Acoustic Cell Sorting Using Gas Vesicles in Microfluidic Channels

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for genotype-based cell selection, such as fluorescence-activated cell sorting (FACS), are complex and expensive, limiting their use to centralized facilities, and there is a need for more efficient and lower cost methods for genotype-based cell sorting.

Innovation Solution

A method using microfluidic channels and ultrasound to sort cells based on their expression or uptake of gas vesicles (GVs), which modulate acoustic contrast, allowing cells to be actuated into specific flow streams using acoustic standing waves.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence-activated cell sorting (FACS) is used for genotype-based cell selection, then cell sorting capability is achieved, but device complexity and cost increase

Engineering Contradiction:

Improvecell sorting capabilityVSAvoidinstrument complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the complex optical detection system of FACS with an acoustic manipulation system. Gas vesicles expressed in target cells create acoustic contrast that enables sorting via acoustic radiation force in a microfluidic channel, eliminating the need for fluorescence detection equipment while achieving genotype-based cell selection

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention changes the detection parameter from optical (fluorescence) to acoustic (compressibility). By expressing gas vesicles that alter cell acoustic properties, the system enables genotype-based sorting through acoustic impedance differences rather than fluorescence signals, simplifying the overall system architecture

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If fluorescence-activated cell sorting (FACS) is used for genotype-based cell selection, then cell sorting capability is achieved, but cost increases

Engineering Contradiction:

Improvecell sorting capabilityVSAvoidcost

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent replaces expensive optical detection and sorting equipment with a low-cost acoustic manipulation system using gas vesicles and acoustic radiation force in microfluidic devices, dramatically reducing the cost of genotype-based cell sorting while maintaining sorting capability

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention uses transient gas vesicle expression in cells rather than permanent genetic modification, allowing cells to be sorted based on temporary acoustic properties. This approach reduces costs by avoiding complex permanent genetic engineering while achieving effective genotype-based selection

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Ease of operation

If gas vesicles are expressed in cells to modulate acoustic contrast, then cell actuation capability is improved, but cell density changes

Engineering Contradiction:

Improvecell actuation capabilityVSAvoidcell density

Core Design Contradiction:

Ease of operationVSWeight of stationary object

Solution Approach 1:

The patent exploits the physical property change caused by gas vesicle expression - the air-filled vesicles decrease cell density and increase compressibility. This parameter change creates acoustic contrast that enables acoustic radiation force to actuate cells into different microfluidic channels based on gas vesicle expression levels

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

Enables efficient and cost-effective sorting of cells into subpopulations with high enrichment, overcoming the limitations of FACS by providing a scalable and accessible solution for genetic engineering and therapeutic cell preparation.

Implementation Method 1

the expression of GVs within a cell increases the compressibility (β) and reduces the density (ρ) of said cell, thereby modulating the acoustic contrast (Φ) of said cell relative to the fluid in the microfluidic channel

Methodology Applied

Scientific EffectAcoustic contrast modulation:

Implementation Method 2

applying ultrasound comprises generating acoustic standing wave(s) in the microfluidic channel, wherein the acoustic standing wave(s) position pressure antinode(s) in the microfluidic channel, and wherein the second subpopulation of cells is actuated towards flow stream(s) comprising the pressure antinode(s)

Methodology Applied

Scientific EffectAcoustic radiation force: Acoustic Radiation Pressure

Data Source

PatentUS12551893B2Genetically encoded actuators for acoustic manipulation

Publication Date: 2026.02.17 CALIFORNIA INST OF TECH

AI summary

Disclosed herein include methods, compositions, and kits suitable for use in sorting a population of cells. In some embodiments, the method comprises flowing a fluid sample comprising a population of cells through a microfluidic channel. The population of cells can be configured to express gas vesicles (GVs) in a context-dependent manner. The expression of GVs within a cell can increase the compressibility (β) and reduce the density (ρ) of said cell, thereby modulating the acoustic contrast (Φ) of said cell relative to the fluid in the microfluidic channel. The method can comprise applying ultrasound to the microfluidic channel. Applying ultrasound can generate acoustic standing wave(s) in the microfluidic channel, thereby positioning pressure antinode(s) in the microfluidic channel.