1 Vortex Biosciences Inc., Menlo Park, CA, USA.
2 Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
SLAS Technol. 2018 Feb;23(1):16-29. doi: 10.1177/2472630317738698.
Tumor tissue biopsies are invasive, costly, and collect a limited cell population not completely reflective of patient cancer cell diversity. Circulating tumor cells (CTCs) can be isolated from a simple blood draw and may be representative of the diverse biology from multiple tumor sites. The VTX-1 Liquid Biopsy System was designed to automate the isolation of clinically relevant CTC populations, making the CTCs available for easy analysis. We present here the transition from a cutting-edge microfluidic innovation in the lab to a commercial, automated system for isolating CTCs directly from whole blood. As the technology evolved into a commercial system, flexible polydimethylsiloxane microfluidic chips were replaced by rigid poly(methyl methacrylate) chips for a 2.2-fold increase in cell recovery. Automating the fluidic processing with the VTX-1 further improved cancer cell recovery by nearly 1.4-fold, with a 2.8-fold decrease in contaminating white blood cells and overall improved reproducibility. Two isolation protocols were optimized that favor either the cancer cell recovery (up to 71.6% recovery) or sample purity (≤100 white blood cells/mL). The VTX-1's performance was further tested with three different spiked breast or lung cancer cell lines, with 69.0% to 79.5% cell recovery. Finally, several cancer research applications are presented using the commercial VTX-1 system.
肿瘤组织活检具有侵袭性、费用高，且只能采集有限的细胞群体，无法完全反映患者癌细胞的多样性。循环肿瘤细胞 (CTC) 可从简单的血液采集分离出来，并且可能代表来自多个肿瘤部位的多样化生物学特性。VTX-1 液体活检系统旨在自动分离具有临床相关性的 CTC 群体，使 CTC 易于分析。本研究介绍了从实验室的尖端微流控创新到直接从全血中分离 CTC 的商业化、自动化系统的转变。随着该技术演变为商业系统，灵活的聚二甲基硅氧烷微流控芯片被刚性的聚甲基丙烯酸甲酯芯片所取代，细胞回收率提高了 2.2 倍。VTX-1 自动进行流体处理，使癌细胞回收率进一步提高了近 1.4 倍，白细胞污染减少了 2.8 倍，整体重现性得到提高。优化了两种分离方案，一种有利于癌细胞回收率（高达 71.6%的回收率），另一种有利于样品纯度（≤100 个白细胞/mL）。使用三种不同的乳腺癌或肺癌细胞系对 VTX-1 的性能进行了进一步测试，细胞回收率为 69.0%至 79.5%。最后，使用商业 VTX-1 系统介绍了几种癌症研究应用。
