Active CMOS biosensor chip for fluorescent-based detection
First Claim
1. A method for operating an imager with time-resolved, time-gated fluorescent-based detection comprising:
- (a) receiving light from a fluorescent source on a complementary metal oxide semiconductor (CMOS) biosensor chip, wherein the fluorescent source is excited by an external pulsed excitation light source;
(b) directing the light source to turn off after a first time period;
(c) measuring a fluorescent light from the fluorescent source on the CMOS biosensor chip after a second time period measured from when the light source is directed to turn off;
(d) repeating (a)-(c) a number of times; and
(e) averaging results from each measuring.
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Abstract
An active CMOS biosensor chip for fluorescent-based detection is provided that enables time-gated, time-resolved fluorescence spectroscopy. In one embodiment, analytes are loaded with fluorophores that are bound to probe molecules immobilized on the surface of the chip. Photodiodes and other circuitry in the chip are used to measure the fluorescent intensity of the fluorophore at different times. These measurements are then averaged to generate a representation of the transient fluorescent decay response unique to the fluorophores. In addition to its low-cost, compact form, the biosensor chip provides capabilities beyond those of macroscopic instrumentation by enabling time-gated operation for background rejection, easing requirements on optical filters, and by characterizing fluorescence lifetime, allowing for a more detailed characterization of fluorophore labels and their environment. The biosensor chip can be used for a variety of applications including biological, medical, in-the-field applications, and fluorescent lifetime imaging applications.
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Citations
26 Claims
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1. A method for operating an imager with time-resolved, time-gated fluorescent-based detection comprising:
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(a) receiving light from a fluorescent source on a complementary metal oxide semiconductor (CMOS) biosensor chip, wherein the fluorescent source is excited by an external pulsed excitation light source;
(b) directing the light source to turn off after a first time period;
(c) measuring a fluorescent light from the fluorescent source on the CMOS biosensor chip after a second time period measured from when the light source is directed to turn off;
(d) repeating (a)-(c) a number of times; and
(e) averaging results from each measuring. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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8. A system for time-resolved, time-gated fluorescent-based detection comprising:
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an external pulsed excitation light source; and
a complementary metal oxide semiconductor (CMOS) biosensor chip coupled to the light source, wherein the CMOS biosensor chip is operative to;
(a) direct the light source to turn on, (b) direct the light source to turn off after a first time period, (c) measure a fluorescent light from a fluorescent source on the CMOS biosensor chip after a second time period measured from when the light source is directed to turn off, (d) repeat (a)-(c) a number of times, and (e) average results from each measure. - View Dependent Claims (9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
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20. Apparatus for time-resolved, time-gated fluorescent-based detection comprising:
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a first printed circuit board on which is mounted a pulsed excitation light source;
a second printed circuit board on which is mounted a complementary metal oxide semiconductor (CMOS) biosensor chip; and
at least one cable with a first connector attached to the first printed circuit board and coupled to the light source and a second connector attached to the second printed circuit board and coupled to the CMOS biosensor chip. - View Dependent Claims (21, 22, 23, 24, 25, 26)
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Specification