CMOS Biomarker Detection Chip With Integrated Control Regions
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Solution Overview
Problem
Current point-of-care diagnostic devices for biomarker detection are less accurate and reliable due to the lack of effective calibration and compensation for sample-to-sample and environmental variations, requiring bulky and expensive equipment.
Innovation Solution
A CMOS-based chip with integrated test, positive, and negative control regions on a reaction zone that generates independent detection signals, allowing for improved accuracy by calibrating and compensating for variations through simultaneous detection and analysis of these regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mass spectrometry or NMR spectroscopy is used for metabolite detection, then measurement precision is improved, but device complexity and cost increase
Solution Approach 1:
The patent employs disposable microfluidic cartridges with pre-loaded reagents and controls that are discarded after single use. This eliminates the need for complex, expensive, and maintainable equipment like mass spectrometers or NMR spectrometers, while maintaining reliable metabolite detection through integrated colorimetric assays and automated fluid handling.
Solution Approach 2:
The system incorporates self-calibrating controls (positive and negative) that automatically compensate for environmental variations and reagent degradation without requiring manual intervention or complex calibration procedures. The positive control contains known analyte concentrations that automatically adjust for sensitivity drift, while the negative control compensates for background interference, enabling reliable measurements with simplified equipment.
2Measurement precision
If spectrophotometer is used for colorimetric enzyme assays, then measurement precision is improved, but device complexity and power consumption increase
Solution Approach 1:
The patent merges the light source, optical detection path, and sensor array into an integrated microfluidic cartridge that interfaces directly with a simple photodetector or smartphone camera. This eliminates the need for bulky spectrophotometers with monochromators and complex optical components, while maintaining colorimetric detection accuracy through optimized reaction zones and reference controls within the same device.
Solution Approach 2:
The microfluidic cartridge with integrated colorimetric detection is designed as a disposable unit that eliminates the need for expensive, power-hungry spectrophotometers. The cartridge contains pre-loaded reagents, reaction chambers, and optical detection elements that provide reliable color change measurement without requiring complex external instrumentation.
3Ease of operation
If point-of-care diagnostic devices are simplified for portability, then ease of operation is improved, but measurement precision deteriorates
Solution Approach 1:
The system divides the diagnostic function into separate modular components: a disposable microfluidic cartridge containing reaction zones, controls, and reagents, and a simple reading device (photodetector or smartphone). This segmentation enables portability and ease of operation while maintaining measurement precision through the integrated design of the cartridge, which includes built-in positive and negative controls that automatically compensate for environmental variations and ensure accurate biomarker detection.
Solution Approach 2:
The microfluidic cartridge is pre-loaded with optimized reagent concentrations, reaction conditions, and control elements before use. This preliminary preparation ensures that when the device is used at the point of care, the biochemical reactions proceed with high precision and reliability without requiring complex instrumentation or skilled operation, thereby maintaining measurement accuracy despite the simplified portable format.
4Measurement precision
If control regions are added to compensate for sample variations, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent merges multiple functions into the microfluidic cartridge: sample processing, biochemical reactions, control measurements, and optical detection all occur within a single integrated device. The positive and negative control regions are incorporated alongside the test reaction zone in the same cartridge, allowing simultaneous measurement and automatic compensation for variations without requiring separate complex instrumentation or multiple devices.
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
Enables accurate and reliable on-the-spot biomarker detection and quantification by minimizing interference from environmental and sample variations, facilitating low-cost, portable, and rapid point-of-care diagnostics.
Implementation Method 1
a CMOS-based sensor unit configured to: independently detect a property of each of the test region, the positive control region, and the negative control region
Implementation Method 2
enzyme-based assays that require a spectrophotometer to measure changes in intensity of colour products from those enzyme reactions
Implementation Method 3
A colour change within this range can be exploited for a range of enzyme assays
Implementation Method 4
a transport structure configured to convey the biological sample received at the sample receiving area to the reaction zone
Data Source
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AI summary
A biomarker detection apparatus in which a CMOS-based chip is used to generate independent detection signals from a reaction zone that receives a biological sample, where the biological sample is provided to both a test region and positive and negative control regions within the reaction zone. The independent detection signals can be processed together (i.e. as a group of input parameters for an algorithm) to identify the presence of a biomarker (or a plurality of biomarkers) in a biological sample. The use of sample-specific, independently detectable positive and negative controls facilitates improved detection accuracy.