Scientists believe the biodegradable device could someday help detect multiple saliva biomarkers. If true, it might provide a new type of test for clinical laboratories
When it comes to tongue depressors, it turns out you can teach an old dog new tricks. Researchers from National and Kapodistrian University of Athens Greece (NKUA) have taken this simple wooden medical tool and developed a high-tech biosensing device that may someday be useful at the point-of-care in hospitals and as a new type of test for clinical laboratories.
Using diode laser engraving, the researchers developed an “eco-friendly disposable sensor that can measure glucose levels and other biomarkers in saliva,” according to LabMedica.
This proof-of-principle biosensing device demonstrates the feasibility of “simultaneous determination of glucose and nitrite in artificial saliva,” according to the NKUA scientists who hope it will help doctors diagnose a variety of conditions.
In their published paper, the scientists at the University of Athens wrote that their wooden electrochemical biosensing tongue depressor (above) “is an easy-to-fabricate disposable point-of-care chip with a wide scope of applicability to other bioassays,” and that “it paves the way for the low-cost and straightforward production of wooden electrochemical platforms.” Might this and other similar biosensing devices eventually find their way to clinical laboratories for use in identifying and tracking certain biomarkers for disease? (Photo copyright: University of Athens.)
How to Make a High-Tech Tongue Depressor
Though wood is affordable and accessible, it doesn’t conduct electricity very well. The researchers’ first attempt to solve this problem was to use the wood as “a passive substrate” to which they coated “metals and carbon-based inks,” LabMedica reported. After that they tried using high-powered lasers to “char specific regions on the wood, turning those spots into conductive graphite.” But that process was complicated, expensive, and a fire hazard.
The researchers eventually turned to “low-power diode lasers” which have been used successfully “to make polyimide-based sensors but have not previously been applied to wooden electronics and electrochemical sensors,” LabMedica noted.
In their Analytical Chemistry paper, the researchers wrote, “A low-cost laser engraver, equipped with a low-power (0.5 W) diode laser, programmably irradiates the surface of the WTD [wooden tongue depressor], forming two mini electrochemical cells (e-cells). The two e-cells consist of four graphite electrodes: two working electrodes, a common counter, and a common reference electrode. The two e-cells are spatially separated via programmable pen-plotting, using a commercial hydrophobic marker pen.”
In other words, the researchers “used a portable, low-cost laser engraver to create a pattern of conductive graphite electrodes on a wooden tongue depressor, without the need for special conditions. Those electrodes formed two electrochemical cells separated by lines drawn with a water-repellent permanent marker,” states a press release from the American Chemical Society.
“The biosensor was then used to quickly and simultaneously measure nitrite and glucose concentrations in artificial saliva. Nitrite can indicate oral diseases like periodontitis, while glucose can serve as a diagnostic for diabetes. The researchers suggest that these low-cost devices could be adapted to detect other saliva biomarkers and could be easily and rapidly produced on-site at medical facilities,” LabMedica reported.
Benefits of Using Wood
One of the major benefits of using wood for their biosensing device is how environmentally friendly it is. “Since wood is a renewable, biodegradable naturally occurring material, the development of conductive patterns on wood substrates is a new and innovative chapter in sustainable electronics and sensors,” the researchers wrote in Analytical Chemistry.
Additionally, the tongue depressor features “An easy-to-fabricate disposable point-of-care chip with a wide scope of applicability to other bioassays, while it paves the way for the low-cost and straightforward production of wooden electrochemical platforms,” the researchers added.
This adds to a growing trend of developing bioassay products that keep the health of our planet in mind.
“This new BC test is non-toxic, naturally biodegradable and both inexpensive and scalable to mass production, currently costing less than $4.00 per test to produce. Its cellulose fibers do not require the chemicals used to manufacture paper, and the test is almost entirely biodegradable,” a UPenn blog post noted.
New Future Tool Use in Clinical Diagnostics
Who could have predicted that the lowly wooden tongue depressor would go high tech with technology that uses lasers to convert it to an electrochemical multiplex biosensing device for oral fluid analysis? This is yet another example of technologies cleverly applied to classic devices that enable them to deliver useful diagnostic information about patients.
