Detector with reduced fluorescence range noise

Abstract

A detector with reduced fluorescence range noise is disclosed. This paper proposes a device comprising: a structure defining a detector surface configured to support a biological or chemical substance; and a sensor array including a light sensor and circuitry for transmitting data signals using photons detected by the light sensor. The device may include one or more features for reducing fluorescence range noise in the detection band of the sensor array.

Description

[0001] This application is a divisional application of the application filed on December 18, 2018, with application number 201811549746.2 and invention title "Detector with Reduced Fluorescence Range Noise".

[0002] Cross-references to related applications

[0003] This application claims priority to U.S. Patent Application No. 62 / 611,464, filed December 28, 2017, entitled "Detector With Reduced Fluorescence Range Noise," which is incorporated herein by reference in its entirety. This application also claims priority to U.S. Patent Application No. 62 / 644,804, filed March 19, 2018, entitled "Detector With Reduced Fluorescence Range Noise," which is incorporated herein by reference in its entirety. background

[0004] Various protocols in biological or chemical research involve conducting controlled reactions. The specified reactions can then be observed or detected, and subsequent analysis can help identify or reveal the properties of the chemical substances involved in the reaction.

[0005] In some multiplex assays, an unknown analyte with an identifiable label (e.g., a fluorescent label) can be exposed to thousands of known probes under controlled conditions. Each known probe can be deposited into a corresponding well in a microplate. Observing any chemical reactions that occur between the known probe and the unknown analyte within the well can help identify or reveal the properties of the analyte. Other examples of this approach include known DNA sequencing procedures such as sequencing-by-synthesis (SBS) or cyclic-array sequencing.

[0006] In some fluorescence detection schemes, an optical system is used to direct excitation light onto a fluorophore (e.g., a fluorescently labeled analyte) and also detect the fluorescence emission signal light emitted from the analyte with the fluorophore attached. However, such optical systems can be relatively expensive and require a larger benchtop footprint. For example, the optical system may include an arrangement of lenses, filters, and a light source.

[0007] In other proposed detection systems, the controlled reaction in the flow cell is determined by a solid-state optical sensor array (e.g., a complementary metal-oxide-semiconductor (CMOS) detector or a charge-coupled device (CCD) detector). These systems do not involve large optical components for detecting fluorescence emission.

[0008] Brief description

[0009] This paper proposes a device comprising: a structure defining a detector surface configured to support a biological or chemical substance; and a sensor array including a light sensor and circuitry for transmitting data signals using photons detected by the light sensor. The device may include one or more features for reducing fluorescence range noise in the detection band of the sensor array.

[0010] This paper proposes a device comprising: a structure defining a detector surface configured to support a biological or chemical sample; and a sensor array including a light sensor and circuitry for transmitting signals using photons detected by the light sensor; a guiding array including a light guide; wherein the light guide of the guiding array receives excitation light and emission signal light from the detector surface, wherein the light guide extends toward each light sensor of the sensor array and includes a filter material that blocks the excitation light and allows the emission signal light to propagate toward each light sensor, and wherein the filter material includes a metal complex dye.

[0011] This paper proposes a method comprising: fabricating a circuit that transmits data signals using photons detected by an array of photons; depositing a filter material within a guide cavity of a guide cavity array, the guide cavity being aligned with and positioned above the respective photons of the photon array, wherein the filter material comprises a dye suspended in a polymer matrix, the dye comprising a photon emission quencher; and fabricating a structure defining a detector surface for supporting a biological or chemical sample, wherein fabricating the structure defining the detector surface comprises fabricating the structure defining the detector surface above the cavity of the guide cavity array and above the photons of the photon array.

[0012] This paper proposes a device comprising: a structure defining a detector surface for supporting a biological or chemical sample; a sensor array including a photosensitive sensor and circuitry for transmitting data signals based on photons detected by the photosensitive sensor; and a guiding array including a light guide; wherein the light guide of the guiding array receives excitation light and emission signal light from the detector surface, wherein the light guide extends toward each photosensitive sensor of the sensor array and includes a filter material that blocks the excitation light and allows the emission signal light to propagate toward each photosensitive sensor, wherein the detector surface includes a reaction recess having a refractive index and size sufficient to counteract background light energy incident on the detector surface in the detection band of the sensor array. Attached Figure Description

[0013] These and other features, aspects, and advantages of the subject matter will become better understood when the following detailed description is read with reference to the accompanying drawings, in which similar characters denote similar parts, wherein:

[0014] Figure 1This is a schematic cross-sectional side view of an example system for biological or chemical analysis, which includes a detector surface for supporting biological or chemical samples.

[0015] Figure 2 This is a spectral profile coordination diagram showing the coordination between the excitation wavelength, absorption wavelength, fluorescence emission signal wavelength, and detection band wavelength according to an example;

[0016] Figure 3 This is a spectral profile illustrating the autofluorescence properties of a filter material according to an example;

[0017] Figure 4 This is an energy state transition diagram showing the energy state transitions of a radiation dye according to an example;

[0018] Figure 5 This is an energy state transition diagram showing the energy state transitions of a dye with a photon emission quencher according to an example;

[0019] Figure 6 This is an energy state transition diagram showing the energy state transitions of a metal complex dye with a photon emission quencher according to an example;

[0020] Figure 7 An optical density (OD) film thickness plot is depicted according to an example, which shows the dependence of OD on the film thickness of a filter material with metal complex dyes.

[0021] Figure 8 It is a cross-sectional side view of an example detector having a detector surface configured to cancel incident light energy in a selective wavelength band;

[0022] Figure 9 This is a cross-sectional side view of an example detector having a sensor array, a photoconductor array, and a reactive array; and

[0023] Figure 10 It is a cross-sectional side view of a detector with an example of a light sensor, a light guide, and a reaction recess defined by the detector surface. Detailed description

[0024] exist Figure 1The image shows a system 100 for use in analysis, such as biological or chemical analysis. System 100 may include a light energy exciter 10 and a detector assembly 20. Detector assembly 20 may include a detector 200 and a flow cell 282. Detector 200 may include multiple light sensors 202 and a detector surface 206 for supporting a sample 502 (such as a biological or chemical sample object to be tested). Detector 200 may also include multiple light guides that direct light from detector surface 206 to light sensors 202. Detector surface 206, sidewalls 284, and flow cap 288 may define and delineate flow cell 282. Detector surface 206 may have an associated detector surface plane 130.

[0025] In another embodiment, the detector surface 206 may be recessed to include a reaction recess 210 (nanotrap). According to one example, each photosensor 202 may be aligned with a photoguide 214 and a reaction recess 210. According to one example, each reaction recess 210 may define one or more reaction sites therein, and the sample 502 may be supported on such reaction sites.

[0026] In another aspect, detector 200 may include a dielectric stack region 218 located in the middle of light guide 214. The dielectric stack region 218 may form circuitry therein, for example for reading signals from light sensor 202, digitizing, storing, and processing them.

[0027] According to one example, detector 200 can be provided by a solid-state integrated circuit detector, such as a complementary metal-oxide-semiconductor (CMOS) integrated circuit detector or a charge-coupled device (CCD) integrated circuit detector.

[0028] According to one example, system 100 can be used for biological or chemical testing using fluorophores. For example, inlet 289 and outlet 290 can be used to allow fluid containing one or more fluorophores to flow into and out of flow cell 282. Fluorophores can attract a variety of samples 502, and therefore, by detecting them, fluorophores can act as markers for samples 502, such as the biological or chemical analytes they attract.

