We Know BioReactors. Dedication to BioReactor Research, Development, Design, and Manufacturing

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4 We Know BioReactors Dedication to BioReactor Research, Development, Design, and Manufacturing BioReactor Sciences (BRS) is a company 100% devoted to the research, development, design, and manufacturing of bioreactors for the production of traditional fermentation products, vaccines, rdna & therapeutic biologics, and cells for cell therapy. Our foundation rests in the collective strength of thirty plus years of designing and manufacturing bioreactors, and extensive knowledge of bioprocessing. We are regarded highly for our workmanship and superior design capability along with our innovation and creativity. Our line of products encompasses a large range of bioreactor systems including conventional mechanicallyagitated, air lift, rotating drum, packed bed, and single use shaking bag bioreactors. The size of our bioreactor systems ranges from 10 ml to over 10,000 liters. Our systems have been applied to all varieties of cell cultures including microbial, plant, animal, human, and insect cells, in both adherent and suspension forms. Single use technology is also applied in many of our systems. Simplicity, Reliability and Functionality are the primary design principles of our bioreactor systems. We adopt open software architecture and a modular design concept utilizing industry standard components and software for reliability, durability and ease of maintenance and repair. Our product s unparalleled quality is bolstered by our industry surpassing warranties. Above all, absolute functionality is our leading design priority in producing the most practical and finest performing products for bioprocessing. Innovation: With profound comprehension of upstream bioprocessing and advanced control technology; and experience in fabrication and production we furnish optimal concepts and solutions of bioreactor systems for upstream bioprocessing. Reflecting our inventive strength we hold numerous granted or pending patents on many of our components and systems, among which is the newly launched MB (Moving Bed) and FB (Fixed Bed) bioreactor systems. Our MB is the only system of its kind in the industry and is the most versatile, functional, and efficient system in today s market. The MB system creates optimal environments for both adherent and suspension cell cultures, and can perform many if not all upstream processes including cell detachment and recovery, all in one device. Customer Service remains as our preeminent interest. Alongside our unparalleled customer service we provide unrivaled technical service in bioprocess development to ensure optimal utilization of our products. We also offer custom design and manufacturing services to meet customer s special process requirements. Our highly capable and cost effective components are also available to our customers. Our future is entrenched in our wish and commitment to provide you with products of the highest quality along with unmatched technical expertise and customer service. We tailor our products and services to your needs to achieve your goals in the most efficient and cost effective manner possible.

5 Table of Contents BioReactor Systems... 6 MA Series: Mechanically Agitated Systems... 6 SB Series: Swirl Bag BioReactor Systems Packed Bed Systems FB Series: Fixed Bed Systems MB Series: Moving Bed Systems AL Series: Air Lift Systems RD Series: Rotating Drum Systems BioProcessing Instruments and Equipment Glucose Monitoring System (GM-100) Pinch Valve (PV-100/150 and PV-200/250) Sampling and Feeding Valves (SV-100 and FV-100) Diaphragm Valve (DV-100) Gas Blending and Distribution Stations Peristaltic Pump (PP-100 and PP-200) For more information, please contact us at: BioReactor Sciences 1150 Home Place Drive Lawrenceville, GA info@bioreactorsciences.com

6 MA Series: Mechanically Agitated BioReactors BioReactor Sciences offers one of the most capable bench top bioreactor systems ever developed Based on proven technology and experience, the Mechanically Agitated (MA) systems are distinguished from other systems with exceptional construction and functional design. The modular layout, open sourced software, and use of industry-standard materials & components result in durability, easy installation, use, and maintenance. To meet a wide range of requirements our complete line of MA bioreactors include 3L bench-top to 50,000L plant-production scale systems; for microbial, plant, insect, animal, and human cells; and for both adherent and suspension cell cultures. Completely customized MA systems are also available. Refined bioreactor has it all Compact design maximizes bench space cgmp-compliant meets all of your needs from research to production Capable of batch, fed-batch, & perfusion modes for high density growth of mammalian, plant, & insect cell lines Fully integrated system is ready for out-of-the box startup Advanced touchscreen controller simplifies operation: large 9 inch touchscreen clearly displays all set points, current values, and more. Display screens are straightforward and easy to use. Available in 10-plus vessel sizes with multiple options: pre-configured packages simplify ordering. Customize by selecting from a range of options such as multiple mass flow controllers for individually controlling gas supplementation, and industrial load cell for precise liquid addition. Features Industrial grade microprocessor Clearly presented graphic user interface with 9 HMI color touch panel and easy parameter adjustment Trend display of up to 8 process values with variable display cycles for quick overview Specially configured gassing systems for microbial and cell culture Control of agitator speed, ph, DO, temp., foam, filling level, substrate addition, gas mixture, & gas vol. Agitation system directly driven by detachable AC servo motor Programmable peristaltic pumps for volume measurement Battery-protected memory storage for vital parameters 6

