Similar health monitoring devices have been popular with chronic disease patients and physicians who treat them; this technology may give clinical laboratories a new diagnostic tool
There is an ever-increasing number of companies working to develop lab testing technologies that would be used outside of the traditional clinical laboratory. One such example is Nutromics, an Australia-based medical technology company which recently announced it has raised US $14 million to fund its new lab-on-a-patch platform, according to a company press release.
Nutromics’ lab-on-a-patch device “uses DNA sensor technology to track multiple targets in the human body, including disease biomarkers and hard-to-dose drugs,” according to MobiHealthNews. Notably, Nutromics’ technology uses interstitial fluid as the sample source.
Nutromics raised $4 million last year to support a manufacturing facility and an initial human clinical trial of its “continuous molecular monitoring (CMM) platform technology that is able to track multiple targets in the human body via a single wearable sensor. The platform provides real-time, continuous molecular-level insights for remote patient monitoring and hospital-at-home systems,” MobiHealthNews reported.
“We are aiming to cause a paradigm shift in diagnostic healthcare by essentially developing a lab-on-a-patch. A lack of timely and continuous diagnostic insights can strongly impact outcomes when dealing with critical disease states. With this strategic industry and VC (venture capital) investment in us, we see more confidence in our technology and hope to accelerate our growth,” said entrepreneur and chemical engineer Peter Vranes (above), co-founder and CEO of Nutromics, in a press release. Clinical laboratory leaders have watched similar biometric monitoring devices come to fruition. (Photo copyright: Nutromics.)
How Nutromics’ Lab-on-a-Patch Works
“Our technology is, in fact, two technologies coming together—a marker and needle. What that does is give us access to fluid under your skin called interstitial fluid. If you’re going to measure something continuously, that’s a really good fluid [to measure],” Vranes told Outcomes Rocket.
Vranes calls the system’s aptamer-based sensor platform technology the “jewel in the crown.” An aptamer is a short sequence of artificial DNA or RNA that binds a specific target molecule. Nutromics’ aptamer sensor, Vranes said, enables targeting of analytes, unlike continuous glucose monitors (CGMs).
“[CGMs] are limited to metabolites—things that are already in the body like glucose and lactate. We’re not limited to those. We can do a whole range of different targets. And what that gives us is a ‘blue ocean’ opportunity to go in and solve problems in areas that other technologies just can’t solve,” Vranes said.
Nutromics plans to develop multiple aptamer-based sensors that measure a variety of analytes in interstitial fluid, Medtech Insight noted.
Nutromics’ wearable DNA sensor lab-on-a-patch technology (above) enables monitoring of multiple targets, including disease biomarkers and some medications, MobiHealthNews explained. The wearable patch contains microneedles that painlessly access interstitial fluid under the skin. Collected data is wirelessly transmitted to a software application and integrates with consumer health software and provider platforms, according to Nutromics. Medical laboratories could have a role in collecting this data and adding it other test results from patients using the wearable patch. (Photo copyright: Nutromics.)
Initial Launch Will Include Antibiotic Monitoring
Nutromics expects to initially launch therapeutic monitoring of vancomycin, a glycopeptide antibiotic medication used to treat various bacterial infections. The company says 60% of doses for this prescription antibiotic are not within therapeutic range.
“Interstitial fluid originates in the blood and then leaks out of capillaries to bring nutrients to cells in the body’s tissues. Because interstitial fluid is in direct communication with the cells, it should have information about the tissues themselves beyond what can be measured from testing the blood,” said Mark Prausnitz, PhD, Regents Professor and J. Erskine Love Jr. Chair, Georgia Tech School of Chemical and Biomolecular Engineering, in a 2020 news release announcing results of human trials of microneedle-based ISF sampling.
“We sampled interstitial fluid from 21 human participants and identified clinically relevant and sometimes distinct biomarkers in interstitial fluid when compared to companion plasma samples based on mass spectrometry analysis,” the scientists wrote.
Clinical laboratory leaders and pathologists will find it useful to monitor the development of diagnostics for use outside the lab. Nutromics is an example of a company developing wearable health technology that painlessly gathers data for lab tests to be conducted in point-of-care and near-patient settings.
Wearable microneedle sensors that track multiple biomarkers in interstitial fluid are finding their way into chronic disease monitoring and sample collecting for clinical laboratory testing
Wearable devices that replace finger sticks and blood draws for monitoring biomarkers of chronic diseases such as diabetes are the holy grail of non-invasive (or at least minimally invasive) technologies that collect specimens for clinical laboratory testing.
