Affordable Fabrication of Conductive Electrodes and Dielectric Films for a Paper-based Digital Microfluidic Chip

In order to fabricate a digital microfluidic (DMF) chip, which requires a patterned array of electrodes coated with a dielectric film, we explored two simple methods: Ballpoint pen printing to generate the electrodes, and wrapping of a dielectric plastic film to coat the electrodes. For precise and programmable printing of the patterned electrodes, we used a digital plotter with a ballpoint pen filled with a silver nanoparticle (AgNP) ink. Instead of using conventional material deposition methods, such as chemical vapor deposition, printing, and spin coating, for fabricating the thin dielectric layer, we used a simple method in which we prepared a thin dielectric layer using pre-made linear, low-density polyethylene (LLDPE) plastic (17-μm thick) by simple wrapping. We then sealed it tightly with thin silicone oil layers so that it could be used as a DMF chip. Such a treated dielectric layer showed good electrowetting performance for a sessile drop without contact angle hysteresis under an applied voltage of less than 170 V. By using this straightforward fabrication method, we quickly and affordably fabricated a paper-based DMF chip and demonstrated the digital electrofluidic actuation and manipulation of drops

Automated sample preparation using adaptive digital microfluidics for lab-on-chip devices

2018 Summer.Includes bibliographical references.There have been many technological advances in the medical industry over the years giving doctors and researchers more information than ever before. Technology has allowed more sensitive and accurate sensors and has also driven the size of many sensor devices smaller while increasing sensitivity. However, while many aspects of technology have seen improvements, the sample preparation of biological tests has seen lagging development. The sample preparation stage is defined here as the extracting of required features from a given sample for the purpose of measurement. A simple example of this is the solid phase extraction of DNA from a blood sample to detect blood borne pathogens. While this process is common in laboratories, and has even been automated by large and expensive equipment, it is a difficult process to mimic in lab-on-chip (LoC) devices. Nucleic Acid isolation requires common bench top equipment such as pipettes, vortexers, and centrifuges. Current lab based methods also use relatively large amounts of reagents to perform the extraction adding to the cost of each test. There has been a lot of research improving sensing techniques proposed for Lab on Chip devices, but many sensing methods still require a sample preparation stage to extract desired features. Without a complimentary LoC sample preparation system, the diversity of LoC device remains limited. The results presented in this thesis demonstrate the general principle of digital microfluidic device and the use of such device in a small hand-held platform capable of performing many sample preparation tasks automatically, such as the extraction and isolation of DNA. Liquids are transported using a technique called Eletro-wetting on Dielectric (EWOD) and controlled via a programmable microprocessor. The programmable nature of the device allows it to be configured for a variety of tests for different industries. The device also requires a fraction of the liquids lab based methods use, which greatly reduces the cost per test. The results of this thesis show a promising step forward to more capable LoC devices

