Guidance to Transfer ‘Bench-Ready’ Medical Technology into Usual Clinical Practice: Case Study – Sensors and Spectrometer Used in EPR Oximetry

Summary As with new drugs, the U.S. Food and Drug Administration’s approval process is intended to provide consumers with assurance that, once it reaches the market place, a medical device is safe and effective in its intended use. Bringing a device to market takes an average of 3 to 7 years, compared with an average of 12 years for drugs. However, there are concerns that Food and Drug Administration processes may not be sufficient to meet the assurances of safety and efficacy as intended. This second part of a 2-part series reviews the basic steps in development and Food and Drug Administration approval of medical devices, and summarizes post-marketing processes for drugs and devices.

The automatic frequency control (AFC) circuit in conventional electron paramagnetic resonance (EPR) spectrometers automatically tunes the microwave source to the resonance frequency of the resonator. The circuit works satisfactorily for samples stable enough that the geometric relations in the resonance structure do not change in a significant way. When EPR signals are measured during in vivo experiments with small rodents, however, the distance between the signal source and the surface-coil detector can change rapidly. When a conventional AFC circuit keeps the oscillator tuned to the resonator under those conditions, the resultant frequency change may exceed +/-5 MHz and markedly shift the position of the EPR signal. Such a shift results in unacceptable effects on the spectra, especially when the experimenter is dealing with narrow EPR lines. The animal movement also causes a mismatching of the resonator and the 50-ohm transmission line. Direct results of this mismatching are increased noise; shifts in the position of the baseline; and a high probability of overdriving the signal preamplifier with consequent loss of the EPR signal. We therefore designed, built, and tested a new surface-coil resonator using varactor diodes for tuning the resonance frequency to the fixed frequency oscillator and for capacitive matching of the resonator to the 50-ohm transmission line. The performance of the automatic matching system was tested in vivo by measuring EPR spectra of lithium phthalocyanine implanted in rats. Stability and sensitivity of the spectrometer were evaluated by measuring EPR spectra with and without the use of the automatic matching system. The overall experimental performance of the spectrometer was found to significantly improve during in vivo experiments using the automatic matching system. Excellent matching between the 50-ohm transmission line and the resonator was maintained under all experimental circumstances that were tested. This should allow us now to carry out experiments that previously were not possible.