Patent Description:
Various protocols in biological or chemical research involve performing controlled reactions. The designated reactions can then be observed or detected and subsequent analysis can help identify or reveal properties of chemicals involved in the reaction.

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

In some fluorescent-detection protocols, an optical system is used to direct excitation light onto fluorophores, e.g. fluorescently-labeled analytes and to also detect the fluorescent emissions signal light that can emit from the analytes having attached fluorophores. However, such optical systems can be relatively expensive and require a larger benchtop footprint. For example, the optical system can include an arrangement of lenses, filters, and light sources. In other proposed detection systems, the controlled reactions in a flow cell define by a solid-state light sensor array (e.g. a complementary metal oxide semiconductor (CMOS) detector or a charge coupled device (CCD) detector). These systems do not involve a large optical assembly to detect the fluorescent emissions.

<CIT> refers to a method of fabricating an integrated detection biosensor comprising an assembly of photodetectors of CCD or CMOS type.

<CIT> describes a known bio-sensor including a substrate having a light-sensing region thereon. <CIT> refers to substrates for use in various applications, including single-molecule analytical reactions and methods for propagating optical energy within a substrate.

<CIT> discloses methods of sequencing molecules based on luminescence lifetimes and/or intensities. In some aspects, methods of sequencing nucleic acids involve determining the luminescence lifetimes, and optionally luminescence intensities, of a series of luminescently labeled nucleotides incorporated during a nucleic acid sequencing reaction. <CIT> refers to the problem to obtain an optical filter which prevents the malfunction of a remote control due to IR rays and provides an optical filter having a transparent support and a filter layer.

There is set forth herein a device, as defined in appended claim <NUM>, amongst other features comprising: structure defining a detector surface configured for supporting biological or chemical substances, and a sensor array comprising light sensors and circuitry to transmit data signals using photons detected by the light sensors. The device and method according to the independent claims include one or more feature sufficient to cancel background light energy incident on the detector surface in a detection band of the sensor array. Further advantageous features are disclosed in the dependent claims.

These and other features, aspects, and advantages of the present subject matter will become better understood when the following detailed description is read with reference to the accompanying drawings in which like characters represent like parts throughout the drawings, wherein:.

In <FIG> there is shown a system <NUM> for use in analysis, such as biological or chemical analysis. System <NUM> can include light energy exciter <NUM> and a detector assembly <NUM>. Detector assembly <NUM> can include detector <NUM> and a flow cell <NUM>. Detector <NUM> can include a plurality of light sensors <NUM> and detector surface <NUM> for supporting samples <NUM> such as biological or chemical samples subject to test. Detector <NUM> can also include a plurality of light guides that guide light from detector surface <NUM> to light sensors <NUM>. Detector surface <NUM>, sidewalls <NUM>, and flow cover <NUM> can define and delimit flow cell <NUM>. Detector surface <NUM> can have an associated detector surface plane <NUM>.

In a further aspect, detector surface <NUM> can be recessed to include reaction recesses <NUM> (nanowells). According to one example, each light sensor <NUM> can be aligned to one light guide <NUM> and one reaction recess <NUM>. Each reaction recess <NUM> can define therein one or more reaction sites and samples <NUM> can be supported on such reaction sites according to one example.

In another aspect, detector <NUM> can include dielectric stack areas <NUM>, intermediate of the light guides <NUM>. Dielectric stack areas <NUM> can have formed therein circuitry, e.g. for read out of signals from light sensors <NUM> digitization storage and processing.

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

According to one example, system <NUM> can be used for performance of biological or chemical testing with use of fluorophores. For example, a fluid having one or more fluorophores can be caused to flow into and out of flow cell <NUM> through inlet port using inlet port <NUM> and outlet port <NUM>. Fluorophores can attract to various samples <NUM> and thus, by their detection fluorophores can act as markers for the samples <NUM> e.g. biological or chemical analytes to which they attract.

To detect the presence of a fluorophore within flow cell <NUM>, light energy exciter <NUM> can be energized so that excitation light <NUM> in an excitation wavelength range is emitted by light energy exciter <NUM>. On receipt of excitation light <NUM> fluorophores attached to samples <NUM> radiate emissions signal light <NUM>, which is the signal of interest for detection by light sensors <NUM>. Emissions signal light <NUM> owing to fluorescence of a fluorophore attached to a sample <NUM> will have a wavelength range red shifted relative to a wavelength range of excitation light <NUM>.

Light energy exciter <NUM> can include at least one light source and at least one optical components to illuminate samples <NUM>. Examples of light sources can include e.g. lasers, arc lamps, LEDs, or laser diodes. The optical components can be, for example, reflectors, dichroics, beam splitters, collimators, lenses, filters, wedges, prisms, mirrors, detectors, and the like. In examples that use an illumination system, the light energy exciter <NUM> can be configured to direct excitation light <NUM> to reaction sites. As one example, fluorophores can be excited by light in the green wavelength range, e.g. can be excited using excitation light <NUM> having a center (peak) wavelength of about <NUM>.

Examples herein recognize that a signal to noise ratio of system <NUM> can be expressed as set forth in the equation of (<NUM>) hereinbelow. <MAT> where "Signal" is the emissions signal light <NUM>, i.e. the signal of interest light attributable to the fluorescence of a fluorophore attached to a sample, "Excitation" is unwanted excitation light reaching the light sensors <NUM>, "AF" is the autofluorescence noise radiation of one or more autofluorescence sources within detector <NUM>, "Background" is unwanted light energy transmitted into detector <NUM> from a source external to detector <NUM>, "Dark Current" is current flow is noise associated to random electron-hole pair generation in the absence of light and "Read Noise" is noise associated to analog-to-digital electronics.

<FIG> is a spectral profile coordination diagram illustrating targeted coordination between a wavelength range of excitation light, a wavelength range of signal light and a detection wavelength range. In the spectral profile coordination diagram of <FIG> spectral profile <NUM> is the spectral profile of excitation light <NUM> as emitted by light energy exciter <NUM>. Spectral profile <NUM> is the spectrum of absorption of a fluorophore being detected with use of excitation light <NUM> having a spectral profile <NUM> and spectral profile <NUM> is the spectral profile of the emissions signal light <NUM> caused by the fluorescence of a fluorophore on being excited by excitation light <NUM>. Spectral profile <NUM> is the transmission profile (detection band) of detector <NUM> and light sensors <NUM> according to one example. Detector <NUM> can be configured to detect light in the wavelength range indicated by spectral profile <NUM>. Thus, referring to the spectral profile coordination diagram of <FIG>, detector <NUM> is able to detect emissions signal light <NUM> in the range of wavelengths wherein the spectral profile <NUM> of the emissions signal light <NUM> and the detection band spectral profile <NUM> of detector <NUM> and light sensors <NUM> intersect.

