At present, to diagnose the bacteria behind an antibiotic-resistant infection, doctors have to send samples to the lab and wait days for a result. Now, researchers have found a way to shrink the days of waiting to hours, using simple chip-based technology that could fit in a benchtop device.
The team, from the University of Toronto in Canada, describes the new technology and how they tested it, in the journal Lab on a Chip.
Antibiotic resistance is a growing public health problem, compounded in part by the imprecise use of antibiotics.
Because it currently takes 2 or 3 days for a lab test to identify the bacteria behind an infection, doctors start patients off on a broad spectrum antibiotic.
Sometimes this “one size fits all” approach works, but sometimes it does not, and it is only when the lab result arrives that doctors can then prescribe a more specific drug that is more likely to kill the bacteria.
A more rapid test that can be done locally means the doctor could give the right drug straight away, and cut down on exposure of bacteria to antibiotics.
Lead author Justin Besant, a PhD researcher in the Institute for Biomaterials and Biomedical Engineering at Toronto, explains:
“Guessing can lead to resistance to these broad-spectrum antibiotics, and in the case of serious infections, to much worse outcomes for the patient.”
Infection with a resistant version of a bacterium can turn a routine hospital stay into a nightmare. Every year in the US, 2 million people contract antibiotic-resistant infections, and more than 23,000 die from them.
The reason current tests take days and not hours is because you need a high concentration of bacteria. So the sample from the patient is grown in a culture for a couple of days until the population of the bacteria increases to a detectable level.
Besant and colleagues combined expertise in electrical and biomedical engineering to design a chip that squeezes bacteria from the patient sample into just two nanolitres in volume. In that minuscule space, the chip can increase the effective concentration of the bacteria.
The chip is made of glass patterned with microfluidic wells. At the bottom of each well is a filter made of microbeads that catch the bacteria as the sample flows through the chip.
The bacteria collect in the tiny wells, together with the test antibiotic and a molecule called resazurin that sends out an electrochemical signature.
Bacteria metabolize resazurin into resorufin, so if they stay alive, the electrochemical signature changes from the resazurin one into the resorufin one. But if the antibiotic kills the bacteria, then the signature stays as the resazurin one.
Electrodes built into the chip detect the change in electrochemical signature and can relay this as a readout of the result.
Besant says their device offers two advantages:
“One, we have a lot of bacteria in a very small space, so our effective starting concentration is much higher. And two, as the bacteria multiply and convert the resazurin molecule, it’s effectively stuck in this nanolitre droplet – it can’t diffuse away into the solution, so it can accumulate more rapidly to detectable levels.”
He and his team believe their approach is the first to bring together a way of increasing the sample concentration with a simple electrochemical readout. The result is a tool that will help diagnose and treat bacterial infections much faster, they suggest.
There are faster ways to diagnose antibiotic resistant bacteria using fluorescence detection, but these methods require bulky and expensive microscopes to look at the results. Besant explains the obvious advantage a device based on their approach offers:
“The electronics for our electrochemical readout can easily fit in a very small benchtop instrument, and this is something you could see in a doctor’s office, for example.”
He sees the next step as the creation of a device that can test several antibiotics at the same time, at various concentrations.
Meanwhile, Medical News Today recently learned of another new microfluidic chip designed to capture very rare clusters of migrating cancer cells. The device, called the Cluster-Chip, promises to open up new ways to study metastasis, the main cause of cancer deaths.