Sheathless hydrodynamic positioning of buoyant drops and bubbles inside microchannels

Particles, bubbles, and drops carried by a fluid in a confined environment such as a pipe can be subjected to hydrodynamic lift forces, i.e., forces that are perpendicular to the direction of the flow. We investigated the positioning effect of lift forces acting on buoyant drops and bubbles suspended in a carrier fluid and flowing in a horizontal microchannel. We report experiments on drops of water in fluorocarbon liquid, and on bubbles of nitrogen in hydrocarbon liquid and silicone oil, inside microchannels with widths on the order of 0.1–1 mm. Despite their buoyancy, drops and bubbles could travel without contacting with the walls of channels; the most important parameters for reaching this flow regime in our experiments were the viscosity and the velocity of the carrier fluid, and the sizes of drops and bubbles. The dependencies of the transverse position of drops and bubbles on these parameters were investigated. At steady state, the trajectories of drops and bubbles approached the center of the channel for drops and bubbles almost as large as the channel, carried by rapidly flowing viscous liquids; among our experiments, these flow conditions were characterized by larger capillary numbers and smaller Reynolds numbers. Analytical models of lift forces developed for the flow of drops much smaller than the width of the channel failed to predict their transverse position, while computational fluid dynamic simulations of the experiments agreed better with the experimental measurements. The degrees of success of these predictions indicate the importance of confinement on generating strong hydrodynamic lift forces. We conclude that, inside microfluidic channels, it is possible to support and position buoyant drops and bubbles simply by flowing a single-stream (i.e., “sheathless”) carrier liquid that has appropriate velocity and hydrodynamic properties.Chemistry and Chemical Biolog

Design and Implementation of Position-Encoded Microfluidic Microsphere-Trap Arrays

Microarray devices are useful for detecting and analyzing biological targets, such as DNAs, mRNAs, proteins, etc. Applications of microarrays range from fundamental research to clinical diagnostics and drug discovery. In this dissertation, we consider a microsphere array device with predetermined positions of the microspheres. The microspheres are conjugate on their surfaces with molecular probes to capture the targets, and the targets are identified by the microspheres\u27 positions. We implement the microsphere arrays by employing microfluidic technology and a hydrodynamic trapping mechanism. We call our device microfluidic microsphere-trap arrays. To fully realize the potential of the device in biomedical applications, we utilize statistical performance analysis, mathematical optimization, and finite element fluid dynamics simulations to optimize device design, fabrication, and implementation. Our device is promising as a cost-effective and point-of-care lab-on-a-chip system. We first analyze the statistical performance of position-encoded microsphere arrays in imaging biological targets at different signal-to-noise ratio (SNR) levels. We compute the Ziv-Zakai bound (ZZB) on the errors in estimating the unknown parameters, including the target concentrations. Through numerical examples, we find the SNR level below which the ZZB provides a more accurate prediction of the error than the posterior Cramer-Rao bound (PCRB) does. We further apply the ZZB to select the optimal design parameters, such as the distance between the microspheres, and to investigate the effects of the experimental variables such as the microscope point-spread function. We implement the arrays by using microfluidic technology and hydrodynamic trapping. We design a novel geometric structure for the device, and develop a comprehensive and robust framework to optimize its geometric parameters that maximize the microsphere arrays\u27 packing density. We also simultaneously optimize multiple criteria, such as high microsphere trapping efficiency and low fluidic and imaging errors. Microsphere-trapping experiments performed using the optimized device and an un-optimized device demonstrate easy control of the microspheres\u27 transportation and manipulation in the optimized device. They also show that the optimized device greatly outperforms the un-optimized one. We extend our optimization framework to build a device that enables simultaneous, efficient, and accurate screening of multiple targets in a single microfluidic channel, by immobilizing different-sized microspheres at different regions. Different biomolecules captured on the surfaces of the different-sized microspheres can thus be detected simultaneously by the microspheres\u27 positions. We employ finite element fluid dynamics simulations to investigate hydrodynamic trapping of microspheres, and to study the effects of the geometric parameters and critical fluid velocity. The accuracy of the time-dependent simulations is validated by experimental results. The simulations guide the device design and experimental operation. The guidelines on the simulation set-up and the openly available model will help researchers apply the simulation to similar microfluidic systems that may accommodate a variety of structured particles

Digital CMOS ISFET architectures and algorithmic methods for point-of-care diagnostics

