- Implantable Sensing – Possible miniaturisation of electrochemical platforms is an important step for the development of a new generation of implantable devices. One of the tasks in the project is development of bio-integrated patch with integrated sensing system. The ultimate goal is the development of miniature/unobtrusive, long-lived biocompatible implants that could detect and measure several analytes in the body at the same time. The major challenge is developing a sensor that is both long-lived and biocompatible.
- Bio-Impedance - Electrical Impedance Spectroscopy: Ohm’s Law relates an applied voltage (potential) difference to the electrical current of electrons that can flow through a material as a function of the resistance that the material imposes to the electrical current. This resistance depends on the material's properties and is related to the geometry and the conductivity (σ) of the material. If this resistance changes as a function of the frequency of the applied voltage from zero Hz (direct current, d.c.) to high frequencies (e.g. 1MHz, alternating current, a.c.) then the material exhibits a reactive part - behaving like a capacitor or an inductor to some extent - and the resistance is now called an impedance. Tissue has a resistive part and a reactive capacitive part as it behaves as a dielectric as well as a conductor. Dielectrics restrict the flow of current and instead charges polarise leading to charge separation, i.e. a capacitance. The capacitance is a function of both geometry and the dielectric properties (dielectric constant, εr) of the material, which dictate its charge storing capacity. Measurements of the electrical properties of tissues give us an insight into a plethora of information related to the human health, as tissue impedance is influenced by metabolic and physiological changes.
- CMOS FET for ASICs - Complementary Metal-Oxide Semiconductor (CMOS) Field Effect Transistor (FET) technology for Application Specific Integrated Circuits (ASICs). Semiconductor technology is based on the use of stencils, similar to the ones artists use to paint graffiti on walls. These stencils are used to pattern nanoscale features on silicon semiconductor substrates to define devices such as resistors, capacitors, inductors, transistors and diodes. These can be arranged by the designer to fabricate active devices such as analog amplifiers and electronic filters, or digital systems such as processors, as well as analog-to-digital and digital-to-analog converters. A variety of such components can be designed and combined on a single substrate, permitting the production entire electronic sensing systems on a single miniature microchip. Such microchips are used regularly in everyday life and can be found in our mobile phones and computers. They are responsible for the rapid advances in technology that we are experiencing daily! We can use these technologies to create novel miniature medical devices to monitor our wellbeing and asses our health. These can be combined with advances in information technology such that your health-related data can be securely accessed and processed by physicians anywhere in the world.
- Ischemia - Ischemia is defined as the restriction of arterial blood supply to a tissue, organ or extremity. This leads to reduced blood oxygenation and glucose. The latter is essential in cellular metabolism and, hence, essential for tissue to remain functional and viable. The removal of waste products through venous return is also deficient. In other words, due to ischemia, oxygen and nutrient supply is inadequate to meet tissue metabolic needs. A series of biochemical reactions are initiated within seconds of ischemia. Mitochondria inside every cell require oxygen and oxygen delivery constriction leads to anaerobic metabolism. As a result tissues are unable to gain energy in the form of ATP by glycolysis. Glucose is broken down into pyruvic acid but it is subsequently converted mainly into lactic acid and protons are produced. Ionic exchange across cell membranes leads to a build-up of hydrogen ions (which are not taken away due to the absence of circulation) and thus tissue becomes acidic and its pH decreases. This pH decrease alters enzyme activity, ion pumps and ion channels, which are responsible for maintaining intracellular and extracellular molecular concentrations at physiological levels. This is a process that requires ATP and so during ischemia ion pumps fail. The result of this is a change in the intracellular and extracellular concentrations of important ions such as potassium (K+), sodium (Na+), chloride (Cl-) and calcium (Ca2+).
Surgical sites deep in the body are difficult to monitor and current diagnostic techniques alert clinicians of complications when it is already too late. Monitoring these sites is necessary for periods up to 4 weeks to ensure there are no complications and that the operation and the healing process is progressing in a satisfactory manner. Currently there are no implantable medical devices that have the ability to post-operatively monitor a surgical site. At the Hamlyn Centre we are working towards the first devices of this kind. For certain types of surgery, inadequate tissue oxygen delivery (ischemia) can serve as a prognostic marker for subsequent complications. The increase in intracellular concentration of certain ions leads to an increase in the intracellular osmotic pressure, resulting in intracellular (anoxic) oedema. The progression of the ischemic event triggers the activation of inflammatory mediators, which in turn disturb membrane permeability. The cell membrane becomes more permeable; more harmful chemicals flow into the cell and metabolic waste products accumulate. Mitochondria also break down, releasing more harmful chemicals into the cell. Ultimately, metabolic processes cease, ion pumps fail and the membrane is disrupted. Cells subsequently die (apoptosis), leading to organ failure and the release of harmful toxins into the surrounding environment. This will poison nearby neurons, cells and organs. Potentiometric (pH, K+, Na+) and impedimetric sensors have been applied to tissue ischemia monitoring; however, there has not been a single miniature flexible multi-modal sensing array that is capable of measuring the variety of sensing targets that we are interested in. Moreover, the limited examples in the literature use tethered approaches leaving the electronics far from the tissue. Additionally, these have thus far been based on commercially available discrete electronic components leading to large bulky arrangements. As a result, currently there is no implantable impedimetric system and, moreover, there in no such system combining impedance and ionic measurements. At the Hamlyn centre we are working towards the first such system using CMOS ASIC technology.
For implantable sensing, a particularly challenging case is colorectal resection via anastomosis in the gastrointestinal tract. Failure of the anastomosis can lead to colorectal anastomotic leakage (CAL), one of the most serious and challenging complications following sigmoid or rectal cancer surgery and the leading cause of death after colorectal surgery. We are investigating the use of commercial flexi/rigid printed circuit board (PCB) fabrication technologies to allow the development of mass-produced, low-cost sensors, as well as in-house fabrication of novel application specific sensors using inkjet printing techniques.
What are we using it for?
At the Hamlyn Centre we are working on the development of the next generation of implantable medical devices for post-surgical monitoring of deep surgical sites. Sites of surgical interventions deep inside the body are difficult to access to evaluate tissue viability, healing and progression. Monitoring these sites would allow physicians to determine whether there are complications that may lead to infections, prolonged post-operative hospital stays, re-operation, poor functional outcome, multiple organ failure or even mortality. Current clinical practices do not allow us to detect complications early enough leading to (as well as the effects described above) increased strains on the NHS, costing approximately one billion pounds per year. Our main goal is to introduce SMART sensing into surgical operations and patient recovery, and to introduce intelligence into passive devices such that we alleviate significant burdens from health care systems and professionals, patients and their family’s.