Effects of hydraulically disconnecting consumer pumps in an intermittent water supply.

We estimate 250 million people receive water using private pumps connected directly to intermittently pressurized distribution networks. Yet no previous studies have quantified the presumed effects of these pumps. In this paper, we investigate the effects of installing pressure-sustaining valves at consumer connections. These valves mimic pump disconnection by restricting flow. Installing these valves during the dry season at 94% of connections in an affluent neighborhood in Delhi, India, cut the prevalence of samples with turbidity > 4 NTU by two thirds. But considering the poor reputation of pumps, installed valves had surprisingly small average effects on turbidity (-8%; p<0.01) and free chlorine (+0.05 mg/L; p<0.001; N = 1,031). These effects were much smaller than the high variability in water quality supplied to both control and valve-installed neighborhoods. Site-specific responses to this variability could have confounded our results. At the study site, installed valves increased network pressure during 88% of the typical supply window; valves had a maximum pressure effect of +0.62 m (95% CI [0.54, 0.71]; a 40% increase vs. control). Further research is needed to generalize beyond our study site. Nevertheless, this paper provides unique evidence showing how the deployed valves mitigated pump effects, increased network pressure and improved water safety.

Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine.

Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis worldwide and kills more Americans than 59 other infections, including HIV and tuberculosis, combined. While direct-acting antiviral (DAA) treatments are effective, limited uptake of therapy, particularly in high-risk groups, remains a substantial barrier to eliminating HCV. We developed a long-acting DAA system (LA-DAAS) capable of prolonged dosing and explored its cost-effectiveness. We designed a retrievable coil-shaped LA-DAAS compatible with nasogastric tube administration and the capacity to encapsulate and release gram levels of drugs while resident in the stomach. We formulated DAAs in drug-polymer pills and studied the release kinetics for 1 mo in vitro and in vivo in a swine model. The LA-DAAS was equipped with ethanol and temperature sensors linked via Bluetooth to a phone application to provide patient engagement. We then performed a cost-effectiveness analysis comparing LA-DAAS to DAA alone in various patient groups, including people who inject drugs. Tunable release kinetics of DAAs was enabled for 1 mo with drug-polymer pills in vitro, and the LA-DAAS safely and successfully provided at least month-long release of sofosbuvir in vivo. Temperature and alcohol sensors could interface with external sources for at least 1 mo. The LA-DAAS was cost-effective compared to DAA therapy alone in all groups considered (base case incremental cost-effectiveness ratio $39,800). We believe that the LA-DAA system can provide a cost-effective and patient-centric method for HCV treatment, including in high-risk populations who are currently undertreated.

A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment.

Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication.

Results of an Ocean Trial of the Symbiotic Machine for Ocean uRanium Extraction.

Amidoxime-based adsorbents have become highly promising for seawater uranium extraction. However, current deployment schemes are stand-alone, intermittent operation systems that have significant practical and economic challenges. This paper presents two 1:10 scale prototypes of a Symbiotic Machine for Ocean uRanium Extraction (SMORE) which pairs with an existing offshore structure. This pairing reduces mooring and deployment costs while enabling continuous, autonomous uranium extraction. Utilizing a shell enclosure to decouple the mechanical and chemical requirements of the adsorbent, one design concept prototyped continuously moves the shells through the water while the other keeps them stationary. Water flow in the shells on each prototype was determined using the measurement of radium adsorbed by MnO2 impregnated acrylic fibers contained within each enclosure. The results from a nine-week ocean trial show that while movement of the shells through the water may not have an effect on uranium adsorption by the fibers encased, it could help reduce biofouling if above a certain threshold speed (resulting in increased uptake), while also allowing for the incorporation of design elements to further mitigate biofouling such as bristle brushes and UV lamps. The trace metal uptake by the AI8 adsorbents in this trial also varied greatly from previous marine deployments, suggesting that uranium uptake may depend greatly upon the seawater concentrations of other elements such as vanadium and copper. The results from this study will be used to inform future work on the seawater uranium production cost from a full-scale SMORE system.

Analytical scaling relations to evaluate leakage and intrusion in intermittent water supply systems.

