Research could lead to new biomarkers for clinical laboratory tests that spot disease early in patients
As we have covered in previous Dark Daily ebriefs, there are ongoing efforts to develop diagnostic assays that use human breath as the specimen. One early example was the breath specimen for Helicobacter pylori (H. pylori) testing—the bacteria that causes peptic ulcers—in the 1990s. Thus, a new sensor developed by scientists at Zhejiang University in China that can detect the presence of lung cancer in human breath will be of interest to medical laboratory scientists and clinical laboratories working on such testing.
In a proof-of-concept study, the Zhejiang University researchers “developed ultrasensitive nanoscale sensors that in small-scale tests distinguished a key change in the chemistry of the breath of people with lung cancer,” according to an American Chemical Society (ACS) news release.
The new research exemplifies how instruments are becoming increasingly sensitive to detection of smaller specimen quantities, making it possible to even use exhaled breath to diagnose lung cancer, noted a review article published in Science Direct.
“This study presents a novel Pt@InNiOx [platinum (Pt), indium (In), nickel (Ni)] nanoflake isoprene sensor that achieves an exceptionally low limit of detection at two parts per billion (2ppb)—the lowest reported for isoprene sensor to date,” wrote study lead author, Pingwei Liu, PhD (above), distinguished research fellow, Zhejiang University, et al, in ACS Sensors. “Our work not only provides a breakthrough in low-cost, noninvasive cancer screening through breath analysis but also advances the rational design of cutting-edge gas sensing materials.” Clinical laboratories working with breath sample biomarkers will be intrigued by this new advancement in the technology. (Photo copyright: Zhejiang University.)
Finding the Breakthrough Sensor
The Zhejiang University researchers were motivated by the potential for rapid gas sensing in diagnostics. Many gases, including carbon dioxide, are exhaled. But one particular gas, isoprene, they found “can indicate the presence of lung cancer,” the news release states.
However, while breath is readily available, it is not easy to isolate breath biomarkers. That is because a detector needs to “differentiate between volatile chemicals, withstand the natural humidity of exhaled breath, and detect tiny quantities of specific chemicals,” New Atlas explained.
To detect small specimen quantities of isoprene, a highly sensitive sensor needed to be developed—one that would be a step up from standard indium oxide-based breath sensors.
The scientists experimented with a series of indium (III) oxide (In203)-based nanoflake sensors until they found the sensor that performed consistently in nine experiments. They called it Pt@InNiOx for the platinum (Pt), indium (In), and nickel (Ni) it contained.
According to the news release, the Pt@InNiOx sensor:
Had “sensitivity that far surpassed earlier sensors” as evidenced by detection of isoprene as low as 2ppb.
Emphasized isoprene attraction over other volatile compounds in breath.
Has advanced sensitivity due to “Pt nanoclusters uniformly anchored on the nanoflakes” activating the isoprene sensing.
Gadget Review described the innovation as a “significant advance in diagnostic capability” that uses nanoscale technology along with “indium oxide nanoflakes with platinum-based nanoclusters.”
Developing the Lung Cancer Diagnostic Device
The scientists put their Pt@InNiOx nanoflakes into a portable sensing device for breath analysis. They then inserted breath samples from 13 people including five who had lung cancer. They found that:
In samples from people with cancer, the device enabled detection of isoprene levels lower than 40 ppb.
In samples from cancer-free participants, the device found isoprene levels more than 60 ppb.
“We integrate these ultrasensitive Pt@InNiOx nanoflakes into a miniaturized portable electronic device that successfully distinguishes lung cancer patients with expiratory isoprene below 40ppb, from the healthy population with isoprene above 60 ppb, enabling an accurate diagnosis in clinics,” wrote study lead author, Pingwei Liu, PhD, distinguished research fellow, Zhejiang University, et al, in ACS Sensors.
“As the isoprene hits the nanoflakes, electron release is sparked in a way that can be measured,” MSN Health reported, adding that the nanoflakes were also able to find isoprene in other chemicals and operate even in humid conditions.