7 MA Series: Mechanically Agitated BioReactors Automated ph/do calibration Gas mixing: N2/O2/Air-O2 mixture (for cell culture); O2/Air (for microbial culture) Communication protocol: RS-232/RS-485 Mass flow and controller (optional) Load cell (optional) Specifications Temperature control range: 5 o C above ambient to 60 o C DO control range: 0-100% Air filter for inlet and exhaust: 0.2 µm Power supply: 220Vac/50-60 Hz Temperature of cooling water supply: o C Type of foaming probe: conductivity Peristaltic pumps: programmable for acid addition, base addition, de-foaming, and/or feeding; adjustable pumping rate. Applications Process development & optimization, scale up & scale down studies, seed expansion, cell bank production, protein supply Cell lines: microbial, plant, insect, and mammalian cells Process modes: batch, fed-batch, or continuous culture Vaccine, recombinant protein, and monoclonal antibody production Adherent cell culture with micro-carriers Biofuel manufacturing Our Complete Line of MA BioReactor Systems: Model Description Application Vessel Size (L) MA-100 Mech agitated bioreactor/ Autoclavable bench model Microbial 4, 7, 14 MA-200 Mech agitated bioreactor/ SIP bench model Microbial 30, 50, 100 MA-300 Mech agitated bioreactor/ SIP pilot model Microbial 200, 250, 500 MA-400 Mech agitated bioreactor/ SIP production model Microbial 1000, >5000 MA-150 Mech agitated bioreactor/ Autoclavable bench model Cell cultures 4, 7, 14 MA-250 Mech agitated bioreactor/ SIP model Cell cultures 30, 50, 100 MA-350 Mech agitated bioreactor/ SIP pilot model Cell cultures 200, 250, 500 MA-450 Mech agitated bioreactor/ SIP production model Cell cultures 1000, >5000 7

8 MA Series: Mechanically Agitated BioReactors MA-100 and 150 Mechanically Agitated BioReactor: MA-100 for microbial culture; MA-150 for cell culture Bench top: vessel size: 4-15L (working volume of 3-10L) Glass vessel with S/S jacketed bottom or thermal glass bottom Heating and cooling with water circulation system Agitation speed: /0-1000/0-600 rpm (impeller ratio: 1/2) for MA-100; 0-100/0-200 rpm (for MA-100C) Pressure for air supply: Kg/cm2 Head plate: multiple sampling/feeding ports, 12mm ports for PH/DO probes, 8mm port for temperature probe, equipped with high efficient air condenser, handles on each side of the head plate for easy transportation, mounted with agitation unit. Dimensions (cm): 60W x 60H x 50D Dry weight: 70 Kg (approximate control console only) MA-200 and 250 Mechanically Agitated BioReactor: MA-200 for microbial culture; MA-250 for cell culture Bench top: vessel size: 30, 50, 100L Sterilization in place Agitation speed: (for 30L)/0-600(for 50L)/0-600 (for 100L) rpm Volume of air inflow: 1-50 slpm(30-50l)/1-100 slpm(100l) Pressure for air supply: Kg/cm2 Working range for pressure: Kg/cm2 Communication protocol: RS-485 two ways (4 or 6) Peristaltic pumps: programmable for acid addition, base addition, defoaming, and/or feeding (optional) Four-gas mixer: taking N2/CO2/Air/O2 (using a proportional or a massflow controller) Method for level detection: conductivity type Power supply: Vac/50-60 Hz An oil pressure jack is used to lift the headplate 8

9 MA Series: Mechanically Agitated BioReactors MA-300 and 350 Mechanically Agitated BioReactor: MA-300 for microbial culture; MA-350 for cell culture Vessel volume: Liters (SS316L used for the inner vessel) Polish on the vessel: 400 mesh(inner), 300 mesh(outer) Agitation speed: rpm Volume of air inflow: slpm (Mass flow) ph control range: DO control range: 0-100% (controlling in cascade AG/AIR/PRESSURE) Air filter for inlet and exhaust: 0.2 μm (autoclavable) Working range for pressure: 0-3 Kg/cm2 Valves: food-industry air-driven diaphragm valves Peristaltic pumps: programmable for acid addition, base addition, defoaming, and/or feeding Power supply: 220 Vac/50-60 Hz in 3 phases Air supply: 2-3 kg/cm2 (for bioreactor), 5-6 Kg/cm2 (for air-driven valves) Water supply: Kg/cm2 Steam supply: Kg/cm2 (option) An oil pressure jack is used to lift the headplate MA-400 and 450 Mechanically Agitated BioReactor: Vessel volume: Liters (SS316L used for the inner vessel) Polish on the vessel: 400 mesh(inner) Agitation speed: rpm Volume of air inflow: SLPM (D.P.Flow/Mass flow) ph control range: DO control range: 0-100% (controlling in cascade AG/AIR/PRESSURE) Air filter for inlet and exhaust: 0.01 μm (autoclavable) Type of foaming probe: conductivity Working range for pressure: 0-3 Kg/cm2 Valves: food-industry air-driven diaphragm valves Communication protocol: RS-485 two ways Peristaltic pumps: programmable for acid addition, base addition, defoaming, and/or feeding Power supply: 220 or 380 Vac/50-60 Hz in 3 phases Air supply: 2-3 kg/cm2 (for bioreactor), 5-6 Kg/cm2 (for air-driven valves) Water supply: Kg/cm2 Steam supply: Kg/cm2 The frame can be designed according to customer s needs. 9

