Sarah Ritter

Encapsulation of FITC to monitor extracellular pH: a step towards the development of red blood cells as circulating blood analyte biosensors

A need exists for a long-term, minimally-invasive system to monitor blood analytes. For certain analytes, such as glucose in the case of diabetics, a continuous system would help reduce complications. Current methods suffer significant drawbacks, such as low patient compliance for the finger stick test or short lifetime (i.e., 3–7 days) and required calibrations for continuous glucose monitors. Red blood cells (RBCs) are potential biocompatible carriers of sensing assays for long-term monitoring. We demonstrate that RBCs can be loaded with an analyte-sensitive fluorescent dye. In the current study, FITC, a pH-sensitive fluorescent dye, is encapsulated within resealed red cell ghosts. Intracellular FITC reports on extracellular pH: fluorescence intensity increases as extracellular pH increases because the RBC rapidly equilibrates to the pH of the external environment through the chloride-bicarbonate exchanger. The resealed ghost sensors exhibit an excellent ability to reversibly track pH over the physiological pH range with a resolution down to 0.014 pH unit. Dye loading efficiency varies from 30% to 80%. Although complete loading is ideal, it is not necessary, as the fluorescence signal is an integration of all resealed ghosts within the excitation volume. The resealed ghosts could serve as a long-term (>1 to 2 months), continuous, circulating biosensor for the management of diseases, such as diabetes.

Engineering erythrocytes to be erythrosensors: First steps

Molecules can be loaded into mammalian erythrocytes through a reversible lysis pore that forms in the membrane when placed in hypotonic media, the result being resealed red cell ghosts. Many studies on the sidedness of transport processes have utilized this approach. In addition, red cell ghosts encapsulated with enzymes have been used in patients to treat specific enzyme deficiencies, particularly when the substrate can cross the red cell membrane. Our long-term goal is to put fluorescent sensors inside erythrocytes, return the loaded red cell ghosts to the animal or patient, and then monitor the fluorescence non-invasively to follow changes in plasma analyte concentration. In this paper, we present a novel dialysis method for making the red cell ghosts. In addition, we present a theoretical analysis showing that it is not necessary that every loaded red cell ghost has the same dye concentration. Finally we discuss the constraints on the optimal affinity for the sensor/analyte interaction.

Characteristics of a 3D-printed prosthetic hand for use in developing countries

Arising out of civil conflict, disease, birth defects, and traumatic accidents, many people in developing countries lack hands or fingers. Prosthetic hands can help give these people a sense of agency and increased ability to perform everyday tasks. Unfortunately, many prostheses are prohibitively expensive and often require frequent maintenance and repair. Therefore, they are financially and geographically inaccessible to most people living in developing countries. A 3D printed, open-source hand is one possible solution owing to its low cost and potential for customization. However, the hand must be appropriate for the environmental conditions and lifestyles found in developing countries. To characterize the functionality of the 3D printed hand, a series of daily task and object tests were carried out. While the prosthesis was able to successfully complete a number of tasks, it had difficulty with those that required intricate movements and with heavy objects.

A review of current upper-limb prostheses for resource constrained settings

In lower-middle income countries (LMICs), untapped land mines, war, and diseases such as diabetes and polio have left many residents in need of a prosthetic device. For many whose primary source of income is derived from manual labor, lack of an appropriate prosthetic device often results in decreased productivity and lower quality of life. Across the world, the primary purpose of prostheses is to restore functional capacity in a manner that is both natural and aesthetically pleasing to the user. Some practices from the Western world, such as manufacturing methods, are transferrable to these contexts. However, the availability of materials, resources, and skilled personnel pose particular challenges for LMICs. In general, prostheses designed for LMICs exhibit simplified designs, as well as limited materials and electronic components. This article reviews current upper-limb prosthetic devices developed specifically for resource-constrained environments. An overview of the materials and design for each device as well as a discussion of their limitations are provided.

Stamping: A low-cost manufacturing method to deposit assays

Treatable diseases often go undetected in developing countries due to low doctor-to-patient ratios and inaccessibility of health care facilities. While many treatable diseases can be screened via urinalysis, commonly used urine test strips are generally distributed through a formal healthcare system, which has limited access to rural communities. To tailor urinalysis devices to developing countries, simple and small-scale ink deposition methods, such as stamping, are being explored to design point-of-care screening test strips. Such test strips combat inaccessibility through the engagement of community health workers, who serve as a liaison between the formal health care network and rural communities. This work investigates the properties of several off-the-shelf stamps and papers in order to design a platform stamping technology that requires low startup capital. The findings validate a mechanism for stamping assays that can be customized to screen for different conditions such as diabetes, urinary tract infections, water purity, and methanol levels in alcohol, among others. Ultimately, this stamping method has wide scope for humanitarian engineering applications in the fields of health care and environmental safety.

