This lateral filter array microfluidic device utilizes both size-based and immunoaffinity-based isolation methods for circulating tumor cells capture and enumeration. Circulating tumor cells are cancer cells that shed from the primary tumor into the circulatory system and act as important biomarkers because their presence can lead to metastasis or provide disease prognosis and therapy monitoring. Metastasis, or the spread of cancer cells away from the primary tumor, is responsible for about 90 percent of cancer-related deaths. Available cancer diagnosis, prognosis, and treatment monitoring techniques use liquid biopsy, which detect circulating tumor cells, exosomes, and/or nucleic acids in the blood, but cell-based liquid biopsy isn’t sensitive enough to detect all circulating tumor cells. Improvements upon this technique combine both physical-property-based isolation and immunoaffinity-based isolation, but this dual-characteristic capture strategy still has limited effectiveness as it requires a complicated sample pretreatment, has low throughputs and is prone to clogging.
Researchers at the University of Florida have developed a device to isolate circulating tumor cells based on physical size and immunoaffinity that addresses many concerns with existing dual-characteristic capture strategies. The device is highly sensitive, which allows a more accurate count of circulating tumor cells in a blood sample, leading to improved cancer diagnosis, prognosis, and treatment.
Isolates circulating tumor cells by size and immunoaffinity for use in cancer diagnosis, prognosis, and treatment monitoring
This lateral filter array microfluidic device works by using parking-space style filter arrangements. The filter array is set up in a serpentine that produces two flow directions. Lateral flow is induced through individual filters and a serpentine flow is created through the rows of filters. Each filter is large enough to allow red and white blood cells through but also small enough to capture circulating tumor cells. Users can configure filter size based on the types and sizes of particles desired for capture. The dual flows ensure that the tumor cells enter the filters and that red and white blood cells continue moving through the device, preventing clogging and increasing capture of circulating tumor cells. Each filter is sized so that it captures the circulating tumor cells and is coated with antibodies with an affinity for these tumor cells to help secure their immunocapture once trapped by the filter. The combination of filter size and antibody coating ensures that the lateral filter array microfluidic device has a high circulating tumor cells capture efficiency (sensitivity) and cell purity (specificity).
Chen, K., Dopico, P., Varillas, J., Zhang, J., George, T., & Fan, Z. H. (2019). Integration of Lateral Filter Arrays with Immunoaffinity for Circulating-Tumor-Cell Isolation. Angewandte Chemie International Edition. doi: 10.1002/anie.201901412.
