Electric fields exist in many forms within the bodies of mammals, such as the electrocardiogram of the heart and the electroencephalogram of the brain. In addition to these more well-known fields, electric fields are also present in the epithelium, which is a tissue composed of layers of cells that line the cavities and surfaces of organs throughout the body, as well as forming part of the skin itself. The epidermis of the skin is composed of stratified squamous epithelial cells and normally generates a voltage across itself called the transepithelial potential. This voltage difference is generated by pumping positive ions from the apical side to the basal side of the epidermis.
FIG. 1A shows a typical epithelial cell with the structures that generate the transepithelial potential. The cell exhibits a polarized distribution of Na+ and K+ channels, where the Na+ channels are concentrated on the apical side of the epithelial cell and K+ channels are on the basal side. Utilizing a Na+/K+-ATPase to lower intracellular [Na+] and raise intracellular [K+] results in a flow of positive ions across the epithelium. The low intracellular [Na+], combined with the negative membrane potential, results in Na+ movement into the cell on the apical side where the channels are localized. Similarly, the high intracellular [K+] results in K+ efflux on the basal side where the K+ channels are localized. This transepithelial ion flux creates a transepithelial potential of between approximately 20-55 mV that is positive on the basal side (inside) of the epithelial layer (FIG. 1B). In the epidermis, current flow is limited by the very high resistance of the stratum corneum and the tight junctions between epidermal cells that form the multilayers composing the epidermis.
When the skin is wounded, such as by a cut, the ionic currents exit the skin at the site of the wound, driven by the voltage generated across the epidermis. As shown in FIG. 1C, after wounding, the transepidermal voltage will immediately drive current out of the low resistance pathway created by the wound, generating a lateral electric field from the flow of wound current on both sides of the epidermis. The field is generated because the positive wound current flows toward the wound on the basal side of the epidermis and flows away from the wound on the apical side. Accordingly, the two sides of the epidermis at the wound site will exhibit opposite polarities: there will be a positive pole at the surface and a negative pole deeper in the epidermal multilayer.
These electric fields are important to wound healing; for example, various studies have shown that the endogenous electrical field near the wound directs epithelial cell migration to improve healing. Manipulation of electric fields near the wound could have direct application in enhancing wound healing, but because there is a lack of reliable information regarding the electric fields associated with normally healing wounds, in humans, no consistent methodology has been established for the use of electric fields in such treatment. To formulate comprehensive treatments, the polarity and magnitude of the endogenous wound current within and directly adjacent to the wound must be determined. In addition, a demonstration that endogenous wound fields are attenuated in chronic wounds would also be necessary. Thus far, the conventional techniques for determining this information have been limited in their usefulness.
Conventional techniques offer two methods for obtaining measurements of the electric fields. First, a direct method involves inserting electrodes into the skin to measure the voltage differences. This method has several disadvantages including risk to the subject from broken or damaged electrodes, difficulty positioning the electrodes, and interference from movement of the subject. In addition, to reduce noise, the measurement setup must be placed in an electromagnetically shielded cage, which severely hampers the portability and ultimate patient utility of the measurement system.
A variation on this direct method uses skin surface electrodes, however this approach is problematic because the electrodes are placed on the highly resistive stratum corneum while the signal that they must detect is beneath that layer at the stratum granulosum. The resistance of the stratum corneum varies from day to day and in different body locations and emotional states, making it difficult to reliably measure the very small potential variations (several millivolts) over the small distances (on the order of 100 μm) involved here.
Second, an indirect method for measuring electric fields in skin utilizes a Kelvin probe, which was originally designed to measure the work function of various metals. A Kelvin probe functions by creating a parallel plate capacitor out of the probe head and the surface being studied. The work function of the surface being studied can be measured quickly by regulating a biasing voltage applied to either the probe or the surface. Although effective for measuring the surface potential of various plant materials, the Kelvin probe has several problems when applied to mammals.
Primarily, the movement of mammals, unlike relatively immobile plants, makes it difficult to obtain accurate measurements using a Kelvin probe. While anesthesia can be used to immobilize a subject, its use poses unacceptable health risks for humans. Even when a subject is not overtly moving, mammalian skin is pliable and subject to constant movement due to respiration and circulation within the body. In addition, signal artifacts are common when measuring mammalian skin from sources such as hair, which has a substantial static charge that influences surface potential readings, and interstitial fluids, which often fill wounds and have a different work function than the surrounding skin that influences the measurement of the electric field.
A particularly good system for overcoming many of the problems with the conventional techniques is presented in the co-pending patent application entitled “Application of the Kelvin Probe Technique to Mammalian Skin and Other Epithelial Structures,” (U.S. patent application Ser. No. 11/031,188), incorporated herein by reference. That application describes a Bioelectric Field Imager (BFI) where a probe detects electric fields in the skin without contacting the region being studied by forming a parallel-plate capacitor between the skin and a sensor tip, then vibrating the sensor tip and taking measurements to determine the electric field. Although the BFI is a very effective system, it is a bench-mounted device and is designed to perform scans in the x-y plane on horizontal, motionless surfaces, which generally requires that subjects be placed under anesthesia. Because of the risks associated with this requirement, the BFI is not suited for general, routine use on human subjects. In addition, because of the physical constraints, the BFI is not ideal for use in medical offices or other outpatient settings.
Accordingly, there is a need for a system that overcomes the problems in the conventional techniques and provides additional features that make measuring the electric field in mammalian skin easier and more convenient. It would be desirable to have a system that measures the electric field non-invasively and without the use of anesthesia to immobilize the subject. It would also be desirable to have a noninvasive system that is hand-held and can be easily manipulated to contact surfaces at a variety of orientations. The hand-held, noninvasive system would preferably adapt to the small continuous motions of mammals and be suitable for monitoring wound healing and for examining skin features such as wrinkles.