Flow Cytometry Plasmodium Detection via Cell Density

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Solution Overview

Problem

Current diagnostic methods for plasmodium infections, such as malaria, face challenges in achieving high sensitivity and specificity, particularly in regions with varying prevalence, leading to false-positive and false-negative results, and are often labor-intensive and time-consuming, which can result in delayed or inappropriate treatment.

Innovation Solution

A method involving differential analysis of polymorphonuclear neutrophil granulocytes, thrombocyte number, and cell density distribution in patient blood samples, using scattered light measurements to derive parameters that assess the presence of a plasmodium infection based on predefined criteria, enhancing sensitivity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional microscopic blood examination is used, then reliability of diagnosis is improved, but productivity deteriorates due to labor- and time-intensive manual analysis

Engineering Contradiction:
Improvediagnostic reliabilityVSAvoidthroughput of sample examination
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent replaces manual microscopic examination with automated flow cytometry technology. The flow cytometer uses optical scattering measurements and electronic data processing to automatically analyze blood cells, eliminating the need for manual microscopy while maintaining diagnostic accuracy. This substitution of mechanical/manual processes with automated electronic systems resolves the contradiction between reliability and productivity.

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

Solution Approach 2:

The automated flow cytometry system performs self-analysis of blood samples without requiring expert personnel for manual evaluation. The instrument automatically measures cell parameters, applies diagnostic algorithms, and generates results, enabling the system to serve itself in the diagnostic process. This automation dramatically increases throughput while preserving diagnostic reliability.

Inventive Principle:
Principle #25Self-service

2Productivity

If Rapid Diagnostic Tests (RDT) with monoclonal antibodies are used, then productivity is improved, but measurement precision deteriorates leading to false-positive and false-negative results

Engineering Contradiction:
Improvespeed of diagnosisVSAvoidsensitivity and specificity
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent measures multiple cellular parameters simultaneously (volume, density, internal complexity, granularity) rather than relying on a single antigen detection method. By analyzing changes in multiple physical parameters of blood cells and platelets, the system achieves both high throughput and high diagnostic accuracy, resolving the contradiction between speed and precision.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent transitions from two-dimensional microscopic visualization to multi-dimensional flow cytometric analysis, measuring cells in suspension with simultaneous detection of multiple parameters. This dimensional expansion allows automated high-throughput analysis while maintaining or improving diagnostic precision through multi-parameter evaluation.

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

3Measurement precision

If polymerase chain reaction (PCR) is used, then measurement precision is improved, but productivity deteriorates due to high material and time outlay

Engineering Contradiction:
Improvesensitivity of detectionVSAvoidtime and material efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent uses a disposable microfluidic chip or test cartridge that integrates the flow cytometry measurement system. This single-use device eliminates the need for expensive, complex PCR laboratories and equipment while providing rapid, sensitive detection. The disposable nature enables high throughput without the time-consuming setup and cleanup required for PCR.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Productivity

If automated cell counters are used, then productivity is improved, but measurement precision deteriorates due to reduced ability to detect subtle pathological changes

Engineering Contradiction:
Improvethroughput of automated analysisVSAvoiddetection of subtle cell changes
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent employs dynamic measurement of multiple cell parameters simultaneously during flow cytometric analysis, rather than static single-parameter counting. The system continuously measures volume, density, and internal complexity as cells pass through the detection zone, enabling automated high-throughput analysis that can detect subtle pathological changes characteristic of malaria infection.

Inventive Principle:
Principle #15Dynamics

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

This approach significantly increases the sensitivity and specificity of malaria detection, reducing false-positive and false-negative results to unprecedented levels, enabling timely and accurate diagnosis, especially in areas with high malaria prevalence.

Implementation Method 1

using scattered light measurements to derive parameters that assess the presence of a plasmodium infection

Methodology Applied
Scientific EffectScattered light measurement: Scattering

Data Source

PatentUS9605293B2Method for detecting a plasmodium infection
Publication Date: 2017.03.28 SIEMENS HEALTHCARE DIAGNOSTICS PRODS
  • US9605293B2 patent drawing
  • US9605293B2 patent drawing
  • US9605293B2 patent drawing

AI summary

The invention relates to a method for detecting a plasmodium infection in a patient blood sample, wherein a differential analysis of the polymorphonuclear neutrophil granulocytes in the sample is performed, and the distribution of the cell volume and the cell density, the number of thrombocytes in the sample, and the distribution of the cell density of the thrombocytes in the sample is determined.