Challenges and opportunities of centrifugal microfluidics for extreme point-of-care testing

The advantages offered by centrifugal microfluidic systems have encouraged its rapid adaptation in the fields of in vitro diagnostics, clinical chemistry, immunoassays, and nucleic acid tests. Centrifugal microfluidic devices are currently used in both clinical and point-of-care settings. Recent studies have shown that this new diagnostic platform could be potentially used in extreme point-of-care settings like remote villages in the Indian subcontinent and in Africa. Several technological inventions have decentralized diagnostics in developing countries; however, very few microfluidic technologies have been successful in meeting the demand. By identifying the finest difference between the point-of-care testing and extreme point-of-care infrastructure, this review captures the evolving diagnostic needs of developing countries paired with infrastructural challenges with technological hurdles to healthcare delivery in extreme point-of-care settings. In particular, the requirements for making centrifugal diagnostic devices viable in developing countries are discussed based on a detailed analysis of the demands in different clinical settings including the distinctive needs of extreme point-of-care settings.ope

CD-based microfluidics for primary care in extreme point-of-care settings

We review the utility of centrifugal microfluidic technologies applied to point-of-care diagnosis in extremely under-resourced environments. The various challenges faced in these settings are showcased, using areas in India and Africa as examples. Measures for the ability of integrated devices to effectively address point-of-care challenges are highlighted, and centrifugal, often termed CD-based microfluidic technologies, technologies are presented as a promising platform to address these challenges. We describe the advantages of centrifugal liquid handling, as well as the ability of a standard CD player to perform a number of common laboratory tests, fulfilling the role of an integrated lab-on-a-CD. Innovative centrifugal approaches for point-of-care in extremely resource-poor settings are highlighted, including sensing and detection strategies, smart power sources and biomimetic inspiration for environmental control. The evolution of centrifugal microfluidics, along with examples of commercial and advanced prototype centrifugal microfluidic systems, is presented, illustrating the success of deployment at the point-of-care. A close fit of emerging centrifugal systems to address a critical panel of tests for under-resourced clinic settings, formulated by medical experts, is demonstrated. This emphasizes the potential of centrifugal microfluidic technologies to be applied effectively to extremely challenging point-of-care scenarios and in playing a role in improving primary care in resource-limited settings across the developing world

Evaluating carbon-electrode dielectrophoresis under the ASSURED criteria

Extreme point-of-care refers to medical testing in unfavorable conditions characterized by a lack of primary resources or infrastructure. As witnessed in the recent past, considerable interest in developing devices and technologies exists for extreme point-of-care applications, for which the World Health Organization has introduced a set of encouraging and regulating guidelines. These are referred to as the ASSURED criteria, an acronym for Affordable (A), Sensitive (S), Specific (S), User friendly (U), Rapid and Robust (R), Equipment-free (E), and Delivered (D). However, the current extreme point of care devices may require an intermediate sample preparation step for performing complex biomedical analysis, including the diagnosis of rare-cell diseases and early-stage detection of sepsis. This article assesses the potential of carbon-electrode dielectrophoresis (CarbonDEP) for sample preparation competent in extreme point-of-care, following the ASSURED criteria. We first discuss the theory and utility of dielectrophoresis (DEP) and the advantages of using carbon microelectrodes for this purpose. We then critically review the literature relevant to the use of CarbonDEP for bioparticle manipulation under the scope of the ASSURED criteria. Lastly, we offer a perspective on the roadmap needed to strengthen the use of CarbonDEP in extreme point-of-care applications

Advances in Microfluidics Technology for Diagnostics and Detection

Microfluidics and lab-on-a-chip have, in recent years, come to the forefront in diagnostics and detection. At point-of-care, in the emergency room, and at the hospital bed or GP clinic, lab-on-a-chip offers the potential to rapidly detect time-critical and life-threatening diseases such as sepsis and bacterial meningitis. Furthermore, portable and user-friendly diagnostic platforms can enable disease diagnostics and detection in resource-poor settings where centralised laboratory facilities may not be available. At point-of-use, microfluidics and lab-on-chip can be applied in the field to rapidly identify plant pathogens, thus reducing the need for damaging broad spectrum pesticides while also reducing food losses. Microfluidics can also be applied to the continuous monitoring of water quality and can support policy-makers and protection agencies in protecting the environment. Perhaps most excitingly, microfluidics also offers the potential to enable entirely new diagnostic tests that cannot be implemented using conventional laboratory tools. Examples of microfluidics at the frontier of new medical diagnostic tests include early detection of cancers through circulating tumour cells (CTCs) and highly sensitive genetic tests using droplet-based digital PCR.This Special Issue on “Advances in Microfluidics Technology for Diagnostics and Detection” aims to gather outstanding research and to carry out comprehensive coverage of all aspects related to microfluidics in diagnostics and detection

mHealth-Based Microfluidic Lab-on-a-Chip for International Health Security

The increasing threats of emerging and reemerging infectious disease outbreaks demand research and development (R&D) of effective and fit-for-all-purpose tools and technologies for international public health security. Recent advances in biomedical engineering, mostly related to the convergence of communication and network technology in health, i.e., mobile health with microfluidic Lab-on-a-Chip technology can improve the international public health crises and employ in international public health security. Lab-on-a-Chip technology is now commonly found in most research centers, hospitals, and clinics where health care infrastructure is weak, and access to quality and timely medical care is challenging. Microfluidic devices—also known as Lab-on-a-Chip (LoC)—are an alternative for accessible, cost-effective, and early detection medical trials. The mHealth-based microfluidic LoC technology has been under rapid development, and they are becoming influential tools in a wide range of biomedical research and international public health applications. The perspective in this chapter demonstrates a potentially transformative opportunity for the deployment of mHealth with LoC with the fabrication protocols and their potential for strengthening and improving the international public health security. This attempt is not conclusive and exhaustive, and it is anticipated that such a discussion will enable the exchange of ideas between biomedical engineering, microfluidic LoC technology professionals, international public health, and health security experts

