Instrument Vendors Research Articles

Trace2PS and FSA2PS: two software toolkits for converting trace and fsa files to PostScript format

BackgroundDue to the advanced techniques in sequencing and fragment analysis, DNA sequencers and analyzers produce vast amounts of data within short time. To administrate the large data volume conveniently, efficient data management systems are used in order to process and to store sequencers' or analyzers' data outcome. The inclusion of graphical reports in such systems is necessary to achieve a comprehensive view of the integrated data. However, the resulting data of sequencing and fragment analysis runs are stored in a proprietary format, the so-called trace or fsa format, which is only readable by programs provided by the instrument's vendor operating on the machine itself or by commercial tools designed for editing the respective data. To allow for a quick conversion of the proprietary data format into a commonly used one, toolkits are required that reach this aim and can be easily integrated into workflow systems.ResultsWe have developed the software toolkits Trace2PS and Fsa2PS which allow to convert sequence and fragment analysis raw data files to PostScript images, respectively. The toolkits are implemented as Perl modules that can be used as standalone command line applications in conjunction with a script-based analysis pipeline, or integrated in software applications for displaying the data content of trace and fsa files. The converter modules support the commonly used file formats for storage of sequencing (ABI and SCF) and fragment analysis data (FSA).ConclusionThe software toolkits provide useful applications to convert sequencing and fragment analysis files from a proprietary into a more common, human-readable format. Trace2PS and FSA2PS are useful and capable in data management workflow systems like SAMS, or laboratory information systems that are used for displaying trace and fragment analysis results via web-based tools over an intranet or internet connection to users that can view their results directly on the screen.

An Accurate-Mass-Based Spectral-Averaging Isotope-Pattern-Filtering Algorithm for Extraction of Drug Metabolites Possessing a Distinct Isotope Pattern from LC-MS Data

Detection and identification (ID) of all drug metabolites following liquid chromatography (LC)/mass spectrometry (MS) analysis of complex biological matrixes are not trivial. To facilitate detection of drug-derived materials that possess highly diagnostic isotopic patterns (e.g., chlorine- and bromine-containing compounds), we report an accurate-mass-based spectral-averaging isotope-pattern-filtering (AMSA-IPF) algorithm developed in the computational language R. The AMSA-IPF algorithm offers three significant improvements over the traditional isotope filtering method often provided by instrument vendors. First, spectral averaging is performed before the IPF to reduce scan-to-scan variability of ion intensities. Second, the IPF process is strictly based on accurate mass typically obtained on high resolution mass spectrometers. The designated isotopic ion-pairs (e.g., M + 2:M or M + 1:M, where M is the molecular ion and M + 1 and M + 2 are the isotopic ions) must fall into the predefined accurate mass tolerance window (e.g., 5 ppm) and at the same time satisfy the predefined relative abundance criteria. Third, both M + 1:M and M + 2:M ion pairs are inspected in the filtering process. The inclusion of M + 1:M ion pair enhanced the specificity of this algorithm by removing background ions that form M:M + 2 ion pairs within predefined isotope ratios by coincidence. The algorithm demonstrated excellent effectiveness in detecting drug-related ions in in vivo samples (plasma, bile, urine and feces) obtained from rats orally dosed with 14C-loratadine. The ion chromatograms of the filtered LC-MS data files showed near perfect qualitative correlation with the corresponding radioprofiles. AMSA-IPF will be another great tool to facilitate detection and ID of drug metabolites in complex LC-MS data without the help of radiolabels. The AMSA-IPF algorithm is applicable to not only compounds containing distinct natural isotopes (such as Cl and Br) but also compounds that contain synthetically incorporated isotopes (13C, 15N, etc) generating a distinct isotope pattern. The ability to detect and identify metabolites from nonradiolabeled studies will be extremely beneficial to achieve compliance with FDA's most recent guidance on metabolites in safety testing (MIST).

Society Spotlight: Spotlight on the Calibration and Validation Group

The Calibration and Validation Group (CVG) was founded in early 1995 by Herman Lam, Chung Chow Chan and YC Lee in Toronto, Canada. At that time, the requirements and the practices of method validation, analytical system qualification and instrument performance verification were only discussed individually among a very small group of professionals; the founders realized that there was a need to form a scientific organization to focus on those subjects and share the learning. Initially, the membership was mainly derived from the regulated pharmaceutical industry, but the participation has grown over the years to include scientists from a wide range of backgrounds, including pharmaceuticals, chemicals, environmental, food, distilleries, biotechnology, instrument vendors, government agencies, local colleges and universities. CVG was officially incorporated as a nonprofit organization in Canada in 1999.