Intermittent water supplies (IWS) deliver piped water to one billion people; this water is often microbially contaminated. Contaminants that accumulate while IWS are depressurized are flushed into customers' homes when these systems become pressurized. In addition, during the steady-state phase of IWS, contaminants from higher-pressure sources (e.g., sewers) may continue to intrude where pipe pressure is low. To guide the operation and improvement of IWS, this paper proposes an analytic model relating supply pressure, supply duration, leakage, and the volume of intruded, potentially-contaminated, fluids present during flushing and steady-state. The proposed model suggests that increasing the supply duration may improve water quality during the flushing phase, but decrease the subsequent steady-state water quality. As such, regulators and academics should take more care in reporting if water quality samples are taken during flushing or steady-state operational conditions. Pipe leakage increases with increased supply pressure and/or duration. We propose using an equivalent orifice area (EOA) to quantify pipe quality. This provides a more stable metric for regulators and utilities tracking pipe repairs. Finally, we show that the volume of intruded fluid decreases in proportion to reductions in EOA. The proposed relationships are applied to self-reported performance indicators for IWS serving 108 million people described in the IBNET database and in the Benchmarking and Data Book of Water Utilities in India. This application shows that current high-pressure, continuous water supply targets will require extensive EOA reductions. For example, in order to achieve national targets, utilities in India will need to reduce their EOA by a median of at least 90%.

A New Phenomenon: Sub-Tg, Solid-State, Plasticity-Induced Bonding in Polymers.

Polymer self-adhesion due to the interdiffusion of macromolecules has been an active area of research for several decades. Here, we report a new phenomenon of sub-Tg, solid-state, plasticity-induced bonding; where amorphous polymeric films were bonded together in a period of time on the order of a second in the solid-state at ambient temperatures, up to 60 K below their glass transition temperature (Tg), by subjecting them to active plastic deformation. Despite the glassy regime, the bulk plastic deformation triggered the requisite molecular mobility of the polymer chains, causing interpenetration across the interfaces held in contact. Quantitative levels of adhesion and the morphologies of the fractured interfaces validated the sub-Tg, plasticity-induced, molecular mobilization causing bonding. No-bonding outcomes (i) during the uniaxial compressive straining of films (a near-hydrostatic setting which strongly limits plastic flow) and (ii) between an 'elastic' and a 'plastic' film further established the explicit role of plastic deformation in this newly reported sub-Tg solid-state bonding.

Enhancing the performance of the T-peel test for thin and flexible adhered laminates.

Symmetrically bonded thin and flexible T-peel specimens, when tested on vertical travel machines, can be subject to significant gravitational loading, with the associated asymmetry and mixed-mode failure during peeling. This can cause erroneously high experimental peel forces to be recorded which leads to uncertainty in estimating interfacial fracture toughness and failure mode. To overcome these issues, a mechanical test fixture has been designed, for use with vertical test machines, that supports the unpeeled portion of the test specimen and suppresses parasitic loads due to gravity from affecting the peel test. The mechanism, driven by the test machine cross-head, moves at one-half of the velocity of the cross-head such that the unpeeled portion always lies in the plane of the instantaneous center of motion. Several specimens such as bonded polymeric films, laminates, and commercial tapes were tested with and without the fixture, and the importance of the proposed T-peel procedure has been demonstrated.

A versatile-deployable bacterial detection system for food and environmental safety based on LabTube-automated DNA purification, LabReader-integrated amplification, readout and analysis.

Contamination of foods is a public health hazard that episodically causes thousands of deaths and sickens millions worldwide. To ensure food safety and quality, rapid, low-cost and easy-to-use detection methods are desirable. Here, the LabSystem is introduced for integrated, automated DNA purification, amplification and detection. It consists of a disposable, centrifugally driven DNA purification platform (LabTube) and a low-cost UV/vis-reader (LabReader). For demonstration of the LabSystem in the context of food safety, purification of Escherichia coli (non-pathogenic E. coli and pathogenic verotoxin-producing E. coli (VTEC)) in water and milk and the product-spoiler Alicyclobacillus acidoterrestris (A. acidoterrestris) in apple juice was integrated and optimized in the LabTube. Inside the LabReader, the purified DNA was amplified, readout and analyzed using both qualitative isothermal loop-mediated DNA amplification (LAMP) and quantitative real-time PCR. For the LAMP-LabSystem, the combined detection limits for purification and amplification of externally lysed VTEC and A. acidoterrestris are 10(2)-10(3) cell-equivalents. In the PCR-LabSystem for E. coli cells, the quantification limit is 10(2) cell-equivalents including LabTube-integrated lysis. The demonstrated LabSystem only requires a laboratory centrifuge (to operate the disposable, fully closed LabTube) and a low-cost LabReader for DNA amplification, readout and analysis. Compared with commercial DNA amplification devices, the LabReader improves sensitivity and specificity by the simultaneous readout of four wavelengths and the continuous readout during temperature cycling. The use of a detachable eluate tube as an interface affords semi-automation of the LabSystem, which does not require specialized training. It reduces the hands-on time from about 50 to 3 min with only two handling steps: sample input and transfer of the detachable detection tube.

