Medical imaging has evolved in recent years from a means to diagnose and evaluate large anatomical changes into a highly specialized tool used by physicians and scientists for the interrogation of events at the cellular and molecular level in living patients. Molecular imaging has enabled the medical community to diagnose and monitor diseases based on specific molecular events. Thus, molecular functional imaging represents a shift in the paradigm of experimental planning, whereby assays are no longer relegated to a test tube or cells in culture, but can be performed in a physiologically-relevant setting. Optical in vivo functional imaging has several advantages over other modalities. It is relatively inexpensive, versatile, sensitive, quick, and easy to implement. One of its drawbacks, however, is its limited ability to easily scale to human imaging due to the scattering and absorption properties of living tissue. This currently limits optical imaging techniques to shallow tissues (a few cm deep) or endoscopy-based probing. Implanting integrated sensors to report on fluorescence from functional imaging probes can overcome this limit.
We are developing the instruments and techniques to accomplish portable, live animal monitoring using implantable sensors. Integrated VCSEL source/PIN photodiode detector chips can be used for fluorescent sensing with filters optimized for specific dye wavelengths. We are currently using devices optimized for use with Cy 5.5 (670 nm/720 nm), but flexible enough to be applied in a number of different dye schemes. Characterization of these devices has shown that signal can be obtained from dye present several millimeters within tissue.
Molecular beacons can be used as functional biomarkers to target specific proteins, potentially revealing the presence of cancerous tissues. We are working with Pyroeophorbide acid-based markers to target fibroblast activation protein (FAP), present only in epithelial tumour stroma. By studying the time course uptake of the marker within a tumour we can learn about metabolization in cancerous tissues, as well as investigate the efficacy of potential treatments such as photodynamic therapy (PDT). Implantable biosensors allow for the continuous monitoring of awake animals, removing the limits inherent to imaging under anaesthesia, and introducing the possibility of long term monitoring over days or weeks.
We are currently investigating other uses of these biosensors, including integration with digital microfluidic devices. The inclusion of a reliable portable sensor with such instruments can allow for real time quantification of reaction dynamics, and lead to better monitoring and control of small volume reactions.