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.)
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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.
Painless technology could one day replace some phlebotomy blood draws as the go-to specimen-collection method for clinical laboratory testing and health monitoring
Clinical laboratories have long sought a non-invasive way to do useful medical laboratory testing without the need for either a venipuncture or a needle stick. Now engineers at the McKelvey School of Engineering at Washington University in St. Louis in Missouri have developed a disposable microneedle patch that one day could be a painless alternative to some blood draws for diagnostics tests and health monitoring.
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 have created a platform technology that anyone can use. And they can use it to find their own biomarker of interest,” study leader Srikanth Singamaneni, PhD (above), Lilyan and E. Lisle Hughes Professor in the Department of Mechanical Engineering and Materials Sciences at Washington University in St. Louis, said in the WashU news release. Singamaneni and his colleagues are developing a new specimen collection method that might someday be widely used by clinical laboratories. (Photo copyright: Washington University in St. Louis.)
“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.
Unlike blood, dermal interstitial fluid often does not contain high enough concentrations of biomarkers to be easily detectable. To overcome this hurdle, the Washington University in St. Louis research team developed a microneedle patch with plasmonic-fluor—ultrabright gold nanolabels (above)—which lit up target protein biomarkers, making them roughly 1,400 times brighter at low concentrations than when using traditional fluorescent labels commonly used in many medical laboratory tests. (Photo copyright: Washington University in St. Louis.)
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.
“Now we can actually use this tool to understand what’s going on with interstitial fluid, and how we’re going to be able to use it to answer healthcare-related or medical problems,” Maral Mousavi, PhD, Assistant Professor of Biomedical Engineering, Viterbi School of Engineering at the University of Southern California, told WIRED. “I think it has the potential to be that kind of a game changer.”
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.
