Abstract A029: Novel high-purity CTC isolation technology for downstream analysis: A “Cell- Circuit” magnetophoretic-microfluidic hybrid device
Authors: Chanhee Lee, Hun Heo, Youngwoo Park, Donghee Ko
Journal: Clinical Cancer Research (2024)

Abstract Circulating Tumor Cells are the only blood analytes that contain comprehensive multi-omic information regarding living tumor cells. As such, CTCs are an essential tool for the precise diagnosis of cancer. This has led to increased interest in both enumeration, and more significantly, the downstream analysis of bulk and single CTCs. One primary technical limitation that limits adoption of CTCs into routine clinical practice is the ability to effectively isolate CTCs from non-target cells. While several technologies have been developed and commercialized including initial clinical adoption, most technologies have fundamental limitations in sample purity which limits the quality of downstream analysis. Another limitation is the number of steps needed to complete enrichment, especially in high purity isolation where 2 techniques are usually required to be performed in sequence. The authors propose a novel, single-cell isolation technology called L:Cell™. This technology utilizes precise micro-magnetic patterns to allow immuno-magnetically labeled cells to be isolated individually and directed to user-defined locations. Such “Cell-Circuits” enable parallel, computer-circuit-like manipulation of a large array of single cells – combining both precision and throughput. Passive and active single-cell control is made possible by circuit components such as gates, single-cell capacitors, and transistors. The technology also enables the classification of cells based on size in addition to the presence of magnetic beads. A "passive component" performs its function under an external rotating magnetic field, manipulating cells without the need for an electrical current. The majority of circuitry on-chip are such passive components, which enable the device's key advantage of parallelized control. In contrast, an "active component" is designed in conjunction with passive components to create a local magnetic field at specific locations. This allows cells to be rerouted or manipulated on-demand. Using active components, users can selectively isolate individual cells (e.g., based on size, morphology, or fluorescence). While micro-magnetophoretic technology has been explored by various research teams, the authors have advanced this technology further by micro-magnetic simulation and integrating microfluidic technology. This integration improves the inlet and outlet structures for cell samples and the alignment of particles’ flow, thereby maximizing the commercialization potential of this sophisticated technology. In lab-scale modeling, the authors demonstrated a high separation purity level of 92%. By allowing manipulation at single-cell level using magnetic fields only, the technology minimizes any stress on the cells during isolation processes. The authors developed a user- friendly interface utilizing microfluidic channels for the extraction of CTCs from whole blood using this hybrid device. Additionally, the authors are conducting further adaptation studies to apply this technology to various downstream techniques, such as genomic analysis and protein profiling. Citation Format: Chanhee Lee, Hun Heo, Youngwoo Park, Donghee Ko. Novel high-purity CTC isolation technology for downstream analysis: A “Cell- Circuit” magnetophoretic-microfluidic hybrid device [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A029.