Design, fabrication and characterisation of components for microfluidic enzymatic biofuel cells

The concept of a biofuel cell takes inspiration from the natural capability of biological systems to catalyse the conversion of organic matter with a subsequent release of electrical energy. Enzymatic biofuel cells are intended to mimic the processes occurring in nature in a more controlled and efficient manner. Traditional fuel cells rely on the use of toxic catalysts and are often not easily miniaturizable making them unsuitable as implantable power sources. Biofuel cells however use highly selective protein catalysts and renewable fuels. As energy consumption becomes a global issue, they emerge as important tools for energy generation. The microfluidic platforms developed are intended to maximize the amount of electrical energy extracted from renewable fuels which are naturally abundant in the environment and in biological fluids. Combining microfabrication processes, chemical modification and biological surface patterning these devices are promising candidates for micro-power sources for future life science and electronic applications. This thesis considered four main aspects of a biofuel cell research. Firstly, concept of a miniature compartmentalized enzymatic biofuel cell utilizing simple fuels and operating in static conditions is verified and proves the feasibility of enzyme catalysis in energy conversion processes. Secondly, electrode and microfluidic channel study was performed through theoretical investigations of the flow and catalytic reactions which also improved understanding of the enzyme kinetics in the cell. Next, microfluidic devices were fabricated from cost-effective and disposable polymer materials, using the state-of-the-art micro-processing technologies. Integration of the individual components is difficult and multiple techniques to overcome these problems have been investigated. Electrochemical characterization of gold electrodes modified with Nanoporous Gold Structures is also performed. Finally, two strategies for enzyme patterning and encapsulation are discussed. Several protein catalysts have been effectively immobilized on the surface of commercial and microfabricated electrodes by electrochemically assisted deposition in sol-gel and poly-(o-phenylenediamine) polymer matrices and characterised with confirmed catalytic activity.

At what price? A cost-effectiveness analysis comparing trial of labour after previous caesarean versus elective repeat caesarean delivery

Background: Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland.Methods: Using a decision analytic model, a cost-effectiveness analysis (CEA) was performed where the measure of health gain was quality-adjusted life years (QALYs) over a six-week time horizon. A review of international literature was conducted to derive representative estimates of adverse maternal health outcomes following a trial of labour after caesarean (TOLAC) and ERCD. Delivery/procedure costs derived from primary data collection and combined both "bottom-up" and "top-down" costing estimations.Results: Maternal morbidities emerged in twice as many cases in the TOLAC group than the ERCD group. However, a TOLAC was found to be the most-effective method of delivery because it was substantially less expensive than ERCD ((sic)1,835.06 versus (sic)4,039.87 per women, respectively), and QALYs were modestly higher (0.84 versus 0.70). Our findings were supported by probabilistic sensitivity analysis.Conclusions: Clinicians need to be well informed of the benefits and risks of TOLAC among low risk women. Ideally, clinician-patient discourse would address differences in length of hospital stay and postpartum recovery time. While it is premature advocate a policy of TOLAC across maternity units, the results of the study prompt further analysis and repeat iterations, encouraging future studies to synthesis previous research and new and relevant evidence under a single comprehensive decision model.

Development of a triple stage heat transformer for the recycling of low temperature heat energy

