A microfluidic device that has the ability to catch and release circulating tumor cells (CTCs) has been developed by bioengineers at Lehigh University. Now Yaling Liu and his team are in the early stages of testing the device in a clinical setting.
"Our circulating tumor cell device can release a tumor cell captured from a blood sample, enabling single cell analysis," says Liu. "It could be used to check the effectiveness of treatment, by identifying the amount of tumor cells circulating. Conducting genetic testing on a released single cell could also reveal whether the primary tumor had metastasized, as metastasized cells have unique genetic markers."
The device could also be used to check the effectiveness of cancer gene therapy. "Genetic tests could be performed on the released CTCs, indicating if the gene therapy is triggering changes in gene expression," says Liu.
Liu is presenting some of his findings today at The Future of Medicine meeting in Istanbul.
Liu's device is part of a clinical drug trial for melanoma and renal cancers at the Lehigh Valley Cancer Institute. Funding for the study was provided by the Andy Derr Foundation for Kidney Cancer Research. The first stage of the trial, which involved an analysis of circulating tumor cells from a single blood draw of several dozen patients, has demonstrated strong potential, Liu says.
"The next step will be to track a few patients over the course of their treatment, taking several blood draws to see if the data captured by the microfluidic device correlates with the data their medical team is collecting through other methods," Liu adds.
The rectangular chip, smaller than a few square centimeters and using as little as a few milliliters of blood, is made of the polymer PDMS. The chip's key feature is a tiny flow channel on a hierarchically designed pad that is optimized to capture tumor cells from the blood flowing across it. Using microfluidic design principles, Liu's group engineered vortices in their device to increase the chance that tumor cells will collide with the surface of the flow channel. The group also arranged ripples in a wavy-herringbone pattern lining the bottom of the capture pad.
"The herringbone surface generates a passive vortex that mixes the cells and increases the chance that they will collide with the capture pad," says Liu. "High selectivity is achieved by smoothing the sharp grooved herringbone pattern into a wavy one, helping to filter out unwanted cells."
The group uses immunoaffinity to make CTCs adhere to the device while normal blood cells flow past. They coat the pad with a layer of anti-epithelial cell adhesion molecules (anti-EpCAM), which bond with CTCs but not with normal cells.
Liu and his team recently improved upon the device's release efficiency. Instead of permanently depositing particles through immunoaffinity, anti-EpCAM coated magnetic microparticles were trapped over the untreated PDMS surface by an external magnetic field and were then released by readily removing the magnet for CTC collection. Those results were published last year in Lab on a Chip.