Test analysis & fault simulation of microfluidic systems

This work presents a design, simulation and test methodology for microfluidic systems, with particular focus on simulation for test. A Microfluidic Fault Simulator (MFS) has been created based around COMSOL which allows a fault-free system model to undergo fault injection and provide test measurements. A post MFS test analysis procedure is also described.A range of fault-free system simulations have been cross-validated to experimental work to gauge the accuracy of the fundamental simulation approach prior to further investigation and development of the simulation and test procedure.A generic mechanism, termed a fault block, has been developed to provide fault injection and a method of describing a low abstraction behavioural fault model within the system. This technique has allowed the creation of a fault library containing a range of different microfluidic fault conditions. Each of the fault models has been cross-validated to experimental conditions or published results to determine their accuracy.Two test methods, namely, impedance spectroscopy and Levich electro-chemical sensors have been investigated as general methods of microfluidic test, each of which has been shown to be sensitive to a multitude of fault. Each method has successfully been implemented within the simulation environment and each cross-validated by first-hand experimentation or published work.A test analysis procedure based around the Neyman-Pearson criterion has been developed to allow a probabilistic metric for each test applied for a given fault condition, providing a quantitive assessment of each test. These metrics are used to analyse the sensitivity of each test method, useful when determining which tests to employ in the final system. Furthermore, these probabilistic metrics may be combined to provide a fault coverage metric for the complete system.The complete MFS method has been applied to two system cases studies; a hydrodynamic “Y” channel and a flow cytometry system for prognosing head and neck cancer.Decision trees are trained based on the test measurement data and fault conditions as a means of classifying the systems fault condition state. The classification rules created by the decision trees may be displayed graphically or as a set of rules which can be loaded into test instrumentation. During the course of this research a high voltage power supply instrument has been developed to aid electro-osmotic experimentation and an impedance spectrometer to provide embedded test

ADVANCING THE SEPARATION SCIENCES THROUGH THE DELIVERY OF NEW MATERIALS, TECHNOLOGY AND METHODOLOGY.

A thesis and collection of works submitted to Plymouth University in partial fulfilment for the degree of DOCTOR OF SCIENC

Molecular Microfluidic Bioanalysis: Recent Progress in Preconcentration, Separation, and Detection

This chapter reviews the state-of-art of microfluidic devices for molecular bioanalysis with a focus on the key functionalities that have to be successfully integrated, such as preconcentration, separation, signal amplification, and detection. The first part focuses on both passive and electrophoretic separation/sorting methods, whereas the second part is devoted to miniaturized biosensors that are integrated in the last stage of the fluidic device

System Integration - A Major Step toward Lab on a Chip

Microfluidics holds great promise to revolutionize various areas of biological engineering, such as single cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Despite the fact that intensive efforts have been devoted into the field in the past decades, microfluidics has not yet been adopted widely. It is increasingly realized that an effective system integration strategy that is low cost and broadly applicable to various biological engineering situations is required to fully realize the potential of microfluidics. In this article, we review several promising system integration approaches for microfluidics and discuss their advantages, limitations, and applications. Future advancements of these microfluidic strategies will lead toward translational lab-on-a-chip systems for a wide spectrum of biological engineering applications

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

Microfluidic manipulation by AC Electrothermal effect

AC Electrokinetics (ACEK) has attracted much research interest for microfluidic manipulation for the last few years. It shows great potential for functions such as micropumping, mixing and concentrating particles. Most of current ACEK research focuses on AC electroosmosis (ACEO), which is limited to solutions with conductivity less than 0.02 S/m, excluding most biofluidic applications. To solve for this problem, this dissertation seeks to apply AC electrothermal (ACET) effect to manipulate conductive fluids and particles within, and it is among the first demonstration of ACET devices, a particle trap and an ACET micropump. The experiments used fluids at a conductivity of 0.224 S/m that is common in bio-applications. Pumping and trapping were demonstrated at low voltages, reaching ~100 um/s for no more than 8 Vrms at 200 kHz. The flow velocity was measured to follow a quadratic relationship with applied voltage which is in accordance with theory. This research also studies ACET effect on low ionic strength microfluidics, since Joule heating is ubiquitous in electrokinetic devices. One contribution is that our study suggested ACET as one possible reason of flow reversal, which has intrigued the researchers in ACEK field. Electrically, a microfluidic cell can be viewed as an impedance network of capacitances and resistors. Heat dissipation in those elements varies with AC frequency and fluid properties, so changes the relative importance of heat generation at the electrode/electrolyte interface and in the resistive fluid bulk, which could change the temperature gradient in the device, hence changing the flow direction. Another contribution of this dissertation is the reaction enhanced ACET micropumping. A dramatic improvement in flow rate over conventional ac micropumps is achieved by introducing a thin fluid layer of high ionic density near the electrodes. Such an ionic layer is produced by superimposing a DC offset on AC signal that induces Faradaic reaction. The velocity improvement, in some cases, is over an order of magnitude, reaching a linear velocity of up to 2.5 mm/s with only 5.4Vrms. This discovery presents an exciting opportunity of utilizing ACET effect in microfluidic applications

Electronically integrated microcatheters based on self-assembling polymer films

Existing electronically integrated catheters rely on the manual assembly of separate components to integrate sensing and actuation capabilities. This strongly impedes their miniaturization and further integration. Here, we report an electronically integrated self-assembled microcatheter. Electronic components for sensing and actuation are embedded into the catheter wall through the self-assembly of photolithographically processed polymer thin films. With a diameter of only about 0.1 mm, the catheter integrates actuated digits for manipulation and a magnetic sensor for navigation and is capable of targeted delivery of liquids. Fundamental functionalities are demonstrated and evaluated with artificial model environments and ex vivo tissue. Using the integrated magnetic sensor, we develop a strategy for the magnetic tracking of medical tools that facilitates basic navigation with a high resolution below 0.1 mm. These highly flexible and microsized integrated catheters might expand the boundary of minimally invasive surgery and lead to new biomedical applications. Copyright © 2021 The Authors, some rights reserved