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APPLICATION NOTES

*Fermentation Production - Online HPLC Analysis of Fermentors Acrobat PDF
In this application note Groton Biosystems describes the use of the ARS-M™ Automated Reactor Sampling System for online HPLC for rapid analysis of fermentation tanks. In this example, bacterial fermentation is converting sugars to organic acids. The interface to the fermentor employs an in-situ membrane probe to separate the solid and liquid components of the fermentation broth. This filtrate is then delivered directly through an automatic injection loop (Shimadzu Prominence HPLC). The HPLC data with OPC feedback control, can be used to adjust the feed, optimize the growth of biomass, and improve the yield of the desired fermentation product.

*Integrated Reactor Feeding System - Amino Acid Feedback Control and Productivity Gains - E.Coli Acrobat PDF
A study was conducted to demonstrate the efficiency and viability of a fully automatic reactor feeding system to regulate essential amino acid concentrations in a microbial fermentation. These studies were conducted using an online amino acid HPLC system integrated with an ARS-M Reactor Sampling System and a programmable Reactor Control System controlling amino acid feedstock pumps. Baseline studies were conducted to determine which amino acids were consumed by the fermentation process and the rates of consumption. Subsequent studies were conducted in which those amino acids were fed to maintain a desired concentration for the entire course of the fermentation. Green Fluorescent Protein ("GFP") was used as a marker for specific productivity measurement. Initial results indicate that productivity is positively correlated to maintaining appropriate levels of essential amino acids. Future studies are in progress to optimize the media and feedstocks.

Biogen IDEC - On-line Amino Acid Analysis from a Small Scale CHO Cell Bioreactor Acrobat PDF
This Application Note describes a fast, accurate and reproducible measurement of 21 amino acids in a Chinese Hamster Ovary (CHO) cell culture using an online HPLC instrument. The hyphenated system combines the automatic sampling and reactor sterility protection of the Groton ARS with a high performance amino acid separation system provided by the Agilent 1100 Series HPLC System. The set-up, which is described in this Application Note, was used for in-process analysis during the course of a 14-day bioreactor run, which has been previously demonstrated using pulsed amperomeric detection. This tool provides immediate sampling and testing of a bioreactor that does not compromise bioreactor or samples, reduces hands on work and improves in-process monitoring of a bioreactor.

DASGIP/YSI/Groton - Automated On-Line Real Time Reactor Feedback Control Acrobat PDF
Integration of the Groton Automated Reactor Sampler, the DASGIP Bioreactor and the YSI Biochemistry Analyzer - Bioprocess monitoring and control of key analytes such as glucose, lactate, amino acids, and ammonia levels is critical to obtain optimal and consistently high productivity of a cell culture system. Improved productivity is critical to the development of high efficiency, economical production processes for therapeutic proteins and monoclonal antibodies. Despite the apparent value of feedback control systems in the biopharmaceutical industry there are few successful demonstrations. Here we present a complete, closed loop feedback control system by integrating a Groton Biosystems Automated Reactor Sample System with an YSI biochemistry analyzer and a DASGIP bioreactor control system in order to achieve a powerful, automated online, real time feedback control system for mammalian cell culture. With real time sampling and feedback control we provide an effective and efficient tool for the optimization of mammalian cell culture bioprocess. This system can easily be adapted to other types of manufacturing systems for biologics, for example, microbial fermentation. In addition, this system would also promote the FDA Process Analytical Technology (PAT) initiative.

MIT - Sterility Testing Acrobat PDF
Simulating a Bacterial Contamination in a Novel Automated Bioprocess

Pfizer - Performance Evaluation of an Automated Bioreactor Sampling System for Mammalian Cell Cultivation Acrobat PDF
Two common goals of biotherapeutics development are reduction in timelines and increased process understanding. An automated bioreactor sampling system developed by Groton Biosystems has proved its capacity to address those two seemingly conflicting needs for the industry. Paper presented at the ACS Meeting in August, 2008.

