The cochlea, or inner ear, is a space fully enclosed within the temporal bone of the skull, except for two membrane-covered portals connecting it to the middle ear space. One of these portals is the round window, which is covered by the Round Window Membrane (RWM). A longstanding clinical goal is to gain reliable and precise access to the cochlea with the purpose of delivering therapeutics to treat a plethora of auditory and vestibular disorders, or to aspirate fluids for diagnostic purposes. Standard of care for several difficult-to-treat diseases calls for injection of a therapeutic substance through the tympanic membrane into the middle ear space, after which a portion of the substance diffuses across the RWM into the cochlea. The efficacy of this technique is limited by an inconsistent rate of molecular transport across the RWM. Other solutions for delivery require either traumatic drilling through the bone of the cochlea, or perforating the delicate RWM, which is prone to rupturing with the use of regular surgical tools. For conducting precision diagnostics, even fewer options exist. In our research group, utilizing a newly available technology called Two-Photon Lithography, (2PP) we have developed a suite of ultra-sharp microneedles that are able to create repeatable and reliable perforations in the RWM without tearing. These holes were seen to spontaneously heal within 48 hours, and did not cause any audiological or functional consequences. Furthermore, we have designed needles that can, while inserted into the cochlea, inject or aspirate fluid of microliter quantities, to and from the inner ear, safely. In this thesis, I will discuss the development of these microneedles: their methods, design, use, and modeling. The results show that the microneedles hold great promise to diagnose and treat hearing and balance disorders.

Thesis (Ph. D.)--University of Montana, 2007. / Title from title screen. Description based on contents viewed Apr. 2, 2007. Includes bibliographical references (p. 87-92).

Microneedles have been developed as a minimally invasive alternative to painful hypodermic needles to deliver modern biotherapeutics. Previously, several in-vitro and in-vivo animal studies have been conducted to show that microneedles increase skin permeability to a wide range of molecules that cannot cross the skin using conventional transdermal patches due to the skin's stratum corneum barrier. However, only a limited number of studies have been performed to study microneedle-based drug delivery in human subjects. Therefore, the objective of this study was to perform the first-in-humans microneedle studies to: a) characterize skin repair responses to solid microneedle insertion to determine the extent of increased skin permeability coupled with predictions of pharmacokinetics of drug delivered through premeabilized skin, b) determine the effect of hollow microneedle-based infusion parameters on flow conductivity of skin and pain and thereby identify barriers to fluid flow into the skin from hollow microneedles, c) assess the safety and efficacy of systemic therapeutic effects through measurement of pharmacokinetic parameters, pain and irritation for microneedle-based insulin delivery in type 1 diabetes subjects, and d) assess the safety and efficacy of local therapeutic effects though delivery of lidocaine to the skin. Results showed for the first time that solid microneedle-treated skin reseals rapidly (< 2 h) in the absence of occlusion whereas occluded skin reseals slowly (3-40 h) depending on microneedle geometry as determined by skin impedance measurements. Increased microneedle length, number, and cross-sectional area led to slower recovery kinetics in the presence of occlusion. This thesis also demonstrated that the flow conductivity of skin decreased as fluid was infused to the dermis through hollow microneedles due to the dense structure of the dermis. Microneedle retraction, low flow rates, and the addition of hyaluronidase helped increase flow conductivity. Microneedles were able to deliver 800 µl of saline to the dermis without causing significant pain. Further, microneedle-based insulin delivery in type 1 diabetes subjects revealed that microneedles provided faster pharmacokinetics and improved glycaemic control than conventional subcutaneous catheters. Lastly, microneedle-based lidocaine injection demonstrated that microneedles were less painful, as effective, and more preferred than hypodermic needles in anesthetizing clinically relevant areas.

