive layer having a first energy gap, the first energy gap is smaller than the photon energy of the short-wavelength light and larger than the photon energy of the long-wavelength light, and a pixel size of the optical device is smaller than 10 μm.

5. The optical device of claim 4, wherein the first energy gap of the first photoactive layer is in the range of 1.5 eV to 2.5 eV, and the first photoactive layer comprises an organic semiconductor, an inorganic semiconductor or a perovskite semiconductor, and the first photoactive layer absorbs the short wavelength light.

6. The optical device as described in claim 4 further includes a second photosensor, including a second photoactive layer with a second energy gap, disposed between the substrate and the first photosensor, wherein the first energy gap of the first photoactive layer is greater than the second energy gap of the second photoactive layer.

7. The optical device as described in claim 6 further includes a third photosensor, including a third photoactive layer having a third energy gap, disposed between the substrate and the second photosensor, wherein the second energy gap of the second photoactive layer is greater than the third energy gap of the third photoactive layer.

8. The optical device as described in claim 7 further includes a fourth photosensor, including a fourth photoactive layer having a fourth energy gap, disposed between the substrate and the third photosensor, wherein the third energy gap of the third photoactive layer is larger than the fourth energy gap of the fourth photoactive layer, and the pixel size of the optical device is less than 20μm.

9. The optical device of claim 8, wherein the first photoactive layer absorbs short-wavelength light having a wavelength of 400 nm to 550 nm, the second photoactive layer absorbs short-wavelength light having a wavelength of 530 nm to 650 nm, the third photoactive layer absorbs short-wavelength light having a wavelength of 580 nm to 700 nm, and the fourth photoactive layer absorbs short-wavelength light having a wavelength of 620 nm to 750 nm.

10. The optical device of claim 2, wherein the nanowell array is loaded with polymerase to convert the short wavelength light into long wavelength light with a wavelength of 500nm to 800nm.

11. The optical device of claim 10, wherein the first photosensor comprises a first photoactive layer having a first energy gap, a second photoactive layer having a second energy gap, a third photoactive layer having a third energy gap, and a fourth photoactive layer having a fourth energy gap, which are arranged in a mosaic form on a horizontal plane, and the first energy gap, the second energy gap, the third energy gap and the fourth energy gap are different, and the thickness of the first photoactive layer, the second photoactive layer, the third photoactive layer and the fourth photoactive layer is greater than 2 μm.

12. The optical device of claim 11, wherein the first photoactive layer absorbs long wavelength light with a wavelength of 550 nm, the second photoactive layer absorbs long wavelength light with a wavelength of 650 nm, the third photoactive layer absorbs long wavelength light with a wavelength of 700 nm, and the fourth photoactive layer absorbs long wavelength light with a wavelength of 750 nm.

13. An optical device as described in claim 10, wherein the first photosensor includes a first photoactive layer having a first energy gap, and the thickness of the first photoactive layer is greater than 2μm, wherein the optical device also includes a second photosensor, including a second photoactive layer having a second energy gap, arranged between the substrate and the first photosensor, wherein the first energy gap of the first photoactive layer is greater than the second energy gap of the second photoactive layer, and the first photoactive layer absorbs long wavelength light with a wavelength of 550nm, and the second photoactive layer absorbs long wavelength light with a wavelength of 530nm to 650nm.

14. The optical device as described in claim 13 further includes a third photosensor, including a third photoactive layer having a third energy gap, disposed between the substrate and the second photosensor, wherein the second energy gap of the second photoactive layer is greater than the third energy gap of the third photoactive layer, and the third photoactive layer absorbs long-wavelength light with a wavelength of 580nm to 700nm.

15. The optical device as described in claim 14 further includes a fourth photosensor, including a fourth photoactive layer having a fourth energy gap, disposed between the substrate and the third photosensor, wherein the third energy gap of the third photoactive layer is greater than the fourth energy gap of the fourth photoactive layer, and the fourth photoactive layer absorbs long wavelength light with a wavelength of 620nm to 750nm.

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