Sheathless Flow Cell for Accurate Blood Cell Counting

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Solution Overview

Problem

Conventional flow cytometry designs, such as those using sheath flow, face challenges in accurately measuring absolute cell counts and other CBC parameters due to complex fluidic structures and difficulty in controlling sample volume, leading to inaccuracies in CBC testing.

Innovation Solution

A sheathless flow cell design with on-board fluidics in a cartridge system that uses size reference beads and optical measurements to achieve accurate counting and characterization of blood cells, allowing for direct measurement of sample streams without sheath flow, enabling precise analysis of leukocyte, erythrocyte, and platelet parameters.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If sheath flow design is used in flow cytometry, then fluidic structure provides stable flow control, but device complexity increases and sample volume control becomes difficult

Engineering Contradiction:
Improveflow control stabilityVSAvoidfluidic structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent removes the sheath flow component from the fluidic system, transitioning from a conventional sheath flow design to a sheathless design. This extraction eliminates the complex fluidic structures associated with sheath flow while maintaining reliable flow control through alternative mechanisms such as capillary forces and surface tension in the microfluidic channels.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical sheath flow control system with a sheathless microfluidic system that relies on passive fluidic control mechanisms. This substitution eliminates the need for complex mechanical fluidic structures while achieving stable flow control through microfluidic principles such as capillary action and controlled pore sizes in the membrane.

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

2Reliability

If sheath flow design is used, then fluidic structure provides flow stabilization, but measurement precision of absolute cell counts deteriorates

Engineering Contradiction:
Improveflow stabilizationVSAvoidabsolute cell count accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

By removing the sheath flow component, the patent eliminates the interference with sample volume control that previously degraded measurement precision. The sheathless design allows direct and accurate measurement of the sample stream without the complicating factor of sheath flow mixing, thereby improving absolute cell count accuracy.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The sheathless flow cell design allows the sample stream to self-align and self-constrain through capillary forces and surface tension at the membrane interface, eliminating the need for sheath flow stabilization. This self-service mechanism maintains flow stability while enabling precise measurement of sample volume and cell counts.

Inventive Principle:
Principle #25Self-service

3Adaptability or versatility

If conventional flow cytometry with sheath flow is used, then leukocyte subtypes can be distinguished into three categories, but optical measurement accuracy and leukocyte subtype differentiation into five categories cannot be achieved

Engineering Contradiction:
Improveleukocyte subtype classification capabilityVSAvoidoptical measurement accuracy
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent replaces the mechanical sheath flow system with a sheathless optical measurement system that provides superior optical measurement accuracy. This substitution enables enhanced leukocyte subtype differentiation into five categories (lymphocytes, monocytes, neutrophils, eosinophils, and basophils) by eliminating flow disturbances and improving signal-to-noise ratio in optical detection.

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

Solution Approach 2:

The patent changes the flow regime parameter from sheath flow to sheathless flow, which fundamentally alters the optical measurement conditions. This parameter change improves optical measurement accuracy by eliminating refractive index mismatches and flow-induced scattering, thereby enabling precise differentiation of all five leukocyte subtypes.

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

The sheathless flow cell design enhances measurement accuracy for CBC parameters by eliminating the need for sheath flow, improving the precision of absolute cell counts and allowing for comprehensive analysis of blood cells, including subtypes and indices, while maintaining simplicity in fluidic structure and control.

Implementation Method 1

measure an electrical impedance signal from the flow sensor

Methodology Applied
Scientific EffectElectrical impedance: Electrical Resistance

Implementation Method 2

measuring light scattering from the sample streams in the flow cell

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentUS10641698B2Methods for complete blood count measurement
Publication Date: 2020.05.05 CYTOCHIP INC
  • US10641698B2 patent drawing
  • US10641698B2 patent drawing
  • US10641698B2 patent drawing

AI summary

The disclosure relates to devices and methods for analyzing blood cells in a sample. In various embodiments, the present disclosure provides devices and methods of performing complete blood count (CBC) testing. In various embodiments, the present disclosure provides a cartridge device and a reader instrument device, wherein the reader instrument device receives, operates, and/or actuates the cartridge device. In various embodiments, the present disclosure provides a method of using a device as disclosed herein for analyzing blood cells in a sample.