10 SB Series: Swirl Bag BioReactor Systems The SB Series Swirl Bag BioReactor is a single use 2D bag bioreactor for suspension cell culture based on the swirl motion of a shaker. The SB-150 has a separate control console with HMI touch screen, additional ph control, and a peristaltic pump for feeding control. Our cell culture bags are proven for a broad range of different cell lines including CHO, NS0, SF9 and mesenchymal stem cells. For adherent cultures, traditional micro-carriers can be used but we recommend our FBS-100 system which is a similar device but utilizes a separate single use container containing carriers on which the cells adhere more effectively and ready separation from medium for medium replacement. Model Description Vessel Size (L) SB-100 SB-150 Swirl bag bioreactor, single use, standing alone bench top model with gas, temperature, and RPM control Swirl bag bioreactor, single use, bench top model with separate control console for additional ph and feeding control 2, 5, 10, 20 2, 5, 10, 20 Specifications Digital orbital shaker range: rpm Bag Sizes: 2, 5, 10, and 20L Applications Mammalian, insect, and plant cell Suspension or adherent cells on microcarriers Shear sensitive cells such as stem cells SB-150 Bench-top model with 7 HMI color touch panel Simple and flexible parameter settings 4 standard peristaltic pumps: programmable and variable speed Baffled platform with acrylic lid Temperature control: heating only with hot air circulation system Communication: R485 SB

11 Packed Bed Bioreactor Systems Packed Bed Bioreactor (PBB) systems have many advantages over microcarrier systems for adherent cell cultures in terms of cell attachment, medium replacement, and high cell density. In recent years PBB systems have therefore gained significant popularity for adherent cell cultures. PBB systems have also served as excellent devices for perfusion cultures because they do not require an external and unreliable cell retaining device. The most well-known PBB bioreactor systems are Eppendorf s Celligen Plus, Pall s icellis, and CESCO s Tidecell. These systems all employ similar PET non-woven PET fiber as their carriers but in different configurations. All of these systems are designed and based however on different mixing and oxygenation principles. Similar to the TideCell we adopt the most efficient oxygen transfer principle, the Principle of Roller Bottles (direct transfer of oxygen from air to cell without transferring through the bulk liquid phase) to all of our PBB systems. Our systems provide the most efficient oxygen transfer capability and yet require the least amount of shear force, resulting in no foaming issues. Both of our fixed packed bed (FB Series) and moving packed bed (MB Series) bioreactors are patent pending and are constructed as single use and reusable. Both the icellis and Celligen Plus bioreactors have been reported to be successfully used for suspension cell cultures as well. With the capability of altering flow pattern in our system we are also able to achieve the same effect as these two systems for suspension culture and yet have mitigated their major shortcomings, such as scalability, shear effect, and foaming issues. Our Fixed Bed (FB) and Moving Bed (MB) bioreactor systems are also the first to adopt a 2D treated PS surface as a carrier to grow cells in a monolayer similar to T-flasks. 11

12 FB Series: Fixed Bed BioReactor Systems The FB Series Fixed Bed BioReactor Systems are available as reusable and single use systems. Our reusable FB systems (FB-100 and FB-200) alternately apply only positive pneumatic pressure to the packed bed chamber and medium mixing chamber to generate medium flow in and out of the packed bed. This mechanism performs oxygenation based on The Principle of Roller Bottles. For our single-use FB systems (FBS-100 and FBS-200) the disposable containers are not compressible so a single-use pump or peristaltic pump is used to generate the medium flow. The mixing of the medium container is conducted by mechanical agitation, medium recirculation, or shaking/rocking in different models. Applications Process development & optimization, scale up & scale down studies, seed expansion, cell bank production Primary for adherent culture, but also adequate for suspension culture. Cell lines: microbial, plant, insect, and mammalian cells Process modes: batch, fed-batch, or continuous culture Vaccine, recombinant protein, monoclonal antibody, stem cell production Features Industrial grade microprocessor Process visualization and control via 9 HMI color touch screen ( except MB-DH and MB-BX systems) Trend display of up to 8 process values with variable display cycles for quick overview Four gas mixer: N 2 /CO 2 /Air/O 2 (manual or optional with mass flow controller) Control of ph, DO, temp., filling level, substrate addition, gas mixture, & gas flow rate 4 standard peristaltic pumps: variable speed, programmable Battery-protected memory storage for vital parameters Automated ph/do calibration Communication protocol: RS-232/RS-485 Load cell (optional) Specifications Temperature control range: 5 o C above ambient to 60 o C DO control range: 0-100% Air filter for inlet and exhaust: 0.2 µm Pressure of air supply/working range: /0-3.5 Kg/cm 2 Power supply: V/50-60 Hz Temperature of cooling water supply: o C 12