Centrifugal LabTube platform for fully automated DNA purification and LAMP amplification based on an integrated, low-cost heating system.

This paper introduces a disposable battery-driven heating system for loop-mediated isothermal DNA amplification (LAMP) inside a centrifugally-driven DNA purification platform (LabTube). We demonstrate LabTube-based fully automated DNA purification of as low as 100 cell-equivalents of verotoxin-producing Escherichia coli (VTEC) in water, milk and apple juice in a laboratory centrifuge, followed by integrated and automated LAMP amplification with a reduction of hands-on time from 45 to 1 min. The heating system consists of two parallel SMD thick film resistors and a NTC as heating and temperature sensing elements. They are driven by a 3 V battery and controlled by a microcontroller. The LAMP reagents are stored in the elution chamber and the amplification starts immediately after the eluate is purged into the chamber. The LabTube, including a microcontroller-based heating system, demonstrates contamination-free and automated sample-to-answer nucleic acid testing within a laboratory centrifuge. The heating system can be easily parallelized within one LabTube and it is deployable for a variety of heating and electrical applications.

Audible frequency vibration of puncture-access medical devices.

Ultrasonic vibration has been proven to help scalpels and puncture devices cut and cauterize, but creates a damaged tissue zone that may not be desirable. We have found that audible frequency vibration applied to a needle not only reduces puncture force more than ultrasonic vibration; it does not cause significant immediate tissue damage. Here we thus present a method for decreasing the force required to insert a puncture-access medical device and an analytical model for predicting performance of a hypodermic needle, which correlates well with tests and shows that needle insertion force is lowered not only by decreasing the outer diameter of the needle, but also by driving the device at its free state resonant (amplitude-maximizing) frequency. Finally, an in vivo histology study is conducted and suggests that audible frequency vibration results in the same degree of immediate local tissue damage as simple manually inserted needles, but that it causes significantly less immediate local tissue damage than ultrasonic vibration.

Evaluation of a minimally invasive renal cooling device using heat transfer analysis and an in vivo porcine model.

Partial nephrectomy is the gold standard treatment for renal cell carcinoma. This procedure requires temporary occlusion of the renal artery, which can cause irreversible damage due to warm ischemia after 30 min. Open surgical procedures use crushed ice to induce a mild hypothermia of 20°C in the kidney, which can increase allowable ischemia time up to 2.5 h. The Kidney Cooler device was developed previously by the authors to achieve renal cooling using a minimally invasive approach. In the present study an analytical model of kidney cooling in situ was developed using heat transfer equations to determine the effect of kidney thickness on cooling time. In vivo porcine testing was conducted to evaluate the cooling performance of this device and to identify opportunities for improved surgical handling. Renal temperature was measured continuously at 6 points using probes placed orthogonally to each other within the kidney. Results showed that the device can cool the core of the kidney to 20°C in 10-20 min. Design enhancements were made based on surgeon feedback; it was determined that the addition of an insulating air layer below the device increased difficulty of positioning the device around the kidney and did not significantly enhance cooling performance. The Kidney Cooler has been shown to effectively induce mild renal hypothermia of 20°C in an in vivo porcine model.

Classroom to Clinic: Merging Education and Research to Efficiently Prototype Medical Devices.

Innovation in patient care requires both clinical and technical skills, and this paper presents the methods and outcomes of a nine-year, clinical-academic collaboration to develop and evaluate new medical device technologies, while teaching mechanical engineering. Together, over the course of a single semester, seniors, graduate students, and clinicians conceive, design, build, and test proof-of-concept prototypes. Projects initiated in the course have generated intellectual property and peer-reviewed publications, stimulated further research, furthered student and clinician careers, and resulted in technology licenses and start-up ventures.

Analysis and design of rolling-contact joints for evaluating bone plate performance.

An apparatus for testing maxillofacial bone plates has been designed using a rolling contact joint. First, a free-body representation of the fracture fixation techniques utilizing bone plates is used to illustrate how rolling contact joints accurately simulate in vivo biomechanics. Next, a deterministic description of machine functional requirements is given, and is then used to drive the subsequent selection and design of machine elements. Hertz contact stress and fatigue analysis for two elements are used to ensure that the machine will both withstand loads required to deform different plates, and maintain a high cycle lifetime for testing large numbers of plates. Additionally, clinically relevant deformations are presented to illustrate how stiffness is affected after a deformation is applied, and to highlight improvements made by the machine over current testing standards, which do not adequately re-create in vivo loading conditions. The machine performed as expected and allowed for analysis of bone plates in both deformed and un-deformed configurations to be conducted. Data for deformation experiments is presented to show that the rolling-contact testing machine leads to improved loading configurations, and thus a more accurate description of plate performance. A machine for evaluation of maxillofacial bone plates has been designed, manufactured, and used to accurately simulate in vivo loading conditions to more effectively evaluate the performance of both new and existing bone plates.

