Microfluidic In Situ Labeling via Acoustic Cell Trapping

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Solution Overview

Problem

Current methods for biological sample preparation, such as blood analysis, face challenges in efficiently isolating and stabilizing cells of interest from whole blood, particularly in microfluidic devices, where size-based separation techniques are limited by the complexity and diversity of blood components.

Innovation Solution

The use of lateral cavity acoustic transducers (LCATs) with stabilized microbubbles and piezoelectric transducers to create microstreaming vortices for trapping and in situ labeling of cells, allowing for size-based separation and enhanced visualization of blood constituents, including the introduction of markers for identification and enumeration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If size-based separation techniques are used in microfluidic devices, then cell isolation from whole blood is achieved, but the complexity and diversity of blood components limit the efficiency of separation

Engineering Contradiction:
Improvecell isolation efficiencyVSAvoidseparation process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent employs acoustic vibration fields generated by piezoelectric transducers to create standing waves in microfluidic channels. These vibrations enable size-based separation of blood cells through acoustic radiation forces, allowing efficient isolation of target cells (e.g., cancer cells, WBCs) from whole blood without complex mechanical moving parts or multiple processing steps

Inventive Principle:
Principle #18Mechanical vibration

Solution Approach 2:

The invention replaces traditional mechanical separation methods (such as centrifugation or physical filtering) with acoustic field-based separation. The acoustic standing waves create radiation pressure that sorts cells by size and density, eliminating the need for complex mechanical systems while maintaining high separation efficiency for diverse blood components

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

2Duration of action of moving object

If air-liquid interfaces are used in LCATs for cell trapping, then size-based separation is enabled, but the interfaces are unstable and LCATs cannot operate for extended periods

Engineering Contradiction:
ImproveLCAT operating timeVSAvoidair-liquid interface stability
Core Design Contradiction:
Duration of action of moving objectVSStability of the object's composition

Solution Approach 1:

The patent introduces surfactants or surface-active agents as intermediaries at the air-liquid interface within LCATs. These substances reduce surface tension and prevent interface collapse, allowing the LCAT to maintain stable operation for extended periods while continuing to perform size-based cell separation through acoustic trapping

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention modifies the physical-chemical parameters of the air-liquid interface by controlling surfactant concentration, temperature, and acoustic power. These parameter changes stabilize the interface properties, enabling prolonged LCAT operation without degradation of separation performance

Inventive Principle:
Principle #35Parameter changes

3Loss of time

If conventional sample preparation methods are used, then cell isolation is achieved, but the process is time-consuming and complex

Engineering Contradiction:
Improvesample preparation timeVSAvoidprocessing procedure complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The patent combines multiple functions (cell separation, trapping, and labeling) into a single integrated microfluidic device. The acoustic field simultaneously separates cells by size and traps them at specific locations for in situ labeling, eliminating the need for sequential processing steps and reducing overall preparation time while maintaining simplicity

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The microfluidic device with acoustic trapping is designed to perform multiple functions: size-based separation of different blood cell types, trapping of target cells at controlled positions, and in situ labeling with markers. This multi-functional approach replaces multiple separate conventional procedures with a single versatile platform

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

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 efficient separation and enrichment of target cells, such as cancer cells, with high enrichment ratios and rapid labeling, reducing the complexity and time of conventional processes, and is suitable for point-of-care diagnostics and research applications.

Implementation Method 1

The air-liquid interface can be actuated by piezoelectric transducer (PZT) or otherwise oscillated

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 2

A sample (e.g., particles or cells) in the liquid can be trapped in vortices generated when the air-liquid interface is actuated by piezoelectric transducer (PZT) or otherwise oscillated

Methodology Applied
Scientific EffectAcoustic microstreaming:

Implementation Method 3

The air-liquid interface can be stabilized by increasing the capillary number of the liquid

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentUS11213823B2Microfluidic in situ labelling on stable interfaces
Publication Date: 2022.01.04 RGT UNIV OF CALIFORNIA
  • US11213823B2 patent drawing
  • US11213823B2 patent drawing
  • US11213823B2 patent drawing

AI summary

A method of trapping constituents of interest in a fluid sample flowing through a microfluidic channel by vibrating an interface of the fluid sample and a gas occupying a lateral channel adjacent the microfluidic channel is described. A marker is flowed into the microfluidic channel such that the marker bonds with constituents of interest. The constituents of interest bonded to the marker can help identification of the constituents of interest.