On-chip isolation and characterization of circulating tumor cells
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Early detection improves the prognosis of cancer patients significantly. Traditional cancer therapy is based on the biology of the primary tumor; however, it is usually the tumor dissemination to other parts of the body (process known as metastasis) that results in a negative prognosis and death. For this reason, the detection and characterization of circulating tumor cells (CTCs) in the blood of cancer patients are believed to be of high prognostic and therapeutic importance. A full tumor cell detection analysis can take more than a day. A lab-on-chip, integrating the many processing steps, would enable a faster, easy-to-use, cost-effective detection of tumor cells in blood.
Imec, together with its partners in the EU integrated project 'MIRACLE' RP95 proposes a method to detect cancer based on isolating circulating CTCs from blood, characterize them via their impedance spectrum, and by downstream molecular analysis. Imec has developed a microfluidic micropore sieving system to filter circulating tumor cells (or magnetically labeled circulating tumor cells) from whole blood. The sieve is made using conventional Si fabrication technologies resulting in a well controlled pore size, required to filter the circulating breast tumor cells from whole blood. The next version of the sieving device will include single- cell impedance analysis and single-cell lysis possibilities.
Fluorescene activated cell sorting (FACS) has been the workhorse of biologist researchers, because of its high throughput and single-cell sensitivity. It is mostly used to count blood cells; but can also be used for detecting rare events such as the occurrence of a circulating tumor cell. The primary shortcomings of modern FACS systems are equipment size and cost and contamination between different samples inhibiting its use as a point of care system. Imec is developing microfluidic cytometry systems, which could be part of mobile devices to be used at a patient's bedside or a doctor's office, depicted in figure below.
Schematic of one channel of imec's microfluidic cell sorter.
Flexible: the sorting algorithm is user definable and flexible and can differentiate cells or other biospecimen based on one or more properties derived from images. Those properties can relate to morphology, size, pigmentation or fluorescent properties such as coming from epithelial or nuclear markers of choice.
High throughput: the system aims to process cells at speeds similar or higher than current microfluidics FACS systems. It will do that using multiple streams that are fractionated in parallel, and intelligent image processing and decision algorithms.
Easy to use: the user interface is user and fully automated, to have minimal manual operations that can lead to contaminations and false analysis caused by inaccurate handlings. The system starts from whole blood.
Low cost and compact: compared to existing FACS systems this system is extremely compact and consists of very few expensive components, which allows the system to be used in situations where ordinary FACS are too big to use. Such situations may include point of care blood cell counting applications and/or bioprocess monitoring applications.