Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Analyst. 2017 Jul 10;142(14):2558-2569. doi: 10.1039/c7an00290d.
Numerous applications in biology and medicine require the efficient and reliable separation of cells for disease diagnosis, genetic analysis, drug screening, and therapeutics. In this work, we demonstrate a novel technology that integrates a passive and an active device to separate, enrich and release cells on-demand from a complex blood sample, or cancer cells derived from a tissue biopsy. We exploit the high throughput (>1 mL min), size-based sorting capability of the passive spiral inertial microfluidic (iMF) device to focus particles/cells towards an active lateral cavity acoustic transducer (LCAT) device for size-selective enrichment. We demonstrate that this platform is capable of efficiently (>90%) removing smaller cells, such as RBCs in a blood sample or smaller cancer cells in a heterogeneous cell line, and providing 44 000× enrichment from the remaining sample within 5 min of device operation. Finally, we use this platform for two applications: selective enrichment of the side-population of DU-145 cells from tissue biopsy and isolation of larger monocytes from blood. Our platform integrates the high throughput (processing rate) capacity of spiral iMF with the high selectivity of LCAT, thereby offering a unique route for highly-selective, label-free particle/cell sorting, with potential application in lab-on-chip platforms for liquid biopsy and diagnostics applications.
在生物学和医学领域，有许多应用需要高效、可靠地分离细胞，以便进行疾病诊断、基因分析、药物筛选和治疗。在这项工作中，我们展示了一种新颖的技术，该技术集成了被动和主动装置，可按需从复杂的血液样本或组织活检中分离、富集和释放细胞，包括癌细胞。我们利用被动螺旋惯性微流控(iMF)装置高通量（>1mL min）、基于尺寸的分选能力，将颗粒/细胞聚焦到主动横向空腔声换能器(LCAT)装置，以实现尺寸选择性富集。我们证明了该平台能够高效（>90%）地去除较小的细胞，如血液样本中的 RBC 或异质细胞系中的较小癌细胞，并在 5 分钟的设备运行时间内，从剩余样本中提供 44,000 倍的富集。最后，我们将该平台用于两个应用：从组织活检中选择性富集侧群 DU-145 细胞，以及从血液中分离较大的单核细胞。我们的平台集成了螺旋 iMF 的高通量（处理速度）能力和 LCAT 的高选择性，从而为高度选择性、无标记的颗粒/细胞分选提供了一条独特的途径，有望应用于液体活检和诊断应用的片上实验室平台。