Advantage of Monitoring Multiple Biomarkers in Real Time
While current glucose monitors on the market only measure glucose, the UCSD wearable device also monitors alcohol and lactate, providing other additional information to diabetics when engaged in activities that affect those biomarkers.
For example, UCSD’s microneedle sensor allows diabetics to monitor their glucose level when drinking alcohol, which can lower glucose levels. Additionally, monitoring lactate while exercising also could be beneficial since physical activity influences the body’s ability to regulate glucose.
“With our wearable, people can see the interplay between their glucose spikes or dips with their diet, exercise, and drinking of alcoholic beverages. That could add to their quality of life as well,” said Farshad Tehrani, a nanoengineering PhD graduate researcher in Wang’s lab at UCSD and one of the co-first authors of the study, in the news release.
Other Microneedle Wearable Monitoring Patches
The quest for a painless alternative to in-patient blood draws for many clinical laboratory tests has been ongoing worldwide for years.
While further research and validation of studies are needed before UC San Diego’s wearable microneedle sensor patch can be deployed to monitor chronic diseases, it is in good company. Diabetics and other suffers of similar chronic diseases can look forward to a future where they can monitor their health conditions in real time without the need for invasive blood draws and clinical laboratory testing.
Platform could be next breakthrough in quest for painless technology to replace in-patient phlebotomy blood draws for many clinical laboratory tests
In a proof-of-concept study, scientists from Israel and China have developed a “smart” microneedle adhesive bandage that measures and monitors in real time three critical biomarkers that currently require invasive blood draws for medical laboratory tests commonly performed on patients in hospitals.
According to a Technion news release, the microneedles are short, thin, and relatively painless because they only extend through the outer layer of skin to reach the interstitial fluid underneath. The needle system attaches to the patient’s skin using an adhesive patch and transfers data wirelessly to both doctor and patient in real time through cloud and Internet of Things (IoT) technologies.
Such a novel technology that allows inpatients to be monitored for key biomarkers without the need for a phlebotomist to collect blood for testing will be attractive and would likely improve the patient’s experience.
It also could reduce the volume of specimen required, potentially eliminating the invasive specimen collection procedure altogether.
Leap Forward in Diagnostic Testing and Disease Monitoring
As pathologists and medical laboratory scientists are aware, sodium is a prominent prognostic biomarker for assessing certain blood conditions such as dysnatremia, the presence of too much or too little sodium. It’s an essential element found in blood cells and blood fluid that plays a vital role in transmitting signals to the nervous system, as well as in other biological functions.
Led by Hossam Haick, PhD, head of the LNDB (Laboratory for Nanomaterials-based Devices) group and Dean of Certification Studies at Technion, the team of scientists tested their device’s effectiveness at monitoring patients’ blood for both hypernatremia (high concentration of sodium in the blood) as well as hyponatremia (low concentration of sodium in the blood).
Both conditions can affect neurological function and lead to loss of consciousness and coma. Thus, early monitoring is critical.
“As of now, detection and monitoring of sodium levels in the human body is carried out by means of laborious and bulky laboratory equipment, or by offline analysis of various bodily fluids,” the study’s authors explained in the news release. Use of the smart microneedle patch, they added, allows the patient to continue about their day as normal, as well as gives their doctor time to attend to more patients.
The “innovative stretchable, skin-conformal and fast-response microneedle extended-gate FET (field-effect transistor) biosensor [integrated with] a wireless-data transmitter and the Internet-of-Things cloud for real-time monitoring and long-term analysis [could] eventually help [bring] unlimited possibilities for efficient medical care and accurate clinical decision-making,” noted the study’s authors in Advanced Materials.
More research will be needed to determine whether this latest medical technology breakthrough will lead to a viable minimally invasive method for measuring, diagnosing, and monitoring medical conditions, but Technion’s platform appears to be another step toward a long-sought alternative to painful blood draws.
Further, pathologists and clinical laboratory managers should expect more products to hit the market that are designed to collect a lab specimen without the need for a trained phlebotomist. Companies developing these products recognize that recruiting and retaining trained phlebotomist is an ongoing concern for medical labs. Thus, to have a method of collecting a lab specimen that is simple and can be done by anyone—including patients themselves—would be an important benefit.
