|CSIRO | SOLVE | Issue 4 Aug 05|
MICROSENSORS: Invisible Watchdogs to Keep Us Safe and Well
By Ava Bentley
NEW TOOLS THAT INSTANTLY IDENTIFY INDIVIDUAL MOLECULES ARE OPENING UP NEW HORIZONS FOR MEDICAL DIAGNOSTICS AND SECURITY.
The doctor’s office of the very near future will have no lengthy pathology tests or swabs, just a hand-held sensor that detects viral or bacterial infection in seconds. The same technology will also be working at border points such as airports, where concealed bioterrorism agents such as anthrax or ricin, even SARS, will be detectable with the click of a button on a unit the size of an iPod.
Advances in the detection of individual molecules that make up potentially hazardous compounds are leading to the development of new tools with a wide range of medical, environmental and security applications. Other potential uses include the detection of disease in food-source animals, toxins in water, contaminated food products or hazardous chemicals in a fire zone.
This developmental work by CSIRO is part of a new research group, Technologies for Safeguarding Australia. Researcher Dr Tim Davis says the project was initiated in response to the Government’s National Research Priorities, one of which is Safeguarding Australia. The aim is to protect Australia from bioterrorism, as well as diseases and pests, by developing technologies that can detect individual biomolecules.
CSIRO has committed two teams of scientists to the project: the Microsensor Technologies Team and the Microfluidics Team. The teams will combine their expertise in physics, biology, microfluidics, surface science, electronics, instrument design and wireless technology.
The researchers hope to develop a process of detecting and identifying single molecules or organisms (bacterial toxins, viruses or spores, for example) using Surface Enhanced Raman Scattering (SERS), which has excited the scientific world for some years.
SERS is an enhanced form of the Raman scattering technique first observed in 1928. The Indian scientist Sir Venkata Raman won a Nobel Prize for it in 1930.
Raman scattering involves scattering light or electromagnetic fields from molecules. When this occurs, some of the light shifts in wavelength, observed as a change in colour. The subtle spectrum of colours, says Dr Davis, is like a fingerprint that identifies the molecule or particle.
With SERS, a sample of molecules is washed over a metallic silver surface prepared with a specially designed nanotexture. Light shone on the surface resonates with the texture, which enhances the electromagnetic fields. These lead to an enormous increase in the strength of the Raman scattering. Dr Davis says the trick is to design the surface texture to get the enhancements needed for single molecule detection.
'Ultimately, the research could change the way Australia responds to pathogenic and biological attack'
At such high sensitivity, contamination of the Raman signal by unwanted molecules then becomes a problem; it is essential to filter the sample first, to remove as many of the unwanted molecules as possible.
The work of the Microfluidics Team will be an important part in eliminating this time-consuming step. The team’s leader, Dr Yonggang Zhu, says that the microfluidics research will assist by providing platforms for the detection of single molecules. These platforms combine most of the labour-intensive, laboratory-based analysis steps such as sample transfer, treatment, molecule separation and stirring into a single microfluidic chip.
“Microfluidics is a new science based on understanding the behaviour of fluids at microscale,” Dr Zhu says. “Tiny dimensions expose new physics in fluid–surface interactions and in the control of chemical reactions.”
Understanding the dynamics of these reactions and interactions will form the basis of the new breed of microdevices. Dr Davis believes such devices could have endless applications. For example, hand-held detection units could help police or customs officers detect drugs. Or, firefighters could protect themselves from toxic air pollution by using held-held units to detect and identify toxins or chemicals that pose a threat to health.
Ultimately, the research could change the way Australia responds to pathogenic and biological attack, or the medical profession makes diagnosis and treatment decisions. The research is not just a small step for Australia, it’s a giant leap.
Australian from bioterrorism, disease and pests is a top priority in the current world climate.
Research into single molecule detection will enhance the detection of hazardous pathogens and other biological or chemical agents.
The possible uses for miniaturised and hand-held detection units are endless.
Good Vibrations for Blood Tests
By Whitney MacDonald
Just a single drop of blood, taken and tested in a GP’s surgery, may soon be all that is required for many diagnoses that currently require lengthy tests in pathology labs. It is a familiar situation: you suspect you are unwell but put off the doctor’s visit because you know how much time will be spent on trips between a pathology lab and doctor’s office as you progress through an inevitable series of tests and follow-ups. It is a common situation and costs both patients and the health sector generally considerable time and money.
So imagine being able to have the results of all preliminary diagnostic screens, complete with a follow-up plan, before leaving the initial consultation – all made possible by using just a drop of blood that has been tested on a tiny device that fits into the palm of a doctor’s hand.
A device such as this could soon be a possibility because of work being undertaken by Australian researchers.
The key to this development is a new way to mix blood and reagents that only needs a drop or two of the blood to be tested.
Scientists in the Microfluidics Team at CSIRO Manufacturing and Infrastructure Technology, in Highett, Melbourne, have developed and patented a microtechnology that uses sound to mix blood. The process, using sonic vibrations, accelerates the biological interactions that are a critical component of standard diagnostic testing, and enables the testing to be done on the spot in a consulting room.
Traditional pathology laboratory tests, which account for 65 per cent of all diagnoses and more than $1 billion of annual Medicare expenditures, typically require larger volumes (often several test tubes’ worth) of fluid to perform a test. The sample is then mixed with a panel of biological reagents, so that immunologically important proteins in the patient’s fluid sample physically interact with the panel of reagents.
This is a process that is highly dependent on the two components mixing – the blood sample and the reagents.
On this larger scale, mixing is done by a simple shaking motion, yet turbulence disappears at the microscale that is required if routine diagnostic testing is to be taken out of the pathology laboratories and into the doctor’s surgery.
“Mixing is one of the key bottlenecks that needs to be overcome to miniaturise diagnostic testing,” explains Dr Richard Manasseh, a member of the Microfluidics Team. “Without a suitable mixing technology at the small scale, the interaction of the components in the fluid relies upon diffusion, a process which can slow a diagnostic test down by many hours.”
In the technology used by the Microfluidics Team, tiny bubbles surrounding the fluid sample within a microfluid channel are excited using piezoelectricity (a type of crystal that can electronically generate a frequency). The small amplitude periodic oscillations act on the bubble. This creates a flowing circular motion in the fluid due to the acoustic field around the bubble, causing a ‘micromixing’ effect.
Such micromixing technology has the ability to reduce the mixing time from hours to seconds; a saving that would be significant in both time and money.
To tackle the task of miniaturising diagnostic testing and developing an effective mixing technique for small fluid samples, researchers looked beyond the fluid dynamics arena by forming collaborations within the fields of protein chemistry and surface physics. The next step after mixing – detecting the test results – is being worked on by other teams.
CSIRO is now patenting one aspect of the micromixing technology. With its research partners, it is seeking potential industry support to target a specific pathology test with which to customise a prototype development.
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