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Publication Number
US-9988668-B2
Publication Date
2018-06-05
Expiration Date
Abstract
Described herein is a chip-based apparatus for amplifying nucleic acids, a cartridge housing the apparatus, and methods of using the apparatus for amplification of nucleic acids. More specifically, this invention provides integrated semiconductor chip, manufactured with standard semiconductor manufacturing process, with on-chip circuitry to perform thermal management and optical sensing necessary for amplification of nucleic acids. The apparatus and methods embodied in this invention makes it possible to build a disease diagnosis and prognosis tool that is easy to use, portable and disposable.
Core Innovation
The invention describes an apparatus for analyzing a biological sample using a semiconductor substrate with integrated circuitry, including a junction temperature sensor and a first light sensor. The integrated circuitry is paired with a biocompatible coating positioned to allow the biological sample to be in proximity to the integrated circuitry.
One or more processors and memory store programs configured to execute noise-aware light signal detection using coordinated light and temperature measurements. The programs detect a first light input measurement at a first time prior to triggering a light signal from the biological sample and a second light input measurement at a second time after triggering the light signal.
The programs also detect a plurality of temperature input measurements from the junction temperature sensor, where the plurality includes a first temperature input measurement at the first time and a second temperature input measurement at the second time. The first light measurement is used to estimate noise signal, and the plurality of temperature input measurements is used to estimate noise signal and improve noise suppression, thereby determining the biological-sample light signal.
Claims Coverage
Independent claim clm-00001 covers an apparatus for analyzing a biological sample using a semiconductor integrated-circuit substrate with a junction temperature sensor and a first light sensor, and programs that use time-sequenced light measurements plus multiple temperature measurements to estimate and suppress noise in order to determine the biological-sample light signal. The main inventive features include temperature-informed noise estimation and time-based light measurement prior to and after triggering the biological-sample light signal.
Semiconductor integrated circuitry with junction temperature sensor and first light sensor
The integrated circuitry comprises a junction temperature sensor and a first light sensor on a semiconductor substrate for analyzing a biological sample.
Biocompatible coating positioned for sample proximity to integrated circuitry
A biocompatible coating is positioned to allow the biological sample to be in proximity to the integrated circuitry over the semiconductor substrate.
Time-sequenced light measurements before and after triggering
The programs detect a first light input measurement at a first time prior to triggering a light signal from the biological sample, and detect a second light input measurement at a second time after triggering the light signal.
Multiple temperature measurements coordinated with light measurement times
The programs detect a plurality of temperature input measurements from the junction temperature sensor, comprising a first temperature input measurement at the first time and a second temperature input measurement at the second time.
Noise estimation using first light measurement
The programs use the first light measurement to estimate noise signal.
Temperature-informed noise estimation and improved noise suppression
The programs use the plurality of temperature input measurements to further estimate noise signal and improve noise suppression.
Determining the biological-sample light signal
The programs determine the light signal from the biological sample based on the noise suppression and the coordinated light and temperature measurements.
Overall, the claim coverage centers on an apparatus with integrated junction temperature sensing and light sensing, together with programs that estimate noise from time-sequenced light measurements and further refine noise estimation using multiple temperature measurements to improve noise suppression, thereby determining the biological-sample light signal.
Stated Advantages
Improve noise suppression to determine the light signal from the biological sample.
Documented Applications
Disease diagnosis/prognosis use cases are described in the document context provided.
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