Tag Archives: Maha Alafeef

Improving implantable technology with borophene

Scientists can be just as competitive as anybody else, from a May 6, 2024 news item on phys.org,

Move over, graphene. There’s a new, improved two-dimensional material in the lab. Borophene, the atomically thin version of boron first synthesized in 2015, is more conductive, thinner, lighter, stronger and more flexible than graphene, the 2D version of carbon.

A May 3, 2024 Pennsylvania State University (Penn State) news release by Jamie Oberdick (also on EurekAlert but published May 7, 2024), which originated the news item, describes the research in more detail,

Now, researchers at Penn State have made the material potentially more useful by imparting chirality — or handedness — on it, which could make for advanced sensors and implantable medical devices. The chirality, induced via a method never before used on borophene, enables the material to interact in unique ways with different biological units such as cells and protein precursors.  

The team, led by Dipanjan Pan, Dorothy Foehr Huck & J. Lloyd Huck Chair Professor in Nanomedicine and professor of materials science and engineering and of nuclear engineering, published their work — the first of its kind, they said — in ACS Nano.  

“Borophene is a very interesting material, as it resembles carbon very closely including its atomic weight and electron structure but with more remarkable properties. Researchers are only starting to explore its applications,” Pan said. “To the best of our knowledge, this is the first study to understand the biological interactions of borophene and the first report of imparting chirality on borophene structures.” 

Chirality refers to similar but not identical physicality, like left and right hands. In molecules, chirality can make biological or chemical units exist in two versions that cannot be perfectly matched, as in a left and right mitten. They can mirror each other precisely, but a left mitten will never fit the right hand as well as it fits the left hand.  

Borophene is structurally polymorphic, which means its boron atoms can be arranged in different configurations to give it different shapes and properties, much like how the same set of Lego blocks can be built into different structures. This gives researchers the ability to “tune” borophene to give it various properties, including chirality.  

“Since this material has remarkable potential as a substrate for implantable sensors, we wanted to learn about their behavior when exposed to cells,” Pan said. “Our study, for the first time ever, showed that various polymorphic structures of borophene interact with cells differently and their cellular internalization pathways are uniquely dictated by their structures.” 

The researchers synthesized borophene platelets — similar to the cellular fragments found in blood — using solution state synthesis, which involves exposing a powdered version of the material in a liquid to one or more external factors, such as heat or pressure, until they combine into the desired product. 

“We made the borophene by subjecting the boron powders to high-energy sound waves and then mixed these platelets with different amino acids in a liquid to impart the chirality,” Pan said. “During this process, we noticed that the sulfur atoms in the amino acids preferred to stick to the borophene more than the amino acids’ nitrogen atoms did.”  

The researchers found that certain amino acids, like cysteine, would bind to borophene in distinct locations, depending on their chiral handedness. The researchers exposed the chiralized borophene platelets to mammalian cells in a dish and observed that their handedness changed how they interacted with cell membranes and entered cells.

According to Pan, this finding could inform future applications, such as development of higher-resolution medical imaging with contrast that could precisely track cell interactions or better drug delivery with pinpointed material-cell interactions. Critically, he said, understanding how the material interacts with cells — and controlling those interactions — could one day lead to safer, more effective implantable medical devices. 

“Borophene’s unique structure allows for effective magnetic and electronic control,” Pan said, noting the material could have additional applications in health care, sustainable energy and more. “This study was just the beginning. We have several projects underway to develop biosensors, drug delivery systems and imaging applications for borophene.” 

Along with Pan, other authors of the study include Teresa Aditya, postdoctoral researcher in nuclear engineering; Parikshit Moitra, research assistant professor of nuclear engineering at Penn State during the study and current assistant professor at the Indian Institutes of Science Education and Research; Maha Alafeef, research scientist at Penn State during the study and current assistant professor at Jordan University of Science and Technology; and David Skrodzki, graduate research assistant in materials science and engineering at Penn State.  

The Centers for Disease Control and Prevention, the U.S. National Science Foundation and the Department of Defense partially supported this research. 

Here’s a link to and a citation for the paper,

Chiral Induction in 2D Borophene Nanoplatelets through Stereoselective Boron–Sulfur Conjugation by Teresa Aditya, Parikshit Moitra, Maha Alafeef, David Skrodzki, and Dipanjan Pan. ACS Nano 2024, 18, 18, 11921–11932 DOOI: https://doi.org/10.1021/acsnano.4c01792 Publication Date:April 23, 2024 Copyright © 2024 American Chemical Society

This paper is behind a paywall.

Detecting COVID-19 in under five minutes with paper-based sensor made of graphene

A Dec. 7, 2020 news item on Nanowerk announced a new technology for rapid COVID-19 testing (Note: A link has been removed),

As the COVID-19 pandemic continues to spread across the world, testing remains a key strategy for tracking and containing the virus. Bioengineering graduate student, Maha Alafeef, has co-developed a rapid, ultrasensitive test using a paper-based electrochemical sensor that can detect the presence of the virus in less than five minutes.

