Design and Implementation of an Integrated Biosensor Platform for Lab-on-a-Chip Diabetic Care Systems

Recent advances in semiconductor processing and microfabrication techniques allow the implementation of complex microstructures in a single platform or lab on chip. These devices require fewer samples, allow lightweight implementation, and offer high sensitivities. However, the use of these microstructures place stringent performance constraints on sensor readout architecture. In glucose sensing for diabetic patients, portable handheld devices are common, and have demonstrated significant performance improvement over the last decade. Fluctuations in glucose levels with patient physiological conditions are highly unpredictable and glucose monitors often require complex control algorithms along with dynamic physiological data. Recent research has focused on long term implantation of the sensor system. Glucose sensors combined with sensor readout, insulin bolus control algorithm, and insulin infusion devices can function as an artificial pancreas. However, challenges remain in integrated glucose sensing which include degradation of electrode sensitivity at the microscale, integration of the electrodes with low power low noise readout electronics, and correlation of fluctuations in glucose levels with other physiological data. This work develops 1) a low power and compact glucose monitoring system and 2) a low power single chip solution for real time physiological feedback in an artificial pancreas system. First, glucose sensor sensitivity and robustness is improved using robust vertically aligned carbon nanofiber (VACNF) microelectrodes. Electrode architectures have been optimized, modeled and verified with physiologically relevant glucose levels. Second, novel potentiostat topologies based on a difference-differential common gate input pair transimpedance amplifier and low-power voltage controlled oscillators have been proposed, mathematically modeled and implemented in a 0.18μm [micrometer] complementary metal oxide semiconductor (CMOS) process. Potentiostat circuits are widely used as the readout electronics in enzymatic electrochemical sensors. The integrated potentiostat with VACNF microelectrodes achieves competitive performance at low power and requires reduced chip space. Third, a low power instrumentation solution consisting of a programmable charge amplifier, an analog feature extractor and a control algorithm has been proposed and implemented to enable continuous physiological data extraction of bowel sounds using a single chip. Abdominal sounds can aid correlation of meal events to glucose levels. The developed integrated sensing systems represent a significant advancement in artificial pancreas systems

Improved Forensic Medical Device Security through Eating Detection

Patients are increasingly reliant on implantable medical device systems today. For patients with diabetes, an implantable insulin pump system or artificial pancreas can greatly improve quality of life. As with any device, these devices can and do suffer from software and hardware issues, often reported as a safety event. For a forensic investigator, a safety event is indistinguishable from a potential security event. In this thesis, we show a new sensor system that can be transparently integrated into existing and future electronic diabetes therapy systems while providing additional forensic data to help distinguish between safety and security events. We demonstrate three bowel sound detection methods, the best of which has an 84.26% bowel sound classification accuracy. We provide additional contextual information by using detected bowel sounds to detect when a patient begins to eat. We achieved 100% eating detection accuracy in a laboratory environment. From the eating data, an algorithm or forensic investigator can identify potential malfeasance in a test subject

Intraductal papillary mucinous neoplasm of the pancreas : a study with magnetic resonance imaging

