New Rapid Test for Deadly Mosquito-borne Dengue Virus

University of the Sunshine Coast researchers have developed a rapid portable test for one of the world's fastest-spreading mosquito-borne diseases.

With World Mosquito Day on 20 August marking the ongoing battle against dengue fever in tropical and subtropical countries including northern Australia, the UniSC research team is taking its findings to the next level.

UniSC Associate Professor of Molecular Engineering Dr. Joanne Macdonald published their results in Gates Open Research with co-authors Dr. Madeeha Ahmed and Dr. Nina Pollak.

"We developed a rapid test, with results that look similar to a COVID-19 home stick test, for each of the four types of dengue virus," said Dr. Macdonald. They were sensitive enough to detect even small amounts of viral genetic material in mosquitoes using only pipettes (tubes) and a heating block, instead of expensive laboratory equipment.

"Our entire testing process took about 35 minutes on-the-spot, compared to hours of travel time and PCR processing required for current sampling."

The method involves reverse transcription-isothermal recombinase polymerase amplification (RT-RPA) combined with lateral flow detection (LFD).

She said the innovative method involved a reagent that inactivated the virus during amplification, enabling simpler, quicker and cheaper detection with a higher level of sensitivity than existing stick tests.

"In practical terms, people and authorities in areas with few resources can set a trap and test mosquitos each week, to check whether dengue is present.

"It has the potential to make mosquito screening more accessible, enhancing surveillance and control efforts in countries where dengue is endemic."

The paper was co-authored by researchers from the QIMR Berghofer Medical Research Institute, Queensland Health and The University of Queensland.

Dr. Nina Pollak has since published a collaborative paper in Microbiology Spectrum investigating the potential of using the tests to detect dengue in human serum, plasma and blood.

Adding co-authors from UniSC (Dr. David McMillan and Malin Olsson), Singapore's National Environment Agency, National University of Singapore, UQ and industry partner BioCifer, this paper also supported the advantages of the new method.

"Our tests provided performance and speed without compromising specificity in human plasma and serum and could become promising tools for the detection of high dengue loads in resource-limited settings," Dr. Pollak said.

The team's next goal is to combine each test for the four dengue serotypes into a single test, to further streamline detection.

Dr. Ahmed said the tests aimed to lay the groundwork for future studies focused on actual use and effectiveness in the field.

"We hope the value of our technology will drive interest among users to conduct field trials in regions where the disease is prevalent," she said.

According to the WHO, dengue fever is a painful and deadly disease that infects up to 400 million people every year. It is a viral infection that spreads to people from mosquito saliva infected with dengue viruses. There is no treatment other than for relief of symptoms, which include high fever, head and body aches, nausea and rash.

More information: 

Madeeha Ahmed et al, Rapid molecular assays for the detection of the four dengue viruses in infected mosquitoes, Gates Open Research (2022). DOI: 10.12688/gatesopenres.13534.2

Nina M. Pollak et al, Rapid Diagnostic Tests for the Detection of the Four Dengue Virus Serotypes in Clinically Relevant Matrices, Microbiology Spectrum (2023). DOI: 10.1128/spectrum.02796-22

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Researchers Develop New Rapid and Reliable COVID-19 Detection Method based on MALDI-TOF

Commercially available mass spectrometers can be reliably used to detect the SARS-CoV-2 coronavirus, according to research from the Martin Luther University Halle-Wittenberg (MLU). In a study recently published in Clinical Proteomics, the researchers introduce a novel method that leverages equipment already in use in hospitals and laboratories for detecting bacterial and fungal infections.

The entire process, from taking a swab to receiving results, takes just two hours. The research team believes that this method can be easily adapted to identify other pathogens, potentially serving as a valuable tool in managing future pandemics.

The new method requires a nasal or throat swab. The sample needs to be prepared before it can be analyzed by a mass spectrometer, which takes only a few seconds. In MALDI-TOF mass spectrometry, a laser pulse is used to transfer the sample to the gas phase – then the mass of the individual components is measured.

