A reliable and inexpensive microprocessor system for collection and transfer of raw immunoassay data

A very low cost microprocessor system has been designed to ease data handling problems in a large workload immunoassay laboratory. The microprocessor collects and stores data from many immunoassay detection devices simultaneously, and transfers the data to a minicomputer for analysis as each measurement batch is completed. Stored data are protected against a mains power failure during collection and against non-availability of the minicomputer at transfer time. The system provides fast and reliable transfer of very large amounts of raw data from measurement devices to computer, and therefore facilitates the use of a statistically sound data reduction software package.     

A novel design of simulated moving bed (SMB) chromatography for separation of ketoprofen enantiomer

A simulated moving bed (SMB) chromatography system is a powerful tool for preparative scale separation, which can be applied to the separation of chiral compound. We have designed our own lab-scale SMB chromatography using 5 HPLC pumps, 6 stainless steel columns and 4 multi-position valves, to separate a racemic mixture of ketoprofen in to its enantiomers. Our design has the characteristics of the low cost for assembly for the SMB chromatography and easy repair of the unit, which differs from the designs suggested by other investigators. It is possible for the flow path through each column to be independently changed by computer control, using 4 multi-position rotary valves and 5 HPLC solvent delivery pumps. In order to prove the operability of our SMB system, attempts were made to separate the (S)-ketoprofen enantiomer from a ketoprofen racemic mixture. The operating parameters of the SMB chromatography were calculated for ketoprofen separation from a batch chromatography experiment as well as by the triangle theory. With a feed concentration of 1 mg/mL, (S)-ketoprofen was obtained with a purity of 96% under the calculated operating conditions.     

Habitat models and their transfer for single and multi species groups: a case study of carabids in an alluvial forest

Environmental factors influencing the occurrence of single species and multi species groups of carabids in alluvial forest al the River Elbe were determined with habitat suitability models. Two representative species for different ecotypes present in the investigated community. Agonum livens and Pterostichus oblongopunctatus. were defined by means of a discriminant analysis. The two species differed greatly in their microhabitat distribution, Agonum livens was chosen as target species for a multi species group of wetland species that inhabited the fringes of temporary waters in the forest. In contrast, P. oblongopunctatus should represent species of deciduous forests. Using stepwise multiple logistic regression statistically significant habitat suitability models were estimated, reliably predicting the species" occurrence, A subsequent evaluation by cross-validations and receiver operating characteristic (ROC) curves indicated a high discriminatory power. A transfer of the model onto different data sets in time was applied to validate the model. Alternatively, a multi species habitat model, taking into account weighted occurrence data of the wetland species group, was estimated. In order to show that the chosen target species truly holds an umbrella effect upon the represented multi species group, we used ROC curves to indicate the transferability of the target species' habitat model for the multi species group and vice versa.     

Closed-loop control of fed-batch cultures of recombinant Escherichia coli using on-line HPLC

This article describes a fully automated system for the on-line monitoring and closed-loop control of a fed-batch fermentation of recombinant Escherichia coli, and presents two case studies of its used in limiting production of unwanted byproducts such as acetic in fed-batch fermentations. The system had two components. The first components, on-line monitoring, comprised an aseptic sampling device, a microcentrifuge, and HPLC System. These instruments removed a Sample from a fermentor, spun it at high speed to separate solid and liquid components, and then automatically injected the supernatant onto an HPLC column for analysis. The second component consisted of control algorithms programmed using the LabView visual programming environment in a control computer that was linked via a remote components were linked so that results from the on-line HPLC were captured and used by the control algorithm was designed to demonstrate coarse feedback control to confirm the operability of the controller. The second case study showed how the system could be used in a more sophisticated feedings strategy providing fine control and limiting acetate concentration to a low level throughout the fermentation. (c) 1994 John Wiley & Sons, Inc.     

A low-cost chromatograph data-collection system

A data collection system has been constructed, based on the low-cost BBC microcomputer, which provides for the digitization and storage of the data from one or more g.l.c. or h.p.l.c. instruments, or from other data sources with similar data rates. The data can be observed during collection on the graphics screen, and are then stored on disk for subsequent processing. This processing is designed to be interactive, so that the operator can influence decisions about base-line drifts, peak separations, etc. when integrating the peaks, and can decide which peaks are to be stored in a time/intensity record, on the basis of a visual display of the trace. A low cost multi-channel precision ADC, using isolated voltage-to-frequency transducers sited at the sources of data, and multiple counters at the computer, may be used to measure several signals simultaneously even when they originate at some distance from the computer, and extra memory can also be added to the BBC microcomputer to allow temporary storage of data. The software is written in machine code (for the data collection) and BASIC (for the analysis routines) so that modifications to the latter routines can be made easily. The user interface is suitable for routine users who have no computing experience.     

