Microfluidic Acoustic Cell Separation via Additive Pretreatment

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Solution Overview

Problem

Current cell separation technologies, such as centrifugation and magnetic separation, are limited in their ability to selectively separate specific cell types like leukocyte subclasses from mixed cell suspensions, often requiring complex procedures, foreign particles, and are not scalable for both small and large sample volumes effectively.

Innovation Solution

The method involves pretreating biofluids with additives to alter cell properties like size, density, and aggregation potential, followed by acoustic energy application in microfluidic channels to separate target cells from non-target cells based on size and density differences, allowing for continuous and efficient separation without the need for affinity-based capture particles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If centrifugation or magnetic separation is used to separate cells, then separation can be achieved, but the procedure becomes complex and requires foreign particles

Engineering Contradiction:
Improveseparation effectivenessVSAvoidprocedure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical separation systems (centrifugation, magnetic separation) with acoustic field-based separation. Acoustic radiation forces act on cells based on their physical properties (size, density, compressibility) without requiring mechanical complexity or foreign particles, thus simplifying the procedure while maintaining separation effectiveness.

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

Solution Approach 2:

The patent introduces acoustic waves as an intermediary mechanism to mediate cell separation. Instead of direct mechanical or magnetic interaction, acoustic energy serves as a mediator that exerts radiation forces on cells, enabling separation based on intrinsic cell properties without requiring antibodies or magnetic beads.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If conventional separation methods are used, then cell separation can be performed, but they are not scalable for both small and large sample volumes

Engineering Contradiction:
Improveseparation capabilityVSAvoidscalability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The acoustic separation system is designed to be universally applicable across different sample volumes. By adjusting acoustic power, flow rate, and channel dimensions, the same fundamental mechanism can effectively separate cells in both small and large volumes, providing scalability that conventional methods lack.

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

Solution Approach 2:

The patent utilizes parameter changes in acoustic fields (frequency, power, waveform) and flow conditions to adapt the separation process to different sample volumes. This allows the system to maintain effective separation across a wide range of volumes without requiring fundamentally different approaches.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If acoustic energy is applied to separate cells, then separation based on size and density is achieved, but pretreatment with additives is required to alter cell properties

Engineering Contradiction:
Improveseparation selectivityVSAvoidpretreatment complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pretreating cells with additives that alter their physical properties (size, density, compressibility) before acoustic separation. This preliminary modification enhances the acoustic contrast between different cell types, improving separation selectivity. The pretreatment is a one-time step that enables more effective subsequent acoustic separation.

Inventive Principle:
Principle #10Preliminary action

4Measurement precision

If foreign particles or antibodies are used for cell capture, then specific cell types can be targeted, but safety concerns arise and the process becomes more complex

Engineering Contradiction:
Improvecell type specificityVSAvoidsafety concerns
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent uses acoustic waves as a safe intermediary that interacts with cells through their intrinsic physical properties rather than requiring foreign particles or antibodies. Acoustic radiation forces can selectively target specific cell types based on size, density, and compressibility differences, achieving specificity without introducing potentially harmful substances into the biological sample.

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

This approach enables high-purity separation of target cells, such as lymphocytes and stem cells, from biofluids, achieving enriched cell concentrations and scalability for various sample volumes without the use of antibodies or foreign particles, improving upon existing methods by enhancing separation efficiency and safety.

Implementation Method 1

applying acoustic energy to the microfluidic separation channel to accumulate target cells within a primary stream along the separation channel and accumulate non-target cells within a secondary stream

Methodology Applied
Scientific EffectAcoustic radiation pressure: Acoustic Radiation Pressure

Data Source

PatentUS20190290829A1Acoustic separation for bioprocessing
Publication Date: 2019.09.26 THE CHARLES STARK DRAPER LABORATORY INC
  • US20190290829A1 patent drawing
  • US20190290829A1 patent drawing
  • US20190290829A1 patent drawing

AI summary

A method for separating cells in a biofluid includes pretreating the biofluid by introducing an additive, flowing the pretreated biofluid through a microfluidic separation channel, and applying acoustic energy to the microfluidic separation channel. A system for microfluidic cell separation, capable of separating target cells from non-target cells in a biofluid includes at least one microfluidic separation channel, a source of biofluid, a source of additive, and at least one acoustic transducer coupled to the microfluidic separation channel. A kit for microfluidic cell separation includes a microfluidic separation channel connected to an acoustic transducer, a source of an additive, and instructions for use.