Breath as Lab Test Biomarker for Cancer
In the United States, more people die from lung cancer than any other form of cancer, according to US Centers for Disease Control and Prevention statistics. The CDC data show there were 209,500 new lung and bronchus cancer cases in 2022, the most recent year for available data.
The Zhejiang University scientists reportedly plan to continue their research on the sensing materials and link between isoprene and lung cancer.
Studies continue to show many components in human breath can be used as clinical laboratory test biomarkers. Assays that use the breath as specimen may one day play an important role in early diagnosis of lung cancer and other diseases.
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.
New nanotechnology device is significantly faster than typical rapid detection clinical laboratory tests and can be manufactured to identify not just COVID-19 at point of care, but other viruses as well
Researchers at the University of Central Florida (UCF) announced the development of an optical sensor that uses nanotechnology to identify viruses in blood samples in seconds with an impressive 95% accuracy. This breakthrough underscores the value of continued research into technologies that create novel diagnostic tests which offer increased accuracy, faster speed to answer, and lower cost than currently available clinical laboratory testing methods.
The innovative UCF device uses nanoscale patterns of gold that reflect the signature of a virus from a blood sample. UCF researchers claim the device can determine if an individual has a specific virus with a 95% accuracy rate. Different viruses can be identified by using their DNA sequences to selectively target each virus.
According to a UCF Today article, the University of Central Florida research team’s device closely matches the accuracy of widely-used polymerase chain reaction (PCR) tests. Additionally, the UCF device provides nearly instantaneous results and has an accuracy rate that’s a marked improvement over typical rapid antigen detection tests (RADT).
Debashis Chanda, PhD (above), holds up the nanotechnology biosensor he and his team at the University of Central Florida developed that can detect viruses in a blood sample in seconds with 95% accuracy and without the need for pre-preparation of the blood sample. Chanda is professor of physics at the NanoScience Technology Center and the College of Optics and Photonics (CREOL) at UCF. Should this detection device prove effective at instantly detecting viruses at the point of care, clinical laboratories worldwide could have a major new tool in the fight against not just COVID-19, but all viral pathogens. (Photo copyright: University of Central Florida.)
Genetic Virus Detection on a Chip
“The sensitive optical sensor, along with the rapid fabrication approach used in this work, promises the translation of this promising technology to any virus detection, including COVID-19 and its mutations, with high degree of specificity and accuracy,” Debashis Chanda, PhD, told UCF Today. Chanda is professor of physics at the NanoScience Technology Center at UCF and one of the authors of the study. “Here, we demonstrated a credible technique which combines PCR-like genetic coding and optics on a chip for accurate virus detection directly from blood.”
The team tested their device using samples of the Dengue virus that causes Dengue fever, a tropical disease spread by mosquitoes. The device can detect viruses directly from blood samples without the need for sample preparation or purification. This feature enables the testing to be timely and precise, which is critical for early detection and treatment of viruses. The chip’s capability also can help reduce the spread of viruses.
No Pre-processing or Sample Preparation Needed for Multi-virus Testing
The scientists confirmed their device’s effectiveness with multiple tests using varying virus concentration levels and solution environments, including environments with the presence of non-target virus biomarkers.
“A vast majority of biosensors demonstrations in the literature utilize buffer solutions as the test matrix to contain the target analyte,” Chanda told UCF Today. “However, these approaches are not practical in real-life applications because complex biological fluids, such as blood, containing the target biomarkers are the main source for sensing and at the same time the main source of protein fouling leading to sensor failure.”
The researchers believe their device can be easily adapted to detect other viruses and are optimistic about the future of the technology.
“Although there have been previous optical biosensing demonstrations in human serum, they still require off-line complex and dedicated sample preparation performed by skilled personnel—a commodity not available in typical point-of-care applications,” said Abraham Vazquez-Guardado, PhD, a Postdoctoral Fellow at Northwestern University who worked on the study, in the UCS Today article. “This work demonstrated for the first time an integrated device which separated plasma from the blood and detects the target virus without any pre-processing with potential for near future practical usages.”
