Biosensor enables early detection of organ transplant failure

SOPHIA CHEN: Welcome to MRS Bulletin’s Materials News Podcast, providing breakthrough news & interviews with researchers on the hot topics in materials research. My name is Sophia Chen. In 2022, some 25,000 people in the US received a kidney transplant. That’s over a majority of organ transplants. These operations help save the lives of those with kidney failure, where these bean-shaped organs located beneath our ribs are no longer able to sufficiently filter toxins out of the blood. However, after the transplant, recipients have to contend with the possibility of their body rejecting the organ. Organ rejection occurs when the recipient’s immune system attacks the donor kidney due to a genetic mismatch. Transplant recipients take medication to suppress the immune system, but organ rejection can still occur, for example, when patients don’t take the medication as prescribed or doctors prescribe the incorrect dosage. 

SURABHI MADHVAPATHY: Rejection can happen at any time. So it can happen within the first three months, it can happen after 10 years. 

SOPHIA CHEN: That’s materials scientist Surabhi Madhvapathy, who recently received her doctorate from Northwestern University. Currently, she explains, physicians check whether patients are experiencing organ rejection by performing a biopsy. The patient comes in to the clinic, and the doctors and nurses use a long needle to go through the patient’s back to extract tissue from the kidney, which they inspect under a microscope.

SURABHI MADHVAPATHY: There are a lot of risks associated with it, such as like internal bleeding, accidental damage to adjacent organs. And it's just not a pleasant process.

SOPHIA CHEN: And because they can only perform biopsies once in a while, doctors may not actually catch the organ rejection right when it occurs. 

SURABHI MADHVAPATHY: There needs to be a way to continuously monitor the health of the kidney from the time of transplantation and continuously through the lifetime of the graft.

SOPHIA CHEN: To that end, her team has developed a sensor that attaches to the kidney itself that could help detect whether the patient’s body is rejecting the kidney. They’ve tested the sensor in rats.

SURABHI MADHVAPATHY: The kidney is basically like a bean structure, and it has this capsule around it naturally, kind of like a garbanzo bean that has an actual skin. We make a little slit in the capsule, and we open it to make a pocket. And then we separate the capsule a little bit from the actual kidney cortex. And then you insert the sensor in that pocket.

SOPHIA CHEN: This hair-thin sensor is 220 microns in thickness. It senses temperature using a gold filament, whose resistance changes according to temperature. Madhvapathy encased the sensor in a rigid inert polymer, polyamide, which she patterned to make it stretchable. The outside of the sensor is a soft silicone so that it did not elicit any foreign body response from the kidney. Once placed on the kidney, the sensor measures the organ’s temperature and its thermal conductivity. They transmit this data outside the rat’s body via Bluetooth. Both of these can point toward inflammation in the kidney, which can be a sign of organ rejection.

SURABHI MADHVAPATHY: During kidney transplant rejection, you have a bunch of different inflammatory processes going on at the cellular level.

SOPHIA CHEN: When the kidney is inflamed, there’s more blood flow and the kidney becomes more thermally conductive. They found that the temperature measurements were more informative than the thermal conductivity measurements. They tested the sensor by performing a kidney transplant between genetically identical rats and comparing them to kidney transplants in genetically different rats. The genetically identical rats would accept the kidney, whereas the genetically different rats would reject it. They were able to measure an increase in thermal conductivity in the kidney when it became inflamed and was being rejected. They also found that kidney temperature of the rats that accepted the kidney transplant sharply differed from those rejecting kidney transplants.

SURABHI MADHVAPATHY: In a normal rat that was, you know, undergoing kidney acceptance, so no problems, basically all you saw was in the temperature data was one circadian rhythm that was going on every single day. So a single, you know, temperature spike and dip during the single 24-hour period corresponding to its active and sleeping stage.

SOPHIA CHEN: The rats that had received a genetically different kidney exhibited very different temperature signs.

SURABHI MADHVAPATHY: It never even developed a circadian rhythm. We saw that they all kind of had this like, inflection point, and like a hump-like feature when increase and decrease, then the temperature tanked. And the animal was like visibly looking, you know, very sick, it was just not going to make it at that point.

SOPHIA CHEN: They also monitored the kidney temperature in rats that received a genetically different kidney transplant, but also took immunosuppressant medication.

SURABHI MADHVAPATHY: In the case where they were medicated, we saw even another feature. So it did develop a circadian rhythm. But it also developed these higher frequency rhythms. So instead of just one peak and trough per day, we started seeing a double hump-like feature. So these are called ultradian rhythms; they occur on higher frequencies than your circadian rhythm.

SOPHIA CHEN: It’s particularly significant that the temperature measurements looked abnormal well before the animals started behaving like they were ill, she says. This could mean they could catch organ rejection before the patient starts to feel sick. The team is working to investigate the sensor’s use in larger animals. They are now testing the sensor in pig models, says Madhvapathy. This work was published in a recent issue of Science. My name is Sophia Chen from the Materials Research Society. For more news, log onto the MRS Bulletin website at mrsbulletin.org and follow us on twitter, @MRSBulletin. Don’t miss the next episode of MRS Bulletin Materials News—subscribe now. Thank you for listening.