Building a microfluidic device that captures cancer cells from blood for a liquid biopsy test

 

Site

MIT

dATES

2012-2013

ROLE

Independent research with Professor Wasserman and Manalis

 

Context

Conducting a biopsy is a critical step in diagnosing cancer. Current techniques typically require a surgical intervention to collect tissue samples, a invasive procedure with high-risk. What if, instead, you could simply do a blood test?

The essential step of a "liquid biopsy" is the ability to capture the "circulating tumor cells" or CTC's from a blood sample. My challenge was to build such a device to capture these CTC's.

Sketch of the device that would capture CTCs from a genetically modified mouse in real time. A peristaltic pump would push the blood into the device, where the CTC's would be captured. The blood is then pumped back into the mouse. [Source: Manalis laboratory proposal]

Sketch of the device that would capture CTCs from a genetically modified mouse in real time. A peristaltic pump would push the blood into the device, where the CTC's would be captured. The blood is then pumped back into the mouse. [Source: Manalis laboratory proposal]

 

Design Modules

I. Microfluidic Platform

 

The system to circulate blood through the device

II. Optical Detection System 

 

The system to detect and trigger the capture of a CTC in the device 

I. Microfluidic Platform

Using silicone micromachining and PDMS microfluidics I designed a device that would enable a suitable flow rate under pressure with parallel channels. 

2D rendering of microfluidic device built with soft-lithographic techniques 

2D rendering of microfluidic device built with soft-lithographic techniques 

AutoCad device design to extract CTCs from mouse blood. 

AutoCad device design to extract CTCs from mouse blood. 

Critical design choices included: 

  • Choosing a push-up valve system because channels were deeper, allowing large particles in blood to flow through
  • Designing parallel flow channels to visualize a larger volume of blood
  • Strategically placing valves to enable switching speeds of the blood flow

These choices were made based on secondary research, expert interviews, prototyping and experimentation.

 

II. Optical Detection System

I designed and built a fluorescence microscope to detect when the CTC's pass through the microfluidic device. A visual trigger would automatically switch valves in the device to capture the CTC. 

 
2D sketch of the fluorescence microscope design

2D sketch of the fluorescence microscope design

 

Critical design choices included:

  • Choosing a high numerical aperture, with a long-distance microscope objective to illuminate the underside of the device
  • Using a high brightness LED in-line with an excitation filter and a mirror as the illumination source
 

Impact

The device was successfully prototyped (after many-many tries!) and tested across multiple scenarios. The preliminary results were used by the Manalis lab to win the National Institute of Health RO1, a 5 year grant for cutting-edge research.