News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

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News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
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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

Innovations in Microsampling Blood Technology Mean More Patients Can Have Blood Tests at Home, and Clinical Laboratories May Advance Toward Precision Medicine Goals

Clinical laboratory leaders aiming for patient-centered care and precision medicine outcomes need to acknowledge that patients do not want to be in hospitals or travel to physician offices and patient care centers for blood tests. It can be inconvenient, sometimes costly, and often painful.

That’s why disease management methods such as remote patient monitoring are appealing to many people. It’s a big market estimated to reach $1 billion by 2020, according to a Transparency Market Research Report. The study also associated popularity of devices such as heart rate and respiratory rate monitors with economic pressures of unnecessary hospital readmissions.

But can remote patient monitoring be used for more than to check heart rates, monitor blood glucose, and track activity levels? Could such technology be effectively leveraged by medical laboratories for remote blood sampling?

Microsampling versus Dried Blood Collecting

Remote patient monitoring must be able to address a large number of diseases and chronic health conditions for it to continue to expand and gain acceptance as a viable way to care for patients in different settings outside of hospitals. However, as most clinical pathologists and laboratory scientists know, clinical laboratory testing has an essential role in patient monitoring. Thus, there is the need for a way to collect blood and other relevant samples from patients in these remote settings.

One promising approach is the development of new microsampling technology that can overcome past obstacles of dried blood collection. Furthermore, microsampling-enabled devices can make it possible for medical laboratories to reach out to the homebound to secure accurate and volumetrically appropriate samples in a cost-effective manner.

“One well-established fact in today’s healthcare system is that an ever-greater proportion of patients want clinical care that is less invasive and less intrusive,” noted Robert Michel, Editor-in-Chief of Dark Daily and The Dark Report. “Patients want to take more control over their treatment and be more effective at maintaining the stability of their chronic conditions, and often are happier than those who need to travel to have chronic conditions monitored. To meet this need there has been significant innovation, particularly in the area of remote blood sampling using microsampling technology.”

For decades, medical laboratories have tried various methods for acquiring and transporting blood samples from remote locations. One such non-invasive alternative to venipuncture is called dried blood spot (DBS) collecting. It involves placing a fingerprick of blood on filter paper and allowing it to dry prior to transport to the lab.

But DBS collected bio samples often do not contain enough hematocrit (volume percentage of red blood cells) for laboratories and clinical pathologists to provide accurate reports and interpretations. Reported reasons DBS cards have not penetrated a wide market include:

  • Hematocrit bias or effect;
  • Costly card punching and automation equipment; and,
  • Possible disruption to existing lab workflows.

Microsampling Technology Enables Collection of Appropriate Samples

Microsampling has to have the capability to enable labs to deliver quality results from reliable blood samples. This remote sampling technology makes it possible for phlebotomists to offer a comfortable collection alternative for homebound patients and rural residents. It also can be useful for physicians stationed in remote areas. Patients themselves can even collect their own blood samples.

Volumetric Absorptive Microsampling (VAMS) technology enables accurate samples of blood or other fluids from amounts as small as 10, 20, or 30 microliters, according to Neoteryx, LLC, of Torrance, Calif., the developer of VAMS. The technology is integrated into the company’s Mitra microsampler blood collection devices (shown above) in formats for patient use and for medical laboratory microsample accessioning and extraction. Click here to watch a video on the Mitra Microsampler Specimen Collection Device. (Photo copyright: Neoteryx.)

One company developing these types of products is Neoteryx, LLC, of Torrance, Calif. It develops, manufactures, and distributes microsampling products. Patients with the company’s Mitra device use a lancet to puncture their skin and draw a small amount of blood, collect it on the device’s absorptive tip, and then mail the samples to a blood lab for testing (Neoteryx does not perform testing).

Fasha-Mahjoor

“Technologies such VAMS are driving [precision medicine] in an extremely cost-effective manner, while only requiring minimal patient effort. Patients are taking a more active role in their healthcare journeys, and at-home sampling is supporting this shift,” stated Fasha Mahjoor, Chief Executive Officer, Neoteryx, in a blog post. (Photo copyright: Neoteryx.)

Advantages of Microsampling

Patient satisfaction survey data collected by Neoteryx suggest patients are comfortable with their role in blood collection:

  • 70% are comfortable or very comfortable with the process;
  • 86% say it is easy or very easy to use the Mitra device;
  • 92% report it is easy to capture blood on the device’s tip;
  • 55% of Mitra device users are likely or very likely to choose microsampling over traditional venipuncture; and,
  • 93% noted they are likely or very likely to choose the device for child care.