“This allows us to directly and unambiguously measure individual virus particles of the coronavirus. Thus false-positive results can be ruled out,” says Professor Andrea Sinz from the Institute of Pharmacy at MLU, who specializes in mass spectrometry and proteins. Her team was already able to show in July 2020 that mass spectrometers are generally capable of detecting SARS-CoV-2. However, at this time, the method was still time-consuming and required very high-end equipment.

The advantage of the new method is that MALDI-TOF mass spectrometers are already being used in many laboratories and clinics to diagnose bacterial or fungal infections and are thus readily available. The devices can even distinguish between different variants of the virus. However, the method is not yet as sensitive as polymerase chain reaction (PCR), the most sensitive corona test to date. This means that not all infections may be detected when there is a very low viral load. On the other hand, it is much faster and more flexible.

“In acute phases, the method would make an ideal addition to PCR because we would be able to analyze a lot of samples very quickly. Rapid and reliable results may make it easier to contain outbreaks,” explains Lydia Kollhoff, lead author of the study. Moreover, the approach could be adapted rather easily to other pathogens in future pandemics and supplement PCR testing.

The scientists from Halle want to further optimize the method in partnership with the University of Leipzig Medical Centre. Following this, the method would undergo a certification process so that it could be used clinically.

Reference: 

“Development of a rapid and specific MALDI-TOF mass spectrometric assay for SARS-CoV-2 detection” by Lydia Kollhoff, Marc Kipping, Manfred Rauh, Uta Ceglarek, Günes Barka, Frederik Barka, and Andrea Sinz, 1 July 2023, Clinical Proteomics. DOI: 10.1186/s12014-023-09415-y

The study was funded by the Federal Ministry for Economic Affairs and Climate Action and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).

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Genie in the LAMP: Rapid Diagnostics Help Protect Horses from Disease Threats

Scientists believe important strides can be made in protecting horses from disease threats, amid growing national and international equine movements, by further developing LAMP technology.

LAMP stands for loop-mediated isothermal amplification. It is a nucleic acid amplification method capable of offering rapid and accurate diagnosis of infectious diseases.

Researchers Alexandra Knox, Gemma Zerna and Travis Beddoe, in a review published in the journal Animals, looked at equine bacterial diseases that pose biosecurity risks and their current diagnostic approaches. For each disease, they looked at developments in terms of LAMP testing.

The trio, with the Department of Animal, Plant and Soil Sciences, part of the Centre for AgriBioscience at La Trobe University in Australia, said the equine industry is an enduring and essential entity worldwide.

It plays a crucial role in many cultures and communities by serving as a source of employment, entertainment, and companionship. It also provides substantial global economic value, estimated at $US300 billion annually.

The authors said the movement and trade of horses have rapidly increased worldwide in recent decades, which has created more opportunities for importation and exposure to diseases. This growth in horse movements has applied pressure on current biosecurity management practices.

“Whilst these measures throughout countries are diligent and ever-adapting to new situations, there remains an apparent urgency for improved surveillance techniques to prevent detrimental disease outbreaks,” they said.

“For a vast number of bacterial diseases of concern, current diagnostics and surveillance methodology rely on out-of-date technology or are time-consuming, with a lengthy turnaround of results.

“In addition to international movement and trade, surveillance at equine events and on farms should remain vigilant; this requires accessible technology that can be utilized in a range of environments, including resource-poor communities.

“Therefore, continuous and rigorous monitoring and detection methods should be of the utmost importance for equine research.”

They said that while attention is largely focused on controlling viral pathogens, bacterial diseases pose similar damaging outcomes.

Many highly contagious bacterial diseases can be transmitted easily from direct contact between horses or indirect contact with contaminated objects, they said.

“Despite extensive biosecurity laws for the importation and exportation of horses worldwide, bacterial outbreaks continue to frequently occur.” Some, they said, are devastating.

