bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Thalassemic Serum on Plasmodium Falciparum Growth in Vitro
Authors: Vattanaviboon Phantip , Sriklup Chaluay , Polkaew Chutaporn , Prawatmurng Pranit , Ittarat Wanida
Published: October 2018

Thalassemia and malaria are present at high frequency in tropic and subtropic regions. Impaired growth of Plasmodium falciparum has been demonstrated in vitro in both α-and β- thalasemic erythrocytes. In this study, we investigated the effects of thalassemic sera on Plasmodium falciparum developement including 5 α-thalasemia1/α-thalasemia2 (HbH) sera, 4 a-thalasemia1/ hemoglobin Constant Springs (HbH/HbCS) sera and 7 β-thalassemia/ HbE sera compared to 7 normal sera. Study on malarial growth in medium containing 10% various sera for 4 days revealed that HbH and b-thalasemia/ HbE sera was significantly inhibited (p<0.05, by Mann-Whitney Utest) the parasite growth comparing to normal serum. Mean percentages of the parasites grown in HbH (2.24+0.75%) and β-thalassemia/ HbE (1.69+0.97%) sera were about 2 times less than that in normal serum (4.55+2.40%). The mean parasitemia cultured in HbH/HbCS serum (2.38+1.54%) was also lower than that in normal serum but it was non-significantly different. Investigation on stage changing of the parasite among the starting, 1st, 2nd, 3rd and 4th day showed that all thalassemic sera retarded the parasite maturation from stage to stage. Decrease in percent ring stage productionwas observed in culture with HbH/HbCS and β-thalassemia/HbE sera. This might be resulted from reduction of merozoite population in mature schizont or failure of re-invasion of the merozoite. Therefore, not only cellular factors but also serum factors of thalassemic patients inhibited P. falciparum development which may be related to the protective mechanism of thalassemic patients from P. falciparum infection
Applications for Sol-Gel-Derived Materials in Medicine and Biology
Authors: Conroy John F. , Power Mary E. , Norris Pamela M.
Published: October 2018

Sol-gel chemistry provides a novel production route for ceramics and composites that have a variety of applications in medicine, biology, and biochemistry. Advantages of sol-gel-derived materials in these applications include simple, low temperature production routes that are capable of achieving temperature, chemical, and radiation-inert porous materials with a wide range of structural and microstructural properties. Furthermore, sol-gel-derived materials display remarkable compatibility with biomacromolecules and are conveniently functionalized with a variety of coupling agents. The properties of these materials and their present and potential applications in medicine and biology are reviewed.
Heraeus cytomat® 6000 Series Incubators and Storage Systems from Kendro Laboratory Products
Authors: Engler Randall
Published: October 2018

There are a number of cases in high throughput screening systems where a controlled environment is desired. These include incubation periods for cell-based assays, incubation for protein detection assays such as ELISA or fluorescence assays, and branching assays for mRNA detection. In addition, as the density of wells in microplates increases and well volumes become smaller, evaporation becomes a concern in all assays.

The cytomat® 6000 is a robot accessible, automated CO2 incubator used for cell-based High Throughput Screening systems. The incubator provides superior environmental conditions, due to the unique access door at the back of the instrument, the PlateShuttle (see Figure 3 ). This small access opening insures that the environment inside the system (temperature, humidity and CO2) is undisturbed as microplates are accessed ( Figure 2 ).

The system provides high speed, random (bar-coded) access to all microplate formats for 24, 96, 384 and 1536 well microplates (up to 261-microplate capacity). Other cytomat configurations offer refrigerated and low humidity environments.
Object Feature Extraction by Using the Searching Temporal and Feature Salient Technique
Authors: Su Ching-Liang
Published: October 2018

This research uses the boundary cutting, spatial-temporal segmentation, block based searching, and gray scale histogram technique to extract the eyes, nose, and mouth images. In this research, gray scale histograms are used to salient the eyes, nose, and mouth features. A spatial-temporal template is designed to slide the eyes, nose, and mouth images to extract the eyes, nose, and mouth image. In order to obtain the best result, the generic algorithm and spatial region partition techniques need to be used to remove noise and to precisely bind the object region to obtain a more accurate result.
Progress in Laboratory Automation at Akita University Hospital
Authors: Kayaba Hiroyuki , Fujita Miyoshi , Oyamada Hajime , Obara Toshikage , Sakari Hisao , Chihara Junichi
Published: October 2018

Akita University Hospital was established in 1971. Since then, we have been introducing automated analysis systems to deal with rapidly increasing tasks and demand in the clinical laboratory. In 1988, in collaboration with Hitachi Ltd. (Tokyo, Japan), we developed an automated analysis system composed of an automatic serum separating-aliquoting system connected to analysis systems through an automatic transport system. In 1998, the systems were integrated, enabling 97.6% of samples to be analyzed automatically. With this integrated system, information including the name of the patient, code number, age, gender, department, test to be performed and so on are all encoded on the label of the sampling tubes which are automatically labeled and sorted at the sampling division. The laboratory automation system succeeded in saving labor and time, yet there are still some areas that need improving. Namely, 1) minimizing the quantity of the sample required for analysis, 2) speeding up of the transportation, and 3) down-sizing the system. The development of less invasive, more compact and speedier analysis systems will make the clinical laboratory mobile or portable in the near future and will expand the working field of the clinical laboratory to remote areas and home-nursing services in the community.
Qualification of a Zymark® Multidose® Automated Dissolution Workstation for Dissolution Testing of Fexofenadine HCL Capsules
Authors: Steinman Tom A.
Published: October 2018