Laboratory Information Management System for Emergency Response: Validation and Quality Assurance of Analytical Methodologies

The Emergency Response Management System is a customizable laboratory information management system (LIMS) developed to support chemical terrorism emergency response laboratory activities at the Centers for Disease Control and Prevention (CDC). Unique features of the LIMS include the following: (I) method profiles that provide an efficient tool for both validation and production experiments, (2) scalability of each assay to accommodate emergency surge-capacity needs, (3) standardized data formats for communicating between different instrument types and vendors, and (4) automated quality assurance communications that allow remote review and approval by CDC statisticians and supervisors. The system has been tested under exercise and real conditions for more than five years and has proved to be robust and effective.

Report on the Barbados Workshop

Report on the Barbados Workshop

A Method for Automatically Interpreting Mass Spectra of 18O-Labeled Isotopic Clusters

16O/18O labeling is one differential proteomics technology among many that promises diagnostic and prognostic biomarkers of disease. Although the incorporation of 18O in the C-terminal carboxyl group during endoproteinase digestion in the presence of H2 18O makes the process of labeling facile, the ease and effectiveness of label incorporation have in some regards been outweighed by the difficulties in interpreting the resulting spectra. Complex isotope patterns result from the composition of unlabeled (18O(0)), singly labeled (18O(1)), and doubly labeled species (18O(2)) as well as contributions from the naturally occurring isotopes (e.g. 13C and 15N). Moreover because labeling is enzymatic, the number of 18O atoms incorporated can vary from peptide to peptide. Finally it is difficult to distinguish highly up-regulated from highly down-regulated or C-terminal peptides. We have developed an algorithm entitled regression analysis applied to mass spectrometry (RAAMS) that automatically, rapidly, and confidently interprets spectra of 18O-labeled peptides without requiring chemical composition information derived from product ion spectra. The algorithm is able to measure the effective 18O incorporation rate due to variable enzyme substrate specificity of the pseudosubstrate during the isotope exchange reaction and corrects for the 18O(0) abundance that remains in the labeled sample when using a two-step digestion/labeling procedure. We have also incorporated a method for distinguishing pure 18O(0) from pure 18O(2) peptides utilizing impure H2 18O. The algorithm operates on centroided peak lists and is therefore very fast: nine chromatograms of, on average, 1,168 spectra and containing, on average, 6,761 isotopic clusters were interpreted in, on average, 45 s per chromatogram. RAAMS is fast enough (average, 38 ms/spectrum) to allow the possibility of performing information-dependent MS/MS on a chromatographic time scale on species exceeding predetermined ratio thresholds. We describe in detail the operation of the algorithm and demonstrate its use on datasets with known and unknown ratios.

Usability in the Lab: Techniques for Creating Usable Products

Laboratory automation and instrumentation vendors frequently claim usability among their long lists of features and benefits—but can they justify that claim? What makes a product usable and how do you design for usability? This article outlines an approach used to create usable products in other application areas, such as eCommerce and medical device development, and suggests that a similar approach could provide benefits for users and developers alike in the field of laboratory automation. The user-centered design process is summarized, together with a set of usability heuristics that can be applied during the design process and used to evaluate usability during development.

Versatile Data Acquisition for a Gas Chromatograph

Data acquisition is reported for a Varian CP 3800 gas chromatograph with affordable and user friendly interface box and software. LabPro was triggered to commence data acquisition upon sample injection and simultaneously monitored two detectors and oven temperature. After acquisition, functions are available for determining the retention time and for peak integration after baseline subtraction. Data may be exported as a text file. The interface box and software are available at a tenth of the cost of the instrument vendor's software. In this work, the determination of optimum carrier gas flow rate is reported as an example.

Overview and Architecture of the Java Integration Framework, Hybrid Scheduler, and Web-Enabled LIMS

