Marker-Free Isolation of Circulating Tumor Cells from Blood of Patients

Marker-Free Isolation of Circulating Tumor Cells from Blood of Patients

By Grigori Singovski

Metastasis occurs when cancerous cells spread from the primary tumor site to invade distant organs and are responsible for more than 90% of deaths. Spreading cancer cells do so by utilizing the lymphatic system and blood stream in an unknown way. The cancer cells detected in the blood stream are called circulating tumor cells (CTCs) and are extremely rare. Typically, a 10mL blood sample from a cancer patient contains billions of healthy blood cells and only about a dozen of CTCs, making impossible any attempt of diagnosis or research.

In 2014, a new technology called CTC-iChip (see figure below) was engineered in order to isolate rare CTCs from patients’ blood without using any specific surface marker as no marker has been proved fully reliable so far since they change during the progression of the disease. The blood is introduced into a microfluidic chip composed of two chambers and magnetic beads, where blood cell specific markers are added.


The role of the first chamber, called deterministic lateral displacement (DLD), is to segregate cells with or without a nucleus. Indeed, most of the blood is composed of none nucleated cells (red blood cells and platelets) that are lighter that than the cells of interest. The cells are then aligned before reaching the second chamber, called the magnetophoresis chamber. The CTC population is then refined by removing the remaining healthy nucleated blood cells using magnetic beads, which attach to these cells, and a magnetic field. The remaining cell fraction contains mostly CTCs and is ready to be analyzed and diagnosed.

This ground-breaking technology allows, with a high work flow, the isolation of CTCs in a sufficient quantity to perform further analyses such as DNA/RNA studies, surface marker investigation and cell identification. The CTC-iChip will facilitate a clearer and more accurate diagnosis for patients suffering from metastatic cancers.


Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nezihi Murat Karabacak, Philipp S Spuhler, Fabio Fachin, Eugene J Lim, Vincent Pai, Emre Ozkumur, Joseph M Martel, Nikola Kojic, Kyle Smith, Pin-i Chen, Jennifer Yang, Henry Hwang, Bailey Morgan, Julie Trautwein, Thomas A Barber, Shannon L Stott, Shyamala Maheswaran, Ravi Kapur, Daniel A Haber & Mehmet Toner. Nature Protocols 9, 694–710 (2014).

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