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Nanochip in a capsule identifies bacterial infections within minutes A microbiologist and an electronic engineer from Stellenbosch University have developed a proof-of-concept nanowire biological sensor that can identify any of the major disease-causing bacteria such as Escherichia coli, Salmonella species or Vibrio cholera within ten to fifteen minutes. In the not too distant future, this combination of nanotechnology and microbiology could make the diagnosis of patients during an epidemic or outbreak an order of magnitude faster, more accurate and more affordable. Prof. Leon Dicks, an internationally acclaimed microbiologist, joined forces with Prof. Willie Perold, the electronic engineer. Together they conceptualised the idea of a nanochip that would be able to detect bacteria and viruses in the patient’s stomach within a few minutes after being swallowed. Deon Neveling, a postgraduate student in the Department of Microbiology at SU, was given the task to put this concept to the test as part of his research for a Master’s degree in microbiology.
Zinc oxide nanowires with antigens at the end bend as soon as antibodies adhere to them. The movement then generates a piezoelectrical signal. Image: Deon Neveling
Prof. Leon Dicks and Prof. Willie Perold in front of the building where they first shared ideas about the possibility of adapting the newly developed nanogenerator for detecting pathogens. With them are the two students involved, Deon Neveling and Dr Stanley van den Heever. Image: Wiida Fourie-Basson
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10 |3 2014
Zinc oxide nanowires as observed with an electron microscope. Image: Deon Neveling
The result? From the engineering side, Prof. Perold and one of his doctoral students, Stanley van den Heever, developed a zinc oxide nanogenerator which generates electricity the moment the nanowires are disturbed. This is the first time that it has been done in South Africa. Then Prof. Perold bumped into Prof. Dicks after a research meeting and they shared thoughts: ‘We came up with the idea to combine the sensor with “biological bait” to selectively attract bacteria. The idea was that the movement would generate an electrical signal which can instantly be picked up,’ he says. In order to prepare the nanogenerator for biological use, the engineers constructed a silicon chip of 1 cm by 1 cm in size. They then stacked zinc oxide molecules on top of each other to form a nanowire (only visible with an electron microscope). Thousands of these nanowires are positioned in such a way that the slightest disturbance of their structure will lead to, what engineers call, piezoelectric energy. This energy is converted to electrical energy and then amplified to produce a voltage reading. Enter the microbiologists. The concept was tested by attaching lysozyme molecules (small disease-fighting proteins present in our saliva) to the tip of each nanowire. As soon as antibodies specific to the lysozyme adhered to the nanowires, it caused a shift in the alignment of the zinc oxide molecules. This was observed as a change in electrical output and proof that the concept works. The reverse of the concept also holds true. That is, by attaching specific antibodies to the nanowires, they will detect the antigens characteristic of a specific pathogen (disease-causing microorganism) and report the presence of the pathogen within seconds. The key to the concept is linking the correct antibody to the nanowires to form a perfect, ‘one and only’, match with the antigen. Prof. Dicks says the concept can best be explained by comparing it with fishing. ‘We use bait (in the form of an antibody) to fish for antigens in the patient’s gastrointestinal tract. In our case the bait is attached to
thousands of zinc oxide nanowires cast on a silicon chip. In real life the chip will be constructed small enough to be encased in a capsule. Ten minutes after swallowing the capsule, the nanochip is released and the fishing trip starts. ‘Our dream is to transfer the electrical signal, which is selected to be unique to each pathogen, to a receiver such as a smartphone,’ he adds. This part of the concept still has to be developed. But, says Prof. Dicks, the important thing is that the nanochip concept works. ‘Instead of prescribing a broad-based antibiotic, or waiting 48 hours for the lab tests to come back, a doctor will be able to immediately prescribe the correct antibiotic to target the pathogen, and by doing so, put less stress on the body’s immune system.’
Could this concept work for identifying deadly viruses like Ebola? ‘Certainly’, he says, ‘as long as you have antibodies specific to antigens that are unique to the Ebola virus.’ Antigens are usually proteins located on the surface of cells. These proteins act as a ‘signature’ of that specific cell. This ‘signature’ is then recognised by specific antibodies. At present it is difficult and timeconsuming to diagnose a patient with the Ebola virus. This is because the early signs and symptoms of Ebola resemble those of several other potentially fatal diseases, such as malaria, typhoid fever, shigellosis, cholera, leptospirosis and meningitis. In the short term, Prof. Dicks plans to work with a group of French scientists to develop a nanochip biosensor implant that would report secondary infections: ‘The idea is to incorporate the biosensor into a patient during, for instance, a hip transplant. This would then allow the surgeons to detect the slightest form of secondary infections that may develop during the recovery phase,’ he explains. The results of the research were recently published in the journal Sensors and Actuators B: Chemical. Issued by: Wiida Fourie-Basson, media: Faculty of Science, Stellenbosch University.