A manual, multi-point dissolution test for powder filled capsules was transferred to an automated dissolution method utilizing a Zymark® Multidose® Automated Dissolution Workstation, a MultiFill® station, and a Distek 2100B dissolution bath system. Both methods require a final HPLC analysis of the sample solutions.

Several MultiDose system parameters were evaluated to ensure product result integrity and equivalency. These included carryover studies, line flush studies, vessel wash studies, filter studies, and sample evaporation studies. The most critical evaluation was the statistical analyses (equivalence) of the product results from both methods.
Polymer Microfabrication for Microarrays, Microreactors and Microfluidics
Authors: Alonso-Amigo M. Goretty
Published: October 2018

Polymer microfabrication methods are becoming increasingly important as low-cost alternatives to the silicon or glass-based MEMS technologies. Polymer hot embossing and injection molding are replication methods applicable to microreplication of a diversity of materials and microstructures.

Equipment with high precision control of pressure and temperature for hot embossing of polymer materials is now available commercially. These systems have made possible the replication of chips containing microchannels for capillary electrophoresis (CE) and microfluidics devices, microoptical components and microreactors. Stable and reproducible polymer microstructures have been demonstrated in several types of materials with structural and optical properties meeting other biocompatibility and detection requirements. The process involves few variable parameters and results in high structural accuracy suited for a wide range of microfabrication applications.

After demonstrating equivalent and, in cases, improved performance, the alternative use of plastic as the microdevice material addresses needs for rapid prototyping in product development and provides cost advantages in product commercialization. Thus an increasing number of devices have been reported recently in the literature, fabricated on a variety of polymer substrates and using different fabrication methods such as laser ablation, injection molding, silicone rubber casting or embossing for microfabrication.
Application of Visual Basic for Automation of LC-MS Analysis
Authors: Choi Bernard Karsten , Hercules David M. , Michelotti Enrique , Martinez Blanca , Eisenschmied Mark , Zhang Tianlan , Gusev Arkady I.
Published: October 2018

An approach to customizing the data acquisition and interpretation process of liquid chromatography electrospray mass spectrometry (LC-MS) analysis of compound libraries is presented. Macro programs, using Microsoft Visual Basic, were applied to allow the seamless flow of data from the sample synthesis stage through data acquisition/interpretation and reporting, with minimum user interaction. Logical functions were also incorporated into the macros to allow automated actions to be performed based on experimental results. The application of this approach as a universal method for supplementing the automation process of other instruments controlled by the Microsoft Windows PC platform is also discussed.
Corning® 384 Well Low Volume Microplate Performance in Miniaturized Assays
Authors: Ennis Catherine A.
Published: October 2018

In response to the ever-increasing demand for microplates that facilitate assay miniaturization without compromising assay integrity, Corning's new 384 well Low Volume (384 LV) microplates were evaluated using a homogenous, fluorescence polarization protease assay. Fluorescently labeled casein substrate was incubated over time with dilutions of protease at working volumes that range from 1 to 20 μL and reagent concentrations that range from 0.125 to 50 pg/μL. Four types of plates were evaluated:

Corning 384 well LV black medium bind Corning 384 well LV black non-binding surface (NBS™) Corning 1536 well black medium bind Competitor 384 well small volume

Protease activity was detected as a decrease in polarized fluorescence resulting from substrate degradation over time. Following assay miniaturization to 20 μL working volumes and protease concentration reduction from 25 to 0.25 pg/μL, Corning 384 well LV medium bind and NBS coated assay plates maintained superior signal to noise ratios compared to competitor's 384 well small volume assay plates. At even lower 10 μL working volumes, Corning 384 well LV medium bind assay plates maintained signal to noise ratios comparable to the competitor's assay plates. However as the reagent concentrations were further reduced to 2.5 pg/μL, Corning 384 well LV medium bind and NBS coated assay plates had significantly greater signal to noise ratios compared to the competitor's assay plates. As working volumes were reduced even further to 5 μL and 1 μL, Corning 384 well LV medium bind and NBS coated assay plates had significantly greater signal to noise ratios than the competitor's 384 well small volume assay plates. Furthermore, at 1 μL working volumes, Corning 384 well LV NBS coated assay plates had significantly greater signal to noise ratios than the competitor's assay plates and standard 1536 well assay plates.