[0029] To detect the presence of fluorophores within flow cell 282, photoexciter 10 can be excited such that excitation light 101 within the excitation wavelength range is emitted by photoexciter 10. Upon receiving excitation light 101, the fluorophore attached to sample 502 radiates emission signal light 501, which is the signal of interest detected by photosensor 202. Due to the fluorescence of the fluorophore attached to sample 502, the emission signal light 501 will have a wavelength range red-shifted relative to the wavelength range of excitation light 101.

[0030] The photoexciter 10 may include at least one light source and at least one optical component to illuminate the sample 502. Examples of the light source may include, for example, a laser, an arc lamp, an LED, or a laser diode. The optical component may be, for example, a reflector, a dichroic mirror, a beam splitter, a collimator, a lens, a filter, an optical wedge, a prism, a mirror, a detector, etc. In an example using an illumination system, the photoexciter 10 may be configured to direct excitation light 101 to the reaction site. As an example, the fluorophore may be excited by light in the green wavelength range, for example, by using excitation light 101 having a center (peak) wavelength of approximately 523 nm.

[0031] The examples in this paper demonstrate that the signal-to-noise ratio of system 100 can be expressed in the equation below (1).

[0032]

[0033] Wherein, “signal” is the emitted signal light 501, which is the signal of interest attributable to the fluorescence of the fluorophore attached to the sample; “excitation” is the unwanted excitation light reaching the photosensor 202; “AF” is the autofluorescence noise radiation of one or more autofluorescence sources within the detector 200; “background” is the unwanted light energy transmitted from sources outside the detector 200 into the detector 200; “dark current” is the current associated with noise and random electron-hole pair generation in the absence of light; and “readout noise” is the noise associated with analog-to-digital electronics.

[0034] Figure 2 This is a spectral profile coordination diagram showing the target coordination between the wavelength ranges of the excitation light, the signal light, and the detection wavelength range. Figure 2 In the spectral profile coordination diagram, spectral profile 1202 is the spectral profile of excitation light 101 emitted by the photoelectric exciter 10. Spectral profile 1204 is the absorption spectrum of a fluorophore detected using the excitation light 101 having spectral profile 1202, and spectral profile 1214 is the spectral profile of the emission signal light 501 caused by the fluorescence of the fluorophore when excited by the excitation light 101. Spectral profile 1220 is the transmission profile (detection band) according to an example detector 200 and photosensitive sensor 202. Detector 200 can be configured to detect light in the wavelength range indicated by spectral profile 1220. Therefore, referring to... Figure 2 The spectral profile coordination diagram shows that the detector 200 can detect the emitted signal light 501 in the wavelength range, wherein the spectral profile 1214 of the emitted signal light 501 intersects with the detection band spectral profile 1220 of the detector 200 and the optical sensor 202.

[0035] Detector 200 may include one or more filters that block excitation light 101, such that detector 200 with optical sensor 202 does not detect excitation light 101. In one aspect, light guide 214 that directs light from detector surface 206 may include a filtering material such that light guide 214 blocks light in the wavelength range of excitation light 101. Therefore, optical sensor 202 may receive emission signal light 501 radiated from the excited fluorophore, instead of excitation light 101.

[0036] The examples in this paper demonstrate that the optical guide 214, designed to improve the signal-to-noise ratio of detector 200, can act as a noise source within detector 200. (Refer to...) Figure 3 The spectral profile, spectral profile 1304, is the spectral profile of a filter material with a dye that does not (is absent) a photon emission quencher typically used in optical systems tested by excitation irradiation in the expected wavelength range of excitation light 101 of system 100. Figure 3 In a specific spectral profile diagram, spectral profile 1304 shows, for example, according to... Figure 2 The spectral profile of the filter material under green excitation light is depicted in the spectral profile coordination diagram with a center (peak) wavelength of approximately 523 nm.

[0037] refer to Figure 3 The spectral profile diagram shows that the filter material with the spectral profile characteristics depicted by spectral profile 1304 is different from that of the filter material with the spectral profile characteristics depicted by spectral profile 1304. Figure 2 The spectral profile 1202 of the spectral profile coordination diagram depicts a redshift in the emission band of the excitation light 101, which means that the material exhibits autofluorescence. The examples in this paper recognize that, for the autofluorescent filter material of photoconductor 214, the signal detected as an emission signal by photosensor 202 can actually be attributed to noise radiation from the excitation light 101 that operates to excite the autofluorescence of photoconductor 214.

[0038] refer to Figure 3-7 An example of resolving unwanted autofluorescence in photoconductor 214 is described. (See reference...) Figure 4-6 The energy state transition diagram, according to one example, shows that the light guide 214 may include a material having a photon emission quencher. In another aspect, the filter material may include dye molecules to provide absorption in the wavelength range of the excitation light 101.

[0039] Figure 4 The energy state transition diagram depicts the energy state transitions of a dye without a photon emission quencher. During excitation and after the excited-state relaxation period, it exhibits the following characteristics: Figure 4 The energy state transition characteristics depicted in the energy state transition diagram show that the dye emits photons when returning to the ground state. Figure 5This is an energy state transition diagram depicting the energy state transitions of a dye possessing a photon emission quencher. (Refer to...) Figure 5 The energy state transition diagram shows that a dye with a photon emission quencher returns to the ground state after an excited-state relaxation period upon excitation. However, through the operation of the photon emission quencher, photons are not released upon returning to the ground state. Instead, phonons are emitted upon returning to the ground state. Returning to the ground state is accompanied by the release of thermal energy, not photons.

[0040] Having such Figure 4 The dyes exhibiting the energy state transition characteristics shown in the energy state transition diagram are radiation dyes, while those possessing the following characteristics are radiation dyes. Figure 5 The dyes whose energy state transition characteristics are shown in the energy state transition diagram are nonradiative dyes.

[0041] As an example, the chemical structure diagram of a dye having a suitable photon emission quencher to quench photon emission is shown in (2).

[0042]

[0043] The chemical structure diagram of (2) illustrates the structural properties of a metal complex dye used as a photon emission quencher to quench photon emission. As an example, the metal complex dye can be provided by an octahedral transition metal complex dye, as shown in (2). The specific metal complex dye shown in (2) comprises two dye molecules + a chromium ion, and some complexes may comprise one dye molecule + a chromium (Cr) ion or other metal ions. The structure depicted in (2) includes six ligand bonds: O, N, and a standard crystal field. Based on the structure depicted in (2), a photon emission quencher provided by a trivalent Cr transition metal ion exists. As an example, Cr³⁺ can provide photon emission quenching functionality. Other transition metals can be used. Transition metals used in this paper for metal complex dyes may include, for example, scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, and copper. To select alternative metals, the energy levels between the metal ion and the dye molecule can overlap. According to one example, the transition metal used for the metal complex dye can be selected to have an absorption spectral profile that overlaps with the fluorescence emission profile of the selected dye, such that the transition metal can provide photon emission quenching through the fluorescence emission spectral profile of the selected dye.

[0044] In the example of the metal complex dye depicted in the structural diagram of (2), the metal complex dye has the depicted associated proton. The counterion associated with the metal complex dye is formed by absorbing the positive (+) charge specified by the proton of the metal complex dye depicted in the structural diagram of (2), and can be selected according to an example for hydrophobic properties and UV absorption properties. In one example, an alkylamine, primary amine, secondary amine, or tertiary amine can associate with the metal complex dye to form a counterion, which, when associated with the metal complex dye, may include an alkylammonium.

