Putting medical devices in context: a systematic review of evidence on design targeting low-resource settings

Most medical devices are inaccessible to healthcare facilities in low-resource settings (LRSs), severely limiting medical care for a vast proportion of the world's population. This article characterises the process used for designing medical devices for LRSs and investigate how the context-of-use is integrated into the process. A systematic review of 64 papers was conducted to identify peer-reviewed studies of devices intended for LRSs. Using the biodesign process as an analytic framework, a qualitative meta-analysis was conducted. Findings show the studies predominantly describe the later stages of medical device design, whilst largely neglecting how knowledge of the context is considered. To support engineers and improve outcomes, it is imperative that an understanding of the context is integrated throughout the design and product development process. This article highlights this gap and hopes to stimulate research into how context can be better incorporated into the design process for medical devices targeting those populations most in need.This is the author accepted manuscript. The final version is available from Inderscience Publishers via http://dx.doi.org/10.1504/IJDE.2015.07637

Engaging Undergraduates to Solve Global Health Challenges: A New Approach Based on Bioengineering Design

Recent reports have highlighted the need for educational programs to prepare students for careers developing and disseminating new interventions that improve global public health. Because of its multi-disciplinary, design-centered nature, the field of Biomedical Engineering can play an important role in meeting this challenge. This article describes a new program at Rice University to give undergraduate students from all disciplines a broad background in bioengineering and global health and provides an initial assessment of program impact. Working in partnership with health care providers in developing countries, students in the Beyond Traditional Borders (BTB) initiative learn about health challenges of the poor and put this knowledge to work immediately, using the engineering design process as a framework to formulate solutions to complex global health challenges. Beginning with a freshman design project and continuing through a capstone senior design course, the BTB curriculum uses challenges provided by partners in the developing world to teach students to integrate perspectives from multiple disciplines, and to develop leadership, communication, and teamwork skills. Exceptional students implement their designs under the guidance of clinicians through summer international internships. Since 2006, 333 students have designed more than 40 technologies and educational programs; 28 have been implemented in sub-Saharan Africa, Latin America, the Caribbean, southeast Asia, and the United States. More than 18,000 people have benefited from these designs. 95% of alumni who completed an international internship reported that participation in the program changed or strengthened their career plans to include a focus on global health medicine, research, and/or policy. Empowering students to use bioengineering design to address real problems is an effective way to teach the new generation of leaders needed to solve global health challenges

Using thermochromism to simulate blood oxygenation in extracorporeal membrane oxygenation

Introduction: Extracorporeal membrane oxygenation (ECMO) training programs employ real ECMO components, causing them to be extremely expensive while offering little realism in terms of blood oxygenation and pressure. To overcome those limitations, we are developing a standalone modular ECMO simulator that reproduces ECMO’s visual, audio and haptic cues using affordable mechanisms. We present a central component of this simulator, capable of visually reproducing blood oxygenation color change using thermochromism. Methods: Our simulated ECMO circuit consists of two physically distant modules, responsible for adding and withdrawing heat from a thermochromic fluid. This manipulation of heat creates a temperature difference between the fluid in the drainage line and the fluid in the return line of the circuit and, hence, a color difference. Results: Thermochromic ink mixed with concentrated dyes was used to create a recipe for a realistic and affordable blood-colored fluid. The implemented “ECMO circuit” reproduced blood’s oxygenation and deoxygenation color difference or lack thereof. The heat control circuit costs 300 USD to build and the thermochromic fluid costs 40 USD/L. During a ten-hour in situ demonstration, nineteen ECMO specialists rated the fidelity of the oxygenated and deoxygenated “blood” and the color contrast between them as highly realistic. Conclusions: Using low-cost yet high-fidelity simulation mechanisms, we implemented the central subsystem of our modular ECMO simulator, which creates the look and feel of an ECMO circuit without using an actual one.Peer reviewedFinal Accepted Versio

Development of Microfluidic Instrumentation for Application in the Diagnosis of Rare Anaemias

