Optical Sensing of Macromolecules and Microparticles Distribution in Tissues K.V. Larin, S. Wang, P. Ruchhoeft, R. Willson, J. D. Morrisett, M.G. Ghosn University of Houston Houston, USA Correspondence: klarin@uh.edu Abstract— This paper describe a highly systematic set of experiments demonstrating capability of Optical Coherence Tomography (OCT) technique for depth-resolved, real-time and truly noninvasive analysis of complex diffusion processes of macromolecules in epithelial and vascular tissues as well to image and detect magnetic microparticles (stationary and moving) under the skin with single-particle sensitivity. For example, we demonstrate that the permeation of VLDL, LDL, HDL, and glucose in normal and diseased human carotid endarterectomy tissues could be quantified that supported previous suggestions of an enhanced transport mechanism specific to LDL. Additionally, we investigated sensitivity of OCT to assess magnetic microbead (d=2.8 um) count under the skin, which could the basis for development of continuous glucose sensing platform. I. INTRODUCTION A broad range of biosensors are used today in clinical applications, ranging from glucose monitoring in diabetic patients, to pathogen detection, and to drug and toxic metabolite detection in tissues. Many applications require performing frequent (or better continuous) measurements. Additionally, availability of a biosensor capable of noninvasive, real-time, and depth-resolved monitoring and quantification of spatial and temporal molecular biodistribution in the ocular or vascular tissues would permit assessment of pharmacokinetic properties of drug delivery systems and would foster development of novel therapeutic agents. In this study, we investigated the use of Optical Coherence Tomography (OCT), a non-invasive and depth-resolved imaging technique, for assessment of complex diffusion processes of macromolecules in epithelial and vascular tissues as well to image and detect magnetic microbeads (stationary and moving) under the skin with single-particle sensitivity. For the latter, we present a reflection-based technology that can potentially be used for absolute blood glucose concentration measurements. This technology employs a biosensor that can be implanted in patients once over a period of several months thereby avoiding daily puncturing or chemical compound injections. For this approach, an array of gold mirrors that are decorated with a chemical compounds, selectively sensitive only to glucose molecules, can be fabricated on a solid substrate. These return incident light with an intensity that is proportional to the glucose concentration directly back to the detector. Figure 1 illustrates the operating principle of such a biosensor: the gold mirror and the glucose- permeable membrane form housing for the sensor, which can be implanted into dermis layer of the skin. The Con A is coated on the gold mirror, and the dextran is coated around the micro-beads. Based on the higher binding affinity of glucose than dextran with Con A, the glucose concentration variation will result in the change of micro-beads number causing reflectivity variation from gold mirror which can be non- invasively assessed using optical methods. Fig 1: Principle of sensor operation that can be implanted in the dermis layer of the skin and reflectivity of the gold mirror is changed as a function of number of microbeads (varied due to glucose conctration) that can be precisely assessed by Optical Coherence Tomography II. MATERIALS AND METHODS A. OCT System Optical Coherence Tomography (OCT) is a non-invasive and depth-resolved imaging technique OCT has high transverse resolution (<10 µm), high SNR (up to 120 dB), high in-depth resolution (~10 µm), and several millimeters of depth penetration in order to image through the stratum corneum and epidermis layers of the skin. In conventional OCT, a two-beam interferometer is used to obtain depth- profiled information on the sample of interest within the coherence length of the laser. A beam from a broadband low- coherence laser source is split into the reference and sample arms of the interferometer. The backscattered light from the sample is recombined with the back-reflected light from the reference arm, resulting in the formation of interference fringes, which are captured by an optical sensor. OCT This study was supported in part by grants from NSF (CMMI-0900743), Welch Foundation (E-1264), and NIAID/NIH (U54 AI057156). 978-1-4577-1767-3/12/$26.00 ©2012 IEEE