[0045] According to one example, the metal complex dye itself may not be particularly soluble in solution, so a counterion can be selected to increase solubility. Counterions can be selected for hydrophobic properties to improve the transparency and visibility of the polymer and / or solvent, and to reduce scattering. For example, counterions can allow the metal complex dye to be distributed more uniformly, enhance visibility and transparency, and reduce scattering. Counterions can be selected for UV absorption properties, for example, so that the counterion does not adversely contribute to fluorescence. For example, the absorption of the counterion can affect fluorescence properties by interfering with the spectrum of the metal dye complex, and can be selected to avoid having an interference spectrum. According to one example, a hydrophobic amine can be used as a counterion. According to another example, it will be understood that, depending on the metal center and the selected ligand, the metal complex dye can be uncharged, net positively charged, or may also have a net negative charge.

[0046] According to one example, the counterion associated with the metal complex dye depicted in the structural diagram of (2) can be provided by an alkylamine. According to one example, the counterion associated with the metal complex dye depicted in the structural diagram of (2) can be provided by a tertiary amine. In the tertiary amine, nitrogen has three organic substituents. According to one example, the counterion associated with the metal complex dye depicted in the structural diagram of (2) can be provided by a tertiary alkylamine.

[0047] Additionally, in other examples of metal complex dyes, counterions with appropriate charges can be selected to associate with the metal complex dye. In some embodiments, negatively or positively charged ions can be selected to counteract the net charge of the metal complex dye molecules, and / or hydrophobicity can be added in some embodiments to allow the metal complex dye to be incorporated into the solution. Furthermore, in some embodiments, counterions may not be necessary when there is no charge. Counterions can include any charged particle and, in some embodiments, include primary, secondary, or tertiary amines. In other embodiments, quaternary ammonium ions can be selected.

[0048] According to one example, the counterion associated with the metal complex dye as depicted in (2) may include an amine, such as NR'R"R"', wherein at least one of the R groups is a straight or branched chain having at least four atoms. In some embodiments, the chain may have at least 10 atoms. The chain may include a long chain and may include a polymer. The chain may be primarily hydrocarbon-based or may include other groups such that the dye may be soluble in any necessary solvent and the polymer may be soluble in the solvent, depending on the functional groups of the polymer. Other R groups may be the same or hydrogen-based, or may include different chains. According to one example, the chain may be C4 to C20, including cyclic chains or rings. In some embodiments, the counterion may include more than one type of counterion. The examples herein recognize that some mixtures of counterions are convenient for use in solutions where more than one polymer material may be used. That is, some alkyl groups may be different, and the counterion may include multiple counterions.

[0049] Figure 6 This is an energy state transition diagram illustrating the properties of metal complex dyes. Figure 6 It is Cr(CN) tBu Energy state transition diagram of Ar3NC3. (Refer to...) Figure 6 The energy state transition diagram shows that, due to the lower energy state of the metal neutral compared to the metal-2-ligand charge transfer (MLCT) complex, the metal complex can lead to ultrafast nonradiative (non-autofluorescence) relaxation. For Figure 6 The energy state transition diagram depicts Cr(CN) tBu Ar3NC)3), the ligand field can be weak enough to make the metal center 3d -d excited states can be lower in energy than MLCT complexes, leading to ultrafast excited states. Metal-complexed dyes can exhibit ultrafast excited state decay via nonradiative relaxation. According to... Figure 6 The energy state transition diagram shows that the metal complex used as a photon emission quencher quenches photons, causing the return to the ground state to be accompanied by phonon emission and the release of thermal energy, rather than photon emission.

[0050] To provide a filter material, such as a powdered dye molecule having a photon emission quencher and according to an example provided by a metal complex dye, the dye molecules can be dissolved in a solvent and added to a liquid polymer binder to form a liquid matrix having dye molecules and polymer molecules. The liquid can be deposited into the media stack cavity of detector 200 and dehydrated to form a filter material comprising a solid dye and a polymer matrix, wherein the dye molecules are suspended in the matrix of polymer binder molecules.

[0051] According to one example, the filter material used to form the photoconductor 214 may include metal-complexed dye molecules suspended in a polymer binder matrix, as illustrated herein. The filter material formed including metal-complexed dye molecules suspended in a polymer binder matrix can exhibit spectral profile characteristics under irradiation with excitation light 101 having a center wavelength of approximately 523 nm, as shown in the reference... Figure 3 The spectral profile shown in the spectral profile diagram 1404 illustrates this. According to reference... Figure 3 As illustrated in one example, providing a filter material to include a dye having a photon emission quencher (such as that provided using, for example, a metal complex dye) can reduce the autofluorescence emission signal radiated from the filter material at wavelengths of about 570 nm or longer to about 5% of their expected value, assuming the filter material includes a dye without a photon emission quencher (the respective autofluorescence emission signal values ​​of spectral profiles 1304 and 1404 observed at wavelengths of about 570 nm) or less.

[0052] Providing a polymer binder molecule to the matrix of dye molecules facilitates processability with a range of semiconductor processes, such as chemical vapor deposition (CVD), spin coating, etching, planarization, etc.

[0053] According to one example, a filter material provided by a metal complex dye matrix can have a dye-to-polymer weight ratio of about 70:30 and about 90:10. Above this concentration range, the structural integrity of the matrix is ​​compromised, while below this concentration range, filtration performance is compromised. According to one example, a filter material provided by a metal complex dye matrix can have a molecular ratio between about 1 dye molecule: 50 polymer molecules and about 1 dye molecule: 150 polymer molecules. According to one example, a filter material provided by a polymer binder and a metal complex dye matrix can have a molecular ratio between about 1 dye molecule: 100 polymer molecules.

[0054] While higher concentrations of dye molecules improve the blocking of excitation light, the examples presented in this paper demonstrate that increased scattering can be observed at higher concentrations. Light scattering can be addressed by further processing the filtered powdered dye particles prior to mixing with the polymer binder liquid.

[0055] Figure 7 This is an optical density (OD) film thickness diagram, which illustrates the filtration performance of the filter material described herein, which comprises a matrix of metal-complexed dyes suspended in a polymer binder matrix. Figure 7 As shown in the OD film thickness diagram, an OD of approximately 10 can be achieved within a space budget of 3.5 μm. (See also...) Figure 2The spectral profile coordination diagram, the spectral profile targeted by the filter is the spectral profile 1202 for excitation light 101 with a center (peak) wavelength of approximately 523 nm. (Refer to...) Figure 7 The OD film thickness diagram shows that, by configuring the photoconductor 214, formed from a matrix of metal complex dyes suspended in a polymer binder matrix, to have a thickness of approximately 3.5 μm, the photoconductor 214 can be configured to exhibit an OD of approximately 10 for a center (peak) excitation wavelength of approximately 523 nm. Alternatively, by configuring the photoconductor 214, formed from a matrix of metal complex dyes suspended in a polymer binder matrix, to have a thickness of approximately 2 μm, the photoconductor 214 can be configured to exhibit an OD of approximately 7 for a center (peak) excitation wavelength of approximately 523 nm.

[0056] For the execution of light sensing, the light sensor 202 can be positioned relative to the detector surface 206 ( Figure 1 It has a specific spacing distance. As an example, the specific spacing distance could be a specific spacing distance in, for example, a range from approximately 4 μm to approximately 6 μm. Figure 1 As shown, the light guide 214 may have spatial limitations depending on the spacing requirements between the light sensor 202 and the detector surface 206. Given... Figure 7 The OD thickness data summarized in the OD film thickness diagram can provide materials for constructing the light guide 214 to meet the target optical density (OD) characteristics according to the spatial characteristics of the detector 200, and can achieve OD performance suitable for many applications even under space-constrained conditions.

