Laboratory unit operations on centrifugal lab-on-a-disc cartridges using dissolvable-film enabled flow control

The suitability of the centrifugal “lab-on-a-disc” (LoaD) platform for point-of-use / point-of-care deployment, where ruggedness, portability, rapid turn-around times and ease-of-use are key, has resulted in increased interest from the academic community over the last decade. Recently, a new, so-called event-triggered valving paradigm was introduced which circumvented a number of the limitations of commonly used, rotationally actuated valves and complex instrument-controlled valving. In the dissolvable-film based event-triggered approach, it is the liquid movement about a disc which actuates a valve; thus enabling the concatenating of a number of liquid handling operations into an automated cascade. Functioning broadly independent of spin rate, the number of discrete valving operations is only limited by the available disc real-estate. In this work we present this valving paradigm to control a network of discrete Laboratory Unit Operations (LUOs) which, with experienced design, can be integrated together to implement complex fluidic assays. We describe how these valves can be configured, using Boolean-like network relationships, to implement LUOs such as sequential washing steps. We also describe how these valves can be configured to enable metering, mixing and selective routing of liquid flows. Finally, we describe how these valves can be configured to provide accurate temporal control of LUOs; thus providing an entire suite of process control technology which can be used to enable many bio-assays

Enhanced liquid retention capacity within plastic food packaging through modified capillary recesses

A novel approach is proposed to isolate meat exudate in plastic packaging trays. This exudate is responsible for limiting meat shelf life, increasing meat loss and non-recycling plastic waste. This study explores the use of specially designed capillary recesses with integrated raised rims as a means of improving liquid retention capacity in thermoformed meat trays. The presence of raised recess rims is used to enhance the valving functionality of the recesses and restrict liquid drainage during and after recess inclination. This resulted in a considerable increase in liquid retention capabilities. For pork exudate, the retention capacity of recess samples (recess diameter: 9 mm) significantly increased (p < 0.05) from 0.79 g for recesses with no rims to 2.12 g for rim-integrated recesses. The corresponding retention capacity of a recess array after introducing these rims was 2921 ± 63 mL/m2. These recesses have comparable liquid scavenging performance to absorbent meat pads (3000 mL/m2) yet are integrated within the tray material. This proves the practicality of using rim-integrated recesses in plastic meat packaging to retain exudate away and ensure fully recyclable plastic packaging. The manufacturing of these recesses is integrated into the thermoforming process for the tray body

The application of biomedical engineering techniques to the diagnosis and management of tropical diseases: A review

This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications

Theoretical development and critical analysis of burst frequency equations for passive valves on centrifugal microfluidic platforms

This paper presents a theoretical development and critical analysis of the burst frequency equations for capillary valves on a microfluidic compact disc (CD) platform. This analysis includes background on passive capillary valves and the governing models/equations that have been developed to date. The implicit assumptions and limitations of these models are discussed. The fluid meniscus dynamics before bursting is broken up into a multi-stage model and a more accurate version of the burst frequency equation for the capillary valves is proposed. The modified equations are used to evaluate the effects of various CD design parameters such as the hydraulic diameter, the height to width aspect ratio, and the opening wedge angle of the channel on the burst pressure.close

User-Friendly, Low-Cost, Microfluidic Devices With Capillary Circuits For Multiplexed, Isothermal, Point-Of-Care, Nucleic Acid Amplification Tests

Rapid, sensitive, and specific detection of causative pathogens is key to personalized medicine and the prompt implementation of appropriate mitigation measures to reduce disease transmission, mortality, morbidity, and cost. Conventional molecular detection methods require trained personnel, sophisticated equipment, and specialized laboratories, which limits their use to centralized laboratories. To enable molecular diagnostics at the point of need and in resource-poor settings, inexpensive, simple devices that combine multiple unit operations and are capable of co-detecting endemic pathogens are needed. In this work, I have developed microfluidic devices with capillary circuits to automate liquid distribution, eliminating the need for expensive equipment, sophisticated laboratory facilities, and skilled personnel to enable molecular diagnostics at the point of need. Capillary valves with different sizes were developed and implemented to aliquot samples and reagents to multiple reaction chambers and to enable draining liquids from supply lines without affecting liquids in the various reaction chambers, enabling bubble-free operation. The sealing of my microfluidic devices to prevent evaporation during incubation is facilitated with phase-change materials and capillary-induced motion. When my microfluidic chip is heated to its incubation temperature, the phase-change material melts and flows to seal ports of entry and air vent. Numerical simulations were carried out to assess the viability of on-chip, in-house developed, two-stage isothermal nucleic acid amplification in the presence of diffusion and advection. An Android-based smartphone application was developed to automate real-time signal monitoring, time series image analysis, and diagnostic result interpretation. Three 3D-printed, portable, microfluidic devices with capillary circuits were designed, fabricated, and tested for single-stage and two-stage, isothermal nucleic acid amplification with either liquid reagents or pre-stored dry reagents that do not require a cold chain. All devices have proved successful for rapid, sensitive, and specific multiplexed detections of human and animal pathogens

THERMOPLASTIC MICROFLUIDIC PCR TECHNOLOGIES FOR NEAR-PATIENT DIAGNOSTICS

Microfluidic technologies have great potential to help create portable, scalable, and cost-effective devices for rapid polymerase chain reaction (PCR) diagnostics in near patient settings. Unfortunately, current PCR diagnostics have not reached ubiquitous use in such settings because of instrumentation requirements, operational complexity, and high cost. This dissertation demonstrates a novel platform that can provide reduced assay time, simple workflow, scalability, and integration in order to better meet these challenges. First, a disposable microfluidic chip with integrated Au thin film heating and sensing elements is described herein. The system employs capillary pumping for automated loading of sample into the reaction chamber, combined with an integrated hydrophilic valve for precise self-metering of sample volumes into the device. With extensive multiphysics modeling and empirical testing we were able to optimize the system and achieve cycle times of 14 seconds and completed 35 PCR cycles plus HRMA in a total of 15 minutes, for successful identification of a mutation in the G6PC gene indicative of von Gierke’s disease. Next, a scalable sample digitization method that exploits the controlled pinning of fluid at geometric discontinuities within an array of staggered microfluidic traps is described. A simple geometric model is developed to predict the impact of device geometry on sample filling and discretization, and validated experimentally using fabricated cyclic olefin polymer devices. Finally, a 768-element staggered trap array is demonstrated, with highly reliable passive loading and discretization achieved within 5 min. Finally, a technique for reagent integration by pin spotting affords simplified workflow, and the ability to perform multiplexed PCR. Reagent printing formulations were optimized for stability and volume consistency during spotting. Paraffin wax was demonstrated as a protective layer to prevent rehydration and reagent cross contamination during sample loading. Deposition was accomplished by a custom pin spotting tool. A staggered trap array device with integrated reagents successfully amplified and validated a 2-plex assay, showing the potential of the platform for a multiplexed antibiotic resistance screening panel

Lab-on-a-Chip Fabrication and Application

The necessity of on-site, fast, sensitive, and cheap complex laboratory analysis, associated with the advances in the microfabrication technologies and the microfluidics, made it possible for the creation of the innovative device lab-on-a-chip (LOC), by which we would be able to scale a single or multiple laboratory processes down to a chip format. The present book is dedicated to the LOC devices from two points of view: LOC fabrication and LOC application