Development of at‐line assay to monitor charge variants of MAbs during production

One major challenge currently facing the biopharmaceutical industry is to understand how MAb microheterogeneity affects therapeutic efficacy, potency, immunogenicity, and clearance. MAb micro‐heterogeneity can result from post‐translational modifications such as sialylation, galactosylation, C‐terminal lysine cleavage, glycine amidation, and tryptophan oxidation, each of which can generate MAb charge variants; such heterogeneity can affect pharmacokinetics (PK) considerably. Implementation of appropriate on‐line quality control strategies may help to regulate bioprocesses, thus enabling more homogenous material with desired post‐translational modifications and PK behavior. However, one major restriction to implementation of quality control strategies is the availability of techniques for obtaining on‐line or at‐line measurements of these attributes. In this work, we describe the development of an at‐line assay to separate MAb charge variants in near real‐time, which could ultimately be used to implement on‐line quality control strategies for MAb production. The assay consists of a 2D‐HPLC method with sequential in‐line Protein A and WCX‐10 HPLC column steps. To perform the 2D‐HPLC assay at‐line, the two columns steps were integrated into a single method using a novel system configuration that allowed parallel flow over column 1 or column 2 or sequential flow from column 1 to column 2. A bioreactor system was also developed such that media samples could be removed automatically from bioreactor vessels during production and delivered to the 2D‐HPLC for analysis. With this at‐line HPLC assay, we have demonstrated that MAb microheterogeneity occurs throughout the cell cycle whether the host cell line is grown under different or the same nominal culture conditions. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:249–255, 2014     

Alternatives in the handling,processing and storage of electrocardiograms.

Physicians and administrators are becoming aware that computer technology can play a significant role in the electrocardiology department. Problems related to the large number of requests for electrocardiograms, the production and communication of electrocardiographic tracings and reports, the access to stored tracings and the overall cost of providing effective services have led administrators to look for assistance through automation. Before expensive equipment and new procedures are introduced, a survey of the electrocardiology department''s functions and procedures can lead to important insights. Automation can be achieved in stages, and problems can be solved by separate steps. Options range from basic word-processing support to completely automated electrocardiographic interpretation and computerized storage of records. Choosing the appropriate equipment and programs requires knowledge of the present system, awareness of the options and analysis of the costs and savings.     

Computer graphics presentation modes for biologic data. Types and examples

New advances in automated cytology, computer microscopy, densitometry and other instrumentation for feature/scene acquisition or analysis have resulted in higher information densities than heretofore encountered. Two-, three- and four-space computer graphics provide favorable bandwidth conditions for transforming complex, large-scale data sets into visual displays that allow a human observer, utilizing the brain's efficient processing of visual information, to rapidly grasp relationships and synthesize concepts. Examples of multidimensional displays are presented, all developed by neuroscientists who are not computer specialists. Because modern graphics and image-synthesis techniques can now be implemented on any one of several commercially available very-high-speed integrated-circuit-based display systems, at moderate cost, exploitation of specifically visual presentation should be carefully considered in any system generating information in high density.     

基于虚拟仪器技术的血管壁动态信息无创检测与辅助诊断系统

为了在体外无损地实现对血管壁动态信息、心电和心音信号等医学信息多参数的综合同步检测以及分析和处理,利用虚拟仪器技术设计了血管壁动态信息多参数的无创检测辅助诊断系统．该系统硬件平台由信号输入模块、信号调理模块以及采集卡等三大模块组成。软件系统由开发虚拟仪器的流行软件LabVIEW编写,实现了数据的采集、实时显示、分析处理和存储等。初步的临床检测结果证实了本无创检测系统的可行性和临床应用的前景,为功能性无创辅助诊断与血管壁弹性（硬化）程度有关的血管疾病提供了一种新的方法。     

Visualization of multidimensional spectra in flow cytometry.

Flow data from a cell sorter have been processed by hardwired circuits which include amplification, discrimination, coincidence requirements, peak sensing and holding, A-D conversion, and a computerized pulse height analysis with storage of the spectra obtained. Two dimensional spectra can be stored directly in memory, on tape and disk. Three and four parametric cellular events can be recorded on line during the flow measurement in a sequential mode on tape for subsequent recall. Simple processing of these data can be performed for displaying of two dimensional projections from these multidimensional spaces based on threshold conditions for the remaining parameters. Interfaced transmission of the stored data to a large scale computer enables more sophisticated data analysis. Data reduction by means of a multidimensional probability analysis has been carried out in order to transfer the spectra to a computerized picture system for display. This system creates perspective two-dimensional images from a three-dimensional data space. Frequency can be converted into grey levels. Hard copy in color (color as the third dimension and color intensity as frequency) simplifies the visualization of multiparametric flow data sets.     

