INTRODUCTION:
UCLA Researchers in the Department of Chemistry and Biochemistry have developed a microfluidic gold nanostar interface for the accurate isolation of CTCs in peripheral blood.
BACKGROUND:
There is an emerging interest in utilizing circulating tumor cells (CTCs), which detach from primary or metastatic lesions as a means of identifying cancer progression. This method of cancer staging, could serve as the most sensitive method to date, due in great deal to the gold standard of identification relying on hyperpolarized tumor metabolism, which is stagnant at early progression stages. However, CTCs are difficult to detect due to their relatively low abundance in peripheral blood. To account for the relatively large sample sizes that would be needed to detect CTCs in patients with traditional cell identifying sensors, researchers have turned attention to microfluidic devices to efficiently isolate CTCs from peripheral blood. However, to date there remains no clinically viable microfluidic device capable of achieving this goal; a major criticism of the current devices is the difficulty in selective targeting, often leading to inaccurate measuring of CTCs. This inaccurate isolation of CTC samples may under or overestimate CTC populations leading to false diagnoses that could affect overall patient care. Therefore, there exists a current need for the development of a microfluidic device that can accurately isolate CTCs in peripheral blood samples for the accurate staging of cancer progression in patients.
INNOVATION:
UCLA Researchers in the Department of Chemistry and Biochemistry have developed a microfluidic gold nanostar interface for the accurate isolation of CTCs in peripheral blood. The device relies on selectively tailored branched gold nanostructures that interact with target biomolecular and cellular targets. Beginning with targeting of the Ewing Sarcoma (EWS) family of tumors, the researchers modified the surface of the gold nanostructure interface with an antibody specific target, that showed efficient capture. Researchers have taken a further step in the introduction of a release mechanism of the target captured cells, via hyperthermia-mediated-cell-detachment. These detached target cells lead to lower incidences of device clogging and can be further characterized. CTCs for example, rely on serial radiographic imaging protocols for the monitoring of disease progression and/or metastasis. However, this device’s utility extends beyond the capture of CTCs, due to the ability of the gold nanostructure surface to be modified with various antibodies or other relevant biomolecules. One example of this device’s utility would be the real time monitoring and concentration of drugs in patient biofluids. Therefore, the presented device capitalizes on previous limitations of other microfluidic devices that looked to efficiently isolate CTCs, while also showing extended utility to other target biomolecules in patient biofluids.
POTENTIAL APPLICATIONS:
• The microfluidic device can be functionalized to effectively capture CTCs for cancer progression
• The microfluidic device has a gold interface that when functionalized with thiol group modifications, can be tethered to cell specific antibodies (efficient capture of cells and/or biological targets)
• The microfluidic device can be used for the real time monitoring and concentration of drugs in patient biofluids.
ADVANTAGES:
• Hypothermia-mediated-cell detachment mechanism, that leads to lower incidences of device clogging, and the ability to further characterize captured species
• The ability to chemically modify the gold surface of the microfluidic device allows for multiple cell specific targets to be used, extending the range of utility of the device comparative to other CTC specific microfluidic devices
• The only microfluidic device that can capture target drug molecules for real time monitoring of metabolism in patient biofluid
DEVELOPMENT-TO-DATE:
The device has been tested for the capture of CTCs as well as chemical analytes.