“To prevent such events, disease surveillance and diagnosis must be heightened throughout the industry.”

However, current common, or “gold-standard” techniques, have been shown to be inadequate at times. At times, they do not serve the wider community due to the inaccessibility of expensive machinery.

“Additionally, the vast majority of current gold-standard detection methods are time-consuming and do not allow for immediate action in cases of outbreaks.”

Thus, newer technologies are required to impede outbreaks.

“LAMP has proven to be a sound molecular technique that overcomes most pitfalls associated with other nucleic acid amplification techniques,” they said.

Further research into improving LAMP tests has shown promising results that can strengthen this method beyond current capabilities. These include the potential use of additives that have been trialed with other nucleic acid amplification techniques. Additives can increase analytical sensitivity and test stability.

However, as studies for enhancing these tests in equine medicine are limited, the review team strongly recommends further investigations on additive effects for disease detection and surveillance, as it is clear that additive improvements are test-specific.

Furthermore, the use of simple field-deployable amplification and detection techniques has the potential to revolutionize LAMP technology.

“There is an apparent need for rapid results for the implementation of control measures to prevent detrimental spread and outbreaks throughout the equine industry, and thus, it is suggested that the development of LAMP methodologies should be a focal point of research in equine medicine.”

The authors said the robust nature and ease of use of LAMP, coupled with continuous advancements, gives little doubt as to why this technology is being rapidly developed in research for equine disease diagnosis and surveillance.

“Yet, despite numerous assays being designed and optimized for equine bacterial diseases of biosecurity importance, LAMP has failed to replace gold-standard techniques thus far.

“This could derive from a gap in communication between researchers and those who perform diagnostic procedures.”

More advocating regarding the advantages of LAMP, such as the cost and time of such tests, could help overcome this.

“Furthermore, as LAMP is designed to have simplistic and flexible methodologies, thus not requiring trained personnel, there should be more endorsement for those who directly work with horses every day, for example, farmers and stud owners, to self-manage surveillance using these assays (tests).”

Eventually, by using a simple field-deployable “lab-on-a-chip” or microfluidic device, horse owners could potentially be able to perform testing themselves.

“Whilst it is evident that LAMP could become a breakthrough technique for the equine industry, continuous development and optimization do need to occur,” they said.

Additionally, bridging the gap of communication between researchers and diagnosticians regarding LAMP test implementation is essential to advance current diagnostic and surveillance techniques, and continue to protect the equine industry.

Reference:

Knox, A.; Zerna, G.; Beddoe, T. Current and Future Advances in the Detection and Surveillance of Biosecurity-Relevant Equine Bacterial Diseases Using Loop-Mediated Isothermal Amplification (LAMP). Animals 2023, 13, 2663. 

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Tiny Magnetic Beads Produce an Optical Signal that Could be Used to Quickly Detect Pathogens

Getting results from a blood test can take anywhere from one day to a week, depending on what a test is targeting. The same goes for tests of water pollution and food contamination. And in most cases, the wait time has to do with time-consuming steps in sample processing and analysis.

Now, MIT engineers have identified a new optical signature in a widely used class of magnetic beads, which could be used to quickly detect contaminants in a variety of diagnostic tests. For example, the team showed the signature could be used to detect signs of the food contaminant Salmonella.

The so-called Dynabeads are microscopic magnetic beads that can be coated with antibodies that bind to target molecules, such as a specific pathogen. Dynabeads are typically used in experiments in which they are mixed into solutions to capture molecules of interest. But from there, scientists have to take additional, time-consuming steps to confirm that the molecules are indeed present and bound to the beads.

The MIT team found a faster way to confirm the presence of Dynabead-bound pathogens, using optics, specifically, Raman spectroscopy. This optical technique identifies specific molecules based on their “Raman signature,” or the unique way in which a molecule scatters light.

