A Wearable 1.6GHz Non-Invasive Midfield Wave-Based Blood Glucose Sensor

A non-invasive glucose sensor has been sought after by millions of Americans living with diabetes and scientists alike. Current blood glucose sensors approved by the FDA involve an invasive collection technique coupled with costly chemical analysis materials, which continue to bring pain to the growing diabetic population in America. Previous research of non-invasive sensing methods has shown promise, but the difficulty of transmitting power through tissue has degraded the sensing consistency and accuracy needed to reach the consumer market. This has been overcome with recent research in midfield wave power transmission at Stanford University, which has provided an opportunity for investigating a new, non-invasive glucose sensing technique. The design proposed in this thesis uses a slot array antenna transmitting through the human arm in the UHF (Ultra High Frequency) range at a wavelength absorbed by glucose to investigate the relationship between blood glucose levels and received power from a loop antenna receiver. The complete system incorporates an RF mixer, a Wilkinson power divider, and an RF detector to enable use with Cal Poly’s lab equipment. Changes in blood glucose levels are tracked within an R value of 0.91 when the testing setup maintains consistency in physical placement of the transmitter and receiver. Ten measurements over the course of seven hours accurately sensed changes in the subject’s blood glucose levels with two outlier data points. The system provides a vehicle for further investigation into a new, non-invasive blood glucose sensing method to improve the quality of life for millions around the world

Shining a light on clinical spectroscopy : translation of diagnostic IR, 2D-IR and Raman spectroscopy towards the clinic

In recent years, the application of vibrational spectroscopy in biomedical research has rapidly expanded; covering aspects of pharmaceutical development, to point-of-care technologies. Vibrational spectroscopy techniques such as Fourier-transform IR (FTIR), and Raman spectroscopy have been at the forefront of this movement, with their complementary information able to shine light onto a range of medical applications. As a relative newcomer to biomedical applications, two-dimensional (2D)-IR is also gaining traction in the field. Here we describe the recent development of these techniques as analytical tools in medical science, and their relative advancements towards the clinic

A dark field illumination probe linked to Raman spectroscopy for non-invasivety determination of ocular biomarkers

For early and effective diagnosis of eye diseases, acquiring biochemical information in the eye is preferred. However, it is obtained by performing a biopsy of the eye tissue. This poses a risk to the integrity of the eye and cannot be performed on a regular basis. Raman spectrometry is a potential and powerful tool for the non-invasive investigation of biochemical information. The challenge to use it in an ophthalmic application is the essential of a high-power laser direct shining through the eye, which raises safety concerns for potential retinal damage .In this thesis, biomedical applications of Raman spectroscopy are explored for eye disease biomarkers and ocular drug measurements in ex vitro, in vitro and in vivo. To ensure a safety measurement by projecting a laser in the eye, two types of dark-field illumination probes are designed, manufactured and validated in conjunction with confocal Raman spectroscopy (CRS) to avoid light damage of the retina. Furthermore, a non-contact dark-field illumination method for the same purpose is proposed and theoretically validated

Dielectrophoretic characterization of particles and erythrocytes

Medical lab work, such as blood testing, will one day be near instantaneous and inexpensive via capabilities enabled by the fast growing world of microtechnology. In this research study, sorting and separation of different ABO blood types have been investigated by applying alternating and direct electric fields using class=SpellE\u3edielectrophoresis in microdevices. Poly(dimethylsiloxane) (PDMS) microdevices, fabricated by standard photolithography techniques have been used. Embedded perpendicular platinum (Pt) electrodes to generate forces in AC dielectrophoresis were used to successfully distinguish positive ABO blood types, with O+ distinguishable from other blood types at \u3e95% confidence. This is an important foundation for exploring DC dielectrophoretic sorting of blood types. The expansion of red blood cell sorting employing direct current insulative class=SpellE\u3edielectrophoresis (DC-iDEP) is novel. Here Pt electrodes were remotely situated in the inlet and outlet ports of the microdevice and an insulating obstacle generates the required dielectrophoretic force. The presence of ABO antigens on the red blood cell were found to affect the class=SpellE\u3edielectrophoretic deflection around the insulating obstacle thus sorting cells by type. To optimize the placement of insulating obstacle in the microchannel, COMSOL Multiphysics® simulations were performed. Microdevice dimensions were optimized by evaluating the behaviors of fluorescent polystyrene particles of three different sizes roughly corresponding to the three main components of blood: platelets (2-4 µm), erythrocytes (6-8 µm) and leukocytes (10-15 µm). This work provided the operating conditions for successfully performing size dependent blood cell insulator based DC dielectrophoresis in PDMS microdevices. In subsequent studies, the optimized microdevice geometry was then used for continuous separation of erythrocytes. The class=SpellE\u3emicrodevice design enabled erythrocyte collection into specific channels based on the cell’s deflection from the high field density region of the obstacle. The channel with the highest concentration of cells is indicative of the ABO blood type of the sample. DC resistance measurement system for quantification of erythrocytes was developed with single PDMS class=SpellE\u3emicrochannel system to be integrated with the DC- class=SpellE\u3eiDEP device developed in this research. This lab-on-a-chip technology application could be applied to emergency situations and naturalcalamities for accurate, fast, and portable blood typing with minimal error

