The cell sensor could potentially be used for safety screenings of water, food, and public facilities, and aid sample surveys during infectious disease outbreaks
Since Sir Alexander Fleming first discovered penicillin in 1928, antibiotics have transformed modern medicine and saved millions of lives. However, success was short-lived as penicillin resistance emerged to become such a substantial clinical problem that by the 1950s, many of the advances of the prior decade were threatened. To this, scientists began to develop alternate forms of antibiotics, only to learn later that the vicious cycle of antibiotic resistance could not be broken by simply manufacturing new antimicrobials.
Today, we are battling various antibiotic-resistant bacteria with methicillin-Vancomycin-resistant Enterococcus and Multidrug-resistant Pseudomonas aeruginosa often being considered the biggest threats. The recent surge in antibiotic resistance has largely been fuelled by the overuse and misuse of antibiotics. To determine which antibiotics can still effectively inhibit the growth of a certain type of bacteria, scientists have developed antimicrobial susceptibility tests. However, conventional testing methods are slow, requiring 16 to 27 hours to produce results, while modern rapid techniques are expensive and require elaborate laboratory equipment.
Recently, a team of researchers led by Dr. Ren Kangning at Hong Kong Baptist University has designed a fully automatic, microscope-free antimicrobial susceptibility testing system that can rapidly screen for drug-resistant bacteria by simply scanning a “barcode” on the cell sensor using a mobile application. The invention is made up of two main parts: a cell culture zone and a “barcode” cell sensor. Unlike previous techniques, the device can complete onsite screening within three hours without relying on expensive instruments.
When conducting antimicrobial susceptibility tests using the system, the bacterial samples are first injected into and incubated in the cell culture zone. The cell culture zone consists of a set of micro-channels filled with fluids that contain cell culture media and different concentrations of a specific antibiotic. Depending on the concentration of the antibiotic, the tested bacteria inside the micro-channels will show different proliferation rates.
Upon completing the culture period, the bacterial cells will be transferred through the “adaptive linear filters” that resembles a barcode structure. The cells will not accumulate on the sidewalls of the micro-channels, instead, they will be driven down by the fluid and collected at the ends of the micro-channels. The accumulated cells will then form visible vertical bars, the lengths of which are proportional to the quantity of cultured bacterial cells. Using a cell phone equipped with a macro-lens, a photograph of the vertical bars or “barcode” can be taken for image analysis by the mobile application.
While the “barcodes” can easily reflect the number of bacteria present, determining whether the bacteria are resistant to antibiotics is much more complicated. If all the “bars” presented on the cell sensor have similar lengths, it means that the tested antibiotic cannot inhibit the growth of bacteria, thus suggesting that the bacterial sample is resistant to the tested antibiotic. If the length of the “bars” is generally inversely proportional to the concentration of the antibiotic in the micro-channels, this shows that the tested antibiotic is generally effective at inhibiting bacterial growth, reflecting non-resistance. However, when two adjacent “bars” show a sharp difference in length, the antimicrobial effect of the antibiotic may change when the concentration reaches a certain level.
To test their invention, the research team subjected E.coli and S.aureus to the “barcode” cell sensor. Their findings revealed that the device’s results were consistent with those of conventional methods. Besides its high performance, the production cost of the “barcode” sensor is also incredibly low, estimated to be below US$1 per piece, thus making it an attractive tool for widespread research and public health purposes.
“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. “We plan to develop our invention into a portable [antimicrobial susceptibility testing] instrument, and ultimately, we hope it can be used in resource-limited regions.”
Source: Chan et al. (2021). “Barcode” cell sensor microfluidic system: Rapid and sample-to-answer antimicrobial susceptibility testing applicable in resource-limited conditions. Biosensors and Bioelectronics, 192, 113516.