HKBU Scientists Develop Barcode Cell Sensor

Research scientists at Hong Kong Baptist University (HKBU) have developed a cell sensor with barcode -like micro-channel structure that allows rapid and low-cost screening of drug-resistant bacteria.

The barcode cell sensor could potentially be used on a large-scale in resource-limited situations such as frequent safety screenings of water, food and public facilities, as well as urgent surveys of massive samples during an infectious disease outbreak, particularly in developing countries.

"Our barcode testing system is a promising new tool in the fight against antimicrobial resistance. We hope
that it will benefit the routine screening of drug-resistant bacteria in the food industry, public areas and healthcare facilities as it does not require advanced clinical facilities or professional testing skills," said Dr. Ren Kangning, associate professor of the Department of Chemistry at HKBU.

Dr. Ren led the research team that designed a fully automatic, microscope-free antimicrobial susceptibility testing (AST) system.  Apart from researchers from HKBU's Department of Chemistry, the research team of the "barcode" cell sensor also included scientists from the Department of Computer Science at HKBU and the School of Medicine at Stanford University.

The team has applied a patent for their invention.

Rapid yet low-cost approach to identifying drug-resistant bacteria

The  overuse and misuse of antibiotics have resulted to drug-resistant bacteria. AST is used to determine which antibiotics can effectively inhibit the growth of a certain type of bacteria effectively.

However, conventional AST methods are too slow, as they require 16 to 24 hours for results, while modern rapid ASTs are expensive and require elaborated laboratory equipment. A rapid and cost-effective strategy is therefore needed to screen bacterial samples onsite, with advanced laboratory testing arranged only for those suspected of containing drug-resistant bacteria.

The barcode cell sensor developed by HKBU enables rapid and low-cost screening of drug-resistant bacteria by scanning the "barcode" on the cell sensor with a mobile app. It is a fully automatic, microscope-free AST system comprising of  two main parts: a cell culture zone and a "barcode" cell sensor.

The cell culture zone consists of a set of micro-channels filled with fluids that contain cell culture media as well as different concentrations of the antibiotic. The "barcode" cell sensor contains an array of "adaptive linear filters" arranged in parallel that resembles a "barcode" structure.

Users can finish the onsite screening within three hours by scanning the "barcode" with a mobile app. Furthermore,  the barcode cell sensor has a  low production cost, estimated at under US$1 per piece.

“We plan to develop our invention into a portable AST instrument, and ultimately, we hope it can be used in resource-limited regions," said Dr. Ren.

How the barcode cell sensor works

When conducting AST with the system, bacterial samples will be injected into and incubated in the cell culture zone. Bacteria in the test sample inside the micro-channels show different proliferation rates depending on different concentrations of the antibiotic.

After completion of the culture period, the bacterial cells will flow through the "adaptive linear filters". The cells will not accumulate around the nanopores on the sidewalls of the micro-channels, instead they will be driven down by the fluid and be collected from the end of the micro-channels. The accumulated cells will then form visible vertical bars, the lengths of which are proportional to the quantity of bacteria cells cultured under the different concentrations of the antibiotic.

A cell phone equipped with a macro-lens can then be used to photograph the "barcode" created by the AST. The image will be analysed automatically by the mobile app.

After the culture period, if all the "bars" of the cell sensor have similar lengths, it means the tested antibiotic cannot inhibit the growth of the bacteria, and thus the bacterial sample is resistant to the tested antibiotic. If the length of the "bars" is in general inversely proportional to the concentration of the antibiotic in the micro-channels, it shows that the tested antibiotic is generally effective at prohibiting the growth of the bacteria, and thus the bacteria is not drug-resistant. When two adjacent "bars" show a sharp difference in terms of length, it indicates that the antimicrobial effect of the antibiotic leaps when its concentration reaches a particular level.

The HKBU  research team tested E. coli and S. aureus with the "barcode" cell sensor and the results were consistent with those of the conventional AST. The test can be completed in three hours, which is much faster than the conventional AST. Microfluidic approaches developed by other researchers can also attain comparable speed, but they rely on expensive instruments for analysis in general. 

Read more

Penn State Researchers Developing Genomic Resources to Identify Novel Pathogens

To enhance the early detection of novel infectious bacteria that could cause outbreaks of infectious disease and public health emergencies, a team of researchers in Penn State's College of Agricultural Sciences will sequence the genomes of 700 Bacilli bacteria — near relatives of the biothreat pathogen that causes anthrax.

Funded by a $1.2 million grant from the U.S. Centers for Disease Control and Prevention, the research will support the development of genomic resources and DNA sequence databases for the federal agency to increase its capacity for rapidly detecting novel pathogens, according to team leader Jasna Kovac, assistant professor of food science and Lester Earl and Veronica Casida Career Development Professor of Food Safety.

