Advances in Microfluidics and Lab-on-a-Chip Technologies

Advances in molecular biology are enabling rapid and efficient analyses for effective intervention in domains such as biology research, infectious disease management, food safety, and biodefense. The emergence of microfluidics and nanotechnologies has enabled both new capabilities and instrument sizes practical for point-of-care. It has also introduced new functionality, enhanced sensitivity, and reduced the time and cost involved in conventional molecular diagnostic techniques. This chapter reviews the application of microfluidics for molecular diagnostics methods such as nucleic acid amplification, next-generation sequencing, high resolution melting analysis, cytogenetics, protein detection and analysis, and cell sorting. We also review microfluidic sample preparation platforms applied to molecular diagnostics and targeted to sample-in, answer-out capabilities

Simplifying microfluidic separation devices towards field-detection of blood parasites

With our sights set on a simple and inexpensive diagnostics device based on extraction and enrichment of parasites from human blood, we present a device design that relies on a combination of multiple different deterministic lateral displacement arrays. Our end goal is a microfluidic device that will be easy to use in the rural, resource-deprived areas where simple-to-use medical tools are crucially needed for rapid and accurate diagnosis. Here, we exemplify this in the application of blood parasite enrichment from a sample of blood. With trypanosomes as a model system we show a combination of functionalities designed into a single device based on several deterministic lateral displacement arrays of different depths arranged in series. With only one inlet and no expensive or complicated pumping mechanisms to run separations we ensure the level of simplicity necessary for field use

Microchips and their significance in isolation of circulating tumor cells and monitoring of cancers

In micro-fluid systems, fluids are injected into extremely narrow polymer channels in small amounts such as micro-, nano-, or pico-liter scales. These channels themselves are embedded on tiny chips. Various specialized structures in the chips including pumps, valves, and channels allow the chips to accept different types of fluids to be entered the channel and along with flowing through the channels, exert their effects in the framework of different reactions. The chips are generally crystal, silicon, or elastomer in texture. These highly organized structures are equipped with discharging channels through which products as well as wastes of the reactions are secreted out. A particular advantage regarding the use of fluids in micro-scales over macro-scales lies in the fact that these fluids are much better processed in the chips when they applied as micro-scales. When the laboratory is miniaturized as a microchip and solutions are injected on a micro-scale, this combination makes a specialized construction referred to as "lab-on-chip". Taken together, micro-fluids are among the novel technologies which further than declining the costs; enhancing the test repeatability, sensitivity, accuracy, and speed; are emerged as widespread technology in laboratory diagnosis. They can be utilized for monitoring a wide spectrum of biological disorders including different types of cancers. When these microchips are used for cancer monitoring, circulatory tumor cells play a fundamental role

Survey of End-to-End Mobile Network Measurement Testbeds, Tools, and Services

Mobile (cellular) networks enable innovation, but can also stifle it and lead to user frustration when network performance falls below expectations. As mobile networks become the predominant method of Internet access, developer, research, network operator, and regulatory communities have taken an increased interest in measuring end-to-end mobile network performance to, among other goals, minimize negative impact on application responsiveness. In this survey we examine current approaches to end-to-end mobile network performance measurement, diagnosis, and application prototyping. We compare available tools and their shortcomings with respect to the needs of researchers, developers, regulators, and the public. We intend for this survey to provide a comprehensive view of currently active efforts and some auspicious directions for future work in mobile network measurement and mobile application performance evaluation.Comment: Submitted to IEEE Communications Surveys and Tutorials. arXiv does not format the URL references correctly. For a correctly formatted version of this paper go to http://www.cs.montana.edu/mwittie/publications/Goel14Survey.pd

Rapid and label-free identification of single leukemia cells from blood in a high-density microfluidic trapping array by fluorescence lifetime imaging microscopy.

The rapid screening and isolation of single leukemia cells from blood has become critical for early leukemia detection and tumor heterogeneity interrogation. However, due to the size overlap between leukemia cells and the more abundant white blood cells (WBCs), the isolation and identification of leukemia cells individually from peripheral blood is extremely challenging and often requires immunolabeling or cytogenetic assays. Here we present a rapid and label-free single leukemia cell identification platform that combines: (1) high-throughput size-based separation of hemocytes via a single-cell trapping array, and (2) leukemia cell identification through phasor approach and fluorescence lifetime imaging microscopy (phasor-FLIM), to quantify changes between free/bound nicotinamide adenine dinucleotide (NADH) as an indirect measurement of metabolic alteration in living cells. The microfluidic trapping array designed with 1600 highly-packed addressable single-cell traps can simultaneously filter out red blood cells (RBCs) and trap WBCs/leukemia cells, and is compatible with low-magnification imaging and fast-speed fluorescence screening. The trapped single leukemia cells, e.g., THP-1, Jurkat and K562 cells, are distinguished from WBCs in the phasor-FLIM lifetime map, as they exhibit significant shift towards shorter fluorescence lifetime and a higher ratio of free/bound NADH compared to WBCs, because of their glycolysis-dominant metabolism for rapid proliferation. Based on a multiparametric scheme comparing the eight parameter-spectra of the phasor-FLIM signatures, spiked leukemia cells are quantitatively distinguished from normal WBCs with an area-under-the-curve (AUC) value of 1.00. Different leukemia cell lines are also quantitatively distinguished from each other with AUC values higher than 0.95, demonstrating high sensitivity and specificity for single cell analysis. The presented platform is the first to enable high-density size-based single-cell trapping simultaneously with RBC filtering and rapid label-free individual-leukemia-cell screening through non-invasive metabolic imaging. Compared to conventional biomolecular diagnostics techniques, phasor-FLIM based single-cell screening is label-free, cell-friendly, robust, and has the potential to screen blood in clinical volumes through parallelization

