Resource-limited settings present unique engineering challenges for medical diagnostics. Diagnosis is often needed for those unable to reach central healthcare systems, making portability and independence from traditional energy infrastructure essential device parameters. In 2014, our group presented a microfluidic device that performed a solar-powered variant of the polymerase chain reaction, which we called solar thermal PCR. In this work, we expand on our previous effort by presenting an integrated, portable, solar thermal PCR system targeted towards the diagnosis of Kaposi's sarcoma. We call this system KS-Detect, and we now report the system's performance as a diagnostic tool using pseudo-biopsy samples made from varying concentrations of human lymphoma cell lines positive for the KS herpesvirus (KSHV). KS-Detect achieved 83% sensitivity and 70% specificity at high (≥ 10%) KSHV+ cell concentrations when diagnosing pseudo-biopsy samples by smartphone image. Using histology, we confirm that our prepared pseudo-biopsies contain similar KSHV+ cell concentrations as human biopsies positive for KS. Through our testing of samples derived from human cell lines, we validate KS-Detect as a viable, portable KS diagnostic tool, and we identify critical engineering considerations for future solar-thermal PCR devices.

The use of point-of-care (POC) devices in limited resource settings where access to commonly used infrastructure, such as water and electricity, can be restricted represents simultaneously one of the best application fits for POC systems as well as one of the most challenging places to deploy them. Of the many challenges involved in these systems, the preparation and processing of complex samples like stool, vomit, and biopsies are particularly difficult due to the high number and varied nature of mechanical and chemical interferents present in the sample. Previously we have demonstrated the ability to use solar-thermal energy to perform PCR based nucleic acid amplifications. In this work demonstrate how the technique, using similar infrastructure, can also be used to perform solar-thermal based sample processing system for extracting and isolating Vibrio Cholerae nucleic acids from fecal samples. The use of opto-thermal energy enables the use of sunlight to drive thermal lysing reactions in large volumes without the need for external electrical power. Using the system demonstrate the ability to reach a 95°C threshold in less than 5 minutes and maintain a stable sample temperature of +/- 2°C following the ramp up. The system is demonstrated to provide linear results between 10(4) and 10(8) CFU/mL when the released nucleic acids were quantified via traditional means. Additionally, we couple the sample processing unit with our previously demonstrated solar-thermal PCR and tablet based detection system to demonstrate very low power sample-in-answer-out detection.

The rapid expansion of mobile technology is transforming the biomedical landscape. By 2016 there will be 260 M active smartphones in the US and millions of health accessories and software "apps" running off them. In parallel with this have come major technical achievements in lab-on-a-chip technology leading to incredible new biochemical sensors and molecular diagnostic devices. Despite these advancements, the uptake of lab-on-a-chip technologies at the consumer level has been somewhat limited. We believe that the widespread availability of smartphone technology and the capabilities they offer in terms of computation, communication, social networking, and imaging will be transformative to the deployment of lab-on-a-chip type technology both in the developed and developing world. In this paper we outline why we believe this is the case, the new business models that may emerge, and detail some specific application areas in which this synergy will have long term impact, namely: nutrition monitoring and disease diagnostics in limited resource settings.

Instruments that can do medical diagnoses at home or other places far from hospitals are the wave of the future. Optofluidic devices, some of which can be used with smartphones, have a part to play in this future.

Nucleic acid-based diagnostic techniques such as polymerase chain reaction (PCR) are used extensively in medical diagnostics due to their high sensitivity, specificity and quantification capability. In settings with limited infrastructure and unreliable electricity, however, access to such devices is often limited due to the highly specialized and energy-intensive nature of the thermal cycling process required for nucleic acid amplification. Here we integrate solar heating with microfluidics to eliminate thermal cycling power requirements as well as create a simple device infrastructure for PCR. Tests are completed in less than 30 min and power consumption is reduced to 80 mW, enabling a standard 5.5 Wh iPhone battery to provide 70 h of power to this system. Additionally, we demonstrate a complete sample-to-answer diagnostic strategy by analyzing human skin biopsies infected with Kaposi's Sarcoma herpesvirus (KSHV/HHV-8) through the combination of solar thermal PCR, HotSHOT DNA extraction and smartphone-based fluorescence detection. We believe that exploiting the ubiquity of solar thermal energy as demonstrated here could facilitate broad availability of nucleic acid-based diagnostics in resource-limited areas.

Kaposi's sarcoma (KS) is an infectious cancer occurring most commonly in human immunodeficiency virus (HIV) positive patients and in endemic regions, such as Sub-Saharan Africa, where KS is among the top four most prevalent cancers. The cause of KS is the Kaposi's sarcoma-associated herpesvirus (KSHV, also called HHV-8), an oncogenic herpesvirus that while routinely diagnosed in developed nations, provides challenges to developing world medical providers and point-of-care detection. A major challenge in the diagnosis of KS is the existence of a number of other diseases with similar clinical presentation and histopathological features, requiring the detection of KSHV in a biopsy sample. In this work we develop an answer to this challenge by creating a multiplexed one-pot detection system for KSHV DNA and DNA from a frequently confounding disease, bacillary angiomatosis. Gold and silver nanoparticle aggregation reactions are tuned for each target and a multi-color change system is developed capable of detecting both targets down to levels between 1 nM and 2 nM. The system developed here could later be integrated with microfluidic sample processing to create a final device capable of solving the two major challenges in point-of-care KS detection.

