Curtis D. Chin

Lab-on-a-chip devices for global health: Past studies and future opportunities

A rapidly emerging field in lab-on-a-chip (LOC) research is the development of devices to improve the health of people in developing countries. In this review, we identify diseases that are most in need of new health technologies, discuss special design criteria for LOC devices to be deployed in a variety of resource-poor settings, and review past research into LOC devices for global health. We focus mainly on diagnostics, the nearest-term application in this field.

A smartphone dongle for diagnosis of infectious diseases at the point of care

A smartphone accessory can perform a point-of-care test that simultaneously detects three infectious disease markers from fingerprick whole blood in 15 min, as operated by health care workers trained on a software app. Dongle + app = mobile test for sexually transmitted diseases There are thousands of health-related “apps” for smartphones, from tracking sleep patterns to recording heart rate to logging caloric intake. The power of such apps in connecting resource-limited communities to health care workers and, in turn, to proper and immediate care is now emerging. In this issue, Laksanasopin and colleagues describe a microfluidic-based diagnostic test for HIV and syphilis that attaches to (and is powered by) the iPod’s headphone jack. The mobile test also comes complete with an easy-to-use app, flashing test results on-screen in under 15 min. The test is based on the standard immunoassay but uses gold-labeled antibodies to detect HIV and syphilis antigens in only 2 μl of whole blood, and then silver reagents to amplify the resulting signal. The authors deployed the dongle in Rwanda, testing its sensitivity and specificity on 96 patients. Evaluated side by side with the gold standard tests for HIV and syphilis, the dongle produced results with a sensitivity and specificity needed for making treatment decisions in the field. In a survey, a vast majority of patients reported satisfaction with dongle performance. After a few next-generation tweaks, including reducing the size of the dongle, the entire diagnostic package is ready for adoption in resource-poor clinics and communities, to improve detection of HIV and syphilis and empower health care workers to administer timely and appropriate treatments. This work demonstrates that a full laboratory-quality immunoassay can be run on a smartphone accessory. This low-cost dongle replicates all mechanical, optical, and electronic functions of a laboratory-based enzyme-linked immunosorbent assay (ELISA) without requiring any stored energy; all necessary power is drawn from a smartphone. Rwandan health care workers used the dongle to test whole blood obtained via fingerprick from 96 patients enrolling into care at prevention of mother-to-child transmission clinics or voluntary counseling and testing centers. The dongle performed a triplexed immunoassay not currently available in a single test format: HIV antibody, treponemal-specific antibody for syphilis, and nontreponemal antibody for active syphilis infection. In a blinded experiment, health care workers obtained diagnostic results in 15 min from our triplex test that rivaled the gold standard of laboratory-based HIV ELISA and rapid plasma reagin (a screening test for syphilis), with sensitivity of 92 to 100% and specificity of 79 to 100%, consistent with needs of current clinical algorithms. Patient preference for the dongle was 97% compared to laboratory-based tests, with most pointing to the convenience of obtaining quick results with a single fingerprick. This work suggests that coupling microfluidics with recent advances in consumer electronics can make certain laboratory-based diagnostics accessible to almost any population with access to smartphones.

Low-Cost Microdevices for Point-of-Care Testing

Microdevices enable clinical diagnostics to be miniaturized for use at the point-of-care (POC). Microdevices can be composed of microfilters, microchannels, microarrays, micropumps, microvalves, and microelectronics, and these mechanical and electrical components can be integrated onto chips to analyze and control biological objects at the microscale. The miniaturization of diagnostic tests offers many advantages over centralized laboratory testing, such as small reagent volumes, rapid analysis, small size, low power consumption, parallel analysis, and functional integration of multiple devices. Here, we review work on the development of microdevices to diagnose disease at POC settings.

A microfabricated porous collagen-based scaffold as prototype for skin substitutes.

An important element of artificial skin is a tissue scaffold that allows for fast host regeneration. We present a microfabrication strategy, based on gelling collagen-based components inside a microfluidic device, that produces well-controlled pore sizes inside the scaffold. This strategy can produce finely patterned tissue scaffolds of clinically relevant dimensions suitable for surgical handling. Compared to porous collagen-based sponges produced by lyophilization, microfabricated tissue scaffolds preserve the fibrous structure and ligand density of natural occurring collagen. A fibroblast migration assay revealed fast cellular migration through the pores, which is desired for rapid tissue ingrowth. Finally, we also demonstrate a strategy to use this microfabrication technique to build anatomically accurate, multi-component skin substitutes in a cost-effective manner.

Biotechnology for Global Health: Solutions for the Developing World

Identifying and developing emerging biotechnologies is important in improving health in the poorest nations because current health products and practices are generally not suited for their developing economies, their inadequate transport and power infrastructures, their largely rural populace, and their rugged and often tropical environments. Advances in biotechnology will more likely be valued and adopted as innovations in developing countries if they are suited to these challenging conditions. These innovations in health will favor a shift away from a centralized, curative-based framework towards a decentralized, prevention-based paradigm. In this article, advances in microfluidics and in vaccine delivery and storage are highlighted within the context of disease diagnosis and prevention in the developing world. 1 Curtis Chin is a PhD student in the Department of Biomedical Engineering at Columbia University. His research interests include microtechnologies for global health diagnostics and tissue engineering. He obtained his BS in Chemical Engineering from the Massachusetts Institute of Technology. He can be contacted at cdc2129@columbia.edu.

Analytical chemistry: Sweet solution to sensing

Glucose meters allow rapid and quantitative measurement of blood sugar levels for diabetes sufferers worldwide. Now a new method allows this proven technology to be used to quantify a much wider range of analytes.

Microfluidic point-of-care diagnostics for resource-poor environments

Point-of-care (POC) diagnostics have tremendous potential to improve human health in remote and resource-poor settings. However, the design criteria for diagnostic tests appropriate in settings with limited infrastructure are unique and challenging. Here we present a custom optical reader which quantifies silver absorbance from heterogeneous immunoassays. The reader is simple and low-cost and suited for POC diagnostics.

Analyte capture in microfluidic heterogeneous immunoassays

Despite the prevalence of microfluidic-based heterogeneous immunoassays, there is incomplete understanding of analyte capture parameters. This study presents computational results and corresponding experimental binding assays of analyte capture. Our results identify: 1) a “reagent-limited” regime, under constraints of finite sample volume and assay time; 2) a critical flow rate; 3) an increase in signal by using a short concentrated plug rather than a long dilute plug; 4) a requirement to eventually reach a reaction-limited operating regime to maximize the capture of analytes [1].