Medical Design Briefs - February 2023 - 59

Now, a UCLA-led research team has developed a wearable
patch that uses inexpensive microneedles to analyze the fluid
between cells less than a millimeter underneath the skin and
continuously record concentrations of medicine in the body.
The technology could be a step toward improving doctors' ability
to administer precise medication doses.
In a study published in Science Advances, the investigators tested
the system in rats that had been treated with antibiotics. Using
data taken by the device within about 15 minutes after the
medication was administered, the researchers reliably forecast
how much of that drug would be effectively delivered to the animal's
system in total.
" This biosensing microneedle technology advances many
different aspects of personalized medicine, " says Sam Emaminejad,
the paper's senior and corresponding author, a
member of the California NanoSystems Institute at UCLA.
" It may allow us to improve treatments by optimizing the
drug dosage for each individual, and it's inexpensive, so everyone
could benefit from this solution. Additionally, it may
allow us to inform care by measuring not only drug molecules
but also naturally occurring molecules in the body that
are relevant to health, offering a new format for wearable
health monitoring. "
Emaminejad is also an associate professor of electrical and
computer engineering at the UCLA Samueli School of Engineering
and the director of the Interconnected and Integrated
Bioelectronics Lab.
The ability to precisely measure drug dosage could also expand
physicians' options for treating their patients. Today, doctors
shy away from prescribing some drugs that can be highly effective
at the proper dose but toxic or even fatal at a dose that's
too high. Enabling them to administer those medicines more
safely may also help mitigate dangerous bacteria's increasing resistance
to antibiotics.
" The emerging microbial antibiotic resistance crisis is in part
rooted in ineffective use of antibiotics, including poor choices of
drugs, " says Stanford University pediatric pulmonologist Carlos
Milla, a co-author of the study. " Oftentimes this is due to the
difficulties of managing the most effective drugs to avoid serious
toxicities. This sensor certainly opens up the chance for great
precision and confidence using the most effective medicines. "
The patch, about a quarter inch in diameter, detects drugs
using engineered strands of DNA called aptamers. When an aptamer
comes in contact with a specific target molecule, it changes
shape. In the device, one end of the aptamers is anchored to
gold nanoparticles deposited on the microneedle. The other
end of the aptamers is attached to special molecules that produce
measurable signals when the aptamers change shape.
The exposed part of the microneedles, which are made by cutting
down clinical-grade acupuncture needles, is only about half
a millimeter long.
The researchers evaluated the device in rats using three
different dosages of the antibiotic tobramycin. They found
that the patch's measurements of drug concentrations correlated
with those produced by conventional blood tests.
The patch's measurement of peak drug concentration in the
body - which occurs in the first 12 to 20 minutes after a
dose is administered - could be used to predict how much
of the medication is effectively delivered to the body over
the course of an hour or more.
Medical Design Briefs, February 2023
" These experiments not only showed that our sensor readings
are reliable, but also validated our models for correlating
minimally invasive measurements to the concentration of drug
circulating in the blood, " says lead author Shuyu Lin, a former
member of Emaminejad's lab who recently earned his doctorate
from UCLA.
The authors estimate that materials to produce the patch
would cost less than $2 per unit, suggesting that it could be manufactured
cost-effectively on a large scale. Future studies will focus
on optimizing the patch and further analyzing its safety, before
it moves to clinical trials. That research will be funded in
part by a grant from CNSI's Noble Family Innovation Fund.
The other lead authors of the paper are UCLA graduate students
Xuanbing Cheng and Jialun Zhu, also from Emaminejad's
lab. Other UCLA authors are former postdoctoral researchers
Bo Wang and Yichao Zhao; graduate students Tsung-Yu Wu, Jiawei
Tan and Wenzhong Yan; undergraduates Justin Yeung and
Sarah Forman; research associate David Jelinek; Abraham Horrillo,
who recently earned a bachelor's degree; and Hilary Coller,
a professor of molecular, cell and developmental biology and of
biological chemistry.
The study was supported by the National Science Foundation,
the Brain & Behavior Foundation, the Melanoma Research Alliance
and the UCLA Innovation Fund.
This article was written by Wayne Lewis, UCLA. Contact: Sam
Emaminejad, emaminejad@ucla.edu. For more information, visit
https://newsroom.ucla.edu.
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