"You may have heard of the 2001 bioterrorist attacks in which spores of the bacteria Bacillus anthracis that cause anthrax were circulated in the mail," she said. "People who inhale these spores can get sick with anthrax, which is often fatal."

From a biodefense standpoint, it is important to understand the diversity of environmental Bacilli that could become novel biothreats such as anthrax, added Kovac, who has extensive experience with the genomics of Bacilli.

"There are known examples among Bacillus cereus group bacteria where 'benign' environmental strains have acquired anthrax-causing capabilities," she said. "We are interested in detecting and characterizing similar strains of Bacilli that have both the characteristics of known biothreats and harmless environmental microorganisms."

If emerging pathogens or biothreats are detected early on, they are more likely to be contained effectively to prevent a public health emergency, Kovac noted. "We are partnering with the CDC to create a large database of Bacilli to support its development of rapid laboratory methods for the detection of novel, naturally occurring or engineered pathogens and potential emerging biothreats," she said.

The databases will enhance and strengthen existing genomics approaches and bioinformatics pipelines developed by the CDC's Division of Preparedness and Emerging Infections group. This will allow for the rapid detection of genomic markers associated with increased biothreat risk, Kovac pointed out.

"We are uniquely positioned to complete the proposed work and support CDC's expansion of reference databases for the detection of novel, emerging infectious diseases," she said. "Here in Penn State's Department of Food Science, we have microbiology and genomic expertise and access to a large number of unique, environmental and food Bacilli, deposited in the Food Microbe Tracker culture collection and database curated by our collaborators at Cornell University."

Also on the research team are Xiaoyuan Wei, postdoctoral scholar; Taejung Chung, doctoral student; Jared Pavlock, research assistant; and Grant Harm, undergraduate research assistant.

Read more

AAD, BARDA Partner to Seek Earlier Detection of Sepsis

AAD, developer of rapid diagnostic and data systems, announced that it has been awarded a federal contract for the development of an innovative system for the earlier detection of severe infection, including sepsis. The easy-to-use system is designed for use at point of care in urgent care clinics, doctors' offices and other prehospital settings, and could result in critical earlier intervention and improved patient outcomes.

AAD's QScout® RLD+ system is being developed as an easy-to-use, rapid-result hematology analyzer to capture a 7-part leukocyte differential, including quantification of band neutrophils and other immature granulocytes (IG). In serious infections, bands are released after mature neutrophils are depleted, and then IGs are released. Having automated band counts and the simultaneous availability of IG counts would be a first in medicine and will enable earlier identification of infection, including sepsis.

The QScout RLD+ system is designed to deliver laboratory-grade results in two minutes, in almost any setting, compared to the approximately two hours required of a traditional manual hospital testing procedure. Each hour delayed for the onset of antibiotic treatment of septic shock can increase mortality nearly 8%.

"According to the CDC, the vast majority of sepsis cases — 87 percent — begin outside of a hospital," said Joy Parr Drach, CEO of AAD. "Having a test system that in about two minutes can give results patient-side that are typically only available in a hospital setting would provide critical information and allow faster intervention for the patient. This new test system represents AAD doing things not before possible in places not before possible."

The development of AAD's new system is being funded in part with federal funds from the Biomedical Advanced Research and Development Authority's (BARDA) Division of Research, Innovation and Ventures under contract number 75A50121C00089; BARDA is part of the U.S. Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response.

According to the Centers for the Disease Prevention and Control (CDC), sepsis is a life-threatening medical emergency that happens when an infection a person already has triggers a chain reaction throughout the body. Infections that lead to sepsis most often start in the lung, urinary tract, skin, or gastrointestinal tract, although almost any infection can trigger sepsis, in which a localized infection progresses to severe infection throughout the body.

In a typical year, at least 1.7 million adults in the United States develop sepsis, and nearly 270,000 die as a result. A 2020 study estimated that sepsis caused approximately 11 million deaths worldwide in 2017 — or nearly 20 percent of all deaths in that year. Other studies show sepsis is the leading pediatric killer and leading cause of hospital deaths in the U.S.

About Advanced Animal Diagnostics

AAD (Advanced Animal Diagnostics) provides rapid point-of-care diagnostic and data systems for fast health care decisions. The company's QScout® line of rapid diagnostic tests empowers more precise care of animals and humans so they live healthier, more productive lives. Its diagnostic offerings inform real-time decisions that increase productivity, prevent losses, protect the food supply, and improve human and animal health well-being.

Read more