[0057] like Figure 2 As depicted in the spectral profile coordination diagram, the optical sensor 202 can sense the emission signal light 501 attributable to the fluorescence of a fluorophore, but, ideally, cannot detect the excitation light 101 represented by spectral profile 1202. To configure the optical sensor 202 to detect the emission signal light 501 attributable to a fluorophore attached to the sample 502 without detecting the excitation light 101, the system 100 may include one or more filters. For example, a light guide 214 may be formed of a filter material that blocks light in the band structure of the excitation light 101 represented by spectral profile 1202. Thus, the emission signal light 501 represented by spectral profile 1214 is detected by using the optical sensor 202 without detecting the excitation light 101. However, as noted, the filter material forming the light guide 214 can spontaneously fluoresce in response to the excitation of the excitation light 101. The examples herein provide a light guide 214 to block the excitation light 101 to exhibit reduced spontaneous fluorescence, thereby maintaining the desired spectral profile coordination between the excitation fluorescence emission and detection spectral profiles, as... Figure 2 The spectral profile is depicted by the coordinate diagram.

[0058] The examples herein recognize that a left shift of the spectral profile 1220 of detector 200 can increase the detection of emitted signal light 501, which has a spectral profile indicated by spectral profile 1214 in the spectral profile of emitted signal light 501. It should be understood that, as used herein, a left shift refers to a hypochromic shift or blue shift. Filter materials, including matrices of metal complex dyes suspended in a polymer binder matrix, can be configured to left-shift the spectral profile 1220 by implementing various features. To left-shift the spectral profile 1220, certain substituents surrounding the ligands of the metal complex dye (2) can be altered. For example, phenyl and other groups can act as fluorophores and can therefore be altered to left-shift the spectrum. For example, in some embodiments, methyl groups can be substituted with trifluoromethyl or other groups, and hydrogen can be substituted with chlorine or bromine. By replacing electron-donating groups with electron-withdrawing groups, the spectrum can be left-shifted or right-shifted, and vice versa, depending on the specific metal complex dye used. As used herein, a right shift refers to a redshift or red-shift of the spectral wavelength. Therefore, in any embodiment, the spectrum can be modulated by adjusting the functional groups of the metal complex dye.

[0059] According to one example, the filter material may include a dye having a photon emission quencher, and the dye may be a non-radiative dye. According to one example, the photon emission quencher may include chromium (Cr). According to one example, the dye may be a metal complex dye having a photon emission quencher provided by a trivalent Cr transition metal ion. According to one example, the filter material may be provided by a matrix having a dye and a polymer binder, wherein the dye has a photon emission quencher. According to one example, the filter material may be provided by a matrix having a dye and a polymer binder, wherein the dye is a metal complex dye. According to one example, the filter material may be provided by a dye suspended in a polymer matrix, wherein the dye has a photon emission quencher. According to one example, the filter material may be provided by a dye suspended in a polymer matrix, wherein the dye is a metal complex dye.

[0060] The examples in this paper recognize that the performance of system 100 can be negatively affected by background noise, which in this paper refers to unwanted light energy radiated from sources outside detector 200. The examples in this paper also recognize that the signal-to-noise ratio of detector 200 can be negatively affected by fluorescence-range background light radiated from sources outside detector 200. Fluorescence-range noise emission in system 100 can be attributed to sources other than the autofluorescent source within detector 200.

[0061] The examples herein recognize that, for example, while the photoexciter 10 may be configured to ideally emit light in a relatively short wavelength band (e.g., the green wavelength band), spontaneously fluorescent sources, such as optical components, may fluoresce, and the light emitted by the photoexciter 10 may include unwanted light rays at longer wavelengths in the fluorescence band of the detector 200 and the photosensor 202. The examples herein also recognize that light in the fluorescence range can enter the system 100 from sources other than the photoexciter 10.

[0062] refer to Figure 8 This describes additional features used to increase the signal-to-noise ratio of detector 200. (Reference) Figure 8 This document describes features for canceling (e.g., partially or completely canceling) background noise radiation in the fluorescence range that would be received in detector 200 if such features were not described. The cancellation features described herein can reduce the fluorescence range wavelengths not attributable to the emitted signal light 501 sensed by the light sensor 202.

[0063] refer to Figure 3-7 The described filter material characteristics reduce fluorescence range noise by decreasing internal autofluorescence within detector 200. (For example, combined with...) Figure 8 The described features of detector surface 206 reduce unwanted fluorescence range background noise by canceling (e.g., partially or entirely) the fluorescence range light energy incident on detector surface 206. Reference Figure 3-7 The described features can be independent of Figure 8 This can be achieved through features, or by combining an example. Figure 8 This is achieved by utilizing the characteristics of the detector ( Figure 3-7 ) and detector surface ( Figure 8 The combination of features can be used to solve the problem of fluorescence range noise.

[0064] Now for reference Figure 8According to one example, detector 200 can be configured such that light energy incident on detector surface 206 can induce an electromagnetic field radiated from detector surface 206 that cancels (e.g., partially or completely) the incident light energy that would otherwise be transmitted through reaction recess 210. The examples herein recognize that as the ratio of the refractive indices between detector surface 206 and the fluid within flow cell 282 increases, the behavior of the induced field radiated from detector surface 206 induced by light rays incident on detector surface 206 can become more controllable and predictable. The refractive index of detector surface 206 can be defined by the refractive index of the material of passivation layer 258 forming detector surface 206 near flow cell 282. The examples herein recognize that, with a sufficiently high refractive index ratio between detector surface 206 and the fluid in flow cell 282, light rays of excitation light 101 can induce an electromagnetic field radiated from detector surface 206 that cancels the incident light energy depending on the size of detector surface 206.

[0065] Reference Figure 8 The reaction recess 210 may include a dimension “D” provided by the diameter of the reaction recess 210 at its top height. As illustrated herein, if the ratio of the refractive indices between the detector surface 206 and the fluid within the flow cell 282 is sufficiently high, the electromagnetic field induced by incident light energy incident on the reaction recess 210 can cancel out the incident light energy according to the dimension “D”. Figure 8 The detector 200 shown may be an integrated circuit detector having a structure 260 defining a detector surface 206, which may include a passivation layer 256 and a passivation layer 258. According to one example, the passivation layer 258 having the detector surface 206 is formed of tantalum pentoxide (Ta2O5) having a refractive index λ206 of approximately λ206≈2.13, and the fluid in the flow cell 282 is water-based and has a refractive index λ282 of approximately λ282≈1.33. The ratio of the refractive indices between the material forming the detector surface 206 and the fluid in the flow cell 282, λ206 / λ282, is approximately λ206 / λ282≈1.60. According to one example, the passivation layer 258 having the detector surface 206 is formed of silicon nitride (SiN) having a refractive index λ206 of approximately λ206 ≈ 2.02, and the fluid in the flow cell 282 is water-based and has a refractive index λ282 of approximately λ282 ≈ 1.33. The ratio of the refractive indices λ206 / λ282 between the material forming the detector surface 206 and the fluid in the flow cell 282 is approximately λ206 / λ282 ≈ 1.52. In some examples, the three-dimensional shape of the reaction recess 210 can be cylindrical or truncated conical, such that along the extension to Figure 8The horizontal plane on the page captures a roughly circular cross-section. The vertical axis 268 can extend through the geometric center of the cross-section.

[0066] The examples in this article recognize that, for example, Figure 8 The detector surface 206, shown with a reaction recess 210 (nanowell) having a size D and a refractive index appropriately higher than λ206 / λ282, exhibits a critical wavelength λc, wherein wavelengths shorter than the critical wavelength λc are transmitted into the interior of the reaction recess 210 and the detector 200, and wherein wavelengths longer than the critical wavelength λc are canceled (e.g., partially or completely canceled) by the detector surface 206 having the reaction recess 210. The examples herein further demonstrate that the described critical wavelength λc depends on the size D, such that the size D can be controlled to tune the critical size λc to a desired value. More specifically, the critical wavelength λc can be increased by increasing the size D, and decreased by decreasing the size D. Without being limited to a specific theory regarding recognition effects, light rays incident on the detector surface 206 can induce an electromagnetic field radiated from the detector surface 206, which (e.g., partially or completely) cancels out the incident light energy that would otherwise be transmitted through the reaction recess 210.

