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UC San Diego Engineers Develop Microneedle Wearable Patch That Measures Glucose, Alcohol, Muscle Fatigue in Real Time

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.

Now, in their quest for alternatives to invasive phlebotomy blood draws, engineers at University of California San Diego’s (UCSD) Center for Wearable Sensors have added their own wearable device to the mix. The scientists developed a “lab-on-the-skin” multi-tasking microneedle sensor that monitors multiple biomarkers simultaneously, according to a UCSD news release.

Joseph Wang, PhD
“This is like a complete lab on the skin,” said Joseph Wang, PhD (above), Distinguished Professor of Nanoengineering at UC San Diego and Director of UCSD’s Center of Wearable Sensors, in a news release. “It is capable of continuously measuring multiple biomarkers at the same time, allowing users to monitor their health and wellness as they perform their daily activities.” UC San Diego’s microneedle patch for monitoring biomarkers of disease certainly would be popular with patients who must regularly undergo painful blood draws for clinical laboratory testing. (Photo copyright: UC San Diego.)

The UCSD engineers published their findings in the journal Nature Biomedical Engineering, titled, “An Integrated Wearable Microneedle Array for the Continuous Monitoring of Multiple Biomarkers in Interstitial Fluid.”

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.

UC San Diego’s wearable microneedle patch
UC San Diego’s wearable microneedle patch (above) is about the size of a stack of six quarters and simultaneously monitors glucose, alcohol, and lactate levels continuously. It affixes to the skin through a patch of microneedles each about one-fifth the width of a human hair. The microneedles barely penetrate the surface of the skin to sample biomolecules in the interstitial fluid and are not painful. The quarter-sized patch is worn on the upper arm and transmits its data to a smartphone app. The microneedle patch is disposable, and the reusable electronic case is rechargeable using an off-the-shelf wireless charging pad. (Photo copyright: Laboratory for Nanobioelectronics/UC San Diego.)

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.

In “Researchers Develop ‘Smart’ Microneedle Adhesive Bandage System for Monitoring Sodium, Glucose, pH, and More,” Dark Daily reported on a proof-of-concept study conducted by scientists from Israel and China who 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.

And in “Researchers at Washington University in St. Louis Use Microneedle Patch with Fluorescent Nanolabels to Detect Biomarkers in Skin’s Interstitial Fluid,” we covered how engineers at the McKelvey School of Engineering at Washington University had developed a microneedle patch with plasmonic-fluor, ultrabright gold nanolabels that light up target proteins making the biomarkers up to 1,400 times brighter at low concentrations compared to traditional fluorescent labels.

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. 

Andrea Downing Peck

Related Information:

An Integrated Wearable Microneedle Array for the Continuous Monitoring of Multiple Biomarkers in Interstitial Fluid

Multi-Tasking Wearable Continuously Monitors Glucose, Alcohol and Lactate

‘A Laboratory on the Skin’: UC San Diego Lab Works to Make New Wearable Health Sensors Part of Our Daily Look

Researchers Develop ‘Smart’ Microneedle Adhesive Bandage System for Monitoring Sodium, Glucose, pH, and More

Researchers at Washington University in St. Louis Use Microneedle Patch with Fluorescent Nanolabels to Detect Biomarkers in Skin’s Interstitial Fluid

German Researchers Create Non-invasive Lab-on-a-Chip Biosensor That Detects Antibiotic Levels from Breath Samples

Should the device prove effective, it could replace invasive point-of-care blood draws for clinical laboratory testing during patient drug therapy monitoring

What if it were possible to perform therapeutic drug monitoring (TDM) without invasive blood draws using breath alone? Patients fighting infections in hospitals certainly would benefit. Traditional TDM can be a painful process for patients, one that also brings risk of bloodline infections. Nevertheless, regular blood draws have been the only reliable method for obtaining viable samples for testing.

One area of critical TDM is in antibiotic therapy, also known as personalized antibiotherapy. However, for antibiotic therapy to be successful it typically requires close monitoring using point-of-care clinical laboratory testing.