U of Maine - On-line Solutions for Bioethanol Fermentation Analyses Acrobat PDF
Yeast fermentation converts sugar to alcohol under anaerobic conditions. In this study and ARS400 was operated to take samples from a BioFlo110 three liter fermentor drawing samples containint E. coli K011 bacteria cells.

*ARS-M Series Product Bulletin Acrobat PDF
Automated Reactor Sampling (ARS) Systems deliver precise on-line sampling of bioreactor contents while ensuring complete, sanitary isolation.

ARS Series for Online Ethanol Sampling Acrobat PDF
Groton Biosystems offers high performance instruments to assay the viscous and dense samples found in both corn and biomass fermentation systems. Groton ARS systems provide online analysis by high pressure liquid chromatography (HPLC - sugar and ethanol), fraction collection, and small molecule nutrient monitors.

ARS Series for Online HPLC/Agilent 1200 Series LC System (MKT-032) Acrobat PDF
The ARS system with the Agilent 1200 Series LC provides a high level of automation for development, scale-up, and production within biopharmaceutical facilities.

Business Case for Automated Sampling Acrobat PDF
Flyer for a concise webcast hosted by Dr. Brian O'Flaherty, Director of Sales at Groton Biosystems, illustrating the compelling value proposition of automating your process - Bringing Value to Your Biopharmaceutical Process.

Nutrient Monitor - YSI - Interface Acrobat PDF
2700 ARS and 7100 ARS - Automated Online Biochemistry Analyzers

*IFPAC Annual Meeting - DASGIP and Groton Biosystems make presentation on automated feeding control. Acrobat PDF
The FDA Process Analytical Technology (PAT) Initiative provides a risk based framework - supported by regulatory authorities - to employ new automation methods in order to improve the efficiency, quality, and yield of biological manufacturing. Reactor feeding is a necessary operation that is still performed manually in most facilities that is easily automated. Reactor samples are currently taken manually by operators then analytical results are obtained from offline nutrient analyzers and the adjustment of feeding additions are based on these results and other factors calculated off line. The correction is done manually. However, fully automatic feeding control of bioreactors is possible today and is a key link in the quest to improve biologics manufacturing. This discussion will explore the mechanisms and requirements to perform automatic feeding of reactors through automatic, sterile, online sampling integrated with nutrient monitoring, process modeling, and reactor control proving a closed loop feedback control for nutrient feedstocks. Automated feeding control of substrates and amino acids has been performed in operating bioreactor facilities and the results will be discussed.

Automated Reactor Sampling and Agilent 1200 Series LC System for Online HPLC Assays Acrobat PDF
Increase efficiency with a powerful process analytical technology solution for the biopharmaceutical Industry.

Genentech - Implementing an Automated Reactor Sampling System for Monitoring Cell Culture Bioreactors Acrobat PDF
Process Development Engineering. Monitoring of cell culture bioreactors is critical to process control and optimization. Currently offline sampling is used in various cell culture operations. This process is time consuming and labor intensive. Automating the sampling process is highly desired but concerns about sterility, sample volume and cross contamination are common. This paper presents the evaluation of an automated sampling system by Groton Biosystems.

Simulating a Bacterial Contamination in a Novel Automated Bioprocess Acrobat PDF
Department of Chemical Engineering at Massachusetts Institute of Technology (MIT), Cambridge, MA

*New Horizons in Bioreactors adn Bioprocessing: Automated Bioreactor Feeding Acrobat PDF
Presentation given by Groton Biosystems, DASGIP and YSI Life Sciences at the Live Demonstration in Ft. Washington, PA (April 20, 2010) and Rockville, MD (April 22, 2010).

ARS - Phase in Closed Loop Solution (MKT-110) Acrobat PDF
Crawl, Walk, Run Approach to Automated Sampling. Start by drawing sample directly to a sample collector, then to analytical instruments and finally to a reactor control system for a complete closed loop solution.

ARS Product List Acrobat PDF
Product listing for automated sampling.

