The hypothesis here is that the difficulties in recording from small cells can be mitigated by using the research advances obtained with the metallic polymers of pyrrole and thiophene in micro-electrodes. The overall research objective is to technically develop micro-electrodes capable of recording from small cells with biosensors for potential and functional molecules. Intracellular recording from small cells below 10-15 um diameter becomes problematic because rapid diffusional exchange occurs between the soluble cytoplasmic components and the saline within the inserted micro-electrode. Similarly, a membrane injury and cytoplasm leakage site is produced upon micro-electrode entry due to the electrode glass being wettable and not sealing to the membrane lipid. The hypothesis here is that these two technical problems can be solved by: 1) replacing the saline within the micro-electrode with a conducting polymer which thus eliminates the electrode saline to cytoplasm diffusional exchange, and 2) having the micro-electrode shank lipophilic so that a tight electrode to lipid membrane seal is made upon electrode insertion. These technical changes should preserve the integrity of cytoplasm with micro-electrode penetration and recordings could last hours instead of briefly. These technical studies will use different polymers at the micro-electrode tip for the desired biosensor. The initial polymer utilized will have a defined stable interfacial voltage to record membrane potential. Other polymer interfaces will be formed to measure salient ions, and biochemicals involved in cellular metabolism, in particular those of catecholamines and second messenger functioning. The existing limitations on micro-electrode technology has directed much research effort to the large cell diameter population, but the need for techniques to examine small cells is ever present. The whole cell patch clamp has been useful here; however, cytoplasmic washout is a problem, and the literature utilizing micro-electrodes for small cell recording is scarce. The need for this technology is thus pressing and should contribute to new advances in cellular physiology.