13 FB Series: Fixed Bed BioReactor Systems Model Description Carrier/Vessel Size (L) FB-100 Fixed bed bioreactor / Autoclavable bench top model 1/7, 3/14 FB-200 Fixed bed bioreactor / SIP pilot & production model 10/50, 100/500 FBS-100 Fixed bed bioreactor / Single-use lab model 2/10, 12/60 FBS-200 FB-100 Fixed Bed BioReactor Fixed bed bioreactor / Single-use pilot & production model 10/50, 100 /500 The FB-100 is an autoclavable bench top glass vessel model. It consists of a bottom driven agitated vessel with a sealed basket container which is attached to the headplate, and filled with BRS 2D or 3D carriers or the equivalent. The basket container is separated from the vessel. A solid tube extends from the bottom of vessel to the top of the basket container. Another solid tube extends from the bottom of the basket container through the head plate and returns back to the top of vessel. A control valve is installed on the tubing above the vessel. The medium is filled just below the bottom of basket. The medium is moved between the vessel and basket by pressure, alternately submerged in media and exposed to air performing The Principle of Roller Bottles for oxygenation. High efficient seeding, infection, transfection and trypsinization Glass vessel with S/S bottom plate Heating and cooling with water circulation system Bottom driven agitation speed: rpm Head plate: multiple sampling/feeding ports, 12mm ports for ph/do probes, 8mm port for temperature probe, handles on each side of the head plate for easy transportation, heating/cooling tube, a mounted motorized lifting unit. Dimensions (cm): 60W x 60H x 50D Dry weight: 70 Kg (approximate control console only) 13

14 FB Series: Fixed Bed BioReactor Systems FB-200 Fixed Bed BioReactor The FB-200 is similar to the FB-100 except the vessel is stainless steel and sterilization occurs in place. Sterilization in place Bottom driven agitation speed: rpm Heating and cooling with water circulation system Air flow rate: 1-5 slpm(30-50l)/1-10 slpm(100l) Power supply: v/50-60 Hz An oil pressure jack is used to lift the head plate FBS-100 Fixed Bed BioReactor The FBS-100 is a single use fixed bed bench top system. It consists of a set of single use packed bed box modules (BX) placed on a stationary platform and a single use bag containing medium. The BX set is a series of box modules connected in series each containing a BRS 2D or 3D carrier cartridge. Both containers are connected with flexible tubing and confined in a temperature controlled chamber. The medium bag is placed on a shaker with speed control. The medium in the mixing bag can be pumped in and out of the set of box modules on the platform by our peristaltic pump system (PP200) to perform the Principle of Roller Bottles for the most efficient oxygenation and for the most efficient seeding, infection, transfection, and trypsinization. Constant gas mixture flows through both containers to maintain positive and constant pressure. PH of the medium bag is measured and controlled in a small recirculated loop. DO is also monitored in the same loop. BX packed bed culture box modules: 2L each connected up to 6 units (12L carrier) Medium bag: 10-60L BRS bag made by LePure Complete system is pre-sterilized by gamma radiation Digital orbital shaker SK110 with variable speed of rpm Peristaltic pump: Model PP200. Tubing WM Bioprene or equivalent In line ph, DO, and temperature reusable sensors placed on recirculation loop. 14

15 FB Series: Fixed Bed BioReactor Systems FBS-200 Fixed Bed BioReactor The FBS-200 is a single use fixed bed pilot and production model. The system is the same as the FBS-100 system except a disposable recirculation pumping system is used to mix the medium inside of the bag, and the BX box module is larger. PH is monitored and controlled in line as part of the recirculation loop. 15

16 MB Series: Moving Bed BioReactor Systems Our MB Series Moving Bed BioReactor systems are similar to the FB Series but the packed bed of carriers is movable, and not stationary. The mobility of the carrier/matrix bed has increased freedom allowing for maximum flexibility in minimizing the volume of seed, virus, DNA and cell detachment enzyme required, resulting in maximum efficiency of cell attachment, infection, transfection and cell detachment/product recovery, respectively. This enhanced functionality allows the system to conduct cell detachment and recovery all in one bioreactor system. Most adherent cells require a detaching protease enzyme such as trypsin to detach the cells from the attached surface or carrier. The degree of difficulty for cell detachment substantially increases from the smooth 2D monolayer growth surface to the 3D porous surfaces of microcarriers or non-woven fiber carriers. Regardless of the type of equipment or attachment surface they all require some form of mechanical means to remove the cells from the carrier after enzymatic treatment. There is no known bioreactor that is able to conduct this mechanical means of detachment inside the same bioreactor. Furthermore, most packed bed bioreactors are unable to remove the carriers from the system for external processing, assay sampling, or microscopic examination. The MB-100/200 reusable systems apply a mechanism to freely move the packed bed basket up and down inside the medium vessel. This system can also perform oxygenation based on the Principle of Roller Bottles in addition to applying the mechanical force needed to detach the enzyme treated cells from either the 2D or 3D surface carriers. With the MBS-100/200/300 single-use systems the medium flow between the packed bed and medium chambers is generated by natural gravity, a result benefited from the mobility of bed. The mixing of the medium container is conducted by mechanical agitation, medium recirculation, or shaking/rocking mechanisms. Features Industrial grade microprocessor Process visualization and control via 9 HMI color touch screen Trend display of up to 8 process values with variable display cycles for quick overview Four gas mixer: N 2 /CO 2 /Air/O 2 (manual or optional with mass flow controller) Control of ph, DO, temp., filling level, substrate addition, gas mixture, & gas flow rate Sequential control for moving beds and cell detachment Peristaltic pumps : programmable and variable speed Battery-protected memory storage for vital parameters Automated ph/do calibration Communication protocol: RS-232/RS-485 two ways Load cell (optional) 16

