BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Boston, MA, USA.
Cancer Center, Massachusetts General Hospital, Boston, MA, USA.
Nature. 2023 Oct;622(7984):735-741. doi: 10.1038/s41586-023-06517-3. Epub 2023 Oct 25.
Microfluidics have enabled notable advances in molecular biology, synthetic chemistry, diagnostics and tissue engineering. However, there has long been a critical need in the field to manipulate fluids and suspended matter with the precision, modularity and scalability of electronic circuits. Just as the electronic transistor enabled unprecedented advances in the automatic control of electricity on an electronic chip, a microfluidic analogue to the transistor could enable improvements in the automatic control of reagents, droplets and single cells on a microfluidic chip. Previous works on creating a microfluidic analogue to the electronic transistor did not replicate the transistor's saturation behaviour, and could not achieve proportional amplification, which is fundamental to modern circuit design. Here we exploit the fluidic phenomenon of flow limitation to develop a microfluidic element capable of proportional amplification with flow-pressure characteristics completely analogous to the current-voltage characteristics of the electronic transistor. We then use this microfluidic transistor to directly translate fundamental electronic circuits into the fluidic domain, including the amplifier, regulator, level shifter, logic gate and latch. We also combine these building blocks to create more complex fluidic controllers, such as timers and clocks. Finally, we demonstrate a particle dispenser circuit that senses single suspended particles, performs signal processing and accordingly controls the movement of each particle in a deterministic fashion without electronics. By leveraging the vast repertoire of electronic circuit design, microfluidic-transistor-based circuits enable fluidic automatic controllers to manipulate liquids and single suspended particles for lab-on-a-chip platforms.
微流控技术在分子生物学、合成化学、诊断学和组织工程学等领域取得了显著的进展。然而,该领域长期以来一直迫切需要一种能够以电子电路的精度、模块化和可扩展性来操控流体和悬浮物质的技术。正如电子晶体管使电子芯片上的电力自动控制取得了前所未有的进展一样,晶体管的微流体模拟技术可以改进微流控芯片上试剂、液滴和单细胞的自动控制。以前创建电子晶体管微流体模拟的工作未能复制晶体管的饱和行为,也无法实现比例放大,而比例放大是现代电路设计的基础。在这里,我们利用流限的流体现象来开发一种能够进行比例放大的微流元件,其流量-压力特性与电子晶体管的电流-电压特性完全相似。然后,我们使用这种微流晶体管将基本的电子电路直接转换到流体领域,包括放大器、稳压器、电平转换器、逻辑门和锁存器。我们还将这些构建模块组合在一起,创建更复杂的流体控制器,如定时器和时钟。最后,我们展示了一种粒子分配器电路,它可以检测单个悬浮粒子,进行信号处理,并相应地以确定性方式控制每个粒子的运动,无需电子元件。通过利用电子电路设计的丰富技术,基于微流晶体管的电路使流体自动控制器能够用于操控液体和单个悬浮粒子,以实现芯片实验室平台。