Rapid and robust detection methods for poison and microbial contamination.

Real-time on-site monitoring of analytes is currently in high demand for food contamination, water, medicines, and ingestible household products that were never tested appropriately. Here we introduce chemical methods for the rapid quantification of a wide range of chemical and microbial contaminations using a simple instrument. Within the testing procedure, we used a multichannel, multisample, UV-vis spectrophotometer/fluorometer that employs two frequencies of light simultaneously to interrogate the sample. We present new enzyme- and dye-based methods to detect (di)ethylene glycol in consumables above 0.1 wt % without interference and alcohols above 1 ppb. Using DNA intercalating dyes, we can detect a range of pathogens ( E. coli , Salmonella , V. Cholera, and a model for Malaria) in water, foods, and blood without background signal. We achieved universal scaling independent of pathogen size above 10(4) CFU/mL by taking advantage of the simultaneous measurement at multiple wavelengths. We can detect contaminants directly, without separation, purification, concentration, or incubation. Our chemistry is stable to ± 1% for >3 weeks without refrigeration, and measurements require <5 min.

Technical communication: design and in vitro testing of a pressure-sensing syringe for endotracheal tube cuffs.

Endotracheal intubation is a frequently performed procedure in the prehospital setting, intensive care unit, and for patients undergoing surgery. The endotracheal tube cuff must be inflated to a pressure that prevents air leaks without compromising tracheal mucosal blood flow. For simultaneous endotracheal tube cuff inflation and measurement, we designed and tested a novel pressure-sensing syringe in vitro. The prototype was developed using a standard 10-mL polycarbonate syringe body that houses a plunger and a silicone rubber bellows, the pressure-sensing element. Bellow feasibility was determined and modeled using finite element analysis. Repeatability testing at each pressure measurement for each bellows (pressure versus deflection) was within an average standard deviation of 0.3 cm to 1.61 cm (1%-5% error). Using an aneroid manometer for comparison, there was excellent linear correlation with a Spearman rank of 0.99 (P < 0.001), up to 30 cm H(2)O.

Design and experimental evaluation of adjustable bone plates for mandibular fracture fixation.

Conventional bone plates are commonly used for surgical mandibular fracture fixation. Improper alignment between bone segments, however, can result in malocclusion. Current methods of fixation require a surgeon to visually align segments of bone and affix a metal plate using bone screws, after which little can be done to adjust alignment. A method of adjusting fracture alignment after plate placement, without screw removal, presents an improvement over costly and risky revision surgery. A modified bone plate has been designed with a deformable section to give surgeons the ability to reduce misalignments at the fracture site. The mechanics of deformation for various adjustment mechanisms was explored analytically, numerically, and experimentally to ensure that the adjustable plate is comparable to conventional bone plates. A static force of 358.8 N is required to deform the adjustable bone plate, compared with predicted values of 351 N using numerical simulation and 362 N using a simple beam theory. Dynamic testing was performed to simulate in vivo loading conditions and evaluate load-capacity in both deformed and un-deformed bone plates. Results indicate that bending stiffness of a rectangular bone plate is 709 N/mm, compared with 174 N/mm for an octagonal plate and 176 N/mm for standard plates. Once deformed, the rectangular and octagonal plates had a stiffness of 323 N/mm and 228 N/mm, respectively. Un-deformed and deformed adjustable bone plates have efficacy in bone segment fixation and healing.

A novel cardioport for beating-heart, image-guided intracardiac surgery.

OBJECTIVE: Intracardiac beating-heart procedures require the introduction and exchange of complex instruments and devices. To prevent potential complications such as air embolism and bleeding, a universal cardioport was designed and tested. METHODS: The design consists of a port body and a series of interchangeable sleeves. The port uses a fluid purging system to remove air from the instrument before insertion into the heart, and a valve system minimizes blood loss during instrument changes. RESULTS: The cardioport was tested ex vivo and in vivo in pigs (n = 5). Beating-heart procedures, such as septal defect closure and mitral valve repair, were modeled. Ex vivo trials (n = 150) were performed, and no air emboli were introduced using the port. In comparison, air emboli were detected in 40% to 85% of the cases without the use of the port-based purging system. Port operation revealed excellent ergonomics and minimal blood loss. CONCLUSIONS: A novel cardioport system designed to prevent air entry and blood loss from transcardiac instrument introduction was shown to be an enabling platform for intracardiac beating-heart surgery. The port system improves safety and facilitates further development of complex instruments and devices for transcardiac beating-heart surgery.