Most of the scheduling software and instrument integration frameworks are written in Visual Basic, C/C++, or the LabView programming environment. A lot of these frameworks are proprietary tools of instrument vendors and are used by these companies during system integration of their instruments. In addition to the closed architecture of these products, the scheduler choice is very limited. ReTiSoft Inc. has created a suite of software products that address these problems. In this article we would like to introduce ReTiSoft's open-architecture framework for instrument integration, a hybrid scheduler (static and dynamic) and a Web-enabled interface to the automated system. In addition to ReTiSoft's integration framework (Genera) and the hybrid-scheduling software (Supra), we recently developed a Web-enabled application that allows scientists to log onto the automated system remotely, set up and run assays, examine and analyze the data produced during the experiment. The software is called DataPilot and is comprised of a high-performance database engine and the Apache Web server. In unison with Genera's and Supra's open-architecture approach, DataPilot can be modified and customized by system integrators to suit their specific application needs. The application serves as a data repository and adheres to guidelines presented by the Code of Federal Regulations for electronic records and electronic signatures; the guidelines are known as 21 CFR Part 11. This article provides an architectural overview of our software products and justifies its merits in comparison to other technologies commonly used in laboratories. We describe our Genera integration framework, give an overview of our scheduling algorithms, describe a Web-enabled data-tracking software and the enzyme-linked immunosorbent assay (ELISA assay), and describe different methods of automated system validation using our software. We also offer some conclusions.

LOINC, a universal standard for identifying laboratory observations: a 5-year update.

The Logical Observation Identifier Names and Codes (LOINC) database provides a universal code system for reporting laboratory and other clinical observations. Its purpose is to identify observations in electronic messages such as Health Level Seven (HL7) observation messages, so that when hospitals, health maintenance organizations, pharmaceutical manufacturers, researchers, and public health departments receive such messages from multiple sources, they can automatically file the results in the right slots of their medical records, research, and/or public health systems. For each observation, the database includes a code (of which 25 000 are laboratory test observations), a long formal name, a "short" 30-character name, and synonyms. The database comes with a mapping program called Regenstrief LOINC Mapping Assistant (RELMA(TM)) to assist the mapping of local test codes to LOINC codes and to facilitate browsing of the LOINC results. Both LOINC and RELMA are available at no cost from http://www.regenstrief.org/loinc/. The LOINC medical database carries records for >30 000 different observations. LOINC codes are being used by large reference laboratories and federal agencies, e.g., the CDC and the Department of Veterans Affairs, and are part of the Health Insurance Portability and Accountability Act (HIPAA) attachment proposal. Internationally, they have been adopted in Switzerland, Hong Kong, Australia, and Canada, and by the German national standards organization, the Deutsches Instituts für Normung. Laboratories should include LOINC codes in their outbound HL7 messages so that clinical and research clients can easily integrate these results into their clinical and research repositories. Laboratories should also encourage instrument vendors to deliver LOINC codes in their instrument outputs and demand LOINC codes in HL7 messages they get from reference laboratories to avoid the need to lump so many referral tests under the "send out lab" code.

Architecture drives test system standards

To automate test and measurement systems in R&D and manufacturing settings, it is common practice to connect the instruments to computers. With modern programming languages and a simple setup, the task is no harder than calling up a simple function. The only remarkable aspect is that this function communicates with a hardware device that either measures or stimulates some aspect of the physical world. Grouping the functions needed for controlling an instrument forms a library, which is called an instrument driver. Above all, instrument drivers are convenient. They can be used to build test and measurement systems having interchangeable elements, so that the systems can be maintained through, and despite, changes in the computer, the instruments, and the device under test (DUT). Basically, the drivers encapsulate the various I/O operations between computer and instrument. They are also a convenient interface for those test programs that use instruments. And-an important benefit-they help to insulate the test system from changes made in the underlying instrument hardware. In theory, a test engineer should be able to exchange a new instrument for an existing one within a system and reconfigure that system to use the appropriate driver. In practice, further work is unavoidable before the system will behave as it did before the exchange. Several solutions are being considered by instrument vendors and end-users, including exactly how to exchange instruments within a system, and to what standards a particular driver or system should conform.

A Capstone Writing Experience in Polymer Chemistry: Writing a Proposal for an Instrument Purchase

A capstone writing experience for upper-level polymer chemistry is described in which students write a proposal to the management of a hypothetical company recommending for or against the purchase of a particular make and model of polymer characterization instrumentation. This project involves background research into the appropriate instrumental method, the collection of quotes and product information from instrumentation vendors, and the development of capital and operating budgets. The students evaluate this information and make value judgments as to whether any purchase is justified and, if so, they suggest which make and model should be purchased. The term papers are to be written for a nonspecialist audience, which forces the students to write the paper in terms that are accessible to the scientifically literate lay person. This exercise has value in its own right, produces an excellent assessment tool, and greatly helps the students once they proceed to permanent employment where such writing skill...

THE SURGICAL TRAY

This article provides an overview of the most commonly used instruments for excisional surgery. It has also discussed some of the specialty instruments that may be of value. It may serve as a starting point for the outfitting of a dermatologic surgery practice. However, it is no substitute for seeing, touching, and handling the instruments. At many of the larger specialty meetings, the instrument vendors will be displaying their wares. These displays offer an excellent opportunity to evaluate the many instruments. All of these fancy shiny instruments are merely tools to be used as an extension of the surgeon's hand and brain. They should work for the surgeon in a manner that is comfortable and efficient. Only the surgeon can decide what works best.

