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.
“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.
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.
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.
“To adapt the technology to daily life, we have developed a unique [adhesive bandage] made of a flexible and soft polymer that stretches and contracts along with the skin and therefore does not interfere with any action whatsoever,” said Hossam Haick, PhD (above), in a Technion news release. “Since it is important for us that the system is available to everyone, we made sure to use relatively inexpensive materials, so the final product will not be expensive. The technology we have developed represents a leap forward in diagnosing diseases and continuous physiological monitoring at home and in the clinic.” Such a real-time monitoring device could eliminate clinical laboratory testing for certain biomarkers that currently require invasive blood draws. (Photo copyright: Technion-Israel Institute of Technology.)
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.
Tuft’s proof-of-concept demonstration study shows how changes in saliva can be employed as biomarkers for development of future diagnostic monitoring devices and applications
For years, pathologists and dentists have recognized that the mouth contains many useful biomarkers for a wide range of health conditions and diseases. Now a study by a research team at Tufts University School of Engineering (Tufts) has demonstrated that a tooth-mounted sensor can reliably measure certain target markers.
In this proof-of-concept study, Tufts researchers developed a tooth-mounted sensor that monitors food consumption as it enters the body. This potentially adds behavioral data to the growing list of exploitable biomarkers available to developers of in vitro diagnostics (IVDs) and wearable medical monitoring devices. For that reason, many clinical laboratory managers and anatomic pathologists will want to track further development of this technology, which uses the mouth as the source of the markers to be measured.
A report detailing the device was first published in the scientific journal Advanced Materials in March of this year.
Sensor Reacts to Biomarkers in Saliva
The 2×2-millimeter flexible sensor consists of three layers and adheres to the tooth like a sticker. It has two gold outer rings surrounding an inner layer of bio-responsive material that is highly sensitive to glucose, salt, and alcohol. The presence of any of these substances alters the electrical properties of the sensor and incites it to transmit radio frequency waves that can be received by mobile devices.
Researchers conducting a proof-of-concept study at Tufts University School of Engineering have developed “a materials‐based strategy to add utility to traditional dielectric sensors by developing a conformal radiofrequency (RF) construct composed of an active layer encapsulated between two reverse‐facing split ring resonators,” their paper published in Advanced Materials notes. The sensor is shown above mounted to a tooth, where it reacts to the presence of certain biomarkers in the saliva, triggering the transmission of an RFID signal. This device has the potential to also measure the same biomarkers used in clinical laboratory tests. (Photo copyright: Smithsonian Magazine/Tufts University School of Engineering.)
There are many possible uses for this tooth-mounted sensor. Individuals with medical conditions such as diabetes, celiac disease, or hypertension, which require them to avoid certain substances in their diet, could benefit from utilizing a device that employs the technology under development at Tufts.
Such a gadget might also help those trying to lose weight. The creators hope to enhance the material, so it has the ability to discern additional nutrients and chemicals.
“If you can evolve the sensor and engineer it to have a database of food consumption, then you could think about nutrition management,” Fiorenzo Omenetto, PhD, Professor, Department of Biomedical Engineering at Tufts and one of the authors of the research told Smithsonian Magazine. “That could be reminding us that we’re indulging too much in sugar or something like that.”
It also could potentially detect physiological or chemical changes taking place in the body by detecting certain bio-markers in the saliva.
“In theory we can modify the bio-responsive layer in these sensors to target other chemicals. We’re really limited only by our creativity,” Omenetto noted in a news release. “We have extended common RFID [radio frequency identification] technology to a sensor package that can dynamically read and transmit information on its environment, whether it is affixed to a tooth, to skin, or any other surface.”
Other Food Intake Devices
There have been previous attempts to develop wearable devices that monitors food intake. However, those gadgets usually required the use of mouth guards and head gear, which are too cumbersome for continuous everyday use. The minute size of the Tufts tooth-mounted device renders it more practical for consumers. And, since it can be mounted anywhere on a tooth—front or back—it can be made undetectable while being worn.
“This study is an interesting proof-of-concept demonstration that small, wireless biosensors can detect changes in saliva due to the presence of compounds such as salt, sugar, and alcohol,” Ben Almquist, PhD, a lecturer in the Department of Bioengineering at Imperial College London, told Smithsonian Magazine.
“For instance, for continuous monitoring of food intake, the sensors will need to be robust enough to withstand abrasion during chewing,” Almquist noted. “In addition, foods are complex mixtures of compounds including salts, sugars and proteins, and the relative amounts of each that enter into saliva will depend on factors such as the nature of the food [i.e., cooked versus fresh], the amount of chewing, and the time in the mouth before swallowing.”
The device currently remains in the prototype stage and more testing will be needed to determine its efficacy and durability. However, the emergence of such wearable devices for medical use suggests valuable opportunities for clinical laboratories.
Because data captured from the tooth-mounted device is transmitted wirelessly, clinical laboratories could potentially store and monitor the data, compare the collected data to other medical laboratory test results for the same patient, then communicate that information to clinicians, other caregivers, and even the patients. This would be a new way for clinical laboratories to provide innovative, value-added services to healthcare professionals and consumers.