Portable High Throughput Digital Microfluidics and On-Chip Bacteria Cultures

An intelligent, portable, and high throughput digital microfluidic (DMF) system is developed. Chapter 1 introduces microfluidics and DMF systems. In Chapter 2, a low-cost and high resolution capacitive-to-digital converter integrated circuit is used for droplet position detection. A field-programmable gate array FPGA is used as the integrated logic hub of the system for highly reliable and efficient control of the circuit. In this chapter a fast-fabricating PCB (printed circuit board) substrate microfluidic system is proposed. Smaller actuation threshold voltages than those previously reported are obtained. Droplets (3 µL) are actuated using 200 V, 500 Hz DC pulses. Droplet positions can be detected and displayed on a PC-based 3D animation in real time. The actuators and the capacitance sensing circuits are implemented on one PCB to reduce the size of the system. In Chapter 3, an intelligent EWOD (electrowetting on dielectric) top plate control system is proposed. The dynamic top plate is controlled by a piezoelectric (PZT) cantilever structure. A high resolution laser displacement sensor is used to monitor the deflection of the top plate. The gap height optimization and the harmonic vibration significantly improve the droplet velocity and decrease the droplet minimum threshold actuation voltage. The top plate vibration induced actuation improvement is magnitude and frequency dependent. 100 µm and 200 µm vibrations are tested at 25 Hz. Vibration frequencies at 5 Hz, 10 Hz, and 20 Hz are tested while the magnitude is 200 µm. Results show greater improvements are achieved at larger vibration magnitudes and higher vibration frequencies. With a vibrated top plate, the largest reduction of the actuation voltage is 76 VRMS for a 2.0 µl DI water droplet. The maximum droplet instantaneous velocity is around 9.3 mm/s, which is almost 3 times faster than the droplet velocity without top plate vibration. Liquid that has different hysteresis such as acetonitrile with various concentrations are used as a control to show its compatibility with the proposed DMF chip. Contact line depinning under top plate vibration is observed, which indicates the underlying mechanism for the improvements in actuation velocity and threshold voltage. The top plate control technique reported in this study makes EWOD DMF chips more reliable for point of care diagnostics. In Chapter 4, the mechanisms of the improvements were investigated by observing the detailed changes in the contact angle hysteresis using both parallel and nonparallel top plates. In Chapter 5, on-chip cell cultures are used for anti-biotic resistant bacteria detection. The passively dispensed on-chip cell cultures realize the isolated micro environment electrochemistry measurement, shorten the culturing time, and reduce the required sample volume. The design of the next generation ultra-portable DMF system is covered in the Appendix. Detailed technical notes and hardware design is covered in the Appendix. The proposed portable and high throughput DMF system with on-chip cell cultures have a great potential to change the standards for micro-environment culturing technologies, which will significantly improve the efficiency of actuation, sensing, and detecting performance of the DMF systems

Motion control of water droplets by means of optical patterns imprinted on Fe:LiNbO3 crystals

Chemical and morphological surface patterning is very common in micro uidic devices to control the ow. In this project, the dynamics of water droplets moving on a iron-doped lithium niobate (Fe:LiNbO3) crystal which has been exposed to optical patterns produced by lenses will be studied. This optowetting technique will exploit the photovoltaic eect of lithium niobate, that creates surface charges upon illumination and enables the control of droplets without xed electrodes. To reduce the friction, the crystal surfaces will be covered with a micrometric lubricant lm (LIS) made of octadecyltrichlorosilane (OTS) impregnated with silicone oil that acts as hydrophobic dielectric layer. The behaviour of the LIS will be investigated by droplet sliding on glass and Fe:LiNbO3 substrates and compared with results from literature. The interaction between charged regions at the Fe:LiNbO3 surface and water will be proved by analyzing pendant droplets falling on the substrates due to the dielectrophoretic force. In the nal experiments, the motion of drops with dierent volumes on straight lines with dierent inclinations imprinted on samples tilted at dierent angles will be observed by means of video recordings

Lab-on-PCB Devices

Lab-on-PCB devices can be considered an emerging technology. In fact, most of the contributions have been published during the last 5 years. It is mainly focussed on both biomedical and electronic applications. The book includes an interesting guide for using the different layers of the Printed Circuit Boards for developing new devices; guidelines for fabricating PCB-based electrochemical biosensors, and an overview of fluid manipulation devices fabricated using Printed Circuit Boards. In addition, current PCB-based devices are reported, and studies for several aspects of research and development of lab-on-PCB devices are described

Micro- and Nanofluidics for Bionanoparticle Analysis

Bionanoparticles such as microorganisms and exosomes are recoganized as important targets for clinical applications, food safety, and environmental monitoring. Other nanoscale biological particles, includeing liposomes, micelles, and functionalized polymeric particles are widely used in nanomedicines. The recent deveopment of microfluidic and nanofluidic technologies has enabled the separation and anslysis of these species in a lab-on-a-chip platform, while there are still many challenges to address before these analytical tools can be adopted in practice. For example, the complex matrices within which these species reside in create a high background for their detection. Their small dimension and often low concentration demand creative strategies to amplify the sensing signal and enhance the detection speed. This Special Issue aims to recruit recent discoveries and developments of micro- and nanofluidic strategies for the processing and analysis of biological nanoparticles. The collection of papers will hopefully bring out more innovative ideas and fundamental insights to overcome the hurdles faced in the separation and detection of bionanoparticles