The utility of polymerase chain reaction (PCR) technology is significantly reduced in resource-limited settings partly due to high energy costs associated with thermal cycling. We introduce a solar-powered PCR technique in which sunlight is used to create a specific thermal profile compatible with PCR. We show preliminary results in which genomic DNA extracted from Kaposi's Sarcoma-associated herpesvirus is amplified. We also characterize the on-chip temperatures under different external temperatures to demonstrate its potential usability over a range of ambient conditions. By circumventing traditional power requirements, solar-powered PCR could help make PCR technology widely available in the developing world.

1 Department of Biomedical Engineering, Cornell University 2 Sibley School of Mechanical and Aerospace Engineering, Cornell University 3 Pathology and Laboratory Medicine, Weill Cornell Medical College ABSTRACT Kaposi’s sarcoma (KS) is the leading cancer in untreated Human immunodeficiency virus (HIV) infected individuals, effecting 1 in 20 patients. Two challenges present themselves in determining the presence of Kaposi’s sarcoma associated herpes virus (KSHV), the cause of KS: 1. The presence of similarly presenting diseases, such as Bacillary angiomatosis (BA) and 2. The detection of KSHV in biopsy samples. Here we show work on creating a multiplexed colorimetric detection scheme for KS and BA based on gold and silver nanoparticles as well as work on integrating this scheme with technology to lyse biopsy samples.

We introduce a highly flexible method for the assembly of microscale components using laser-activated bubble latching. Arbitrary structures are created through combining directed fluidic assembly and surface tension-driven latching. The bubbles are generated through laser degradation of the SU-8 tile. This gives the user control over the time and location of latching, as opposed to predefined latching locations in other microscale assembly methods. Shear force experiments show that each bubble is able to support a tensile force of 0.33μN. By utilizing the compressibility of bubbles, assembled objects are switched between rigid and flexible states, facilitating motion through irregular channel geometries. Further, through the use of bubble hinging at component corners, reconfiguration is quickly and effectively achieved. This novel hybrid approach to the assembly of microscale components offers significant controllability to the user.

Point-of-care diagnostics for resource limited settings is a much-researched application of microfluidics technology due to its great potential. Unfortunately, one of the current limitations is the difficulty in creating tools that are both inexpensive and simple to use but also able to perform complex tasks. Light-governed microfluidic systems are of interest because, in principle, sunlight could provide the power source to operate these tools, potentially allowing for increased functionality with minimal device complexity. Here, we study the use of light to perform both the fundamental function of fluid actuation and valving and the more sophisticated process of on-chip polymerase chain reaction (PCR). To facilitate light-driven flow, we use poly(N-isopropylacrylamide) (PNIPAAm), a “smart” polymer that changes wettability as a function of temperature. It is grafted onto a carbon black-polydimethylsiloxane (PDMS) surface, which absorbs light and converts it to heat, to produce various temperature profiles. We use this to create switchable hydrophobic and hydrophilic regions that respectively stop and activate flow and show that light can valve off flow within 4 s after illumination. We also perform continuous-flow PCR by fabricating PDMS lenses that concentrate light onto a carbon black layer to produce the necessary heat pattern, and demonstrate amplification of a 43bp segment of genomic DNA. These investigations show the potential for development of light-operated microfluidics to provide both the simple architecture and advanced functionality needed in point-of-care devices for low resource environments.

Light-based flow systems for point-of-care devices are of interest because, in principle, sunlight could be used to operate them, potentially allowing for high functionality with minimal device complexity and expense. A light-operated method to drive flow using poly(N-isopropylacrylamide), a 'smart' polymer that changes wettability as a function of temperature, is introduced. It is grafted onto a carbon black-polydimethylsiloxane surface, which converts light into a thermal pattern that valves flow at user-defined locations. Flow rates are demonstrated ranging from 4 μL min(-1) at 25 °C to 0.1 μL min(-1) at 40 °C. The valving dynamics are also characterised, and a response time of less than 4 s is shown. Light-operated flow could provide the simple architecture and advanced functionality needed in low-resource point-of-care devices.

Optofluidics is a rapidly advancing field that utilizes the integration of optics and microfluidics to provide a number of novel functionalities in microsystems. In this review, we discuss how this approach can potentially be applied to address some of the greatest challenges facing both the developing and developed world, including healthcare, food shortages, malnutrition, water purification, and energy. While medical diagnostics has received most of the attention to date, here we show that some other areas can also potentially benefit from optofluidic technology. Whenever possible we briefly describe how microsystems are currently used to address these problems and then explain why and how optofluidics can provide better solutions. The focus of the article is on the applications of optofluidic techniques in low-resource settings, but we also emphasize that some of these techniques, such as those related to food production, food safety assessment, nutrition monitoring, and energy production, could be very useful in well-developed areas as well.

This article introduces a method for microscale assembly using laser-activated bubble latching. The technique combines the advantages of directed fluidic assembly and surface tension-driven latching to create arbitrarily complex and irregular structures with unique properties. The bubble latches, generated through the laser degradation of the tile material, are created on the fly, reversibly linking components at user-determined locations. Different phases of latching bubble growth are analyzed, and shear force calculations show that each bubble is able to support a tensile force of approximately 0.33 μN. We demonstrate that by exploiting the compressibility of bubbles, assembled objects can be made to switch between rigid and flexible states, facilitating component assembly and transport. Furthermore, we show reconfiguration capabilities through the use of bubble hinging. This novel hybrid approach to the assembly of microscale components offers significant user control while retaining a simplistic design environment.