These results suggest that Corning 384 well LV medium bind and NBS coated assay plates facilitate assay miniaturization while maintaining assay integrity. Furthermore, as working volumes were significantly reduced to those typically found in 1536 deep well and standard 1536 well assay plates (5 and 1 μL, respectively), Corning's 384 well LV NBS coated assay plates provided superior assay performance.
Automated Nucleic Acid Purification for Large Samples
Authors: O'Brien Darin P. , Campbell Kristen A. , Morken Nathaniel W. , Bair Robert J. , Heath Ellen M.
Published: October 2018

Advancements in the fields of genomic screening, molecular pathology and clinical research have resulted in a major increase in the demand for high quality DNA and RNA. This escalating demand has resulted in a sample preparation bottleneck and an emphasis on the development of new technologies to automate the purification process. Gentra has developed the AUTOPURE LS™ nucleic acid purification instrument, a platform capable of high-throughput sample purification from large samples, such as 10 mL whole blood. This article presents data showing the equivalency of DNA purified using manual and automated processing.
Simlab 1 — A Laboratory Workflow Recorder for Process Assessment
Authors: Hoffmann Georg , Howell Peter , Robert Hingley
Published: October 2018

Process management and workflow optimisation have become key issues of good laboratory management 1 and now seem to be predominant over traditional challenges such as the quality of analytical testing. The first author of this paper has conducted several workflow optimisation studies for clinical laboratories in Europe (Universities of Zurich 2 and Amsterdam, Manchester Royal Infirmary and others) and in the US (University of Virginia 3 ), using a laboratory-specific simulation software called Simlab™ for realistic computer modeling of laboratory scenarios 4 . Since data input and calibration of the models against reality have always been a challenge in these studies, we looked into possibilities of using automated data extraction to extract as much information as possible from the laboratory information system. In this paper we describe our first experience with a Microsoft Excel™-based software program called Simlab 1, which uses the ASCII file transfer protocol to extract data from the LIS.
Connectivity Infrastructure and Components for POCT Environments — Overall Infrastructure
Authors: Hakman Mikael , Groth Torgny
Published: October 2018

Connectivity infrastructure, hardware and software components for point-of-care testing (POCT) environments at medium-to-large sized hospitals with expected number of POCT instruments in the order of hundreds or thousands are described. The instruments include both network-ready and non-network-ready devices. The latter are connected to the network by means of a hardware-based Instrument Network Adapter. Instrument messages are converted to standardized form and, depending on message content, are routed and delivered to appropriate destinations by a software-based Message Routing System consisting of a Message Router and a Delivery Agent. Target information systems consist of departmental and central information systems.
Automated Lab-on-a-Chip Analysis of DNA Fragments
Authors: Ausserer Walter A. , Bousse Luc , Gallagher Steven J. , Kennedy Colin B. , Phan Huan L.
Published: October 2018

The design of a fully automated system for the analysis of DNA fragments in 96–well plates is described. Microfluidic technology is used to integrate sample loading, electrophoretic analysis, and fragment detection onto a miniature lab-on-a-chip device. The microfluidic chip operates in an instrument platform that automates sample access, data collection, and data reporting. Each microfluidic chip provides sizing and concentration values for more than 1000 DNA samples.
The Second Generation of the Laboratory Information System and the Laboratory Automation System in Osaka City University Hospital
Authors: Tatsumi Noriyuki , Morita Kanji , Tsudai Izumi , Naka Keiichi , Park Kunshuk
Published: October 2018

The first total clinical laboratory system (TCLA) in the Osaka City University Hospital was introduced in 1993. After six years of operation, it was recently replaced by a new system. The goals of this replacement were as follows: 1. Improve the analytical performance. 2. Make the system operate more efficiently. 3. Improve the quality of laboratory analyses. We successfully reduced the labor required to operate the laboratory; made the laboratory reports quicker; reduced the number of retraction and revalidation of the results; and minimized the system downtime.
Automated High Throughput Screening of Fluorescent Imaging Plate Reader (FLIPR) Assays Using Assay Platform™ Integrated with Activity Base for ‘on the fly’ Compound Reconfirmation
Authors: Allenby Gary , Dodgson Kathy , Harper Paul , Kassam Adel , Leam Michael , Dale Ian , Sullivan Elaine
Published: October 2018

Advances in the field of automation have meant hitherto complex manual cell-based assays can now be automated. These improvements have brought significant enhancements in throughput, data fidelity and consistency, and allowed a re-allocation of constrained resources.

Building upon these improvements, we have linked our automated cell-based screening system, Assay Platform™, to Activity Base (IDBS), a software package designed to automate the analysis of HTS data. Customisation of this package has resulted in software that can identify ‘active’ compounds and re-pick them ‘on the fly’ from the original compound plates for triplicate re-testing without operator intervention.