More research and additional studies are needed to develop the University of Central Florida scientists’ technology and prove its efficacy. However, should the new chip prove viable for point-of-care testing, it would give clinical laboratories and microbiologists an ability to test blood samples without any advanced preparation. Combined with the claims for the device’s remarkable accuracy, that could be a boon not only for COVID-19 testing, but for testing other types of viruses as well.
VCU scientists used the technique to measure mutations associated with acute myeloid leukemia, potentially offering an attractive alternative to DNA sequencing
More accurate but less-costly cancer diagnostics are the Holy Grail of cancer research. Now, research scientists at Virginia Commonwealth University (VCU) say they have developed a clinical laboratory diagnostic technique that could be far cheaper and more capable than standard DNA sequencing in diagnosing some diseases. Their method combines digital polymerase chain reaction (dPCR) technology with high-speed atomic force microscopy (HS-AFM) to generate nanoscale-resolution images of DNA.
The technique allows the researchers to measure polymorphisms—variations in gene lengths—that are associated with many cancers and neurological diseases. The VCU scientists say the new technique costs less than $1 to scan each dPCR reaction.
“We chose to focus on FLT3 mutations because they are difficult to [diagnose], and the standard assay is limited in capability,” said physicist Jason Reed, PhD, Assistant Professor in the Virginia Commonwealth University Department of Physics, in a VCU press release.
Reed is an expert in nanotechnology as it relates to biology and medicine. He led a team that included other researchers in VCU’s physics department as well as physicians from VCU Massey Cancer Center and the Department of Internal Medicine at VCU School of Medicine.
“The technology needed to detect DNA sequence rearrangements is expensive and limited in availability, yet medicine increasingly relies on the information it provides to accurately diagnose and treat cancers and many other diseases,” said Jason Reed, PhD (above center, with Andrey Mikheikin, PhD, on left and Sean Koebley, PhD, on right), in a press release from Virginia Commonwealth University (VCU). “We’ve developed a system that combines a routine laboratory process with an inexpensive yet powerful atomic microscope that provides many benefits over standard DNA sequencing for this application, at a fraction of the cost.” (Photo copyright: Virginia Commonwealth University.)
Validating the Clinical Laboratory Test
The physicists worked with two VCU physicians—hematologist/oncologist Amir Toor, MD, and hematopathologist Alden Chesney, MD—to compare the imaging technique to the LeukoStrat CDx FLT3 Mutation Assay, which they described as the “current gold standard test” for diagnosing FLT3 gene mutations.
The researchers said their technique matched the results of the LeukoStrat test in diagnosing the mutations. But unlike that test, the new technique also can measure variant allele frequency (VAL). This “can show whether the mutation is inherited and allows the detection of mutations that could potentially be missed by the current test,” states the VCU press release.
“We plan to continue developing and testing this technology in other diseases involving DNA structural mutations,” Reed said. “We hope it can be a powerful and cost-effective tool for doctors around the world treating cancer and other devastating diseases driven by DNA mutations.”
“In our approach we first used digital PCR, in which a mixed sample is diluted to less than one target molecule per aliquot and the aliquots are amplified to yield homogeneous populations of amplicons,” he said. “Then, we deposited each population onto an atomically-flat partitioned surface.”
The VCU researchers “scanned each partition with high-speed atomic force microscopy, in which an extremely sharp tip is rastered across the surface, returning a 3D map of the surface with nanoscale resolution,” he said. “We wrote code that traced the length of each imaged DNA molecule, and the distribution of lengths was used to determine whether the aliquot was a wild type [unmutated] or variant.”
In Diagnostics World, Reed said the method “doesn’t really have any more complexity than a PCR assay itself. It can easily be done by most lab technicians.”
Earlier Research
A VCU press release from 2017 noted that Reed’s research team had developed technology that uses optical lasers (similar to those in a DVD player) to accelerate the scanning. The researchers previously published a study about the technique in Nature Communications, and a patent is currently pending.
