3D Printing of Microfluidics for Point of Care Diagnosis

Author(s):  
John P. Sibbitt ◽  
Mei He

Microfluidic lab-on-a-chip (MLOC) technology is a promising approach for point-of-care (POC) diagnosis; low reagent consumption, high sensitivity and quick analysis time are the most prominent benefits. However, microfabrication of MLOCs utilizes specialized techniques and infrastructure, making conventional fabrication time consuming and difficult. While relatively inexpensive production techniques exist for POC diagnoses, such as replication of polymer-based (e.g., PDMS) microfluidic POC devices on lithographic molds, this approach has limitations including: further hydrophilic surface modifications of PDMS, inability to change lithographic mold Z dimensions, and slow prototyping. In contrast, stereo-lithographical (SLA) printing can integrate all of the necessary fabrication resources in one instrument, allowing highly versatile microfluidic devices to be made at low cost. In this paper, we report two microfabrication approaches of microfluidics utilizing (SLA) 3D printing technology: I) Direct SLA printing of channels and structures of a monolithic microfluidic POC device; II) Indirect fabrication, utilizing SLA 3D printed molds for PDMS based microfluidic device replication. Additionally, we discuss previous work providing a proof of concept of applications in POC diagnosis, using direct 3D printing fabrication (approach I). The robustness and simplicity of these protocols allow integrating 3D design and microfabrication with smartphone-based disease diagnosis as a stand-alone system, offering strong adaptability for establishing diagnostic capacity in resource-limited areas and low-income countries.

Biosensors ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 133
Author(s):  
Benjamin Heidt ◽  
Williane Siqueira ◽  
Kasper Eersels ◽  
Hanne Diliën ◽  
Bart van Grinsven ◽  
...  

Point of care (PoC) diagnostics are at the focus of government initiatives, NGOs and fundamental research alike. In high-income countries, the hope is to streamline the diagnostic procedure, minimize costs and make healthcare processes more efficient and faster, which, in some cases, can be more a matter of convenience than necessity. However, in resource-limited settings such as low-income countries, PoC-diagnostics might be the only viable route, when the next laboratory is hours away. Therefore, it is especially important to focus research into novel diagnostics for these countries in order to alleviate suffering due to infectious disease. In this review, the current research describing the use of PoC diagnostics in resource-limited settings and the potential bottlenecks along the value chain that prevent their widespread application is summarized. To this end, we will look at literature that investigates different parts of the value chain, such as fundamental research and market economics, as well as actual use at healthcare providers. We aim to create an integrated picture of potential PoC barriers, from the first start of research at universities to patient treatment in the field. Results from the literature will be discussed with the aim to bring all important steps and aspects together in order to illustrate how effectively PoC is being used in low-income countries. In addition, we discuss what is needed to improve the situation further, in order to use this technology to its fullest advantage and avoid “leaks in the pipeline”, when a promising device fails to take the next step of the valorization pathway and is abandoned.


2021 ◽  
Vol 118 (30) ◽  
pp. e2106724118
Author(s):  
Lucas F. de Lima ◽  
André L. Ferreira ◽  
Marcelo D. T. Torres ◽  
William R. de Araujo ◽  
Cesar de la Fuente-Nunez

COVID-19 has led to over 3.47 million deaths worldwide and continues to devastate primarily middle- and low-income countries. High-frequency testing has been proposed as a potential solution to prevent outbreaks. However, current tests are not sufficiently low-cost, rapid, or scalable to enable broad COVID-19 testing. Here, we describe LEAD (Low-cost Electrochemical Advanced Diagnostic), a diagnostic test that detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 6.5 min and costs $1.50 per unit to produce using easily accessible and commercially available materials. LEAD is highly sensitive toward SARS-CoV-2 spike protein (limit of detection = 229 fg⋅mL−1) and displays an excellent performance profile using clinical saliva (100.0% sensitivity, 100.0% specificity, and 100.0% accuracy) and nasopharyngeal/oropharyngeal (88.7% sensitivity, 86.0% specificity, and 87.4% accuracy) samples. No cross-reactivity was detected with other coronavirus or influenza strains. Importantly, LEAD also successfully diagnosed the highly contagious SARS-CoV-2 B.1.1.7 UK variant. The device presents high reproducibility under all conditions tested and preserves its original sensitivity for 5 d when stored at 4 °C in phosphate-buffered saline. Our low-cost and do-it-yourself technology opens new avenues to facilitate high-frequency testing and access to much-needed diagnostic tests in resource-limited settings and low-income communities.


2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Vivian Avelino-silva ◽  
Aggrey Semeere ◽  
Miriam Laker-Oketta ◽  
Helen Byakwaga ◽  
Mark Pletcher ◽  
...  