The team led by professor Dipanjan Pan reported their findings in ACS Nano (“Rapid, Ultrasensitive, and Quantitative Detection of SARS-CoV-2 Using Antisense Oligonucleotides Directed Electrochemical Biosensor Chip”).

“Currently, we are experiencing a once-in-a-century life-changing event,” said Alafeef. “We are responding to this global need from a holistic approach by developing multidisciplinary tools for early detection and diagnosis and treatment for SARS-CoV-2.”

I wonder why they didn’t think to provide a caption for the graphene substrate (the square surface) underlying the gold electrode (the round thing) or provide a caption for the electrode. Maybe they assumed anyone knowledgeable about graphene would be able to identify it?

Caption: COVID-19 electrochemical sensing platform. Credit: University of Illinois

A Dec. 7, 2020 University of Illinois Grainger College of Engineering news release (also on EurekAlert) by Huan Song, which originated the news item, provides more technical detail including a description of the graphene substrate and the gold electrode, which make up the cheaper, faster COVID-19 sensing platform,

There are two broad categories of COVID-19 tests on the market. The first category uses reverse transcriptase real-time polymerase chain reaction (RT-PCR) and nucleic acid hybridization strategies to identify viral RNA. Current FDA [US Food and Drug Administration]-approved diagnostic tests use this technique. Some drawbacks include the amount of time it takes to complete the test, the need for specialized personnel and the availability of equipment and reagents.

The second category of tests focuses on the detection of antibodies. However, there could be a delay of a few days to a few weeks after a person has been exposed to the virus for them to produce detectable antibodies.

In recent years, researchers have had some success with creating point-of-care biosensors using 2D nanomaterials such as graphene to detect diseases. The main advantages of graphene-based biosensors are their sensitivity, low cost of production and rapid detection turnaround. “The discovery of graphene opened up a new era of sensor development due to its properties. Graphene exhibits unique mechanical and electrochemical properties that make it ideal for the development of sensitive electrochemical sensors,” said Alafeef. The team created a graphene-based electrochemical biosensor with an electrical read-out setup to selectively detect the presence of SARS-CoV-2 genetic material.

There are two components [emphasis mine] to this biosensor: a platform to measure an electrical read-out and probes to detect the presence of viral RNA. To create the platform, researchers first coated filter paper with a layer of graphene nanoplatelets to create a conductive film [emphasis mine]. Then, they placed a gold electrode with a predefined design on top of the graphene [emphasis mine] as a contact pad for electrical readout. Both gold and graphene have high sensitivity and conductivity which makes this platform ultrasensitive to detect changes in electrical signals.

Current RNA-based COVID-19 tests screen for the presence of the N-gene (nucleocapsid phosphoprotein) on the SARS-CoV-2 virus. In this research, the team designed antisense oligonucleotide (ASOs) probes to target two regions of the N-gene. Targeting two regions ensures the reliability of the senor in case one region undergoes gene mutation. Furthermore, gold nanoparticles (AuNP) are capped with these single-stranded nucleic acids (ssDNA), which represents an ultra-sensitive sensing probe for the SARS-CoV-2 RNA.

The researchers previously showed the sensitivity of the developed sensing probes in their earlier work published in ACS Nano. The hybridization of the viral RNA with these probes causes a change in the sensor electrical response. The AuNP caps accelerate the electron transfer and when broadcasted over the sensing platform, results in an increase in the output signal and indicates the presence of the virus.

The team tested the performance of this sensor by using COVID-19 positive and negative samples. The sensor showed a significant increase in the voltage of positive samples compared to the negative ones and confirmed the presence of viral genetic material in less than five minutes. Furthermore, the sensor was able to differentiate viral RNA loads in these samples. Viral load is an important quantitative indicator of the progress of infection and a challenge to measure using existing diagnostic methods.

This platform has far-reaching applications due to its portability and low cost. The sensor, when integrated with microcontrollers and LED screens or with a smartphone via Bluetooth or wifi, could be used at the point-of-care in a doctor’s office or even at home. Beyond COVID-19, the research team also foresees the system to be adaptable for the detection of many different diseases.

“The unlimited potential of bioengineering has always sparked my utmost interest with its innovative translational applications,” Alafeef said. “I am happy to see my research project has an impact on solving a real-world problem. Finally, I would like to thank my Ph.D. advisor professor Dipanjan Pan for his endless support, research scientist Dr. Parikshit Moitra, and research assistant Ketan Dighe for their help and contribution toward the success of this study.”

Here’s a link to and a citation for the paper,

Rapid, Ultrasensitive, and Quantitative Detection of SARS-CoV-2 Using Antisense Oligonucleotides Directed Electrochemical Biosensor Chip by Maha Alafeef, Ketan Dighe, Parikshit Moitra, and Dipanjan Pan. ACS Nano 2020, 14, 12, 17028–17045 DOI: https://doi.org/10.1021/acsnano.0c06392 Publication Date:October 20, 2020 Copyright © 2020 American Chemical Society

I’m not sure where I found this notice but it is most definitely from the American Chemical Society: “This paper is freely accessible, at this time, for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.”

