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10.18.22 by Hokkaido University Press Room

Detecting Alzheimer’s disease in the blood

This blog originated as a press release from Hokkaido University. Thanks to them for allowing us to repost it here.

Researchers from Hokkaido University and Toppan have developed a method to detect build-up of amyloid β in the brain, a characteristic of Alzheimer’s disease, from biomarkers in blood samples.

Alzheimer’s disease is a neurodegenerative disease, characterised by a gradual loss of neurons and synapses in the brain. One of the primary causes of Alzheimer’s disease is the accumulation of amyloid β (Aβ) in the brain, where it forms plaques. Alzheimer’s disease is mostly seen in individuals over 65 years of age, and cannot currently be stopped or reversed. Thus, Alzheimer’s disease is a major concern for nations with ageing populations, such as Japan.

A team of scientists from Hokkaido University and Toppan, led by Specially Appointed Associate Professor Kohei Yuyama at the Faculty of Advanced Life Science, Hokkaido University, have developed a biosensing technology that can detect Aβ-binding exosomes in the blood of mice, which increase as Aβ accumulates in the brain. Their research was published in the journal Alzheimer’s Research & Therapy.

12.14.21 by Laurie Fickman

Advance in Rapid Cancer Detection and Monitoring

This blog originated as a press release from the University of Houston. Thanks to them for allowing us to repost it here.

Economical, Ultra-sensitive Biosensing in Point-of-Care Applications

When it comes to cancer detection, size matters. Traditional diagnostic imaging cannot detect tumors smaller than a certain size, causing missed opportunities for early detection and treatment. Circulating tumor exosomes are especially small cancer biomarkers and easy to miss. These nanovesicles are composed of molecules that reflect the parental cells. But, because they are tiny (~30-150nm in diameter) and complex, the precise detection of exosome-carried biomarkers with molecular specificity has been elusive, until now.

Wei-Chuan Shih, professor of electrical and computer engineering at the University of Houston Cullen College of Engineering, reports the findings in IEEE Sensors Journal.

“This work demonstrates, for the first time, that the strong synergy of arrayed radiative coupling and substrate undercut can enable high-performance biosensing in the visible light spectrum where high-quality, low-cost silicon detectors are readily available for point-of-care application,” said Shih. “The result is a remarkable sensitivity improvement, with a refractive index sensitivity increase from 207 nm/RIU to 578 nm/RIU.”

Professor Wei0Chuan Shih, University of Houston

Wei-Chuan Shih, professor of electrical and computer engineering at the University of Houston, is reporting rapid cancer detection as a cost-effective, high-performance platform for molecularly specific exosome biosensing.

08.23.21 by Broad Institute

Scientists harness human protein to deliver RNA cargoes to cells

This blog originated as a press release from the Broad Institute of MIT and Harvard. Thanks to MIT News for allowing us to repost it here.

Made of components found in the human body, the programmable system is a step toward safer, targeted delivery of gene editing and other molecular therapeutics.

A new system to deliver molecular therapies to cells, called SEND, can be programmed to encapsulate and deliver different RNA cargoes, potentially provoking less of an immune response than other delivery approaches.
Credit: Courtesy of the researchers

Researchers from MIT, the McGovern Institute for Brain Research at MIT, the Howard Hughes Medical Institute, and the Broad Institute of MIT and Harvard have developed a new way to deliver molecular therapies to cells. The system, called SEND, can be programmed to encapsulate and deliver different RNA cargoes. SEND harnesses natural proteins in the body that form virus-like particles and bind RNA, and it may provoke less of an immune response than other delivery approaches.

06.16.21 by Singapore-MIT Alliance for Research and Technology

Researchers Develop Method for Rapid, Accurate Detection of Viruses

This blog originated as a press release from the Singopore-MIT Alliance for Research and Technology (SMART). Thanks to them for allowing us to repost it here.

Four times faster than conventional PCR methods, a new approach called RADICA is highly specific, sensitive, and resistant to inhibitors.