Based on an operator initially defining ‘normal’ parameters for assay activity in Activity Base, combined with an automated quality control software module that checks data fidelity, wells containing ‘active’ compounds can be re-picked and re-tested at the end of an automated screening run. Automating cell-based assays has significantly improved productivity, and, with the synergism of Activity Base, has given us greater power to complete each screening run and report ‘active’ compounds to Chemistry more rapidly. This article presents our approach to the automation of cell-based Fluorescent Imaging Plate Reader (FLIPR) screening together with automated active re-test confirmation using Activity Base.
The Biophile Sample Process Management System — Automated Sample Access at Ultra Low Temperatures
Authors: Davis Alan , Graves Sean , Murray Terry
Published: October 2018

The genomics, proteomics, clinical, and drug discovery laboratories have a growing need to maintain valuable samples at ultra-low (−80°C) temperatures in a validated, secure environment. Automated sample processing systems have until now required manual (off-line) storage of samples at −80°C, reducing system reliability and speed. Both of these important needs are addressed by the Sample Process Management System being introduced by BIOPHILE Inc. Conventional sample management processes, such as storage, retrieval, and cataloging, are increasingly strained by the growing sample populations. There are variable sample types, access requirements and storage requirements. Security and inventory procedures are implemented manually. The evolving technologies present in the laboratory cannot interface with conventional manual storage techniques. Addressing these limitations, the primary benefits of BIOPHILE's solutions are:

Fully validated sample management process that coordinates the life-cycles of samples and their related data. Robotic technology to securely store and retrieve samples, improving their accessibility and stability. Thermal shock is reduced, improving sample longevity and quality. The robotic technology allows integration with larger automation systems. A process program to develop a Sample Management Strategy. This strategy is developed by analyzing long-term research goals, current baseline processes, and identification of current sample life cycles. A full validation documentation package can be generated, providing a high level of quality assurance. Improved sample visibility and quality assurance — auto mated sample population cataloging; controlled sample management access and security.
Dispensing Precision for the SciClone™ Automated Liquid Handling Workstation for 96-Channel Pipetting
Authors: Willebrords Rudy
Published: October 2018

One of the first steps in drug discovery involves identification of novel compounds that interfere with therapeutically relevant biological processes. Identification of ‘lead’ compounds in all therapeutic areas included in a drug discovery program requires labor-intensive evaluation of numerous samples in a battery of therapy targeted biological assays. To accelerate the identification of ‘lead’ compounds, Janssen Research Foundation (JRF) has developed in the past an automated high throughput screening (HTS) based on the unattended operation of a custom Zymark tracked robot system. Automation of enzymatic and cellular assays was realized with this system adapted to the handling of microtiter plates. The microtiter plate technology is the basis of our screening. All compounds within our chemical library are stored and distributed in micronic tube racks or microtiter plates for screening. An efficient in-house developed mainframe based laboratory information management system supported all screening activities. Our experience at JRF has shown that the preparation of test compounds and serial dilutions has been a rate-limiting step in the overall screening process. In order to increase compound throughput, it was necessary both to optimize the robotized assays and to automate the compound supply processes. In HTS applications, one of the primary requirements is highly accurate and precise pipetting of microliter volumes of samples into microplates. The SciClone(tm) is an automated liquid handling workstation capable of both 96- and 384-channel high precision pipetting. For high throughput applications, the SciClone™ instrumentation is able to pipette a variety of liquid solutions with a high degree of accuracy and precision between microplates (inter-plate variability) and tip-to-tip (intra-plate variability) within a single plate. The focus of this presentation is to review the liquid handling performance of the SciClone™ system as a multipurpose instrument for pipetting aqueous or organic solutions, and virus suspensions into 96- and 384-well microplates. The capabilities of the system and the resulting benefits for our screening activities will be described.
Spectro ML-A Markup Language for Molecular Spectrometry Data
Authors: Rühl M. Alexander , Schaefer Reinhold , Kramer Gary W.
Published: October 2018

SpectroML is a markup language for molecular spectrometry data that can be used as a “web-aware” mechanism for instrument-to-instrument, instrument-to-application, and application-to-application data interchange and archiving. SpectroML was developed using XML (extensible mark up language), and its vocabulary was gleaned from the terminology, data dictionaries, and concepts embodied in existing standards, instrument software, and data interchange formats. Currently, we have created a SpectroML vocabulary, document type definition, schema, stylesheets, and some demonstration applications for UV-visible spectroscopy data; however, the structure and flexible data model embodied in SpectroML should make it easily adaptable to other spectroscopy techniques.
Engineering an Experimental Platform for High Throughput Reactivity Screening
Authors: Kiser Patrick F. , Collupy Glenn C. , Eichenbaum Gary M. , Rush Chad , Baumann Stephan , Kust Mark P. , Greaves Michael D. , Frederick Erik D. , Soltmann Bernd , Vasina Helen , Orji Charles , Bienfiat Bruno , Brown John D. , Davies John , Atkins Marquitta , Lee Jeffrey R. , Labow Eric , Harp Melissa , Goodrich Ann F. , Conyers Hilton , Geysen H. Mario
Published: October 2018

