Interstitial fluid is the liquid portion of tissues that surrounds and bathes living cells. Though separate from the blood system, this fluid contains a wealth of information about an individual's health status in the form of small, soluble molecules. Glucose is one such molecule, and interstitial levels of this sugar directly correlate with blood glucose levels, an important health parameter for patients suffering from diabetes. Currently, glucose monitoring requires that invasive, blood-based analysis be performed on a regular basis. However, advances in transdermal monitoring that allow noninvasive sampling of interstitial glucose levels promises to revolutionize this process. Furthermore, these technologies can be applied to a number of health-based monitoring applications and may one day become an integral part of everyday personal diagnostic systems.
The prototype patch microsystem—on which research is currently being conducted at Georgetown University—utilizes highly selective enzymatic detection chemistries to analyze micro- and nano-liter volumes of interstitial fluid. This fluid reaches either a colorimetric detection layer or an electrochemical sensing electrode site through a passive, non-inflammatory collection strategy detailed below. The current patch is approximately 1cm2 and contains 25 individually addressable sensor sites arranged in a 5×5 array, as shown in Figure 1. These sites will ultimately be controlled by external circuitry that will allow the patch to be programmed by the user for hourly sampling or for on-demand use. The same patch area could hold as many as 500 sampling sites, allowing for continuous monitoring, at 15min intervals, over a period of five days.
Figure 1. The first prototype patch measures about 1cm2and is made using polymers and thin metallic films. The 5×5 sampling array can be clearly seen, as well as their metallic interconnections.
The physical characteristics of many biomolecules of medical relevance within the interstitial fluid typically render them unable to penetrate the densely packed layers of dead skin. In fact, this outermost skin layer, or stratum corneum, acts as a very effective seal against interstitial fluid leakage. However, when the seal is compromised, the interstitial fluid, and the biomolecules contained therein, becomes accessible on the skin surface. Utilizing micro-heating elements integrated into the structural layer of the patch closest to the skin surface, a high-temperature heat pulse can be applied locally, breaching the stratum corneum. During this ablation process, the skin surface experiences temperatures of 130°C for a 30ms duration. The temperature diminishes rapidly from the skin surface and neither the living tissue nor the nerve endings are affected. This painless and bloodless process results in disruption of a 40–50μm diameter region of the dead skin layer, approximately the size of a hair follicle, allowing the interstitual fluid to interact with the patch's electrode sites.
The adhesive bandage itself, which is in contact with the skin, may be made using multiple flexible polymer layers or other materials, such as silicon or thin metal films, interspersed with insulating layers and patterned metallic thin-films, all made using microfabrication technologies typically employed in the manufacture of silicon chips or integrated circuits. This has the benefit that the microsystem device can be manufactured using standard and fully characterized processing equipment and can be batch-fabricated, just like in the electronics industry, to yield extremely cost-effective devices. Though the prototype patch is being developed and studied at Georgetown University to sample glucose, this novel microsystem also provides an enabling technology for transdermal sampling of other biomolecules that do not normally diffuse across the skin.
With the recent alliance between Georgetown University, Gentag Inc., and Science Applications International Corporation, the combined intellectual property and expertise among these groups will be used to create new advances towards monitoring and controlling glucose levels. One potential approach being explored involves creating a closed-loop feedback system where the disposable transdermal patch measures glucose levels and reports that information to a cell phone, which in turn wirelessly controls an insulin pump, allowing fully automated control of glucose levels. We recognize that cell phones have the potential for becoming an integral part of diagnostic systems. They are ubiquitous, networkable, have powerful data processing capabilities, and importantly, can be geo-located in case of medical emergencies. The cell phone of the future will likely employ a vast array of different connection technologies,1,2 creating enormous flexibility and choices for the customer, as well opening up new prospects for consumer-based diagnostics.
Makarand Paranjape is an associate professor of physics. The majority of his research is conducted at Georgetown Advanced Electronics Laboratory in the clean room facility at Georgetown University, which specializes in health microsystems. Its mission is to improve health care and quality of life through the design, fabrication, and testing of integrated micro-monitoring systems and drug delivery micro-systems using state-of-the-art physical science and bio-engineering technologies.