Dengue Detection via Automated Blood Cell Analysis

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Solution Overview

Problem

Current methods for detecting dengue infections in blood samples lack sufficient sensitivity and specificity, often resulting in false positives and negatives, and require isolation of serum, which is not feasible within standard blood cell count tests.

Innovation Solution

A method utilizing automated cell counters to analyze prespecified parameters of blood platelets and cells, such as cell volume, number, and density, to determine if a dengue infection is present by evaluating sample parameters against a predefined criterion, allowing for high sensitivity and specificity without the need for serum isolation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If PCR or ELISA assays are used to detect dengue infections, then detection capability is achieved, but the methods require serum isolation which is not feasible within standard blood cell count tests and have insufficient sensitivity and specificity

Engineering Contradiction:
Improvedetection sensitivity and specificityVSAvoidcomplexity of detection procedure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines dengue virus detection with the routine complete blood count (CBC) procedure by analyzing platelet parameters and red blood cell parameters that are already measured during standard CBC. This merging eliminates the need for separate serum isolation and specialized assays, achieving high sensitivity (90-99%) and specificity (90-99%) using existing automated blood analysis devices.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention makes the automated blood analysis device perform multiple functions: it not only conducts routine CBC analysis but also detects dengue virus infections by evaluating specific parameter combinations (platelet count, platelet distribution width, red blood cell count, and their ratios). This multi-functionality allows standard devices to provide both routine hematology and infectious disease detection.

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

2Reliability

If PCR methods are used for dengue detection, then virus genome detection is achieved, but the method is not commercially available for real-time PCR and requires specialized procedures

Engineering Contradiction:
Improvedetection accuracyVSAvoidease of implementation
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent enables automated blood analysis devices to perform dengue detection using their own existing measurement capabilities without requiring external specialized equipment or procedures. The device uses its built-in parameters (platelet count, platelet distribution width, red blood cell count) and applies algorithmic evaluation to achieve reliable detection, making the process self-sufficient and easily implementable.

Inventive Principle:
Principle #25Self-service

3Measurement precision

If ELISA assays are used to detect dengue antibodies, then infection detection is achieved, but false positives and cross reactions with other mosquito-borne viruses occur

Engineering Contradiction:
Improvedetection specificityVSAvoidtesting throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent uses a combination of multiple parameters (platelet count, platelet distribution width, red blood cell count, and their ratios) where no single parameter is sufficient alone. This partial action approach, combining multiple measurements with algorithmic evaluation, achieves high specificity (90-99%) while maintaining high throughput through automated analysis, avoiding the false positives associated with single-marker ELISA assays.

Inventive Principle:
Principle #16Partial or excessive action

4Measurement precision

If PRNT assays are used for dengue detection, then serotype-specific detection is achieved, but the method is not standardized leading to variability in results

Engineering Contradiction:
Improvedetection consistencyVSAvoidstandardization of procedure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent transforms the detection approach by changing from measuring viral neutralization activity (PRNT) to measuring hematological parameters (platelet count, platelet distribution width, red blood cell count) that result from dengue infection. This parameter change enables standardized, automated measurement with consistent results across different laboratories and devices, eliminating the variability inherent in manual PRNT assays.

Inventive Principle:
Principle #35Parameter 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

This approach significantly increases sensitivity and specificity to 90-99% for dengue infection detection, reducing false-positive and false-negative results, and can be performed efficiently and cost-effectively using standard automated blood analysis devices.

Implementation Method 1

With the impedance method, the counting of the cells and also the determination of their size is done on the basis of the detection and the measurement of changes in the electrical conductivity (impedance), which are caused by a particle which is moving through a small opening.

Methodology Applied
Scientific EffectImpedance measurement: Electrical Resistance

Implementation Method 2

the optical method comprises the passing of a laser light beam through a thinned blood sample, which is detected in a continuous stream by the laser beam. Each cell which passes through the detection zone of the throughflow cells scatters the focused light.

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentUS11815510B2Method for detecting a dengue infection
Publication Date: 2023.11.14 SIEMENS HEALTHCARE DIAGNOSTICS INC
  • US11815510B2 patent drawing
  • US11815510B2 patent drawing
  • US11815510B2 patent drawing

AI summary

The invention relates to a method for detecting a dengue infection in a patient blood sample, comprising the steps: a) Performing an analysis of prespecified parameters of blood platelets and prespecified types of blood cells in the sample and determining parameter values for the prespecified parameters of the platelets and the prespecified types of cells; b) Obtaining sample parameters from the values determined in step a); and c) Evaluating the sample parameters in relation to a prespecified criterion, wherein, if the criterion is fulfilled, a dengue infection is present.