Acoustic Buffer Switching in Microchannels for Timed Cell Exposure
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for timed, sequential exposure of particles to reagents and buffers, such as in electroporation processes, are limited by slow buffer exchange rates and adverse effects on cell health due to prolonged residence times in low-conductivity buffers, which can lead to cell death and inefficient payload delivery.
Innovation Solution
A microfluidic device utilizing parallel co-flow streams with acoustic manipulation enables rapid buffer switching and precise control over particle residence times, allowing for sequential exposure to different fluid streams through acoustic radiation pressure, facilitating quick transitions between buffers and reagents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If traditional centrifugation and resuspension methods are used for buffer exchange, then buffer exchange can be performed, but the process is slow and requires cells to reside in each buffer for several minutes
Solution Approach 1:
The patent replaces the mechanical centrifugation-based buffer exchange system with an acoustophoretic manipulation system. Acoustic radiation forces generated by ultrasonic transducers enable contactless, rapid manipulation of cell position and buffer exchange, eliminating the need for centrifugation and resuspension steps that require prolonged cell residence in buffers.
Solution Approach 2:
The patent introduces acoustic radiation pressure as an intermediary force to mediate buffer exchange. By using acoustic standing waves created by ultrasonic transducers, the system can rapidly transfer cells between different buffer streams without direct mechanical contact, achieving fast buffer exchange with minimal cell residence time in each buffer.
2Object-affected harmful factors
If cells are electroporated in low-conductivity electroporation buffers, then the amount of electrical current and heat generated is reduced, but cells can only survive for a very limited amount of time in these buffers
Solution Approach 1:
The patent enables cells to rapidly skip through the low-conductivity electroporation buffer stream using acoustophoresis. Cells are quickly transported into the electroporation buffer, subjected to the electric field pulse, and then rapidly transferred out to a recovery buffer, minimizing the total time cells spend in the harmful low-conductivity environment to seconds or less.
Solution Approach 2:
The patent performs preliminary acoustic manipulation to position cells precisely in the electroporation buffer stream before the actual electroporation event. This allows cells to be pre-positioned in the optimal location for electroporation while maintaining minimal exposure time to the low-conductivity buffer, ensuring both effective electroporation and cell survival.
3Ease of operation
If traditional bulk electroporation methods are used, then multiple payloads can be delivered sequentially, but the process involves touch labor and requires cells to reside in each buffer for several minutes
Solution Approach 1:
The patent replaces manual touch-based operations with an automated acoustophoretic manipulation system. Ultrasonic transducers provide contactless, programmable control over cell positioning and buffer exchange, eliminating the need for manual centrifugation, resuspension, and buffer transfer operations while enabling rapid sequential payload delivery.
Solution Approach 2:
The patent employs periodic acoustic actuation to enable sequential delivery of multiple payloads. By controlling the timing and duration of acoustic field application, the system can rhythmically transfer cells between different buffer streams containing different payloads, achieving automated sequential delivery with precise temporal control and minimal cell residence time in each buffer.
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 allows for rapid buffer exchanges in seconds or less, maintaining cell viability and enhancing the efficiency of processes like electroporation by minimizing exposure to harmful buffers and controlling payload delivery kinetics.
Implementation Method 1
moves the particles from a first flowing fluid to a second flowing fluid, then moves the particles out of the second flowing fluid using acoustic radiation generated by the acoustic actuator device
Data Source
AI summary
A system for sequential exposure of particles to different fluid streams includes an acoustic actuator device for acoustically driving one or more substrates and a microchannel device of the one or more substrates that receive particles in a first flowing fluid, moves the particles to a second flowing fluid, then moves the particles out of the second flowing fluid using acoustic radiation generated by the acoustic actuator device. The system can control residence times in the streams. According to one use, the first flowing fluid is a cell buffer and the second flowing media is an electroporation buffer. An electroporation system is placed in or downstream of the acoustic actuator device. However, in other uses, the second flowing media might be a wash buffer.