17 MB Series: Moving Bed BioReactor Systems Specifications Temperature control range: 5 o C above ambient to 60 o C DO control range: 0-100% Air filter for inlet and exhaust: 0.2 µm Power supply: V/50-60 Hz Temperature of cooling water supply: o C Peristaltic pumps: variable speed, programmable Applications Process development & optimization, scale up & scale down studies, seed expansion, cell bank production Primary for adherent culture, but also adequate for suspension culture. Cell lines: microbial, plant, insect, and mammalian cells Process modes: batch, fed-batch, or continuous culture Vaccine, recombinant protein, monoclonal antibody, stem cell production Model Description Carrier/Vessel Size (L) MB-DH Moving bed dish bioreactor / Pre-sterilized / 0.02 MB-BX Moving bed box bioreactor / Pre-sterilized 0.2,0.4/2 MB-100 Moving bed bioreactor / Autoclavable bench top 1/7, 3/14 MB-200 model Moving bed bioreactor / SIP pilot & production 10/50, 100/500 MBS-100 model Moving bed bioreactor, Lab & pilot plant model 2/10, 12/60 MBS-200 Moving bed bioreactor, Production model 10/50, 100 /500 17

18 MB Series: Moving Bed BioReactor Systems MB-DH Moving Bed Dish BioReactor The MB-DH Bioreactor system consists of a programmable rocker (the RK 100/200 or 150/250) and single or multiple regular or modified 100 mm-size petri dishes (DH). The dishes have a chamber that holds a small quantity of fibrous carriers such as NBS FibraCel, CESCO s Bionoc II or BRS 2D & 3D carrier sheets to form a carrier bed. The rocker creates rocking movement allowing the cell-embedded carrier bed to move and be alternately submerged in media and exposed to air performing The Principle of Roller Bottles. The RK200 rocks at a fully adjustable desired angle and speed, and can also hold either or both ends at a desired position for an adjustable amount of time. RK150/250 is also equipped with temperature control with an acrylic lid. This mini system is a direct scale down of our MB-BX box bioreactor systems. It is ideal for preliminary process evaluation and development, and also ideal for efficient small scale production of biologics for screening or for cell based assay applications. Modified Dish (DH) A modified 100 mm size petri-dish with a PP (polypropylene) screen attached to the cover. Included is 108 mg of BRS 3D sheets, 108 mg of BioNOCII cell culture carriers or 196 mg of Fibra-Cel, confined to one end of the dish inside of the screen when the cover is on. The dish is pre-sterilized by gamma radiation. RK-100/200 and RK-150/250 The RK-100/200 is a digital slow-speed rocker specifically designed to be used with our MB-DH and MB-BX systems. Together, this system provides all operating parameters to simulate a larger scale version of this type of packed bed bioreactor such as our MB-BX, MB, MBS, FB and FBS bioreactors. Linear scale-ability allows this mini system to conveniently and economically determine the optimal conditions for large scale operation. The BRS RK-200's low profile design incorporates a rocking baffled platform that accepts a variety of optional trays. The RK-250 is similar to the RK-200 but is also equipped with a heater, temperature control, and a lid. The RK-250 can also be supplied with desired % CO2 gas through our GB-100 gas blending station. In this arrangement a CO2 incubator is not required. 18

19 MB Series: Moving Bed BioReactor Systems Features 24V Brushless Low Maintenance DC Motor and Speed Controller Digital Display with control of speed and holding time settings Specifications Range of Motion: 0 to 12 Degrees (Adjustable), 5-30 Cycles/Minute Range of holding time on both ends: 0-10 min. Electrical Rating: line voltage, 1 Amp Maximum Load: 20lbs (9kg) MB-BX Moving Bed Box Bioreactor The MB-BX Bioreactor system consists of a programmable rocker (RK- 200 or RK-250) and 1-3 single use 2L culture box modules (BX), each of which has 1-2 compartments to hold a desirable quantity of BRS 2D or 3D carrier cartridges to form a carrier bed. The rocker s rocking movement allows the cell-embedded carrier bed to move and be alternately submerged in media and exposed to air enacting The Principle of Roller Bottles. The RK-200 rocks at a fully adjustable desired angle and speed, and can also hold either or both ends at a desired position for an adjustable amount of time. The RK-250 is also equipped with temperature control with an acrylic lid. Packed Bed Culture Box Module (BX) A single use 2L culture box module contains a compartment on one end separated by a PP screen. The compartment can be filled with BRS 2D or 3D carrier cartridges or the equivalent to form a carrier bed. If desired, another compartment can be used. Our 2D carrier is made of virgin GS for monolayer growth as in a regular T-flask. The3D carrier is made of non-woven PET such as the Fibra-Cel disc and BioNOC II carrier but in cartridge form for 3D growth. Each module has two gas inlet/outlet ports, one feeding port, one sampling ports, and two caps for carrier sampling. The module is typically filled with 1L of medium. The entire module is pre-sterilized by gamma radiation. 19