The researchers found that Dynabeads have an unusually strong Raman signature that can be easily detected, much like a fluorescent tag. This signature, they found, can act as a “reporter.” If detected, the signal can serve as a quick confirmation, within less than one second, that a target pathogen is indeed present in a given sample. The team is currently working to develop a portable device for quickly detecting a range of bacterial pathogens, and their results will appear in an Emerging Investigators special issue of the Journal of Raman Spectroscopy.

“This technique would be useful in a situation where a doctor is trying to narrow down the source of an infection in order to better inform antibiotic prescription, as well as for the detection of known pathogens in food and water,” says study co-author Marissa McDonald, a graduate student in the Harvard-MIT Program in Health Sciences and Technology. “Additionally, we hope this approach will eventually lead to expanded access to advanced diagnostics in resource-limited environments.”

Study co-authors at MIT include Postdoctoral Associate Jongwan Lee; Visiting Scholar Nikiwe Mhlanga; Research Scientist Jeon Woong Kang; Tata Professor Rohit Karnik, who is also the associate director of the Abdul Latif Jameel Water and Food Systems Lab; and Assistant Professor Loza Tadesse of the Department of Mechanical Engineering.

Oil and water

Looking for diseased cells and pathogens in fluid samples is an exercise in patience.

“It’s kind of a needle-in-a-haystack problem,” Tadesse says.

The numbers present are so small that they must be grown in controlled environments to sufficient numbers, and their cultures stained, then studied under a microscope. The entire process can take several days to a week to yield a confident positive or negative result.

Both Karnik and Tadesse’s labs have independently been developing techniques to speed up various parts of the pathogen testing process and make the process portable, using Dynabeads.

Dynabeads are commercially available microscopic beads made from a magnetic iron core and a polymer shell that can be coated with antibodies. The surface antibodies act as hooks to bind specific target molecules. When mixed with a fluid, such as a vial of blood or water, any molecules present will glom onto the Dynabeads. Using a magnet, scientists can gently coax the beads to the bottom of a vial and filter them out of a solution. Karnik’s lab is investigating ways to then further separate the beads into those that are bound to a target molecule, and those that are not. “Still, the challenge is, how do we know that we have what we’re looking for?” Tadesse says.

The beads themselves are not visible by eye. That’s where Tadesse’s work comes in. Her lab uses Raman spectroscopy as a way to “fingerprint” pathogens. She has found that different cell types scatter light in unique ways that can be used as a signature to identify them.

In the team’s new work, she and her colleagues found that Dynabeads also have a unique and strong Raman signature that can act as a surprisingly clear beacon.

“We were initially seeking to identify the signatures of bacteria, but the signature of the Dynabeads was actually very strong,” Tadesse says. “We realized this signal could be a means of reporting to you whether you have that bacteria or not.”

Testing beacon

As a practical demonstration, the researchers mixed Dynabeads into vials of water contaminated with Salmonella. They then magnetically isolated these beads onto microscope slides and measured the way light scattered through the fluid when exposed to laser light. Within half a second, they quickly detected the Dynabeads’ Raman signature — a confirmation that bound Dynabeads, and by inference, Salmonella, were present in the fluid.

“This is something that can be used to rapidly give a positive or negative answer: Is there a contaminant or not?” Tadesse says. “Because even a handful of pathogens can cause clinical symptoms.”

The team’s new technique is significantly faster than conventional methods and uses elements that could be adapted into smaller, more portable forms — a goal that the researchers are currently working toward. The approach is also highly versatile.

“Salmonella is the proof of concept,” Tadesse says. “You could purchase Dynabeads with E.coli antibodies, and the same thing would happen: It would bind to the bacteria, and we’d be able to detect the Dynabead signature because the signal is super strong.”

The team is particularly keen to apply the test to conditions such as sepsis, where time is of the essence, and where pathogens that trigger the condition are not rapidly detected using conventional lab tests.

“There are a lot cases, like in sepsis, where pathogenic cells cannot always be grown on a plate,” says Lee, a member of Karnik’s lab. “In that case, our technique could rapidly detect these pathogens.”

