Label-free measurement of microbicidal gel thickness using low-coherence interferometry

Abstract

Abstract. Spectral-domain low-coherence interferometry ͑LCI͒ was used to measure the thickness of microbicidal gels applied to a cylindrical calibration test socket. Microbicides are topical formulations containing active ingredients targeted to inhibit specific pathogens that are currently under development for application to the epithelial lining of the lower female reproductive tract to combat sexually transmitted infections such as HIV. Understanding the deployment and drug delivery of these formulations is vital to maximizing their effectiveness. Previously, in vivo measurements of microbicidal formulation thickness were assessed using fluorescence measurements of fluorescein-labeled gels via an optical endoscope-based device. Here we present an LCI-based device that measures the thickness of a formulation without the use of any exogenous agents by analyzing the interference pattern generated between the reflections from the front and back surface of the sample. Results are presented that validate the effectiveness and performance of the LCI measurement in a clinically relevant system as compared to an existing fluorescence-based method. The impact of the new LCIbased design on in vivo measurements is discussed.

Development of an integrated endoscopic device for multiplexed low coherence interferometry measurements of microbicide gel coating thickness

“…The LCI measurements correlated very well with the digital indicator, as a correlation coefficient was determined to be R = 0.9877, and the slope of the line-of-best fit was 0.9177. These values were once again comparable to those found with the initial multiplexed system, as well as those by Braun et al [8,10].…”

“…Previous studies by Braun et al verified the ability of LCI to measure microbicide gel thicknesses in a test socket with a basic common-path LCI system [8]. The commonpath system demonstrated results with accuracy and linearity comparable to the clinical fluorescence system.…”

“…The results of these preliminary studies indicated that LCI had comparable precision and accuracy to a clinical fluorescence system in measuring gel distributions [8,9]. A multiplexed Fourier-domain LCI system was then built in order to achieve broad area scanning without the use of typical mechanical scanner.…”

Clinical evaluation of microbicide formulations

“…The first generation of luminally active drugs were uncommonly evaluated for luminal PK, but methods to assess PK in the vaginal and rectal compartments were not well developed when those drugs were moving into clinical development. Subsequently, considerable PK method development has been undertaken to provide these tools, primarily by several active groups (Barnhart et al, 2009; Barnhart et al, 2006; Braun et al, 2006; Dumond et al, 2009; Henderson et al, 2007; Hendrix et al, 2009; Hendrix et al, 2008; Mauck et al, 2008; Talameh et al, 2010). These groups have pioneered novel methods for direct luminal and tissue sampling or indirect imaging methods using MR and gamma imaging agents.…”

Design and validation of a multiplexed low coherence interferometry instrument for in vivo clinical measurement of microbicide gel thickness distribution

“…There is concern, however, that the label may separate from the gel over time, thereby confounding the interpretation of the scans of local fluorescence intensity. Consequently, we have developed a multiplexed, Fourier-domain low coherence interferometry system for label free measurement of gel distribution [6,7]. This system was successfully validated in phantom studies [3,4,6,7].…”