And while a biosensing tongue depressor is certainly a diagnostic tool that may be useful for nurses and physicians in clinic and hospital settings, with further technology advancements, it could someday be used to collect specimens that measure more than glucose and nitrites.
Federal class action lawsuit looms as genetics company searches for what went wrong; a reminder to clinical laboratories of the importance of protecting patient information
Several years ago, security experts warned that biotechnology and genomics company 23andMe, along with other similar genetics companies, would be attacked by hackers. Now those predictions appear to have come true, and it should be a cautionary tale for clinical laboratories. In an October 6 blog post, the genetic testing company confirmed that private information from thousands of its customers was exposed and may be being sold on the dark web.
According to Wired, “At least a million data points from 23andMe accounts appear to have been exposed on BreachForums.” BreachForums is an online forum where users can discuss internet hacking, cyberattacks, and database leaks, among other topics.
“Hackers posted an initial data sample on the platform BreachForums earlier this week, claiming that it contained one million data points exclusively about Ashkenazi Jews,” Wired reported, adding that “hundreds of thousands of users of Chinese descent” also appear to be impacted.
The leaked information included full names, dates of birth, sex, locations, photos, and both genetic and ancestry results, Bleeping Computer reported.
For its part, 23andMe acknowledges the data theft but claims “it does not see evidence that its systems have been breached,” according to Wired.
Anne Wojcicki (above) is the co-founder and CEO of genetics company 23andMe, which on October 24 told its customers in an email, “There was unauthorized access to one or more 23andMe accounts that were connected to you through DNA Relatives. As a result, the DNA Relatives profile information you provided in this feature was exposed to the threat actor.” Clinical laboratories must work to ensure their patient data is fully secured from similar cyber theft. (Photo copyright: TechCrunch.)
23andMe Claims Data Leak Not a Security Incident
The data leaked has been confirmed by 23andMe to be legitimate. “Threat actors used exposed credentials from other breaches [of other company’s security] to access 23andMe accounts and steal the sensitive data. Certain 23andMe customer profile information was compiled through access to individual 23andMe.com accounts,” a 23andMe spokesperson told Bleeping Computer.
However, according to the company, the leak does not appear to be a data security incident within the 23andMe systems. “The preliminary results of this investigation suggest that the login credentials used in these access attempts may have been gathered by a threat actor from data leaked during incidents involving other online platforms where users have recycled login credentials,” the spokesperson added.
What the genetics company has determined is that compromised accounts were from users choosing the DNA Relative feature on their website as a means to find and connect to individuals related to them. Additionally, “the number of accounts sold by the cybercriminal does not reflect the number of 23andMe accounts breached using exposed credentials,” Bleeping Computer noted.
Price of Private Information
Following the 23andMe data leak, the private genetic information was quickly available online … for a price.
“On October 4, the threat actor offered to sell data profiles in bulk for $1-$10 per 23andMe account, depending on how many were purchased,” Bleeping Computer reported.
Stolen medical records are becoming hotter than credit card information, the experts say. “Stolen records sell for as much as $1,000 each,” according to credit rating agency Experian, Bleeping Computer noted.
In its 2018 Global Security Report, “cybersecurity firm Trustwave pegged the black-market value of medical records at $250 each. Credit card numbers, on the other hand, sell for around $5 each on the dark web … while Social Security numbers can be purchased for as little as $1 each,” Fierce Healthcare reported.
Clinical laboratory managers and pathologists should take note of the value that the dark web places on the medical records of a patient, compared to the credit card numbers of the same individual. From this perspective, hacking a medical laboratory to steal patient health data can be much more lucrative than hacking the credit card data from a retailer.
“Victims of the breach are now at increased risk of fraud and identity theft, and have suffered damages in the form of invasion of privacy, lost time and out-of-pocket expenses incurred responding to the breach, diminished value of their personal information, and lost benefit of the bargain with 23andMe,” according to court documents.
“The lawsuit brings claims of negligence, breach of implied contract, invasion of privacy/intrusion upon seclusion, unjust enrichment, and declaratory judgment,” Bloomberg Law noted. Additionally, the claim states that 23andMe “failed to provide prompt and adequate notice of the incident.”
