Heidi Fleischer

A LC-MS integration approach in life science automation: Hardware integration and software integration

Robots are widely used in life science automation due to their advantages, such as reducing manpower, ensuring uniformity and eliminating contaminations. Single-arm robots, with multiple degrees of freedom, have been used to transport labware, e.g. transporting microplates. Nowadays dual-arm robots draw much attraction due to their flexibility, but their applications in life sciences are still limited. In this case, a platform based on a Yaskawa CSDA10F dual-arm robot has been realized in the Center for Life Science Automation (celisca), Germany. In this platform, the robot is not only used to prepare samples by using labware, including pipettes, glass vials, microplates, thermoshaker and so on, in a human-like way, but also employed to integrate a liquid chromatography-mass spectrometry instrument (LC-MS) to the platform for sample analysis purposes. In order to enhance the degree of automation, the analysis process needs to be started automatically after the prepared samples are fed to the LC-MS. This was achieved by integrating the software system of the LC-MS to the SAMI Workstation EX Software system (SAMI EX, Beckman Coulter Inc.), which is user friendly and used for process scheduling. The integration was realized based on the user interface and eXtensible Markup Language (XML). The LC-MS can be controlled by imitating the signals of mouse events and keystrokes to the user interface (such as starting or stopping analysis process); XML data is used for detailed control information.

Application of a Dual-Arm Robot in Complex Sample Preparation and Measurement Processes

Automation systems with applied robotics have already been established in industrial applications for many years. In the field of life sciences, a comparable high level of automation can be found in the areas of bioscreening and high-throughput screening. Strong deficits still exist in the development of flexible and universal fully automated systems in the field of analytical measurement. Reasons are the heterogeneous processes with complex structures, which include sample preparation and transport, analytical measurements using complex sensor systems, and suitable data analysis and evaluation. Furthermore, the use of nonstandard sample vessels with various shapes and volumes results in an increased complexity. The direct use of existing automation solutions from bioscreening applications is not possible. A flexible automation system for sample preparation, analysis, and data evaluation is presented in this article. It is applied for the determination of cholesterol in biliary endoprosthesis using gas chromatography–mass spectrometry (GC-MS). A dual-arm robot performs both transport and active manipulation tasks to ensure human-like operation. This general robotic concept also enables the use of manual laboratory devices and equipment and is thus suitable in areas with a high standardization grade.

Application of dual-arm robot in biomedical analysis: Sample preparation and transport

The use of automated systems in life science laboratories is rising in recent years. Robots play a vital role in laboratory procedures, ranging from chemical analysis to drug development. In high degrees of automation situations, such as transferring plates, adding covers to the plates or transferring bulk liquids, single-arm robots with multiple degrees of freedom are used. Recently, dual-arm robots also draw much attraction due to their flexibility. However, applications of dual-arm robot in life science are still limited. In this paper a dual-arm robot platform, designed for sample preparation and transport in life science, is introduced. As programming for dual-arm robots is more challenging than single-arm robots, especially in life science automation, an efficient and flexible programming method is also discussed. Besides, a liquid chromatography-mass spectrometry (LC-MS) instrument is also integrated into this platform, which is automatically fed with the samples on 96-well microtiter plates using the robot. A fully automated sample preparation method with subsequent mass spectrometric measurements for fast enantiomeric excess determination of chiral compounds was implemented and applied to the dual-arm robot platform.

Flexible software solution for rapid manual and automated data evaluation in ICP-MS

In the field of chemical analysis a high amount of data is generated especially in the scope of high-throughput measurement and automation systems. In general, analytical laboratories involve a multitude of analytical devices with different measurement principles. This results in devices from different vendors with a heterogeneous control software environment and often with different export data formats. One of the main tasks in laboratory automation is the integration of various devices to increase the applicative flexibility. This requires homogenous communication protocols and data formats. In this study, a data evaluation software is presented which enables an effective data processing of elemental analysis measurement data. The raw data are imported form the device software and the processed data are saved using Excel files. The data processing is performed using individual settings stored in filter and calculation methods. This provides a maximum in flexibility related to the raw data structure and the required statistical parameters to be calculated. The modular software concept allows the application to different analytical devices not only limited to elemental analysis also for techniques delivering structural compound information. The software Analytical Data Evaluation (ADE) presented was applied to an inductive coupled plasma mass spectrometer (ICP-MS) and used both in method development and in routine analysis. The integration into an existing process management system provides a maximum of automation.

A cross-platform modular software solution for automated data evaluation applied in elemental and structural mass spectrometry

High-throughput solutions and automation systems are commonly used in bioscreening tasks. In the last years, automation has become more and more important in the field of elemental and structural chemical analysis. A high amount of data points is generated, what requires a fast and ideally fully automated data processing and evaluation. Analytical laboratories involve a multitude of analytical devices with different measurement principles from various vendors with a heterogeneous control software environment often with different export data formats. This results in one of the main tasks in laboratory automation: the integration of various devices to increase the applicative flexibility. Therefore, homogenous communication protocols and data formats are required. Furthermore, to increase the mobility and a spatial independence of the operator modern mobile devices such as tablet PCs and mobile phones can be involved in laboratory processes. In this study, a data evaluation software is presented, which enables an effective data processing of measurement data acquired with various instruments for elemental and structural analysis. The raw data are imported from the device software and the processed data are saved using Excel files. The software Analytical Data Evaluation (ADE) was implemented according to a modular concept as a web application, what enables a simple adjustment to different devices using individual settings stored in filter and calculation methods. Hence, a maximum in flexibility related to the various raw data structure and the required statistical parameters to be calculated can be provided. The cross-platform data evaluation software is independently usable from the users location with stationary PCs or mobile devices. The integration into an existing hierarchical workflow management system provides a maximum of automation applied both in method development and in routine tasks using various types of analytical principles in a fully automated environment.