A list of published studies describes certain advantages of VAMS technology that have implications for medical laboratories and clinical pathologists:

  • Microsampling has benefits and implications for therapeutic drug monitoring, infectious disease research, and remote specimen collection;
  • Dried blood microsamples from fingerstick can generate reliable data “correlating” to traditional blood collection processes;
  • Bioanalytical data collected with the Mitra device are accurate and dependable; and,
  • In a study for a panel of anti-epileptic drugs, VAMS led to optimized extraction efficiency above 86%, which means there was no hematocrit bias.

Learn More by Requesting the Dark Daily Microsampling White Paper

To help medical laboratories and clinical pathologists learn more about microsampling and VAMS devices, Dark Daily and The Dark Report have produced a white paper titled “How to Create a Patient-Centered Lab with Breakthrough Blood Collection Technology: Microsampling Takes Blood Collection Out of the Clinic.” The paper includes sections addressing these topics:

  • Rise of patient-centered care and remote patient monitoring;
  • Dried blood collection over the years and the hematocrit effect;
  • A look at microsampling and how it takes blood collection out of the clinic;
  • How Volumetric Absorptive Microsampling (VAMS) technology works;
  • Patient satisfaction data;
  • Research about microsampling including extensive graphics;
  • Launching new VAMS technology; and,
  • Frequently asked questions.

neoteryx-white-paper-cover

Innovative medical laboratory leaders who want to increase their understanding of how microsampling technology and remote patient monitoring relates to the goal of becoming a patient-centered lab are encouraged to request a copy of the white paper. It can be downloaded at no cost by clicking here, or placing https://www.darkdaily.com/how-to-create-a-patient-centered-lab-with-breakthrough-blood-collection-technology-9-2018/ into your browser.

—Donna Marie Pocius

Related Information:

Remote Patient Monitoring Devices Market

Neoteryx, LLC, and Cedars Sinai Partner to Investigate at Home Blood Sampling Possibilities for Patients with Inflammatory Bowel Disease

Creating a Patient-Centered Lab with Breakthrough Blood Collection Technology Using New Microsampling Methods Provides Reliable, Economic Collection, Shipping and Storage Solutions

How to Create a Patient-Centered Lab with Breakthrough Blood Collection Technology: Microscopy Takes Blood Collection Out of the Clinic

 

JCAHO Has Hospitals Scrambling to Reach Medication-Reconciliation Goal, Why McCleod Hospital in Florence, South Carolina Is an Early Success

Laboratory directors and pathologists are probably watching the scramble inside hospitals to meet new requirements for “medication-reconciliation.” Medication-reconciliation was first brought up by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in 2004, when they stated that it would be a goal on their 2005 Hospital National Patient Safety Goals. The goal was as follows:

Goal 8 Accurately and completely reconcile medications across the continuum of care.
8A During 2005, for full implementation by January 2006, develop a process for obtaining and documenting a complete list of the patient’s current medications upon the patient’s admission to the organization and with the involvement of the patient. This process includes a comparison of the medications the organization provides to those on the list.
8B A complete list of the patient’s medications is communicated to the next provider of service when it refers or transfers a patient to another setting, service, practitioner or level of care within or outside the organization.

JCAHO’s timetable, as published, is proving to be too ambitious. A November article in Modern Healthcare has revealed that many hospitals struggled to meet this goal. About 25% of hospitals surveyed by JCAHO were not in compliance by 2006.

Why is it difficult for one-quarter of the nation’s hospitals to achieve this goal? There are several key explanations for the problem. For example, an internal study by Froedtert Memorial Lutheran Hospital determined that pharmacists produced the most accurate list of medication lists. However, it is nurses who typically have this responsibility. This was documented in a study of hospital practices by the Institute for Safe Medication Practices that found that 94% of the time nurses were responsible for collecting the initial medication history and 77% of the time they were responsible for making sure the list was accurate. Hospitals lack the resources necessary to have pharmacists compile these lists. Besides inadequate budgets to pay appropriate staff to compile medication lists, hospitals reported that a major difficulty in compiling accurate lists was that patients simply did not know what drugs they were taking.

Given these widespread challenges, JCAHO’s timetable has provided inadequate time for many hospitals to successfully implement a functional and successful medication-reconciliation plan. One of the shining stars that emerged in the Modern Healthcare article was McLeod Health in Florence, SC. McLeod started instituting its medication-reconciliation program five years ago and it’s still working out the bugs. “At this point, “said Leanne Huminski, associate Vice President of Nursing, “we are perfecting where other hospitals are just starting.”

For laboratory directors and pathologists, the mandate for hospitals to implement medication reconciliation is instructive on at least three levels. First, it is an example of how evolving JCAHO requirements, with ambitious timetables, are designed to push hospital administrators to implement change more quickly. Second, medication reconciliation is directly linked to the national goal of improving patient safety. Third, as the nation’s hospitals successfully fulfill medication reconciliation requirements, it is likely that future initiatives to improve patient safety will begin to utilize more effective use of TDM (therapeutic drug monitoring). Increased TDM testing will require a closer level of support between clinical laboratories and the referring physicians.

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