Detector <NUM> can include one or more filters that block excitation light <NUM> so that detector <NUM> having light sensors <NUM> does not detect excitation light <NUM>. In one aspect, light guides <NUM> that guide light from detector surface <NUM> can comprise filter material so that light guides <NUM> block light in the wavelength range of excitation light <NUM>. Light sensors <NUM> accordingly can receive emissions signal light <NUM> radiating from an excited fluorophore but not excitation light <NUM>.

Examples herein recognize that light guides <NUM> designed to improve a signal to noise ratio of detector <NUM> can act as a source of noise within detector <NUM>. Referring to the spectral profile diagram of <FIG> spectral profile <NUM> is a spectral profile of a filter material having a dye that is without (absent) a photon emission quencher commonly used in optical systems under test by excitation illumination in an expected wavelength range of excitation light <NUM> of system <NUM>. In the specific spectral profile diagram of <FIG>, spectral profile <NUM> illustrates a spectral profile of a filter material under illumination by green excitation light, e.g. according to the excitation light spectral profile <NUM> depicted in the spectral profile coordination diagram of <FIG>, having a center (peak) wavelength of about <NUM>.

Referring to the spectral profile diagram of <FIG> it is seen that the filter material having spectral profile characteristics depicted by spectral profile <NUM> red shifts with respect to the emission band of excitation light <NUM> depicted by spectral profile <NUM> of the spectral profile coordination diagram of <FIG>, meaning that the material exhibits autofluorescence. Examples herein recognize that with filter material of light guides <NUM> autofluorescing, signal detected by light sensors <NUM> as an emissions signal can actually be noise radiation attributable to excitation light <NUM> operating to excite autofluorescence of light guides <NUM>.

Examples to address unwanted autofluorescence of light guides <NUM> are described with reference to <FIG>. Referring to the energy state transition diagrams of <FIG>, light guides <NUM> according to one example can comprise material having a photon emission quencher. In another aspect, a filter material can include dye molecules to provide absorption in a wavelength band of excitation light <NUM>.

The energy state transition diagram of <FIG> depicts energy state transition of a dye without a photon emission quencher. On excitation and after an excitation state relaxation period the dye having the energy state transition characteristics as depicted in the energy state transition diagram of <FIG> emits photons on return to a ground state. <FIG> is an energy state transition diagram depicting energy state transitions of a dye having a photon emission quencher. Referring to the energy state transition diagram of <FIG>, the dye having a photon emission quencher on excitation returns to a ground state after an excitation state relaxation period. However, by operation of the photon emission quencher, photons are not released on return to the ground state. Rather phonons are emitted on return to the ground state. The return to ground state is accompanied by the release of thermal energy rather than photons.

Dyes having the energy state transition characteristics as shown in the energy state transition diagram of <FIG> are radiant dyes and dyes having energy state transition characteristics as shown in the energy state transition diagram of <FIG> are non-radiant dyes.

A chemical structure diagram of a dye, according to one example, having a suitable photon emission quencher that quenches photon emissions is shown in (<NUM>).

The chemical structural diagram of (<NUM>) illustrates structural characteristics of a metal complex dye that functions as a photon emission quencher to quench photon emissions. According to one example, a metal complex dye can be provided by an octahedral transition metal complex dye as shown in (<NUM>). The specific metal complex dye shown in (<NUM>) includes two dye molecules + chromium ion, and some complexes can include one dye molecule + one chromium (Cr) ion or other metal ion. The structure depicted in (<NUM>) includes six ligand bonds: O, N and a standard crystal field. According to the structure depicted in (<NUM>), there is a photon emission quencher provided by a trivalent Cr transition metal ion. According to one example Cr3 + can provide photon emission quenching functionality. Other transition metals can be used. Transition metals for use in a metal complex dye herein can include e.g. Scandium, Titanium, Vanadium, Chromium, Manganese, Iron, Cobalt, Nickel, Copper. For selection of alternative metals, energy levels can be overlapping between the metal ion and a dye molecule. According to one example, a transition metal for use in a metal complex dye can be selected to have an absorption spectral profile overlapping a fluorescence emissions profile of the selected dye so that the transition metal can provide photon emission quenching functionality through the fluorescence emission spectral profile of the selected dye.

In the example of the metal complex dye depicted in the structural diagram of (<NUM>), the metal complex dye has an associated proton depicted. The counter ion associated to 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 (<NUM>) and can be selected according to one example for hydrophobicity performance and UV absorption performance. In one example, an alkyl amine, a primary amine, a secondary amine, or a tertiary amine may associate with the metal complex dye forming a counter ion, which can include an alkylammonium when associated with the metal complex dye.

The metal complex dye according to one example may not be particularly soluble in a solution on its own, and so the counter ion can be chosen to increase solubility. The counter ion can be selected for hydrophobicity performance in order to promote transparency and visibility of the polymer and/or solvent, and for reducing scattering. For instance, the counter ion can allow for the metal complex dye to be more evenly distributed, enhancing the visibility and transparency, and reducing scattering. The counter ion can be selected for UV absorption performance e.g. so that the counter ion does not undesirably contribute to fluorescence. For instance, absorption of the counter ion can affect the fluorescence characteristics by interfering with the spectrum of the metal dye complex, and can be chosen so as not to have an interfering spectrum. According to one example, a hydrophobic amine can be used as a counter ion. According to another example, it will be understood that depending on the metal center and the ligands chosen, a metal complex dye may have no charge, a net positive charge, or may have a net negative charge as well.

According to one example a counter ion associated to the metal complex dye depicted in the structural diagram of (<NUM>) can be provided by an alkyl amine. According to one example a counter ion associated to the metal complex dye depicted in the structural diagram of (<NUM>) can be provided by a tertiary amine. In a tertiary amine, a nitrogen has three organic substituents. According to one example, a counter ion associated to the metal complex dye depicted in the structural diagram of (<NUM>) can be provided by a tertiary alkyl amine.