Globally, the number of children born every year with a rare anaemia exceeds 500,000. The symptoms of rare anaemias range, depending on the mutation, from mild to severe, and in many cases prove to be fatal. The geographical prevalence of rare anaemias is concentrated in developing countries where resources available for diagnosis and treatment are scarce. The gold standard diagnosis of rare anaemia requires a three-tier investigation which is costly and not readily available in the areas most afflicted. As such, there is a need for a low-cost and user friendly method of diagnosis for these diseases. This thesis investigates the diagnostic abilities of a bio-chemical assay that exposes red blood cells to a low pH shock using microfluidic techniques. This involved the development of a novel low-cost microfluidic instrument, which has been named MeCheM, to run Lab-on-a-Chip devices. The experimental techniques and protocols developed are critically reviewed using healthy blood samples as the control. The results from the control population establish baselines for comparison against the diseased samples. Subsequently, the developed methods are investigated for diagnostic capabilities using rare anaemia blood samples. The results from these investigations suggest that there are observable differences for the developed Flow Test in the case of the Thalassaemia and Hereditary Spherocytosis disorders. Similarly, the developed Cell-Surface Adhesion measurements highlighted significant differences among the Sickle Cell samples. Additionally, secondary investigations indicated correlations between the gold standard Red Blood Cell Count and the RBC Count as measured using MeCheM, and Mean Corpuscular Volume and Average Cell Projected Area (pre-acid addition). The development of MeCheM, a novel microfluidic instrument, as a stand-alone device is a key output from this body of work

Mechanical Stimulator for Tissue-Engineered Skeletal Muscle

This project set out to develop a system to mechanically stimulate in vitro skeletal muscle tissue to produce more accurate models of in vivo tissue for use in studying human muscular diseases. Active and passive contractions play a key role in the in vivo development of skeletal muscle. A device was produced in which tissue was cultured in fibrin gel to grow dogbone-shaped tissue around sets of posts in the device. The device is able to: statically or cyclically strain the tissue, control the amount of strain from -50% to +50%, allow for stimulation of up to 96 samples, and minimize the construct size of the tissues. Mechanical stimulation by the device led to greater myofiber alignment, higher fiber density, and overall a closer resemblance to in vivo tissue

Doctor of Philosophy

dissertationMedical error causes preventable death in nearly 100,000 patients per year in the US alone. Common sources for error include medication related problems, technical equipment failure, interruptions, complicated and error-prone devices, information overload (providing too much patient data for one person to process effectively), and environmental problems like inadequate lighting or distracting ambient noise. Intensive care units are one of the riskiest locations in a hospital, with up to 9 reported events per 100 patient days. This risk is in large contrast to anesthesia in the operating rooms. Here much advancement in the area of patient safety has been made in the past, dropping the average risk for anesthesia related death to less than 1 in 200,000 anesthetics-an improvement by a factor of 20 in the past 30 years. Improvements in technology and other innovations contributing to this success now need to be adapted for and implemented in the intensive care unit setting. Nurses are increasingly regarded as key decision makers within the healthcare team, as they outnumber physicians 4:1. Reducing nurses' workload and improving medical decision making by providing decision support tools can have a significant impact in reducing the chances of medical errors. This dissertation consists of four manuscripts: 1) a review of previous medical display evaluations, providing insight into solutions that have worked in the past; 2) a study on reducing false alarms and increasing the usefulness of the remaining alarms by introducing alarm delays and detecting alarm context;, such as suctioning automatically silencing ventilator alarms; 3) a study of simplifying the frequent but complicated task of titrating vasoactive medications by providing a titration support tool that predicts blood pressure changes 5 minutes into the future; and 4) a study on supporting the triage of unfamiliar patients by introducing a far-view display that incorporates information from previously disparate devices and presents trend and alarm information at one easy to scan and interpret location

Device Engineering for Infectious Disease Diagnosis using Isothermal DNA Amplification and Lateral Flow Detection

