ClearSERS - A Novel Imaging Concept

We live in a world where we can image the deepest ravines in our oceans or the farthest objects in our Universe and as such it may come as a surprise to many that imaging inside of our living bodies without limitations still constitutes a major challenge. Although an array of powerful imaging techniques does exist, including Magnetic Resonance Imaging (MRI), X-ray Computed Tomography (CT), Positron Emission Tomography (PET) and Ultrasound (US), these are often unable to detect subtle chemical alternations inside our bodies associated with very early stages of diseases, such as cancers, infectious diseases and others. This is an ideal stage for these to be diagnosed; as the associated impact on the patient and their resulting symptoms are much reduced and, most importantly, associated treatments are most effective and least aggressive. This deficiency is often due to insufficient sensitivity and low bio-chemical specificity to detect the presence of low concentration biomarkers signalling the onset of a disease inside our bodies. High costs (MRI, PET) and the presence of ionising radiation (CT, PET) are additional factors precluding their wider applicability as early disease diagnostic tools. Here we propose a radically new imaging concept, ClearSERS, that addresses many of the above limitations. The method combines the ultrahigh sensitivity and bioselectivity to low level biomarkers of Surface Enhanced Raman Spectroscopy (SERS), which uses gold nanoparticles (NP’s) to boost Raman signals billions of times or more, and the noninvasive depth probing capability of Spatially Offset Raman Spectroscopy (SORS), uniquely, with focussed ultrasound (US) resulting in a high spatial resolution, unattainable by light itself. In this approach ultrasound is focussed onto SERS gold nanoparticles located within diseased tissue inducing a small change to their signal (e.g. intensity change or spectral shift). This signal change is read at the surface of tissue noninvasively using SORS. As the signal originates primarily from the focal point of ultrasound its location is known and can be confined to sub-millimetre dimensions. By rastering the sample one can then map the distribution of NP’s inside body with correspondingly high spatial resolution. The NP’s can be delivered to the target zone by intravenous injection coupled with functionalised specific targeting. As the nanoparticles can be attached selectively to the diseased tissue (e.g. cancer lesion or infected zone), using bio-selective functionalisation (e.g. antibodies), the method enables the extent of such diseased zones to be mapped inside our bodies simultaneously with high spatial resolution, ultrahigh sensitivity and ultrahigh biological and chemical specificity. In this project, we will construct and optimise such a device, develop a range of suitable NP’s exhibiting an augmented sensitivity to ultrasound, demonstrate the imaging concept in excised tissue and characterise its performance. We estimate that ClearSERS could achieve spatial resolution on a scale of submillimetre at depths of several centimetres inside tissue. In effect, as if rendering tissue transparent from the viewpoint of SERS NP’s. This novel imaging platform underpins prospects for a host of new clinical applications including early cancer diagnosis, cancer classification, grading and staging, monitoring of cancer treatment at all stages of the disease (e.g. shrinking of lesion in response to treatment), guiding cancer lesion excision, diagnosing and monitoring of infectious diseases (e.g. extent and nature of subsurface infection and response to treatment), detection and treatment of atherosclerosis (location and spatial extent of plaques within artery).