Search results for: automated microscope

Authors: L. Ereku, R. E. Mackay, A. Naveenathayalan, K. Ajayi, W. Balachandran

Abstract:

Over the past decade the increase of sexually transmitted infections (STIs) especially in the developing world due to high cost and lack of sufficient medical testing have given rise to the need for a rapid, low cost point of care medical diagnostic that is disposable and most significantly reproduces equivocal results achieved within centralised laboratories. This paper present the development of a disposable PDMS microfluidic cartridge incorporating blisters filled with reagents required for isothermal DNA amplification in clinical diagnostics and point-of-care testing. In view of circumventing the necessity for external complex microfluidic pumps, designing on-chip pressurised fluid reservoirs is embraced using finger actuation and blister storage. The fabrication of the blisters takes into consideration three proponents that include: material characteristics, fluid volume and structural design. Silicone rubber is the chosen material due to its good chemical stability, considerable tear resistance and moderate tension/compression strength. The case of fluid capacity and structural form go hand in hand as the reagent need for the experimental analysis determines the volume size of the blisters, whereas the structural form has to be designed to provide low compression stress when deformed for fluid expulsion. Furthermore, the top and bottom section of the blisters are embedded with miniature polar opposite magnets at a defined parallel distance. These magnets are needed to lock or restrain the blisters when fully compressed so as to prevent unneeded backflow as a result of elasticity. The integrated chip is bonded onto a large microscope glass slide (50mm x 75mm). Each part is manufactured using a 3D printed mould designed using Solidworks software. Die-casting is employed, using 3D printed moulds, to form the deformable blisters by forcing a proprietary liquid silicone rubber through the positive mould cavity. The set silicone rubber is removed from the cast and prefilled with liquid reagent and then sealed with a thin (0.3mm) burstable layer of recast silicone rubber. The main microfluidic cartridge is fabricated using classical soft lithographic techniques. The cartridge incorporates microchannel circuitry, mixing chamber, inlet port, outlet port, reaction chamber and waste chamber. Polydimethylsiloxane (PDMS, QSil 216) is mixed and degassed using a centrifuge (ratio 10:1) is then poured after the prefilled blisters are correctly positioned on the negative mould. Heat treatment of about 50C to 60C in the oven for about 3hours is needed to achieve curing. The latter chip production stage involves bonding the cured PDMS to the glass slide. A plasma coroner treater device BD20-AC (Electro-Technic Products Inc., US) is used to activate the PDMS and glass slide before they are both joined and adequately compressed together, then left in the oven over the night to ensure bonding. There are two blisters in total needed for experimentation; the first will be used as a wash buffer to remove any remaining cell debris and unbound DNA while the second will contain 100uL amplification reagents. This paper will present results of chemical cell lysis, extraction using a biopolymer paper membrane and isothermal amplification on a low-cost platform using the finger actuated blisters for reagent storage. The platform has been shown to detect 1x105 copies of Chlamydia trachomatis using Recombinase Polymerase Amplification (RPA).

Keywords: finger actuation, point of care, reagent storage, silicone blisters

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Authors: Camille Perréard, Yoann Ladner, Fanny D'Orlyé, Stéphanie Descroix, Vélan Taniga, Anne Varenne, Cédric Guyon, Michael. Tatoulian, Frédéric Kanoufi, Cyrine Slim, Sophie Griveau, Fethi Bedioui

Abstract:

The development of micro total analysis systems is of major interest for contaminant and biomarker analysis. As a lab-on-chip integrates all steps of an analysis procedure in a single device, analysis can be performed in an automated format with reduced time and cost, while maintaining performances comparable to those of conventional chromatographic systems. Moreover, these miniaturized systems are either compatible with field work or glovebox manipulations. This work is aimed at developing an analytical microsystem for trace and ultra trace quantitation in complex matrices. The strategy consists in the integration of a sample pretreatment step within the lab-on-chip by a confinement zone where selective ligands are immobilized for target extraction and preconcentration. Aptamers were chosen as selective ligands, because of their high affinity for all types of targets (from small ions to viruses and cells) and their ease of synthesis and functionalization. This integrated target extraction and concentration step will be followed in the microdevice by an electrokinetic separation step and an on-line detection. Polymers consisting of cyclic olefin copolymer (COC) or fluoropolymer (Dyneon THV) were selected as they are easy to mold, transparent in UV-visible and have high resistance towards solvents and extreme pH conditions. However, because of their low chemical reactivity, surface treatments are necessary. For the design of this miniaturized diagnostics, we aimed at modifying the microfluidic system at two scales : (1) on the entire surface of the microsystem to control the surface hydrophobicity (so as to avoid any sample wall adsorption) and the fluid flows during electrokinetic separation, or (2) locally so as to immobilize selective ligands (aptamers) on restricted areas for target extraction and preconcentration. We developed different novel strategies for the surface functionalization of COC and Dyneon, based on plasma, chemical and /or electrochemical approaches. In a first approach, a plasma-induced immobilization of brominated derivatives was performed on the entire surface. Further substitution of the bromine by an azide functional group led to covalent immobilization of ligands through “click” chemistry reaction between azides and terminal alkynes. COC and Dyneon materials were characterized at each step of the surface functionalization procedure by various complementary techniques to evaluate the quality and homogeneity of the functionalization (contact angle, XPS, ATR). With the objective of local (micrometric scale) aptamer immobilization, we developed an original electrochemical strategy on engraved Dyneon THV microchannel. Through local electrochemical carbonization followed by adsorption of azide-bearing diazonium moieties and covalent linkage of alkyne-bearing aptamers through click chemistry reaction, typical dimensions of immobilization zones reached the 50 µm range. Other functionalization strategies, such as sol-gel encapsulation of aptamers, are currently investigated and may also be suitable for the development of the analytical microdevice. The development of these functionalization strategies is the first crucial step in the design of the entire microdevice. These strategies allow the grafting of a large number of molecules for the development of new analytical tools in various domains like environment or healthcare.

