Platelet Analysis System Using Flow Cytometry for HIT Diagnosis

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Solution Overview

Problem

Current methods for diagnosing platelet-related disorders, such as immune thrombocytopenia and heparin-induced thrombocytopenia, are limited by lack of sensitivity, specificity, and practicality, leading to incomplete clinical information and potential misdiagnosis, particularly in routine clinical settings.

Innovation Solution

A comprehensive platelet analysis system using flow cytometry and diagnostic kits that include specific reagents for testing platelet activation, auto-antibodies, and functional capacity, enabling the diagnosis of various platelet-related disorders, including immune thrombocytopenia, heparin-induced thrombocytopenia, and platelet functional defects, with improved sensitivity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If flow cytometry is used for platelet analysis, then measurement precision and analysis speed are improved, but device complexity and cost increase

Engineering Contradiction:
Improveplatelet analysis precisionVSAvoidflow cytometer complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The flow cytometer is designed to perform multiple functions including platelet counting, activation state analysis, and antibody detection using the same instrument platform. The system can analyze various platelet parameters (CD62p expression, P-selectin levels, activation markers) and different sample types (whole blood, platelet-rich plasma) without requiring separate specialized devices, thereby reducing overall system complexity while maintaining high measurement precision.

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

Solution Approach 2:

The platelet analysis process is divided into distinct functional modules: sample preparation, fluorescence labeling with specific antibodies (anti-CD62p, anti-P-selectin), flow cytometric detection, and data analysis. This segmentation allows each module to be optimized independently while using a standardized flow cytometer platform, reducing the complexity burden on the core instrument while achieving high precision measurements.

Inventive Principle:
Principle #1Segmentation

2Reliability

If comprehensive platelet analysis is performed, then diagnostic reliability is improved, but analysis time and operational complexity increase

Engineering Contradiction:
Improvediagnostic reliabilityVSAvoidanalysis time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The flow cytometer operates in continuous flow mode, analyzing thousands of platelets per second without interruption. The hydrodynamic focusing technique maintains a continuous single-file stream of platelets through the detection zone, enabling rapid data acquisition. This continuous analysis approach provides comprehensive diagnostic information while minimizing total analysis time compared to discrete, step-by-step examination methods.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

Samples are pre-treated with fluorescently labeled antibodies specific to platelet activation markers (CD62p, P-selectin) before analysis. This preliminary labeling step ensures that when platelets pass through the detection zone, their activation state is already marked and ready for immediate detection, eliminating the need for time-consuming activation assays during the measurement phase and thus reducing overall analysis time while maintaining diagnostic reliability.

Inventive Principle:
Principle #10Preliminary action

3Loss of information

If multiple platelet parameters are measured simultaneously, then information completeness is improved, but measurement complexity and data interpretation difficulty increase

Engineering Contradiction:
Improveclinical information completenessVSAvoidmeasurement system complexity
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The system employs multi-parameter flow cytometry that measures multiple platelet characteristics simultaneously by detecting fluorescence at different wavelengths and angles. Forward scatter provides information on platelet size, side scatter on internal complexity, and fluorescent detectors capture activation marker expression. This multi-dimensional measurement approach captures comprehensive clinical information in a single analysis run, with automated software handling the complexity of integrating and interpreting multiple parameters, thus reducing the perceived measurement complexity for the operator.

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

Solution Approach 2:

Different fluorescently labeled antibodies emit light at distinct wavelengths (colors) when excited by the laser. The system uses fluorophores with different emission spectra (e.g., FITC, PE, APC) to label different platelet markers simultaneously. The flow cytometer's optical system separates and detects these different colors independently, allowing multiple platelet parameters (activation state, surface marker expression, granule content) to be measured concurrently without cross-interference, thus providing complete clinical information while managing measurement complexity through optical signal separation.

Inventive Principle:
Principle #32Color changes

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 system provides reliable and rapid diagnostic assays for platelet-related disorders, enhancing clinical decision-making by identifying patients at risk for thrombosis or bleeding, and guiding appropriate medical interventions.

Implementation Method 1

A beam of light (usually laser light) of a single wavelength is directed onto a hydrodynamically-focused stream of liquid. Each suspended particle from 0.2 to 150 micrometers passing through the beam scatters the ray

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 2

fluorescent chemicals found in the particle or attached to the particle may be excited into emitting light at a longer wavelength than the light source

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

A beam of light (usually laser light) of a single wavelength is directed onto a hydrodynamically-focused stream of liquid

Methodology Applied
Scientific EffectHydrodynamic focusing:

Data Source

PatentEP2665830B1Platelet analysis system
Publication Date: 2019.11.06 TOMER AARON
  • EP2665830B1 patent drawingFigure 1
  • EP2665830B1 patent drawingFigure 2
  • EP2665830B1 patent drawingFigure 3

AI summary

A method for diagnosis of HIT (Heparin-induced thrombocytopenia) in a patient's serum or plasma sample and a system comprising kits for performing the method.