Plaintiffs are “seeking actual damages, compensatory damages, statutory damages, punitive damages, lifetime credit-monitoring services, restitution, disgorgement, injunctive relief, attorneys’ fees and costs, and pre-and post-judgment interest,” Bloomberg Law reported.
Preventing Future Data Leaks
Years of experts warning genetics companies like 23andMe that they need more strict data security have proven to be true. “This incident really highlights the risks associated with DNA databases,” Brett Callow, a threat analyst at data security firm Emsisoft, told Wired. “The fact that accounts had reportedly opted into the ‘DNA Relatives’ feature is particularly concerning as it could potentially result in extremely sensitive information becoming public.”
“Callow notes that the situation raises broader questions about keeping sensitive genetic information safe and the risks of making it available in services that are designed like social networks to facilitate sharing. With such platforms come all of the data privacy and security issues that have plagued traditional social networks, including issues related to data centralization and scraping,” Wired noted.
Clinical laboratory databases are full of protected health information (PHI). Wise lab managers will work to ensure that their medical lab’s patient data is secure from today’s cyberthreats.
Proteins in human saliva make up its proteome and may be the key to new, precision medicine diagnostics that would give clinical pathologists new capabilities to identify disease
Clinical pathologists may soon have an array of new precision medicine diagnostic tools based on peoples’ saliva. There are an increasing number of “–omes” that can be the source of useful diagnostic biomarkers for developing clinical laboratory tests. The latest is the world’s first saliva protein biome wiki.
Called the Human Salivary Proteome Wiki (HSP Wiki), the “public data platform,” which was created by researchers at the University of Buffalo, is the “first of its kind,” according to Labroots, and “contains data on the many thousands of proteins present in saliva.”
The HSP Wiki brings together data from independent studies on proteins present in human saliva. One of the researchers’ goals is to speed up the development of saliva-based diagnostics and personalized medicine tools.
In “The Human Salivary Proteome Wiki: A Community-Driven Research Platform,” published in the Journal of Dental Research, the researchers wrote, “Saliva has become an attractive body fluid for on-site, remote, and real-time monitoring of oral and systemic health. At the same time, the scientific community needs a saliva-centered information platform that keeps pace with the rapid accumulation of new data and knowledge by annotating, refining, and updating the salivary proteome catalog.
“We developed the Human Salivary Proteome (HSP) Wiki as a public data platform for researching and retrieving custom-curated data and knowledge on the saliva proteome. … The HSP Wiki will pave the way for harnessing the full potential of the salivary proteome for diagnosis, risk prediction, therapy of oral and systemic diseases, and preparedness for emerging infectious diseases,” they concluded.
“This community-based data and knowledge base will pave the way to harness the full potential of the salivary proteome for diagnosis, risk prediction, and therapy for oral and systemic diseases, and increase preparedness for future emerging diseases and pandemics,” Stefan Ruhl, DDS, PhD (above right, with Omer Gokcumen, PhD, Associate Professor of Biological Sciences on left), Professor, Department of Oral Biology, University of Buffalo, and lead researcher of the study, told Labroots. Development of precision medicine clinical laboratory diagnostics is part of their research goals. (Photo copyright: University of Buffalo.)
Where Does Saliva Come From?
Saliva is a complex biological fluid that has long been linked to oral health and the health of the upper gastrointestinal tract. Only recently, though, have scientists begun to understand from where in the body saliva proteins originate.
The authors wrote: “Salivary proteins are essential for maintaining health in the oral cavity and proximal digestive tract, and they serve as potential diagnostic markers for monitoring human health and disease. However, their precise organ origins remain unclear.
“Through transcriptomic analysis of major adult and fetal salivary glands and integration with the saliva proteome, the blood plasma proteome, and transcriptomes of 28+ organs, we link human saliva proteins to their source, identify salivary-gland-specific genes, and uncover fetal- and adult-specific gene repertoires,” they added.
“Our results pave the way for future investigations into glandular biology and pathology, as well as saliva’s use as a diagnostic fluid,” the researchers concluded.
