Engineers from Stanford University, Georgia Tech, USC Viterbi School of Engineering and the University of Tokyo have created a small, self-contained device with a stretchy/flexible sensor that can be stuck to the skin to measure the changing size of tumors below. The non-invasive, battery-operated device is sensitive to hundredths of a millimeter (10 micrometers) and can transmit results to a wireless smartphone app in real time at the push of a button.
Concretely, according to the researchers, their device – dubbed FAST for “Flexible Autonomous Sensor Measuring Tumours” – represents an entirely new, fast, inexpensive, hands-free and precise means of testing the effectiveness of anti-cancer drugs. On a larger scale, this could lead to promising new directions in cancer treatment.
Each year, researchers test thousands of potential cancer drugs on mice with subcutaneous tumors. Few of them make it to human patients, and the process of finding new therapies is slow because technologies for measuring tumor regression from drug treatment take weeks to read a response. The inherent biological variation of tumors, the shortcomings of existing measurement approaches, and the relatively small sample sizes make drug screenings challenging and labor-intensive.
Yasser Khan, an assistant professor of electrical and computer engineering in the Ming Hsieh Department of Electrical and Computer Engineering at USC, helped design the device as a postdoctoral fellow at Stanford.
“In some cases, tumors under observation have to be measured by hand with calipers,” says Alex Abramson, the study’s first author and recent post-doctoral fellow in Zhenan Bao’s lab at the Stanford School of Engineering.
The use of forceps-like metal calipers to measure soft tissue is not ideal, and radiological approaches cannot provide the kind of continuous data needed for real-time assessment. FAST can detect changes in tumor volume on a minute scale, while thickness and bioluminescence measurements often require observation periods of several weeks to read changes in tumor size.
FAST’s sensor is made of a soft, stretchy, 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 Khan and Naoji Matsuhisa, now at the University of Tokyo. The device measures the pressure exerted on the membrane – how much it stretches or shrinks – and transmits this data to a smartphone. Using the FAST backpack, potential therapies related to tumor size regression can be quickly and confidently ruled out as ineffective or expedited for further study.
The researchers say the new device offers at least three significant advancements. First, it provides continuous monitoring, as the sensor is physically connected to the mouse and remains in place throughout the experimental period. Second, the flexible sensor envelopes the tumor and is therefore able to measure changes in shape that are difficult to discern with other methods. Third, FAST is both self-contained and non-invasive. It is connected to the skin, much like a bandage, battery operated and connects wirelessly. The mouse is free to move around unhindered by the device or wires, and scientists do not need to actively handle the mice after sensor placement. FAST packs are also reusable, only cost around $60 to assemble, and can be attached to the mouse in minutes.
“This work is a great example of how wearable electronics can advance precision health technologies – we can monitor tumor growth with a resolution of tens of microns just by using a sensor and an app to cellphone. We can observe the progression 24/7, unlike all existing imaging techniques, and tell precisely if a drug is acting on the tumor and not on the treatment,” Khan said.
The breakthrough lies in FAST’s flexible electronic hardware. Above 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 the number of cracks increases, which also leads to an increase in electronic resistance in the sensor. When the material contracts, the cracks come back into contact and the conductivity improves.
Abramson and co-author Naoji Matsuhisa, associate professor at the University of Tokyo, explained how these crack propagations and exponential changes in conductivity can be mathematically likened to changes in dimension and volume.
One hurdle the researchers had to overcome was the fear that the sensor itself would compromise the measurements by applying excessive pressure to the tumor, effectively squeezing it. To circumvent this risk, they carefully matched the mechanical properties of the flexible material to the skin itself to make the sensor as soft and flexible as real skin.
“It’s a deceptively simple design,” says Abramson, “But these inherent benefits should be of great interest to the pharmaceutical and oncology communities. FAST could dramatically speed up, automate, and reduce the cost of the screening process for cancer therapies.” »
Citation: Abramson et al., Sei. Adv. 8, eabn6550 (2022) DOI: 10.1126/sciadv.abn6550
Alex Abramson is now an assistant professor of chemical and biomolecular engineering at the Georgia Institute of Technology; Yasser Khan is Assistant Professor in the Ming Hsieh Department of Electrical and Computer Engineering at the University of Southern California; Carmel T. Chan is a former Chief Scientific Officer at Stanford University; Alana Mermin-Bunnell is a student at Stanford University; Naoji Matsuhisa is an associate professor in the Department of Computer Science and Electronics, Institute of Industrial Sciences, University of Tokyo; Robyn Fong is Professor of Life Sciences Research in the Department of Cardiothoracic Surgery at Stanford University; Rohan Shad is a former postdoctoral fellow at Stanford University School of Medicine; William Hiesinger is assistant professor of cardiothoracic surgery at Stanford University; Parag Mallick is an associate professor of radiology at Stanford University; Zhenan Bao is the KK Lee Professor of Chemical Engineering at Stanford University.
The research was supported in part by an NIH F32 fellowship (Grant 1F32EB029787) and the Stanford Wearable Electronics Initiative (eWEAR).
The eWEAR-TCCI Award for Scientific Writing is a project sponsored by the Wearable Electronics Initiative (eWEAR) at Stanford University and made possible with funding from Shanda Group, a member of the eWEAR Industry Affiliate Program, and the Tianqiao and Chrissy Chen Institute (TCCI®).
Posted on September 17, 2022
Last updated September 17, 2022