Now, a team of engineers and biotechnologists from the University of Freiburg in Germany have developed a biosensor that can use breath samples to measure antibiotic concentrations present in blood, according to a University of Freiburg press release.

The team’s non-invasive collection method requires no needle sticks and can allow for frequent specimen collections to closely monitor the levels of an antibiotic prescribed for a patient. The biosensor also provides physicians the ability to tailor antibiotic regimens specific to individual patients, a core element of precision medicine.

The researchers published their findings in the journal Advanced Materials, titled, “Biosensor-Enabled Multiplexed On-Site Therapeutic Drug Monitoring of Antibiotics.”

Can Dincer, PhD
 
“Until now researchers could only detect traces of antibiotics in the breath,” said Can Dincer, PhD (above), Junior Research Group Leader at the University of Freiburg, and one of the authors of the study, in the press release. “With our synthetic proteins on a microfluid chip, we can determine the smallest concentrations in the breath condensate and [how] they correlate with the blood values.” Should the breath biosensor prove effective in clinical settings, painful blood draws for clinical laboratory testing at the point of care could become obsolete. (Photo copyright: Conny Ehm/University of Freiburg.)

Can a Breath Biosensor Be as Accurate as Clinical Laboratory Testing?

The University of Freiburg’s biosensor is a multiplex, microfluid lab-on-a-chip based on synthetic proteins that react to antibiotics. It allows the simultaneous measurement of several breath samples and test substances to determine the levels of therapeutic antibiotics in the blood stream.

To perform their research, the University of Freiburg team tested their biosensor on blood, plasma, urine, saliva, and breath samples of pigs that had been given antibiotics. The results the researchers achieved with their device using breath samples were as accurate as standard clinical laboratory testing, according to the press release.

The microfluidic chip contains synthetic proteins affixed to a polymer film via dry film photoresist (DFR) technology. These proteins are similar to proteins used by drug-resistant bacteria to sense the presence of antibiotics in their environment. Each biosensor contains an immobilization area and an electrochemical cell which are separated by a hydrophobic stopping barrier. The antibiotic in a breath sample binds to the synthetic proteins which generates a change in an electrical current. 

“You could say we are beating the bacteria at their own game,” said Wilfried Weber, PhD, Professor of Biology at the University of Freiburg and one of the authors of the research paper, in the press release.

Rapid Monitoring at Point-of-Care Using Breath Alone

The biosensor could prove to be a useful tool in keeping antibiotic levels stable in severely ill patients who are dealing with serious infections and facing the risk of sepsis, organ failure, or even death. Frequent monitoring of therapeutic antibiotics also could prevent bacteria from mutating and causing the body to become resistant to the medications.

“Rapid monitoring of antibiotic levels would be a huge advantage in hospital,” said H. Ceren Ates, PhD, scientific researcher at the University of Freiburg and one of the authors of the study in the press release. “It might be possible to fit the method into a conventional face mask.”

Along those lines, the researchers are also working on a project to create wearable paper sensors for the continuous measurement of biomarkers of diseases from exhaled breath. Although still in the development stages, this lightweight, small, inexpensive paper sensor can fit into conventional respiratory masks, according to a University of Freiburg press release.

Other Breath Analysis Devices Under Development

Devices that sample breath to detect biomarkers are not new. Dark Daily has regularly reported on similar developments worldwide.

In “NIST Scientists Enhance Frequency Comb Breathalyzer Enabling It to Detect Multiple Disease Biomarkers,” we reported on research conducted at JILA, a research center jointly operated by the National Institutes of Standards and Technology (NIST) and the University of Colorado Boulder, that could pave the way for real-time, noninvasive breath analysis to detect and monitor diseases, and potentially eliminate the need for many blood-based clinical laboratory tests.