Saliva plays a crucial role in digestion by breaking down starches. It also provides a protective barrier in the mouth. When salivary glands malfunction, patients can face serious health consequences. Although clinicians and scientists have long understood the importance of saliva to good health, the question now is whether it contains markers of specific diseases.
“The Human Salivary Proteome Wiki contains proteomic, genomic, transcriptomic data, as well as data on the glycome, sugar molecules present on salivary glycoproteins. New data goes through an interdisciplinary team of curators, which ensures that all input data is accurate and scientifically sound,” noted Labroots.
The graphic above “shows the interconnectedness of the thousands of salivary proteins originating from blood plasma, parotid glands, and submandibular and sublingual glands. The diagram is one of many tools available to researchers and clinicians through the Human Salivary Proteome Wiki,” noted a UBNow blog post. (Graphic copyright: University of Buffalo.)
Omics and Their Role in Clinical Laboratory Diagnostics
Proteomics is just one of several hotly-researched -omics that hold the potential to develop into important personalized medicine and diagnostics tools for pathologists. Genomics is a related area of research being studied for its potential to benefit precision medicine diagnostics.
However, unlike genomes, which do not change, proteomes change constantly. That is one of the main reasons studying the human salivary proteome could lead to valuable diagnostics tools.
Combining the study of the -omes with tools like mass spectrometry, a new era of pathology may be evolving. “With the rapid decrease in the costs of omics technologies over the past few years, whole-proteome profiling from tissue slides has become more accessible to diagnostic labs as a means of characterization of global protein expression patterns to evaluate the pathophysiology of diseases,” noted Pathology News.
Saliva and the Age of Precision Medicine
The study of the -omes may be an important element in the evolution of precision medicine, because of its ability to provide information about what is happening in patients’ bodies at the point of care.
Thus, a full understanding of the proteome of saliva and what causes it to change in response to different health conditions and diseases could open the door to an entirely new branch of diagnostics and laboratory medicine. It is easy and non-invasive to gather and, given that saliva contains so much information, it offers an avenue of study that may improve patients’ lives.
It also would bring us closer to the age of precision medicine where clinical laboratory scientists and pathologists can contribute even more value to referring physicians and their patients.
Identifying patients who will likely develop prolonged concussion symptoms could lead to new clinical laboratory tests and personalized medicine treatments
Researchers are homing in on a new diagnostic assay for concussion that could potentially generate significant numbers of test referrals to the nation’s clinical laboratories. This innovative work is targeting how concussions are diagnosed and treated.
Each year, thousands of children receive sports-related injuries, including concussions. There are ways for anatomic pathologists and hospital medical laboratories to diagnose concussions; however, testing can be invasive and doesn’t always reveal a complete picture of the injury state.
Additionally, about one third of children with concussions develop prolonged symptoms. However, when prescribing treatment plans, physicians have been unable to predict which patients are likely to recover quickly versus those who will have a longer recovery.
Now, researchers at Penn State College of Medicine (Penn State) believe they have discovered five microRNAs in saliva that could be used to identify patients who will likely experience prolonged concussion symptoms even one month after the initial injury.
The study also found that certain materials in saliva can help diagnose the severity of concussions and could hold the key to more effective clinical laboratory tests and personalized medicine treatments.
The Penn State researchers published their study results in JAMA Pediatrics, a publication of the Journal of the American Medical Association (JAMA).
Concussion Leading Sports-related Brain Injury
There are approximately 3.8 million sports and recreation-related traumatic brain injuries in the United States each year and the majority of those cases are concussions, according to The Concussion Place. Most concussions treated in emergency rooms are due to falls, motor-vehicle related injuries, being struck by an object, assaults, or playing sports.
Also known as mild traumatic brain injuries (mTBI), concussions are caused by blows or jolts to the head or body that cause the brain to move with excessive force inside the skull. The sudden impact damages brain cells and causes chemical changes within the brain that alter normal functioning. Though usually not life threatening, the damage can be serious and linger for months.
Symptoms of concussion include: headaches, fatigue, nausea, vomiting, dizziness, balance problems, confusion, memory problems, sleep disturbances, and double or blurry vision. Symptoms usually occur immediately, but could take days or even weeks to appear.
