Electrical Differential Counter for CD4+ T Cell Counting

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Solution Overview

Problem

Current methods for counting particles, such as cells, in mixed populations are limited by the need for complex and costly optical devices, and existing electrical methods are inadequate for distinguishing and counting specific subsets of cells like CD4+ T cells in whole blood.

Innovation Solution

A low-cost electrical differential counting method using two impedance sensors to selectively count and subtract the number of CD4+ T cells from whole blood samples, employing microfluidic chips with capture chambers functionalized with antibodies to isolate and count these cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If optical devices such as flow cytometers are used to count particles, then measurement precision is improved, but device complexity and cost increase

Engineering Contradiction:
Improveparticle counting accuracyVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces optical detection systems with electrical impedance sensing to count particles. Instead of using lasers and fluorescent markers, the system uses electrical sensors to detect changes in impedance caused by particles passing through a microfluidic channel, thereby reducing device complexity while maintaining counting capability

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

Solution Approach 2:

The patent extracts and removes red blood cells from the blood sample using a microfluidic device before counting white blood cells. This separation step simplifies the counting process by eliminating the need to distinguish between different cell types based on optical properties, reducing both device complexity and measurement difficulty

Inventive Principle:
Principle #2Taking out (Extraction)

2Device complexity

If electrical impedance methods are used to count cells, then device complexity is reduced, but measurement precision is inadequate for distinguishing specific cell subsets

Engineering Contradiction:
Improvesystem simplicityVSAvoidcell subset differentiation accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent segments the blood sample into different cell types by first removing red blood cells, then counting only the remaining white blood cells. This segmentation approach allows the simple electrical impedance sensor to accurately count specific cell subsets without needing to distinguish between multiple cell types simultaneously

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary removal of red blood cells before the actual cell counting process. This pre-processing step prepares the sample by eliminating interfering cell types, enabling the subsequent electrical counting to focus on and accurately measure specific white blood cell subsets

Inventive Principle:
Principle #10Preliminary action

3Manufacturing precision

If traditional Coulter counting methods are used, then manufacturing precision is maintained, but adaptability for counting specific cell subsets in whole blood is limited

Engineering Contradiction:
Improvecounting accuracyVSAvoidcell subset counting capability
Core Design Contradiction:
Manufacturing precisionVSAdaptability or versatility

Solution Approach 1:

The patent employs dynamic flow control in the microfluidic device to selectively remove red blood cells and then count white blood cells. The system can adjust flow rates and timing to optimize the separation and counting process, enabling accurate counting of various cell subsets including CD4+ T cells in whole blood samples

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 enables accurate and cost-effective counting of CD4+ T cells, reducing the need for expensive reagents and infrastructure, allowing for point-of-care diagnostics and improved cell analysis with higher throughput and simplicity compared to traditional methods.

Implementation Method 1

counting all types of particles in a portion of the sample using a first electrical differential counter

Methodology Applied
Scientific EffectElectrical impedance sensing: Electrical Resistance

Implementation Method 2

capture chamber functionalized with antibodies to isolate and count these cells

Methodology Applied
Scientific EffectAntibody binding: Adsorption

Data Source

PatentUS10527568B2Counting particles using an electrical differential counter
Publication Date: 2020.01.07 DAKTARI DIAGNOSTICS INC
  • US10527568B2 patent drawing
  • US10527568B2 patent drawing
  • US10527568B2 patent drawing

AI summary

This disclosure relates to methods and devices to count particles of interest, such as cells. The methods include obtaining a fluid sample that may contain particles of interest; counting all types of particles in a portion of the sample using a first electrical differential counter to generate a first total; removing any particles of interest from the portion of the fluid sample; counting any particles remaining in the portion of the fluid sample using a second electrical differential counter after the particles of interest are removed to generate a second total; and calculating a number of particles of interest originally in the fluid sample by subtracting the second total from the first total, wherein the difference is the number of particles of interest in the sample. These methods and related devices can be used, for example, to produce a robust, inexpensive diagnostic kit for CD4+ T cell counting in whole blood samples.