And in “Will Blowing in a Device Be Useful in Screening for COVID-19? FDA Grants Its First EUA for a Breathalyzer SARS-CoV-2 Screening Test,” Dark Daily covered the FDA’s first ever emergency use authorization (EUA) for a portable breath test device designed to screen for SARS-CoV-2 infection. Developed by InspectIR Systems, the COVID-19 Breathalyzer identifies a chemical signature associated with SARS-CoV-2 in about three minutes with 91.2% sensitivity and 99.3% specificity.

Thus, University of Freiburg’s non-invasive lab-on-a-chip biosensor is worth watching. More research is needed to validate the effectiveness of the biosensor before it could be employed in hospital settings, however, monitoring and managing antibiotic levels in the body via breath samples could prove to be an effective, non-invasive method of providing personalized antibiotic therapy to patients.

Clinical trials on human breath samples are being planned by the University of Freiburg team. This type of precision medicine service may give medical professionals the ability to maintain proper medication levels within an optimal therapeutic window.

JP Schlingman

Related Information:

Antibiotic Levels Measurable in Breath for the First Time

Biosensor-Enabled Multiplexed On-Site Therapeutic Drug Monitoring of Antibiotics

A Breath of Fresh Information

NIST Scientists Enhance Frequency Comb Breathalyzer Enabling It to Detect Multiple Disease Biomarkers

Will Blowing in a Device Be Useful in Screening for COVID-19? FDA Grants Its First EUA for a Breathalyzer SARS-CoV-2 Screening Test

Legal Experts Predict Ex-Theranos President/COO Ramesh ‘Sunny’ Balwani Faces Uphill Battle for Acquittal

‘Balwani is no Johnny Depp,’ says an expert on juror behavior, as prosecution and defense rest in fraud trial of the former executive of the now-defunct lab test company

Clinical Laboratory directors and pathologists continue to focus like a laser beam on the trials of former founders and executives of the now-defunct blood test company Theranos. But as the criminal fraud trial of ex-president and COO Ramesh “Sunny” Balwani comes to a close, legal experts maintain the 57-year-old businessman may face an uphill battle to win an acquittal.

Balwani faces 12 counts of wire fraud and conspiracy to commit wire fraud while serving as second in command at Theranos, the former Silicon Valley medical laboratory test startup. The fraud trials of Balwani and Theranos founder Elizabeth Holmes have made headlines for more than a year as the two once-high-flying executives face a reckoning for allegedly defrauding patients, investors, and physicians about their proprietary Edison blood-testing device, which they claimed could conduct hundreds of blood tests using a finger-prick of blood.

Before resting their case, Balwani’s defense team called only two witnesses: information-technology consultant Richard Sonnier III, and naturopathic physician Tracy Wooten, NMD, of Arizona, who sent more than 100 patients to Theranos.

According to The Wall Street Journal(WSJ), Wooten “backtracked some of her support for Theranos on the stand.”

The WSJ reported that Sonnier’s testimony “had been hotly litigated by attorneys,” and that US District Judge Edward Davila ruled in May that Sonnier would be permitted to testify—with limitations—about the Theranos Laboratory Information System (LIS), which contained patient test results.

Theranos LIS Not Accessible to Government Prosecutors

Sonnier was hired by Balwani’s legal team to assess the accessibility of data held in the LIS, which the defense believed would have provided evidence of Theranos test accuracy.

The WSJ noted that in 2018, the year Balwani and Holmes were indicted, the government subpoenaed a copy of the LIS, which Theranos provided. However, the LIS data was delivered on an encrypted hard drive.

“Not only was the hard drive itself encrypted, but the data it contained was also encrypted with a separate passcode required,” the WSJ wrote. “The government didn’t have the passcode to access the data, and a day or two after sending the hard drive to US attorneys, Theranos officials ordered the entire original database dismantled, according to court testimony.”

The WSJ reported that Sonnier testified he was unable to access the encrypted data on a backup hard drive despite having a list of possible passcodes found in Theranos documents. Sonnier also testified that it would have been “very straightforward” to reassemble the original LIS and “recover that data.” The missing password wouldn’t be an issue, Sonnier testified.