Peering Into The Analytical Ciystal Ball

In the field of analytical chemistry, according to chemistry professor M. Bonner Denton of the University of Arizona, Tucson, we would all like to have is the Mark I Magic Analyzer, into which you throw any kind of sample, tell it what you want to know about the sample, and it gives you the answer. The next thing you want is a handheld unit, he said. This has been widely acclaimed for many years on a popular TV show—showing a photo of a tricorder, a portable instrument used on Star Trek for materials analysis and medical diagnosis. Tricorders may not have been available at the Pittcon '97 exposition, but presentations by Denton and four other speakers at a symposium on The Future of Analytical Instrumentation suggest that instrument vendors may be getting ever closer to that ideal. Before a standing-room-only audience, the presenters did their best to review the current status and divine the ...

Customer Service in Neurophysiology Laboratories

.Customers of a neurophysiology laboratory include not only patients and their families, but physicians, insurance companies, instrument vendors, and members of many other departments in the hospital. Technologists need to recognize customers and their needs, then address those needs. The Seven Habits of Highly Effective People suggested by Steven Covey can be used successfully by electroneurodiagnostic technologists to provide effective customer service.

Total reflection x-ray fluorescence analysis of planarized semiconductor product wafers

The use and effectiveness of total reflection x-ray fluorescence (TXRF) have been widely reported. The application of this technique in semiconductor fabrication has become popular and several instrument vendors now make equipment optimized for this particular purpose. Because sample surfaces must be optically flat in order to achieve the total reflectance condition, the majority of the work in investigating semiconductor processing is performed on monitor wafers. The use of TXRF for in-line process control, therefore, has been limited to silicon or dielectric film substrates, either on the surface or the backside of the wafer. This article details the use of TXRF analysis for monitoring the contamination present on production-wafer surfaces, after planarization techniques have been used. The wafer surfaces at several of these planarization steps meet the criteria for the application of the TXRF technique using the normal operating conditions of the TXRF instrument. This technique can be used as process-monitoring tool to study wafer surfaces for particular contaminants that affect wafer yield. TXRF is being used on IBM’s state-of-the-art DRAM and logic circuits.

Validating automated analytical instruments to meet regulatory and quality standard requirements

Analytical laboratories are more and more faced to meet official regulatory requirements as described in FDA and EPA good laboratory practice, good automated laboratory practice and good manufacturing practice regulations or to officially establish quality systems, such as specified in the ISO 9000 Series quality standards, in the ISO Guide 25 or in the EN 45001 guidelines. The impact on analytical instrumentation will be the requirement for stringent validation of analytical equipment and methods which increase the overall analysis costs. An overview is presented on the validation requirements using e.g. gas chromatography, high performance liquid chromatography, capillary electrophoresis and UV-visible spectroscopy and on the strategy to meet such needs at minimal extra costs with the help of an instrument vendor. It is recommended to use instrument hardware that has already built-in tools for self-verification and which is to be validated at the vendor's site. Performance testing in the user's laboratory is done using standard operating procedures as supplied with the instrument. If resources in the user's laboratory are limited, the performance verification is done by the vendor. Software and the entire computer system is validated prior to shipment at the vendor's site. Acceptance testing is done in the user's environment following the vendor recommendations. Analytical methods are validated automatically at the end of method development using a dedicated software. The software can be customized such that it can also be used for daily automated system suitability testing. Security and integrity of analytical data are ensured by saving the raw data together with instrument conditions and instrument log-books in check-sum protected binary register files for long-term archiving.

Al-27 NMR without Probe Background

Al-27 NMR is a useful tool in studying structural features of aluminum chemicals. However, Al-27 NMR is hindered by an Al-27 background from NMR probes. This background is a very broad, featureless Al-27 resonance with a chemical shift of about 50 ppm. It is often difficult to distinguish resonances of many aluminum species, which are themselves usually very broad, from the probe background. At least three literature references note the Al-27 probe background. Further, we have observed virtually identical probe backgrounds in standard 10-mm broad-band probes of all major vendors of NMR instruments. In this discussion we report elimination of the probe background through modification of a standard NMR probe.