The technology uses an easy-to-administer low-cost patch that can be applied to the skin like an adhesive bandage. The patch is virtually painless because the microneedles are too small to reach nerve receptors. Another unique aspect to this innovative approach to collecting a specimen for diagnostic testing is that the Washington University in St. Louis (WashU) research team designed the microneedle patch to include plasmonic-fluor. These are ultrabright gold nanolabels that light up target protein biomarkers and can make the biomarkers up to 1,400 times brighter at low concentrations, compared to traditional fluorescent labels.
The patch, states a WashU news release, “… can be applied to the skin, capture a biomarker of interest and, thanks to its unprecedented sensitivity, allow clinicians to detect its presence.”
The technology is low cost, easy for clinicians or patients themselves to use, and could eliminate the need for a trip to patient service center where a phlebotomist would draw blood for clinical laboratory testing, the news release states.
“We used the microneedle patch in mice for minimally invasive evaluation of the efficiency of a cocaine vaccine, for longitudinal monitoring of the levels of inflammatory biomarkers, and for efficient sampling of the calvarial periosteum [a skull membrane]—a challenging site for biomarker detection—and the quantification of its levels of the matricellular protein periostin, which cannot be accurately inferred from blood or other systemic biofluids,” the researchers wrote. “Microneedle patches for the minimally invasive collection and analysis of biomarkers in interstitial fluid might facilitate point-of-care diagnostics and longitudinal monitoring.”
Mark Prausnitz, PhD, Regents’ Professor, J. Erskine Love Jr. Chair in Chemical and Biomolecular Engineering, and Director of the Center for Drug Design, Development, and Delivery at Georgia Tech, told WIRED, “Blood is a tiny fraction of the fluid in our body. Other fluids should have something useful—it’s just hard to get those fluids.”
“Previously, concentrations of a biomarker had to be on the order of a few micrograms per milliliter of fluid,” said Zheyu (Ryan) Wang, a PhD candidate in Srikanth Singamaneni’s lab at McKelvey School of Engineering and a lead author of the paper, in the WashU news release. By using plasmonic-fluor, researchers were able to detect biomarkers on the order of picograms per milliliter—one millionth of the concentration.
“That’s orders of magnitude more sensitive,” Wang said.
Can Microneedles Be Used as a Diagnostic Tool?
As reported in WIRED, the polystyrene patch developed by Srikanth Singamaneni’s lab at McKelvey School of Engineering removes interstitial fluid from the skin and turns the needles into “biomarker traps” by coating them with antibodies known to bind to specific proteins, such as Interleukin 6 (IL-6). Once the microneedles are mixed with plasmonic-fluor, the patch will glow if the IL-6 biomarkers are present.
The development of such a highly sensitive biomarker-detection method means skin becomes a potential pathway for using microneedles to diagnose conditions, such as myocardial infarction or to measure COVID-19 antibodies in vaccinated persons.
Because the WashU study is a proof-of-concept in mice, it may be many years before this technology finds its way to clinical application. Many skin biomarkers will need to be verified for direct links to disease before microneedle patches will be of practical use to clinicians for diagnostics. However, microneedle patch technology has already proven viable for the collection of blood.
In 2017, Massachusetts-based Seventh Sense Biosystems (7SBio) received 510(k) clearance for a new microneedle blood collection device. Called TAP, the device is placed on the upper arm and blood collection starts with a press of a button. The process takes two to three minutes.
Initially, the FDA clearance permitted only healthcare workers to use the device “to collect capillary blood for hemoglobin A1c (HbA1c) testing, which is routinely used to monitor blood sugar levels in diabetic or pre-diabetic patients,” a Flagship Pioneering news release noted.
Then, in 2019, the FDA extended its authorization “to include blood collection by laypersons. Regulators are also allowing the device to be used ‘at-home’ for wellness testing,” a 7SBio news release stated. This opened the door for a microneedle device to be used for home care blood collection.
“No one likes getting blood drawn, but blood is the single-most important source of medical information in healthcare today, with about 90% of all diagnostic information coming from blood and its components,” Howard Weisman, former CEO of 7SBio and current CEO of PaxMedica, a clinical-stage biopharmaceutical company, said in the Flagship Pioneering news release. “TAP has the potential to transform blood collection from an inconvenient, stressful, and painful experience to one people can do themselves anywhere, making health monitoring much easier for both healthcare professionals and patients.”
As microneedle technology continues to evolve, clinical laboratories should expect patches to be used in a growing number of drug delivery systems and diagnostic tests. But further research will be needed to determine whether interstitial fluid can provide an alternate pathway for diagnosing disease.