Method and system for fluorescence lifetime based sequencing
US-2015293021-A1 · Oct 15, 2015 · US
US11237326B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-11237326-B2 |
| Application number | US-201816042968-A |
| Country | US |
| Kind code | B2 |
| Filing date | Jul 23, 2018 |
| Priority date | Jul 24, 2017 |
| Publication date | Feb 1, 2022 |
| Grant date | Feb 1, 2022 |
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An integrated device and related instruments and systems for analyzing samples in parallel are described. The integrated device may include sample wells arranged on a surface of where individual sample wells are configured to receive a sample labeled with at least one fluorescent marker configured to emit emission light in response to excitation light. The integrated device may further include photodetectors positioned in a layer of the integrated device, where one or more photodetectors are positioned to receive a photon of emission light emitted from a sample well. The integrated device further includes one or more photonic structures positioned between the sample wells and the photodetectors, where the one or more photonic structures are configured to attenuate the excitation light relative to the emission light such that a signal generated by the one or more photodetectors indicates detection of photons of emission light.
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What is claimed is: 1. An integrated device comprising: a plurality of sample wells arranged on a first layer of the integrated device, wherein individual sample wells of the plurality of sample wells are configured to receive a sample configured to emit emission light in response to excitation light; a plurality of photodetectors arranged on a second layer of the integrated device and positioned to receive photons of emission light emitted from the plurality of sample wells, wherein the plurality of sample wells and the plurality of photodetectors form pixels, each of at least some of the pixels including a sample well of the plurality of sample wells aligned with at least one photodetector of the plurality of photodetectors, and a signal generated by the at least one photodetector indicates photons of emission light emitted by a sample in the sample well; and at least one photonic structure configured to attenuate the excitation light relative to the emission light, wherein the at least one photonic structure includes at least one spatial filter including a first spatial filter with first openings each having a first size and a second spatial filter with second openings each having a second size, wherein a first opening of the first spatial filter and a second opening of the second spatial filter overlap with a sample well, the first spatial filter is positioned between the first layer and the second spatial filter, and the first size is greater than the second size. 2. The integrated device of claim 1 , wherein the at least one photonic structure is positioned to align on a common axis with an individual sample well and its respective at least one photodetector. 3. The integrated device of claim 1 , wherein a sample well of the plurality of sample wells is positioned to overlap with its respective at least one photodetector. 4. The integrated device of claim 1 , wherein individual sample wells of the plurality of sample wells align with individual photodetectors of the plurality of photodetectors. 5. The integrated device of claim 1 , wherein one first opening of the plurality of first openings aligns on a common axis with an individual sample well and its respective at least one photodetector. 6. The integrated device of claim 1 , further comprising at least one waveguide configured to couple excitation light to a portion of the plurality of sample wells. 7. The integrated device of claim 6 , wherein a first waveguide of the at least one waveguide is positioned to overlap with a first sample well of the portion of sample wells and a first photodetector of the plurality of photodetectors along a common axis. 8. The integrated device of claim 7 , wherein the at least one photonic structure is positioned between the first waveguide and the first photodetector along the common axis. 9. The integrated device of claim 1 , wherein the at least one spatial filter is configured to block transmission of at least a portion of the excitation light. 10. The integrated device of claim 9 , wherein the at least one spatial filter includes at least one metal layer configured to block transmission of at least a portion of the excitation light. 11. The integrated device of claim 10 , wherein the integrated device further comprises circuitry that includes the at least one metal layer, wherein the circuitry is electrically coupled to at least one photodetector of the plurality of photodetectors. 12. The integrated device of claim 1 , wherein the at least one photonic structure includes at least one spectral filter configured to transmit a first range of wavelengths at a higher level than a second range of wavelengths, wherein the first range of wavelengths includes at least one characteristic wavelength of the emission light and the second range of wavelengths includes at least one characteristic wavelength of the excitation light. 13. The integrated device of claim 12 , wherein the at least one spectral filter is positioned between the first spatial filter and the second spatial filter. 14. The integrated device of claim 12 , wherein the at least one spectral filter includes a plurality of low refractive index layers having a low refractive index material and a plurality of high refractive index layers having a high refractive index material. 15. The integrated device of claim 14 , wherein the at least one spectral filter includes alternating layers of the plurality of high refractive index layers and the plurality of low refractive index layers. 16. The integrated device of claim 12 , wherein the integrated device further includes an excitation source coupling region configured to receive a beam of excitation light and optically couple excitation light to a waveguide of the integrated device, wherein the at least one spectral filter overlaps with the excitation source coupling region. 17. The integrated device of claim 1 , wherein the at least one photonic structure includes at least one polarization filter configured to attenuate transmission of light having a type of polarization. 18. The integrated device of claim 17 , wherein the excitation light is transverse electric (TE) polarized light, and the at least one polarization filter is configured to attenuate TE polarized light. 19. The integrated device of claim 17 , wherein the at least one polarization filter includes a periodic array of slits. 20. The integrated device of claim 1 , wherein the excitation light is a pulse of excitation light and the emission light is a photon emitted by at least one fluorescent marker emitted in response to the pulse of excitation light, wherein individual photodetectors of the plurality of photodetectors are further configured to generate a signal indicative of a lifetime of the emission light. 21. The integrated device of claim 1 , wherein individual photodetectors of the plurality of photodetectors are configured to discard charge carriers produced from photons of excitation light. 22. The integrated device of claim 21 , wherein the excitation light is a pulse of excitation light, and individual photodetectors are further configured to discard charge carriers produced from photons of the excitation light pulse over a first period of time. 23. The integrated device of claim 22 , wherein individual photodetectors are further configured to selectively direct, over a second period of time, charge carriers produced by incident photons into respective charge carrier storage regions based upon times at which the charge carriers are produced. 24. The integrated device of claim 1 , wherein the at least one photonic structure is configured to attenuate excitation light over a range of angles from normal to the at least one photonic structure. 25. The integrated device of claim 1 , wherein a characteristic wavelength of the emission light is between 550 nm and 650 nm. 26. The integrated device of claim 1 , wherein a characteristic wavelength of the excitation light is 532 nm. 27. The integrated device of claim 1 , wherein a characteristic wavelength of the excitation light is 515 nm. 28. The integrated device of claim 1 , further comprising vertical sidewalls positioned between the at least one spatial filter and at least a portion of the plurality of photodetectors. 29. The integrated device of claim 1 , further comprising vertical sidewalls positioned between the first spatial filter
Package configurations · CPC title
the at least one element covered by H10F30/00 having potential barriers, e.g. integrated devices comprising photodiodes or phototransistors · CPC title
using evanescent coupling or surface plasmon coupling for the excitation of fluorescence · CPC title
Stray light conditioning · CPC title
using an integrated detector array · CPC title
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