Abstract 5374: Rapid microfluidic isolation and detection of circulating tumor cells/clusters with zero sample preparation

Abstract

Abstract Background: Circulating tumor cells (CTCs) and clusters of liquid biopsy permits continual access to phenotypic and genotypic landscape of primary and metastatic tumors for optimized personalized therapy. In addition, it holds the promise of deciphering the tumor heterogeneity which is one of the major sources of treatment resistance. Due to the extreme rarity of CTCs in peripheral blood, rapid and reliable isolation remains challenging amid new technologies being tested. Herein, we developed and demonstrated a novel microfluidic approach capable of direct isolation of CTCs and clusters from untreated whole blood within 20 min. Methods: Our microfluidic approach takes advantages of the intrinsic strong cell-cell interactions when whole blood flows in a microchannel, which leads to faster lateral migration of larger cells and thus label-free isolation of CTCs based on size. Our biochip integrates cell isolation and cell immobilization units and allows processing of untreated whole blood at high throughput (2 mL in 20 min). Immobilized CTCs and clusters were subsequently characterized onchip by immunocytochemistry as CD45-, CK+ and DAPI+. Results: Blood samples of 9 deidentified patients diagnosed with non-small-cell-lung cancer (NSCLC) were directly processed through our microfluidic biochip. 2 mL whole blood of each sample were used without pretreatment. Immunofluorescence assay identified at least 1 CTC in the blood samples from all patients (100%). CTC count ≥ 5 was found in 8/9 samples (89%). The median of CTC count was 9 per 2 mL blood. A maximum of 38 CTCs per 2 mL whole blood was found in the sample of a late stage patient. Grape-like CTC cluster was also detected in one of the nine samples (11%). Conclusions: These “proof of concept” results suggest that our novel, label-free microfluidic technology is capable of rapid isolation and detection of CTCs and clusters directly from patient peripheral blood without sample pretreatment. It completely spares the need of costly, time-consuming and laborious sample pretreatment required by other methods. Further validation studies with cases and controls using patient lung tumor compared to the obtained CTC from our microfluidic approach are required before its implementation in the real-world practice. Citation Format: Jian Zhou, Bin Liu, Qiyue Luan, Apurva Mallisetty, Alicia Hulbert, Ian Papautsky. Rapid microfluidic isolation and detection of circulating tumor cells/clusters with zero sample preparation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5374.