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a cystic tumor that has the potential of malignant transformation. In this thesis, our aims were to investigate the natural course of IPMN disease and possible causes that may associate with IPMN disease or its severity. Additionally, we examined whether a shorter and thus more cost-effective imaging protocol could be used in IPMN surveillance without losing any of its diagnostic value. First, we studied the natural course of side-branch IPMN disease by evaluating patient images and medical records from 521 patients who visited the Helsinki University Hospital pancreatic outpatient clinic between 2014 and 2016. Every patient´s first and last surveillance images were evaluated retrospectively. A total of 377 side-branch IPMN patients were identified and classified into the following groups: presence or absence of worrisome features (WF) or high-risk stigmata (HRS) at the beginning of surveillance, the appearance of WF or HRS during surveillance, elevated or normal level of carbohydrate antigen 19-9 (CA 19-9), and stable or growing cysts that are under 15 mm. At the beginning of surveillance, 50% of patients had an under 15-mm primary cyst, of which 40% did not grow during surveillance. High-grade dysplasias or carcinomas did not exist in patients with normal CA 19-9 levels during surveillance. In conclusion, patients having side-branch IPMN cysts smaller than 15 mm that do not increase in size under surveillance and have no WF or HRS can be surveilled less frequently in the future. Second, we examined whether a shorter magnetic resonance imaging (MRI) protocol—the so-called ultrashort-protocol (USP) MRI—could be used for IPMN surveillance. Retrospectively, 183 IPMN patients that visited the Helsinki University Hospital pancreatic outpatient clinic between April 2015 and December 2016 were collected in this study. A total of 112 patients were included in the study. Two radiologists compared two imaging sets (USP versus long-protocol [S-LP]) per every patient separately, measuring the largest cyst and the main pancreatic duct (MPD) diameters and evaluating the presence or absence of MPD or cystic mural nodules and solid pancreatic tumors. Cyst or MPD nodules detection coincided in 95% and 99% of cases, WF or HRS detection in 92%, and solid pancreatic tumors in 99%. In conclusion, an ultrashort-protocol MRI provides nearly identical information compared to the longer protocols. Last, we studied if anatomical ductal variations have any association with IPMN disease. We retrospectively collected 108 IPMN patients and 106 subjects with healthy pancreas for the control population. Patients with meandering main pancreatic duct (MMPD) were more likely to belong to the IPMN group (odds ratio [OR] 6.4). The N-shape, which is one form of MMPD, associated with cystic mural nodules (OR 5.9), which are one of the worrisome features. The presence of ansa pancreatica associated with more extent cysts in the pancreas (OR 12.8). In conclusion, IPMN patients exhibit more often MMPD than control patients.Haiman intraduktaalinen papillaarinen musinoosi kasvain (IPMN) on kystinen tuumori, jolla on potentiaalia malignisoitua. Tämän malignisoitumisriskin vuoksi potilaat ovat seurannassa, mikä puolestaan aiheuttaa potilaille ja terveydenhuollolle merkittävää taakkaa. Tässä väitöskirjassa tavoitteenamme oli tutkia IPMN-taudin luonnollista kulkua ja mahdollisia syitä taudin syntyyn ja kehitykseen. Lisäksi tutkimme voisiko lyhyempää ja näin ollen kustannustehokkaampaa kuvantamisprotokollaa käyttää IPMN-seurannassa ilman, että diagnostiikan laatu kärsii. Ensimmäisessä osatyössä tutkimme sivutiehyt IPMN-taudin luonnollista kulkua arvioimalla 521 potilasta, jotka olivat vuosien 2014–2016 välillä käyneet Helsingin yliopistollisen sairaalan haimakirurgian poliklinikalla ensimmäistä kertaa. Jokaisen potilaan ensimmäinen ja viimeinen seurantakuvaus arvioitiin jälkikäteen tutkimukseen. Yhteensä 377 sivutiehyt IPMN-potilasta havaittiin ja luokiteltiin seuraaviin ryhmiin: huolestuttavien tai korkean riskin piirteiden olemassaolo seurannan alussa, huolestuttavien tai korkean riskin piirteiden kehittyminen seuranta-aikana, normaali tai kohonnut CA 19-9 antigeenipitoisuus veressä, sekä stabiili tai kasvava alle 15 mm kokoinen kysta. Seurannan alussa 50%:lla potilaista oli alle 15 mm kokoinen kookkain kysta, joista 40%:ia ei kasvanut seurannan aikana. Potilailla, joilla oli normaali CA 19-9 pitoisuus seurannan ajan ei havaittu vahva-asteista dysplasiaa eikä karsinoomia. Tutkimuksemme perusteella niitä sivutiehyt IPMN-potilaita, joilla on alle 15 mm kokoisia kystiä, jotka eivät kasva seurannan aikana eivätkä omaa huolestuttavia eikä korkean riskin piirteitä, voitaisiin seurata jatkossa harvemmin. Toisessa osatyössä tutkimme voisiko lyhyempää magneettikuvantamis (MRI) protokollaa, niin kutsuttua ultralyhytprotokollaa, käyttää IPMN-seurannassa. Retrospektiivisesti otimme tutkimukseen mukaan 183 IPMN-potilasta, jotka kävivät Helsingin yliopistollisen sairaalan haimakirurgian poliklinikalla huhtikuun 2015 ja joulukuun 2016 välillä. Yhteensä 112 potilasta sisällytettiin tutkimukseen. Kaksi radiologia analysoi potilaan kuvat kahteen kertaan: ensin alkuperäisillä kuvasarjoilla ja uudelleen vain tietyillä kahdella kuvasarjalla. Kuvista kerättiin mm. seuraavat tiedot: kookkaimman kystan koko, haimatiehyeen leveys, ja arvioitiin seinämänoduluksen tai haimatuumorin mahdollista esiintymistä. Kystan tai haimatiehyeen sisäisen seinämänoduluksen havaitseminen vastaavuus ultralyhyen ja alkuperäisten kuvien välillä oli 95%:ia ja 99%:ia, huolestuttavien tai korkean riskin piirteiden havaitsemisen 92%:ia, ja haimatuumorin 99%:ia. Tutkimuksemme perusteella ultralyhytprotokolla on verrannollinen pidemmän protokollan kanssa. Kolmannessa osatyössä tutkimme onko anatomisilla haimatiehyeen variaatioilla yhteyttä IPMN-tautiin. Retrospektiivisesti keräsimme 108 IPMN-potilasta sekä näille 106 vertailupotilasta, joilla oli terve haima. Potilaat, joilla oli niin kutsuttu kiemurteleva haiman päätiehyt (MMPD) olivat todennäköisemmin IPMN-potilaita (odds ratio [OR] 6.4). MMPD tiehyeen tietynlainen N-muoto puolestaan oli yhteydessä kystan seinämänodulusten esiintymisen kanssa (OR 5.9), mikä on yksi ns. huolestuttavista piirteistä. Tietynlaisen kiepin tekevän haiman lisätiehyeen, ns. ansa pancreatican, esiintyminen oli yhteydessä laajemmin haimaparenkyymin kattaviin kystiin (OR 12.8). Johtopäätöksenämme on, että IPMN-potilailla on useammin kiemurteleva haiman päätiehyt

