Date:6 November 2014
Stellenbosch scientists have achieved a significant breakthrough in the fight against disease with a proof-of-concept ‘nanochip in a capsule’ that 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 or Vibrio cholera within 10 to 15 minutes.
In the not too distant future, say the scientists, 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.
Professor Leon Dicks, an internationally acclaimed microbiologist, joined forces with Professor Willie Perold, also an internationally respected scientist in the field of superconductors and nanoelectrical devices, to pursue the concept of a nano-chip that would be able to detect bacteria and viruses in a patient’s stomach within a few minutes of being swallowed.
Deon Neveling, a postgraduate student in the Department of Microbiology at Stellenbosch University, was tasked with putting the concept to the test as part of his research for a master’s degree in microbiology – and the result was encouraging. Perold and one of his doctoral students, Stanley van den Heever, developed a zinc oxide nanogenerator that generates electricity the moment the nanowires are disturbed – a first in South Africa.
Soon afterwards, Perold bumped into Dicks after a research meeting, and they shared their thoughts. Recalls Perold: “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 that could instantly be picked up.”
To prepare the nanogenerator for biological use, the engineers constructed a silicon chip measuring 1cm square, then stacked zinc oxide molecules on top of each other to create a nanowire (visible only 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 is called piezoelectric energy. This energy is converted to electrical energy and 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 (a disease-causing microorganism) and report the presence of the pathogen within seconds.
The key to the concept, say the researchers, lies in linking the correct antibody to the nanowires to form a perfect “one and only” match with the antigen.
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 gastro-intestinal 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 nano-chip is released, and the fishing trip starts. Says Dicks: “Our dream is to transfer the electrical signal, which is selected to be unique to each pathogen, to a receiver such as a smartphone.”
This part of the concept still has to be developed. But, says Dicks, the important thing is that the nano-chip 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 such as 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’s difficult and time-consuming to diagnose a patient with the Ebola virus. This is because the early signs and symptoms of Ebola resemble that of several other potentially fatal diseases such as malaria, typhoid fever, shigellosis, cholera, leptospirosis and meningitis.
In the short term, Dicks plans to work with a group of French scientists to develop a nano-chip 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 article titled “A nanoforce ZnO nanowire-array\ biosensor for the detection and quantification of immunoglobulins” in the journal Sensors and Actuators B: Chemical. The basics of the biosensor are described in the article, “Effect of seed layer deposition, Au film layer thickness and crystal orientation on the synthesis of hydrothermally grown ZnO nanowires”, which was submitted to Current Nanoscience.