Editorial – the latest thinking and developments in optical diagnosis

This latest Optical Diagnosis themed issue of Analyst, guest-edited by Dr Bayden Wood and Professor Don McNaughton, highlights the seventh SPEC conference: SPEC 2012 – Shedding New Light on Disease, held in Thailand, November 11–16, 2012. The conference was located in the northern Thai city of Chiang Mai and reflects a surge in interest from the South Asian region to develop rapid and inexpensive solutions to pathological testing in the areas of medical and agricultural science. As its full title suggests, the SPEC conference series is dedicated to advances in medical diagnostics using biophotonic approaches, mainly Raman and infrared spectroscopy. It was fitting that Professor Henry Mantsch, Emeritus Professor at the Institute for Biodiagnostics, National Research Council of Canada, regarded by many as one of the founding fathers in this field, gave the opening plenary address outlining the historical development of the field from its foundation to the present day and whose written account features as the first article in this themed issue (c3an90035e). Some might remember Henry in the mid-1990s, showing an image from the TV series Star Trek of Dr McCoy's tricorder, an analogy of where he thought the field was heading: the possibility of devices using light to non-invasively diagnose human health. Indeed, the SPEC 2012 meeting showed that the field is rapidly maturing, with the bench-to-bedside translation quickly becoming a reality, suggesting prescience in Henry's early vision.

The expansion phase currently being witnessed in this field is connected with recent keystone advances in fundamental knowledge which include: the understanding of light-scattering phenomena and how to correct the effects; resolving the so-called ‘dark DNA’ conundrum; and more recently the identification of artefacts with measurements made on reflecting substrates due to the electric field standing wave (EFSW) effect. Spectral distortion resulting from the EFSW effect has been identified to occur with a change in sample thickness. A consequence of the EFSW artefact could be that researchers have to desist from using the only currently available inexpensive IR substrate for cell and tissue studies (Kevley glass slides), leading to vigorous debate. This issue contains important work by Diem's group (c3an00185g) on this topic that argues in a compelling fashion that the confounding effects of spectral artefacts with transflectance measurements can be rendered insignificant by appropriate spectral data transformations including second derivative processing and normalisation. The work by Heraud et al. (c3an00321c) shows empirical evidence in support of this, demonstrating no difference between transflectance and transmission measurements on dried cellular monolayers with this pre-processing approach. The work of Diem's group also points out that, at least with cytological work, where there is often very uniform inter-sample thickness, nullifying the influence of EFSW, as demonstrated by Heraud et al. for dried cytospun human embryonic stem cell monolayers.

As mentioned above, the field has started an accelerated period with research programs in many laboratories moving from the proof-of-concept phase and becoming more translational in nature. Never before has there been a closer engagement with clinicians and clinical studies. Current research of this kind published in this themed issue builds upon a strong research foundation, establishing the efficacy for using IR or Raman spectroscopy for early disease detection, with a major focus on cancer diagnosis (approximately one-third of the publications), with new diagnostics for other diseases beginning to emerge as well, including diabetes (Baranska et al., c3an00216k), malaria (Smith et al., c3an00255a), Alzheimer's (Gough et al., c3an00295k) and regenerative medicine (Heraud et al., c3an00321c). Notable for translational advances in the spectro-diagnostics of cancer are the studies aimed at the rapid detection of pathology to assist real-time decisions in surgery such as the in vivo Raman detection of the tumour boundaries advanced by the work of Sato et al. (c3an00169e) or automated rapid diagnostics for the same purposes with FTIR imaging of tissue sections in the work by Krafft et al. (c3an00326d). Backing up the research on cancer diagnostics is the continuing fundamental research focussed on understanding spectral changes during the cell cycle, particularly those associated with nucleic acids, including studies by Whelan, Wood and co-workers (c3an00316g), Vaccari et al. (c3an00318c) and Bassan and Gardner et al. (c3an00507k).

Another research stream prominent in this edition is diagnostics using Raman and IR spectroscopy of body fluids, comprising about a quarter of the published works in the themed issue. Although these approaches rely on invasive sample procurement, they capitilise on the decreased complexity of chemical systems involving biofluids compared with cells and tissues, but nevertheless have benefited enormously from recent advances in sampling approaches, instrumental improvement and fundamental leaps in knowledge such as understanding of sample scattering phenomena. The papers included in this edition mainly concern analysis of blood sera, with notable progress in the area of of cancer diagnostics (e.g. Martin et al., c3an36654e, c3an36527a; Zeng et al., c3an36890d; Chilakapati et al., c3an00308f, c3an36761d; and Sockalingum et al., c3an00245d). Advances in the analysis of biofluids involving improved micro-sampling approaches (Ollesch et al., c3an00337j) and the refinement of instrumental measurement (Bassan et al., c3an00363a) are also highlighted in this edition.

The area of spectro-diagnosis of disease is currently burgeoning and is poised to make the next translational leap to commercialised diagnostic systems that have advantages over traditional diagnostics approaches, promising automated objective discrimination not relying on expert opinion, also being rapid and inexpensive, label-free and non-invasive. This translation process in the field is being driven both by continuing advances in fundamental knowledge complemented by rapid evolution in instrumentation. Notable instrumental advances discussed in this themed issue include: new multimodal non-linear microscopy systems (Popp et al., c3an00354j); laboratory-based IR microscopy utilising more brilliant source of IR light based on quantum cascade lasers (Lendl et al., c3an00300k); improvements in IR measurement that minimise light scattering artefacts (Lasch et al., c3an00381g; Kazarian et al., c3an00327b); and advances in fibre optic based probes (Sakharov et al., c3an00248a; Lindahl et al., c3an00243h). Complementary to instrumental advances is software development that systematises quality testing, pre-processing and analysis of biospectroscopic datasets, such as the approaches advocated by Diem et al. (c3an00185g), which are also key to translation to the clinic. Moreover, recent engagement by the Asian research community of this area of research offers the opportunity to further accelerate translation activity because of the more favourable regulatory environment enhancing the testing of new diagnostics as well as providing the opportunity for rapid uptake in a vast marketplace that is crying out for less expensive alternatives to traditional pathological diagnostics.

The current rapid evolution in this field is truly fascinating with this Analyst themed issue, commended for providing readers with a comprehensive snapshot of latest thinking and developments in the area.

Phil Heraud and Bayden Wood

Centre for Biospectroscopy, Monash University, Australia


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