Why studying CTCs?
Circulating tumour cells (CTCs) represent a rare population of cells which have shed from a primary tumour into the bloodstream and are responsible for initiating metastases at distant sites. CTCs can be obtained via a minimally invasive ‘liquid biopsy’ to aid the diagnosis, prognosis and monitoring of disease, as well as to study resistance to treatment. The phenotypic heterogeneity of melanoma CTCs poses difficulties in isolating these cells using marker-dependent approaches and therefore other methods were sought.
Circulating Tumour Cells (CTCs) are extremely rare cells that have detached from solid tumours, travel in the bloodstream and can cause the cancer to spread. They are considered the seeds of metastasis and could be a clear indication of disease progression.
A blood test, or liquid biopsy that can detect and profile these CTCs presents a quick, non-invasive way to obtain real-time information about the cancer disease status. In combination with other diagnostic methods, doctors may be able to design specific responses to fight the diagnosed cancer.
Combining this insight with the ability to match drugs according to disease mutation and resistance, isolating wholly intact CTCs could be the potential gold standard for the detection of cancer metastasis.
All from a simple blood draw.
ClearCell® FX1 System:
The Next Generation Non-Invasive “Liquid Biopsy” for Cancer Management
The ClearCell® FX1 System, driven by the CTChip® FR, is one of the world’s first automated cell retrieval systems that can enrich wholly intact and viable Circulating Tumour Cells (CTCs) from small amounts of blood in a relatively short time. Combined with the high levels of purity, the CTCs are enriched in suspension, which allows for easy integration with downstream molecular analyses and diagnostic assays. This means that researchers and clinicians can use these insights to provide timely, tailored treatment options.
Workflow
How it works?
The ClearCell® FX1 System, driven by the CTChip® FR1S. This microfluidic biochip isolates CTCs based on size, deformability and inertia, relative to other blood components, by using inherent Dean vortex flows present in curvilinear channels, termed Dean Flow Fractionation (DFF).
Through the process of DFF, blood cells separate and distribute themselves within the channels of the CTChip® FR1S, with the larger cells along the inner wall and the smaller cells away from it. The ClearCell® FX1 System thus enables effective and rapid separation without compromising the quality of retrieved cells.
Applications
Fluorescence In Situ Hybridization (FISH)
CTCs isolated using the ClearCell® FX System can be characterized by FISH, a technique that allows cytogeneticists to identify chromosomal abnormalities in cells. Fluorescent probes that bind specific chromosomal locations are applied to the cells, and the presence or absence of specific DNA sequences is detected by noting the location and counts of fluorescent dots after probe hybridization.
Cell Culture
The ClearCell® FX System isolates CTCs with high viability and intergrity, so the cells can be subsequently cultured in vitro. The in vitro culture of cancer cells has numerous applications, ranging from studying the biology of cancer to the development of novel therapeutics. Culturing CTCs could enable the creation of patient-derived tumour xenograft models that could provide invaluable insights into metastasis.
Molecular Analysis
Gene mutations can be key predictors of cancer. The targeted molecular analysis of CTCs could offer a powerful companion diagnostic test for treatment selection and patient monitoring. The ClearCell® FX System yields CTC-enriched samples that can be seamlessly integrated into troditional laboratory protocols for DNA and RNA extraction. Options for analysis include qPCR, Nanostring, dPCR, or NGS for targeted molecular profiling
Immunofluorescence (IF)/Immunocytochemistry (ICC)
The visualization of antibodies specific to cellular antigens provides a simple way to differentiate cancer cells from healthy cells. Cells enriched using the ClearCell® FX System can be stained with various antibodies to identify CTCs, as well as to measure target antigen expression levels
CTC Patient-Derived Xenograft (CTC PDX)
Patients' CTCs isolated using the ClearCell® FX System can be implanted into immune-deficient mice to create patient-specific CTC-derived xenograft models (CTC PDX). These CTC PDX models will be used to develop metastatic tumour models, study drug sensitivity and determine patient specific dosage, a hallmark of personalised medicine. Additionally, these models can be used by pharmaceutical companies for novel drug development and clinical studies.
Protein Analysis
CTCs isolated using the ClearCell® FX System retain high cell integrity and can be used for a wide range of protein analysis. Protein analysis helps identify intracellular pathways in CTCs, providing important information on pathway-specific drug activity and guide dosing selection. This is an important tool for targeted drug development and treatment, such as PD-L1 for immunotherapy.