High-resolution 3D direct-write prototyping for healthcare applications

The healthcare sector has much to benefit from the vast array of novelties erupting from the manufacturing world. 3D printing (additive manufacturing) is amongst the most promising recent inventions with much research concentrated around the various approaches of 3D printing and applying this effectively in the health sector. Amongst these methods, the direct-write assembly approach is a promising candidate for rapid prototyping and manufacturing of miniaturised medical devices/sensors and in particular, miniaturised flexible capacitive pressure sensors. Microstructuring the dielectric medium of capacitive pressure sensors enhances the sensitivity of the capacitive pressure sensor. The structuring has been predominantly achieved with photolithography and similar subtractive approaches. In this project high-resolution 3D direct write printing was used to fabricate structured dielectric mediums for capacitive pressure sensors. This involved the development and rheological characterisation of printability-tuned water soluble polyvinyl pyrrolidone (PVP) based inks (10%-30% polymer content) for stable high-resolution 3D printing. These inks were used to print water soluble micromoulds that were filled and cured with otherwise difficult to structure low G’ materials like PDMS. Our approach essentially decouples ink synthesis from printability at the micrometre scale. The developed micro moulding approach was employed for printing pyramidal micro moulds, that were used as templates for fabricating pyramid structured dielectric mediums for capacitive pressure sensing. The power of the approach was used to alter the microstructures and reap enhanced pressure sensing characteristics for effective miniaturised capacitive pressure sensors. A pressure sensing ring – that could be worn by doctors and surgeons – was prototyped with our approach and employed successfully to monitor in real-time the radial pulse signal of a 29 year old male volunteer. The print resolution of the inks was enhanced by formulating and rheologically characterising a PVP/PVDF polymer blend ink that would wet the printing nozzle less due to the hydrophobicity of the PVDF

Methods for immobilizing receptors in microfluidic devices: A review

In this review article, we discuss state-of-the-art methods for immobilizing functional receptors in microfluidic devices. Strategies used to immobilize receptors in such devices are essential for the development of specific, sensitive (bio)chemical assays that can be used for a wide range of applications. In the first section, we review the principles and the chemistry of immobilization techniques that are the most commonly used in microfluidics. We afterward describe immobilization methods on static surfaces from microchannel surfaces to electrode surfaces with a particular attention to opportunities offered by hydrogel surfaces. Finally, we discuss immobilization methods on mobile surfaces with an emphasis on both magnetic and non-magnetic microbeads, and finally, we highlight recent developments of new types of mobile supports

Triboelectric Effect Enabled Self-Powered, Point-of-Care Diagnostics: Opportunities for developing ASSURED and REASSURED devices

The use of rapid point-of-care (PoC) diagnostics in conjunction with physiological signal monitoring has seen tremendous progress in their availability and uptake, particularly in low- and middle-income countries (LMICs). However, to truly overcome infrastructural and resource constraints, there is an urgent need for self-powered devices which can enable on-demand and/or continuous monitoring of patients. The past decade has seen the rapid rise of triboelectric nanogenerators (TENGs) as the choice for high-efficiency energy harvesting for developing self-powered systems as well as for use as sensors. This review provides an overview of the current state of the art of such wearable sensors and end-to-end solutions for physiological and biomarker monitoring. We further discuss the current constraints and bottlenecks of these devices and systems and provide an outlook on the development of TENG-enabled PoC/monitoring devices that could eventually meet criteria formulated specifically for use in LMICs.Ulster Universityhttp://www.mdpi.com/journal/micromachineshj2021Electrical, Electronic and Computer Engineerin

Development of an insitu quantitative measurement system for stress hormones : towards open microfluidic system