● RApid DIgital Crispr Approach (RADICA) is a molecular rapid testing methodology that allows absolute quantification of viral nucleic acids in 40-60 minutes.

● RADICA is four times faster and significantly less expensive than conventional polymerase chain reaction (PCR) methods as it does not require costly equipment for precise temperature control and cycling.

● The method has been tested on SARS-CoV-2 synthetic DNA and RNA, Epstein–Barr virus in human B cells and serum, and can be easily adapted to detect other kinds of viruses.

Researchers from Critical Analytics for Manufacturing Personalized-Medicine (CAMP), an Interdisciplinary Research Group (IRG) at the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have developed a new method for rapid and accurate detection of viral nucleic acids – a breakthrough that can be easily adapted to detect different DNA/RNA targets in viruses like the coronavirus.

10.19.20 by Matt Schutte

Improving cancer diagnostics through microfluidics

This blog originated as a press release from The Ohio State University. Thanks to them for allowing us to repost it here.

Dr. Raphael Pollock has earned the reputation as one of the world’s best surgical oncologists for patients facing one of the toughest cancers to treat, sarcoma. Frequently these tumors start out in the very deepest recesses of the retroperitoneum, the part of the abdomen where the kidneys, pancreas and inferior vena cava are located.

Dr. Raphael Pollock

Director of The Ohio State University Comprehensive Cancer Center, Pollock’s 30 years of experience in the operating room naturally led him to ponder the steps before surgery, specifically if there were better ways to diagnose or detect sarcomas. In early 2019, he tapped into Ohio State’s scientific breadth and depth to investigate a new diagnostic method based upon research he conducted while at MD Anderson Cancer Center in Houston. He reached out to Shaurya Prakash, associate professor of mechanical and aerospace engineering and an expert in microfluidics.

Currently, there are two predominant options to acquire a diagnostic biopsy of a tumor deep in the abdomen: invasive surgery under general anesthesia; or a method utilizing computed tomography (CT) scans to guide a long needle through the skin to acquire tissue from the mass. Both are expensive and take time to schedule.

“I’ve been interested for a while in the role of exosomes in the spread of cancers,” Pollock said. Exosomes are extracellular vesicles containing constituents—protein, DNA, and RNA—of the cells that secrete them. They can affect function and behavior of other cells with which they interact. Until recently, they were regarded as merely cell waste products without much clinical research relevance.

Dr. Shaurya Prakash

“We learned that there are a number of things inside the exosomes that interact potentially with cells in the tumor microenvironment,” he added. “Then they circulate in the bloodstream and land in other parts of the body.”

So Pollock asked Prakash if there could be an efficient way of extracting these exosomes from a peripheral blood sample to obtain the contents that might be used to diagnose a tumor deep within the body. The microfluidics expert was intrigued.

“I learned that often by the time sarcomas are diagnosed, the disease state is very advanced,” Prakash said. “The value of isolating these circulating biomarkers is earlier detection. Prognosis is better with earlier detection and diagnosis.”

In the past, Pollock had employed ultracentrifugation to isolate exosomes from blood, but it was arduous and expensive. He and Prakash reviewed the literature and realized there might be several different engineering concepts that could be leveraged to improve the process.

Size-based filtration was first, since exosome size is quite specific. Prakash’s previous water treatment research was useful in developing a microfluidic filtration system. Their second area of focus was targeting a surface marker or protein with monoclonal antibodies to attach, secure and extract the exosomes.

Microfluidic device prototype

The duo’s prototype microfluidic device integrates size-based separation followed by immunoaffinity-based capture of extracellular vesicles in one process. They also are exploring the use of electrical charge to enhance the exosome filtering.

Prakash and Pollock have submitted two manuscripts—one of which was published recently in the Journal of Microelectromechanical Systems—demonstrating their device is more effective than ultracentrifugation in terms of time, yield, and purity.

The collaboration is just the latest example of an emerging partnership between the College of Engineering and The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute.