Thesis (MBA)--Stellenbosch University, 2001. / ENGLISH ABSTRACT: Daily more than 300 000 health care workers in South Africa are to a lesser or greater extent exposed to the risk of deadly viruses which can be transferred through neediestick injuries. It is estimated that currently 9,8 million people in South Africa are HIV positive. This high incidence of HIV has a great impact on the danger of infection from neediestick injuries. It is estimated that 44 000 neediestick injuries takes place annually in South Africa. Despite such a high risk there are currently few safety regulations or official efforts to prevent or determine the true impact and incidence of needlesticks in South Africa. This study project investigated the number of neediestick injuries that could potentially be prevented by the use of needles with safety features and estimated the ranges of benefits and costs of using such safety devices. With the financial constraints that are imposed on South African hospitals, infection control through the use of safety syringes makes economic sense. Prevention of infections is clearly far cheaper than cure. / AFRIKAANSE OPSOMMING: Daagliks word meer as 300 000 gesondheids personeel in Suid Afrika in 'n mindere of meerdere mate blootgestel aan die risiko van lewens gevaarlike viruse wat deur middel van naaldprik ongelukke oorgedra kan word. Hierdie risiko word spesifiek in Suid Afrika verhoog deur die hoë insidensie van HIV. Dit word beraam dat daar tans 9,8 miljoen mense in Suid Afrika is wat HIV positief is. Daar word beraam dat daar tans 44 000 naaldprik ongelukke per jaar in Suid Afrika plaasvind. Ten spyte van die hierdie hoë risko is daar tans min veiligheids regulasies of amptelike pogings om die omvang en voorkoming van naaldprik insidente te bepaal nie. Hierdie studie het die getal naaldprikke wat voorkom kan word deur die gebruik van veiligheids inspuitnaalde ondersoek en het die voordele en kostes van sulke veiligheidsmaatreëls beraam. Gegewe die finasiële druk wat ons tans in Suid Afrikaanse hospitale ondervind, is bewys dat die gebruik van veiligheids inspuitnaalde ekonomiese sin maak. Voorkoming op hierdie manier is bewys as 'n ver goedkoper opsie as nasorg.

Safer injection facilities (SIFs) provide a clean and supervised environment, thereby reducing health risks to drug users. Potential benefits include fewer overdoses, decreased rates of HIV, Hepatitis, and other blood-borne viruses, a reduction in open drug use, increased opportunities for health services and treatments, and cost savings to society. A pilot safer injection site is expected to open in Vancouver's Downtown Eastside in September 2003. This study assesses community attitudes and concerns with respect to SIFs. Focus groups with police officers, street nurses, and injection drug users in February and March 2003 revealed that they are supportive of the sites. Concerns related to the community impacts, external supports, administration, process, safety, and special populations (e.g. women, youth) were indicated. Special attention should be paid to the involvement of injection drug users in planning and programming, the inclusion of peer workers, the relationships between injection drug users, the wider population, and the police, and safety for marginalized populations. Recommendations to address concerns and ensure inclusive processes are provided.

No description available.

Accessing the inner ear presents a significant challenge for the diagnosis and treatment of inner ear diseases. Many existing techniques to access the inner ear are invasive and can cause permanent damage to the cochlea. Recently, a novel microneedle has been fabricated to perforate the round window membrane (RWM) – a membrane sealing one of the two openings in the cochlea. These perforations enhance drug delivery into the inner ear, potentially improving the efficacy of therapeutics. Furthermore, they allow for the aspiration of perilymph samples, which is essential for diagnosing inner ear diseases. However, owing to limited knowledge about the mechanical properties of the RWM, certain technical aspects remain unexplored. Specifically, the interaction between the RWM and the microneedle during perforation is yet to be examined. This investigation is pivotal for the optimal design of microneedles — those robust enough to perforate RWMs yet delicate enough to minimize damage. In this thesis, we conduct a thorough examination of the guinea pig RWM, encompassing its geometry and its mechanical responses to pressures from the middle ear and inner ear. Additionally, we also formulate a comprehensive constitutive law for the guinea pig RWM. Our exploration begins with the creation of a U-Net model tailored to automatically segment the RWM. Despite the presence of other structures in the same image—such as bone, the basilar membrane, and ambient noise—the model proved invaluable for efficiently and automatically segmenting the RWM. To enhance accuracy, post-processing techniques like connected component analysis and majority voting were incorporated. Using this 3D model, we proceeded to study the RWM’s geometry. Recognizing the shrinkage observed in fixed RWMs, we integrated fresh RWM data to estimate the shrinkage ratio. Subsequently, we analyzed both the overall RWM thickness and that of the middle connective tissue layer—crucial metrics for future RWM modeling. Next, we proposed a method to evaluate the in-plane deformation of the RWM due to applied pressure. This involved using a bulge test system to pressurize and deform the RWM, combined with confocal microscopy to track stained nuclei or pre-introduced fluorescent beads on the RWM. We then utilized the coherent point drift (CPD) algorithm to measure the displacement of beads and nuclei. Results indicated that both markers could be successfully used to measure the RWM’s displacement. Further analysis revealed the in-plane Lagrangian strain of the RWM, with a significant observation being that the direction of maximum in-plane Lagrangian strain is perpendicular to the fiber direction. This underscores the crucial role of collagen fibers in determining the RWM’s mechanical properties. To conclude our study, we devised a constitutive law for the RWM, conceptualizing it as a combination of the ground substance and a family of dispersed fibers. This model was integrated into a FEBioStudio plugin, facilitating simulations of the RWM’s mechanical reactions to different pressures. Although our simulations closely aligned with experimental findings, some discrepancies were noted, likely stemming from an incomplete understanding of fiber dispersions. Nevertheless, our constitutive law reinforces the notion that fibers primarily govern the RWM’s mechanical characteristics.