“DNA sequencing is a powerful tool, but it is still quite expensive and has several technological and functional limitations that make it difficult to map large areas of the genome efficiently and accurately,” Reed said in the 2017 VCU press release. “Our approach bridges the gap between DNA sequencing and other physical mapping techniques that lack resolution. It can be used as a stand-alone method or it can complement DNA sequencing by reducing complexity and error when piecing together the small bits of genome analyzed during the sequencing process.”
Using CRISPR technology, the team also developed what they described as a “chemical barcoding solution,” placing markers on DNA molecules to identify genetic mutations.
New DNA Clinical Laboratory Testing?
Cancer diagnostics are constantly evolving and improving. It is not clear how long it will be before VCU’s new technique will reach clinical laboratories that perform DNA testing, if at all. But VCU’s new technique is intriguing, and should it prove viable for clinical diagnostic use it could revolutionize cancer diagnosis. It is a development worth watching.
The self-cleaning material has been proven to repel even the deadliest forms of antibiotic resistant (ABR) superbugs and viruses. This ultimate non-stick coating is a chemically treated form of transparent plastic wrap which can be adhered to surfaces prone to gathering germs, such as door handles, railings, and intravenous therapy (IV) stands.
“We developed the wrap to address the major threat that is posed by multi-drug resistant bacteria,” Leyla Soleymani, PhD, Associate Professor at McMaster University and one of the leaders of the study, told CNN. “Given the limited treatment options for these bugs, it is key to reduce their spread from one person to another.”
According to research published in the peer-reviewed Southern Medical Journal, “KPC-producing bacteria are a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality.”
Were those surfaces covered in this new bacterial-resistant
coating, life-threatening infections in hospital ICUs could be prevented.
Taking Inspiration from Nature
In designing their new anti-microbial wrap, McMaster researchers took their inspiration from natural lotus leaves, which are effectively water-resistant and self-cleaning thanks to microscopic wrinkles that repel external molecules. Substances that come in contact with surfaces covered in the new non-stick coating—such as a water, blood, or germs—simply bounce off. They do not adhere to the material.
The “shrink-wrap” is flexible, durable, and inexpensive to
manufacture. And, the researchers hope to locate a commercial partner to
develop useful applications for their discovery.
“We’re structurally tuning that plastic,” Soleymani told SciTechDaily. “This material gives us something that can be applied to all kinds of things.”
In the video above, Leyla Soleymani, PhD, Associate Professor at McMaster University, explains how “The new plastic surface—a treated form of conventional transparent wrap—can be shrink-wrapped onto door handles, railings, IV stands, and other surfaces that can be magnets for bacteria such as MRSA and C. difficile. This may be technology that has great value to clinical laboratories and microbiology laboratories. Click here to watch the video. (Image and video copyright: McMaster University/YouTube.)
Industries Outside of Healthcare Also Would Benefit
According to the US Centers for Disease Control and Prevention (CDC), at least 2.8 million people get an antibiotic-resistant infection in the US each year. More than 35,000 people die from these infections, making it one of the biggest health challenges of our time and a threat that needs to be eradicated. This innovative plastic coating could help alleviate these types of infections.
And it’s not just for healthcare. The researchers said the coating could be beneficial to the food industry as well. The plastic surface could help curtail the accidental transfer of bacteria, such as E. coli, Salmonella, and Listeria in food preparation and packaging, according to the published study.
“We can see this technology being used in all kinds of institutional and domestic settings,” Tohid Didar, PhD, Assistant Professor at McMaster University and co-author of the study, told SciTechDaily. “As the world confronts the crisis of anti-microbial resistance, we hope it will become an important part of the anti-bacterial toolbox.”
Clinical laboratories also are tasked with preventing the
transference of dangerous bacteria to patients and lab personnel. Constant
diligence in application of cleaning protocols is key. If this new anti-bacterial
shrink wrap becomes widely available, medical laboratory managers and
microbiologists will have a new tool to fight bacterial contamination.