Abstract Focus of Presentation Many low-income countries cannot support faculty to develop contemporary graduate-level courses in epidemiology and biostatistics. There are also insufficient resources to support all students who are interested in traveling abroad to study in resource-rich settings. To address this, we describe our experience with training a few students from resource-limited countries in the U.S. who have subsequently returned to their home countries and became instructors in a novel online plus in-person teaching model. Findings Most courses at our major U.S. training program in epidemiology videotape lectures for viewing on one’s own and post all other materials (e.g., homework) on the course’s website. The weekly learning cycle culminates with an in-person high-level small group discussion, led by a faculty member who facilitates 10-15 students. For the past 5 years, non-U.S. scholars from Africa and South America who have taken our courses in the U.S. have travelled back to their countries and become small group leaders for our courses. Identical to U.S. students, the students in these international venues view videotaped lectures, access other materials online, and have weekly in-person small group discussions. These international students represent another concurrent small group for the U.S-based course; they have identical access and evaluation. Conclusions By pairing online resources from a resource-rich setting with local in-person instruction, we provide students in resource-limited settings access to contemporary instruction in epidemiology at very low cost. Key messages Online plus local in-person teaching is a feasible model for providing instruction regarding epidemiologic methods in resource-limited settings.


Neurology ◽  
2019 ◽  
Vol 93 (4) ◽  
pp. 176-180 ◽  
Author(s):  
Farrah J. Mateen

This position piece is meant to extend the humanitarian argument for assisting people with multiple sclerosis (MS) in resource-limited settings, in this case, through research. It is also meant to highlight areas of strength of some low- and middle-income countries (LMICs), and therefore emphasize how the field of MS could best be served globally by more research with and for resource-limited populations. Possible areas of particular strength include (1) ethnicity, genetic diversity, and migration studies; (2) analysis of possibly emerging environmental and lifestyle-related risk factors; (3) understanding the immune system when exposed to novel pathogens and various infectious agents; (4) reverse innovation to promote better point-of-care diagnostic tests; (5) high participation rates in clinical registries and research; (6) appreciation of MS in special populations including a higher focus on pediatrics and pregnancy; (7) culturally adept means of treatment and rehabilitating disability; (8) models of care delivery for chronic, complex neurologic diseases; and (9) use of off-label, generic, and less commonly implemented disease-modifying therapy sequences. Strategies for strengthening the MS research landscape include (1) creation of centers of research excellence in LMICs and twinning of institutions between high- and low-income countries; (2) standardization of research procedures and reduction of bureaucracies; (3) consensus meetings and network building; (4) opening additional avenues for publications and expanding the types of available publications; (5) identifying and establishing dedicated funding mechanisms; (6) focus on local relevance; and (7) setting expectations to include patients from LMICs in international clinical trials. These underutilized opportunities build an argument that global partnerships for research and knowledge coordination could better reach across populations, geographies, economies, and expertise.


Informatics ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 63
Author(s):  
Olawande Daramola ◽  
Peter Nyasulu ◽  
Tivani Mashamba-Thompson ◽  
Thomas Moser ◽  
Sean Broomhead ◽  
...  

A conceptual artificial intelligence (AI)-enabled framework is presented in this study involving triangulation of various diagnostic methods for management of coronavirus disease 2019 (COVID-19) and its associated comorbidities in resource-limited settings (RLS). The proposed AI-enabled framework will afford capabilities to harness low-cost polymerase chain reaction (PCR)-based molecular diagnostics, radiological image-based assessments, and end-user provided information for the detection of COVID-19 cases and management of symptomatic patients. It will support self-data capture, clinical risk stratification, explanation-based intelligent recommendations for patient triage, disease diagnosis, patient treatment, contact tracing, and case management. This will enable communication with end-users in local languages through cheap and accessible means, such as WhatsApp/Telegram, social media, and SMS, with careful consideration of the need for personal data protection. The objective of the AI-enabled framework is to leverage multimodal diagnostics of COVID-19 and associated comorbidities in RLS for the diagnosis and management of COVID-19 cases and general support for pandemic recovery. We intend to test the feasibility of implementing the proposed framework through community engagement in sub-Saharan African (SSA) countries where many people are living with pre-existing comorbidities. A multimodal approach to disease diagnostics enabling access to point-of-care testing is required to reduce fragmentation of essential services across the continuum of COVID-19 care.


Sensors ◽  
2020 ◽  
Vol 20 (12) ◽  
pp. 3593
Author(s):  
Kushal Joshi ◽  
Vanessa Velasco ◽  
Rahim Esfandyarpour

Electrowetting on dielectric-based digital microfluidic platforms (EWOD-DMF) have a potential to impact point-of-care diagnostics. Conventionally, EWOD-DMF platforms are manufactured in cleanrooms by expert technicians using costly and time consuming micro-nanofabrication processes such as optical lithography, depositions and etching. However, such high-end microfabrication facilities are extremely challenging to establish in resource-poor and low-income countries, due to their high capital investment and operating costs. This makes the fabrication of EWOD-DMF platforms extremely challenging in low-income countries, where such platforms are most needed for many applications such as point-of-care testing applications. To address this challenge, we present a low-cost and simple fabrication procedure for EWOD-DMF electrode arrays, which can be performed anywhere with a commercial office inkjet printer without the need of expensive cleanroom facilities. We demonstrate the utility of our platform to move and mix droplets of different reagents and physiologically conductive buffers, thereby showing its capability to potentially perform a variety of biochemical assays. By combining our low-cost, inkjet-printed EWOD-DMF platform with smartphone imaging technology and a compact control system for droplet manipulation, we also demonstrate a portable and hand-held device which can be programmed to potentially perform a variety of biochemical assays.


