Brent D. Cameron

Low-sidelobe limited diffraction optical coherence tomography

Optical Coherence Tomography (OCT) is a relatively new type of imaging system for medical diagnosis. Because most current OCT systems use a sharply focused beam in tissues, they have a short depth of field (high image resolution is near the focus only). In this paper, limited diffraction beams of different orders are used to increase depth of field and to reduce sidelobes in OCT. Results show that the proposed OCT system has a lateral resolution of about 4.4 wavelengths (the central wavelength of the source is about 940 nm with a bandwidth of about 70 nm) and lower than -60 dB sidelobes over an entire depth of field of 4.5 mm with the diameter of the objective lens of 1 mm.

Development of a noninvasive corneal birefringence-compensated glucose-sensing polarimeter

In the recent past, optical polarimetry has been shown as a potential method for noninvasive physiologic glucose sensing in the eye. Although the necessary sensitivity and accuracy have been demonstrated experimentally through in vitro studies using a range of media from simplistic glucose doped-water to more complex media such as aqueous humor, the main problem currently hindering long-term in vivo measurements is corneal birefringence coupled with motion artifact. This is due to the inability to distinguish E-field rotation due to glucose from the effects of time varying corneal birefringence. In this investigation, the effect of corneal birefringence will be discussed and a potential method to overcome this problem will be presented with supporting results.

Polarimetric glucose sensing in aqueous humor utilizing digital closed-loop control

The development of a non-invasive glucose sensor would be beneficial to patients inflicted with diabetes mellitus. In this study, polarimetric glucose sensing using both water and the aqueous humor of the eye doped with glucose are investigated. The polarimeter developed for this research differs from previously investigated systems in that it utilizes a digital closed-loop control system. In vitro results were obtained for both water and bovine aqueous humor mediums using a hyperglycemic concentration range of 100-600 mg/dl in 50 mg/dl increments. Both water and aqueous humor data sets exhibit a high degree of linearity with correlation coefficients of 0.9997 and 0.9925, respectively. The computed linear regression models yielded standard prediction errors of 4.207 mg/dl and 20.24 mg/dl, respectively. Future research will focus on coupling light in and out of the eye as well as problems encountered due to the birefringence of the cornea.

Development and calibration of an automated Mueller matrix polarization system for skin lesion differentiation

In this paper, we describe the use of the full sixteen element Mueller matrix to differentiate between surface lesions on the skin, as an eventual noninvasive diagnostic technique for detection of certain types of skin cancers. A semi-automated system using a polarized light beam and a computer controlled CCD camera was developed to collect 16 polarization images of a sample and to calculate the complete Mueller matrix in near real time. The system was initially calibrated and the accuracy and precision were evaluated with a mirror and polarizer. This study also includes in vivo results from normal skin, a benign nevus, and a known cancerous lesion acquired from a single Sinclair swine. Differences were observed between the Mueller matrices of all three in vivo cases. These preliminary results demonstrate the potential for using an automated polarization imaging apparatus for eventual clinical cancer diagnostics.

Multivariate image processing technique for noninvasive glucose sensing

A potential noninvasive glucose sensing technique was investigated for application towards in vivo glucose monitoring for individuals afflicted with diabetes mellitus. Three dimensional ray tracing simulations using a realistic iris pattern integrated into an advanced human eye model are reported for physiological glucose concentrations ranging between 0 to 500 mg/dL. The anterior chamber of the human eye contains a clear fluid known as the aqueous humor. The optical refractive index of the aqueous humor varies on the order of 1.5x10-4 for a change in glucose concentration of 100 mg/dL. The simulation data was analyzed with a developed multivariate chemometrics procedure that utilizes iris-based images to form a calibration model. Results from these simulations show considerable potential for use of the developed method in the prediction of glucose. For further demonstration, an in vitro eye model was developed to validate the computer based modeling technique. In these experiments, a realistic iris pattern was placed in an analog eye model in which the glucose concentration within the fluid representing the aqueous humor was varied. A series of high resolution digital images were acquired using an optical imaging system. These images were then used to form an in vitro calibration model utilizing the same multivariate chemometric technique demonstrated in the 3-D optical simulations. In general, the developed method exhibits considerable applicability towards its use as an in vivo platform for the noninvasive monitoring of physiological glucose concentration.

Basic Science Symposium II: MEMS Technology.

Introduction For a long time surgeons and basic scientists have been working together in developing instrumentation to restore function across a diseased human joint. In the quest to achieve their objectives during this long journey, they have developed analytical and experimental methods to quantify various parameters across a normal and a diseased joint, like the hip joint. For example, back in the late 80s and early 90s, 1-3 using crude (from todays perspective) sensor technology, a number of researchers quantified the forces across the hip after total hip arthroplasty. The findings helped the joint replacement industry in several ways including validating the analytical models, contributing to the design of implants that will last longer (hopefully for the life span of the patient), and establishing guidelines for exercise in the immediate postoperative time period. All these results have led to hip arthroplasty improvements to the point that it has become the gold standard for all other joint replacement systems. It is not a surprise that spine surgeons and engineers, with the exponential growth of the bioMEMS technology in the last 5 years, are looking into ways this technology can be used in the area of spine. Dr. Lisa Ferrara, co-organizer of this symposium, has posed questions ranging from the basic definition of bioMEMS to future/potential applications of the technology in the area of spine. The eminent panel members have provided thought-provoking responses reflecting their experiences in the area. We are fortunate that they agreed to take part in this initiative, and we thank them for their participation. I hope you will enjoy this symposium. We look forward to your comments and submission of your full length manuscripts for the coming issues of the journal.