[0067] The light energy cancellation feature can be advantageously incorporated into the design of the detector surface 206. According to reference... Figure 8 In one example, dimension D can be chosen to establish a critical wavelength λc, such that approximately the center (peak) wavelength λa and shorter wavelengths of the excitation light 101 propagate through the reaction recess 210 and into the detector 200, and further, such that the detector surface 206 cancels approximately the shortest detection wavelength λb and longer wavelengths. The wavelength propagation at approximately the center (peak) wavelength λa and shorter wavelengths of the excitation light 101 ensures proper excitation of the fluorophore according to the design of system 100, and the wavelength cancellation of approximately the shortest detection wavelength λb and longer wavelengths increases the signal-to-noise ratio of the detector 200.

[0068] Although λc can be tuned according to D, the precise relationship between D and the D-dependent cancellation effect can vary depending on the materials, configuration (including the configuration of the photoexciter 10), and process control parameters of the specially manufactured system 100. Nevertheless, information on the relationship between size D and the size-dependent cancellation effect for a specific design of detector 200 can be determined experimentally. In experimentally determining the relationship between D and the cancellation effect for a specific design of detector 200, this information can be used to establish the value of D; that is, D = d1, where D = d1 is chosen to establish the critical wavelength λc, such that approximately the center (peak) wavelength λc of the excitation light 101 and wavelengths at shorter wavelengths are transmitted to the reaction recess 210 and detector 200, and further such that detector surface 206 cancels approximately the shortest detection band wavelength λb and wavelengths at longer wavelengths (i.e., in the fluorescence range).

[0069] According to a process, detector 200 can be manufactured and tested using one or more test samples. Testing may include testing the transmission of excitation light 101 through the reaction recess 210. One or more test samples may be provided and tested to determine a minimum dimension D, D = dc, at which the reaction recess 210 transmits excitation light 101 according to one or more transmission criteria. One or more transmission criteria may be, for example, a threshold amount (e.g., 90%, 100%) of the maximum energy excitation light 100 transmitted through the reaction recess 210. One or more test samples are provided and tested to determine a maximum dimension D, D = de, at which the reaction recess 210 cancels out fluorescence range light (e.g., a discriminable amount of fluorescence range light) in the detection band of the photosensitive sensor 202. For such testing, the signal read out by the photosensitive sensor 202 can be checked using a light guide 214 manufactured according to its production specifications. Detector 200 can be provided according to the production design based on one or more of the determined dimensions D = dc or D = de. In a manufacturing design according to one example, D = d1 can be provided in the range from approximately D = dc to approximately D = de. In a manufacturing design according to one example, D = d1 can be provided at approximately the midpoint distance between D = dc and D = de. In a manufacturing design according to one example, D = d1 can be provided as approximately D = dc. In a manufacturing design according to one example, D = d1 can be provided as approximately D = de. In the described example, a size D can be provided to establish a critical wavelength λc such that λc is in the wavelength range between approximately λa and approximately λb, wherein wavelengths shorter than λc are transmitted by the reaction recess 210, and wherein wavelengths longer than λc are canceled by the reaction recess 210, wherein λa is the center wavelength of the excitation light 101, and wherein λb is the shortest detection band wavelength of the sensor array 201.

[0070] refer to Figure 2 According to the spectral profile coordination diagram, the excitation light 101 can have a center (peak) wavelength (λa) of approximately 523 nm, and the detector 200 with the photosensor 202 can have a detection band starting from approximately 580 nm (the shortest detection band wavelength λb). Therefore, according to an example, the reaction recess 210, configured with a suitable refractive index, can be sized to allow the entry of incident light energy at wavelengths of approximately 523 nm and shorter wavelengths, and can be sized to counteract incident light energy at wavelengths of approximately 580 nm and longer wavelengths. In the case where the detector 200 has a configuration where D = d1 ≈ λc such that the distance d1 is the same as the critical wavelength λc, D can be sized based on D = 550 nm to transmit the excitation light 101 into the reaction recess 210, and according to... Figure 2 The spectral profile is coordinated to cancel out unwanted fluorescence wavelengths. Using the described configuration, detector surface 206 can be sized to allow incident light energy at wavelengths of approximately 523 nm and shorter, and can be sized to cancel out incident light energy at wavelengths of approximately 580 nm and longer.

[0071] This document describes a method comprising: subjecting a test sample detector of detector 200 (having a structure 260 defining a detector surface 206) to testing to determine information (e.g., including information such as dc, de and / or other information relating D to λc) about the relationship between a specified detector surface 206 and an electromagnetic field cancellation effect; and wherein fabricating the structure 260 defining the detector surface 206 includes using the determined information to determine the dimensions of a reaction recess 210 of the detector surface 206 to transmit excitation light 101 in the excitation wavelength band (including the center (peak) wavelength λa) and to cancel light energy incident on the detector surface 206 in the detection band of the optical sensor array 201.

[0072] In some examples, the three-dimensional shape of the reaction recess 210 can be cylindrical or truncated conical, such that along the extension to Figure 8 The horizontal plane on the page captures a circular cross-section. The vertical axis 268 may extend through the geometric center of the cross-section. However, other geometries may be used in alternative examples. For example, the cross-section may be square or octagonal. According to one example, the shielding structure 250 may have a thickness from about 100 nm to about 600 nm, the passivation layer 256 may have a thickness from about 100 nm to about 600 nm, the passivation layer 256 may have a thickness from about 50 nm to about 500 nm, the hole 252 may have a diameter from about 700 nm to about 1.5 μm, and the reaction recess 210 (if present) may have a height H from about 50 nm to about 500 nm.

[0073] Figure 9 and Figure 10 Further details of an example of detector 200 are shown, which has one or more fluorescence range noise reduction features as illustrated herein.

[0074] refer to Figure 9-10 This document describes a detector surface 206 for supporting biological or chemical substances; a sensor array 201 including a photosensitive sensor 202 and a circuit 246 for transmitting data signals based on photons detected by the photosensitive sensor 202; and a guiding array 213 including a light guide 214; wherein the light guide 214 of the guiding array 213 receives excitation light 101 and emission signal light 501 from the detector surface 206, wherein the light guide 214 extends toward each photosensitive sensor 202 of the sensor array 201 and includes a filter material that blocks the excitation light 101 and allows the emission signal light 501 radiated from a fluorescent fluorophore to propagate toward each photosensitive sensor 202, wherein the detector surface includes a reaction recess 210, the reaction recess including a refractive index and size that cancels the background light energy incident on the detector surface in the detection band of the sensor array 201.

[0075] Detector 200 may include a sensor array 201 of light sensors 202, a guide array 213 of light guides 214, and a reaction array 209 of reaction recesses 210. In some examples, the components are arranged such that each light sensor 202 is aligned with a single light guide 214 and a single reaction recess 210. However, in other examples, a single light sensor 202 may receive photons through more than one light guide 214. In some examples, more than one light guide and / or reaction recess may be provided for each light sensor in the light sensor array. In some examples, more than one light guide and / or light sensor may be provided that is aligned with the reaction recesses of the reaction recess array. The term "array" does not necessarily include every item of a particular type that a detector may have. For example, a sensor array of a light source may not include each light sensor of detector 200. As another example, guide array 213 may not include each light guide of detector 200. As another example, reaction array 209 may not include each reaction recess 210 of detector 200. Therefore, unless explicitly stated otherwise, the term "array" may or may not include all of these items of detector 200.