Keywords: alkyne-azide click chemistry (CuAAC), electrochemical modification, microsystem, plasma bromination, surface functionalization, thermoplastic polymers

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Authors: Chia-Jung Chen, Yu-Chi Hsu, June-Dong Lin, Kun-Chen Chan, Chieh-Tien Wang, Li-Ching Wu, Chung-Feng Liu

Abstract:

With fast advances in healthcare technology, various total laboratory automation (TLA) processes have been proposed. However, adopting TLA needs quite high funding. This study explores an early adoption experience by Taiwan’s large-scale hospital group, the Chimei Hospital Group (CMG), which owns three branch hospitals (Yongkang, Liouying and Chiali, in order by service scale), based on the five stages of Everett Rogers’ Diffusion Decision Process. 1.Knowledge stage: Over the years, two weaknesses exists in laboratory department of CMG: 1) only a few examination categories (e.g., sugar testing and HbA1c) can now be completed and reported within a day during an outpatient clinical visit; 2) the Yongkang Hospital laboratory space is dispersed across three buildings, resulting in duplicated investment in analysis instruments and inconvenient artificial specimen transportation. Thus, the senior management of the department raised a crucial question, was it time to process the redesign of the laboratory department? 2.Persuasion stage: At the end of 2013, Yongkang Hospital’s new building and restructuring project created a great opportunity for the redesign of the laboratory department. However, not all laboratory colleagues had the consensus for change. Thus, the top managers arranged a series of benchmark visits to stimulate colleagues into being aware of and accepting TLA. Later, the director of the department proposed a formal report to the top management of CMG with the results of the benchmark visits, preliminary feasibility analysis, potential benefits and so on. 3.Decision stage: This TLA suggestion was well-supported by the top management of CMG and, finally, they made a decision to carry out the project with an instrument-leasing strategy. After the announcement of a request for proposal and several vendor briefings, CMG confirmed their laboratory automation architecture and finally completed the contracts. At the same time, a cross-department project team was formed and the laboratory department assigned a section leader to the National Taiwan University Hospital for one month of relevant training. 4.Implementation stage: During the implementation, the project team called for regular meetings to review the results of the operations and to offer an immediate response to the adjustment. The main project tasks included: 1) completion of the preparatory work for beginning the automation procedures; 2) ensuring information security and privacy protection; 3) formulating automated examination process protocols; 4) evaluating the performance of new instruments and the instrument connectivity; 5)ensuring good integration with hospital information systems (HIS)/laboratory information systems (LIS); and 6) ensuring continued compliance with ISO 15189 certification. 5.Confirmation stage: In short, the core process changes include: 1) cancellation of signature seals on the specimen tubes; 2) transfer of daily examination reports to a data warehouse; 3) routine pre-admission blood drawing and formal inpatient morning blood drawing can be incorporated into an automatically-prepared tube mechanism. The study summarizes below the continuous improvement orientations: (1) Flexible reference range set-up for new instruments in LIS. (2) Restructure of the specimen category. (3) Continuous review and improvements to the examination process. (4) Whether installing the tube (specimen) delivery tracks need further evaluation.

