Acoustic Flow Cytometry Particle Focusing and Velocity Control

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Solution Overview

Problem

Traditional flow cytometry faces challenges in high-throughput analysis and efficient rare event detection due to short particle transit times, inability to redirect or hold particles at interrogation points, and limitations in sensitivity and resolution, which existing methods have not adequately addressed.

Innovation Solution

The development of acoustic flow cytometry systems that use acoustic radiation pressure to focus and reorient particles, allowing for longer transit times and improved sensitivity by controlling particle velocity and concentration, enabling efficient detection of rare events without increasing photobleaching or background scatter.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If particles flow at very fast linear velocities through the interrogation point, then high-throughput analysis is achieved, but transit time is too short (1-10 μs) limiting sensitivity and resolution

Engineering Contradiction:

Improvehigh-throughput analysisVSAvoidsensitivity and resolution

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The system dynamically adjusts particle velocity by controlling sheath fluid flow rate, allowing particles to be accelerated for high-throughput analysis or decelerated for enhanced sensitivity and resolution during interrogation

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The system changes the flow velocity parameter of particles by adjusting sheath fluid pressure and flow rate, enabling optimization between throughput (high velocity) and measurement precision (low velocity) based on experimental requirements

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If sheath fluid is used to focus particles, then particles can be concentrated to a small core diameter, but flow cannot be reversed and particles cannot be held at the interrogation point

Engineering Contradiction:

Improveparticle concentrationVSAvoidflow control flexibility

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent replaces the mechanical hydrodynamic focusing system with an acoustic field-based focusing system, allowing non-contact control of particle positioning and flow direction without requiring high-velocity sheath fluid

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The acoustic focusing system allows dynamic adjustment of particle flow direction and positioning by changing acoustic field parameters, enabling flow reversal and particle holding at interrogation points that were impossible with traditional hydrodynamic focusing

Inventive Principle:

Principle #15Dynamics

3Measurement precision

If photon flux is increased to extract more signal, then detection sensitivity improves, but fluorophores photobleach and background scatter increases

Engineering Contradiction:

Improvesignal detectionVSAvoidphotobleaching and background scatter

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The system uses feedback control to optimize photon flux levels, adjusting excitation intensity based on detected signal quality to achieve sufficient detection sensitivity while preventing fluorophore photobleaching and minimizing background scatter

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The system dynamically adjusts photon flux intensity during particle interrogation, using higher flux only when necessary for dim signals and lower flux for bright signals, thereby reducing overall photobleaching while maintaining detection sensitivity

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

Acoustic flow cytometry systems achieve high-throughput analysis with enhanced sensitivity and resolution, enabling the detection of rare events more efficiently and effectively than traditional methods, with improved photon collection and reduced photobleaching.

Implementation Method 1

at least one vibration producing transducer coupled to the capillary, the at least one vibration producing transducer being configured to produce an acoustic signal inducing acoustic radiation pressure within the sample channel to acoustically concentrate particles

Methodology Applied

Scientific EffectAcoustic radiation pressure: Acoustic Radiation Pressure

Data Source

PatentEP2507639B1Apparatuses, systems, methods, and computer readable media for acoustic flow cytometry

Publication Date: 2020.04.01 LIFE TECHNOLOGIES CORP

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Figure 3~4B
Figure 5A~5D

AI summary

A flow cytometer includes a capillary having a sample channel; at least one vibration producing transducer coupled to the capillary, the at least one vibration producing transducer being configured to produce an acoustic signal inducing acoustic radiation pressure within the sample channel to acoustically concentrate particles flowing within a fluid sample stream in the sample channel; and an interrogation source having a violet laser and a blue laser, the violet and blue lasers being configured to interact with at least some of the acoustically concentrated particles to produce an output signal.