Painless Microneedles Used for Extracting Interstitial Fluid

The lab is clean and well organized besides being calm and quiet; boxes of small needles and sample tubes are neatly arranged above a pristine paper-covered countertop.

This is considered to be a far cry from the dusty battlefield, hectic emergency room or sweaty training center Sandia National Laboratories and University of New Mexico Researchers assume will soon host their microneedle-based sensors.

The Author is here, at this UNM lab, to be part of a research study in order to help these microneedles make that leap from fundamental research to helping soldiers on vital missions.

Ronen Polsky, a Sandia Materials Scientist who heads the design of the microneedle sensor, stated the technology is the initial way for extracting huge volumes of pure interstitial fluid for further study. In September, Polsky presented his hopes and vision for the microneedle-based sensor system at the Albuquerque TEDx conference.

Microneedles are a few hairsbreadths wide and are capable of sipping the clear fluid between cells in the middle layer of skin. This is beneath the topmost layer of dead skin cells and above the layer of skin where nerves and veins reside. The clear, colorless fluid is known as interstitial fluid and is very much like blood plasma.

Microneedles constantly sample interstitial fluid to track physiological conditions

The microneedles are capable of containing minuscule sensors or extracting the interstitial fluid for further testing. Microneedles are practically painless since they are small and do not go extremely deep. When five microneedles clasped in a 3D printed holder were placed into the author’s forearm, a little pain was felt by the author. It was less than a standard needle prick and quickly faded.

For the study the Author participated in, the needles were left in for 30 minutes and three lengths of needles were then tested in order to determine the proper length for extracting interstitial fluid from the Author.

Since the needles are minimally invasive and painless, it is possible for them to be left in for hours or even one full day without irritation, permitting continuous monitoring, said Polsky.

Continual sampling of vital biomarkers in this interstitial fluid could help monitor and then diagnose many disorders and diseases. These markers include electrolytes, salts such as sodium and potassium that get out of balance during dehydration; lactose, a potential marker of physical exhaustion or life-threatening sepsis; and glucose, a sugar that diabetics need to monitor continually.

Diabetes, dehydration and exhaustion biomarker detection

A tiny, wearable sensor capable of monitoring these markers could have a number of uses. It could help endurance athletes fulfill their training goals without plunging into severe exhaustion or dehydration. Tracking their physiological conditions would help soldiers on strenuous missions, warning them before they get so exhausted it could compromise their objectives. Polsky explained the microneedle sensor could also be part of a sense-and-respond device that is capable of detecting high glucose levels and automatically delivering insulin.

To move toward something that is market-ready, you need to start adding components that make it a bit more user-friendly and increase the reproducibility of the readouts.

Philip Miller, a Sandia Biomedical Engineer

Otherwise the sensors could be used in emergency rooms and critical care facilities in order to track the response of a septic patient to a course of antibiotics or determine which salts are out of balance in cases of severe dehydration, said Dr. Justin Baca, Assistant Professor of Emergency Medicine at UNM who heads the human testing of the sensor.

“There are a lot of great uses for these microneedle sensors,” said Baca. “It has the ability to help a lot in the medical sphere and in national security, but it could also be something that’s useful to somebody who’s just trying to improve their performance as a cyclist.”

1.5-millimeter-long needles extract interstitial fluid

The first research study in humans focused on determining the best length of needle in order to extract the most interstitial fluid from healthy volunteers and then bring about a comparison of the contents of the interstitial fluid to blood.

“Now we have a pretty good sense of what the average length we should use for most people, but some people’s skin is a little thicker or a little thinner in that area and the flow rate may be decreased,” said Baca. Typically, the best microneedles are 1.5-millimeter long, or as long as a U.S. penny is thick.

The Author admits that she is pretty thick skinned, and that this study proves it. The 2 mm long microneedles extracted more interstitial fluid from the Author than the 1.5 or 1 mm long needles.

In addition to the sugars and salts with well-studied roles in physiological monitoring, interstitial fluid comprises of many proteins and exosomes, free-floating balls containing genetic information including cancer markers.

Additional research is needed in order to unravel everything these components can signal, but Polsky believes that someday interstitial fluid will join urine and blood as a fluid Doctors regularly test for their clinical diagnoses. That is the focus of the study the Author participated in.

After Robert Taylor, a Postdoctoral Fellow who works with Baca at UNM, cleaned the Author’s forearm with an alcohol wipe, the third five-needle holder was then pressed into the Author’s arm. There was a brief blow of pain and pressure similar to tugging on strands of hair. Then, except for the fact that the Author was asked not to move her hand and someone was pressing a finger-sized piece of plastic against her arm, she hardly noticed it. Taylor stated that future sensor systems will be set up to be simpler to use.

After about 10 minutes, the Author saw clear, water-like liquid seeping out of herself, into small glass straw-like capillaries. In 30 minutes, the five microneedle-capillaries collected about 2 microliters, or 1/30 of a drop.

Wearable sensors, early cancer detection, the bright future of microneedle-based sensors

For a number of applications the Researchers envision, the biomarker sensors would be on the extreme tip of the microneedle in order to allow persistent detection of the conditions inside the body. Future studies will make use of larger needle arrays in order to increase sample volume. For several other applications, such as early cancer detection, collecting the interstitial fluid may take a longer time than a standard blood draw, but could offer varied clues.

Future work deals with testing the tip-based sensors in people — they have already proved that it works well in solutions — and then observing the lactate levels in people undergoing vigorous exercise.

In June, the Researchers announced their interest in business partners to help incorporate the microneedle sensors into a self-contained device. The main goal of commercialization or a partnership with industry would be to bring technology to the market in a manner that benefits the public.

Sandia’s Laboratory Directed Research and Development program funded the early work on the sensor. The human studies are being funded by the U.S. Defense Threat Reduction Agency.

After four 30 minute interstitial fluid collections, the Author’s part is done. The red marks from the needle holder fade away after a few hours but the satisfaction of helping science lasts much longer. Baca’s team will carry out different tests on the Author’s interstitial fluid, bringing them one step closer to microneedle-based sensors for athletes, soldiers and patients.