Hong Kong Baptist University invents novel cell sensor for rapid and low-cost screening of drug-resistant bacteria

HONG KONG
SAR – Media
OutReach – 29 September 2021 – A research team led by scientists at
Hong Kong Baptist University (HKBU)
has developed a novel cell sensor with a barcode-like micro-channel structure that enables rapid and
low-cost screening of drug-resistant bacteria. The invention 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.

A research paper on the novel invention was published in the
international academic journal Biosensors and
Bioelectronics.

A research team led by Dr Ren Kangning, Associate
Professor of the Department of Chemistry at HKBU (left),
designed a fully automatic, microscope-free antimicrobial
susceptibility testing (AST) system. It enables rapid and low-cost screening of
drug-resistant bacteria by scanning the “barcode” on the cell sensor with a
mobile app, which is shown by Chan Chiu-wing, a member of the research team and
a PhD student of the Department of Chemistry at HKBU
(right).

The cell
sensor with a barcode-like micro-channel structure comprises two main parts: a
cell culture zone and a “barcode” cell sensor.

A rapid and low-cost testing approach

Antibiotics are often used to treat bacterial infections, but the
overuse and misuse of antibiotics have created the problem of drug resistance.
Antimicrobial susceptibility testing (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.

In response to this need, a research team led by Dr Ren Kangning, Associate Professor of the Department of Chemistry at
HKBU designed a fully automatic, microscope-free AST system. It comprises
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 developed by the researchers, and it will indicate whether any
drug-resistant pathogenic bacteria is present in the sample.

Quantity of bacteria represented by bar length

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.

Results consistent with conventional AST

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 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.  

Potential for use in resource-limited regions

“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.

The “barcode” cell
sensor has a low production cost, and it
is estimated to be below one US dollar per piece. The research team has
filed a patent application for the “barcode” cell sensor. “We plan to develop
our invention into a portable AST instrument, and ultimately, we hope it can be
used in resource-limited regions,” Dr Ren added.

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.

#HongKongBaptistUniversity #HKBU