Additionally, in other examples of a metal complex dye, a counter ion of appropriate charge can be selected to be associated to the metal complex dye. In some embodiments, a negatively or positively charged ion can be selected to counteract the net charge of the metal complex dye molecule, and/or adding to the hydrophobicity in some embodiments to allow for the metal complex dye to be incorporated into a solution. Additionally, when there is no charge, no counter ion may be necessary in some embodiments. The counter ion may include any charged particles, and in some embodiments includes primary, secondary, or tertiary amines. In further embodiments, a quaternary ammonium ion can be selected.

According to one example, the counter ion associated to the metal complex dye as depicted in (<NUM>) can include an amine, for instance an NR'R"R"', where at least one of the R groups is a chain, straight or branched, with at least four atoms. In some embodiments, there can be at least <NUM> atoms in the chain. The chain can include a long chain, and can include a polymer. The chain may be a mostly hydrocarbon group, or could include other moieties, such that the dye can possibly be soluble in any solvent necessary, and the polymer can be soluble in a solvent depending on the functional groups of the polymer. The other R groups can be the same or hydrogen, or can comprise a different chain. The chain can be according to one example a C4 to C20, including cyclic, chains or rings. In some embodiments, the counter ion can include more than one type of counter ion. Examples herein recognize that some mixtures of counter ions are convenient for use in solutions where more than one polymer material can be used. That is, some alkyl groups can be different, and the counter ion can include a plurality of counter ions.

<FIG> is an energy state transition diagram illustrating properties of metal complex dyes. <FIG> is an energy state transition diagram for Cr (CNtBuAr<NUM>NC)<NUM>. Referring to the energy state transition diagram of <FIG>, metal complexes can lead to ultrafast non-radiative (non-autofluorescence) relaxation due to metal centered states being below the metal-<NUM>-ligand charge-transfer (MLCT) complex. For Cr (CNtBuAr<NUM>NC)<NUM>) depicted in the energy state transition diagram in <FIG>, the ligand field can be sufficiently weak that metal centered 3d-d excited states can be energetically below the MLCT complex leading to ultrafast excited state. Metal complex dyes can exhibit ultrafast excited state depopulation via non-radiative relaxation. According to the energy state transition diagram of <FIG> a metal complex functioning as a photon emission quencher quenches photons so that a return to ground state is accompanied by phonon emission and release of thermal energy rather than photon emission.

To provide filter material, dye molecules in powder form, e.g. having photon emission quencher, and according to one example provided by a metal complex dye, can be dissolved with 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 a dielectric stack cavity of detector <NUM> and evaporated to form a filter material comprising a solid dye and polymer matrix wherein dye molecules are suspended within a matrix of polymer binder molecules.

A filter material for forming light guide <NUM> according to one example can include metal complex dye molecules suspended in a polymer binder matrix as set forth herein. A formed filter material including metal complex dye molecules suspended in a polymer binder matrix can exhibit spectral profile characteristics under illumination with excitation light <NUM> having a center wavelength of about <NUM> as set forth with reference to spectral profile <NUM> as shown in the spectral profile diagram of <FIG>. According to one example as set forth in reference to <FIG> providing filter material to include a dye having a photon emission quencher (as provided with use e.g. of a metal complex dye) can reduce autofluorescence emissions signals radiating from filter material at wavelengths of about <NUM> or longer to values that are about <NUM> percent (observing the respective autofluorescence emissions signal values of spectral profile <NUM> and spectral profile <NUM> at a wavelength of about <NUM>) or less of their expected values in the case filter material is provided that includes a dye without a photon emission quencher.

Providing a matrix of dye molecules with a polymer binder molecule facilitates processability with a range of semiconductor processes e.g. chemical vapor deposition (CVD), spin coating, etching, planarizing, and the like.

According to one example filter material provided by a metal complex dye matrix can have a weight ratio of between about <NUM>:<NUM> dye to polymer and about <NUM>: <NUM> dye to polymer. At concentrations above this range, the structural integrity of the matrix can become compromised and at concentrations below, filtering performance can become compromised. According to one example filter material provided by a metal complex dye matrix can have a molecule ratio of between about <NUM> dye molecule: <NUM> polymer molecules to about <NUM> dye molecule: <NUM> polymer molecules. According to one example filter material provided by a polymer binder and metal complex dye matrix can have a molecule ratio of between about <NUM> dye molecule: <NUM> polymer molecules.

While higher concentrations of dye molecules improve blockage of excitation light, examples herein recognize that increased scattering can be observed at higher concentrations. Light scattering can be addressed with further processes for filtering powder dye particles prior to mixing with a polymer binder liquid.

<FIG> is an optical density (OD) film thickness diagram illustrating filtering performance of a filter material herein comprising a matrix of metal complex dye suspended in a polymer binder matrix. As seen in the OD film thickness diagram of <FIG>, an OD of about <NUM> can be achieved within a spatial budget of <NUM>. Referring again to the spectral profile coordination diagram of <FIG>, the spectral profile targeted for filtering is spectral profile <NUM> for excitation light <NUM> having a center (peak) wavelength of about <NUM>. Referring to the OD film thickness diagram of <FIG>, by configuring light guide <NUM> formed of a matrix of metal complex dye suspended in a polymer binder matrix to have a thickness of about <NUM> light guide <NUM> can be configured to exhibit an OD of about <NUM> for the center (peak) excitation light wavelength of about <NUM>. By configuring light guide <NUM> formed of a matrix of metal complex dye suspended in a polymer binder matrix to have a thickness of about <NUM> light guide <NUM> can be configured to exhibit an OD of about <NUM> for the center (peak) excitation wavelength of about <NUM>.

For performance of light sensing, light sensor <NUM> can have a particular spacing distance in reference to detector surface <NUM> (<FIG>). According to one example, the particular spacing distance can be a particular spacing distance in the range, e.g. of from about <NUM> to about <NUM>. As seen in <FIG>, light guides <NUM> can have space restrictions in dependence on the spacing requirements between light sensors <NUM> and detector surface <NUM>. In view of the OD thickness data summarized in the OD film thickness diagram <FIG> material for construction of light guides <NUM> can be provided to satisfy targeted optical density (OD) properties in dependence on spatial properties of detector <NUM>, and OD performance suitable for many applications is achievable even where spatial budget is restricted.