Over the past decade, the surge of infectious diseases outbreaks across the globe is redefining how healthcare is provided and delivered to patients, with a clear trend towards distributed diagnosis at the Point-of-Care (PoC). In this context, Ion-Sensitive Field Effect Transistors (ISFETs) fabricated on standard CMOS technology have emerged as a promising solution to achieve a precise, deliverable and inexpensive platform that could be deployed worldwide to provide a rapid diagnosis of infectious diseases. This thesis presents advancements for the future of ISFET-based PoC diagnostic platforms, proposing and implementing a set of hardware and software methodologies to overcome its main challenges and enhance its sensing capabilities. The first part of this thesis focuses on novel hardware architectures that enable direct integration with computational capabilities while providing pixel programmability and adaptability required to overcome pressing challenges on ISFET-based PoC platforms. This section explores oscillator-based ISFET architectures, a set of sensing front-ends that encodes the chemical information on the duty cycle of a PWM signal. Two initial architectures are proposed and fabricated in AMS 0.35um, confirming multiple degrees of programmability and potential for multi-sensing. One of these architectures is optimised to create a dual-sensing pixel capable of sensing both temperature and chemical information on the same spatial point while modulating this information simultaneously on a single waveform. This dual-sensing capability, verified in silico using TSMC 0.18um process, is vital for DNA-based diagnosis where protocols such as LAMP or PCR require precise thermal control. The COVID-19 pandemic highlighted the need for a deliverable diagnosis that perform nucleic acid amplification tests at the PoC, requiring minimal footprint by integrating sensing and computational capabilities. In response to this challenge, a paradigm shift is proposed, advocating for integrating all elements of the portable diagnostic platform under a single piece of silicon, realising a ``Diagnosis-on-a-Chip". This approach is enabled by a novel Digital ISFET Pixel that integrates both ADC and memory with sensing elements on each pixel, enhancing its parallelism. Furthermore, this architecture removes the need for external instrumentation or memories and facilitates its integration with computational capabilities on-chip, such as the proposed ARM Cortex M3 system. These computational capabilities need to be complemented with software methods that enable sensing enhancement and new applications using ISFET arrays. The second part of this thesis is devoted to these methods. Leveraging the programmability capabilities available on oscillator-based architectures, various digital signal processing algorithms are implemented to overcome the most urgent ISFET non-idealities, such as trapped charge, drift and chemical noise. These methods enable fast trapped charge cancellation and enhanced dynamic range through real-time drift compensation, achieving over 36 hours of continuous monitoring without pixel saturation. Furthermore, the recent development of data-driven models and software methods open a wide range of opportunities for ISFET sensing and beyond. In the last section of this thesis, two examples of these opportunities are explored: the optimisation of image compression algorithms on chemical images generated by an ultra-high frame-rate ISFET array; and a proposed paradigm shift on surface Electromyography (sEMG) signals, moving from data-harvesting to information-focused sensing. These examples represent an initial step forward on a journey towards a new generation of miniaturised, precise and efficient sensors for PoC diagnostics.Open Acces

Ono: an open platform for social robotics

In recent times, the focal point of research in robotics has shifted from industrial ro- bots toward robots that interact with humans in an intuitive and safe manner. This evolution has resulted in the subfield of social robotics, which pertains to robots that function in a human environment and that can communicate with humans in an int- uitive way, e.g. with facial expressions. Social robots have the potential to impact many different aspects of our lives, but one particularly promising application is the use of robots in therapy, such as the treatment of children with autism. Unfortunately, many of the existing social robots are neither suited for practical use in therapy nor for large scale studies, mainly because they are expensive, one-of-a-kind robots that are hard to modify to suit a specific need. We created Ono, a social robotics platform, to tackle these issues. Ono is composed entirely from off-the-shelf components and cheap materials, and can be built at a local FabLab at the fraction of the cost of other robots. Ono is also entirely open source and the modular design further encourages modification and reuse of parts of the platform

Electrochemical microfluidic multiplexed biosensor platform for point-of-care testing