The genomics revolution coupled to advances in computational power, informatics and robotics is driving drug discovery programs to produce drug candidates faster. This need has resulted in advances in high throughput methods for performing organic chemistry such as combinatorial and parallel synthesis. Yet there has not been a corollary advance in the ability to collect quantitative information on reactions that can be used to produce these drug candidates. This lack of an efficient and robust analytical method has resulted in a significant chemistry bottleneck. This work outlines a set of methods that helps address this chemistry bottleneck by using analytical constructs to detect and quantify reaction outcomes. To accomplish this, an integrated experimental-cheminformatics platform has been developed which couples an experimental design system, automated high throughput parallel and combinatorial synthesis methodology, sample processing, quantitative mass spectroscopy and automated data analysis. This platform is being used to optimize single reactions and the syntheses of whole libraries of compounds, and to generate large databases on specific reaction classes.
UV Laser Micromachining of Polymers for Microfluidic Applications
Authors: Waddell Emanuel A. , Locascio Laurie E. , Kramer Gary W.
Published: October 2018

We have recently begun to explore the use of UV laser ablation micromachining to construct microfluidic devices in polymers. This technique can create microchannels rapidly and modify the resulting polymer surface in a single step. By ablating under different atmospheres, it is possible to alter both the surface chemistries and physical surface morphologies of the microchannels. We have employed electroosmotic flow measurements, chemical mapping, and optical microscopy to characterize the microfluidic devices. In addition, we have studied the parameters affecting the ablation, such as the laser wavelength, laser fluence, laser firing repetition rate, and the material being ablated.
“Electric” Zip Tips™, Preliminary Results
Authors: Sauter Andrew D. , Sauter Andrew D.
Published: October 2018

Induction based fluidics (IBF), a new, simple patented approach for transporting liquids in the micro and the macro world, is discussed. Electric fields are shown to energize liquid/s in a container/s to execute an array of purposes. IBF is shown uniquely to energize N liquids in simple off the shelf devices, inductively. We discuss calibration and other issues, as we demonstrate how simple devices can dispense nanoliters and microliters with high precision and accuracy. Furthermore, we show preliminary single and eight channel data for the Zip Tip™ made by Millipore where the device transports liquids “electrically.” We briefly consider how such new devices, “electric” Zip Tips™, might automate desalting and the placement of digests for MALDI TOF analysis.
21 CFR Part 11: How Does it Affect Laboratory Automation Software Developers?
Authors: Brown Robert M.
Published: October 2018

Just what is “21 CFR Part 11”?

Do I need to consider it when designing lab automation software? Sure, I store data electronically, but my “official” copy is a signed hardcopy stored in my documentation control system, so Part 11 doesn't apply to me, right?

These and similar questions are being asked with increasing frequency during the development process for both off-the-shelf and custom lab automation software. This article presents a brief overview of the FDA regulation concerning the use of electronic records and electronic signatures and a guide for software analysts and developers.
“The Spotting Accelerator™”, Customizable Head Assembly for Advanced Microarraying
Authors: Weibel Curtis
Published: October 2018

Microarraying technologies have emerged as key tools for determining genomic expression. The quality of gene arrays is reliant on spotting pins for production of uniform spots, which are consistent in volume, shape, size and alignment.

Point Technologies, Inc., has developed an advanced spotting technology. Emphasis has been placed on producing the “perfect spots” customized to each microarraying application. Uniform surface texturing such as highly polished or matte finishes, and hydrophilic/hydrophobic zonal coating is produced using Point Technologies' proprietary micro-machining technology. Micro-fabrication also permits the production of advanced pin designs, and high density, high throughput print-head assemblies of 1536 pins and greater. Point Technologies specializes in the micro-electrochemical machining of spotting pins in any size, shape and configuration.

Presented data will demonstrate spotting pin design solutions, such as: variety of tip dimensions, surface finishes, specialized coatings, and material options instrumental in producing the ideal spot size, shape and spot density during extended usage.
Stochastic Optimisation Methods for Biomolecular Structure Prediction
Authors: Herges T. , Merlitz H. , Wenzel W.
Published: October 2018

We discuss the use of stochastic optimization methods for biomolecular structure prediction, particularly applied to protein structure prediction and receptor ligand docking. After a brief introduction we give an overview of the dominating physical effects that are important for protein structure prediction and outline our strategy to address this problem. We discuss the strengths and weaknesses of several possible optimization methods, including the stochastic tunneling method. Finally we give examples of applications of this methodology both for protein structure prediction and receptor ligand docking.
A 384-Well, Fully-Automatable, Superparamagnetic-Particle Based Dye Terminator Removal Kit
Authors: Spicer Douglas A. , Astle Thomas , Booth Lisa R. , House Russell , Hughes Karin A. , Kaiser Robert J. , Springer Amy L.
Published: October 2018