Technologies that enable infectious diseases diagnosis in low-resource settings could greatly facilitate effective treatment and containment of such diseases. Nucleic acid amplification testing can be used to identify pathogens, but typically requires highly-trained personnel and large, expensive lab equipment, neither of which is available in low-resource settings. Our overall goal is to develop a portable diagnostic system that utilizes a low-cost, disposable, mesofluidic cartridge and a handheld electronics unit to perform fully-integrated nucleic acid testing at the point of care in low-resource settings. As a first step toward this goal, we developed a subunit to execute isothermal nucleic acid amplification coupled with lateral flow detection, in parallel with the development of a sample preparation subunit by our collaborators at Claremont BioSolutions. Fluid handling inside the amplification and detection cartridge is facilitated through one-way passive valves, flexible pouches, and electrolysis-driven pumps, which promotes a compact and inexpensive instrument design. The closed-system disposable prevents workspace amplicon contamination. The cartridge design is based on standard, scalable manufacturing techniques, such as injection molding. Using an initial prototype system, we demonstrated detection of purified Mycobacterium tuberculosis genomic DNA. We then developed a refined amplification and detection cartridge in conjunction with an improved portable instrument, which automates pumping, heating, and timing, using a design format compatible with eventual integration with the sample preparation subunit. This refined cartridge incorporates a novel, inexpensive, stand-alone, passive valve, smaller, integrated pump components, a more complex injection molded polycarbonate cartridge core piece, and enhanced lateral flow chambers to improve visual detection. The independent valve component can be tailored for a variety of fluidic systems. We demonstrated appropriate fluidic and thermal control, and successful isothermal nucleic acid amplification within this refined amplification and detection subunit. We have developed a separate fluidic module for master-mix reagent storage and reconstitution that is designed to act as the interface between the amplification and detection subunit and the upstream sample preparation subunit. We envision that the merger of these two subunits into a fully-integrated cartridge will enable user-friendly, automated sample-in to answer-out diagnosis of infectious diseases in primary care settings of low-resource countries with high disease burden

Drug delivery during breastfeeding: investigations of formulations and clinical feasibility

Research presented in this thesis was jointly supervised by the Department of Chemical Engineering and Biotechnology (School of Technology) and the Department of Paediatrics (School of Clinical Medicine).At an age when breastfeeding is the optimal nutritional support for infants, oral drug delivery can be challenging. In the past, the concept of drug delivery during breastfeeding was developed as a means to address challenges in low-income countries by facilitating administration using solid dosage forms without the need for clean water. Hereby, a silicone nipple shield, containing a formulation inside its teat, is meant to be worn by a mother during breastfeeding, enabling drug delivery to the sucking infant through the flow of human milk. Furthering past research, this doctoral work aimed to investigate novel dosage forms for this application, including a fibrous matrix and a gel formulation, as well as the clinical potential, feasibility, and acceptability of therapeutic delivery during breastfeeding. In a clinical context, a descriptive qualitative study revealed the need for alternative infant oral drug delivery technologies in high-resource settings, and parents' and nursing staff's positive response to the concept of drug delivery during breastfeeding. Findings were supported by the anecdotal evidence of difficulties in infant compliance and accurate dosing, and indicated high relevance for a use case in neonatal intensive care. Formulation investigations included zinc sulphate loaded non-woven fibre mats, and iron sulphate loaded liquid-core alginate hydrogels, using a modified and a commercially available nipple shield design. While full release during breastfeeding simulation was not achieved, both formulations enabled superior delivery of their loaded therapeutic dose compared to previously studied dosage forms. In addition, a clinical feasibility study involving the delivery of vitamin B12 from a commercially available nipple shield during breastfeeding was conducted, supported by a qualitative mixed methods approach. Results illustrated the successful delivery of vitamin B12 to breastfed infants and unanimous maternal advocacy for the availability of therapeutic delivery during breastfeeding in the future.University of Cambridge's W.D. Armstrong Fund (W.D. Armstrong Studentship for the Application of Engineering in Medicine) University of Cambridge's Kurt Hahn Trust (Kurt Hahn Scholarship) German Academic Scholarship Foundation (PhD Scholarship