Active CMOS Biosensor Chip for Time-Gated Fluorescent Detection

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Solution Overview

Problem

Existing surface-based sensing assays are limited by the need for expensive, large, and complex external instruments for fluorescent-based detection, which restricts their application and efficiency, especially in terms of sensitivity and compactness.

Innovation Solution

An active complementary metal oxide semiconductor (CMOS) biosensor chip is developed for time-resolved, time-gated fluorescent-based detection, enabling the measurement of fluorescent intensity at different times to characterize transient decay responses, thereby allowing for more detailed analysis of analytes without the need for extensive optical filtering.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional microarray scanners with external instruments are used for fluorescent-based detection, then detection capability is achieved, but device complexity and cost increase

Engineering Contradiction:
Improvedetection capabilityVSAvoidinstrument complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent integrates the fluorescent detection functions (excitation source, optical path, and detector) directly into the CMOS biosensor chip, merging previously separate external instruments into a single integrated device. This eliminates the need for complex external microarray scanners while maintaining detection capability.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The CMOS biosensor chip performs multiple functions including excitation light emission, fluorescent signal detection, and time-gated measurement within a single device. This multi-functional integration reduces the need for separate specialized instruments, thereby reducing overall device complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If optical filtering is used to improve signal-to-noise ratio in fluorescent detection, then background light is reduced, but device complexity and cost increase

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidoptical filtering complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and removes the optical filtering components from the detection system. Instead of using external optical filters to improve signal-to-noise ratio, the invention relies on time-gated detection methodology that achieves background rejection without requiring complex optical filtering hardware.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical/optical filtering system with an electronic/time-based detection system. By using time-gated measurement that exploits the temporal characteristics of fluorescent decay, the system achieves background rejection through temporal discrimination rather than spatial/optical filtering.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If passive solid supports with immobilized probes are used for surface-based sensing, then assay functionality is achieved, but sensitivity and compactness are limited

Engineering Contradiction:
Improveassay functionalityVSAvoidsensitivity
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent merges the passive solid support with active CMOS sensor elements, creating an integrated active CMOS biosensor chip. This combination enables the chip to perform both the assay function (probe immobilization and binding) and the detection function (fluorescent measurement) in a single compact device, thereby improving sensitivity and compactness while maintaining assay functionality.

Inventive Principle:
Principle #5Merging (Combining)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The CMOS biosensor chip provides a low-cost, compact solution for surface-based sensing, enhancing sensitivity and reducing background interference, enabling applications in biological and medical fields with improved detection capabilities for DNA and protein microarrays and other imaging systems.

Implementation Method 1

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.

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

The present invention provides time-gated, time-resolved fluorescent-based detection on an active complementary metal oxide semiconductor (CMOS) biosensor chip.

Methodology Applied
Scientific EffectTime-gated detection:

Data Source

PatentUS7738086B2Active CMOS biosensor chip for fluorescent-based detection
Publication Date: 2010.06.15 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
  • US7738086B2 patent drawing
  • US7738086B2 patent drawing
  • US7738086B2 patent drawing

AI summary

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.