Design of CHAMP-3: Controlled Heating Apparatus for Microfluidics and Portability

Breast cancer diagnosis using magnetic resonance imaging (MRI) often requires contrast agent-aided scans (e.g., gadolinium (Gd)-chelates). Gd-chelates lack specificity and accumulate in the brain and bone, causing toxicity concerns. This has led to a new age in MRI contrast agent discovery, which typically involves static 2D culture and in vivo MRI studies. In vitro cell culture often does not accurately predict the outcomes from in vivo studies due to its simplistic setup, which lacks flow. Long-term in vivo MRI studies have time-limiting factors such as anesthesia usage for murine models and temperature contraindications as well as high cost, long set-up time, and regulatory approval. Microfluidic tumor models (MTMs) bridge the gap between cell culture and animal models to create a platform that is cost-effective, reproducible, customizable, and high throughput; however, the MRI environment still prevents their long-term imaging. Our proposed device called CHAMP-3 prevents model loss by perfusing warmed media to the MTMs in the MRI machine to facilitate longitudinal imaging.

Our device has 3 parts: (1) a 3D printed MTM holder (2) a heated water perfusion device and (3) a portable power source. The design of this device took an iterative engineering approach. Both the MTM holder and the feedthroughs for CHAMP-3 were created in SolidWorks and 3D printed with either poly(lactic acid) or polyethylene terephthalate glycol. The CHAMP-3 apparatus is composed of a heated water bath circulator, 3ft of flexible PVC tubing, two stainless steel plumbing clamps, two 3D printed feedthroughs, parafilm, and silicone sealant.

The MTM holder design required several iterations to create a durable prototype for securing and centering the MTM into the MRI bore as well as properly housing the reference water tube needed for signal normalization. Extensive troubleshooting led to the first functional prototype of the CHAMP-3 apparatus. The results of the initial build of CHAMP-3 settled on two major constraints including ease of disassembly and being watertight. Several leak points were assessed in the tubing holes of the feedthroughs, around the barbs of the feedthroughs, and through the bulk 3D printed material. To prevent leakage at these points, parafilm, plumbing clamps, and silicone sealant were used. The leakage through the bulk of the feedthrough material required a change to the 3D printer’s extrusion temperature but a material change was also assessed. This initial prototype is capable of temperature maintenance and is now ready for temperature validation and MRI contrast agent testing.