As seen by the coordination depicted by the spectral profile coordination diagram of <FIG>, light sensors <NUM> can sense emissions signal light <NUM> attributable to fluorescence of a fluorophore but, in accordance with ideal operation, cannot detect excitation light <NUM> represented by spectral profile <NUM>. For configuring of light sensors <NUM> to detect emissions signal light <NUM> attributable to a fluorophore attached to a sample <NUM> without detecting excitation light <NUM>, system <NUM> can include one or more filters. For example, light guides <NUM> can be formed of filtering material that blocks light in the energy band of excitation light <NUM> represented by spectral profile <NUM>. Thus, emissions signal light <NUM> represented by spectral profile <NUM> is subject to detection with use of light sensors <NUM> without detection of excitation light <NUM>. However, as noted, filter material forming light guide <NUM> can autofluoresce in response to excitation by excitation light <NUM>. Examples herein provide light guides <NUM> to block excitation light <NUM> to exhibit reduced autofluorescence so as to preserve desired spectral profile coordination between excitation fluorescence emission and detection spectral profiles as depicted in the spectral profile coordination diagram of <FIG>.

Examples herein recognize that left shifting of spectral profile <NUM> of detector <NUM> can increase detection of emissions signal light <NUM> having a spectral profile indicated by spectral profile <NUM> in the spectral profile of the emissions signal light <NUM>. It should be understood that as used herein, left shifting refers to hypsochromic shifting, or blue shifting. Filter material herein comprising a matrix of metal complex dye suspended in a polymer binder matrix can be configured for left shifting of spectral profile <NUM> by implementation of various features. In order to left shift spectral profile <NUM> certain substituents of the ligands surrounding metal complex dye (<NUM>) can be altered. For instance, the phenyl groups and other moieties can act as fluorophores, and can so be altered to left shift the spectrum. For instance, methyl groups can be replaced with trifluoromethyl or other groups, and hydrogens be replaced with chlorine or bromine, in some embodiments. The spectrum can be shifted left or right, depending on the particular metal complex dye used, by replacing electron donating groups with electrons withdrawing groups and vice versa. As used herein, right shifting refers to bathochromic shifting, or red shifting, of the spectral wavelength. Thus, in any embodiment, the spectrum can be adjusted with adjustments to the functional groups of the metal complex dye.

According to one example, a filter material can include a dye having a photon emission quencher and the dye can be a non-radiant dye. According to one example, the photon emission quencher can include chromium (Cr). According to one example, the dye can 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 can be provided by matrix having a dye and polymer binder, wherein the dye has a photon emission quencher. According to one example the filter material can be provided by matrix having a dye and polymer binder, wherein the dye is a metal complex dye. According to one example the filter material can 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 can be provided by a dye suspended in a polymer matrix, wherein the dye is a metal complex dye.

Examples herein recognize that performance of system <NUM> can be negatively impacted by background noise, which herein refers to unwanted light energy radiating from a source external to detector <NUM>. Examples herein recognize that a signal to noise ratio of detector <NUM> can be negatively impacted by fluorescence range background light radiating for sources external to detector <NUM>. Fluorescence range noise emissions in system <NUM> can be attributable to sources other than auto-fluorescing sources within detector <NUM>.

Examples herein recognize for example that while light energy exciter <NUM> can be configured to ideally emit light in a relatively shorter wavelength band, e.g. in a green wavelength band, autofluorescent sources therein, e.g. optical components can autofluoresce and light that is emitted by light energy exciter <NUM> can include unwanted light rays at longer wavelengths in the fluorescence band of detector <NUM> and light sensors <NUM>. Examples herein recognize that fluorescence range light can enter system <NUM> from sources other than light energy exciter <NUM>.

In reference to <FIG> there are set forth additional features for increasing a signal to noise ratio of detector <NUM>. In reference to <FIG> there are described features for cancellation (e.g. partial or entire cancellation) of fluorescence range background noise radiation that without the described features would be received into detector <NUM>. Cancellation features herein can reduce fluorescence range wavelengths sensed by light sensors <NUM> not attributable to emissions signal light <NUM>.

The filter material features set forth in reference to <FIG> reduce fluorescence range noise by reduction of internal autofluorescence within detector <NUM>. Features of detector surface <NUM> as set forth in connection with <FIG> reduce undesirable fluorescence range background noise by cancellation (e.g. partial or entire) fluorescence range light energy incident on detector surface <NUM>. The features described with reference to <FIG> can be implemented independently of the features of <FIG> or according to one example in combination with the features of <FIG> to address the problem of fluorescence range noise with use of a combination of detector internal (<FIG>) and detector surface (<FIG>) features.

Now referring to <FIG> detector <NUM> according to one example can be configured so that light energy incident on detector surface <NUM> can induce electromagnetic fields radiating from detector surface <NUM> that cancel (e.g. partially or entirely) incoming light energy which would otherwise be transmitted through reaction recess <NUM>. Examples herein recognize that behavior of induced fields radiating from detector surface <NUM> induced from light rays incident on detector surface <NUM> can become more controllable and predictable as an index of refraction ratio between a detector surface <NUM> and fluid within flow cell <NUM> increases. An index of refraction of detector surface <NUM> can be defined by the index of refraction of the material of passivation layer <NUM> adjacent flow cell <NUM> forming the detector surface <NUM>. Examples herein recognize that with a sufficiently high index of refraction ratio between detector surface <NUM> and a fluid of flow cell <NUM> light rays of excitation light <NUM> can induce electromagnetic fields radiating from detector surface <NUM> that cancel incoming light energy in dependence on a dimension of detector surface <NUM>.