This research was supported, in part, by the MIT Laser Biomedical Research Center, the National Cancer Institute, and the Abdul Latif Jameel Water and Food Systems Lab at MIT.

Source: MIT News 

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Clinical Application of Next-Generation Sequencing for Microbiological Diagnosis

Scientists from Belgium have surveyed to understand clinicians’ perspectives on the need for clinical application of next-generation sequencing (NGS) in microbiology laboratories. The study is published in the journal Frontiers in Medicine.

Next-generation sequencing: what are the needs in routine clinical microbiology? A survey among clinicians involved in infectious diseases practice

The survey finds that application of NGS is mostly expected for the diagnosis of neurological and respiratory infections.

Background

The usage of next-generation sequencing (NGS) is increasing firmly in clinical pathology, genetics, and cancer diagnosis. However, the widespread application of this valuable technology as a routine diagnostic tool in clinical microbiology laboratories is still facing major challenges.   

In the field of microbiology, the application of NGS is mostly limited to academic or reference laboratories. The major obstacle against its implementation in clinical microbiology is the lack of standardized protocols or tools.

Major decision-making regarding technologies, operational models, infrastructure, human resources, and professional expertise is needed before the widespread clinical application of NGS.

To facilitate such decision-making, the current survey was conducted among clinicians involved in infectious diseases with the aim of understanding their expectations regarding the added value of NGS for routine clinical care. Another aim of the survey was to identify the factors in which prioritization is needed the most.        

Survey design

This online survey was conducted between January and August 2019 among clinicians practicing in hospitals located in Brussels, Belgium. The survey covered three major topics, including knowledge related to NGS, the expected diagnostic value of NGS, and the expected impact on antimicrobial prescription. 

A total of 24 clinicians completed the survey. Of them, 65.5% were infectious disease specialists, 25% were intensive care specialists, and 12.5% were infectious disease pediatricians.

Survey findings  

The clinician’s knowledge of NGS was analyzed using a scale of 0 to 4, where 0 referred to “none” and 4 referred to “very well.” About 25%, 54.2%, 8.3%, and 12.5% of clinicians rated 0, 1, 2, and 3 on the scale, respectively.

The analysis of answers provided by most of the clinicians in open fields indicated that a wide range of syndromes and samples often remain negative even if there is a strong suspicion of infection.

According to clinicians’ expectations, NGS can provide the highest diagnostic benefit for neurological and respiratory infections, followed by cardiologic and bone and joint infections.

Regarding acute infection sample types, NGS was expected to be beneficial for analyzing cerebrospinal fluid (CSF), pericardial, pleural fluid, and prosthetic materials, as these samples often lack microbiological documentation. Regarding chronic infection sample types, NGS was expected to benefit the analysis of prosthetic materials and bone-derived samples.  

About 83% of clinicians reported considering empirical treatment because of the lack of identification of the exact causative pathogen. Specifically, the survey findings indicated that antibiotics are prescribed blindly in most cases, followed by the prescription of corticoids and antivirals in 40% and 25% of cases, respectively.

All clinicians reported treating patients with low white blood cell counts (neutropenic patients) on a daily basis. About 83% of clinicians reported that identification of a causative pathogen is difficult in these patients. About 46% of clinicians reported that this lack of microbiological diagnosis is due to the lack of sensitivity of routine diagnostic tools.

Significance

The survey evaluates the potential utility of NGS as a routine diagnostic tool in clinical microbiology laboratories. A small group of infectious disease-related clinicians who participated in the survey expect that NGS can potentially improve the quality of microbiological diagnosis, especially for neurological and respiratory infections.

NGS-based identification of actual causative pathogens can prevent the widespread use of empirical treatments, which is a major driving factor for antibiotic resistance.  

Notably, the survey finds a gap between clinicians’ expectations and the actual performance, technical limitations, and lack of interpretability of NGS in clinical microbiology. Thus, more efforts are needed to develop appropriate infrastructure, design routine diagnostic protocols, and involve professional experts for NGS-based microbiological diagnosis.