Ramesh “Sunny” Balwani
Ramesh “Sunny” Balwani (above) ex-president and COO of now defunct blood test startup Theranos, faces 12 counts of wire fraud and conspiracy to commit wire fraud. In an interview with Insider, an expert in conducting jury research, focus groups, witness preparation, and jury selections said that “both the evidence and the way Balwani is perceived would affect his chances of being acquitted.” And that, “He has a lot of problems that [Elizabeth Holmes] didn’t have. He kind of fits the part from a juror’s standpoint.” Clinical laboratory directors will learn much from how Balwani’s role as the primary decision-maker in the Theranos lab is perceived by the jury. (Photo copyright: Justin Sullivan/Getty Images/Newsweek.)

The Prosecution Rests

Federal prosecutors rested their case last month after calling more than 24 witnesses. The government alleges Balwani worked closely with Holmes and conspired with her to defraud investors and patients about the startup’s blood testing technology. They allege he knew about the accuracy and reliability problems that plagued Theranos’ Edison blood-testing device.

Holmes was convicted in January on three of the nine fraud counts and one of two conspiracy counts. She was acquitted on four counts related to defrauding patients, one charge of conspiracy to commit wire fraud and three charges of wire fraud.

While prosecutors failed to persuade jurors that Holmes intentionally sought to defraud patients, Bloomberg legal reporter Joel Rosenblatt told the Bloomberg Law Podcast he believes Balwani is “inherently more vulnerable” on the patient-related fraud counts because he “oversaw” the operation of Theranos’ clinical laboratories.

“As a result of that role, [Balwani] was more aware of not only the faulty Theranos blood test results, but all the problems that employees were pointing out about those results,” Rosenblatt added. “So, he was the first high-level executive to be dealing with those complaints.”

Rosenblatt noted that Balwani’s defense centers not only on trying to show that Theranos’ proprietary blood-testing machine worked, but that it “works maybe well enough or worked as well as other [medical] laboratories.” He said Balwani also maintains that Holmes, as CEO and founder, was in charge long before he joined Theranos as president.

“It’s a difficult argument to make because all the emails show how cooperative they were, how closely they worked together. They were intimately involved but they were working side by side for years and really during the years where all the money started coming in,” Rosenblatt said in the podcast.

Jill Huntley Taylor, PhD, CEO of Taylor Trial Consulting, told Insider that Balwani has an uphill battle to win an acquittal.

“He has a lot of problems that [Elizabeth Holmes] didn’t have,” Taylor said. “He kind of fits the part from a juror’s standpoint. He’s got the power, the authority, he’s got the personal traits that make the allegations more credible from a perceptual standpoint for the jury.”

In contrast, Taylor says, “People don’t love Elizabeth Holmes, but I think what she had going for her was that she pitched herself as a true believer in the company. She was the voice and the face of Theranos.”

‘Balwani is not Johnny Depp’

While a jury recently awarded actor Johnny Depp significantly more damages than actress Amber Heard in their well-publicized defamation trial, Taylor maintains jurors are unlikely to view Balwani as a sympathetic figure.

“Sunny Balwani is not Johnny Depp. He doesn’t have the halo that Johnny Depp has, or the fan base,” Taylor said. “He does not present as that type of person, so I don’t know that the jurors will have any sympathy towards him. And I think they would actually be more inclined to believe Holmes’ allegations.”

The Theranos fraud trials of Holmes and Balwani continue to capture the attention of clinical laboratory directors and pathologists who are now witnessing the final chapters in the downfall of the one-time Silicon Valley power couple. 

Andrea Downing Peck

Related Information:

Former Theranos President’s Defense Rests in Criminal-Fraud Trial

Will Sunny Balwani Beat Charges of Patient Fraud?

Elizabeth Holmes’ Ex-boyfriend Sunny Balwani ‘Is No Johnny Depp,’ Says an Expert on Juror Behavior

Legal Victory for Johnny Depp after He and Amber Heard found Liable for Defamation

The United States of America vs Elizabeth A. Holmes and Ramesh “Sunny” Balwani

Will Sunny Balwani Beat Charges of Patient Fraud?