We have developed a method for the automated purification of DNA sequencing reactions using the RapXtract(tm) 384 Dye Terminator Removal Kit and the Quadra 3(tm) Workstation. The process enables purification of 384 reactions in five minutes, significantly impacting the throughput potential of sequencing laboratories. The RapXtract technology utilizes superparamagnetic particles, (i.e., particles that are not themselves magnetic but that respond to a magnetic field) and eliminates the need for centrifugation, vacuum filtration, or modified primers. The Quadra 3 Workstation is a 384-channel liquid handling system, fitted with a retractable magnetic nest designed to incorporate a 384 magnetic separator. The combined technologies result in reduced variability associated with manual methods for sequencing reaction purification.
Introduction of the Personal Digital Assistant into the Analytical Laboratory
Authors: Brooke Daniel Ll. D. , Hunter Peter , Organ Andrew J.
Published: October 2018

High throughput drug discovery is currently undergoing a change, moving away from the traditional chemistry laboratory toward a ‘factory’ environment. Analytical disciplines are changing to fit this environment. PDAs combined with wireless LAN interfaces offer a way to enter, search and retrieve data in a way that is not limited to fixed network connections. Both submission of samples for analysis and monitoring of instruments, can be accomplished via a wireless network, this allows analysts and clients to access data whilst roaming in a large laboratory or suite of laboratories. Html and Java applications have been developed to enable analysts and chemists a greater degree of flexibility to control and monitor automated equipment.
Detection of Cellular Parameters Using a Microfluidic Chip-Based System
Authors: Preckel Tobias , Luedke Gerd , Chan Samuel D. H. , Wang Benjamin N. , Dubrow Robert , Buhlmann Carsten
Published: October 2018

Lab-on-a-chip technology achieves a reduction of sample and reagent volume and automates complex laboratory processes. Here, we present the implementation of cell assays on a microfluidic platform using disposable microfluidic chips. The applications are based on the controlled movement of cells by pressure-driven flow inside networks of microfluidic channels. Cells are hydrodynamically focused and pass the fluorescence detector in single file. Initial applications are the determination of protein expression and apoptosis parameters. The microfluidic system allows unattended measurement of six samples per chip. Results obtained with the microfluidic chips showed good correlation with data obtained using a standard flow cytometer.
Applicatons of Ink-Jet Printing Technology to BioMEMS and Microfluidic Systems
Authors: Cooley Patrick , Wallace David , Antohe Bogdan
Published: October 2018

Applications of microfluidics and MEMS (micro-electromechanical systems) technology are emerging in many areas of biological and life sciences. Non-contact microdispensing systems for accurate, high-throughput deposition of bioactive fluids can be an enabling technology for these applications. In addition to bioactive fluid dispensing, ink-jet based microdispensing allows integration of features (electronic, photonic, sensing, structural, etc.) that are not possible, or very difficult, with traditional photolithographic-based MEMS fabrication methods.

Our single fluid and multifluid (MatrixJet™) piezoelectric microdispensers have been used for spot synthesis of peptides, production of microspheres to deliver drugs/biological materials, microprinting of biodegradable polymers for cell proliferation in tissue engineering applications, and spot deposition for DNA, diagnostic immunoassay, antibody and protein arrays. We have created optical elements, sensors, and electrical interconnects by microdeposition of polymers and metal alloys. We have also demonstrated the integration of a reversed phase microcolumn within a piezoelectric dispenser for use in the fractionation of peptides for mass spectrometer analysis.
Project Control for Laboratory Automation Outsourced to Consultants a 10-Step Process to Optimize the Effectiveness of Custom Information Technology Development
Authors: Hilt Lynn , Berlin Jim , Weeks Terry
Published: October 2018

This article outlines a 10-step process for business leaders in the pharmaceutical, biotech, health sciences, and clinical fields, who hire information technology (IT) applications consultants to design, develop, implement, and integrate custom laboratory automation systems. The goal of this model is to identify steps to dramatically improve the effectiveness of the consultant and to reduce implementation risk factors. The probability of project success can be increased significantly when the basics of IT systems development is understood by those internal to the organization and management guides the consultant to the finish line using a defined project control process.
Developing an Automated Enzyme Immunoassay for High-Throughput Screening of Bovine Serum Antibodies to Neospora Caninum
Authors: Wu John T. Y. , Dreger Sally , Chow Eva Y. W. , Bowlby Evelyn E. , Wong Lester S. Y.
Published: October 2018

An enzyme-linked immunosorbent assay (ELISA) for Neospora caninum antibodies was automated with a robotic workstation, the Beckman Coulter Biomek 2000, to screen 200 bovine sera. Comparing these results with manually run ELISA data, a 95.92% agreement (K = 0.9592) between the two assays was obtained. The automated assay was specific and sensitive with excellent positive and negative predictive values. The results were repeatable and reproducible. The automation flexibility was high and the operation complexity was minimal. High-throughput screening (HTS) for bovine antibodies to Neospora caninum was achieved. The assay was developed according to the internationally recognized ISO17025 standard requirements.
High-Throughput Measurement of Drug pKa Values for ADME Screening
Authors: Comer John , Box Karl
Published: October 2018

