Microfluidic Coagulation Assay Using Glass Surface Activation

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Solution Overview

Problem

Current coagulation assays are cumbersome, require extensive preparation time, and lack a universal, rapid, and accurate point-of-care solution for assessing clotting status, especially in emergency situations involving anticoagulated patients.

Innovation Solution

A microfluidic chip-based device that activates the coagulation cascade using a glass surface and shear flow, allowing for rapid and accurate measurement of clotting times without chemical reagents, using integrated sensors to detect changes in viscosity, optical transmission, and electrical impedance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional coagulation assays are used, then coagulation status can be measured, but the assays are cumbersome and require extensive preparation time

Engineering Contradiction:
Improvecoagulation status measurementVSAvoidpreparation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention extracts the coagulation activation function from complex chemical reagent systems and concentrates it into a simple glass surface contact mechanism. By removing the need for multiple chemical additives and simplifying the activation process to merely exposing blood to a glass surface, the device achieves rapid coagulation measurement without extensive preparation

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The glass surface automatically activates the coagulation cascade through simple contact with blood, eliminating the need for manual addition of chemical activators. The system serves itself by using the inherent properties of the glass surface to initiate clotting, requiring no operator intervention beyond sample application

Inventive Principle:
Principle #25Self-service

2Measurement precision

If traditional coagulation assays are used, then coagulation status can be measured, but they lack a universal, rapid, and accurate point-of-care solution

Engineering Contradiction:
Improveclotting time measurementVSAvoidpoint-of-care usability
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The invention segments the coagulation measurement process into discrete, simplified steps: blood application to glass surface, automated sensor detection, and digital output. This segmentation transforms a complex laboratory procedure into an easily operable point-of-care device that maintains measurement precision while improving usability

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention replaces manual mechanical operations (mixing, timing, visual assessment) with automated sensor systems that optically and electrically detect clot formation. This substitution maintains accurate measurement while dramatically improving ease of operation by eliminating skilled technical steps

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

3Speed

If chemical reagents are used to activate coagulation, then coagulation can be initiated, but the device complexity increases

Engineering Contradiction:
Improvecoagulation activation speedVSAvoidchemical reagent system
Core Design Contradiction:
SpeedVSDevice complexity

Solution Approach 1:

The invention extracts the activation function from chemical reagents and transfers it to the physical glass surface itself. By removing all chemical additives and using only the glass surface contact to activate coagulation, the device achieves rapid activation while minimizing complexity

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The glass surface serves multiple functions: it activates the coagulation cascade, provides structural support for the microfluidic channel, and enables sensor detection. This multi-functionality eliminates the need for separate chemical reagent systems while maintaining activation speed

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

4Measurement precision

If large sample volumes are used, then adequate blood is available for measurement, but the portability and rapidity of the device decreases

Engineering Contradiction:
Improveclotting time assessmentVSAvoidblood sample volume
Core Design Contradiction:
Measurement precisionVSVolume of moving object

Solution Approach 1:

The invention transitions from bulk volume measurement to surface-area-based measurement by spreading a small blood volume across a glass surface in a microfluidic channel. This dimensional change allows adequate measurement precision with minimal sample volume, enabling portability and rapid testing

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 rapid, accurate, and reproducible assessment of clotting status with minimal sample volume, independent of anticoagulant presence, facilitating optimal dosing of anticoagulation drugs and their reversal agents in a universal and portable format.

Implementation Method 1

The coagulation cascade of secondary hemostasis has two pathways which lead to fibrin formation. These are the contact activation pathway (also known as the intrinsic pathway), and the tissue factor pathway (also known as the extrinsic pathway).

Methodology Applied
Scientific EffectContact activation pathway: Coagulation

Implementation Method 2

A microfluidic chip-based device that activates the coagulation cascade using a glass surface and shear flow

Methodology Applied
Scientific EffectShear flow: Shear Stress

Implementation Method 3

using integrated sensors to detect changes in viscosity, optical transmission, and electrical impedance

Methodology Applied
Scientific EffectViscosity change: Viscometer

Implementation Method 4

using integrated sensors to detect changes in viscosity, optical transmission, and electrical impedance

Methodology Applied
Scientific EffectOptical transmission: Absorption Spectroscopy

Implementation Method 5

using integrated sensors to detect changes in viscosity, optical transmission, and electrical impedance

Methodology Applied
Scientific EffectElectrical impedance: Electrical Resistance

Data Source

PatentUS20240085440A1Microfluidic chip-based, universal coagulation assay
Publication Date: 2024.03.14 PEROSPHERE TECHNOLOGIES INC
  • US20240085440A1 patent drawing
  • US20240085440A1 patent drawing
  • US20240085440A1 patent drawing

AI summary

A microfluidic, chip-based assay device has been developed for measuring physical properties of an analyte (particularly, whole blood or whole blood derivatives). The technologies can be applied to measure clotting times of whole blood or blood derivatives, determine the effects of anticoagulant drugs on the kinetics of clotting/coagulation, as well as evaluate the effect of anticoagulant reversal agents. These technologies can additionally be used to optimize the dosage of anticoagulation drugs and/or their reversal agents. The assay is independent of the presence of anticoagulant; clotting is activated by exposure of the blood sample in the device to a glass (or other negatively charged material such as oxidized silicon) surface, which activates the intrinsic pathway and can be further hastened by the application of shear flow across the activating materials surface. The absence of chemical activating agents and highly controlled and reproducible micro-environment yields a point of care universal clotting assay.