The researchers claim that their FAST device, which stands for “Flexible Autonomous Sensor measuring Tumors,” is a completely novel, fast, affordable, hands-free, and accurate method of evaluating the effectiveness of cancer drugs. On a larger scale, it might pave the way for exciting new directions in cancer treatment. The researchers’ findings were recently published in the journal Science Advances. Every year, researchers use mice with subcutaneous tumors to test thousands of potential cancer drugs. Few make it to human patients, and the process of developing new drugs is time-consuming since tools for evaluating tumor regression following drug treatment take weeks to read out a response. The inherent biological variation of tumors, the shortcomings of available measurement techniques, and the relatively limited sample sizes make drug screening challenging and labor-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 postdoc in the lab of Zhenan Bao, the K.K. Lee Professor in Chemical Engineering in the Stanford School of Engineering. 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.
The power of gold
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 postdocs 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. Based on studies with mice, 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 an adhesive bandage – 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 skinlike polymer is a layer of gold, which, when stretched, develops small cracks that change the electrical conductivity of the material. Stretch the material and the 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 Matsuhisa, an associate professor at the University of Tokyo, characterized 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.” Reference: “A flexible electronic strain sensor for the real-time monitoring of tumor regression” by Alex Abramson, Carmel T. Chan, Yasser Khan, Alana Mermin-Bunnell, Naoji Matsuhisa, Robyn Fong, Rohan Shad, William Hiesinger, Parag Mallick, Sanjiv Sam Gambhir and Zhenan Bao, 16 September 2022, Science Advances.DOI: 10.1126/sciadv.abn6550 The study was funded by the National Institutes of Health and the Stanford Wearable Electronics Initiative (eWEAR).