Journal reference:

Michel C (2023). Next-generation sequencing: what are the needs in routine clinical microbiology? A survey among clinicians involved in infectious diseases practice. Frontiers in Medicine. doi: 10.3389/fmed.2023.1225408. 

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Rapid Infection Test in Dogs Could Curb Antibiotic Resistance

Scientists have developed a new way to rapidly diagnose bacterial infections in dogs, enabling testing and treatment with appropriate antibiotics on the same day.

The method could eliminate the delays associated with conventional diagnosis, in which a sample has to be cultured for days to identify the bacteria present before the appropriate treatment is prescribed.

It is a significant step towards the appropriate use of antibiotics by limiting the use of inappropriate or a wide spectrum of antibiotics for unidentified infections and preventing lengthy courses of treatment.

The development could also be applied across animal and human medicine, for bacterial and other types of infections, researchers say.

New approach

The team used kits optimized for common bacterial species to allow them extract all the DNA from a sample without prior knowledge of which species are present—so-called metagenomic DNA extraction.

They combined this with an existing technology that generates DNA code from samples, known as nanopore sequencing, and a data analysis tool that identifies bacteria according to their DNA fingerprint.

Fast results

This approach allows identification of bacteria in real time, enabling results in a few hours.

The genes identified in the sample also give valuable insight on how the bacteria present are likely to respond to antibiotic treatment, enabling clinicians to prescribe the drug best suited to the infection.

The team tested their system with skin and urinary bacterial infections in dogs, and were able to detect bacteria within five hours.

They were able to identify bacterial species that are difficult to identify with conventional culturing and determine with high sensitivity whether the bacteria present were likely to be resistant to antibiotics.

Wider use

The system is designed to be adaptable for use in various samples and infections across animal species.

In the future it could be useful across a range of animal and human infections, potentially aiding the diagnosis and treatment of other types of infections caused by viruses and parasites, researchers say. The study is published in Microbial Genomics.

"Our method offers a swift way to diagnose bacterial infections and prescribe appropriate antibiotics within hours of patient testing. Following our work with skin and urinary infections in dogs, we are confident that this approach has potential for use across many animal species, and in humans, and has applications in other infection types. It could play a significant role in enabling responsible use of antimicrobial treatments and limiting antimicrobial resistance," says Dr. Natalie Ring.

Reference

Natalie Ring et al, Rapid metagenomic sequencing for diagnosis and antimicrobial sensitivity prediction of canine bacterial infections. Microbial Genomics (2023). 

Abstract

Antimicrobial resistance is a major threat to human and animal health. There is an urgent need to ensure that antimicrobials are used appropriately to limit the emergence and impact of resistance. In the human and veterinary healthcare setting, traditional culture and antimicrobial sensitivity testing typically requires 48–72 h to identify appropriate antibiotics for treatment. In the meantime, broad-spectrum antimicrobials are often used, which may be ineffective or impact non-target commensal bacteria. Here, we present a rapid, culture-free, diagnostics pipeline, involving metagenomic nanopore sequencing directly from clinical urine and skin samples of dogs. We have planned this pipeline to be versatile and easily implementable in a clinical setting, with the potential for future adaptation to different sample types and animals. Using our approach, we can identify the bacterial pathogen present within 5 h, in some cases detecting species which are difficult to culture. For urine samples, we can predict antibiotic sensitivity with up to 95 % accuracy. Skin swabs usually have lower bacterial abundance and higher host DNA, confounding antibiotic sensitivity prediction; an additional host depletion step will likely be required during the processing of these, and other types of samples with high levels of host cell contamination. In summary, our pipeline represents an important step towards the design of individually tailored veterinary treatment plans on the same day as presentation, facilitating the effective use of antibiotics and promoting better antimicrobial stewardship.