Inexpensive urinalysis test strips to screen for diabetes in developing countries

Sub-Saharan Africa is increasingly experiencing the double burden of communicable and noncommunicable diseases. Many of these diseases, including diabetes, remain prevalent despite the availability of viable treatment options. Lack of access to screening tools frequently prevents individuals from seeking a diagnosis or pursuing treatment. The development of alternative screening devices in the form of low cost test strips has the potential to surmount existing barriers to treatment, allowing earlier intervention in the progression of diabetes. This article presents a demonstration that modified published protocols for glucose and ketone detection in solution — two of the principal chemical signatures of diabetes — are reproducible on test strips manufactured using composite rubber-foam stamps to print chemical reagents on filter paper. These test strips contain specific chemicals which, in the presence of disease markers, cause a visible color change and defined intensity gradient that can be experimentally verified. The creation of an affordable and effective urinalysis test strip has the ability to make screening for disease more accessible in developing nations.

Loading of red blood cells with an analyte-sensitive dye for development of a long-term monitoring technique

Measurement of blood analytes, such as pH and glucose, provide crucial information about a patients health. Some such analytes, such as glucose in the case of diabetes, require long-term or near-continuous monitoring for proper disease management. However, current monitoring techniques are far from ideal: multiple-per-day finger stick tests are inconvenient and painful for the patient; implantable sensors have short functional life spans (i.e., 3-7 days). Red blood cells serve as an attractive alternative for carriers of analyte sensors. Once reintroduced to the blood stream, these carriers may continue to live for the remainder of their life span (120 days for humans). They are also biodegradable and biocompatible, thereby eliminating the immune system response common for many implanted devices. The proposed carrier system takes advantage of the ability of the red blood cells to swell in response to a decrease in the osmolarity of the extracellular solution. Just before the membranes lyse, they develop small pores on the scale of tens of nanometers. Analyte-sensitive dyes in the extracellular solution may then diffuse into the perforated red blood cells and become entrapped upon restoration of physiological temperature and osmolarity. Because the membranes contain various analyte transporters, intracellular analyte levels rapidly equilibrate to those of the extracellular solution. A fluorescent dye has been loaded inside of red blood cells using a preswelling technique. Alterations in preparation parameters have been shown to affect characteristics of the resulting dye-loaded red blood cells (e.g., intensity of fluorescence).

mBody health: Digitizing disabilities in Sierra Leone

Disability and poverty are linked in a vicious cycle in the developing world. With limited access to healthcare resources, the disabled population often lacks necessary diagnosis, treatment, and medication. They experience stigma and neglect within their communities. With severely limited healthcare and education for disabilities, both the disabled population and the community remain unaware of not only prevention and treatment but also of social realities and the mistake of stigmatization. In Sierra Leone, a number of social, private, and public sector entities have embraced the opportunity to offer informal disability screening and education through a mobile application (app) preinstalled on smartphones. The app development team has since identified relevant disabilities; compiled a database of descriptions, causes, symptoms, treatments, and support resources; and designed a screening tool. The initial version of the app was field tested in Sierra Leone in May 2016, including extensive engagement with health workers and community members. This article reviews the strategic case for the app, its initial design, the results of field testing, and current and future trajectories for the venture.

PubHub: A web-based compendium to catalyze undergraduate research publication

Research publication and presentation provides undergraduate students with invaluable benefits including career preparation and increased confidence. At the same time, it provides the scientific community with better-prepared professionals while contributing to the larger knowledge base. Since opportunities and resources for undergraduate research are growing, larger numbers of students are now engaged in formal disciplinary research and creative inquiry across disciplines. However, only a few students disseminate their research findings in scholarly forums like refereed journals and conference proceedings. Barriers to undergraduate research publication include lack of faculty time to devote to mentoring students in writing, limited institutional funding for undergraduate research, and students unfamiliarity with the publication process. This article describes PubHub, an online compendium of 50+ learning modules across five categories to assist students through the publication and presentation processes. A pilot assessment of PubHub amongst students and faculty members indicates its usability. While resources like PubHub cannot increase funding for undergraduate researchers or shorten the timescale of the peer-review process, they can lower barriers and democratize the publication process, while refocusing faculty time on intellectual aspects of research rather than the scholarly writing process by providing students the knowledge and specific insights they need in a just-in-time manner.

Optimization of prosthetic hand manufacturing

3D printing is a manufacturing method that holds much promise for customized prosthetic devices, particularly in developing countries. There are many open-source prosthetic hands designed specifically for the additive manufacturing process. However, the excessive time (i.e., 32-53 hours) required for printing and assembly hinders scale up. This article analyzes 3D printing and injection molding strategies to determine the optimal manufacturing method that balances manufacturing time and cost. While injection molding is less suited to individualization of prosthetic hands due to high upfront costs and long development times associated with the creation of each new mold, production time and cost significantly decrease thereafter. After analyzing manufacturing costs and times as well as anthropometric data, a hybridized process was selected in which the palm would be 3D printed and other parts injection molded. For the injection molded components, a set of three standard sizes was selected to fit the majority of the population by analyzing anthropometric data from both the U.S. military and general populations.