[0076] In the example shown, flow cell 282 is defined by sidewall 284 and flow cap 288, which is supported by sidewall 284 and other sidewalls (not shown). The sidewalls are attached to detector surface 206 and extend between flow cap 288 and detector surface 206. In some examples, the sidewalls are formed of a curable adhesive layer that bonds flow cap 288 to detector 200.

[0077] The flow cell 282 may include a height H1. By way of example only, the height H1 may be between approximately 50 and 400 μm, or more specifically, approximately 80 to 200 μm. The flow cap 288 may include a material that allows the excitation light 101 to propagate from the outside of the detector assembly 20 into the flow cell 282.

[0078] It is also shown that the flow cap 288 may define an inlet 289 and an outlet 290 configured to fluidly engage other ports (not shown). For example, the other ports may originate from a box (not shown) or a workstation (not shown).

[0079] Detector 200 has a detector surface 206 that can be functionalized (e.g., chemically or physically modified in a manner suitable for performing a specified reaction). For example, detector surface 206 can be functionalized and can include multiple reaction sites to which one or more biomolecules are immobilized. Detector surface 206 may have a reaction array 209 with reaction recesses 210. Each of the reaction recesses 210 may include one or more reaction sites. The reaction recesses 210 may be defined by, for example, indentation or variation along the depth of detector surface 206. In other examples, detector surface 206 may be planar.

[0080] Figure 10 This is a magnified cross-section of detector 200, which shows various features in more detail. More specifically, Figure 10 A single optical sensor 202, a single light guide 214 for directing the emitted signal light 501 to the optical sensor 202, and associated circuitry 246 for transmitting signals based on the emitted signal light 501 (e.g., photons) detected by the optical sensor 202 are shown. It should be understood that the sensor array 201 ( Figure 9 Other optical sensors 202 and associated components may be configured in the same or similar manner. However, it should also be understood that detector 200 does not need to be manufactured exactly the same or uniformly. Instead, one or more optical sensors 202 and / or associated components may be manufactured differently or have different relationships with each other.

[0081] Circuit 246 may include interconnected conductive elements (e.g., conductors, traces, vias, interconnects, etc.) capable of conducting current, such as the transmission of data signals based on detected photons. Detector 200 includes an integrated circuit with a planar array of light sensors 202. Circuit 246 formed within detector 200 may be configured to at least one of the following: readout of signal from light sensor 202 after an exposure cycle (integration cycle) in which charge accumulates on light sensor 202; signal amplification; digitization; storage; and processing. Circuit 246 may collect and analyze detected emitted signal light 501 and generate a data signal for transmitting detection data to a bioassay system. Circuit 246 may also perform additional analog and / or digital signal processing within detector 200. Light sensor 202 may be electrically connected to circuit 246 via gates 241-243.

[0082] According to one example, the detector 200 can be provided by a solid-state integrated circuit detector, such as a CMOS integrated circuit detector or a CCD integrated circuit detector. According to one example, the detector 200 can be an integrated circuit chip manufactured using an integrated circuit manufacturing process, such as a complementary metal-oxide-semiconductor (CMOS) manufacturing process.

[0083] The resolution of the sensor array 201 defined by the light sensor 202 can be greater than approximately 0.5 megapixels (Mpixel). In a more specific example, the resolution can be greater than approximately 5 Mpixels, and more specifically, greater than approximately 14 Mpixels.

[0084] Detector 200 may include multiple stacked layers 231-237 comprising a sensor layer 231, which may be a silicon layer. The stacked layers may include multiple dielectric layers 232-237. In the illustrated example, each of the dielectric layers 232-237 includes a metallic element (e.g., W (tungsten), Cu (copper), or Al (aluminum)) and a dielectric material, such as SiO2. Various metallic elements and dielectric materials can be used, such as those suitable for integrated circuit fabrication. However, in other examples, one or more dielectric layers 232-237 may consist only of a dielectric material, such as one or more layers of SiO2.

[0085] about Figure 10 In a specific example, dielectric layers 232-237 may include metallization layers, in Figure 10 The layers are labeled M1-M5. As shown, the metallization layers M1-M5 can be configured to form at least a portion of the circuit 246.

[0086] In some examples, detector 200 includes a shielding structure 250 having one or more layers extending over a region above the metallization layer M5. In the illustrated example, shielding structure 250 may include a material configured to block, reflect, and / or significantly attenuate optical signals propagating from flow cell 282. The optical signals may be excitation light 101 and / or emission signal light 501. By way of example only, shielding structure 250 may include tungsten (W). By way of specific example only, excitation light 101 may have a center (peak) wavelength of approximately 523 nm, and emission signal light 501 may include wavelengths of approximately 570 nm and longer. Figure 2 ).

[0087] like Figure 10 As shown, the shielding structure 250 may include through-holes 252. The shielding structure 250 may include an array of such through-holes 252. The through-holes 252 are sized to allow signal-emitted light to propagate to the light guide 214. The detector 200 may also include a passivation layer 256 extending along the shielding structure 250 and across the through-holes 252. The detector 200 may also include a passivation layer 258 including a detector surface 206 extending along the passivation layer 256 and across the through-holes 252. The shielding structure 250 may extend over the through-holes 252, thereby directly or indirectly covering the through-holes 252. The passivation layers 256 and 258 may be configured to protect the lower-height layer and the shielding structure 250 from the fluid environment of the flow cell 282. According to one example, the passivation layer 256 is formed of SiN or a similar material. According to one example, the passivation layer 258 is formed of tantalum pentoxide (Ta2O5) or a similar material. Structure 260 having passivation layer 256 and passivation layer 258 can define detector surface 206 having reaction recess 210. Structure 260 defining detector surface 206 can have any number of layers, such as 1 to N layers.

[0088] Structure 260 may define a solid surface (i.e., detector surface 206) that allows biomolecules or other analytes of interest to be immobilized thereon. For example, each reaction site of the reaction recess 210 may include a cluster of biomolecules immobilized to the detector surface 206 of the passivation layer 258. Therefore, the passivation layer 258 may be formed of a material that allows the reaction sites of the reaction recess 210 to be immobilized thereon. The passivation layer 258 may also include a material that is at least transparent to the desired fluorescence. The passivation layer 258 may be physically or chemically modified to facilitate the immobilization of biomolecules and / or to facilitate the detection of the emitted signal light 501.

[0089] In the illustrated example, a portion of the passivation layer 256 extends along the shielding structure 250, and another portion of the passivation layer 256 extends directly along the filter material defining the light guide 214. The reactive recess 210 may be aligned with and formed directly on the light guide 214. According to one example, each of the reactive recess 210 and the light guide 214 may have a geometric center centered on the longitudinal axis 268.

[0090] As this article combines Figure 8 As described, the detector surface 206 can be sized such that light energy incident on the detector surface 206 in the fluorescence range can be canceled out by the operation of an induced electromagnetic field. According to one example, the shielding structure 250 may have a thickness from about 100 nm to about 600 nm, the passivation layer 256 may have a thickness from about 100 nm to about 600 nm, the passivation layer 256 may have a thickness from about 50 nm to about 500 nm, the aperture 252 may have a diameter from about 700 nm to about 1.5 μm, and the reaction recess 210 (if present) may have a height from about 50 nm to about 500 nm.

