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

Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood

As the tissue that contains the largest representation of the human proteome [1], blood is the most important fluid for clinical diagnostics [2, 3, 4]. However, although changes of plasma protein profiles reflect physiological or pathological conditions associated with many human diseases, only a handful of plasma proteins are routinely used in clinical tests. Reasons for this include the intrinsic complexity of the plasma proteome [1], the heterogeneity of human diseases and the rapid degradation of proteins in sampled blood [5]. We report an integrated microfluidic system, the integrated blood barcode chip that can sensitively sample a large panel of protein biomarkers over broad concentration ranges and within 10 min of sample collection. It enables on-chip blood separation and rapid measurement of a panel of plasma proteins from quantities of whole blood as small as those obtained by a finger prick. Our device holds potential for inexpensive, noninvasive and informative clinical diagnoses, particularly in point-of-care settings

Improving root cause analysis through the integration of PLM systems with cross supply chain maintenance data

The purpose of this paper is to demonstrate a system architecture for integrating Product Lifecycle Management (PLM) systems with cross supply chain maintenance information to support root-cause analysis. By integrating product-data from PLM systems with warranty claims, vehicle diagnostics and technical publications, engineers were able to improve the root-cause analysis and close the information gaps. Data collection was achieved via in-depth semi-structured interviews and workshops with experts from the automotive sector. Unified Modelling Language (UML) diagrams were used to design the system architecture proposed. A user scenario is also presented to demonstrate the functionality of the system

Developement of real time diagnostics and feedback algorithms for JET in view of the next step

Real time control of many plasma parameters will be an essential aspect in the development of reliable high performance operation of Next Step Tokamaks. The main prerequisites for any feedback scheme are the precise real-time determination of the quantities to be controlled, requiring top quality and highly reliable diagnostics, and the availability of robust control algorithms. A new set of real time diagnostics was recently implemented on JET to prove the feasibility of determining, with high accuracy and time resolution, the most important plasma quantities. With regard to feedback algorithms, new model–based controllers were developed to allow a more robust control of several plasma parameters. Both diagnostics and algorithms were successfully used in several experiments, ranging from H-mode plasmas to configuration with ITBs. Since elaboration of computationally heavy measurements is often required, significant attention was devoted to non-algorithmic methods like Digital or Cellular Neural/Nonlinear Networks. The real time hardware and software adopted architectures are also described with particular attention to their relevance to ITER.Comment: 12th International Congress on Plasma Physics, 25-29 October 2004, Nice (France

Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics.

We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process

Yield Enhancement of Digital Microfluidics-Based Biochips Using Space Redundancy and Local Reconfiguration

As microfluidics-based biochips become more complex, manufacturing yield will have significant influence on production volume and product cost. We propose an interstitial redundancy approach to enhance the yield of biochips that are based on droplet-based microfluidics. In this design method, spare cells are placed in the interstitial sites within the microfluidic array, and they replace neighboring faulty cells via local reconfiguration. The proposed design method is evaluated using a set of concurrent real-life bioassays.Comment: Submitted on behalf of EDAA (http://www.edaa.com/

An Infrastructural IP for Interactive MPEG-4 SoC Functional Verification

This paper introduces a specific architecture including an infrastructural IP for functional verification and diagnostics, which is suitable for functional core-based testing of an MPEG4 SoC. Our advanced MPEG4 SoC results in a high complexity SoC with limited physical access to many different functional cores. The proposed test method provides direct monitoring and control for each core, which enables core verification at actual speed. It significantly decreases the verification time due to the large number of required test vectors in typical MPEG4 verification. Furthermore, it also makes the system scalable for functional core expansion due to upgrading of standards. The proposed infrastructural IP is also linked to PC-based interactive tools to simplify the verification of individual and integrated cores. It also provides detailed diagnostic data that enables simple system debugging. The debugging tools also feature test-pattern generation and simulation of expected values. Actual system implementation has shown full functionality of our proposed method

Control charts for the on-line diagnostics of CMM performance

The quality of a production process is increasing its dependence on both the manufacturing technology, and the production control. In most applications controls are operated by relying on intelligent instrumentation to 'automatically' perform the programmed checks. However, the performance systems that verify the product's quality can deteriorate, as can the production process. This paper presents a method for the on-line verification of the performance of a coordinate measuring machine (CMM) using statistically based control charts. The method is automated and performed on-line during a normal measurement cycle. Some experimental results are then presented and discussed