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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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UCF Researchers Develop an Optical Sensor That Identifies Viruses in Blood Samples in Seconds with 95% Accuracy

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).

However, both the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) have cautioned that rapid antigen tests could produce inaccurate test results if viral loads are low or test instructions are not followed properly.

The UCF researchers published their findings in the journal Nano Letters, titled, “DNA-Modified Plasmonic Sensor for the Direct Detection of Virus Biomarkers from the Blood.”

Debashis Chanda, PhD
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.

JP Schlingman

Related Information:

UCF Researchers Develop Rapid, Highly Accurate Test to Detect Viruses like COVID-19

Researchers Develop Rapid, Highly Accurate Virus Detection Test

DNA-Modified Plasmonic Sensor for the Direct Detection of Virus Biomarkers from the Blood

Researchers at Several Top Universities Unveil CRISPR-Based Diagnostics That Show Great Promise for Clinical Laboratories

Three innovative technologies utilizing CRISPR-Cas13, Cas12a, and Cas9 demonstrate how CRISPR might be used for more than gene editing, while highlighting potential to develop new diagnostics for both the medical laboratory and point-of-care (POC) testing markets

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is in the news again! The remarkable genetic-editing technology is at the core of several important developments in clinical laboratory and anatomic pathology diagnostics, which Dark Daily has covered in detail for years.

Now, scientists at three universities are investigating ways to expand CRISPR’s use. They are using CRISPR to develop new diagnostic tests, or to enhance the sensitivity of existing DNA tests.

One such advancement improves the sensitivity of SHERLOCK (Specific High Sensitivity Reporter unLOCKing), a CRISPR-based diagnostic tool developed by a team at MIT. The new development harnesses the DNA slicing traits of CRISPR to adapt it as a multifunctional tool capable of acting as a biosensor. This has resulted in a paper-strip test, much like a pregnancy test, that can that can “display test results for a single genetic signature,” according to MIT News.

Such a medical laboratory test would be highly useful during pandemics and in rural environments that lack critical resources, such as electricity and clean water.

One Hundred Times More Sensitive Medical Laboratory Tests!

Co-lead authors Jonathan Gootenberg, PhD Candidate, Harvard University and Broad Institute; and Omar Abudayyeh, PhD and MD student, MIT, published their findings in Science. They used CRISPR Cas13 and Cas12a to chop up RNA in a sample and RNA-guided DNA binding to target genetic sequences. Presence of targeted sequences is then indicated using a paper-based testing strip like those used in consumer pregnancy tests.

MIT News highlighted the high specificity and ease-of-use of their system in detecting Zika and Dengue viruses simultaneously. However, researchers stated that the system can target any genetic sequence. “With the original SHERLOCK, we were detecting a single molecule in a microliter, but now we can achieve 100-fold greater sensitivity … That’s especially important for applications like detecting cell-free tumor DNA in blood samples, where the concentration of your target might be extremely low,” noted Abudayyeh.

Feng-Zhang-Broad-Institute-500w@96ppi

“The [CRISPR] technology demonstrates potential for many healthcare applications, including diagnosing infections in patients and detecting mutations that confer drug resistance or cause cancer,” stated senior author Feng Zhang, PhD. Zhang, shown above in the MIT lab named after him, is a Core Institute Member of the Broad Institute, Associate Professor in the departments of Brain and Cognitive Sciences and Biological Engineering at MIT, and a pioneer in the development of CRISPR gene-editing tools. (Photo copyright: MIT.)

Creating a Cellular “Black Box” using CRISPR

Another unique use of CRISPR technology involved researchers David Liu, PhD, and Weixin Tang, PhD, of Harvard University and Howard Hughes Medical Institute (HHMI). Working in the Feng Zhang laboratory at the Broad Institute, they developed a sort of “data recorder” that records events as CRISPR-Cas9 is used to remove portions of a cell’s DNA.

They published the results of their development of CRISPR-mediated analog multi-event recording apparatus (CAMERA) systems, in Science. The story was also covered by STAT.

“The order of stimuli can be recorded through an overlapping guide RNA design and memories can be erased and re-recorded over multiple cycles,” the researchers noted. “CAMERA systems serve as ‘cell data recorders’ that write a history of endogenous or exogenous signaling events into permanent DNA sequence modifications in living cells.”