20 MB Series: Moving Bed BioReactor Systems MB-100 Moving Bed BioReactor The MB-100 is an autoclavable bench top moving packed bed bioreactor. It consists of a motorized lifting unit mounted on the head plate, a moving basket holding carriers as a packed bed, and a stirrer in the bottom of vessel. The basket can be moved up and down inside of the vessel by the motorized lifting unit on the top of vessel. The moving basket allows the cell-embedded carrier bed to move and be alternately submerged in media and exposed to air implementing The Principle of Roller Bottles. - As the bed moves to the bottom the liquid level can be controlled to reaches just above the basket and the most efficient seeding, infection, transfection or trysinization can be performed. The rapid movement of the basket towards against the bottom of the vessel creates the mechanical impact force to shake cells off the carriers for cell detachment and recovery. Glass vessel with S/S bottom plate Heating and cooling with water circulation system Bottom agitation speed: rpm Pressure for air supply: Kg/cm 2 Head plate: multiple sampling/feeding ports, 12mm ports for PH/DO probes, 8mm port for temperature probe, handles on each side of the head plate for easy transportation, heating/cooling tube, a mounted motorized lifting unit. Dimensions (cm): 60W x 60H x 50D Dry weight: 70 Kg (approximate control console only) MB-200 Moving Bed BioReactor The MB-200 is a sterilization-in place-pilot and production model. This system is similar to the MB-100 except the vessel is constructed by stainless steel. Sterilization in place Bottom driven agitation speed: rpm Volume of air inflow: 1-5 SLPM (30-50L)/1-10 SLPM (100L) Pressure for air supply: Kg/cm2 Working range for pressure: Kg/cm2 Power supply: V/50-60 Hz An oil pressure jack is used to lift the head plate 20

21 MB Series: Moving Bed BioReactor Systems MBS-100 Moving Bed BioReactor The MBS-100 is a single use moving bed bench top bioreactor. It consists of a set of single use packed bed box modules (BX) placed on a moving platform and a single use bag containing medium. The BX set is a series of box modules connected in series, each of them filled with BRS 2D or 3D carrier cartridge. Both containers are connected with flexible tubing and confined in either a separate or common temperature controlled chamber. The medium bag is placed on a shaker with speed control. The moving platform can be moved up and down by a motorized pulley system with a stepping motor and with speed control. The moving platform creates the medium flow between the two containers through gravity. Constant gas mixture flows through both containers to maintain positive and constant pressure. PH of the medium bag is measured and controlled in the recirculated loop. DO is also monitored in this same loop. Similar to the MB systems the movement of the platform performs the principle of roller bottle for oxygenation and achieves high efficiency of seeding, infection, transfection, trypsinization, and cell detachment for cell recovery all in one closed system. BX packed bed culture box modules: 2L each connected up to 6 units (12L carrier) Medium bag: 10-60L BRS bag made by LePure Complete system is pre-sterilized by gamma radiation Digital orbital shaker SK110 with variable speed of rpm In line ph, DO, and temperature reusable sensors placed on recirculation loop. MBS-200 Moving Bed BioReactor The MBS-200 is a single use moving bed pilot and production bioreactor. This system is the same as the MBS-100 system except a disposable recirculation pumping system is used to mix the medium inside of the bag. PH is monitored and controlled in line as part of the recirculation loop. 21

22 AL Series: Air-Lift Systems The Air-Lift (AL) Series BioReactors are an alternative to mechanically agitated systems in applications where the process is extremely sensitive to shear stress and heat. The AL Series systems eliminate shear stress and reduce heat generation by removing the mechanical agitator, and achieve oxygen transfer, internal circulation, and mixing by bubbling air. The AL Series systems contain an inner draft tube that creates the drafting force required for liquid circulation and possible improvement of bulk mixing. Utilization of an air lift system may also demonstrate cost savings in the elimination of the aforementioned mechanical agitator and from the reduction of extra cooling requirements. Features Industrial grade microcomputer system HMI touch panel Roof-mounted mixing design Equipped with thermally controlled jacketed vessel Software-based calibration Bi-directional control computer Simple and flexible parameter settings Autoclave sterilization Custom dimension construction available Model Description Vessel Size (Liter) AL-100 Air-lift bioreactor / Autoclavable, bench top model 5, 10 AL-200 Air-lift bioreactor / Sterilize-in-place pilot to industrial scale model 30, 50, 100, 300,

23 AL Series: Air-Lift Systems AL-100 Air-Lift BioReactor Vessel volume: 5, 10 Liters Temperature control range: 5oC above ambient to 60oC Mixer speed: 0 to 1000rpm Air inflow volume: slpm (5L) ph control range: DO control range: 0-100% (controlling in cascade AG/AIR/PRESSURE) Air filter for inlet and exhaust: 0.2 μm (autoclavable) Type of foaming probe: conductivity Signal output: RS485 Peristaltic pumps: programmable for acid addition, base addition, defoaming, and/or feeding Stainless steel bottom / thermal jacketed Upper reinforced glass vessel Sampling tube from top into bottom (6 or 8mm) Roof mounted ph / DO port (12mm) Three (3) standard 12 mm feeding Height-adjustable foaming probe Temperature probe port (8mm) Equipped with air condenser (optional) AC-servo motor driven control mixer (optional) Mass air-flow meter AL-200 Air-Lift BioReactor Vessel volume: 30, 50, 100,300 and 500L or specified Temperature control range: 5C above ambient to 60C Air inflow volume: VVM ph control range: DO control range: 0-100% (controlled in cascade Agit/AIR/PRESSURE) Air filter for inlet and exhaust: 0.2 μm (autoclavable) Type of foaming probe: conductivity Type of liquid-level detection: conductivity type (batch-fed) Working range for pressure: 0-3 Kg/cm2 Valves: food industry-grade pneumatic diaphragm valves Communication protocol: two way RS485 Peristaltic pumps: programmable for acid addition, base addition, de-foaming, and/or feeding Power supply: 220 Vac/50-60 Hz 3 phase Separated in two parts for convenient maintenance Three (3) 19mm feeding ports Height-adjustable foaming probes Pressure probe port with 1.5 sanitary quick-connect Equipped with air condenser Upper-entry feeding valve (25mm and autoclavable) Headplate upper portion has air-lift device for easy operation (optional) Automated Sterilization-in-Place (optional) 4-gas mixer: N2/CO2/Air/O2 (proportional or MassFlow) (optional) Biomass in-line analyzer 23