Brass & Glass: Scientific Instrument Making Workshops in Scotland as Illustrated by Instruments from the Arthur Frank Collection at the Royal Museum of Scotland by T. N. Clarke, et al

TECHNOLOGY AND CULTURE Book Reviews 171 Brass Cf Glass: Scientific Instrument Making Workshops in Scotland as Illustrated by Instruments from the Arthur Frank Collection at the Royal Museum ofScotland. By T. N. Clarke, A. D. Morrison-Low, and A. D. C. Simpson. Edinburgh: National Museums of Scotland, 1989. Pp. xiii + 320; illustrations, notes, index. £25.00 (paper). This volume gives flesh and blood to the names of a host of Scottish scientific instrument makers. Over the past twenty years, the Royal Museum of Scotland has acquired numerous instruments collected by the optician Arthur Frank. These “objects in brass & glass,” to use Charles Dickens’s phrase, date from the 18th to the early 20th century, with a wide spectrum of vendors represented. T. N. Clarke, A. D. Morrison-Low, and A. D. C. Simpson have not only prepared a catalog of the Frank collection but also present accounts of the life and work of the makers and retailers represented. Instruments are grouped by vendor, the vendors by geographical location, and those from one area in roughly chronological order. A few Scots, like James Short, the famed 18th-century maker of telescope mirrors; Alexander Adie and his relatives, the 19th-century makers of drawing instruments and meteorological equipment; and James White and his family, who sold instruments designed by Lord Kelvin, were known internationally. The authors discuss the vendors’ firms in detail, giving accounts of several generations of makers where it is appropriate and tracing ties of apprenticeship and of acquain­ tanceship in institutions like the Royal Scottish Society of Arts. The book also presents a wealth of information about the other makers and retailers of instruments represented in the Frank collection. Thus, for example, one learns of David Stalker, a watch- and clockmaker in the port town of Leith who also occasionally sold nautical instruments, of the cutler Alexander Cameroon of Dundee, who sold and repaired scientific instruments on the side, and of Charles Gerletti, one of several Italians who sold looking glasses and barometers in 19th-century Glasgow. These and numerous other examples illustrate the widely different meanings of the names appearing on a scientific instrument. A name may be that of the firm that introduced the apparatus, it may be the mark of the maker of all or part of the instrument, or it may only be the mark of a retailer. These diverse meanings suggest useful comparisons between the role of instrument vendors in Scotland, who often relied on English suppliers, and those who sold apparatuses in countries like the United States, who also frequently obtained instruments elsewhere. This handsome volume is illustrated with photographs of both the instruments in the Frank collection and of appropriate portraits, drawings of workshops, and trade cards. Those trying to identify and date Scottish scientific instruments will find it an indispensable source. The book will also intrigue scholars interested in the business history of Scotland, in Scottish science in an era that boasted David Brewster, 172 Book Reviews TECHNOLOGY AND CULTURE Thomas Graham, and William Thomson, and in the general efflores­ cence of technical activity that accompanied the Industrial Revolu­ tion. More generally, the authors’ use of evidence provided by objects, of archival and legal records, of city directories and newspapers, and of the work of other historians offers a model for anyone exploring the social history of Scotland. Peggy Aldrich Kidwell Dr. Kidwell watches over the collection of mathematical instruments in the National Museum of American History. Her research interests include the history of astrophys­ ics, the role of women in science, and the history of computing devices. Science in Sweden: The Royal Swedish Academy of Sciences 1739—1989. Edited by Tore Frangsmyr. Nantucket, Mass.: Science History Publications, 1989. Pp. vii + 291; illustrations, notes, appendix, index. $45.00. The Royal Swedish Academy of Sciences is best known for its activities in connection with the Nobel Prizes. In Sweden the academy has played a leading role in the promotion of science and technology since it was founded in 1739. This semiofficial collection of essays, issued on the academy’s 250th birthday, analyzes some of the more important activities in its long history. Essays are by definition not comprehensive, and obviously one could suggest...

Digital's lab standards program is growing

Digital Equipment Corp/s new program to aid laboratories in developing an integrated multivendor computing environment is growing. Four laboratory applications vendors recently added their products to Digital's integrated laboratory automation (ILA) standards program portfolio. That addition brought the total number of vendors in the program to 23, with 37 products meeting the program's criteria. The program was introduced by Digital in September. defines how products from Digital and thirdparty laboratory instrument and software vendors communicate and share data among applications such as real time data acquisition and laboratory information management. The approach being taken in the ILA standards program, according to Gary Eichhorn, manager of laboratory data products at Digital, helps Digital customers who are moving from automation of individual tasks to laboratorywide automation by ensuring the availability of broad range of applications solutions. It also means, says Eichhorn, a laboratory...