Esfandyarpour Rahim, DiDonato Matthew J, Yang Yuxin, Durmus Naside Gozde, Harris James S, Davis Ronald W
Department of Biochemistry, School of Medicine, Stanford University, Stanford, CA 94304.
Stanford Genome Technology Center, Stanford University, Stanford, CA 94304.
Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):E1306-E1315. doi: 10.1073/pnas.1621318114. Epub 2017 Feb 6.
Isolation and characterization of rare cells and molecules from a heterogeneous population is of critical importance in diagnosis of common lethal diseases such as malaria, tuberculosis, HIV, and cancer. For the developing world, point-of-care (POC) diagnostics design must account for limited funds, modest public health infrastructure, and low power availability. To address these challenges, here we integrate microfluidics, electronics, and inkjet printing to build an ultra-low-cost, rapid, and miniaturized lab-on-a-chip (LOC) platform. This platform can perform label-free and rapid single-cell capture, efficient cellular manipulation, rare-cell isolation, selective analytical separation of biological species, sorting, concentration, positioning, enumeration, and characterization. The miniaturized format allows for small sample and reagent volumes. By keeping the electronics separate from microfluidic chips, the former can be reused and device lifetime is extended. Perhaps most notably, the device manufacturing is significantly less expensive, time-consuming, and complex than traditional LOC platforms, requiring only an inkjet printer rather than skilled personnel and clean-room facilities. Production only takes 20 min (vs. up to weeks) and $0.01-an unprecedented cost in clinical diagnostics. The platform works based on intrinsic physical characteristics of biomolecules (e.g., size and polarizability). We demonstrate biomedical applications and verify cell viability in our platform, whose multiplexing and integration of numerous steps and external analyses enhance its application in the clinic, including by nonspecialists. Through its massive cost reduction and usability we anticipate that our platform will enable greater access to diagnostic facilities in developed countries as well as POC diagnostics in resource-poor and developing countries.
从异质群体中分离和鉴定稀有细胞及分子对于疟疾、结核病、艾滋病毒和癌症等常见致命疾病的诊断至关重要。对于发展中世界而言,即时护理(POC)诊断设计必须考虑到资金有限、公共卫生基础设施薄弱以及电力供应不足等因素。为应对这些挑战,我们在此整合了微流体技术、电子技术和喷墨打印技术,构建了一个超低成本、快速且小型化的芯片实验室(LOC)平台。该平台能够进行无标记快速单细胞捕获、高效细胞操作、稀有细胞分离、生物物种的选择性分析分离、分选、浓缩、定位、计数和鉴定。小型化形式允许使用少量样品和试剂。通过将电子元件与微流体芯片分开,前者可重复使用,从而延长了设备的使用寿命。也许最值得注意的是,与传统的LOC平台相比,该设备的制造成本显著降低、耗时更少且复杂度更低,仅需一台喷墨打印机,而无需技术人员和洁净室设施。生产仅需20分钟(相比长达数周),成本仅为0.01美元——这在临床诊断中是前所未有的成本。该平台基于生物分子的固有物理特性(如大小和极化率)运行。我们展示了该平台的生物医学应用并验证了细胞活力,其众多步骤和外部分析的多重化和集成增强了其在临床中的应用,包括非专业人员的应用。通过大幅降低成本和提高易用性,我们预计我们的平台将使发达国家有更多机会使用诊断设施,并使资源匮乏和发展中国家能够进行即时护理诊断。