Acoustic T Cell Separation Using Standing Waves
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Solution Overview
Problem
Current methods for separating Jurkat T cells from cell cultures, such as centrifugation and physical filtration, often damage the cells, making it desirable to develop a non-damaging separation and filtration process.
Innovation Solution
The use of acoustophoretic systems that generate multi-dimensional acoustic standing waves to separate biological cells from a host fluid, utilizing ultrasonic transducers and reflectors to create a flow chamber where cells can be trapped, agglomerate, and settle out without physical filters, allowing for efficient cell concentration and clarification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If centrifugation or physical filtration is used to separate Jurkat T cells from cell cultures, then cell separation is achieved, but cell damage occurs
Solution Approach 1:
The patent replaces mechanical separation methods (centrifugation and physical filtration) with an acoustic field-based separation system. Ultrasonic transducers generate acoustic standing waves that exert acoustic radiation pressure on cells, enabling separation without mechanical stress or physical filters that would damage cell integrity.
Solution Approach 2:
The patent introduces an acoustic field as an intermediary between the separation force and the cells. The acoustic standing waves create regions of high and low pressure that indirectly manipulate cell positioning and separation, avoiding direct mechanical contact that would cause damage.
2Reliability
If acoustophoresis with ultrasonic transducers is used to separate cells, then cell damage is minimized, but device complexity increases
Solution Approach 1:
The patent divides the separation system into distinct functional modules: ultrasonic transducers for generating acoustic fields, a flow chamber for cell suspension introduction, and collection systems for separated cells. This modular segmentation makes the complex acoustophoretic system more manageable and easier to implement.
Solution Approach 2:
The patent designs the flow chamber to serve multiple functions: introducing cell suspension, maintaining laminar flow, providing acoustic field interaction, and enabling cell collection. This multi-functionality reduces the need for separate components, thereby reducing overall system complexity despite the sophisticated separation mechanism.
3Productivity
If multi-dimensional acoustic standing waves are generated to trap and aggregate cells, then separation efficiency is improved, but energy consumption increases
Solution Approach 1:
The patent utilizes periodic acoustic oscillations from ultrasonic transducers to create standing waves that periodically trap and release cells. This periodic action allows cells to be progressively aggregated and separated through repeated cycles of acoustic forcing, improving separation efficiency while using controlled energy input.
Solution Approach 2:
The patent optimizes separation efficiency by adjusting acoustic parameters (frequency, amplitude, wavelength) and flow conditions (flow rate, residence time). By changing these parameters, the system achieves effective cell aggregation and separation while minimizing excessive energy consumption, balancing productivity and energy use.
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 method effectively concentrates cells while minimizing damage, achieving a cell concentration twice that of the original mixture with a volume reduction of half, and can be used in dual-pass systems for enhanced separation efficiency.
Implementation Method 1
generate multi-dimensional acoustic standing waves to separate biological cells from a host fluid, utilizing ultrasonic transducers and reflectors to create a flow chamber where cells can be trapped
Implementation Method 2
acoustophoresis is the separation of particles and secondary fluids from a primary or host fluid using high intensity acoustic standing waves
Implementation Method 3
at least one ultrasonic transducer includes a piezoelectric material configured to be driven to create a multi-dimensional acoustic standing wave in the flow chamber
Implementation Method 4
subsequently settle out of the host fluid due to enhanced gravitational settling forces
Data Source
AI summary
Acoustophoretic devices and methods for separating biological cells (particularly T-cells) from other fluids/materials using multi-dimensional acoustic standing waves are disclosed. The devices include an inlet, at least two outlets, and a flow chamber having an ultrasonic transducer-reflector pair. Specifically, T cells, B cells, or NK cells can be separated from other blood components. A dual-pass acoustophoretic system including two acoustophoretic devices arranged in series and fluidly connected to one another is also illustrated. Means for pre-chilling the mixture prior to separation in the devices or system can be used to improve retention, concentration, and clarification and to prevent outgassing.