Referring to <FIG>, reaction recess <NUM> can include a dimension "D" provided by the diameter of the reaction recess <NUM> at a top elevation of reaction recess <NUM>. Examples herein recognize that electromagnetic fields induced by incident light energy incident on reaction recess <NUM> can cancel incoming light energy in dependence on the dimension "D", where an index of refraction ratio between detector surface <NUM> and fluid within flow cell <NUM> is sufficiently high. Detector <NUM> as shown in <FIG> can be an integrated circuit detector having structure <NUM> defining detector surface <NUM> which can include passivation layer <NUM> and passivation layer <NUM>. According to one example where passivation layer <NUM> having detector surface <NUM> is formed of tantalum pentoxide (Ta2O5) having an index of refraction λ206 of about <NUM>≈<NUM> and where fluid of flow cell <NUM> is water based and has an index of refraction λ282 of about λ282≈<NUM> the index of refraction ratio λ206/ λ282 between a material forming detector surface <NUM> and a fluid of flow cell <NUM> is about λ206/ <NUM>≈<NUM>. According to one example where passivation layer <NUM> having detector surface <NUM> is formed of silicon nitride (SiN) having an index of refraction λ206 of about λ206≈<NUM> and where fluid of flow cell <NUM> is water based and has an index of refraction λ282 of about λ282≈<NUM> the index of refraction ratio λ206/ λ282 between a material forming detector surface <NUM> and a fluid of flow cell <NUM> is about λ206/ <NUM>≈<NUM>. A three-dimensional shape of reaction recess <NUM> can be cylindrical or frustro-conical in some examples such that a cross-section taken along a horizontal plane that extends into the page of <FIG> is substantially circular. A longitudinal axis <NUM> can extend through a geometric center of the cross-section.

Examples herein recognize that for a detector surface <NUM> as set forth in <FIG> having a reaction recess <NUM> (nanowell) with the dimension D and with an index of refraction ratio λ206/ λ282 suitably high there is a critical wavelength λc wherein wavelengths shorter than the critical wavelength λc are transmitted into an interior of reaction recess <NUM> and detector <NUM> and wherein wavelengths longer than the critical wavelength λc are cancelled (e.g. partially cancelled or entirely cancelled) by detector surface <NUM> having reaction recess <NUM>. Examples herein further recognize that the described critical wavelength λc is in dependence of the dimension D so that the dimension D can be controlled to tune the critical dimension λc to a desired value. More specifically the critical wavelength λc can be increased by increasing the dimension D and the critical wavelength λc can be decreased by decreasing the dimension D. Without being bound to a particular theory in regard to the recognized effect, light rays incident on detector surface <NUM> may induce electromagnetic fields radiating from detector surface <NUM> that cancel (e.g. partially or entirely) incoming light energy which would otherwise be transmitted through reaction recess <NUM>.

Light energy cancellation features can be advantageously incorporated into the design of detector surface <NUM>. According to one example described with reference to <FIG> the dimension D can be selected to establish the critical wavelength λc so that wavelengths at about the center (peak) wavelength λa of excitation light <NUM> and shorter are transmitted through reaction recess <NUM> and into detector <NUM> and further so that wavelengths of about the shortest detection band wavelength λb and longer are cancelled by detector surface <NUM>. Transmission of wavelengths at about the center (peak) wavelength λa of excitation light <NUM> and shorter can assure that fluorophores are properly excited according to the design of system <NUM> and cancellation of wavelengths of about the shortest detection band wavelength λb and longer can increase a signal to noise ratio of detector <NUM>.

While λc can be tuned in dependence on D, the precise relationship between D and cancellation effects in dependence thereon can vary depending on materials, configuration (including light energy exciter <NUM> configuration), and process control parameters of a particularly fabricated system <NUM>. Notwithstanding, information of the relationship between the dimension D and a cancellation effect in dependence thereon for a particular design of detector <NUM> can be determined by experimentation. On determination of information by experimentation that specifies a relationship between D and a cancellation effect for a particular design of detector <NUM>, the information can be used to establish a value for D; that is, D=d1 where D=d1 is selected to establish the critical wavelength λc so that wavelengths at about a center (peak) wavelength λc of excitation light <NUM> and shorter are transmitted into reaction recess <NUM> and detector <NUM> and further so that wavelengths of about the shortest detection band wavelength λb and longer (i.e. in the fluorescence range) are cancelled by detector surface <NUM>.

According to one process, one or more test sample detectors according to detector <NUM> can be fabricated and subject to test. The test can include testing for transmission of excitation light <NUM> by reaction recess <NUM>. One or more test samples can be provided and subject to testing to determine the smallest dimension of D, D=dc at which reaction recess <NUM> transmits excitation light <NUM> in accordance with one or more transmission criterion. The one or more transmission criterion can be e.g. that a threshold amount (e.g. <NUM> percent, <NUM> percent) of maximum energy excitation light <NUM> is transmitted through reaction recess <NUM>. One or more test samples can be provided and subject to testing to determine the largest dimension of D, D=de at which reaction recess <NUM> cancels fluorescence range light (e.g. a discernible amount of fluorescence range light) in a detection band of light sensors <NUM>. For such testing signals read out by light sensors <NUM> can be examined with light guides <NUM> fabricated according to their production specifications. With one or more of dimensions D=dc or D=de determined, detector <NUM> according to a production design can be provided. In the production design according to one example, D=d1 can be provided to be in the range of from about D=dc to about D=de. In the production design according to one example, D=d1 can be provided to be at about the midpoint distance of between D=dc and D=De. In the production design according to one example, D=d1 can be provided to be about D=dc. In the production design according to one example, D=d1 can be provided to be about D=de. In the described examples, the dimension D can be provided to establish a critical wavelength λc so that λc is within a range of wavelengths of between about λa and about λb, wherein wavelengths shorter than λc are transmitted by reaction recess <NUM> and wherein wavelengths longer than λc are cancelled by reaction recess <NUM>, wherein λa is the center wavelength of excitation light <NUM> and wherein λb is the shortest detection band wavelength of the sensor array <NUM>.

Referring to the spectral profile coordination diagram of <FIG>, excitation light <NUM> can have a center (peak) wavelength of about <NUM> (λa), and detector <NUM> with light sensors <NUM> can have a detection band commencing at about <NUM> (shortest detection band wavelength λb). Thus, reaction recess <NUM> according to one example, configured to have a suitable index of refraction, can be dimensioned to permit entry of incident light energy at wavelengths of about <NUM> and shorter and can be dimensioned to cancel incident light energy at wavelengths of about <NUM> and longer. In the case where detector <NUM> is of a configuration wherein D=d1 ≈ λc so that the distance d1 is in common with the critical wavelength λc, D can be dimensioned according to D=<NUM> to transmit excitation light <NUM> into reaction recess <NUM> and to cancel unwanted fluorescence range wavelengths according to the spectral profile coordination diagram of <FIG>. With the described configuration, the detector surface <NUM> can be dimensioned to permit entry of incident light energy at wavelengths of about <NUM> and shorter and can be dimensioned to cancel incident light energy at wavelengths of about <NUM> and longer.