ARS-Interface Steam-in-Place Sterilized Sample Acrobat PDF
Steam Sterilized Sample Interface for Automated Online Sampling from Bioreactors and Fermentors - The Groton Automated Sampling Systems are designed to connect to stock steamable reactor sample valves.

Sample Collectors for Automated Reactor Sampling - Refrigerated and Sub-Zero Acrobat PDF
The ARS-M™ Automated Reactor Sampling Systems automatically acquires samples from up to 8 bioreactors and, in our Phase 1 configuration, delivers the sample to a Sample Collector. A dual channel option is available to collect cell containing or cell free samples.

ARS - Closed Loop Solution Acrobat PDF
BioProcess International - May, 2008

Automated Bioprocess Sampling and Analysis Acrobat PDF
Genetic Engineering News (GEN) - August, 2004

Automated Bioreactor Feeding Acrobat PDF
BioProcess International - July, 2009

Automated Sanitary Sampling Acrobat PDF
BioProcess International - January, 2006

Downstream Process Optimization Opportunities Using On-Line and At-Line PAT Instrumentation Acrobat PDF
BioPharm International - June, 2006

Improve Production Efficiencies and Yields Using Automated On-line Sampling Systems for Fermentors and Bioreactors Acrobat PDF
BioProcess International - August, 2006

Increase Efficiency with a powerful Process Analytical Technology Solution for the Biopharmaceutical Industry Acrobat PDF
Agilent, Pharmaceutical Analysis e-Newsletter - 2007

Integrated Equipment to Offer 24/7 Sampling and Analysis Solutions for Liquid Processes Acrobat PDF
Technical Insights - Frost & Sullivan

Online Fermentation Analyzer Optimizes Production Acrobat PDF
Ethanol Producer Magazine - May, 2007

Reference Letter - BioTrend Acrobat PDF

Cell Counter Interface to ARS-M Acrobat PDF
Online Automated Sampling for Cell Counting - ARS interfaces to industry standard cell counters and provides a sterile and automatic connection between the bioreactor sample and the cell counter.

DeltaV Systems Integrate Seamlessly Acrobat PDF
Solutions designed for seamless integration with an array of bioprocess control platforms. Integration of these platforms to the ARS can deliver improved process quality and reliability while reducing operating costs. This note focuses on the integration of the ARS to the industry leading DeltaV Bioprocess Controller and the realized benefits from this integration.

Online HPLC for Biotechnology: ARS and Agilent 1200 Acrobat PDF
Online analytical instrumentation facilitates productive, efficient monitoring of fermentation or cell culture processes in real time. The ARS in combination with the Agilent 1200 Series LC system introduces and complies with the goals of the FDA's Process Analytical Technology (PAT) initiative. Described here is a new technology which introduces automatic, hands-free, online sampling of HPLC analysis. This Technical Note demonstrates this instrumentation for amino acid analysis.

Value Proposition for Automated Bioreactor Sampling (MKT-152) Acrobat PDF
Achieve corporate goals and Automate Sampling. Learn how automation will save you money by putting in place the tool to track product quality, increase yield, reduce product development cycles, reduce labor and reduce the human eror factor.

Application Questionnaire (MKT-015) Acrobat PDF
To better serve you, please take a moment to fill out our survey. This survey is also available online - paste this link into your browser to fill out survey oneline. http://survey.constantcontact.com/survey/a07e2jntirifx62sruc/start

Business Case for Automated Sampling PowerPoint
Link to Register for Gift Card

Business Case for Automated Sampling - Bringing Value to Your Biopharmaceutical Process PowerPoint
Concise webcast hosted by Dr. Brian O'Flaherty, Director of Sales at Groton Biosystems, illustrating the compelling value proposition of automating your process - Bringing Value to Your Biopharmaceutical Process.

Financial Calculator Link Text
Interactive calculator demonstrating the savings of automated sampling. To access calculator past this link into your browser. http://www.grotonbiosystems.com/calculator/arscalculator.php