“These circulating biomarkers are a very small fraction of the overall constituency of blood,” explained Prakash. “The real engineering challenge is extracting that proverbial needle from a haystack. And how do you sort that out and get the right needle.”

Exploded view of microfluidic channels separated by a nanocapillary array membrane. The dotted line represents the cross-section that was utilized for SEM characterization of the device, as seen inset. Only a portion of captured exosomes may have been connected to the tumor, so capturing as many as possible within a blood sample is critical.

Beyond the manuscripts, the research team is gearing up to submit a proposal. Coincidentally, the National Cancer Institute is now seeking proposals that focus on developing new methodologies to extract exosomes to investigate whether the cargo inside may be applicable as biomarkers for cancer.

“We’re now in a position to really drill down into the engineering concepts of the device,” Pollock said.

He added that while this type of device could be applied to many types of cancers, it is especially advantageous for sarcoma diagnosis.

“After a long operation to remove a confirmed tumor, it is very difficult in scans to differentiate tumor recurrence from post-surgical scarring,” he explained. “But if you can detect something a tumor releases in the bloodstream, that provides you with a higher index of suspicion of what you may be seeing on a scan.

“Instead of relying on repeat scans over months to determine size increase or decrease, we can potentially identify recurrence at a very early point when the total volume of recurrence is small and more amenable to treatment. We’re very excited about the potential.”

Looking ahead, Prakash and Pollock want to build toward a systematic clinical trial. While there is nothing in the prototype device that cannot be used in a clinical trial, Prakash said some optimization would be required.

“It’s been a total partnership,” Pollock said. “None of this would have happened without the mutual interest and opportunities to communicate about possibilities.”

The research team included mechanical and aerospace engineering PhD student Prashanth Mohana Sundaram, and Lucia Casadei, Gonzalo Lopez, Danielle Braggio and Gita Balakirsky from the Comprehensive Cancer Center.

10.05.20 by Sarah Avery

Blood-based test accurately identifies viral infection before symptoms develop

This blog originated as a press release from Duke Health. Thanks to them for allowing us to repost it here.

DURHAM, N.C. – A team of Duke Health scientists have identified biomarkers that accurately identify numerous viral infections across the clinical stages of disease, advancing a potential new way to guide treatment, quarantine decisions, and other clinical and public health interventions in the setting of endemic and pandemic infectious diseases.

The blood-based test uses a gene expression assay to correctly predict nine different respiratory viral infections including influenza, enterovirus, adenovirus, and coronaviruses known to cause common colds. It shows the body’s genes responding to a pathogen before symptoms are present.

04.10.20 by Jessica Sieff

ERCC researcher explores potential of highly sensitive point-of-care tests for novel coronavirus detection

This blog originated as a press release from Notre Dame News.

As testing for the coronavirus continues throughout the United States, researchers have been closely watching results, particularly reported rates of false negatives.

According to the Radiological Society of North America, a reported 40 to 70 percent of coronavirus tests from throat swab samples returned false negatives at the onset of the epidemic. Given the highly infectious nature of this particular coronavirus, individuals receiving false negative results — told they do not carry the virus when in fact they do — could continue to infect others.

“It is very concerning,” said Hsueh-Chia Chang, the Bayer Professor of Chemical and Biomolecular Engineering at the University of Notre Dame. “In an overcrowded hospital, where there is only room to quarantine the COVID-19 carriers, false negatives would mean some carriers can continue to infect other patients and healthcare workers. This, unfortunately, is also true for other infectious viral diseases such as dengue and malaria, when there is an epidemic. False negatives are usually not an urgent problem, when every symptomatic patient can be quarantined and there are fewer people to infect — until an epidemic overcrowds our hospitals and we have only enough space to sequester the carriers.”

At Notre Dame, Chang’s research lab focuses on the development of new diagnostic and micro/nanofluidic devices that are portable, sensitive and fast. His work includes diagnostics with applications to DNA/RNA sensing. Current coronavirus tests are RNA-based.

Chang said technology his lab developed for other uses could easily be extended to apply to testing for the coronavirus.