The Computerized Laboratory Notebook concept for genetic toxicology experimentation and testing

We describe a microcomputer system utilizing the Computerized Laboratory Notebook (CLN) concept developed in our laboratory for the purpose of automating the Battery of Leukocyte Tests (BLT). The BLT was designed to evaluate blood specimens for toxic, immunotoxic, and genotoxic effects after in vivo exposure to putative mutagens. A system was developed with the advantages of low cost, limited spatial requirements, ease of use for personnel inexperienced with computers, and applicability to specific testing yet flexibility for experimentation. This system eliminates cumbersome record keeping and repetitive analysis inherent in genetic toxicology bioassays. Statistical analysis of the vast quantity of data produced by the BLT would not be feasible without a central database. Our central database is maintained by an integrated package which we have adapted to develop the CLN. The clonal assay of lymphocyte mutagenesis (CALM) section of the CLN is demonstrated. PC-Slaves expand the microcomputer to multiple workstations so that our computerized notebook can be used next to a hood while other work is done in an office and instrument room simultaneously. Communication with peripheral instruments is an indispensable part of many laboratory operations, and we present a representative program, written to acquire and analyze CALM data, for communicating with both a liquid scintillation counter and an ELISA plate reader. In conclusion we discuss how our computer system could easily be adapted to the needs of other laboratories.     

微流控芯片在水环境污染分析中的应用

近年来,一种新型技术——微流控芯片技术因其分析速度快、消耗低、体积小、操作简单等特点而备受世界各国的广泛重视.该技术以微通道网络为基本特征,以微机电系统(MEMS)工艺为技术依托,将整个实验室的功能集成在微小芯片上,即构成所谓“芯片实验室”.本文从该技术的基本情况出发,介绍了微流控芯片的发展,并从仪器小型化、系统集成化、不同的芯片材料以及多种检测技术等方面,着重讨论了其在水环境污染分析方面的实际应用和发展前景,指出了它当前所面临的一些问题.随着微流控芯片的不断发展,高速多通道检测装置、低成本设备以及集成了多种方法的高通用性微流控检测芯片,都将成为未来研究的热点.     

Early diagnostic esophagoscopy in the management of corrosive burns of the esophagus

Effective methods developed to review and study the care of patients in hospital have not been applicable to ambulatory care, in which definitive diagnosis is the exception rather than the rule. A reasonable alternative to using diagnosis as the basis for assessing ambulatory care is to use the problems or requests presented by the patients themselves. A system has been developed for classifying and coding this information for flexible computer retrieval. Testing indicates that the system is simple in design, easily mastered by nonphysicians and provides reliable, useful data at a low cost.     

GENEUS, a computer system for DNA and protein sequence analysis containing an information retrieval system for the EMBL data library.

We describe a comprehensive computer system, GENEUS, for extensive DNA, RNA and protein sequence analysis. The analysis system is developed for the DEC VAX/VMS computer and uses the EMBL Nucleic Acid Sequence Data Library. Help information is available on-line on terminal screen. To speed up system handling, a qualifier oriented user communication is employed. All results are stored on files making them accessible to the computer editor. An information retrieval system for the EMBL Nucleotide Sequence Data Library is also described. A defined data-base interface allows connection to other analysis programs.+     

Novel device for quick measurement of glucose in POCT areas without pre‐analytical steps based on a multi‐way glucose biosensor

Professional Point of Care testing demands rapid analysis and professional quality. To assure rapid analysis of high quality the analytical tool ideally should be able to work without sample pre‐treatment and should offer the opportunity to calibrate and/or control the analytical performance of the tool. In contrast to an enormous number of different disposable‐strips used for patient self monitoring today and based on an extended knowledge with respect to multi‐way biosensors used in laboratory analyzers we decided to develop a professional Point of Care Testing system for glucose analysis based on a multi‐way biosensor. The multi‐way glucose biosensor placed in the instrument for 30 days did reduce the lag time between blood withdrawal and availability of a result of lab quality in a bedside area to about 10 seconds. No pre‐analytical steps are necessary for measuring capillary whole blood, no crossing over was observed, and the data could be transferred into a laboratory information system or a hospital information system. Thus, we were able to realize tools for professional health control able to measure glucose values in laboratory quality at places outside laboratories: e.g., in doctor's offices, hospital wards, critical care units, and training units of athletes. By combining the advantages of laboratory analyzers (high quality and low sample price) and the advantages of disposable strips (simple procedure and immediate results after sample withdrawal) with the Glukometer 3000 and LactatProfi 3000 we did start to fill the gap between the two basic technologies available on the market for diagnosis today. Glukometer 3000 and LactatProfi 3000 are worldwide the first and only mobile glucose and lactate measuring instruments for decentralized locations based on multi‐way biosensors.     