Absorption heat transformers are thermodynamic systems which are capable of recycling industrial waste heat energy by increasing its temperature. Triple stage heat transformers (TAHTs) can increase the temperature of this waste heat by up to approximately 145˚C. The principle factors influencing the thermodynamic performance of a TAHT and general points of operating optima were identified using a multivariate statistical analysis, prior to using heat exchange network modelling techniques to dissect the design of the TAHT and systematically reassemble it in order to minimise internal exergy destruction within the unit. This enabled first and second law efficiency improvements of up to 18.8% and 31.5% respectively to be achieved compared to conventional TAHT designs. The economic feasibility of such a thermodynamically optimised cycle was investigated by applying it to an oil refinery in Ireland, demonstrating that in general the capital cost of a TAHT makes it difficult to achieve acceptable rates of return. Decreasing the TAHT's capital cost may be achieved by redesigning its individual pieces of equipment and reducing their size. The potential benefits of using a bubble column absorber were therefore investigated in this thesis. An experimental bubble column was constructed and used to track the collapse of steam bubbles being absorbed into a hotter lithium bromide salt solution. Extremely high mass transfer coefficients of approximately 0.0012m/s were observed, showing significant improvements over previously investigated absorbers. Two separate models were developed, namely a combined heat and mass transfer model describing the rate of collapse of the bubbles, and a stochastic model describing the hydrodynamic motion of the collapsing vapour bubbles taking into consideration random fluctuations observed in the experimental data. Both models showed good agreement with the collected data, and demonstrated that the difference between the solution's temperature and its boiling temperature is the primary factor influencing the absorber's performance.

Development of low-cost sensing and separation devices based on macro, micro and nano technology for health applications

The work presented in this thesis described the development of low-cost sensing and separation devices with electrochemical detections for health applications. This research employs macro, micro and nano technology. The first sensing device developed was a tonerbased micro-device. The initial development of microfluidic devices was based on glass or quartz devices that are often expensive to fabricate; however, the introduction of new types of materials, such as plastics, offered a new way for fast prototyping and the development of disposable devices. One such microfluidic device is based on the lamination of laser-printed polyester films using a computer, printer and laminator. The resulting toner-based microchips demonstrated a potential viability for chemical assays, coupled with several detection methods, particularly Chip-Electrophoresis-Chemiluminescence (CE-CL) detection which has never been reported in the literature. Following on from the toner-based microchip, a three-electrode micro-configuration was developed on acetate substrate. This is the first time that a micro-electrode configuration made from gold; silver and platinum have been fabricated onto acetate by means of patterning and deposition techniques using the central fabrication facilities in Tyndall National Institute. These electrodes have been designed to facilitate the integration of a 3- electrode configuration as part of the fabrication process. Since the electrodes are on acetate the dicing step can automatically be eliminated. The stability of these sensors has been investigated using electrochemical techniques with excellent outcomes. Following on from the generalised testing of the electrodes these sensors were then coupled with capillary electrophoresis. The final sensing devices were on a macro scale and involved the modifications of screenprinted electrodes. Screen-printed electrodes (SPE) are generally seen to be far less sensitive than the more expensive electrodes including the gold, boron-doped diamond and glassy carbon electrodes. To enhance the sensitivity of these electrodes they were treated with metal nano-particles, gold and palladium. Following on from this, another modification was introduced. The carbonaceous material carbon monolith was drop-cast onto the SPE and then the metal nano-particles were electrodeposited onto the monolith material

Electromagnetic tracking and steering for catheter navigation

This thesis explores the use of electromagnetics for both steering and tracking of medical instruments in minimally invasive surgeries. The end application is virtual navigation of the lung for biopsy of early stage cancer nodules. Navigation to the peripheral regions of the lung is difficult due to physical dimensions of the bronchi and current methods have low successes rates for accurate diagnosis. Firstly, the potential use of DC magnetic fields for the actuation of catheter devices with permanently magnetised distal attachments is investigated. Catheter models formed from various materials and magnetic tip formations are used to examine the usefulness of relatively low power and compact electromagnets. The force and torque that can be exerted on a small permanent magnet is shown to be extremely limited. Hence, after this initial investigation we turn our attention to electromagnetic tracking, in the development of a novel, low-cost implementation of a GPS-like system for navigating within a patient. A planar magnetic transmitter, formed on a printed circuit board for a low-profile and low cost manufacture, is used to generate a low frequency magnetic field distribution which is detected by a small induction coil sensor. The field transmitter is controlled by a novel closed-loop system that ensures a highly stable magnetic field with reduced interference from one transmitter coil to another. Efficient demodulation schemes are presented which utilise synchronous detection of each magnetic field component experienced by the sensor. The overall tracking accuracy of the system is shown to be less than 2 mm with an orientation error less than 1°. A novel demodulation implementation using a unique undersampling approach allows the use of reduced sample rates to sample the signals of interest without loss of tracking accuracy. This is advantageous for embedded microcontroller implementations of EM tracking systems. The EM tracking system is demonstrated in the pre-clinical environment of a breathing lung phantom. The airways of the phantom are successfully navigated using the system in combination with a 3D computer model rendered from CT data. Registration is achieved using both a landmark rigid registration method and a hybrid fiducial-free approach. The design of a planar magnetic shield structure for blocking the effects of metallic distortion from below the transmitter is presented which successfully blocks the impact of large ferromagnetic objects such as operating tables. A variety of shielding material are analysed with MuMetal and ferrite both providing excellent shieling performance and an increased signal to noise ratio. Finally, the effect of conductive materials and human tissue on magnetic field measurements is presented. Error due to induced eddy currents and capacitive coupling is shown to severely affect EM tracking accuracy at higher frequencies.

