Self-Focusing Acoustic Transducer for Contactless Cell Extraction

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Solution Overview

Problem

Current methods for extracting cells from a solid surface for regenerative medicine are limited by poor precision, low throughput, and potential damage to cells, with existing technologies like pipettes, micromanipulation, and laser capture microdissection being either imprecise, time-consuming, or requiring complex and expensive systems.

Innovation Solution

A self-focusing acoustic transducer (SFAT) device using focused ultrasonic waves to eject cells or particles contactlessly, allowing for precise and repeatable control of cell extraction and transfer without damaging the cells or the surrounding tissue, utilizing a Fresnel acoustic lens and piezoelectric substrate to generate high-intensity focused ultrasound for non-damaging cell detachment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If manual extraction methods (pipette, scoop, knife) are used, then device complexity is low, but manufacturing precision and measurement precision are poor

Engineering Contradiction:
Improveprecision of cell extractionVSAvoidcomplexity of extraction system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces manual mechanical extraction tools (pipette, scoop, knife) with a focused ultrasound system that uses acoustic waves to detach and eject cells. The FUS transducer generates focused ultrasonic waves that create mechanical resonance and cavitation in the liquid medium, enabling precise cell extraction without physical contact. This substitution of mechanical manual operations with acoustic field-based automation achieves high precision while maintaining relatively simple device architecture.

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

Solution Approach 2:

The patent utilizes parameter changes in the ultrasound field (frequency, intensity, focal depth) to precisely control cell extraction. By adjusting the focal depth of the ultrasound waves and controlling the acoustic pressure parameters, the system can selectively target and extract specific cells at different layers of the cell monolayer with high precision, transforming the extraction process from manual approximation to parameter-controlled precision.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If micromanipulation is used, then measurement precision is improved, but productivity decreases due to low throughput

Engineering Contradiction:
Improvethroughput of cell extractionVSAvoidtime required for extraction
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent employs periodic pulsed ultrasound actuation to extract multiple cells in rapid succession. The FUS system can be activated in a pulsed manner, with each pulse ejecting a droplet containing extracted cells. This periodic action enables high-throughput extraction by continuously producing droplets at rapid rates, dramatically improving productivity compared to single-cell micromanipulation methods while maintaining precision through controlled pulsed delivery.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent replaces time-consuming manual micromanipulation operations with automated acoustic field-based extraction. The focused ultrasound system can simultaneously process multiple cells across a large area of the cell monolayer, extracting cells in parallel rather than sequentially. This substitution of manual sequential operations with automated parallel acoustic processing achieves high throughput and reduces extraction time significantly.

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

3Productivity

If laser capture microdissection is used, then productivity is improved, but device complexity and cost increase

Engineering Contradiction:
Improvethroughput of cell extractionVSAvoidcomplexity of extraction system
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent replaces complex laser-based optical systems with a simpler acoustic field-based FUS system. Instead of using lasers for capture and mechanical tools for dissection, the system uses focused ultrasonic waves to directly detach and eject cells in a single automated step. This substitution of complex optical-mechanical laser systems with simpler acoustic field generation achieves high productivity while reducing device complexity and cost.

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

Solution Approach 2:

The patent extracts the essential function of cell extraction from complex multi-step laser capture microdissection procedures. By using focused ultrasound, the system directly extracts cells from the monolayer in a single action, eliminating the need for separate laser capture and mechanical dissection steps. This extraction approach maintains high throughput while significantly simplifying the overall system architecture.

Inventive Principle:
Principle #2Taking out (Extraction)

4Reliability

If conventional extraction methods are used, then device complexity is low, but object-affected harmful factors increase due to cell damage

Engineering Contradiction:
Improveintegrity of extracted cellsVSAvoiddamage to cells and surrounding tissue
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by focusing ultrasound energy at a specific focal depth where the cell monolayer is located. The FUS transducer generates a highly localized acoustic field that concentrates energy precisely at the target depth, enabling selective extraction of cells at that layer while leaving surrounding cells at different depths unaffected. This localized energy application maintains cell integrity by avoiding excessive energy distribution throughout the entire sample.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses liquid droplets as an intermediary medium between the ultrasound field and the cells. The FUS waves first act on the liquid medium, which then transfers the acoustic energy to the cells, causing them to detach and be ejected in droplet form. This intermediary liquid medium protects the cells from direct exposure to high-intensity acoustic energy, reducing mechanical damage while still achieving effective extraction.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 SFAT device enables high-precision, damage-free extraction and transfer of cells with controlled droplet size and frequency, achieving high throughput and allowing cells to proliferate without scarring, as demonstrated by successful ejection and re-cultivation of human RPE cells.

Implementation Method 1

The focused ultrasonic transducer includes a piezoelectric substrate having a top face and a bottom face

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 2

A Fresnel acoustic lens including a plurality of annular rings of air cavities disposed on the top face

Methodology Applied
Scientific EffectRefraction: Refraction

Implementation Method 3

self-focusing acoustic transducers (SFATs) based on Fresnel air-cavity lens

Methodology Applied
Scientific EffectAcoustic lens focusing: Acoustic Lens

Implementation Method 4

focused ultrasonic waves to eject cells or particles contactlessly

Methodology Applied
Scientific EffectAcoustic radiation pressure: Acoustic Radiation Pressure

Implementation Method 5

focused ultrasonic transducer positioned to focus an acoustic wave onto the substrate such that a droplet that includes at least one cell or particle is ejected

Methodology Applied
Scientific EffectUltrasonic vibration: Ultrasonic Vibration

Data Source

PatentUS12017210B2Contactless, damage-free, high-precision cell extraction and transfer through acoustic droplet ejection
Publication Date: 2024.06.25 UNIV OF SOUTHERN CALIFORNIA
  • US12017210B2 patent drawing
  • US12017210B2 patent drawing
  • US12017210B2 patent drawing

AI summary

A device for contactless, damage-free, high-precision cell and/or particle extraction and transfer through acoustic droplet ejection includes a substrate having a first surface and a second surface and a focused ultrasonic transducer positioned to focus an acoustic wave onto the substrate such that a droplet that includes at least one cell or particle is ejected from the bulk or from the first surface per each actuation of the focused ultrasonic transducer through droplet ejection. The substrate includes cells or particles inside the substrate or on top of the substrate. The focused ultrasonic transducer includes a piezoelectric substrate having a top face and a bottom face, a Fresnel acoustic lens including a plurality of annular rings of air cavities disposed on the top face, and a first patterned circular electrode disposed over the top face and a second patterned circular electrode disposed over the bottom face. The first patterned circular electrode overlaps the second patterned circular electrode.