Current lab-on-a-chip systems
Effective and reliable diagnosis is an essential tool in medical practice. The convergence of new technologies such as biology, materials science, information technology, molecular chemistry and microelectronics has been revolutionising developments in diagnostics. New knowledge and the ability to manipulate at the nanoscale are also beginning to have a significant impact.
The term lab-on-a-chip (LOC) is usually applied to devices that integrate a variety of functions onto a substrate such as glass, ceramic or polymer. Typically, these devices are a few square centimetres in surface area and may be of a similar size and shape to a traditional standardised microscope slide, but other designs and sizes also exist. LOC systems can include a combination of a number of the following components.
Benefits of LOC approaches
LOC approaches offer significant advantages over conventional methods. These include
LOC techniques can already be applied to a wide variety of applications including pharmaceutical screening and testing, toxicological studies, medical laboratory analyses such as blood and disease screening, measurement of metabolic and physiological status, the detection of individual cells, biomolecules or markers, immunoassays, deoxyribonucleic acid (DNA) testing and genomic studies.
Applying nanotechnology to improve LOC functionality
Many of the features of LOC systems are already at the microscale and further physical scaling down may present significant technical challenges. Entities such as individual cells and proteins would be too large to pass through or interact with certain features if the size of those features was reduced too far; and more complex physical and chemical effects may be manifested at the nanoscale, thus resulting in measurement difficulties. There are, however, many ways that systems can provide greatly extended functionality. These include
One important aspect of developments of this type are that they are highly multidisciplinary in nature with a strong convergence of bio-logical, physical, chemical, engineering, materials science and informatics approaches, each often involving a nanotechnological aspect.
New LOC systems
An example of the use of other physical features to provide extended functionality is a cell array currently under development in the ToxDrop FP6 Project, Highly Parallel Cell Culture in Nanodrops.1 This employs a glass surface containing individual hydrophilically and hydrophobically functionalised areas and 800 drops per slide. Each individual drop contains 100 cells of a selected type that may be cultured for up to five days. As many as 50 parameters can be measured individually for each cell and the system is ultimately expected to be used for high throughput toxicity testing.
Another example developed by a group at Arizona University, USA, together with other collaborators, employs nanoscale superhydrophobic surfaces.2 Onto these go individual droplets in which magnetic or paramagnetic nanoparticles can be readily manipulated, split and mixed in various ways using magnetofluidics with minimal surface tension effects.
Drivers of further development
There are a number of factors that are driving further advancement of LOC technology and the increased application of nanotechnology in this field. These include opportunities for LOC based systems to contribute in an important way in the following applications.
Novel pharmaceuticals. In the rapid screening of novel pharmaceutical molecules for activity and safety, for example, from combinatorial or antibody fragment libraries.
Emerging health risks. For rapid and highly specific testing of health risks such as prion diseases, nosocomial infections and severe acute respiratory syndrome.
Developing world. For tackling growing health problems in the developing world, for example, monitoring HIV/AIDS, tuberculosis and other large-scale killer diseases. The ability to engineer testing into highly portable and “smart” systems that are usable by workers, who do not necessarily have specialist training, would be extremely valuable in areas that do not have adequate laboratory facilities.
Replacing tests. The replacement of traditional and sometimes unreliable or inappropriate animal testing by effective alternatives, in many cases using human-derived cells and tissues, for many types of toxicity testing. These include the large volume of regulatory testing foreseen under the amended European Cosmetics Directive and the Registration, Evaluation, Authorisation and Restriction of Chemicals Regulation (REACH), whereby thirty thousand chemicals will require testing under REACH.
Testing nanoparticles. The safety testing of novel nanoparticles and other nanomaterials. Materials with nanoscale dimensions do not necessarily have the same properties as the same materials in bulk or particle size and shape, and a number of other characteristics also affect the materials’ potential toxicity. There are already many thousands of new nanomaterials that require characterisation and toxicity testing prior to being used on a large scale.
Prevalent Western diseases. Screening for problems such as cardiovascular disease, cancer and diabetes, which are increasingly prevalent in a Western society that is rapidly ageing and placing high pressure on available health care resources. Diagnosis and treatment at an early stage would prove highly cost-effective, particularly if available in point-of-care devices that are usable outside the laboratory in doctors’offices or patients’ homes.
The future for LOC technologies
Some challenges still remain such as how to understand and overcome novel effects associated with further miniaturisation of features, how to standardise components to work between different LOC systems, and how to integrate widespread application of LOC systems into general health care management. However, the progress made in the past 15 years and the developments already underway suggest a healthy future for LOC technologies.
1. A new format for high content cell-based toxicity screening on cell on chips, Project Coordinator, Dr Béatrice Schaack, iRTSV/Biopuces, CEA Grenoble, France, www-dsv.cea.fr/biopuces/toxdrop
2. A. Egatz-Gomez and A.A. Garcia, Ira A. Fulton School of Engineering, Arizona State University, Tempe, Arizona, USA < www.fulton.asu.edu/fulton/people/page.php?profile=74> Applied Surface Science, 254, 1 (2007).
Richard Moore is Manager, Nanomedicine and Life Sciences, at The Institute of Nanotechnology, Suite 5/9 Scion House, Stirling University Innovation Park, Stirling FK9 4NF, UK tel. +44 1786 458 020 e-mail: email@example.com, www.nano.org.uk www.nanomednet.org