Combinatorial chemistry is now widely used to synthesize large numbers of new chemical entities. New methods have been developed for early-stage pharma-cokinetic tests, to help decide which molecules have the properties required to make them efficacious and successful in the marketplace. Of the various physicochemical tests that are used to assess ADME, pKa (aqueous ionization constant) is the key to understanding how other properties will be affected by pH. A new method is described for rapid measurement of pKa of samples drawn from 96 well DMSO stock solutions.
The Synergy™ HT: A Unique Multi-Detection Microplate Reader for HTS and Drug Discovery
Authors: Held Paul , Buehrer Lenore
Published: October 2018

Pharmaceutical and biotechnology research requires instrumentation to be both functional and versatile. In the HTS and Drug Discovery environments, microplate-based assays are developed to make determinations on large numbers of samples. Regardless of the assay protocol, the end result is the measurement by some sort of detection device. Towards that end, Bio-Tek has developed the Synergy™ HT Multi-Detection Microplate Reader. Synergy HT utilizes two independent sets of optics to provide uncompromised performance. For absorbance measurements, there is a xenon-flash lamp with a monochromator for wavelength selection and photodiode detection. This allows the selection of any wavelength for endpoint or kinetic measures from 200 nm to 999 nm in 1 nm increments, as well as spectral scans. Traditional visible wavelength fluorescence measurements are made using a tungsten-halogen lamp with interference filters (excitation and emission) for wavelength selection and photomultiplier (PMT) detection. Glow luminescence measurements are also easily accomplished in Synergy H T. If time-resolved or UV excitation fluorescence measurements are required, Synergy HT automatically integrates the xenon-flash-monochromator excitation with the interference emission filter and PMT detection. Typical applications include antibody-antigen binding, receptor-liquid binding, ELISA, nucleic acid quantitation using fluorescent dyes or direct UV analysis. Synergy HT is capable of reading any plate format up to 384-well plates and provides temperature control up to 50°C and shaking as standard features. It is compact (16″ W × 15″ D × 10″ H) and robotics-compatible through the OLE functionality of the KC4™ data reduction software that is bundled with the instrument. An upgrade to CFR 21 Part 11 compliant software is also available.
High Throughput Primer Walking of cDNA Clones
Authors: Stewart Claudia , Lum Nicole , Hill Robert , Stephens Robert , Rudnick Paul , Rassmussen Lynn , Munroe David
Published: October 2018

Primer walking of cloned DNA is a standard research tool. It has been used in the past to determine the sequence of individual clones of interest. With the expansion of DNA sequencing capacity the need to be able to walk larger numbers of clones has become necessary.

Our laboratory is a mid-sized genomics facility. In conjunction with the Advanced Biomedical Computing Center (ABCC) we have developed methods for automating the primer selection, DNA sequencing, contig assembly and sequence analysis for clones arrayed in microtiter format. This approach has allowed us to walk 475 clones (five microtiter plates) selected from a cDNA library.
Optimization of Measurement Parameters and Performance Comparison for Analyst™ GT and Analyst HT or Acquest
Authors: Zhang Yan , McGown Evelyn , Su Michael , Lavis Luke
Published: October 2018

The new Analyst™ GT is a multi-mode plate reader supporting all five leading technologies: fluorescence polarization (FP), fluorescence intensity, time-resolved fluorescence (TRF), absorbance and luminescence. It can be easily integrated into both workstation and robotic environments for HTS for all major non-radiometric applications. Analyst™ GT is based on second-generation SmartOptics™, a patented system that combines light sources, optical components and detectors together for fast high-precision measurements in 96-, 384-, and 1536-well microplates. Applications include kinase and photophase assays, receptor ligand binding assays, protease assays, cAMP, and cGMP, signal transduction, reporter gene assays and many others.

In this study, we not only optimized measurement parameters on Analyst™ GT for all five modalities but also compared instrument settings and performance with the first generation Analyst HT and Acquest.
Patterned Live Neural Networks by Induced Electrical Fields for Bio-Sensing
Authors: Prasad Shalini , Yang Mo , Zhang Xuan , Ozkan Cengiz S. , Ozkan Mihrimah
Published: October 2018

It is estimated that about 18 million people worldwide suffer from dementia and it is projected to increase to about 35 million by the year 2025. All types of dementia occur due to an aberration in memory retention and development, caused by malfunctioning neurons. Experimental investigation of the dynamics of biological networks is a fundamental step towards understanding how the nervous system works. Activity-dependant modification of synaptic strength is widely recognized as cellular basis of learning, memory and developmental plasticity. Understanding memory formation and development, thus translates to changes in the electrical activity of the neurons. It is not possible to achieve this understanding at a cellular level by in vivo studies. To map the changes in the electrical activity it is essential to conduct in-vitro studies on individual neurons. Hence there is an enormous need to develop novel ways for assembly of highly controlled neuronal networks. To this end, we used a 5 × 5 multiple microelectrode array system to spatially arrange neurons, by combination of applied DC and AC fields We characterized electric field distribution inside our test platform by using two dimensional finite element modeling (FEM). As the first stage in the formation of a neural network dielectrophoretic AC fields were used to position the neurons over the electrodes. We used DC electric field to control axon growth direction within the network. Applied electric field direction is found to be an important parameter for axon growth. Electrical impulses were recorded from the individual neurons in the network during positioning and network formation.
Self Assembly of Polymer Structures Induced by Electric Field
Authors: Yang Mo , Ozkan Cengiz S. , Gao Huajian
Published: October 2018