There is set forth herein a method including subjecting a test sample detector according to detector <NUM> (having a structure <NUM> defining detector surface <NUM>) to determine information that specifies a relationship between a dimension e.g. D of detector surface <NUM> and an electromagnetic field cancellation effect (e.g. including information such dc, de and/or other information relating D to λc ) and wherein the fabricating the structure <NUM> defining a detector surface <NUM> includes dimensioning, using the determined information, a reaction recess <NUM> of the detector surface <NUM> to transmit excitation light <NUM> in an excitation wavelength band of excitation light <NUM> (including at the center (peak) wavelength λa) and to cancel light energy incident on the detector surface <NUM> in a detection band of the light sensor array <NUM>.

A three-dimensional shape of reaction recess <NUM> can be cylindrical or frustro-conical in some examples such that a cross-section taken along a horizontal plane that extends into the page of <FIG> is circular. A longitudinal axis <NUM> can extend through a geometric center of the cross-section. However, other geometries can be used in alternative examples. For example, the cross-section can be square-shaped or octagonal. According to one example, shield structure <NUM> can have a thickness of from about <NUM> to about <NUM>, passivation layer <NUM> can have a thickness of from about <NUM> to about <NUM>, passivation layer <NUM> can have a thickness of from about <NUM> to about <NUM>, aperture <NUM> can have a diameter of from about <NUM> to about <NUM>, and reaction recess <NUM> if present can have a height H of from about <NUM> to about <NUM>.

<FIG> and <FIG> illustrate further details of an example of detector <NUM> having one or more fluorescence range noise reducing features as set forth herein.

Referring to <FIG> there is set forth herein a detector surface <NUM> for supporting biological or chemical substances; a sensor array <NUM> comprising light sensors <NUM>, and circuitry <NUM> to transmit data signals based on photons detected by the light sensors <NUM>; a guide array <NUM> comprising light guides <NUM>; wherein light guides <NUM> of the guide array <NUM> receive excitation light <NUM> and emissions signal light <NUM> from the detector surface <NUM>, wherein the light guides <NUM> extend toward respective light sensors <NUM> of the sensor array <NUM> and comprise filter material that blocks the excitation light <NUM> and permits emissions signal light <NUM> radiating from fluorescing fluorophores to propagate toward the respective light sensors <NUM>, wherein the detector surface includes a reaction recess <NUM>, the reaction recess comprising an index of refraction and a dimension to cancel background light energy incident on the detector surface in a detection band of the sensor array <NUM>.

Detector <NUM> can include a sensor array <NUM> of light sensors <NUM>, a guide array <NUM> of light guides <NUM>, and a reaction array <NUM> of reaction recesses <NUM>. In certain examples, the components are arranged such that each light sensor <NUM> aligns with a single light guide <NUM> and a single reaction recess <NUM>. However, in other examples, a single light sensor <NUM> can receive photons through more than one light guide <NUM>. In some examples there can be provided more than one light guide and/or reaction recess for each light sensor of a light sensor array. In some examples there can be provided more than one light guide and/or light sensors aligned to a reaction recess of a reaction recess array. The term "array" does not necessarily include each and every item of a certain type that the detector can have. For example, the sensor array of light source may not include each and every light sensor of detector <NUM>. As another example, the guide array <NUM> may not include each and every light guide of detector <NUM>. As another example, the reaction array <NUM> may not include each and every reaction recess <NUM> of detector <NUM>. As such, unless explicitly recited otherwise, the term "array" may or may not include all such items of detector <NUM>.

In the illustrated example, flow cell <NUM> is defined by sidewall <NUM> and a flow cover <NUM> that is supported by the sidewall <NUM> and other sidewalls (not shown). The sidewalls are coupled to the detector surface <NUM> and extend between the flow cover <NUM> and the detector surface <NUM>. In some examples, the sidewalls are formed from a curable adhesive layer that bonds the flow cover <NUM> to detector <NUM>.

The flow cell <NUM> can include a height H1. By way of example only, the height H1 can be between about <NUM>-<NUM> or, more particularly, about <NUM>-<NUM>. The flow cover <NUM> can include a material that is light transmissive to excitation light <NUM> propagating from an exterior of the detector assembly <NUM> into the flow cell <NUM>.

Also shown, the flow cover <NUM> can define inlet and outlet ports <NUM>, <NUM> that are configured to fluidically engage other ports (not shown). For example, the other ports can be from a cartridge (not shown) or a workstation (not shown).

Detector <NUM> has a detector surface <NUM> that can be functionalized (e.g. chemically or physically modified in a suitable manner for conducting designated reactions). For example, the detector surface <NUM> can be functionalized and can include a plurality of reaction sites having one or more biomolecules immobilized thereto. The detector surface <NUM> can have a reaction array <NUM> of reaction recesses <NUM>. Each of the reaction recesses <NUM> can include one or more of the reaction sites. The reaction recesses <NUM> can be defined by, for example, an indent or change in depth along the detector surface <NUM>. In other examples, the detector surface <NUM> can be planar.

<FIG> is an enlarged cross-section of detector <NUM> showing various features in greater detail. More specifically, <FIG> shows a single light sensor <NUM>, a single light guide <NUM> for directing emissions signal light <NUM> toward the light sensor <NUM>, and associated circuitry <NUM> for transmitting signals based on emissions signal light <NUM> (e.g. photons) detected by the light sensor <NUM>. It is understood that the other light sensors <NUM> of the sensor array <NUM> (<FIG>) and associated components can be configured in an identical or similar manner. It is also understood, however, the detector <NUM> is not required to be manufactured identically or uniformly throughout. Instead, one or more light sensors <NUM> and/or associated components can be manufactured differently or have different relationships with respect to one another.