[0091] In some cases, before the passivation layer 256 is deposited along the shielding structure 250, and before the shielding structure 250 is deposited, the cavity defined by the sidewall 254 may be formed by a dielectric stack defined by dielectric layers 232-237. For example, the dielectric stack defined by dielectric layers 232-237 may be etched to form an array of cavities defined by the sidewall 254, wherein one cavity is formed for each photosensor 202 of the photosensor array 201. In a particular example, the cavity defined by the sidewall 254 is a vertically elongated space extending from the access hole 252 toward the photosensor 202.

[0092] The cavity may extend perpendicularly along the longitudinal axis 268. In some examples, the three-dimensional shape of the cavity defined by the sidewall 254 may be cylindrical or truncated conical, such that along the extension to... Figure 10 The horizontal plane on the page captures a circular cross-section. The vertical axis 268 can extend through the geometric center of the cross-section. However, other geometries can be used in alternative examples. For example, the cross-section can be square or octagonal. According to one example, the vertical axis 268, serving as the vertical axis of the light guide 214, can extend through the geometric center of the light sensor 202 and the reaction recess 210.

[0093] The filter material defining the light guide 214 can be deposited within the cavity defined by the sidewall 254 after the cavity is formed. For the fabrication of the light guide 214 according to one example, dye molecules in powder form (e.g., having a photon emission quencher) can be dissolved in a solvent and added to a liquid polymer binder to form a homogeneous liquid matrix having dye molecules and polymer molecules. According to one example, the dye molecules in powder form can be metal-complexed dye particles.

[0094] A homogeneous liquid matrix can be deposited into the media stack cavity of detector 200 and dehydrated to form a filter material comprising a solid dye and a polymer matrix, wherein dye molecules are suspended in the matrix of polymer binder molecules. The homogeneous polymer binder and dye matrix filter material can be deposited into the cavity defined by sidewall 254 using, for example, chemical vapor deposition (CVD) or physical vapor deposition (PVD). Deposition can be performed to overfill the cavity defined by sidewall 254 with the filter material, and then patterned, for example, by planarization or etching, to reduce the height of the filter material defining light guide 214. According to one example, the filter material used to form light guide 214 may include metal-complexed dye molecules suspended in the polymer binder molecular matrix.

[0095] A filter material (e.g., after curing) can be formed into a light guide 214. The light guide 214 can be configured to block the excitation light 101 and allow the emission of signal light 501. Figure 1 This propagates to the corresponding optical sensor 202. The optical guide 214 can be referenced herein. Figure 2-7 The described filter material is formed. The filter material may comprise a homogeneous matrix of dye and polymer binder, wherein the dye may comprise a photon emission quencher and, according to one example, is provided by a metal complex dye. The dye and polymer matrix, according to one example, may comprise a weight concentration ranging from about 70:30 dye-to-polymer to about 90:10 dye-to-polymer. The filter material mixture may have a molecular ratio of about 1 dye molecule to about 100 polymer molecules.

[0096] The light guide 214 can be configured relative to the surrounding material of the dielectric stack defined by dielectric layers 231-237 to form a light guide structure. For example, the light guide 214 can have a refractive index of at least about 2.0, such that light propagating through the light guide is reflected at the interface between the light guide 214 and the surrounding dielectric stack defined by dielectric layers 231-237. In some examples, the light guide 214 is configured such that the optical density (OD) or absorbance of the excitation light 101 is at least about 4OD. More specifically, a filter material can be selected, and the light guide 214 can be sized to achieve at least 4OD. In more specific examples, the light guide 214 can be configured to achieve at least about 5OD or at least about 6OD. Other features of the detector 200 can be configured to reduce electrical and optical crosstalk.

[0097] It should be recognized that all combinations of the foregoing concepts and other concepts discussed in more detail below (assuming these concepts do not contradict each other) are considered part of the subject matter disclosed herein. In particular, all combinations of the claimed subject matter appearing at the end of this disclosure are considered part of the subject matter disclosed herein. It should also be recognized that terms expressly adopted herein may also appear in any disclosure incorporated by reference, and should be given the meaning most consistent with the specific concepts disclosed herein.

[0098] This written description uses examples of the disclosed subject matter and also enables any person skilled in the art to practice the subject matter, including making and using any device or system and performing any combined methods. The patentable scope of this subject matter is defined by the claims and may include other examples that would occur to a person skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that are not different from the literal language of the claims, or if they include equivalent structural elements that are not substantially different from the literal language of the claims.

[0099] It will be understood that the above description is intended to be illustrative and not restrictive. For example, the above examples (or one or more aspects thereof) may be used in combination with each other. Furthermore, many modifications may be made to adapt particular situations or materials to the teachings of the various examples without departing from their scope. While the dimensions and types of materials described herein are intended to define parameters of the various examples, they are by no means restrictive and are merely exemplary. Many other examples will be apparent to those skilled in the art in reviewing the above description. Therefore, the scope of the various examples should be determined by reference to the entire scope of the appended claims together with the equivalents claimed by those claims. In the appended claims, the terms “including” and “in which” are used authentically in English and are equivalent to the corresponding terms “comprising” and “wherein”. Furthermore, in the claims, the terms “first,” “second,” and “third,” etc., are used merely as labelling and are not intended to impose numerical requirements on their objects. The term “based on” in this document includes relationships of partial and complete element-based relationships. The term “defined” in this document includes relationships of partially defined and complete element-defined relationships. Furthermore, the limitations of the claims are not drafted in the form of "means plus function," nor are they interpreted based on 35 U.S.SC § 112, paragraph 6, unless and until these claims explicitly use the phrase "means for..." followed by a functional statement without further structure. It should be understood that, according to any particular example, it is not necessarily possible to achieve all of the foregoing objectives or advantages. Therefore, for example, those skilled in the art will recognize that the systems and techniques described herein may be embodied or performed in a manner that achieves or optimizes one or more advantages taught herein, without necessarily achieving other objectives or advantages taught or suggested herein.

[0100] Although the subject matter has been described in detail with reference to only a limited number of examples, it should be readily understood that the subject matter is not limited to these disclosed examples. Rather, the subject matter can be modified to incorporate any number of variations, alterations, substitutions, or equivalent arrangements not described to date but commensurate with the spirit and scope of the subject matter. Furthermore, although various examples of the subject matter have been described, it should be understood that aspects of this disclosure may include only some of the described examples. Moreover, while some examples are described as having a certain number of elements, it should be understood that the subject matter can be practiced with fewer or more than a certain number of elements. Therefore, the subject matter should not be considered limited to the foregoing description but only to the scope of the appended claims.

[0101] Various aspects of this disclosure may be implemented in one or more of the embodiments described below.

[0102] 1) An apparatus comprising:

[0103] The structure defines the detector surface configured to support biological or chemical samples;

[0104] A sensor array comprising a light sensor and circuitry for transmitting photon signals detected using the light sensor; and

[0105] A guiding array, which includes optical guides;

[0106] The light guide of the guiding array receives excitation light and emission signal light from the detector surface, wherein the light guide extends toward each photosensor of the sensor array and includes a filter material that blocks the excitation light and allows the emission signal light to propagate toward each photosensor, wherein the filter material includes a metal complex dye.

[0107] 2) The device according to 1), wherein the filter material comprises a metal complex dye suspended in a polymer binder matrix.

[0108] 3) The device according to 1), wherein the filter material comprises a homogeneous matrix of a metal complex dye and a polymer binder, and wherein the homogeneous matrix comprises a weight concentration ratio of the metal complex dye to the polymer binder in the range of about 70:30 to about 90:10.

[0109] 4) The device according to 1), wherein the detector surface includes a reaction recess for supporting the sample, wherein the reaction recess includes a refractive index and size for counteracting background radiation in the detection band of the sensor array.

[0110] 5) The apparatus according to 1), wherein the metal complex dye comprises a transition metal complex dye.