This creates a system much like the “black box” recorders in aircraft. However, using Cas9, data is recorded at the cellular level. “There are a lot of questions in cell biology where you’d like to know a cell’s history,” Liu told STAT.

While researchers acknowledge that any medical applications are in the far future, the technology holds the potential to capture and replay activity on the cellular level—a potentially powerful tool for oncologists, pathologists, and other medical specialists.

Using CRISPR to Detect Viruses and Infectious Diseases

Another recently developed technology—DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR)—shows even greater promise for utility to anatomic pathology groups and clinical laboratories.

Also recently debuted in Science, the DETECTR system is a product of Jennifer Doudna, PhD, and a team of researchers at the University of California Berkeley and HHMI. It uses CRISPR-Cas12a’s indiscriminate single-stranded DNA cleaving as a biosensor to detect different human papillomaviruses (HPVs). Once detected, it signals to indicate the presence of HPV in human cells.

Despite the current focus on HPVs, the researchers told Gizmodo they believe the same methods could identify other viral or bacterial infections, detect cancer biomarkers, and uncover chromosomal abnormalities.

Future Impact on Clinical Laboratories of CRISPR-based Diagnostics

Each of these new methods highlights the abilities of CRISPR both as a data generation tool and a biosensor. While still in the research phases, they offer yet another possibility of improving efficiency, targeting specific diseases and pathogens, and creating new assays and diagnostics to expand medical laboratory testing menus and power the precision medicine treatments of the future.

As CRISPR-based diagnostics mature, medical laboratory directors might find that new capabilities and assays featuring these technologies offer new avenues for remaining competitive and maintaining margins.

However, as SHERLOCK demonstrates, it also highlights the push for tests that produce results with high-specificity, but which do not require specialized medical laboratory training and expensive hardware to read. Similar approaches could power the next generation of POC tests, which certainly would affect the volume, and therefore the revenue, of independent clinical laboratories and hospital/health system core laboratories.

—Jon Stone

 

Related Information:

Multiplexed and Portable Nucleic Acid Detection Platform with Cas13, Cas12a, and Csm6

Rewritable Multi-Event Analog Recording in Bacterial and Mammalian Cells

CRISPR-Cas12a Target Binding Unleashes Indiscriminate Single-Stranded DNase Activity

Researchers Advance CRISPR-Based Tool for Diagnosing Disease

CRISPR Isn’t Just for Gene Editing Anymore

CRISPR’s Pioneers Find a Way to Use It as a Glowing Virus Detector

With New CRISPR Inventions, Its Pioneers Say, You Ain’t Seen Nothin’ Yet

New CRISPR Tools Can Detect Infections Like HPV, Dengue, and Zika

Breakthrough DNA Editing Tool May Help Pathologists Develop New Diagnostic Approaches to Identify and Treat the Underlying Causes of Diseases at the Genetic Level

CRISPR-Related Tool Set to Fundamentally Change Clinical Laboratory Diagnostics, Especially in Rural and Remote Locations

Harvard Researchers Demonstrate a New Method to Deliver Gene-editing Proteins into Cells: Possibly Creating a New Diagnostic Opportunity for Pathologists

University of Pennsylvania Researchers Develop $2 Zika Proof-of-Concept Test That Needs Neither Electricity Nor a Clinical Laboratory to Return Accurate Results

Using 3D printing and a chemical heat source, University of Pennsylvania researchers have created a proof-of-concept for an affordable Zika test that returns results in just 40 minutes

There’s a gap in Zika virus testing that researchers at the University of Pennsylvania hope to fill. That gap is a point-of-care test for the Zika virus that can produce a fast and accurate result, whether in developed nations or in developing countries that don’t have many state-of-the art clinical laboratories.

Although numerous Zika virus tests have earned Emergency Use Authorizations from the US Food and Drug Administration (FDA), gold standard detection is still limited to medical laboratories. To date, the FDA’s list of current and terminated Emergency Use Authorizations include no point-of-care options to help medical professionals quickly screen patients for Zika infection.

As noted by the Center for Disease Control and Prevention’s “Interim Guidance for Interpretation of Zika Antibody Test Results,” the antibodies that indicate Zika virus activity also share similarities with other flavivirus viruses. Of particular note is similarities with Dengue virus—a virus prevalent in many of the areas in which Zika is found. (more…)

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