Research on heterogeneous data integration model of group enterprise based on cluster computing

Cluster, consisting of a group of computers, is to act as a whole system to provide users with computer resources. Each computer is a node of this cluster. Cluster computer refers to a system consisting of a complete set of computers connected to each other. With the rapid development of computer technology, cluster computing technique with high performance–cost ratio has been widely applied in distributed parallel computing. For the large-scale close data in group enterprise, a heterogeneous data integration model was built under cluster environment based on cluster computing, XML technology and ontology theory. Such model could provide users unified and transparent access interfaces. Based on cluster computing, the work has solved the heterogeneous data integration problems by means of Ontology and XML technology. Furthermore, good application effect has been achieved compared with traditional data integration model. Furthermore, it was proved that this model improved the computing capacity of system, with high performance–cost ratio. Thus, it is hoped to provide support for decision-making of enterprise managers.     

HPLC-based analysis of serum N-glycans on a 96-well plate platform with dedicated database software

We present a robust, fully automatable technology platform that includes computer software for the detailed analysis of low femtomoles of N-linked sugars released from glycoproteins. Features include (i) sample immobilization in 96-well plates, glycan release, and fluorescent labeling; (ii) quantitative HPLC analysis, including monosaccharide sequence, linkage, and arm-specific information for charged and neutral glycans; (iii) automatic structural assignment of peaks from HPLC profiles via web-based software that accesses our database (GlycoBase) of more than 350 N-glycan structures, including 117 present in the human serum glycome; and (iv) software (autoGU) that progressively analyzes data from exoglycosidase digestions to produce a refined list of final structures. The N-glycans from a plate of 96 samples can be released and purified in 2 or 3 days and profiled in 2 days. This strategy can be used for (i) identification and screening of disease biomarkers and (ii) monitoring the production of therapeutic glycoproteins, allowing optimization of production conditions. This technology is also suitable for preparing released glycans for other analytical techniques. Here we demonstrate its application to rheumatoid arthritis using 5 μl of patient serum.     

Analysis of hemoglobin variants using nondenaturing gel electrophoresis and matrix-assisted laser desorption ionization mass spectrometry

Molecular analysis of hemoglobin variants is crucial in the diagnosis of hemoglobinopathies. Routinely used techniques for identifying variants include alkaline gel electrophoresis and automated HPLC. Sometimes comigration of variants in electrophoresis or coelution in HPLC provides ambiguous results. Due to high sequence homology between normal and variant hemoglobin, proteomic analysis using LC/ESI-MS data is also challenging. Here we describe a novel method wherein alkaline gel electrophoresis and MALDI-MS were used in combination to characterize variant samples such as Hb FSD and Hb D-Iran unambiguously. The method is rapid, efficient, and cost effective. In the future, it can be applied as a diagnostic tool.     

A Low Picomole Fluorometric Detection System for Amino Acid Analysis

An amino acid detection system was developed for low picomole analysis of amino acids including proline, based on OPA-post-labeling with a non-switching NaCIO flow system. A computer-controlled HPLC equipped with a three-solvent gradient mixer was assembled with the detection system to analyze 17 kinds of amino acids in 85 min with a stable base line. The optimum conditions of the NaCIO and OPA solutions were determined as 0.002%–0.22ml/min and 0.16%–0.26ml/min, respectively. The use of NaCIO caused only approximately 30% decrease in fluorescence response of the usual amino acids, except for Pro and Cys, the latter even being enhanced by about 10 times. The detection limit for Pro and Cys was 500 and 1000 fmol, respectively, and that of the usual amino acids was 100 fmol. The calibration curves of all amino acids showed good linearity in a range between 5 and 500 pmol. This system was used as a detector for enantiomeric analysis of glutamic acid and cysteic acid with a reversed phase HPLC during stereochemical studies on the natural peptide derivative, oxycadystin.     

头孢他啶联合阿米卡星对多重耐药的鲍曼不动杆菌的体外抗菌作用分析

目的了解头孢他啶与阿米卡星联合对鲍曼不动杆菌体外药敏试验效果,探索多药耐药的临床用药新途径。方法采用微量肉汤稀释法、棋盘法分别测定头孢他啶、阿米卡星两药单独及两种不同浓度药物组合时对临床分离的24株多重耐药的鲍曼不动杆菌最低抑菌浓度(MIC),计算部分抑菌浓度(FIC)指数,应用FIC指数来计算及判读两种抗菌药物联用对多重耐药的鲍曼不动杆菌体外抗菌作用的效果。结果头孢他啶与阿米卡星联合应用,能显著降低各自的MIC值,分别有75%的菌株表现为协同作用,20.8%的菌株表现为相加作用,有4.2%发生无关作用,没有拮抗作用发生。结论对多重耐药的鲍曼不动杆菌的感染,可使用头孢他啶与阿米卡星进行联合治疗。