Amethod has been developed for fabricating polymer microstructures based on electric field induced self assembly and pattern formation. A dielectric fluid placed in between two conductive plates experience a force in an applied electric field gradient across the plates, which can induce a diffusive surface instability and self construction of the fluid surface. This process is exploited for the fabrication of self assembled polymer microstructures as well as replicated patterns through the use of pre-patterned plates or electrodes. FEM simulation is used to decide the minimum wavelength and electric gradient distribution of polymer structures. A variety of structures in the micron and nanometer scales including bio-fluidic MEMS, polymer optoelectronic devices can be fabricated using this method.
The First Automated High Content Screening System
Authors: Allison Karen
Published: October 2018

With biological discovery and technology advancing in parallel, AstraZeneca (AZ) announced that it would soon take delivery of what is thought to be the first fully automated high-throughput high-content screening system. This custom designed assay platform from RTS Life Science International (RTS) automates the IN Cell Analyzer 3000 sub cellular analysis system from Amersham Biosciences. RTS has integrated its advanced scheduling system with the imaging tool to enable AZ to evaluate the effect of drug compounds on cellular processes.
Microfluidic Patterning of Cellular Biopolymer Matrices
Authors: Tan Wei , Desai Tejal A.
Published: October 2018

Due to the complex structures of living systems, the use of microtechnology to recreate in vivo architecture has exciting potential applications. Living tissues maintain a well-organized three-dimensional (3-D) architecture, with “micro” and “nano” scale features. Microtechnologies offer the new possibility of designing and building sensors and devices in dimensional scales close to that of living tissues.1–2 However, most available microscale systems are two-dimensional, and few 3-D systems are being explored. Therefore, we have developed a versatile technique to create a 3-D microscale hierarchical system for cells and biopolymers. By taking advantage of the contraction of hydrogel matrix biopolymers, one can achieve multiple layers of cells within biopolymers using microchannels, and eventually form a hierarchical layered microstructure of cells and biopolymer. Pressure-driven microfluidics using a syringe pump (Harvard Apparatus, Model 11‘) was applied to transport cells within matrix biopolymers through the channels with controlled flow rates. Flow imaging was used to estimate the shear stress and examine the useful range of flow rates for biopolymer fluids to form the layered structure. The 3-aminopropyltriethoxysilane (APTES) — glutaraldehyde activated glass chips were found to effectively immobilize cell-matrix assemblies. Collagen or collagen-chitosan matrix biopolymers were used as constructs throughout the layers. The final structure was characterized using scanning electron microscopy (SEM). Using this approach, the “neotissue” is formed with cellular and biopolymer components engineered to model the in vivo system.
Incorporating Automation in Undergraduate Laboratories
Authors: Ingersoll Christine M. , Widmann Kimberly A. , Szakal Christopher W. , Fermier Adam M. , Troisi John M.
Published: October 2018

Automated techniques and philosophies, which have become increasingly important in modern laboratories, are not traditionally covered in undergraduate chemistry curricula. To this end, we have been incorporating automated sample preparation methods using standard robotic workstations in our undergraduate analytical chemistry laboratory. Using a Benchmate™ II Workstation, an automated method has been developed and implemented for the solid phase extraction of capsaicins from commercial hot pepper sauces prior to liquid chromatographic analysis. This paper reports on pedagogical aspects of incorporating automation into the undergraduate curriculum as well as results obtained for manual and automated extractions conducted by students.
Setting up High-Throughput Low-Volume Sequencing and PCR Reactions Using an Automated System Equipped with Precision Glass Syringes and a Non-Contact Microsolenoid Dispenser
Authors: Wu Hui-Chung , James Alex , Braunthal Nelson , Shieh Jean , Azarani Arezou
Published: October 2018

The advantages of using a new automated system, the Hydra-Plus-One System equipped with 96 or 384 precision glass syringes and a non-contact microsolenoid dispenser, in setting up high-throughput low-volume sequencing reactions and PCR are described. Using the syringe-based dispenser, which is the Hydra-PP part of this system, wet dispenses of as small as 100 nL with CVs of less than 10% can be accomplished. The single-channel, non-contact microsolenoid dispenser part of the system can dispense samples as low as 100 nL (with CVs of less than 10%) at a speed of 58s per 96 dispenses into any plate format (SBS footprint). The advantages associated with the use of the Hydra-Plus-One System for setting up PCR and sequencing reactions are high precision at nanoliter-dispense range; speed; and minimal waste of precious and expensive samples. The single-channel dispenser eliminates the dead volume associated with aspirating from reservoirs or troughs and thereby reduces sample waste. In addition, virtually all material can be recovered from the dispenser. Finally, non-contact dispensing enables distribution of sample into wells without any in-between-dispenses washing requirements.