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Biochip Detects Multiple Viruses, Cancers, or Toxins in Minutes

Rapid COVID-19 tests gave many people a firsthand appreciation for the value of quick and cheap diagnostics. Now, researchers have shown how to conduct thousands of rapid molecular screenings simultaneously, using light to identify target molecules snared on top of an array of tiny silicon blocks. In theory, the tool could be used to spot 160,000 different molecules in a single square centimeter of space. Developed to spot gene fragments from the SARS-CoV-2 virus and other infectious organisms, the technology should also be able to identify protein markers of cancer and small molecules flagging toxic threats in the environment.

“This technology could have a big role to play in how we detect things in the environment,” says Chris Scholin, a molecular biologist and president and CEO of the Monterey Bay Aquarium Research Institute. The tool could also be useful in clinical diagnostics, he adds, although it has several competing technologies already in wide use.

Genetic tests are nothing new. Most of these technologies rely on measuring light absorption or emission from probe molecules tailored to latch onto the target gene. But to produce a signal large enough to detect, most of the technologies rely on amplifying techniques such as polymerase chain reaction to produce many copies of the target before trying to detect them, adding to the cost and time of the tests.

Researchers have devised a variety of more sensitive technologies. “But previous sensors have not been able to detect a wide range of target molecules,” from very low to very high abundance, says Jennifer Dionne, an applied physicist at Stanford University.

In hopes of getting around these problems, Dionne and her colleagues turned to an optical detection approach that relies on metasurfaces, arrays of tiny silicon boxes—each roughly 500 nanometers high, 600 nanometers long, and 160 nanometers wide—that focus near-infrared light on their top surface. This focusing makes it easy for a simple optical microscope to detect the shift in the wavelength of light coming from each silicon block, which varies depending on what molecules sit on top.

A rapid screen detects gene fragments tethered to arrays of silicon boxes, each just 500 nanometers tall and 600 nanometers across.

To test the idea, the researchers tethered single-stranded gene fragments 22 nucleotides long to the silicon boxes and immersed the array in a buffer solution. When they added the complementary DNA strands to the solution, the strands quickly bound to the tethered ones, shifting the wavelength of light emitted from the surface of each box. Dionne and her colleagues report that their setup could detect the presence of as few as 4000 copies of target genes per microliter, a result they published in Nature Communications.

That’s a concentration typically present in a nasal sample from a person infected with SARS-CoV-2. So the technique could allow doctors to detect viral infections without first having to amplify the genetic material from a patient, Dionne says. Perhaps as important, she notes, an array can be designed to reveal how much target DNA has bound, making it possible to detect in minutes not just whether a particular virus is present, but how intense the infection is. Such information could help doctors tailor their treatments. Current tests can also do this, but they normally take several hours to amplify the genetic material and quantify the results.

Scholin argues that the technology could find more immediate widespread use in tracking molecules outside the lab or doctor’s office. For example, environmental scientists currently use genetic probes to detect toxic algae in waterways. But this normally requires added processing steps to amplify target genes and then test for their abundance, which can take hours, if not days, of lab work.

In that situation, the new technique’s speed could be a game changer, Scholin says. Another enticing option, he says, is to tether antibodies on top of the silicon boxes. This might allow researchers to directly grab the corresponding antigen, whether a toxin or a protein marker of disease. He hopes to use the Stanford team’s detectors to see whether they can detect microbial toxins in the water directly on the fly. “That would have a real impact on people, ecology, and wildlife,” he says.

Dionne and her colleagues have formed a company called Pumpkinseed Bio to commercialize their new detectors, specifically aimed at detecting minute levels of proteins and other molecules that can’t readily be amplified to make them easier to detect. And because only a small number of silicon blocks would be needed to spot individual target molecules, researchers should be able to craft arrays to track a multitude of disease biomarkers simultaneously. “We hope to look at many disease states at the same time,” says Jack Hu, a former graduate student in Dionne’s lab and head of the new startup. “That’s the vision.”

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