Keywords: innovation decision process, total laboratory automation, health care

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Authors: Yannick Willemin

Abstract:

Carbon fibre-reinforced plastic (CFRP) offers outstanding value. However, like all materials, CFRP also has its challenges. Many forming processes are largely manual and hard to automate, making it challenging to control repeatability and reproducibility (R&R); they generate significant scrap and are too slow for high-series production; fibre costs are relatively high and subject to supply and cost fluctuations; the supply chain is fragmented; many forms of CFRP are not recyclable, and many materials have yet to be fully characterized for accurate simulation; shelf life and outlife limitations add cost; continuous-fibre forms have design limitations; many materials are brittle; and small and/or thick parts are costly to produce and difficult to automate. A majority of small structural parts are metal due to high CFRP fabrication costs for the small-size class. The fact that CFRP manufacturing processes that produce the highest performance parts also tend to be the slowest and least automated is another reason CFRP parts are generally higher in cost than comparably performing metal parts, which are easier to produce. Fortunately, business is in the midst of a major manufacturing evolution—Industry 4.0— one technology seeing rapid growth is additive manufacturing/3D printing, thanks to new processes and materials, plus an ability to harness Industry 4.0 tools. No longer limited to just prototype parts, metal-additive technologies are used to produce tooling and mold components for high-volume manufacturing, and polymer-additive technologies can incorporate fibres to produce true composites and be used to produce end-use parts with high aesthetics, unmatched complexity, mass customization opportunities, and high mechanical performance. A new hybrid manufacturing process combines the best capabilities of additive—high complexity, low energy usage and waste, 100% traceability, faster to market—and post-consolidation—tight tolerances, high R&R, established materials, and supply chains—technologies. The platform was developed by Zürich-based 9T Labs AG and is called Additive Fusion Technology (AFT). It consists of a design software offering the possibility to determine optimal fibre layup, then exports files back to check predicted performance—plus two pieces of equipment: a 3d-printer—which lays up (near)-net-shape preforms using neat thermoplastic filaments and slit, roll-formed unidirectional carbon fibre-reinforced thermoplastic tapes—and a post-consolidation module—which consolidates then shapes preforms into final parts using a compact compression press fitted with a heating unit and matched metal molds. Matrices—currently including PEKK, PEEK, PA12, and PPS, although nearly any high-quality commercial thermoplastic tapes and filaments can be used—are matched between filaments and tapes to assure excellent bonding. Since thermoplastics are used exclusively, larger assemblies can be produced by bonding or welding together smaller components, and end-of-life parts can be recycled. By combining compression molding with 3D printing, higher part quality with very-low voids and excellent surface finish on A and B sides can be produced. Tight tolerances (min. section thickness=1.5mm, min. section height=0.6mm, min. fibre radius=1.5mm) with high R&R can be cost-competitively held in production volumes of 100 to 10,000 parts/year on a single set of machines.

Keywords: additive manufacturing, composites, thermoplastic, hybrid manufacturing

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Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

Abstract:

Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

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Authors: Justin Woulfe

Abstract:

Siloed logistics and supply chain management systems throughout the Department of Defense (DOD) has led to disparate approaches to modeling and simulation (M&S), a lack of understanding of how one system impacts the whole, and issues with “optimal” solutions that are good for one organization but have dramatic negative impacts on another. Many different systems have evolved to try to understand and account for uncertainty and try to reduce the consequences of the unknown. As the DoD undertakes expansive digital transformation initiatives, there is an opportunity to fuse and leverage traditionally disparate data into a centrally hosted source of truth. With a streamlined process incorporating machine learning (ML) and artificial intelligence (AI), advanced M&S will enable informed decisions guiding program success via optimized operational readiness and improved mission success. One of the current challenges is to leverage the terabytes of data generated by monitored systems to provide actionable information for all levels of users. The implementation of a cloud-based application analyzing data transactions, learning and predicting future states from current and past states in real-time, and communicating those anticipated states is an appropriate solution for the purposes of reduced latency and improved confidence in decisions. Decisions made from an ML and AI application combined with advanced optimization algorithms will improve the mission success and performance of systems, which will improve the overall cost and effectiveness of any program. The Systecon team constructs and employs model-based simulations, cutting across traditional silos of data, aggregating maintenance, and supply data, incorporating sensor information, and applying optimization and simulation methods to an as-maintained digital twin with the ability to aggregate results across a system’s lifecycle and across logical and operational groupings of systems. This coupling of data throughout the enterprise enables tactical, operational, and strategic decision support, detachable and deployable logistics services, and configuration-based automated distribution of digital technical and product data to enhance supply and logistics operations. As a complete solution, this approach significantly reduces program risk by allowing flexible configuration of data, data relationships, business process workflows, and early test and evaluation, especially budget trade-off analyses. A true capability to tie resources (dollars) to weapon system readiness in alignment with the real-world scenarios a warfighter may experience has been an objective yet to be realized to date. By developing and solidifying an organic capability to directly relate dollars to readiness and to inform the digital twin, the decision-maker is now empowered through valuable insight and traceability. This type of educated decision-making provides an advantage over the adversaries who struggle with maintaining system readiness at an affordable cost. The M&S capability developed allows program managers to independently evaluate system design and support decisions by quantifying their impact on operational availability and operations and support cost resulting in the ability to simultaneously optimize readiness and cost. This will allow the stakeholders to make data-driven decisions when trading cost and readiness throughout the life of the program. Finally, sponsors are available to validate product deliverables with efficiency and much higher accuracy than in previous years.

Keywords: artificial intelligence, digital transformation, machine learning, predictive analytics

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