IMPACT's Research Challenges
Initially, the system will be developed as a set of individual chips. The final system will integrate sensors, instrumentation and communications on a single device.
Biomarkers that are directly implicated in cancer progression, cancer cell death (apoptosis) or necrosis will be targeted, including Caspase-9, transcription factors such as Hypoxia-inducible factors (HIFs) and the nucleic acids (specifically DNA) released by dying cells. The caspases are ideal monitors of apoptosis (cell death). IMPACT's challenge is to detect relevant cancer biomarkers, specifically and sensitively. This approach will, however, be applicable generically to other protein and nucleic acid biomarkers, enabling a suite of specific biomarker sensors to be incorporated readily on chip.
The body's immune system responds to an object implanted over long periods by developing protein plaques or scar tissue to encapsulate it. This may affect sensor performance and may require suppression. We will extend a drug delivery technology developed at the University of Edinburgh to protect sensors from biofouling and expose them to the tumour microenvironment at defined times. Over 200 such elements will be generated per biomarker with ten exposed at a time to allow signal averaging and internal controls. Radiation damage is also a concern. We have demonstrated that the electronic components of CMOS sensor chips can survive exposure to radiation, if they are powered down during RT - the same tests will be applied to sensor chips.
Initially, in the interests of simplicity, the implanted sensors will be connected to the outside world via wires for power delivery and data transfer. However, this is undesirable due to the problems presented by wires breaking through the skin and the ultimate aim will be to develop an implant which communicates wirelessly and either has power supplied to it by wireless power transfer or has an on-board battery. IMPACT's biosensor and instrumentation designs must take misalignment and misregistration of an implant with its external power and communications into account, additionally requiring low power operation and possible digitisation and compression of hypoxia measurement results to reduce transmission power requirements. It may be necessary to use a combination of inductive communications (across the skin barrier) with ultrasound communications (within the body).
To deliver its technology to patients as rapidly as possible, IMPACT will use a strategic planning or roadmapping technique for the sensor chips to analyse and optimise future value chains (the sequences of activities that a company performs in order to bring a valuable, and therefore profitable, product to the marketplace). This will take account of current and future regulatory developments for implantable biosensors, currently a vibrant and rapidly-changing area in the European regulatory system. IMPACT will also take account of patients' and public understandings and perspectives on acceptability and future use of its technology. Experience from previous research using this approach has shown that decisions taken early in the research process can have profound and unexpected implications for the future development and uptake of a new technology in a public health or commercial context. This approach will enable IMPACT researchers to explore the downstream implications of such decisions and to refine them with future opportunities in mind.