Innovative software solution for special data evaluation in mass spectrometry

Qualitative and quantitative determination of the composition of chiral compounds is an important task in drug development, chemical and biological industries and scientific research. Usually, enantiomers are analyzed with conventional analytical techniques such as chromatography or spectroscopy. Due to their relative long run times and high material consumption these techniques are only suitable to a limited extent for using in high-throughput screenings. In contrast, mass spectrometry without previous chromatographic separation provides very short analysis times, but it requires a suitable derivatization of the chiral substrates. In this interdisciplinary study the technique of parallel kinetic resolution with mass tagged pseudo enantiomeric auxiliaries was applied for measuring the enantiomeric excess of amino acids, carboxylic acids, alcohols, amino alcohols and natural compounds. Beside the method development for sample preparation and mass spectrometric measurements a high-throughput suitable processing network was constructed. This includes automated sample preparation, sample transport, analysis and data processing. The special tasks in data evaluation such as calibration and enantiomeric excess calculation are realized by an additional software module connected to existing mass spectrometer data acquisition software. The automation system with its software solution shows great potential for its use in high-throughput screenings in various fields of industry and research.

A Highly Flexible, Automated System Providing Reliable Sample Preparation in Element- and Structure-Specific Measurements

Life science areas require specific sample pretreatment to increase the concentration of the analytes and/or to convert the analytes into an appropriate form for the detection and separation systems. Various workstations are commercially available, allowing for automated biological sample pretreatment. Nevertheless, due to the required temperature, pressure, and volume conditions in typical element and structure-specific measurements, automated platforms are not suitable for analytical processes. Thus, the purpose of the presented investigation was the design, realization, and evaluation of an automated system ensuring high-precision sample preparation for a variety of analytical measurements. The developed system has to enable system adaption and high performance flexibility. Furthermore, the system has to be capable of dealing with the wide range of required vessels simultaneously, allowing for less cost and time-consuming process steps. However, the system’s functionality has been confirmed in various validation sequences. Using element-specific measurements, the automated system was up to 25% more precise compared to the manual procedure and as precise as the manual procedure using structure-specific measurements.

Flexible Automation System for Determination of Elemental Composition of Incrustations in Clogged Biliary Endoprostheses Using ICP-MS

Automation systems are well established in industries and life science laboratories, especially in bioscreening and high-throughput applications. An increasing demand of automation solutions can be seen in the field of analytical measurement in chemical synthesis, quality control, and medical and pharmaceutical fields, as well as research and development. In this study, an automation solution was developed and optimized for the investigation of new biliary endoprostheses (stents), which should reduce clogging after implantation in the human body. The material inside the stents (incrustations) has to be controlled regularly and under identical conditions. The elemental composition is one criterion to be monitored in stent development. The manual procedure was transferred to an automated process including sample preparation, elemental analysis using inductively coupled plasma mass spectrometry (ICP-MS), and data evaluation. Due to safety issues, microwave-assisted acid digestion was executed outside of the automation system. The performance of the automated process was determined and validated. The measurement results and the processing times were compared for both the manual and the automated procedure. Finally, real samples of stent incrustations and pig bile were analyzed using the automation system.

Generic and Automated Data Evaluation in Analytical Measurement

In the past year, automation has become more and more important in the field of elemental and structural chemical analysis to reduce the high degree of manual operation and processing time as well as human errors. Thus, a high number of data points are generated, which requires fast and automated data evaluation. To handle the preprocessed export data from different analytical devices with software from various vendors offering a standardized solution without any programming knowledge should be preferred. In modern laboratories, multiple users will use this software on multiple personal computers with different operating systems (e.g., Windows, Macintosh, Linux). Also, mobile devices such as smartphones and tablets have gained growing importance. The developed software, Project Analytical Data Evaluation (ADE), is implemented as a web application. To transmit the preevaluated data from the device software to the Project ADE, the exported XML report files are detected and the included data are imported into the entities database using the Data Upload software. Different calculation types of a sample within one measurement series (e.g., method validation) are identified using information tags inside the sample name. The results are presented in tables and diagrams on different information levels (general, detailed for one analyte or sample).

Flexible robot platform for sample preparation automation with a user-friendly interface

Robots play a vital role in life science automations. This paper is to present an industrial dual-arm robot platform used to transfer sample preparation processes from the manual to automated ones, with a user-friendly interface for designing the processes. Due to its two multi-axis arms, the robot is flexible to handle various tools, such as pipettes, syringes, vials, microplates, thermoshakers or ultrasonic machines, which are identical to manually used tools. This endows the platform with the potential of “copying” (without major changing, most parts keeping the same) multi manual processes to automated ones. However, the complexity of programming for industrial robots is one of the major barriers preventing automation and limiting flexibility, especially for an industrial dual-arm robot. In this paper, a flexible and easy-to-use software system has been developed for the robot platform, which consists of three parts: (1) a user interface software, (2) robot programs and (3) an interface program. Finally, an automated process of sample preparation for determining cholesterol by the dual-arm robot has been described. And prepared samples by the robot had been analyzed by a gas chromatography-mass spectrometry (GC-MS) instrument, with the coefficient of variance being below 10%.