Personalized health diagnostic and monitoring has gained serious attention in recent years and one area of interest is the analysis of hormones which indicate increased stress levels. Cortisol (known also as hydrocortisone) and cortisone are steroid hormone (also known as stress hormones) that plays an important role in the regulation of many physiological processes such as glucose levels, blood pressure, and carbohydrate metabolism and they are considered as a potent biomarker for post-traumatic stress. The determination of stress hormones represents a challenge because their secretion follows a circadian rhythm (all day cycle) and their secretion are dependent on environmental and behavioral triggers. As a result, there is a need to develop a system for cheaply and rapidly monitoring their levels using approaches such as lab-on-a-chip (LOC) which combine high selectivity and sensitivity to provide valuable health informatics, not just in human but in animals such as fish being bred in a fish farm.Selectivity in these devices can be achieved utilising an immunoassay approach taking advantage of the lock and key mechanism that is related to the antibody-antigen interaction. In this work, a new immunoassay method was developed to measure the stress hormones which involved the reproducible immobilization of cortisol and cortisone antibodies onto a tin-doped indium oxide (ITO) electrode. This was achieved by modifying the electrode in a two process step; the deposition of a nitro group onto the ITO electrode followed by the reduction of the nitro group to amino group using cyclic voltammetry. This approach enables a good orientation of the antibody on the surface. The antibodies were then immobilized using an EDC/Sulfo-NHS linkage. To enable electrochemical detection the antibodies were tagged with ferrocene to give a redox tag. When square wave voltammetry was utilised the method gave good limits of detection (LOD) of 1.03 pg ml-1 for cortisol and 0.68 pg ml-1 for cortisone.The methodology was carried out using biological sample including Zebrafish whole- body sample and artificial saliva and reliable results were obtained without the need for complex extraction procedure.The results of the analysis suggest that the proposed method has promise for the routine detection of stress hormones, which gives a good reason to detect cortisol and cortisone based on a chemiluminescence immunoassay. The antibodies were immobilised using the electrochemical method but then chemiluminescence detection was selected due to its high sensitivity and the simple instrumentation required. A static system was first constructed using a micropipette to add the chemiluminescence reagents with the use of a CCD camera and image J software to capture the chemiluminescence. To achieve chemiluminescence detection the ferrocene tag on the antibodies was first oxidised and then this acted as a catalyst for luminol and hydrogen peroxide chemiluminescence reaction. Optimum conditions were investigated and 20 mM luminol and 10 mM hydrogen peroxide were used with a 200 seconds exposure to the camera and an incubation time of 30 minutes. Using this approach limits of detection were obtained of 0.47 pg ml-1 and 0.34 pg ml-1 also R2 0.9912 and 0.9902 for cortisol and cortisone respectively. The method was also applied to Zebrafish and artificial saliva without analyte extraction and good results were obtained.Once the successful chemiluminescence immunoassays had been developed it could be incorporated into in situ measurement devices. In this work, an open microfluidic approach was investigated to overcome the problems of blockages, high back pressure and air bubbles seen in closed microfluidic systems. A superhydrophobic ITO electrode substrate was prepared depending on the lotus leaf effect of extreme water repellence by the deposition of dichlorodimethylsilane (DCDMS) onto the substrate, followed by dip coating the hydrophobised ITO electrode into fumed silica nanoparticle suspensions to increase the hydrophobicity. Superhydrophilic patterns were then produced using a mask and a UV/ozone lamp. The wetting properties were investigated in detail using a drop shape analysis system. Optimum conditions for the formation of a homogeneous coating were established giving the following results; fumed silica suspension concentration 4%, dip coating velocity 3.18 cm min-1, and sonication time of 10 minutes. The results obtained from fluorescence microscopy showed the capability of fluid to flow along the superhydrophilic pattern acting as an open microfluidic channel.Finally, the open microfluidic approach was combined with the immobilisation procedure. Although further work will be needed to optimise the system, chemiluminescence detection was achieved when the chemiluminescence reagents were passed through the open microfluidic channels over the immobilised antibodies.To conclude an electrochemical immobilization platform has been exploited to reproducibly immobilize the antibodies and develop a quantitative novel chemiluminescence assay for stress hormone analysis in combination with an open microfluidic device