[0111] 6) The apparatus according to 1), wherein the metal complex dye comprises a transition metal and a dye component, and wherein the transition metal has an absorption spectral profile that overlaps with the fluorescence emission spectral profile of the dye component.

[0112] 7) The apparatus according to 1), wherein the metal complex dye reduces the autofluorescence of the filter material.

[0113] 8) The device according to 1), wherein the filter material comprises counterions associated with the metal complex dye.

[0114] 9) The apparatus according to 8), wherein the counterion comprises alkylamine.

[0115] 10) The apparatus according to 9), wherein the alkylamine comprises at least one hydrocarbon group having at least four carbon atoms.

[0116] 11) A method comprising:

[0117] To manufacture a circuit that uses photons detected by an array of optical sensors to transmit data signals;

[0118] A filter material is deposited within a guide cavity of a guide cavity array, the guide cavity being aligned with and positioned above each photosensor of the photosensor array, wherein the filter material comprises a dye suspended in a polymer matrix, the dye comprising a photon emission quencher; and

[0119] Manufacturing a structure defining a detector surface for supporting a biological or chemical sample, wherein manufacturing the structure defining the detector surface includes manufacturing the structure defining the detector surface above the cavity of the guide cavity array and the photosensor of the photosensor array.

[0120] 12) The method according to 11), wherein depositing the filter material includes using chemical vapor deposition, and wherein after said deposition, the deposited filter material is treated with one or more of etching and planarization.

[0121] 13) The method according to 11), wherein the fabrication of the circuit includes using complementary metal-oxide-semiconductor (CMOS) fabrication technology.

[0122] 14) The method according to 11), wherein the filter material comprises a homogeneous matrix of metal complex dye and polymer binder.

[0123] 15) The method according to 11), wherein the filter material comprises a matrix of a metal complex dye and a polymer binder, and wherein the weight concentration of the metal complex dye to the polymer binder is in the range of about 70:30 to about 90:10.

[0124] 16) The method according to 11), wherein manufacturing the structure defining the sample support surface includes forming a reaction recess defined in the sample support surface, wherein the forming includes configuring the reaction recess such that, based on the refractive index of the detector surface and the size characteristics of the reaction recess, an induced electromagnetic field radiated from the detector surface cancels background light energy incident on the detector surface in the detection wavelength band of the optical sensor array.

[0125] 17) The method according to 11), wherein the method includes testing one or more test sample detectors to determine information relating the size of the detector surface to the electromagnetic field cancellation effect, and wherein manufacturing the structure defining the detector surface includes using the determined information to set the size of the reaction recesses on the detector surface to cancel the light energy incident on the detector surface in the detection band of the optical sensor array.

[0126] 18) The method according to 11), wherein the filter material comprises counterions associated with a metal complex dye comprising the dye.

[0127] 19) The method according to 18), wherein the counterion comprises an alkylamine.

[0128] 20) The method according to 19), wherein the alkylamine comprises at least one hydrocarbon group having at least four carbon atoms.

[0129] 21) An apparatus comprising:

[0130] The structure defines the detector surface for supporting biological or chemical samples;

[0131] A sensor array comprising a light sensor and circuitry for transmitting data signals based on photons detected by the light sensor; and

[0132] A guiding array, which includes optical guides;

[0133] The light guide of the guiding array receives excitation light and emission signal light from the detector surface, wherein the light guide extends toward each photosensor of the sensor array and includes a filter material that blocks the excitation light and allows the emission signal light to propagate toward each photosensor, wherein the detector surface includes a reaction recess with a refractive index and size sufficient to counteract background light energy incident on the detector surface in the detection band of the sensor array.

[0134] 22) The device according to 21), wherein the reaction recess includes a refractive index and size sufficient to transmit the center wavelength of the excitation light.

[0135] 23) The device according to 21), wherein the reaction recess includes a refractive index and size sufficient to establish a critical wavelength λc such that λc is in the wavelength range between approximately λa and approximately λb, wherein wavelengths shorter than λc are transmitted by the reaction recess, and wherein wavelengths longer than λc are canceled by the reaction recess, wherein λa is the center wavelength of the excitation light, and wherein λb is the shortest detection wavelength of the sensor array.

[0136] 24) The apparatus according to 21), wherein the filter material comprises a metal complex dye.

[0137] 25) The device according to 21), wherein the filter material comprises a matrix of metal complex dye and polymer binder, and wherein the weight concentration of the metal complex dye to the polymer binder in the matrix is ​​in the range of about 70:30 to about 90:10.

[0138] 26) The device according to 21), wherein the filter material comprises a metal complex dye, the metal complex dye comprising a transition metal complex dye.

Claims

1. An apparatus with reduced fluorescence range noise, comprising: The detector surface is configured to support biological or chemical samples; A sensor array, comprising a light sensor and multiple light guides; The light guide receives excitation light and emission signal light from the detector surface. The light guide extends toward each photosensor of the sensor array and includes a filter material that blocks light in the energy band of the excitation light and allows the emission signal light to propagate toward each photosensor. The filter material includes a metal complex dye comprising a transition metal and dye molecules, wherein the transition metal is a photon emission quencher and has an absorption spectral profile that overlaps with the fluorescence emission spectral profile of the dye molecules.

2. The device according to claim 1, wherein, The metal complex dye is suspended in a polymer binder matrix.

3. The device according to claim 1, wherein, The filter material comprises a homogeneous matrix of the metal complex dye and the polymer binder, wherein the homogeneous matrix comprises a metal complex dye to polymer binder weight ratio in the range of 70:30 to 90:

10.

4. The device according to claim 1, wherein, The detector surface includes a reaction recess for supporting the sample, wherein the reaction recess includes a refractive index and size for counteracting background radiation in the detection band of the sensor array.

5. The device according to claim 1, wherein, The metal complex dye is a transition metal complex dye.

6. The device according to claim 1, wherein, The filter material also includes counterions associated with the metal complex dye.

7. The device according to claim 6, wherein, The counterion includes an alkylamine having at least one hydrocarbon group having at least four carbon atoms.

8. A method for reducing fluorescence range noise, comprising: A filter material is deposited in the guide cavity of the guide cavity array, the guide cavity being aligned with and positioned above each photosensor of the photosensor array, wherein the filter material comprises a metal complex dye, the metal complex dye comprising a transition metal and dye molecules, wherein the transition metal is a photon emission quencher and has an absorption spectral profile that overlaps with the fluorescence emission spectral profile of the dye molecules. and Structures defining detector surfaces for supporting biological or chemical samples are fabricated above the cavities of the guide cavity array and the photosensors of the photosensor array.

9. The method according to claim 8, wherein, The deposition of filter materials includes the use of chemical vapor deposition, wherein, after the deposition, the deposited filter material is treated with one or both of etching and planarization.

10. The method according to claim 8, wherein, The filter material comprises a homogeneous matrix of the metal complex dye and the polymer binder.

11. The method according to claim 8, wherein, The filter material comprises a matrix of metal complex dye and polymer binder, wherein the weight ratio of the metal complex dye to the polymer binder is in the range of 70:30 to 90:

10.

12. The method according to claim 8, wherein, The method includes testing one or more test sample detectors to determine information relating the size of the detector surface to electromagnetic field cancellation effects, and wherein manufacturing the structure defining the detector surface includes using the determined information to set the size of a reactive recess on the detector surface to cancel background light energy incident on the detector surface in the detection band of the optical sensor array.

13. The method according to claim 9, wherein, The filter material includes counterions associated with the metal complex dye.

14. The method according to claim 13, wherein, The counterion includes an alkylamine having at least one hydrocarbon group having at least four carbon atoms.

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