Two University of North Carolina School of Medicine Laboratories Develop Technique for Seeing How Proteins Change Shape In Vivo

UNC’s novel way to visualize the human proteome could lead to improved clinical laboratory tests along with the development of new therapies

Diagnostic testing based on proteomics is considered to be a field with immense potential in diagnostics and therapeutics. News of a research breakthrough into how scientists can visualize protein activity within cells will be of major interest to the pathologists, PhDs, and medical laboratory scientists who specialize in clinical laboratory testing involving proteins.

Proteins are essential to all life and to the growth, maintenance, and repair of the human body. So, a thorough understanding of how they function within living cells would be essential to informed medical decision-making as well. And yet, how proteins go about doing their work is not well understood.

That may soon change. Scientists at the University of North Carolina (UNC) School of Medicine have developed an imaging method that could provide new insights into how proteins alter their shapes within living cells. And those insights may lead to the development of new therapies and medical treatments.

Dubbed “binder-tag” by the UNC scientists, their new technique “allows researchers to pinpoint and track proteins that are in a desired shape or ‘conformation,’ and to do so in real time inside living cells,” according to a UNC Health news release.

Two labs in the UNC School of Medicine’s Department of Pharmacology collaborated to develop the binder-tag technique:

The scientists published their findings in the journal Cell, titled, “Biosensors Based on Peptide Exposure Show Single Molecule Conformations in Live Cells.”

Klaus Hahn PhD
 
“No one has been able to develop a method that can do, in such a generalizable way, what this method does. So, I think it could have a very big impact,” said lead author of the UNC study Klaus Hahn PhD (above), in the news release. “With this method we can see, for example, how microenvironmental differences across a cell affect, often profoundly, what a protein is doing,” he added. This research may enlarge scientists’ understanding of how the human proteome works and could lead to new medical laboratory tests and therapeutic drugs. (Photo copyright: UNC School of Medicine.)
 

How Binder-Tag Works

During their study, the UNC scientists developed binder-tag “movies” that allow viewers to see how the binder-tag technique enables the tracking of active molecules in living cells.

According to Cosmos:

  • The technique involves two parts: a fluorescent binder and a molecular tag that is attached to the proteins of interest.
  • When inactive, the tag is hidden inside the protein, but when the protein is ready for action it changes shape and exposes the tag.
  • The binder then joins with the exposed tag and fluoresces. This new fluorescence can easily be tracked within the cell.
  • Nothing else in the cell can bind to the binder or tag, so they only light up when in contact on the active protein.
  • This type of visualization will help researchers understand the dynamics of a protein in a cell.

“The method is compatible with a wide range of beacons, including much more efficient ones than the interacting beacon pairs required for ordinary FRET [fluorescence resonance energy transfer]. Binder-tag can even be used to build FRET sensors more easily. Moreover, the binder-tag molecules were chosen so that nothing in cells can react with them and interfere with their imaging role,” Hahn said in the news release.

“Only upon exposure can the peptide specifically interact with a reporter protein (the binder). Thus, simple fluorescence localization reflects protein conformation. Through direct excitation of bright dyes, the trajectory and conformation of individual proteins can be followed,” the UNC researchers wrote in Cell. “The simplicity of binder-tag can provide access to diverse proteins.”  

The UNC researchers’ binder-tag technique is a way to overcome the dire challenge of seeing tiny and hard-working proteins, Cosmos noted. Typical light microscopy does not enable a view of molecules at work. This paves the way for the new binder-tag technique, UNC pointed out.

“With this method, we can see, for example, how microenvironmental differences across a cell affect—and often profoundly—what a protein is doing,” Hahn said. “For a lot of protein-related diseases, scientists haven’t been able to understand why proteins start to do the wrong thing. The tools for obtaining that understanding just haven’t been available.”

More Proteins to Study

More research is needed before the binder-tag method can be used in diagnostics. Meanwhile, the UNC scientists intend to show how binder-tag can be applied to other protein structures and functions. 