The circuitry <NUM> can include interconnected conductive elements (e.g. conductors, traces, vias, interconnects, etc.) that are capable of conducting electrical current, such as the transmission of data signals that are based on detected photons. Detector <NUM> comprises an integrated circuit having a planar array of the light sensors <NUM>. The circuitry <NUM> formed within detector <NUM> can be configured for at least one of read out signals from light sensors <NUM> after an exposure period (integration period) in which charge accumulates on light sensor <NUM>, signal amplification, digitization, storage, and processing. The circuitry <NUM> can collect and analyze the detected emissions signal light <NUM> and generate data signals for communicating detection data to a bioassay system. The circuitry <NUM> can also perform additional analog and/or digital signal processing in detector <NUM>. Light sensors <NUM> can be electrically coupled to circuitry <NUM> through gates <NUM>-<NUM>.

Detector <NUM> according to one example can be provided by a solid-state integrated circuit detector such as a CMOS integrated circuit detector or a CCD integrated circuit detector. Detector <NUM> according to one example can be an integrated circuit chip manufactured using integrated circuit manufacturing processes such as complementary metal oxide semiconductor (CMOS) fabrication processes.

The resolution of the sensor array <NUM> defined by light sensors <NUM> can be greater than about <NUM> megapixels (Mpixels). In more specific examples, the resolution can be greater than about <NUM> Mpixels and, more particularly, greater than about <NUM> Mpixels.

Detector <NUM> can include a plurality of stacked layers <NUM>-<NUM> including a sensor layer <NUM>, which can be a silicon layer. The stacked layers can include a plurality of dielectric layers <NUM>-<NUM>. In the illustrated example, each of the dielectric layers <NUM>-<NUM> includes metallic elements (e.g. W (tungsten), Cu (copper), or Al (aluminum)) and dielectric material, e.g. SiO2. Various metallic elements and dielectric material can be used, such as those suitable for integrated circuit manufacturing. However, in other examples, one or more of the dielectric layers <NUM>-<NUM> can include only dielectric material, such as one or more layers of SiO2.

With respect to the specific example of <FIG>, the dielectric layers <NUM>-<NUM> can include metallization layers that are labeled as layers M1-M5 in <FIG>. As shown, the metallization layers, M1-M5, can be configured to form at least a portion of the circuitry <NUM>.

In some examples, detector <NUM> includes a shield structure <NUM> having one or more layers that extend throughout an area above metallization layer M5. In the illustrated example, the shield structure <NUM> can include a material that is configured to block, reflect, and/or significantly attenuate the light signals that are propagating from the flow cell <NUM>. The light signals can be the excitation light <NUM> and/or emissions signal light <NUM>. By way of example only, the shield structure <NUM> can comprise tungsten (W). By way of specific example only, the excitation light <NUM> may have a center (peak) wavelength of about <NUM> and emissions signal light <NUM> can include wavelengths of about <NUM> and longer (<FIG>).

As shown in <FIG>, shield structure <NUM> can include an aperture <NUM> therethrough. The shield structure <NUM> can include an array of such apertures <NUM>. Aperture <NUM> is dimensioned to allow signal emission light to propagate to light guide <NUM>. Detector <NUM> can also include a passivation layer <NUM> that extends along the shield structure <NUM> and across the apertures <NUM>. Detector <NUM> can also include a passivation layer <NUM> comprising detector surface <NUM> that extends along passivation layer <NUM> and across the apertures <NUM>. Shield structure <NUM> can extend over the apertures <NUM> thereby directly or indirectly covering the apertures <NUM>. Passivation layer <NUM> and passivation layer <NUM> can be configured to protect lower elevation layers and the shield structure <NUM> from the fluidic environment of the flow cell <NUM>. According to one example, passivation layer <NUM> is formed of SiN or similar. According to one example, passivation layer <NUM> is formed of tantalum pentoxide (Ta2O5) or similar. Structure <NUM> having passivation layer <NUM> and passivation layer <NUM> can define detector surface <NUM> having reaction recesses <NUM>. Structure <NUM> defining detector surface <NUM> can have any number of layers such as one to N layer.

Structure <NUM> can define a solid surface (i.e., the detector surface <NUM>) that permits biomolecules or other analytes-of-interest to be immobilized thereon. For example, each of the reaction sites of a reaction recess <NUM> can include a cluster of biomolecules that are immobilized to the detector surface <NUM> of the passivation layer <NUM>. Thus, the passivation layer <NUM> can be formed from a material that permits the reaction sites of reaction recesses <NUM> to be immobilized thereto. The passivation layer <NUM> can also comprise a material that is at least transparent to a desired fluorescent light. Passivation layer <NUM> can be physically or chemically modified to facilitate immobilizing the biomolecules and/or to facilitate detection of the emissions signal light <NUM>.

In the illustrated example, a portion of the passivation layer <NUM> extends along the shield structure <NUM> and a portion of the passivation layer <NUM> extends directly along filter material defining light guide <NUM>. The reaction recess <NUM> can be aligned with and formed directly over light guide <NUM>. According to one example each of reaction recess <NUM> and light guide <NUM> can have geometric centers centered on longitudinal axis <NUM>.

As set forth herein in connection with <FIG> detector surface <NUM> can be dimensioned so that light energy incident on detector surface <NUM> in a fluorescence range can be cancelled by the operation of induced electromagnetic fields. According to one example, shield structure <NUM> can have a thickness of from about <NUM> to about <NUM>, passivation layer <NUM> can have a thickness of from about <NUM> to about <NUM>, passivation layer <NUM> can have a thickness of from about <NUM> to about <NUM>, aperture <NUM> can have a diameter of from about <NUM> to about <NUM>, and reaction recess <NUM> if present can have a height of from about <NUM> to about <NUM>.

In some cases, prior to the passivation layer <NUM> being deposited along the shield structure <NUM>, and prior to a depositing of shield structure <NUM> a cavity defined by sidewalls <NUM> can be formed the dielectric stack defined by dielectric layers <NUM>-<NUM>. For example, the dielectric stack defined by dielectric layers <NUM>-<NUM> can be etched to form an array of the cavities defined by sidewalls <NUM>, wherein one cavity is formed for each light sensor <NUM> of light sensor array <NUM>. In particular examples, a cavity defined by sidewalls <NUM> is a vertically elongated space that extends from proximate the aperture <NUM> toward the light sensor <NUM>.