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Optoacoustic Imaging in Inflammation.

Optoacoustic or photoacoustic imaging (OAI/PAI) is a technology which enables non-invasive visualization of laser-illuminated tissue by the detection of acoustic signals. The combination of "light in" and "sound out" offers unprecedented scalability with a high penetration depth and resolution. The wide range of biomedical applications makes this technology a versatile tool for preclinical and clinical research. Particularly when imaging inflammation, the technology offers advantages over current clinical methods to diagnose, stage, and monitor physiological and pathophysiological processes. This review discusses the clinical perspective of using OAI in the context of imaging inflammation as well as in current and emerging translational applications

VISUALIZATION OF ULTRASOUND INDUCED CAVITATION BUBBLES USING SYNCHROTRON ANALYZER BASED IMAGING

Ultrasound is recognized as the fastest growing medical modality for imaging and therapy. Being noninvasive, painless, portable, X-ray radiation-free and far less expensive than magnetic resonance imaging, ultrasound is widely used in medicine today. Despite these benefits, undesirable bioeffects of high-frequency sound waves have raised concerns; particularly, because ultrasound imaging has become an integral part of prenatal care today and is increasingly used for therapeutic applications. As such, ultrasound bioeffects must be carefully considered to ensure optimal benefits-to-risk ratio. In this context, few studies have been done to explore the physics (i.e. ‘cavitation’) behind the risk factors. One reason may be associated with the challenges in visualization of ultrasound-induced cavitation bubbles in situ. To address this issue, this research aims to develop a synchrotron-based assessment technique to enable visualization and characterization of ultrasound-induced microbubbles in a physiologically relevant medium under standard ultrasound operating conditions. The first objective is to identify a suitable synchrotron X-ray imaging technique for visualization of ultrasound-induced microbubbles in water. Two synchrotron X-ray phase-sensitive imaging techniques, in-line phase contrast imaging (PCI) and analyzer-based imaging (ABI), were evaluated. Results revealed the superiority of the ABI method compared to PCI for visualization of ultrasound-induced microbubbles. The second main objective is to employ the ABI method to assess the effects of ultrasound acoustic frequency and power on visualization and mapping of ultrasound-induced microbubble patterns in water. The time-averaged probability of ultrasound-induced microbubble occurrence along the ultrasound beam propagation in water was determined using the ABI method. Results showed the utility of synchrotron ABI for visualizing cavitation bubbles formed in water by clinical ultrasound systems working at high frequency and output powers as low as used for therapeutic systems. It was demonstrated that the X-ray ABI method has great potential for mapping ultrasound-induced microbubble patterns in a fluidic environment under different ultrasound operating conditions of clinical therapeutic devices. Taken together, this research represents an advance in detection techniques for visualization and mapping of ultrasound-induced microbubble patterns using the synchrotron X-ray ABI method without usage of contrast agents. Findings from this research will pave the road toward the development of a synchrotron-based detection technique for characterization of ultrasound-induced cavitation microbubbles in soft tissues in the future