Holographic indicator for heart problems

Good health is a basic human requirement for a high quality of life. Diagnostic tests and procedures are vital tools in the armoury of the physician to help confirm or rule out affliction with a medical condition.

Holographic images can be made to appear or disappear under an appropriate chemical or biological stimulus and be used to display visual interpretations of the analyte concentrations.

Professor Christopher Lowe

Today, diagnosis is based on the measurement of a range of chemical parameters in accessible biological fluids such as blood and urine. In most cases, the samples are sent to a central laboratory for analysis and the results become available minutes, hours or even days later. Such delays can hamper timely diagnosis and impede medical decision-making. Nevertheless, a typical hospital laboratory has evolved over the years into a fully automated system of sample collection, bar coded patient identification, sample pre-treatment and passage via high throughput computer-controlled instruments. Human intervention is now limited to engineers rather than biomedical scientists.

However, in recent years, there has been something of a quiet revolution in diagnostics practice, with a discernible trend to take tests to the patient. Technological advances in assay chemistry, sensor and transducer platforms, electronic processing, instrumentation and miniaturisation has seen the emergence of ‘alternate site’ diagnostic testing in the ward, outpatients, surgery, home, and workplace. This type of near-patient testing, or point-of-care (POC) testing as it is now known, is set to expand dramatically. POC testing can reduce the cost per test by 35% with additional savings in manpower. It simplifies the steps involved in sample handling and has been proved to reduce the turn-around-time for cardiac markers from 72 hours in the central laboratory to 20 minutes patient-side, with clinical decisions made proportionately quickly.

POC testing is likely to be preferred in situations where rapid diagnostic monitoring can improve medical decision-making. For example, in A&Es, it may be used to measure drugs-of-abuse in critically ill patients who need to be assessed and treated quickly. Similarly, POC testing can be applied to monitor patients on anticoagulant therapy in the operating theatre where time is of the essence. POC testing is also an attractive option where the frequency of monitoring necessitates sample taking close to the patient, such as in a physician’s office, care home or patient’s home. Other recommended applications range from testing for diabetes to pregnancy to inflammatory diseases. The diversity of potential near-patient tests suggests that POC systems must offer a broad portfolio of tests. The question is what technology platform can accommodate such a plethora of diagnostic tests to generate rapid, accurate, reliable and fool-proof clinical data.

At the University of Cambridge, research at the Institute of Biotechnology is investigating biosensors as one of the principal contenders. A biosensor is an analytical device which uses a physico-chemical transducer to convert the recognition of an analyte directly into an electrical signal. Cambridge scientists are concentrating on simplified and generic biosensor platforms that will find application in a wide range of POC tests.

Holographic biosensors are at the cutting edge of this research. Pioneered by a multi-disciplinary team of physicists, chemists and biochemists at the Institute, the concept is based on using reflection holograms which respond to all classes of analyte including ions, gases, enzymes, metobolites, oligonucleotides, antigens and whole cells. Holographic sensors can be fabricated as test strips which provide changing optical images to indicate the test result. This approach is unique in the field of biochemical sensors: the hologram per se provides the analyte-specific response polymer, the optical interrogation and reporting transducer all in one robust, inexpensive and easily manufactured sensor.

Currently these sensors are being developed for POC testing of the key clinical analytes, patient self-testing, and for roadside and first responder testing for pathogens. However, an interesting feature of the holographic sensors is that holographic images can be made to appear or disappear under an appropriate chemical or biological stimulus and be used to display visual interpretations of the analyte concentrations. Obvious applications for these visual indicators include breathalysers, and the monitoring of heart conditions and diabetes. A further important extension of this programme is to develop holograms for indwelling catheters, subcutaneous sensors and contact lenses for minimally invasive real-time monitoring of glucose in diabetes management.

The Institute also has a strong focus on developing diagnostics for complex neuropsychiatric disorders, such as schizophrenia and bipolar affective disorder. This is a particularly challenging area for several reasons: diagnosis is usually via interpretation of a complex behavioural and cognition questionnaire by a competent clinical psychiatrist; there are currently no known clinically accepted biochemical markers for these disorders since biomarkers for brain dysfunction are not obviously found in readily accessible biological fluids; the disorders manifest themselves slowly over extended periods of time and their onset may be dependent on environmental, dietary and lifestyle triggers; and finally, the efficacy of current therapies are at best somewhat serendipitous and the patients tend to be non-compliant and resistant to patient testing and care.

Nevertheless, the work of Cambridge scientist, Dr Sabine Bahn has already identified a number of promising biomarkers in cerebral spinal fluid (CSF), serum and peripheral tissues and it is expected that these will form the basis of a new category of psychiatric diagnostics. It is anticipated that near-patient POC technology will eventually measure a panel of genetic, protein, metabolite and drug analytes and benefit this branch of psychiatric medicine in a number of ways. It will: identify genetic susceptibility to these disorders, predicting the risk of developing the condition; offer pre-symptomatic diagnosis, and prognosis; allow patients to be stratified according to patient, drug and dose type; monitor patient response and compliance with treatment regimes; and finally, identify any adverse drug reactions at an early stage. Thus, neuropsychiatric disorders and other complex medical conditions are amenable to ‘personalisation’ in that therapeutic regimes can be tailored to the individual patient following analysis of their genetic and pharmacokinetic profiles.

The effect of POC testing can also be assessed in terms of the overall clinical outcome. It is clear that POC technology can impact faster decision-making, allow treatments to commence earlier, improve compliance, reduce the incidence of complications, optimise treatment, reduce re-operation or re-admission rates, improve patient satisfaction and ultimately reduce the costs of healthcare provision.

For further information, please go to www.biotech.cam.ac.uk

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