Stockslager Max A, Olcum Selim, Knudsen Scott M, Kimmerling Robert J, Cermak Nathan, Payer Kristofor R, Agache Vincent, Manalis Scott R
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Rev Sci Instrum. 2019 Aug;90(8):085004. doi: 10.1063/1.5100861.
Measuring the size of micron-scale particles plays a central role in the biological sciences and in a wide range of industrial processes. A variety of size parameters, such as particle diameter, volume, and mass, can be measured using electrical and optical techniques. Suspended microchannel resonators (SMRs) are microfluidic devices that directly measure particle mass by detecting a shift in resonance frequency as particles flow through a resonating microcantilever beam. While these devices offer high precision for sizing particles by mass, throughput is fundamentally limited by the small dimensions of the resonator and the limited bandwidth with which changes in resonance frequency can be tracked. Here, we introduce two complementary technical advancements that vastly increase the throughput of SMRs. First, we describe a deconvolution-based approach for extracting mass measurements from resonance frequency data, which allows an SMR to accurately measure a particle's mass approximately 16-fold faster than previously possible, increasing throughput from 120 particles/min to 2000 particles/min for our devices. Second, we describe the design and operation of new devices containing up to 16 SMRs connected fluidically in parallel and operated simultaneously on the same chip, increasing throughput to approximately 6800 particles/min without significantly degrading precision. Finally, we estimate that future systems designed to combine both of these techniques could increase throughput by nearly 200-fold compared to previously described SMR devices, with throughput potentially as high as 24 000 particles/min. We envision that increasing the throughput of SMRs will broaden the range of applications for which mass-based particle sizing can be employed.
测量微米级颗粒的大小在生物科学和众多工业过程中都起着核心作用。可以使用电学和光学技术测量各种尺寸参数，如颗粒直径、体积和质量。悬浮微通道谐振器（SMR）是一种微流体装置，当颗粒流经谐振微悬臂梁时，通过检测共振频率的变化直接测量颗粒质量。虽然这些装置在通过质量对颗粒进行尺寸测量方面具有高精度，但通量从根本上受到谐振器小尺寸以及跟踪共振频率变化的有限带宽的限制。在此，我们介绍两项互补的技术进步，它们极大地提高了SMR的通量。首先，我们描述了一种基于反卷积的方法，用于从共振频率数据中提取质量测量值，这使得SMR能够以比以前快约16倍的速度准确测量颗粒质量，对于我们的装置，通量从120个颗粒/分钟提高到2000个颗粒/分钟。其次，我们描述了新型装置的设计和操作，该装置包含多达16个以流体方式并联连接并在同一芯片上同时运行的SMR，通量提高到约6800个颗粒/分钟，而不会显著降低精度。最后，我们估计，与先前描述的SMR装置相比，设计用于结合这两种技术的未来系统通量可能提高近200倍，通量可能高达24000个颗粒/分钟。我们设想，提高SMR的通量将拓宽基于质量的颗粒尺寸测量可应用的范围。
