Each year researchers test thousands of potential cancer drugs on mice with subcutaneous tumors. Few make it to human patients, and the process of finding new therapies is slow because technologies for measuring tumour regression from drug treatment take weeks to read out a response.
The inherent biological variation of tumors, the shortcomings of existing measuring approaches, and the relatively small sample sizes make drug screenings difficult and labour-intensive.
“In some cases, the tumors under observation must be measured by hand with calipers,” says Alex Abramson, first author of the study and a recent post-doc in the lab of Zhenan Bao at the Stanford School of Engineering and now an assistant professor at Georgia Tech.
The use of metal pincer-like calipers to measure soft tissues is not ideal, and radiological approaches cannot deliver the sort of continuous data needed for real-time assessment. FAST can detect changes in tumor volume on the minute-timescale, while caliper and bioluminescence measurements often require weeks-long observation periods to read out changes in tumor size.
FAST’s sensor is composed of a flexible and stretchable skin-like polymer that includes an embedded layer of gold circuitry. This sensor is connected to a small electronic backpack designed by former post-docs and co-authors Yasser Khan and Naoji Matsuhisa.
The device measures the strain on the membrane -- how much it stretches or shrinks -- and transmits that data to a smartphone. Using the FAST backpack, potential therapies that are linked to tumor size regression can quickly and confidently be excluded as ineffective or fast-tracked for further study.
The researchers say that the new device offers at least three significant advances. First, it provides continuous monitoring, as the sensor is physically connected to the mouse and remains in place over the entire experimental period. Second, the flexible sensor enshrouds the tumor and is, therefore, able to measure shape changes that are difficult to discern with other methods. Third, FAST is both autonomous and non-invasive. It is connected to the skin, not unlike a band-aid, battery operated and connected wirelessly. The mouse is free to move unencumbered by the device or wires, and scientists do not need to actively handle the mice following sensor placement. FAST packs are also reusable, cost just $60 or so to assemble and can be attached to the mouse in minutes.
The breakthrough is in FAST’s flexible electronic material. Coated on top of the skin-like polymer is a layer of gold, which, when stretched, develops small cracks that change the electrical conductivity of the material. Stretch the material and number of cracks increases, causing the electronic resistance in the sensor to increase as well. When the material contracts, the cracks come back into contact and conductivity improves.
Both Abramson and co-author Naoji Matsuhisa, an associate professor at the University of Tokyo, characterised how these crack propagation and exponential changes in conductivity can be mathematically equated with changes in dimension and volume.
One hurdle the researchers had to overcome was the concern that the sensor itself might compromise measurements by applying undue pressure to the tumor, effectively squeezing it. To circumvent that risk, they carefully matched the mechanical properties of the flexible material to the skin itself to make the sensor as pliant and as supple as real skin.
“It is a deceptively simple design,” Abramson says, “But these inherent advantages should be very interesting to the pharmaceutical and oncological communities. FAST could significantly expedite, automate and lower the cost of the process of screening cancer therapies.”