Partial thermal imidization of polyelectrolyte multilayer cell tethering surfaces (TetherChip) enables efficient cell capture and microtentacle fixation for circulating tumor cell analysis
JournalLab on a chip
PublisherRoyal Society of Chemistry
MetadataShow full item record
AbstractThe technical challenges of imaging non-adherent tumor cells pose a critical barrier to understanding tumor cell responses to the non-adherent microenvironments of metastasis, like the bloodstream or lymphatics. In this study, we optimized a microfluidic device (TetherChip) engineered to prevent cell adhesion with an optically-clear, thermal-crosslinked polyelectrolyte multilayer nanosurface and a terminal lipid layer that simultaneously tethers the cell membrane for improved spatial immobilization. Thermal imidization of the TetherChip nanosurface on commercially-available microfluidic slides allows up to 98% of tumor cell capture by the lipid tethers. Importantly, time-lapse microscopy demonstrates that unique microtentacles on non-adherent tumor cells are rapidly destroyed during chemical fixation, but tethering microtentacles to the TetherChip surface efficiently preserves microtentacle structure post-fixation and post-blood isolation. TetherChips remain stable for more than 6 months, enabling shipment to distant sites. The broad retention capability of TetherChips allows comparison of multiple tumor cell types, revealing for the first time that carcinomas beyond breast cancer form microtentacles in suspension. Direct integration of TetherChips into the Vortex VTX-1 CTC isolation instrument shows that live CTCs from blood samples are efficiently captured on TetherChips for rapid fixation and same-day immunofluorescence analysis. Highly efficient and unbiased label-free capture of CTCs on a surface that allows rapid chemical fixation also establishes a streamlined clinical workflow to stabilize patient tumor cell samples and minimize analytical variables. While current studies focus primarily on CTC enumeration, this microfluidic device provides a novel platform for functional phenotype testing in CTCs with the ultimate goal of identifying anti-metastatic, patient-specific therapies.
non adherent tumor cells
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85089405744&doi=10.1039%2fd0lc00207k&partnerID=40&md5=d4a8c57ceeca73d8389cb7acfc7ac808; http://hdl.handle.net/10713/13571
- Nanoroughened adhesion-based capture of circulating tumor cells with heterogeneous expression and metastatic characteristics.
- Authors: Chen W, Allen SG, Reka AK, Qian W, Han S, Zhao J, Bao L, Keshamouni VG, Merajver SD, Fu J
- Issue date: 2016 Aug 8
- Lipid tethering of breast tumor cells enables real-time imaging of free-floating cell dynamics and drug response.
- Authors: Chakrabarti KR, Andorko JI, Whipple RA, Zhang P, Sooklal EL, Martin SS, Jewell CM
- Issue date: 2016 Mar 1
- Liquid biopsy using the nanotube-CTC-chip: capture of invasive CTCs with high purity using preferential adherence in breast cancer patients.
- Authors: Loeian MS, Mehdi Aghaei S, Farhadi F, Rai V, Yang HW, Johnson MD, Aqil F, Mandadi M, Rai SN, Panchapakesan B
- Issue date: 2019 Jun 7
- High-purity and label-free isolation of circulating tumor cells (CTCs) in a microfluidic platform by using optically-induced-dielectrophoretic (ODEP) force.
- Authors: Huang SB, Wu MH, Lin YH, Hsieh CH, Yang CL, Lin HC, Tseng CP, Lee GB
- Issue date: 2013 Apr 7
- Precisely Enumerating Circulating Tumor Cells Utilizing a Multi-Functional Microfluidic Chip and Unique Image Interpretation Algorithm.
- Authors: Zhou M, Zheng H, Wang Z, Li R, Liu X, Zhang W, Wang Z, Li H, Wei Z, Hu Z
- Issue date: 2017