“The human proteome has between 80,000 and 400,000 proteins, but not all at one time. They are expressed by 20,000 to 25,000 human genes. So, the human proteome has great promise for use in diagnostics, understanding disease, and developing therapies,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.

Medical scientists and diagnostics professionals will want to stay tuned to discover more about the tiny—though mighty—protein’s contributions to understanding diseases and patient treatment.     

Donna Marie Pocius

Related Information:

Biosensors Based on Peptide Exposure Show Single Molecule Conformations in Live Cells

Powerful Technique Allows Scientists to Study How Proteins Change Shape Inside Cells

Watching Proteins Dance

Binder-Tag: A Versatile Approach to Probe and Control the Conformational Changes of Individual Molecules in Living Cells

NIST Scientists Enhance Frequency Comb Breathalyzer Enabling It to Detect Multiple Disease Biomarkers

Device could pave the way for real-time, noninvasive breath analysis to detect and monitor diseases and be a new service medical laboratories can offer

Breathalyzer technology is not new, but until now human breath detection devices have not been comparable to clinical laboratory blood testing for disease detection and monitoring. That may soon change and there are implications for clinical laboratories, partly because breath samples are considered to be non-invasive for patients.

Scientists with JILA, a research center jointly operated by the National Institutes of Standards and Technology (NIST) and the University of Colorado Boulder, recently increased the sensitivity of their laser frequency comb breathalyzer one thousand-fold. This created a device that can detect four disease biomarkers simultaneously, with the potential to identify six more, according to an NIST news release.

Medical laboratory scientists will understand the significance of this development. JILA’s enhanced breathalyzer device could pave the way for real-time, noninvasive breath analysis to detect and monitor diseases, and potentially eliminate the need for many blood-based clinical laboratory tests.

The JILA researchers published their findings in the journal Proceedings of the National Academy of Sciences (PNAS), titled, “Ultrasensitive Multispecies Spectroscopic Breath Analysis for Real-Time Health Monitoring and Diagnostics.”

Measuring Light to Spot Biomarkers of Disease

During their research, physicist Jun Ye, PhD, and David Nesbitt, PhD, both Fellows at JILA and professors at University of Colorado Boulder, detected and monitored four biomarkers in the breath of a volunteer:

These chemicals can be indicators of various health conditions. Methane in the breath, for example, can indicate intestinal problems.

The researchers say the JILA breathalyzer also could detect six additional biomarkers of disease without any further modifications to the device. They would include:

Jun Ye, PhD and David Nesbitt, PhD
 
NIST/JILA Research Fellows Jun Ye, PhD (left), and David Nesbitt, PhD (right) of the University of Colorado Boulder, “built a breathalyzer that identifies biomarkers of disease by measuring the colors and amounts of light absorbed as a laser frequency comb passes through breath samples inside a glass tube,” according to an NIST news release. Should they succeed in creating a portable version, their noninvasive device could become an option compared to conventional clinical laboratory blood testing methods used to identify and monitor diseases. (Photos copyright: University of Colorado Boulder.)
 

“Determining the identity and concentration of the molecules present in breath is a powerful tool to assess the overall health of a person, analogous to blood testing in clinical medicine, but in a faster and less invasive manner,” the researchers wrote in PNAS.

“The presence of a particular molecule (or combination of molecules) can indicate the presence of a certain health condition or infection, facilitating a diagnosis. Monitoring the concentration of the molecules of interest over time can help track the development (or recurrence) of a condition, as well as the effectiveness of the administered treatment,” they added.

How the JILA Breathalyzer Detects Biomarkers

According to a 2008 NIST news release, JILA researchers had developed a prototype comb breathalyzer in that year. However, the research did not continue. But then the COVID-19 pandemic brought the JILA/NIST laboratories focus back to the breathalyzer with hopes that new research could lead to a breath test for detecting the SARS-CoV-2 coronavirus and other conditions.

“We are really quite optimistic and committed to pushing this technology to real medical applications,” Ye said in the 2021 NIST news release.