Gold nanoparticles could help detect the presence of COVID-19 in ten minutes

If this works out, it would make testing for COVID-19 an infinitely easier task. From a May 29, 2020 news item on phys.org,

Scientists from the University of Maryland School of Medicine (UMSOM) developed an experimental diagnostic test for COVID-19 that can visually detect the presence of the virus in 10 minutes. It uses a simple assay containing plasmonic gold nanoparticles to detect a color change when the virus is present. The test does not require the use of any advanced laboratory techniques, such as those commonly used to amplify DNA, for analysis. The authors published their work last week [May 21, 2020] in the American Chemical Society’s nanotechnology journal ACS Nano.

“Based on our preliminary results, we believe this promising new test may detect RNA [ribonucleic acid] material from the virus as early as the first day of infection. Additional studies are needed, however, to confirm whether this is indeed the case,” said study leader Dipanjan Pan, PhD, Professor of Diagnostic Radiology and Nuclear Medicine and Pediatrics at the UMSOM.

Caption: A nasal swab containing a test sample is mixed with a simple lab test. It contains a liquid mixed with gold nanoparticles attached to a molecule that binds to the novel coronavirus. If the virus is present, the gold nanoparticles turns the solution a deep blue color (bottom of the tube) and a precipitation is noticed. If it is not present, the solution retains its original purple color. Credit: University of Maryland School of Medicine

A May 28, 2020 University of Maryland news release (also on EurekAlert), which originated the news item, provides more detail,

Once a nasal swab or saliva sample is obtained from a patient, the RNA is extracted from the sample via a simple process that takes about 10 minutes. The test uses a highly specific molecule attached to the gold nanoparticles to detect a particular protein. This protein is part of the genetic sequence that is unique to the novel coronavirus. When the biosensor binds to the virus’s gene sequence, the gold nanoparticles respond by turning the liquid reagent from purple to blue.

“The accuracy of any COVID-19 test is based on being able to reliably detect any virus. This means it does not give a false negative result if the virus actually is present, nor a false positive result if the virus is not present,” said Dr. Pan. “Many of the diagnostic tests currently on the market cannot detect the virus until several days after infection. For this reason, they have a significant rate of false negative results.”

Dr. Pan created a company called VitruVian Bio to develop the test for commercial application. He plans to have a pre-submission meeting with the U.S. Food and Drug Administration (FDA) within the next month to discuss requirements for getting an emergency use authorization for the test. New FDA policy allows for the marketing of COVID-19 tests without requiring them to go through the usual approval or clearance process. These tests do, however, need to meet certain validation testing requirements to ensure that they provide reliable results.

“This RNA-based test appears to be very promising in terms of detecting the virus. The innovative approach provides results without the need for a sophisticated laboratory facility,” said study co-author Matthew Frieman, PhD, Associate Professor of Microbiology and Immunology at UMSOM.

Although more clinical studies are warranted, this test could be far less expensive to produce and process than a standard COVID-19 lab test; it does not require laboratory equipment or trained personnel to run the test and analyze the results. If this new test meets FDA expectations, it could potentially be used in daycare centers, nursing homes, college campuses, and work places as a surveillance technique to monitor any resurgence of infections.

In Dr. Pan’s laboratory, research scientist Parikshit Moitra, PhD, and UMSOM research fellow Maha Alafeef conducted the studies along with research fellow Ketan Dighe from UMBC.

Dr. Pan holds a joint appointment with the College of Engineering at the University of Maryland Baltimore County and is also a faculty member of the Center for Blood Oxygen Transport and Hemostasis (CBOTH).

“This is another example of how our faculty is driving innovation to fulfill a vital need to expand the capacity of COVID-19 testing,” said Dean E. Albert Reece, MD, PhD, MBA, who is also Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor, University of Maryland School of Medicine. “Our nation will be relying on inexpensive, rapid tests that can be dispersed widely and used often until we have effective vaccines against this pandemic.”

Here’s a link to and a citation for the paper,

Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic Nanoparticles by Parikshit Moitra, Maha Alafeef, Ketan Dighe, Matthew B. Frieman, and Dipanjan Pan. ACS Nano 2020, XXXX, XXX, XXX-XXX DOI: https://doi.org/10.1021/acsnano.0c03822 Publication Date:May 21, 2020 Copyright © 2020 American Chemical Society

This paper appears to be open access.

I tried to find Dr. Pan’s company, VitruVian Bio and found a business with an almost identical name, Vitruvian Biomedical, which does not include Dr. Pan on its management team list and this company’s focus is on Alzheimer’s Disease. Finally, there is no mention of the COVID-19 test anywhere on the Vitruvian Biomedical website.