3G networks in emergency telemedicine - An in-depth evaluation & analysis

The evolution of telecommunications technologies in connection with the robustness and the fidelity these new systems provide, have opened up many new horizons as regards the provision of healthcare and the quality of service from the side of the experts to that of the patients. The purpose of this paper is to evaluate the third generation telecommunications systems that are only recently being deployed in Europe, as well as argue on why a transition from 2G and 2.5G to 3G telecommunications systems could prove to be crucial, especially in relation to emergency telemedicine. The experimental results of the use of these systems are analyzed, the implementation of a tele-consultation unit is presented and their exploitation capabilities are explored

Self-partitioning SlipChip for slip-induced droplet formation and human papillomavirus viral load quantification with digital LAMP

Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide, and persistent HPV infection can cause warts and even cancer. Nucleic acid analysis of HPV viral DNA can be very informative for the diagnosis and monitoring of HPV. Digital nucleic acid analysis, such as digital PCR and digital isothermal amplification, can provide sensitive detection and precise quantification of target nucleic acids, and its utility has been demonstrated in many biological research and medical diagnostic applications. A variety of methods have been developed for the generation of a large number of individual reaction partitions, a key requirement for digital nucleic acid analysis. However, an easily assembled and operated device for robust droplet formation without preprocessing devices, auxiliary instrumentation or control systems is still highly desired. In this paper, we present a self-partitioning SlipChip (sp-SlipChip) microfluidic device for the slip-induced generation of droplets to perform digital loop-mediated isothermal amplification (LAMP) for the detection and quantification of HPV DNA. In contrast to traditional SlipChip methods, which require the precise alignment of microfeatures, this sp-SlipChip utilized a design of “chain-of-pearls” continuous microfluidic channel that is independent of the overlapping of microfeatures on different plates to establish the fluidic path for reagent loading. Initiated by a simple slipping step, the aqueous solution can robustly self-partition into individual droplets by capillary pressure-driven flow. This advantage makes the sp-SlipChip very appealing for the point-of-care quantitative analysis of viral load. As a proof of concept, we performed digital LAMP on an sp-SlipChip to quantify human papillomaviruses (HPVs) 16 and 18 and tested this method with fifteen anonymous clinical samples

Sustainable Fault-handling Of Reconfigurable Logic Using Throughput-driven Assessment

A sustainable Evolvable Hardware (EH) system is developed for SRAM-based reconfigurable Field Programmable Gate Arrays (FPGAs) using outlier detection and group testing-based assessment principles. The fault diagnosis methods presented herein leverage throughput-driven, relative fitness assessment to maintain resource viability autonomously. Group testing-based techniques are developed for adaptive input-driven fault isolation in FPGAs, without the need for exhaustive testing or coding-based evaluation. The techniques maintain the device operational, and when possible generate validated outputs throughout the repair process. Adaptive fault isolation methods based on discrepancy-enabled pair-wise comparisons are developed. By observing the discrepancy characteristics of multiple Concurrent Error Detection (CED) configurations, a method for robust detection of faults is developed based on pairwise parallel evaluation using Discrepancy Mirror logic. The results from the analytical FPGA model are demonstrated via a self-healing, self-organizing evolvable hardware system. Reconfigurability of the SRAM-based FPGA is leveraged to identify logic resource faults which are successively excluded by group testing using alternate device configurations. This simplifies the system architect\u27s role to definition of functionality using a high-level Hardware Description Language (HDL) and system-level performance versus availability operating point. System availability, throughput, and mean time to isolate faults are monitored and maintained using an Observer-Controller model. Results are demonstrated using a Data Encryption Standard (DES) core that occupies approximately 305 FPGA slices on a Xilinx Virtex-II Pro FPGA. With a single simulated stuck-at-fault, the system identifies a completely validated replacement configuration within three to five positive tests. The approach demonstrates a readily-implemented yet robust organic hardware application framework featuring a high degree of autonomous self-control