Analytical Scientist explained that JILA’s new and improved breathalyzer system “fingerprints” chemicals by measuring the amount of light absorbed as a laser frequency comb passes back and forth through breath samples loaded into a mirrored glass tube.

JILA’s original 13-year-old prototype comb analyzed colors and amounts of light in the near-infrared band. However, JILA’s recent improvements include advances in optical coatings and a shift to analyzing mid-infrared band light, allowing detection sensitivity up to parts-per-trillion level, a thousand-fold improvement over the prototype. 

Corresponding study author Jutta Toscano, PhD, postdoctoral researcher at the University of Basel in Switzerland and previously Lindemann fellow at JILA, told Physics World the new frequency comb can “probe the molecular fingerprint region where fundamental, and more intense, spectroscopic transitions are found.

“By matching the frequency of the comb teeth with the cavity modes—the ‘standing modes’ of the cavity—we can increase the interaction path length between molecules inside the cavity and laser light by a factor of around 4000, equivalent to an effective path length of a few kilometers,” she added. “We then probe the light that leaks out of the cavity by sending it into an FTIR [Fourier-transform infrared] spectrometer to find out which exact comb teeth have been absorbed and by how much. In turn, this tells us which molecules are present in the breath sample and their concentration.”

Even Hippocrates Studied Breath

Ye noted in the NIST statement that JILA is the only institution that has published research on comb breathalyzers.

In their PNAS paper, the researchers wrote, “Breath analysis is an exceptionally promising and rapidly developing field of research, which examines the molecular composition of exhaled breath. … Despite its distinctive advantages of being a rapid, noninvasive technique and its long history dating back to Hippocrates, breath analysis has not yet been as widely deployed for routine diagnostics and monitoring as other methods, such as blood-based analysis.

“We have shown that this technique offers unique advantages and opportunities for the detection of light biomarkers in breath,” the researchers noted, “and it is poised to facilitate real-time, noninvasive monitoring of breath for clinical studies, as well as for early detection and long-term monitoring of temporary and permanent health conditions.”

Validation of these findings and further design research to make the system portable are required before JILA’s frequency comb breathalyzer can become a competitor to clinical laboratory blood tests for disease identification and monitoring. Nevertheless, JILA’s research brings breathalyzer technology a step closer to offering real-time, non-invasive analysis of human biomarkers for disease.

Andrea Downing Peck

Related Information:

Ultrasensitive Multispecies Spectroscopic Breath Analysis for Real-Time Health Monitoring and Diagnostics

Ultrasensitive Frequency Comb Breathalyzer Targets Real-Time Disease Diagnosis

JILA’s Comb Breathalyzer Is Now a Thousand-Fold More Sensitive to Disease Biomarkers

Breath Analysis with a (Very) Fine Toothed Comb

Optical ‘Frequency Comb’ Can Detect the Breath of Disease

Smart Pacifier That Monitors Electrolyte Levels in Saliva Could Prove to Be Beneficial for Vital Care of Infants in Newborn Intensive Care Units

Tiny sensors with Bluetooth technology that measure useful biomarkers may eliminate need for invasive blood draws used for clinical laboratory tests

What if a baby’s pacifier could be used to measure electrolyte levels in newborns? An international research team has developed just such a device, and it has the potential to reduce invasive blood collections required to provide specimens for clinical laboratory testing of critical biomarkers. At the same time, this device may allow continuous monitoring of electrolyte levels with wireless alerts to caregivers.

Developed at Washington State University (WSU) Vancouver with researchers from the United States and South Korea, the wireless bioelectronic pacifier monitors electrolyte levels in newborn intensive care unit (NICU) babies and sends the collected data to caregivers and hospital information systems in real time.

Reliable Information from Consistent Monitoring

Typical blood draws for NICU babies can cause information gaps as they are usually  only performed twice a day. This can be problematic in cases where more frequent monitoring of these biomarkers is required to monitor the infant’s condition.