Valuing maternity care: a comparison of stated preference methods with an application to cost-benefit analysis

This research investigates whether a reconfiguration of maternity services, which collocates consultant- and midwifery-led care, reflects demand and value for money in Ireland. Qualitative and quantitative research is undertaken to investigate demand and an economic evaluation is performed to evaluate the costs and benefits of the different models of care. Qualitative research is undertaken to identify women’s motivations when choosing place of delivery. These data are further used to inform two stated preference techniques: a discrete choice experiment (DCE) and contingent valuation method (CVM). These are employed to identify women’s strengths of preferences for different features of care (DCE) and estimate women’s willingness to pay for maternity care (CVM), which is used to inform a cost-benefit analysis (CBA) on consultant- and midwifery-led care. The qualitative research suggests women do not have a clear preference for consultant or midwifery-led care, but rather a hybrid model of care which closely resembles the Domiciliary Care In and Out of Hospital (DOMINO) scheme. Women’s primary concern during care is safety, meaning women would only utilise midwifery-led care when co-located with consultant-led care. The DCE also finds women’s preferred package of care closely mirrors the DOMINO scheme with 39% of women expected to utilise this service. Consultant- and midwifery-led care would then be utilised by 34% and 27% of women, respectively. The CVM supports this hierarchy of preferences where consultant-led care is consistently valued more than midwifery-led care – women are willing to pay €956.03 for consultant-led care and €808.33 for midwifery-led care. A package of care for a woman availing of consultant- and midwifery-led care is estimated to cost €1,102.72 and €682.49, respectively. The CBA suggests both models of care are cost-beneficial and should be pursued in Ireland. This reconfiguration of maternity services would maximise women’s utility, while fulfilling important objectives of key government policy.

Does higher hospital cost imply higher quality of care?

This study investigates whether higher input use per stay in the hospital (treatment intensity) and longer length of stay improve outcomes of care. We allow for endogeneity of intensity and length of stay by estimating a quasi-maximum-likelihood discrete factor model, where the distribution of the unmeasured variable is modeled using a discrete distribution. Data on elderly persons come from several waves of the National Long-Term Care Survey merged with Medicare claims data for 1984-1995 and the National Death Index. We find that higher intensity improves patient survival and some dimensions of functional status among those who survive.

Cost of wind energy: comparing distant wind resources to local resources in the midwestern United States.

The best wind sites in the United States are often located far from electricity demand centers and lack transmission access. Local sites that have lower quality wind resources but do not require as much power transmission capacity are an alternative to distant wind resources. In this paper, we explore the trade-offs between developing new wind generation at local sites and installing wind farms at remote sites. We first examine the general relationship between the high capital costs required for local wind development and the relatively lower capital costs required to install a wind farm capable of generating the same electrical output at a remote site,with the results representing the maximum amount an investor should be willing to pay for transmission access. We suggest that this analysis can be used as a first step in comparing potential wind resources to meet a state renewable portfolio standard (RPS). To illustrate, we compare the cost of local wind (∼50 km from the load) to the cost of distant wind requiring new transmission (∼550-750 km from the load) to meet the Illinois RPS. We find that local, lower capacity factor wind sites are the lowest cost option for meeting the Illinois RPS if new long distance transmission is required to access distant, higher capacity factor wind resources. If higher capacity wind sites can be connected to the existing grid at minimal cost, in many cases they will have lower costs.