24 AL Series: Air-Lift Systems Total VOL (Liters) A (Inner Diameter: mm) B (Height: mm) C (mm) D (mm) E (mm) F (mm)

25 RD Series: Rotating Drum Systems The Rotating Drum (RD) Series BioReactors are often used in solid state or plant cell cultures. These types of cultures are ideally cultivated in a rotating vessel system for aeration and mixing. The RD-100 model is a console containing multiple (nominally 6) rotating bottles, capable of air, ph, and feeding control for each bottle. The RD-200 is a stationery horizontal vessel equipped with a rotating impeller set specifically designed for solid state culture, and capable for air, ph, feeding and illuminating control. Ideal for solid state fermentation or cell culture Capable of use with bottles of different sizes All-in-one design facilitates easy maintenance and installation Easily re-designed for variety of number of bottles Volume of the vessel can be fully customized to customer s details Equipped with two layers of glass for optimal thermal control efficiency Impeller can be re-designed according to customer s requirements Complete with illumination units for photosynthesis Model Description Vessel Size (L) RD-100 Rotating drum bioreactor / Autoclavable, bench top model 0.5, 1 RD-200 Rotating drum bioreactor / Autoclavable, bench top model 5, 10, 20 Features: Temperature control: external thermal control unit Agitation: rpm (direction can be adjusted according to time and/or system feedback) Drive: v-shape conveyer belts Material: aluminum alloy for conveyer belt wheels and PU-coated wheels for rolling bottles, 316SS stainless steel, Pyrex class (autoclavable) Airflow: 1-5 SPLM Air filter: 0.2 um (autoclavable) Temperature control: water circulation between two layers of glass Algorithm: PID control with overheating prevention Illumination units: 6.8W RGB solar lamps Humidity control range: 50-90% R.H. Humidity control: PID controller (ultrasonic atomizing humidifier optional) 25

26 BioProcessing Instruments and Equipment GlucCell Glucose Monitoring System The GlucCell is a palm-sized and economical glucose meter designed for measuring glucose content primarily in cell culture media and in some microbial cultures. It is made by CESCO BioEngineering and is simple to use, requires a very small sample size, and measures quickly. The principle technology behind the GlucCell Glucose Monitoring System is a merging of glucose biosensor science with microprocessor-based instrumentation. The associated Glucose Test Strip requires a sample volume of less than 2 ul and has a testing time of less than 12 seconds. The meter has a large, easy-to-read display and can store up to 100 test results with corresponding times and dates. Disposable test strips and compact size enables operation of the GlucCell Glucose Monitoring System in a biosafety cabinet, eliminating risk of contamination from bioharzardous samples. Easy-to-Use Quick response time: 12 seconds Small sample size: 2.5µL No major set-up requirements Ready to test, right out of the box Large LCD, easy-to-read digital display Features Suitable for both serum and serum-free culture medium Portable, calibration-free, ready-to-use 99.5% correlation with NOVA and YSI biochemical analyzer Direct measurement without needing to separate cells from culture medium User-programmable units of measurement for mg/dl or mmol/l Zero risk of contamination to device or to the environment Specifications Dimensions: 96mm x 60mm x 18.5mm Weight: 70g including battery Power Source: one (1) CR2032 3V Li coin battery Battery Life: approximately 1000 tests Display: large LCD Automation: auto-electrode insert detection, auto-sample loading detection, auto-reaction time countdown, auto-turn off Memory: stores up to 180 test results Environment: degree C Req'd Sample Size: 2 ul Measurement Range: mg/dl ( mmol/l) Test result time: < 12 secs. Product Information - Contact Us for a Price Quotation GM-100 Glucose Monitoring System: includes one (1) GM-100 meter & fifty (50) test strips GMS Glucose Test Strips: 1 bottle with fifty (50) test strips per bottle 26