Identifying Severity/Predicting Prolonged Symptoms of Traumatic Brain Injuries
After a concussion occurs, brain cells release small fragments of genetic material known as microRNAs while they attempt to repair themselves. A portion of these microRNAs appear in the injured person’s blood and saliva.
In order to determine whether these microRNAs could be used to determine the severity of a traumatic brain injury and predict whether prolonged symptoms would occur, the prospective cohort study researchers gathered saliva samples from 52 concussion patients between the ages of seven and 21:
The average age of the subjects was 14;
Twenty-two of the participants were female;
They were all athletes; and,
The majority of the samples were collected one to two weeks after the initial injury.
The researchers examined distinct microRNAs in the samples and identified some that enabled them to predict how long a patient’s concussion symptoms might last. In addition, they found one microRNA in children and young adults that accurately predicted which subjects would experience memory and problem-solving difficulties as part of their symptomatology.
The researchers also evaluated the concussion patients using the Sport Concussion Assessment Tool (SCAT-3), Third Edition. Physicians use this questionnaire to assess the symptoms and severity of concussions. The researchers also asked the parents of the concussed patients for observations about their children’s symptoms.
During follow up visits, which occurred at four- and eight-week increments following the original assessment, the Penn State researchers collected additional saliva samples and re-evaluated the patients using SCAT-3.
New Biomarkers Based on MicroRNAs Instead of Protein
“There’s been a big push recently to find more objective markers that a concussion has occurred, instead of relying simply on patient surveys,” Steven Hicks, MD, PhD, Assistant Professor of Pediatrics, Penn State College of Medicine, Hershey, Pa., one of the study researchers, told Penn State News.
“Previous research has focused on proteins, but this approach is limited because proteins have a hard time crossing the blood-brain barrier. What’s novel about this study is we looked at microRNAs instead of proteins, and we decided to look in saliva rather than blood,” he noted.
According to Steven Hicks, MD, PhD (above), who worked on the Penn State College of Medicine study, microRNAs could be more accurate than the traditional questionnaire when diagnosing and forecasting the effects of concussions. “The microRNAs were able to predict whether symptoms would last beyond four weeks with about 85% accuracy,” he told Penn State News. “In comparison, using the SCAT-3 report of symptoms alone is about 64% accurate. If you just go off the parent’s report of symptoms, it goes down to the mid-50s. In this pilot study, these molecular signatures are outperforming survey tools.” (Photo copyright: MD Magazine.)
The goal of this research was to develop a way to definitively ascertain that a concussion had occurred, predict the length and type of symptoms, and then use that data to improve and personalize care for children and young adults who have had a concussion.
“With that knowledge physicians could make more informed decisions about how long to hold a child out of sports, whether starting more aggressive medication regimens might be warranted, or whether involving a concussion specialist might be appropriate,” Hicks told MD Magazine. “Anytime we can use accurate, objective measures to guide medical care, I think that represents an opportunity to improve concussion treatment.”
Further research and clinical trials will be needed to solidify the effectiveness and accuracy of these new biomarkers. However, a rapid, non-invasive saliva test that can determine the severity of a concussion, and predicted whether prolonged symptoms will likely occur, would be widely used and could be an important assay for clinical laboratories. Particularly those associated with hospital medical laboratories and emergency rooms.
Clinical laboratory-on-a-chip would cost under £1 and allow young people to test themselves for sexually-transmitted diseases
Some wags call a new diagnostic testing concept the “pee in the cell phone” pathology lab test. The humor is directed at cell phone-based medical laboratory tests under development in the hopes that this confidential and private diagnostic test method will encourage more young people to undergo testing for sexually-transmitted diseases (STDs).
Newspapers in the United Kingdom are reporting on a research project—funded in part by the government—to develop STD tests that can be run on a USB-size chip that is inserted into a smart phone or a personal computer.
This project is a response to the significant rise in sexually transmitted infections (STIs) among young people. In the United Kingdom, the rate of new infections for herpes, chlamydia and gonorrhea are rising to record levels.
Clinical Laboratory Test on a Cell Phone or Personal Computer