The design of polymeric microneedles for the delivery of sensors for real-time physiological monitoring

Ce mémoire de maîtrise porte sur le développement d’un système d’administration de microaiguilles pour livrer des sondes et des capteurs fluorescents dans le contexte du diagnostic et de la surveillance des soins de santé. Bien que parfois négligés en faveur des soins de santé axés sur le traitement, le diagnostic précoce de la maladie et la surveillance préventive des paramètres biologiques peuvent considérablement améliorer les résultats des soins de santé et joueront probablement un rôle plus important dans les années à venir. Cependant, il reste des obstacles importants à cette approche, à savoir le caractère relativement invasif et perturbateur des analyses biologiques. La nécessité de se rendre dans une clinique et de subir un prélèvement de sang (ou de liquide biologique) invasif présente des inconvénients importants par rapport aux traitements classiques, qui consistent souvent de médicaments pouvant être pris à domicile sans douleur. Une solution à ces problèmes réside dans la mise au point de systèmes minimalement invasifs de diagnostic et de suivi médical, idéalement ceux qui peuvent être utilisés à domicile sans nécessiter de personnel qualifié. À cet égard, les microaiguilles sont une technologie au potentiel énorme, car leur petite taille les rend peu invasives et pratiquement indolores, et leur nature simple à usage unique permet potentiellement une administration à domicile par le patient. Particulièrement prometteuses pour les applications de diagnostic et de surveillance sont les microaiguilles en polymère soluble; fabriquées à partir de polymères synthétiques ou biologiques injectables, ces microaiguilles sont solubilisées après la perforation de la peau, libérant ainsi les composés qu’elles contiennent. Bien que prévu initialement pour la livraison d'agents thérapeutiques, en utilisant ces microaiguilles pour livrer des molécules fluorescentes spécifiquement conçues, il est possible de créer un tatouage médical de diagnostic affichant un signal fluorescent précis. En associant cette technologie à un détecteur de fluorescence portable, la surveillance en temps réel d’un large éventail de paramètres biologiques pourrait devenir accessible en dehors du contexte clinique. Afin de fournir un contexte pour le développement de cette technologie, cette mémoire commence par une revue des principes et des avancées majeures récentes dans le domaine des applications diagnostiques des microaiguilles (Chapitre 1). Par la suite, un tatouage par microaiguille est présenté sous la forme d'un capteur de ROS délivré sur la peau, avec des implications diagnostiques pour le vieillissement et la carcinogenèse de la peau liés aux UV, ainsi que pour des affections inflammatoires telles que le psoriasis, comme validation de concept (Chapitre 2). En outre, un autre tatouage par microaiguille est introduit, consistant d’un capteur spécialement adapté ciblant le système lymphatique, permettant la quantification en temps réel du drainage lymphatique, avec des implications pour la détection précoce de plusieurs affections, notamment le lymphœdème (Chapitre 3).This Master’s thesis concerns the development of a microneedle (MN) delivery system for fluorescent dyes and sensors in the context of diagnostics and healthcare monitoring. While sometimes overlooked in favor of treatment-focused healthcare, early disease diagnosis and preventative monitoring of biological parameters can meaningfully improve healthcare outcomes and will likely play a greater role in coming years. However, significant obstacles to this approach remain, namely the relatively invasive and disruptive nature of biological analyses. The need to travel to a clinic and undergo invasive blood (or biological fluid) sampling presents significant inconveniences relative to common treatments, often consisting of medications that can be taken painlessly at home. A solution to these problems lies in the development of minimally invasive systems for diagnostics and healthcare monitoring, ideally ones which can be used at home without the need for trained personnel. In this regard, MNs are a technology with tremendous potential, as their small size renders them minimally invasive and virtually painless, and their simple, single-use nature potentially allows for at-home administration by the patient. Showing particular promise for diagnostic and monitoring applications are dissolving polymeric MNs; made from injectable synthetic or biological polymers, these MNs are solubilized after breaching the skin, releasing any compound contained within. Though initially envisioned for the delivery of therapeutic agents, by using these MNs to deliver specifically designed fluorescent molecules, it is possible to create a diagnostic medical tattoo displaying a precise fluorescent signal. By pairing this technology with a portable fluorescence detector, real-time monitoring of a wide range of biological parameters could become accessible outside of a clinical setting. To provide context for the development of this technology, this thesis begins with a review of the principles and major recent advances in the field of diagnostic applications of MNs (Chapter 1). Subsequently, a proof-of-concept MN tattoo is introduced in the form of a ROS-sensor delivered to the skin, with diagnostic implications for UV-related skin aging and carcinogenesis, as well as inflammatory conditions such as psoriasis (Chapter 2). Further, another MN tattoo is introduced, consisting of a specifically tailored sensor targeting the lymphatic system, allowing the real-time quantification of lymphatic drainage, with implications in the early detection of several conditions, including lymphedema (Chapter 3)