At the height of their popularity in the 1980s, no one could have guessed that Shrinky Dinks would inspire tiny diagnostic tests or sensors to detect changes in a person’s health. While these inexpensive and easy-to-access toys may have started as a childhood pastime for Michelle Khine, a bioengineer at the University of California (UC), Irvine, they became her inspiration for a new way to diagnose and monitor disease.
After drawing on sheets of polystyrene plastic with pens or paint and placing her doodles in the oven as a child, Khine watched her drawings shrink to about one third of their original sizes. Excited by the potential of these shrinking properties, Khine first developed her technology by using a standard laser-jet printer to print microfluidic patterns onto the Shrinky Dink polystyrene plastic sheets. When she placed these sheets in the oven for a few minutes, they shrunk, creating wells and channels where liquids and cells could mix. She started out engineering microfluidic chips for studying stem cell biology and diagnosing diseases. Now she has developed a diagnostic sensor to detect SARS-CoV-2 in saliva samples and wearable sensors for respiratory and cardiovascular disease based on these shrinking creations.
What inspired you to develop diagnostic sensors based on Shrinky Dink toys?
Shrinky Dinks were my favorite toys as a kid. My mom was a chemist, and she used to do a lot of fun science experiments with us, including playing with Shrinky Dinks. When I started as an assistant professor at UC Merced in 2006, the campus was just starting, so I didn't have the big fancy fabrication rooms that I needed to make microfluidic chips. I got really desperate, so I thought, “What if I used my favorite toy as a child? We can make these microfluidic chips really inexpensively.”
My colleagues told me that trying to publish these devices based on a children's toy could be career suicide. But I did publish it, and it got an insane number of downloads (1). The editor of the journal called me saying that the CEO of Shrinky Dinks contacted him because all of these labs were buying Shrinky Dinks. We ended up winning a bunch of awards, and people started taking notice.
How are you using Shrinky Dinks in your research now?
When my lab moved to UC Irvine three years later, we still thought that the principle of Shrinky Dinks was really cool. We started putting more exotic materials like metals on them. We realized that the metal doesn’t shrink, it buckles. If we took the metal off of the Shrinky Dinks, we could stretch it back out and put it into a different material to make Band-Aid-like devices with nice electronic properties. Based on this, we started making wearable sensors. We actually spun out a bunch of companies in this space. We have a wearable blood pressure sensor and a wearable respiratory sensor based on Shrinky Dinks.
When the COVID-19 pandemic hit, everything came to a stop. We were told that we had to shut down the lab unless we were working on a COVID project. We were like, “We're a diagnostics lab. We need to be working on a COVID project.” We showed that we could develop a SARS-CoV-2 sensor based on this Shrinky Dink toy (2).
How does your SARS-CoV-2 Shrinky Dink-based diagnostic work?
It's an electro-chemical sensor. We use aptamers, which are just short oligonucleotide probes, to detect the SARS-CoV-2 spike protein. Because our sensors have a wrinkled surface, we have a large surface area to fit a lot of aptamer probes on a really small platform, so we could get really sensitive recordings. We tested it by changing the concentrations of the spike protein to see if it could detect that, and then we started testing saliva samples to see if it could detect the whole virus.
But I have to say that people are not that interested in the SARS-CoV-2 sensor. There are a lot of rapid tests now. We have a couple of undergraduate capstone project teams working on developing it further by applying different aptamers to it so that we can do different things with it.
What other kinds of diagnostic applications could you use your SARS-CoV-2 sensor for?
We're working with an ear, nose, and throat doctor who's very interested in using this sensor to detect cerebral spinal fluid. It turns out that when people have neural surgeries, sometimes they have cerebral spinal fluid leaking from their noses, and they think it's just snot. There's really no good way to test for that, so he asked if we could adapt this technology by changing out the aptamers to be specific to cerebral spinal fluid. We have a team of students working on that right now.
How do your wearable respiratory and blood pressure biosensors work?
Our respiratory sensor is worn on the chest like a little Band-Aid. We put our sensor on a rubber-like material. It matches the softness of skin, and it has really nice electrical responses. I was interested in looking at children with asthma to see if we could detect and predict exacerbations. We compared our sensor with the gold standard, which is a medical grade spirometer. A spirometer is the only device that can actually measure breathing volume and flow. We showed that our sensor correlated nicely with the spirometer, and we could track a person’s breathing even when they were running (3). The respiratory sensor is being commercialized by a company I started with my former student, and they're planning to go through FDA submission within the next few months.
In terms of the blood pressure sensor, a person’s blood pressure is actually pretty variable from beat to beat. When taking someone’s blood pressure with a standard blood pressure cuff, we only get a static measurement which isn't very indicative of their health. People have been trying to look at beat to beat blood pressure variability for a long time, but most of the technology still uses an invasive approach, which has a risk of infection and is only available in the ICU or operating room setting.
We developed a little sticker sensor that we can put wherever a pulse can be felt. We measured it against FDA approved devices and the arterial line, which is the standard method used in operating rooms. Our sensor compared well against the arterial line (4), and we’re now testing it in patients with heart failure. If doctors catch heart failure symptoms early, they can be very effective in keeping patients out of the hospital. A person can't go to the doctor once or twice a year, get their blood work, and have a good picture of their health.[SD7] We spun out a company to develop this blood pressure sensor as well, and they’re planning to go through FDA submission by the end of this year or early next year.
What do you find most exciting about developing these new diagnostics and wearable health sensors?
I really want to revolutionize medicine. It's ridiculous that if someone is not feeling well, they have to go see the doctor and then go somewhere else to get their blood work done. I want to do what Uber and Airbnb have done with commerce. I think that a revolution in medicine is happening, and I just want to be part of it. I want to help it along because I think we could be doing so much better.
This interview has been condensed and edited for clarity.
References
- Grimes, A. et al. Shrinky-Dink microfluidics: rapid generation of deep and rounded patterns. Lab Chip 8, 170-172 (2008).
- Zakashansky, J.A. et al. Detection of the SARS-CoV-2 spike protein in saliva with Shrinky-Dink electrodes. Analytical Methods 13, 874-883 (2021).
- Chu, M. et al. Respiration rate and volume measurements using wearable strain sensors. npj Digital Med 2, 8 (2019).
- Chou, E.F. et al. Clinical Validation of a Soft Wireless Continuous Blood Pressure Sensor During Surgery. Frontiers in Digital Health 3, 80 (2021).