Biosensing on the centrifugal microfluidic lab-on-a-Disc platform

Lab-on-a-Disc (LoaD) biosensors are increasingly a promising solution for many biosensing applications. In the search for a perfect match between point-of-care (PoC) microfluidic devices and biosensors, the LoaD platform has the potential to be reliable, sensitive, low-cost, and easy-to-use. The present global pandemic draws attention to the importance of rapid sample-to-answer PoC devices for minimising manual intervention and sample manipulation, thus increasing the safety of the health professional while minimising the chances of sample contamination. A biosensor is defined by its ability to measure an analyte by converting a biological binding event to tangible analytical data. With evolving manufacturing processes for both LoaDs and biosensors, it is becoming more feasible to embed biosensors within the platform and/or to pair the microfluidic cartridges with low-cost detection systems. This review considers the basics of the centrifugal microfluidics and describes recent developments in common biosensing methods and novel technologies for fluidic control and automation. Finally, an overview of current devices on the market is provided. This review will guide scientists who want to initiate research in LoaD PoC devices as well as providing valuable reference material to researchers active in the field

A centrifugal microfluidic platform for capturing, assaying and manipulation of beads and biological cells

Microfluidics is deemed a field with great opportunities, especially for applications in medical diagnostics. The vision is to miniaturize processes typically performed in a central clinical lab into small, simple to use devices - so called lab-on-a-chip (LOC) systems. A wide variety of concepts for liquid actuation have been developed, including pressure driven flow, electro-osmotic actuation or capillary driven methods. This work is based on the centrifugal platform (lab-on-a-disc). Fluid actuation is performed by the forces induced due to the rotation of the disc, thus eliminating the need for external pumps since only a spindle motor is necessary to rotate the disc and propel the liquids inside of the micro structures. Lab-on-a-disc systems are especially promising for point-of-care applications involving particles or cells due to the centrifugal force present in a rotating system. Capturing, assaying and identification of biological cells and microparticles are important operations for lab-on-a-disc platforms, and the focus of this work is to provide novel building blocks towards an integrated system for cell and particle based assays. As a main outcome of my work, a novel particle capturing and manipulation scheme on a centrifugal microfluidic platform has been developed. To capture particles (biological cells or micro-beads) I designed an array of V-shaped micro cups and characterized it. Particles sediment under stagnant flow conditions into the array where they are then mechanically trapped in spatially well-defined locations. Due to the absence of flow during the capturing process, i.e. particle sedimentation is driven by the artificial gravity field on the centrifugal platform, the capture efficiency of this approach is close to 100% which is notably higher than values reported for typical pressure driven systems. After capturing the particles, the surrounding medium can easily be exchanged to expose them to various conditions such as staining solutions or washing buffers, and thus perform assays on the captured particles. By scale matching the size of the capturing elements to the size of the particles, sharply peaked single occupancy can be achieved. Since all particles are arrayed in the same focal plane in spatially well defined locations, operations such as counting or fluorescent detection can be performed easily. The application of this platform to perform multiplexed bead-based immunoassays as well as the discrimination of various cell types based on intra cellular and membrane based markers using fluorescently tagged antibodies is demonstrated. Additionally, methods to manipulate captured particles either in batch mode or on an individual particle level have been developed and characterized. Batch release of captured particles is performed by a novel magnetic actuator which is solely controlled by the rotation frequency of the disc. Furthermore, the application of this actuator to rapidly mix liquids is shown. Manipulation of individual particles is performed using an optical tweezers setup which has been developed as part of this work. Additionally, this optical module also provides fluorescence detection capabilities. This is the first time that optical tweezers have been combined with a centrifugal microfluidic system. This work presents the core technology for an integrated centrifugal platform to perform cell and particle based assays for fundamental research as well as for point-of- care applications. The key outputs of my specific work are: 1. Design, fabrication and characterization of a novel particle capturing scheme on a centrifugal microfluidic platform (V-cups) with very high capture efficiency (close to 100%) and sharply peaked single occupancy (up to 99.7% single occupancy). 2. A novel rotation frequency controlled magnetic actuator for releasing captured particles as well as for rapidly mixing liquids has been developed, manufactured and characterized. 3. The V-cup platform has successfully been employed to capture cells and perform multi-step antibody staining assays for cell discrimination. 4. An optical tweezers setup has been built and integrated into a centrifugal teststand, and successful manipulation of individual particles trapped in the V-cup array is demonstrated

Microfluidics for Biosensing

There are 12 papers published with 8 research articles, 3 review articles and 1 perspective. The topics cover: Biomedical microfluidics Lab-on-a-chip Miniaturized systems for chemistry and life science (MicroTAS) Biosensor development and characteristics Imaging and other detection technologies Imaging and signal processing Point-of-care testing microdevices Food and water quality testing and control We hope this collection could promote the development of microfluidics and point-of-care testing (POCT) devices for biosensing