Polarimetric detection of glucose in biologically based fluids

The use of polarimetry in the investigation of chiral molecules has been researched for over a century. However, it has not been until recently that the sensitivity and accuracy of this technology has improved enough to be applied to the quantification of the low optically metabolite concentrations seen within the body. The long term goal of this research is the development of a polarimetric detection system with presence of other confounders. In this study, a robust polarimeter utilizing digital closed-loop control was designed and constructed that can effectively measure millidegree rotations of plane- polarized light within biological media. In vitro experiments were conducted using a 1 cm path length sample cell in both glucose doped cell culture and bovine aqueous humor media with analyte concentrations on the order of those seen in the body. A high degree of linearity between the measured signal and glucose concentration is seen during calibration of both the cell culture and aqueous humor experiments with correlation coefficients of 0.9995 and 0.9912, respectively. In addition, validation of the obtained calibration models yielded standard errors of prediction of 8.469 and 20.25 mg/dl for each media, respectively. Overall, we feel the conducted experiments are a logical step to furthering the development of using polarimetry in the detection of optically active metabolites, and our results indicate that accurate detection of glucose in the presence of additional confounders can be accomplished in both cell culture and aqueous humor media.

Aptamer-based surface plasmon resonance sensing of glycated human blood proteins

The concentration ratio of glycated to non-glycated forms of various blood proteins can be used as a diagnostic measure in diabetes to determine a history of glycemic compliance. Depending on a protein’s half-life in blood, compliance can be assessed from a few days to several months in the past, which can then be used to provide additional therapeutic guidance. Current glycated protein detection methods are limited in their ability to measure multiple proteins, and are susceptible to interference from other blood pathologies. In this study, we developed and characterized DNA aptamers for use in Surface Plasmon Resonance (SPR) sensors to assess the blood protein hemoglobin. The aptamers were developed by way of a modified Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process which selects DNA sequences that have a high binding affinity to a specific protein. DNA products resulting from this process are sequenced and identified aptamers are then synthesized. The SELEX process was performed to produce aptamers for a glycated form of hemoglobin. Equilibrium dissociation constants for the binding of the identified aptamer to glycated hemoglobin, hemoglobin, and fibrinogen were calculated from fitted Langmuir isotherms obtained through SPR. These constants were determined to be 94 nM, 147 nM, and 244 nM respectively. This aptamer can potentially be used to create a SPR aptamer based biosensor for detection of glycated hemoglobin, a technology that has the potential to deliver low-cost and immediate glycemic compliance assessment in either a clinical or home setting.

Development and optimization of an integrated Faraday modulator and compensator design for optical polarimetry

In the past, Faraday based optical polarimetry approaches have shown considerable potential for the measurement of optical activity with application towards the noninvasive measurement of physiological glucose concentration. To date, most reported closed-loop systems incorporate separate Faraday components for modulation and compensation requiring two optical crystals. These systems have demonstrated significant stability and sub-millidegree rotational sensitivities; however, the main drawbacks to this approach are the optical materials (e.g., terbium gallium garnet) can be quite expensive and often custom fabricated induction coils are required. In this investigation, we propose a new design for the Faraday components capable of achieving both modulation and compensation in a single crystal device. The design is more compact and is capable of achieving similar performance with low cost commercially available inductive components. To facilitate prototype optimization, our group has developed a finite element model (FEM) that can simulate various physical parameters such as geometry, inductance, and orientation with respect to the optical rod in order to minimize power consumption and size while maintaining appropriate field strength. Performance is comparable to existing nonintegrated approaches and is capable of achieving modulation depths < 1° under similar operating conditions while attaining sub-millidegree linear polarization sensitivity. There is also excellent correlation between the FEM and experimental prototype with operational performance shown to be within 1.8%. The use of FEM simulations allows for the analysis of a vast range of parameters before prototypes are fabricated and can facilitate custom designs as related to development time, anticipated performance, and cost reduction.

The development of an integrated Faraday modulator and compensator for continuous polarimetric glucose monitoring

In recent years, significant advances have been made in the development of noninvasive polarimetric glucose detection systems, salutary for the treatment of our rapidly increasing diabetic population. This area of research utilizes the aqueous humor as the detection medium for its strong correlation to blood glucose concentration and highlights three major features: the optical activity of glucose, minimal scattering of the medium, and the ability to detect sub-millidegree rotation in polarized light. However, many of the current polarimetric systems are faced with size constraints based on the paramount optical components. As a step toward developing a low cost hand-held design, our group has designed a miniaturized integrated single-crystal Faraday modulator/compensator. This device is capable of replacing the traditional two component arrangement that has been widely reported on in many Faraday-based polarimetric configurations. In this study, the newly designed prototype is compared with a theoretical model and its performance is evaluated experimentally under both noninvasive static and dynamic glucose monitoring conditions. The combined rotator can achieve modulation depths above 1°, and when operating in a compensated closed-loop configuration, it has demonstrated glucose prediction errors of 1.8 mg/dL and 5.4 mg/dL under hypoglycemic and hyperglycemic conditions, respectively. These results demonstrate that such an integrated design can perform similar if not better than its larger two-part predecessors. This technology could also be extended to facilitate the use of multispectral polarimetry by considerably reducing the required number of physical components. Such multispectral techniques have demonstrated usefulness for in vivo and multi-analyte noninvasive sensing.