The cavity can extend vertically along longitudinal axis <NUM>. A three-dimensional shape of cavity defined by sidewalls <NUM> can be cylindrical or frustro-conical in some examples such that a cross-section taken along a horizontal plane that extends into the page of <FIG> is circular. The longitudinal axis <NUM> can extend through a geometric center of the cross-section. However, other geometries can be used in alternative examples. For example, the cross-section can be square-shaped or octagonal. According to one example the longitudinal axis <NUM> which is the longitudinal axis of light guide <NUM> can extend through a geometric center of light sensor <NUM> and reaction recess <NUM>.

The filter material defining light guide <NUM> can be deposited within the cavity defined by sidewalls <NUM> after the cavity defined by sidewalls <NUM> is formed. For fabrication of light guide <NUM> according to one example, dye molecules in powder form, e.g. having photon emission quencher, can be dissolved with 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 complex dye particles.

The homogeneous liquid matrix can be deposited into a dielectric stack cavity of detector <NUM> and evaporated to form a filter material comprising a solid dye and polymer matrix wherein dye molecules are suspended within a matrix of polymer binder molecules. The homogeneous polymer binder and dye matrix filter material can be deposited into the cavity defined by sidewalls <NUM>, using e.g. chemical vapor deposition (CVD) physical vapor deposition (PVD). The depositing can be performed to overfill the cavity defined by sidewalls <NUM> with filter material and then subject to patterning such as by planarization or etching to reduce the elevation of the filter material defining light guide <NUM>. A filter material for forming light guide <NUM> according to one example can include metal complex dye molecules suspended in a polymer binder molecule matrix.

The filter material can form (e.g. after curing) a light guide <NUM>. The light guide <NUM> can be configured to block the excitation light <NUM> and permit emissions signal light <NUM> (<FIG>) to propagate therethrough toward the corresponding light sensor <NUM>. The light guide <NUM> can be formed of filter material described in reference to <FIG> herein. The filter material can include a homogeneous matrix of dye and polymer binder, wherein the dye can include 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 can include a weight concentration in the range of from about <NUM>:<NUM> dye to polymer to about <NUM>:<NUM> dye to polymer. The filter material mixture can have a molecule ratio of about <NUM> dye molecule to about <NUM> polymer molecules.

The light guide <NUM> can be configured relative to surrounding material of the dielectric stack defined by dielectric layers <NUM>-<NUM> to form a light-guiding structure. For example, the light guide <NUM> can have a refractive index of at least about <NUM> so that light energy propagating through light guide is reflected at an interface between light guide <NUM> and the surrounding dielectric stack defined by dielectric layers <NUM>-<NUM>. In certain examples, the light guide <NUM> is configured such that the optical density (OD) or absorbance of the excitation light <NUM> is at least about <NUM> OD. More specifically, the filter material can be selected and the light guide <NUM> can be dimensioned to achieve at least <NUM> OD. In more particular examples, the light guide <NUM> can be configured to achieve at least about <NUM> OD or at least about <NUM> OD. In more particular examples, the light guide <NUM> can be configured to achieve at least about <NUM> OD or at least about <NUM> OD. Other features of the detector <NUM> can be configured to reduce electrical and optical crosstalk.

It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein. In particular, all combinations of claims subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein. However, the precise combination of subject-matter of embodiments in accordance with the present invention are defined by the claims and their dependencies.

This written description uses examples to disclose the subject matter, and also to enable any person skilled in the art to practice the subject matter, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the subject matter is defined by the claims, and can include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims.

It is to be understood that the above description is intended to be illustrative, and not restrictive. For example, the above-described examples (and/or aspects thereof) can be used in combination with each other. In addition, many modifications can be made to adapt a particular situation or material to the teachings of the various examples without departing from the scope of the invention defined by the claims. While the dimensions and types of materials described herein are intended to define the parameters of the various examples, they are by no means limiting and are merely exemplary. Many other examples will be apparent to those of skill in the art upon reviewing the above description. The scope of the various examples should, therefore, be determined with reference to the appended claims. In the appended claims, the terms "including" and "in which" are used as the plain-English equivalents of the respective terms "comprising" and "wherein. " Moreover, in the following claims, the terms "first," "second," and "third," etc. are used merely as labels, and are not intended to impose numerical requirements on their objects. Forms of term "based on" herein encompass relationships where an element is partially based on as well as relationships where an element is entirely based on. Forms of the term "defined" encompass relationships where an element is partially defined as well as relationships where an element is entirely defined. Further, the limitations of the following claims are not written in means-plus-function format and are not intended to be interpreted based on <NUM> U. § <NUM>, sixth paragraph, unless and until such claim limitations expressly use the phrase "means for" followed by a statement of function void of further structure. It is to be understood that not necessarily all such objects or advantages described above can be achieved in accordance with any particular example. Thus, for example, those skilled in the art will recognize that the systems and techniques described herein can be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objects or advantages as can be taught or suggested herein.

Claim 1:
A device comprising:
a structure (<NUM>) defining a detector surface (<NUM>) for supporting biological or chemical samples (<NUM>);
a sensor array (<NUM>) comprising light sensors (<NUM>), and circuitry to transmit data signals based on photons detected by the light sensors (<NUM>); and
a guide array (<NUM>) comprising light guides (<NUM>);
wherein light guides (<NUM>) of the guide array (<NUM>) are arranged to receive excitation light (<NUM>) of an light energy exciter (<NUM>) and emissions signal light (<NUM>) from the detector surface (<NUM>), wherein the emissions signal light (<NUM>) is fluorescence of a fluorophore of the biological or chemical sample being excited by the excitation light (<NUM>),
wherein the light guides (<NUM>) extend toward respective light sensors (<NUM>) of the sensor array (<NUM>) and comprise filter material that is configured to block the excitation light and that is configured to permit the emissions signal light (<NUM>) to propagate toward the respective light sensors (<NUM>),
wherein the detector surface (<NUM>) includes reaction recesses (<NUM>), each reaction recess (<NUM>) comprising an index of refraction and a dimension (D), provided by the diameter of the reaction recess (<NUM>) at a top elevation of reaction recess (<NUM>) and sufficient to cancel background light energy incident on the detector surface (<NUM>) in a detection band of the sensor array (<NUM>),
wherein the background light energy incident on the detector surface (<NUM>) is fluorescence range noise not attributable to the emissions signal light (<NUM>), and defining in each reaction recess (<NUM>) one or more reaction sites for supporting the biological or chemical samples (<NUM>).