FOLLOWING an explosion at a chemical plant, employees and neighbors may find themselves in a triage facility where a nurse will apply a small, disposable patch to each person’s arm. In a few minutes, a simple color change in this colorimetric patch will indicate whether the person was exposed to dangerous levels of a toxic substance.
Using this novel microneedle design, the UC Davis team went on to develop a patch that could, for the first time, extract fluid from the body. If the fluid to be withdrawn is blood, the microneedles on the colorimetric patch need be only 350 micrometers long. If the target is interstitial fluid, which lies in the epidermis (the outer, nonvascular, nonsensitive layer of the skin), the microneedles can be even shorter—a mere 250 micrometers long. “We have an amazing amount of freedom during the microfabrication process,” say Mukerjee, who now works in Livermore’s Engineering Directorate. “We can easily modify the shape and length of the microneedles to suit a specific application.”
Using a patch made of microneedles and tiny microchannels that lead to a common reservoir, the team tested the application by monitoring blood glucose in interstitial fluid. The needles on the patch were just long enough to enter the epidermis and collect a fluid sample. Says Mukerjee, “Although a 10-minute lag exists between glucose level changes in the blood and in the interstitial fluid, it is still the perfect fluid for glucose monitoring. The epidermis has only a few nerve endings and no blood capillaries. By targeting interstitial fluid, we can painlessly and continuously monitor a person’s glucose levels. This method eliminates the need for testing blood with painful needle sticks.”
Following proper protocols, Mukerjee applied the patch—which he could not feel—to his own arm, drank a soda sweetened with high-fructose corn syrup, and watched his interstitial-fluid glucose levels rise as glucose diffused from the blood into the fluid. UC Davis has licensed this painless technology to a private company, which is now developing a commercial product for use by diabetics.
Integrated Real-Time Detection
Currently, medical staff must either draw blood or collect a urine sample to determine whether a person has been exposed to a dangerous substance. Blood samples can at times take days to analyze. Results from a urine sample can be determined quickly, but some agents can take hours to find their way into the body’s urine. For on-the-scene triage by first responders and for optimal follow-up care, a faster and easier-to-use system is essential.
Mukerjee has begun working with chemical engineer Elizabeth Wheeler of the Engineering Directorate to integrate the microneedle fluid-extraction technique with an in situ detection system. Biological systems integration is Wheeler’s forte. She has experience with both lateral flow immunoassay methods and DNA sampling.
Lateral flow assay devices draw fluid through a wicking substrate into an immobilized chemical detector. Color change in the chemical detector indicates the presence of a targeted chemical. A home pregnancy test is an example of a simple lateral flow device.
Wheeler was also involved in the development of the BioBriefcase, a prototype system for detecting environmental biological contaminants. The unique DNA preparation methods in the BioBriefcase could be used with the microneedle patch. A bed of silica beads traps the DNA, separating it out from the bits of dirt and other environmental particles that are also in the sample. The DNA is then amplified on the silica surface. This process minimizes the loss of DNA prior to detection.
A Colorful Future
In the future, DNA and RNA detection assays may be incorporated in the microneedle detector. The patch may also be made to detect multiple substances at the same time, a process called multiplexing. Mukerjee adds, “This system may not be the fictional Star Trek tricorder, but our research brings us one tantalizing step closer.”
Key Words: BioBriefcase, DNA sampling, exposure monitoring, lateral flow assay, microneedle.
Lawrence Livermore National Laboratory
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