Nanofabrication at high throughput and low cost.

The task of nanofabrication can, in principle, be divided into two separate tracks: generation and replication of the patterned features. These two tracks are different in terms of characteristics, requirements, and aspects of emphasis. In general, generation of patterns is commonly achieved in a serial fashion using techniques that are typically slow, making this process only practical for making a small number of copies. Only when combined with a rapid duplication technique will fabrication at high-throughput and low-cost become feasible. Nanoskiving is unique in that it can be used for both generation and duplication of patterned nanostructures.

Hand hygiene noncompliance and the cost of hospital-acquired methicillin-resistant Staphylococcus aureus infection.

BACKGROUND: Hand hygiene noncompliance is a major cause of nosocomial infection. Nosocomial infection cost data exist, but the effect of hand hygiene noncompliance is unknown. OBJECTIVE: To estimate methicillin-resistant Staphylococcus aureus (MRSA)-related cost of an incident of hand hygiene noncompliance by a healthcare worker during patient care. DESIGN: Two models were created to simulate sequential patient contacts by a hand hygiene-noncompliant healthcare worker. Model 1 involved encounters with patients of unknown MRSA status. Model 2 involved an encounter with an MRSA-colonized patient followed by an encounter with a patient of unknown MRSA status. The probability of new MRSA infection for the second patient was calculated using published data. A simulation of 1 million noncompliant events was performed. Total costs of resulting infections were aggregated and amortized over all events. SETTING: Duke University Medical Center, a 750-bed tertiary medical center in Durham, North Carolina. RESULTS: Model 1 was associated with 42 MRSA infections (infection rate, 0.0042%). Mean infection cost was $47,092 (95% confidence interval [CI], $26,040-$68,146); mean cost per noncompliant event was $1.98 (95% CI, $0.91-$3.04). Model 2 was associated with 980 MRSA infections (0.098%). Mean infection cost was $53,598 (95% CI, $50,098-$57,097); mean cost per noncompliant event was $52.53 (95% CI, $47.73-$57.32). A 200-bed hospital incurs $1,779,283 in annual MRSA infection-related expenses attributable to hand hygiene noncompliance. A 1.0% increase in hand hygiene compliance resulted in annual savings of $39,650 to a 200-bed hospital. CONCLUSIONS: Hand hygiene noncompliance is associated with significant attributable hospital costs. Minimal improvements in compliance lead to substantial savings.

A low-cost, portable, and quantitative spectral imaging system for application to biological tissues.

The ability of diffuse reflectance spectroscopy to extract quantitative biological composition of tissues has been used to discern tissue types in both pre-clinical and clinical cancer studies. Typically, diffuse reflectance spectroscopy systems are designed for single-point measurements. Clinically, an imaging system would provide valuable spatial information on tissue composition. While it is feasible to build a multiplexed fiber-optic probe based spectral imaging system, these systems suffer from drawbacks with respect to cost and size. To address these we developed a compact and low cost system using a broadband light source with an 8-slot filter wheel for illumination and silicon photodiodes for detection. The spectral imaging system was tested on a set of tissue mimicking liquid phantoms which yielded an optical property extraction accuracy of 6.40 +/- 7.78% for the absorption coefficient (micro(a)) and 11.37 +/- 19.62% for the wavelength-averaged reduced scattering coefficient (micro(s)').

Cost of innovation in the pharmaceutical industry.

The research and development costs of 93 randomly selected new chemical entities (NCEs) were obtained from a survey of 12 U.S.-owned pharmaceutical firms. These data were used to estimate the pre-tax average cost of new drug development. The costs of abandoned NCEs were linked to the costs of NCEs that obtained marketing approval. For base case parameter values, the estimated out-of-pocket cost per approved NCE is $114 million (1987 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a 9% discount rate yielded an average cost estimate of $231 million (1987 dollars).

