Research Goals

The Nagrath Laboratory's research goal is to bring the next generation of engineering tools to patient care, especially in cancer. Our major research objective is to develop advanced MEMS tools to understand cell trafficking in cancer through isolation, characterization, and study of circulating cells in the peripheral blood of cancer patients. We focus our efforts on designing and developing smart chips using microfluidics and nanotechnology to make impact in medicine and life sciences. Our goal is to create cutting edge engineering solutions for clinical medicine with novel translational biomedical research tools. We strongly believe in building a team where engineers, biologists and clinicians will come together to solve the complex problems with better approaches.

Circulating Tumor Cells

Circulating tumor cells (CTCs) are rare cells shed from the primary tumor that can be found in the blood stream. To isolate them is an elusive goal: they are present at a frequency of as low as only one CTC in one billion blood cells. However, it is these target cells that may provide clinically useful answers to questions such as "what cells are capable of metastasis?" and "how do we stop them?"

Clinical Relevance of CTC Capture

Previous research has demonstrated that the isolation of circulating tumor cells (CTCs) from circulation can be a useful and noninvasive diagnostic tool. By monitoring the concentration of CTCs in a cancer patient's blood stream, an oncologist may determine the effectiveness of an applied therapy on a day-to-day basis as well as other prognostic indicators. The number of CTCs varies significantly among patients and among different types of cancer, but in all cases, CTCs are rare relative to other blood cells. The field of microfluidics shows a promising capability to capture the cells specifically and enable subsequent genomic and proteomic analysis.

Microfluidic Devices

Researchers at the Nagrath Laboratory are developing microfluidic devices for isolating and studying circulating tumor cells (CTCs) as related to metastasis, the cause of over 90% of cancer related deaths.

We use microfluidic devices to detect CTCs in the blood, characterize the cell populations that are able to spread, and study the microenvironmental cues needed to sustain and grow tumor metastases. Through a wide variety of separation techniques and materials, we are making strides towards understanding the biology behind tumor metastasis and using CTCs as a prognostic tool in the clinical setting.

CTCs

Isolation of CTCs can be approached in several of ways. Our lab has developed a host of technologies that separate these rare cells based on how they differ from the surrounding normal blood cells. Two of our premiere technologies use 'immunocapture,' in which tethered antibodies capture CTCs based on antigens expressed on their cells surfaces but not the surfaces of white blood cells. The graphene oxide (GO) Chip takes advantage of the high surface area afforded by the GO nanomaterial for highly sensitive capture, while the radial flow design of the Oncobean facilitates high throughput sample processing. For cancers in which CTCs are larger than surrounding blood cells, the Labyrinth enables size-based sorting based on inertial focusing. The Integrated Microfluidic Immunomagnetic (IMI) Device takes advantage of both types of cell sorting to first pre-enrich the sample using inertial focusing followed by high-purity CTC isolation through immunomagnetic sorting.

Future Directions

Our research interests are unified by the drive to develop creative new devices that are ultimately able to traverse the gap from benchside to bedside. We are currently exploring novel nanomaterials, processing clinical samples, and conducting downstream analysis of captured cells in order to design and optimize state-of-the-art technology for early disease detection and the study of fundamental cancer biology.