“We know that premature babies have a better chance of survival if they get a high quality of care in the first month of birth,” said Jong-Hoon Kim, PhD, Associate Professor at the WSU School of Electrical Engineering and Computer Science, in a WSU news release. “Normally, in a hospital environment, they draw blood from the baby twice a day, so they just get two data points. This device is a non-invasive way to provide real-time monitoring of the electrolyte concentration of babies.”

Kim is a co-corresponding author of the WSU study published in the peer-reviewed journal Biosensors and Bioelectronics, titled, “Smart Bioelectronic Pacifier for Real-Time Continuous Monitoring of Salivary Electrolytes.”

The smart pacifier (above) developed by researchers at the Washington State University School of Electrical Engineering and Computer Science—in collaboration with scientists in two South Korean institutions—provides continuous monitoring of sodium and potassium ion levels. This can help detect and prevent potentially dangerous dehydration issues in NICU babies without invasive blood draws for traditional clinical laboratory testing. (Photo copyright: University of Washington.)

How the Smart Pacifier Works

The miniature system developed by the WSU researchers utilizes a typical, commercially available pacifier outfitted with ion-selective sensors, flexible circuits, and microfluidic channels that monitor salivary electrolytes. These flexible, microfluidic channels attract the saliva when the pacifier is in the infant’s mouth which enables continuous and efficient saliva collection without the need for any type of pumping system. The gathered data is relayed wirelessly to caregivers using Bluetooth technology.

When the researchers tested their smart pacifier on infants, they discovered that the results captured from the device were comparable to information obtained from normal blood draws and standard clinical laboratory tests. Kim noted in the press release that technology currently in use to test infant saliva for electrolytes tend to be bulky, rigid devices that require a separate sample collection.

“You often see NICU pictures where babies are hooked up to a bunch of wires to check their health conditions such as their heart rate, the respiratory rate, body temperature, and blood pressure,” said Kim in the press release. “We want to get rid of those wires.”

The researchers intend to make the components for the device more affordable and recyclable. They also plan to perform testing for their smart pacifier on larger test groups to prove efficacy and hope the gadget will help make NICU treatment less disruptive for infant patients.

Co-authors on the WSU study include researchers from the Georgia Institute of Technology, and Pukyong National University and Yonsei University College of Medicine in South Korea.

Before the ‘Smart’ Pacifier Were ‘Smart’ Diapers!

Going as far back as 2013, Dark Daily has covered research into the use of sensors placed in wearables and disposables to detect and monitor health issues.

In “New ‘Smart Diaper’ Tests Baby’s Urine for Urinary Tract Infections, Dehydration, and Kidney Problems—then Alerts Baby’s Doctor,” Dark Daily reported on how the advent of digital technology and smartphones was moving medical laboratory testing out of the central laboratory and into the bedside, homes, and into diapers!

And this past fall, in “Researchers in Japan Have Developed a ‘Smart’ Diaper Equipped with a Self-powered Biosensor That Can Monitor Blood Glucose Levels in Adults,” we reported on researchers who were combining diagnostics with existing products to help medical professionals and patients monitor bodily functions and chronic diseases.

“It should be noted that the ability to put reliable diagnostic sensors in disposables like diapers has been around for almost a decade and does not seem to have caught on with either caregivers or the public,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication, The Dark Report. “Because the researchers who developed the pacifier are attempting to solve a problem for NICU babies, this solution might find acceptance.”

This is another example of how researchers are thinking outside the box as to how to measure critical biomarkers without the need to send a specimen to the core clinical laboratory and wait hours—sometimes overnight—for results.

JP Schlingman

Related Information:

Smart Pacifier Developed to Monitor Infant Health in Hospitals

Smart Bioelectronic Pacifier for Real-time Continuous Monitoring of Salivary Electrolytes

Researchers in Japan Have Developed a ‘Smart’ Diaper Equipped with a Self-powered Biosensor That Can Monitor Blood Glucose Levels in Adults

New ‘Smart Diaper’ Tests Baby’s Urine for Urinary Tract Infections, Dehydration, and Kidney Problems—then Alerts Baby’s Doctor

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