Microfluidic Luminescence Sensor for Nanoliter Plasma Coagulation Testing
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Solution Overview
Problem
Existing blood coagulation activity assays require large volumes of blood, typically 0.5 mL or more, which are invasive and burdensome for patients, especially chronic patients and young children, necessitating phlebotomy and standard laboratory equipment.
Innovation Solution
A sensor system with a microfluidic substrate capable of processing blood plasma and buffer in volumes as low as 0.44 μL, utilizing single photon avalanche photodiodes to detect luminescence without the need for light excitation or optics, allowing for real-time photon emission counting and eliminating the need for complex manufacturing and trained professionals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If standard lab equipment with large dead/void volumes is used, then measurement precision is maintained, but volume of blood required increases
Solution Approach 1:
The detection system is segmented into multiple independent photodiode arrays, each corresponding to a specific microfluidic detection chamber. This segmentation allows for precise photon counting in small volumes while eliminating the need for large dead volumes associated with traditional single-channel detection systems.
Solution Approach 2:
The invention transitions from traditional bulk optical detection to a microfluidic dimension where detection chambers with volumes of less than 5 μL are used. The photodiode arrays are positioned in close proximity (no more than 1,000 micrometres) to the chambers, enabling accurate measurement in a three-dimensional micro-scale environment that eliminates the large dead volumes of conventional equipment.
2Reliability
If phlebotomy by trained technician is performed, then blood sample quality is ensured, but patient burden and invasiveness increase
Solution Approach 1:
The sensor system is designed to accept small blood volumes that can be obtained through minimal invasive means, potentially allowing patients to self-collect samples. The system processes these small volumes through microfluidic channels to produce reliable coagulation activity results without requiring trained technicians or standard phlebotomy procedures.
3Quantity of substance
If standard commercial blood tubes with 1 mL or 2 mL volume are used, then sample sufficiency is ensured, but invasiveness and patient discomfort increase
Solution Approach 1:
The invention uses only a small portion (less than 5 μL) of the blood sample for detection, which is a partial action compared to the traditional requirement of 0.5 mL to 2 mL. This partial usage of sample volume significantly reduces the invasiveness of blood collection while still providing sufficient material for accurate coagulation activity measurement through the sensitive photodiode detection system.
4Quantity of substance
If luminescence detection with photodiode arrays is implemented, then volume requirement is reduced, but device complexity increases
Solution Approach 1:
The invention merges the microfluidic substrate containing detection chambers with integrated photodiode arrays directly positioned beneath or adjacent to the chambers. This merging of fluid handling and optical detection functions into a single compact sensor structure reduces the overall device complexity compared to traditional systems that separate sample preparation and detection into different equipment components.
Solution Approach 2:
The photodiode arrays serve multiple functions: they detect photons emitted from luminescence reactions, they are positioned to define detection volumes, and they can be integrated with the microfluidic substrate to provide both structural support and detection capability. This multi-functionality reduces the number of separate components needed, thereby simplifying the overall device structure.
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, low-cost, and non-invasive blood coagulation analysis using significantly smaller blood volumes, eliminating the need for phlebotomy and standard lab equipment, suitable for point-of-care diagnostics.
Implementation Method 1
detecting photon emissions... such photon emissions may be released during a chemical reaction (chemiluminescence)
Implementation Method 2
single photon avalanche photodiodes... receive photons emitted within the corresponding microfluidic detection chamber
Data Source
AI summary
A sensor for sensing photons in liquids comprises: a microfluidic substrate comprising a blood inlet, a buffer inlet, a mixing region configured to mix blood with buffer to provide a sample, and a plurality of microfluidic detection chambers each configured to receive a volume of analyte of less than 5 micro litres, wherein the microfluidic substrate is nontransparent and has a planar face. The sensor also comprises a semiconductor substrate comprising a plurality of single photon avalanche photodiodes facing the planar face of the microfluidic substrate and arranged in a plurality of primary arrays of photodiodes and at least one secondary array of photodiodes. The sensor also comprises a plurality of sensing channels, wherein each sensing channel of the plurality of sensing channels comprises one of the microfluidic detection chambers and a corresponding one of the primary arrays of photodiodes. Each one of the photodiodes in the secondary array of photodiodes is covered to prevent ingress of light and a secondary charge count derived from the secondary array of photodiodes is indicative of a dark count. An adjusted charge count is provided by using the dark count value to adjust the primary charge count.