27 BioProcessing Instruments and Equipment PV-100/150 & PV-200/250 Pinch Valve Motor Driven and Position Controllable Industrial Pinch Valve The PV Series pinch valve is a motor driven, position controllable industrial pinch valve. The panel-mount ready unit supports tubing sizes ranging from 0.1 to 0.8 inches (3-20mm). The PV150 and PV250 models can stop and start anywhere along their pinch motion and be used to control flow rate. Applications BioProcessing o Single Use Disposable SSD o Filling o Mixing o Dispensing o Media Production Medical Applications o Dialysis Equipment o Intravenous (IV) Systems Flexible Tubing Mid-Large Volumes Features Electrical motor driven generates little to no heat Safe for use in clean-room cleaning regimens Accommodate s OD tubing from 3 to 20 mm Available in 316L stainless steel or industrial plastic material formats No deformation of hose shape and structural integrity Increased range of pinch motion Adjustable maximum motor torque current cut-off per hose size Specifications Input Voltage: 12 Vdc or 24Vdc Controller: ATMel ATMega85 Timing: open to close 1-8 secs varies on end user motor selection. Dimensions (mm): 100mm L x 38mm dia. (PV ); 132mm L x 55mm dia. (PV ) Optional waterproof motor enclosure Model Description Tubing (OD, mm) PV-100 ON/OFF motor driven pinch valve 3-10 PV-150 Position controllable motor driven pinch valve 3-10 PV-200 ON/OFF motor driven pinch valve PV-250 Position controllable motor driven pinch valve

28 BioProcessing Instruments and Equipment SV-100 Sampling Valve and FV-100 Feeding Valve The SV-100 and FV-100 valves are patented and designed for sampling and feeding. These valves are used exclusively in our pilot and production scale bioreactor systems. Features Stainless Steel, Reusable, Patented, easy and effective sterilization 25mm standard port Double O ring stanch as needed Steam sterilization cleaning: zero dead space 1/8" PT steam interface FV-100 Open position with locking mechanism Feed aperture: 10mm SV-100 Adjustable sampling rate Sampling aperture: 10mm Sterile sampling head cover 28

29 BioProcessing Instruments and Equipment DV-100: Diaphragm Valve The DV-100 diaphragm valve is a 1/2" or 12mm, EPDM Wetted Material, 316L SS valve. It has no dead space and is easy to clean and maintain. It is utilized most effectively in applications requiring high sanitation. It is also used exclusively in our pilot and production scale bioreactor systems. Designed for: BioTechnology Food Industry Pharmaceutical Markets Medical Applications Features Fluids are hermetically sealed from operating system Zero dead volume eliminating any chance of contamination CIP and SIP cleaning and sterilizing capabilities Compact design (when space is at a premium) Manual or pneumatic operation Easy diaphragm replacement Specifications Material: 316 Stainless Steel Orifice: 1/2" or 12mm Connection types: weld, threaded, tri-clamp Diaphragm material: EPDM Diaphragm Temperature range: 0 ~ 150 C Air pressure control: 4 ~ 6Kg/cm2 Valve dimensions (mm): 60W X 56D X 65H 29

30 BioProcessing Instruments and Equipment Gas Blending and Distribution Stations Our gas blending stations are for bioprocessing control to provide various percentages of N2, CO2, O2, and AIR into the gas supply line. Our gas distribution stations supply individual gas to multiple individual bioreactor systems including our MB-BX system where multiple bioreactors are on a common platform. Features Gas mixing of up to 4 independent gases Easily adjustable flow by knob on front of rotometers Optional control solenoid valves can be added to interface Specifications Inlet/outlet connections made via ¼ hose barb fittings Supplied gas must be dried, filtered and regulated to less than 15PSI Standard flow rates: 200ML AND 10L (adjustable per customer request) Model GB-100 GB-110 GD-100 GD-110 GD-120 Description Four rotameters for mixing of 4 independent gases Four rotameters for mixing of 4 independent gases plus an air pump Three rotameters for 3 independent gas lines Three rotameters for 3 independent gas lines; one air pump Three rotameters for 3 independent gas lines; three air pumps 30

31 BioProcessing Instruments and Equipment PP-100 & -200 Peristaltic Pumps The PP Series pumps are ideally suited for fermentation and cell culture applications. They are equipped with Watson-Marlow quick-change pump head units, and with a fixed speed, variable speed or automatic drive. The PP-200 is used in our FBS-100 Fixed Bed, Single-Use, Bench-Top Model BioReactor. This process pump is fitted with 1.6mm thick walled, continuous-tubing pump heads designed for extreme industrial conditions. Features Easy to install, operate, & maintain Watson-Marlow head unit Accurate & repeatable flow rates Pumps act as their own check valve Manually or automatic remote controlled Superior speed control, 1% set speed accuracy Easily-altered wide range of speed Maintenance-free, brushless DC motor Smooth, wipe down case with no sharp edges Timer function allows for programmed intermittent on/off PP-100 PP-200 PP-100 Specifications Manual or Automatic Control (via 4-20mA or 0-10V inputs) Range of speed: 0-30 rpm (can be customized to customer s requirements) Speed accuracy: 1% full scale Tube specifications: mm ID Flow volume: 50 ml (tube size dependent) Approx. weight (dry): 3 Kg PP-200 Specifications 520R Continuous tubing pumphead Speed control range from 0.1 to 220 rpm in 0.1 rpm increments Control method: manual or remote Input control: 4-20mA or 0-10 Vdc Speed accuracy: 1% full scale Flow rates from 4 microlitres/min up to 2.4 liter/min 31