02.04.20 by Roger Alexander

MIFlowCyt-EV framework for reporting EV flow cytometry experiments published

Flow cytometry (FC) is a powerful method for counting single cells and measuring their molecular components. There is increasing interest in applying flow cytometry to the analysis of extracellular vesicles (EV), but EVs are orders of magnitude smaller than the cells for which FC instruments and protocols were originally designed. To catalyze the development of new instruments and assays for EV flow cytometry, three scientific societies came together to form the EV Flow Cytometry Working Group (evflowcytometry.org):

ISEV, the International Society of Extracellular Vesicles
ISAC, the International Society for Advancement of Cytometry, and
ISTH, the International Society for Thrombosis and Haemostasis.

The working group first performed two standardization studies, distributing standards and samples to EV-FC laboratories worldwide to enable an objective comparison of methods, instruments, controls, and analytical tools. Those initial studies led to the realization that a standard framework for reporting experimental results is essential.

01.06.20 by Liz Ahlberg Touchstone

Single-molecule detection of miRNA cancer markers brings liquid biopsy closer to clinic

Illinois researchers developed a method to detect microRNA cancer markers with single-molecule resolution, a technique that could be used for liquid biopsies.

From left: Taylor Canady, postdoctoral scholar; Andrew Smith, professor of bioengineering; Nantao Li, graduate student; Lucas Smith, postdoctoral scholar; and Brian Cunningham – professor of Electrical and Computer Engineering; director of Micro and Nanotechnology Laboratory.
Photo by L. Brian Stauffer

Thanks to the University of Illinois News Bureau for allowing us to share this article here.

CHAMPAIGN, Ill. — A fast, inexpensive yet sensitive technique to detect cancer markers is bringing researchers closer to a liquid biopsy – a test using a small sample of blood or serum to detect cancer, rather than the invasive tissue sampling routinely used for diagnosis.

Researchers at the University of Illinois developed a method to capture and count cancer-associated microRNAs, or tiny bits of messenger molecules that are exuded from cells and can be detected in blood or serum, with single-molecule resolution. The team published its results in the Proceedings of the National Academy of Science.

12.13.19 by The Journal of Molecular Diagnostics

Saliva test shows promise for earlier and easier detection of mouth and throat cancer

Thanks to Eileen Leahy from Elsevier and Chhavi Chauhan, Director of Scientific Outreach for the Journal of Molecular Diagnostics, for sharing this post here.

A novel non-invasive technique may detect human papilloma virus-16, the strain associated with oropharyngeal cancer, in saliva samples, reports The Journal of Molecular Diagnostics.

Philadelphia, December 13, 2019 – Unfortunately, cancers that occur in the back of the mouth and upper throat are often not diagnosed until they become advanced, partly because their location makes them difficult to see during routine clinical exams. A report in The Journal of Molecular Diagnostics, published by Elsevier, describes the use of acoustofluidics, a new non-invasive method that analyzes saliva for the presence of human papilloma virus (HPV)-16, the pathogenic strain associated with oropharyngeal cancers (OPCs). This novel technique detected OPC in whole saliva in 40 percent of patients tested and 80 percent of co published by Elsevier, describes the use of acoustofluidics, a new non-invasive method that analyzes saliva for the presence of human papilloma virus (HPV)-16, the pathogenic strain associated with oropharyngeal cancers (OPCs). This novel technique detected OPC in whole saliva in 40 percent of patients tested and 80 percent of confirmed OPC patients.

“OPC has an approximate incidence of 115,000 cases per year worldwide and is one of the fastest-rising cancers in Western countries due to increasing HPV-related incidence, especially in younger patients. It is paramount that surveillance methods are developed to improve early detection and outcomes,” explained co-lead investigator Tony Jun Huang, PhD, Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA.

“Considering these factors, the successful detection of HPV from salivary exosomes isolated by our acoustofluidic platform offers distinct advantages, including early detection, risk assessment, and screening,” added Dr. Huang. This technique may also help physicians predict which patients will respond well to radiation therapy or achieve longer progression-free survival.