2019 ◽  
Vol 11 (4) ◽  
pp. 314-315
Author(s):  
James S Leathers ◽  
Maria Belen Pisano ◽  
Viviana Re ◽  
Gertine van Oord ◽  
Amir Sultan ◽  
...  

Abstract Background Treatment of HCV with direct-acting antivirals has enabled the discussion of HCV eradication worldwide. Envisioning this aim requires implementation of mass screening in resource-limited areas, usually constrained by testing costs. Methods We validated a low-cost, rapid diagnosis test (RDT) for HCV in three different continents in 141 individuals. Results The HCV RDT showed 100% specificity and sensitivity across different samples regardless of genotype or viral load (in samples with such information, 90%). Conclusions The HCV test validated in this study can allow for HCV screening in areas of need when properly used.


Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1352
Author(s):  
Darius Riziki Martin ◽  
Nicole Remaliah Sibuyi ◽  
Phumuzile Dube ◽  
Adewale Oluwaseun Fadaka ◽  
Ruben Cloete ◽  
...  

The transmission of Tuberculosis (TB) is very rapid and the burden it places on health care systems is felt globally. The effective management and prevention of this disease requires that it is detected early. Current TB diagnostic approaches, such as the culture, sputum smear, skin tuberculin, and molecular tests are time-consuming, and some are unaffordable for low-income countries. Rapid tests for disease biomarker detection are mostly based on immunological assays that use antibodies which are costly to produce, have low sensitivity and stability. Aptamers can replace antibodies in these diagnostic tests for the development of new rapid tests that are more cost effective; more stable at high temperatures and therefore have a better shelf life; do not have batch-to-batch variations, and thus more consistently bind to a specific target with similar or higher specificity and selectivity and are therefore more reliable. Advancements in TB research, in particular the application of proteomics to identify TB specific biomarkers, led to the identification of a number of biomarker proteins, that can be used to develop aptamer-based diagnostic assays able to screen individuals at the point-of-care (POC) more efficiently in resource-limited settings.


Author(s):  
Antonia Perju ◽  
Nongnoot Wongkaew

AbstractLateral flow assays (LFAs) are the best-performing and best-known point-of-care tests worldwide. Over the last decade, they have experienced an increasing interest by researchers towards improving their analytical performance while maintaining their robust assay platform. Commercially, visual and optical detection strategies dominate, but it is especially the research on integrating electrochemical (EC) approaches that may have a chance to significantly improve an LFA’s performance that is needed in order to detect analytes reliably at lower concentrations than currently possible. In fact, EC-LFAs offer advantages in terms of quantitative determination, low-cost, high sensitivity, and even simple, label-free strategies. Here, the various configurations of EC-LFAs published are summarized and critically evaluated. In short, most of them rely on applying conventional transducers, e.g., screen-printed electrode, to ensure reliability of the assay, and additional advances are afforded by the beneficial features of nanomaterials. It is predicted that these will be further implemented in EC-LFAs as high-performance transducers. Considering the low cost of point-of-care devices, it becomes even more important to also identify strategies that efficiently integrate nanomaterials into EC-LFAs in a high-throughput manner while maintaining their favorable analytical performance.


Sensors ◽  
2021 ◽  
Vol 21 (11) ◽  
pp. 3774
Author(s):  
Pavlos Topalidis ◽  
Cristina Florea ◽  
Esther-Sevil Eigl ◽  
Anton Kurapov ◽  
Carlos Alberto Beltran Leon ◽  
...  

The purpose of the present study was to evaluate the performance of a low-cost commercial smartwatch, the Xiaomi Mi Band (MB), in extracting physical activity and sleep-related measures and show its potential use in addressing questions that require large-scale real-time data and/or intercultural data including low-income countries. We evaluated physical activity and sleep-related measures and discussed the potential application of such devices for large-scale step and sleep data acquisition. To that end, we conducted two separate studies. In Study 1, we evaluated the performance of MB by comparing it to the GT3X (ActiGraph, wGT3X-BT), a scientific actigraph used in research, as well as subjective sleep reports. In Study 2, we distributed the MB across four countries (Austria, Germany, Cuba, and Ukraine) and investigated physical activity and sleep among these countries. The results of Study 1 indicated that MB step counts correlated highly with the scientific GT3X device, but did display biases. In addition, the MB-derived wake-up and total-sleep-times showed high agreement with subjective reports, but partly deviated from GT3X predictions. Study 2 revealed similar MB step counts across countries, but significant later wake-up and bedtimes for Ukraine than the other countries. We hope that our studies will stimulate future large-scale sensor-based physical activity and sleep research studies, including various cultures.


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