Early and accurate diagnosis of a specific disease plays a decisive role for its effective treatment. However, in many cases the clinical findings, based on a single biomarker detection alone, are not sufficient for the appropriate diagnosis as well as monitoring of its treatment. Furthermore, it is highly desirable to screen multi-analytes (e.g. various diseases and drugs) at the same time enabling a low-cost, quick and reliable quantification. Thus, multiplexing, simultaneous detection of different analytes from a single sample, has become in recent years essential for diagnostics, especially for point-of-care testing (POCT). This thesis focuses on the scientific issue regarding the sensitivity enhancement of microfluidic biosensor platforms. Simulations, design studies and experiments are employed to investigate the interplay between the immobilization area and the resulting sensitivity. Thereby, a novel concept comprising design rules for microfluidic biosensors using the stop-flow technique has been introduced. In combination with different technical measures it allows the realization of an electrochemical lab-on-a-chip (LOC) platform for the fast, sensitive and simultaneous POCT in clinically relevant samples. This system employs a universally applicable, bioaffinity based biomolecule immobilization along with an amperometric readout. By means of the dry film photoresist technology, the fabrication of disposable microfluidic biosensors is enabled with high yield on wafer-level. The presented LOC platform offers three different biosensors with a microfluidic channel network of two, four or eight discrete immobilization sections, each with a volume of 680  nl. They can be actuated by individual channel inlets allowing a high flexibility in the assay design with respect to its format (e.g. competitive) and its technology (e.g. genomics). The feasibility for multiplexing is successfully demonstrated with DNA-based antibiotic assays for tetracycline and streptogramin, both important growth promoters in livestock breeding. The extensive usage of antibiotics is one of the major causes of the multi-drug-resistant bacteria and so, it has to be kept under surveillance. This platform allows the simultaneous POCT of different antibiotics from human plasma along with a limit of detection of less than 10  ng  ml⁻¹, a wide working range up to 1,600  ng ml⁻¹ and inter-assay precisions of about 10  %. Moreover, the microfluidic LOC system provides a low consumption of reagent and sample, reduces the total assay time drastically with a sample-to-result time of only 10  min. The shelf-life of the biosensors is proven to be at least 3 months at +4  °C. The introduced design concept with specific technical measures facilitates the implementation of microfluidic multiplexed biosensors in a low-cost, compact, and at the same time sensitive manner. This platform targets the POCT in the first place, yet, owing to its multiplexing approach it can be expanded for in vitro diagnostics

Modification and Optimization of Conducting Polymer-Modified, Redox-Magnetohydrodynamics (R-MHD) Pumping for Enhanced and Sustained Microfluidics Applications

In this work, a novel microfluidic pumping approach, redox-magnetohydrodynamics (R-MHD) has improved by materials and device optimization to use in lab-on-a-chip applications. In R-MHD, magnetic flux (B) and ionic current density (j) interacts to generate body force (FB) in between active electrodes, according to the equation FB = j×B. This unique fluid pumping approach is scalable, tunable, generates flat flow profile, and does not require any channels or valves. Pumping performance, such as speed scales with the ionic current density (j) and duration depends on the total charge (Q). The ionic current density (j) results from the conversion of electronic current through redox reactions of a conducting polymer like PEDOT (poly-EDOT). The enhancement of j can be obtained by the modification of polymer morphology. Therefore, electropolymerization parameters such as solvent, monomer, electrolyte, and deposition method have been optimized to improve the electrochemical performance of PEDOT. Electrodeposited PEDOT film from propylene carbonate solvent and TBAPF6 electrolyte generated a maximum of 820 µm/s flow velocity and 210 s flow duration. This enhanced system used as an imaging cytometer by coupling with a light sheet confocal microscope. This microfluidic imaging platform was able to differentiate various leukocytes cells with ~ 5000 cell/s theoretical throughput and 0.6 µm image resolution. As, our existing microscope could not analyze the R-MHD velocity profile in height direction, astigmatism particle tracking velocimetry (APTV) was employed to analyze flow profiles in three dimensions. In a microfluidic setup, flow profile is dominated by stream wise component but with no significant contributions in y and z direction. Though we achieved significant improvement in fluidic speed, flow duration was still dependent upon the total charge. Therefore, an automated magnet switching device was built which synchronized the current and magnetic field to push fluid in single direction, for unlimited time

Mixing and internal dynamics of droplets impacting and coalescing on a solid surface.

The coalescence and mixing of a sessile and an impacting liquid droplet on a solid surface are studied experimentally and numerically in terms of lateral separation and droplet speed. Two droplet generators are used to produce differently colored droplets. Two high-speed imaging systems are used to investigate the impact and coalescence of the droplets in color from a side view with a simultaneous gray-scale view from below. Millimeter-sized droplets were used with dynamical conditions, based on the Reynolds and Weber numbers, relevant to microfluidics and commercial inkjet printing. Experimental measurements of advancing and receding static contact angles are used to calibrate a contact angle hysteresis model within a lattice Boltzmann framework, which is shown to capture the observed dynamics qualitatively and the final droplet configuration quantitatively. Our results show that no detectable mixing occurs during impact and coalescence of similar-sized droplets, but when the sessile droplet is sufficiently larger than the impacting droplet vortex ring generation can be observed. Finally we show how a gradient of wettability on the substrate can potentially enhance mixing.This work was supported by the Engineering and Physical Sciences Research Council (Grant No. EP/H018913/, Innovation in industrial inkjet technology) and the KACST-Cambridge Research Centre.This is the accepted version of the original article published in Physical Review E and available online here: http://link.aps.org/doi/10.1103/PhysRevE.88.023023