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| Image created by Dr. Michael J. Miller |
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.