The cost of biopharmaceutical R&D: Is biotech different?

The costs of developing the types of new drugs that have been pursued by traditional pharmaceutical firms have been estimated in a number of studies. However, similar analyses have not been published on the costs of developing the types of molecules on which biotech firms have focused. This study represents a first attempt to get a sense for the magnitude of the R&D costs associated with the discovery and development of new therapeutic biopharmaceuticals (specifically, recombinant proteins and monoclonal antibodies [mAbs]). We utilize drug-specific data on cash outlays, development times, and success in obtaining regulatory marketing approval to estimate the average pre-tax R&D resource cost for biopharmaceuticals up to the point of initial US marketing approval (in year 2005 dollars). We found average out-of-pocket (cash outlay) cost estimates per approved biopharmaceutical of $198 million, $361 million, and $559 million for the preclinical period, the clinical period, and in total, respectively. Including the time costs associated with biopharmaceutical R&D, we found average capitalized cost estimates per approved biopharmaceutical of $615 million, $626 million, and $1241 million for the preclinical period, the clinical period, and in total, respectively. Adjusting previously published estimates of R&D costs for traditional pharmaceutical firms by using past growth rates for pharmaceutical company costs to correspond to the more recent period to which our biopharmaceutical data apply, we found that total out-of-pocket cost per approved biopharmaceutical was somewhat lower than for the pharmaceutical company data ($559 million vs $672 million). However, estimated total capitalized cost per approved new molecule was nearly the same for biopharmaceuticals as for the adjusted pharmaceutical company data ($1241 million versus $1318 million). The results should be viewed with some caution for now given a limited number of biopharmaceutical molecules with data on cash outlays, different therapeutic class distributions for biopharmaceuticals and for pharmaceutical company drugs, and uncertainty about whether recent growth rates in pharmaceutical company costs are different from immediate past growth rates. Copyright © 2007 John Wiley & Sons, Ltd.

The impact of geologic variability on capacity and cost estimates for storing CO 2 in deep-saline aquifers

While numerous studies find that deep-saline sandstone aquifers in the United States could store many decades worth of the nation's current annual CO 2 emissions, the likely cost of this storage (i.e. the cost of storage only and not capture and transport costs) has been harder to constrain. We use publicly available data of key reservoir properties to produce geo-referenced rasters of estimated storage capacity and cost for regions within 15 deep-saline sandstone aquifers in the United States. The rasters reveal the reservoir quality of these aquifers to be so variable that the cost estimates for storage span three orders of magnitude and average>$100/tonne CO 2. However, when the cost and corresponding capacity estimates in the rasters are assembled into a marginal abatement cost curve (MACC), we find that ~75% of the estimated storage capacity could be available for<$2/tonne. Furthermore, ~80% of the total estimated storage capacity in the rasters is concentrated within just two of the aquifers-the Frio Formation along the Texas Gulf Coast, and the Mt. Simon Formation in the Michigan Basin, which together make up only ~20% of the areas analyzed. While our assessment is not comprehensive, the results suggest there should be an abundance of low-cost storage for CO 2 in deep-saline aquifers, but a majority of this storage is likely to be concentrated within specific regions of a smaller number of these aquifers. © 2011 Elsevier B.V.

Balancing Cost and Emissions Certainty: An Allowance Reserve for Cap-and-Trade

On efficiency grounds, the economics community has to date tended to emphasize price-based policies to address climate change - such as taxes or a "safety-valve" price ceiling for cap-and-trade - while environmental advocates have sought a more clear quantitative limit on emissions. This paper presents a simple modification to the idea of a safety valve - a quantitative limit that we call the allowance reserve. Importantly, this idea may bridge the gap between competing interests and potentially improve efficiency relative to tax or other price-based policies. The last point highlights the deficiencies in several previous studies of price and quantity controls for climate change that do not adequately capture the dynamic opportunities within a cap-and-trade system for allowance banking, borrowing, and intertemporal arbitrage in response to unfolding information.