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1、Bioreactor selection,Scale-Up,Bringing a Process to Scale,Each product creates its own unique challenges for process development: Developing a Biofuels process to the 300,000L scale faces different challenges than developing a Pharmaceutical production process to the 100L-25,000L scale. Developing a
2、 Pharmaceutical production process in a microbial host faces different challenges than would be faced in a mammalian process. Despite the wide range of differences, most process development efforts require the same basic steps and these steps are a result of shared end goals.,What is the Goal?...,To
3、 run a multi-million (billion) dollar production facility at full capacity producing end products worth millions (billions) of dollars.,How is this Goal Achieved?,At the heart of the process is a stable, reliable cell line and culture approach which has been well characterized at a smaller and more
4、manageable scale.,Create Cell Line,Select in Well-Plates,Advance to Flasks, Select Further.,,Expand Cell Line,,,,,,,Develop the Process,Scale the Process,,Identify ProductR&D,Large Scale Process,,,,,,,,Identify ProductR&D,,,Selection Steps,Development Steps,Because these steps provide very little in
5、formation to the researcher, “Selection” is possible, but true process development is difficult.,The data recorded at each step during process development is what allows the researcher to control and therefore scale the process.,Information Available at Different Stages.,,,,,,,,Identify ProductR&D,,
6、,Early, High-throughput stages provide little information. Researchers are often limited to Cell Counts and Titers.,Process Development stages track and control many parameters: pH, DO, pCO2, OTR, Osmolarity, Nutrient Feeds, Cell Viability, Cell Count,Selection Steps,Development Steps,Scaling a Proc
7、ess Requires Information.,Scaling Steps Require Control.,,,Selection Steps, Approach: Nutrients, keep media the same and hope for the best. Oxygen Transfer Rate, keep mixing the same and hope for the best. pH, use buffers to control the process you get the idea. Temperature.,Process Development Step
8、s, Approach: Nutrients, keep constant - control media composition, feed timing and rates. Oxygen Transfer Rate, keep OTR the same, control agitator speeds and sparge gas compositions. pH, dual sided pH controller, use the same acid or base at each scale. Temperature, closed loop control over tempera
9、ture. pCO2, Osmolarity, Cell Counts and Viabilities monitored, controls may be adjusted to match performance of previous scales.,Selection Steps must be predictive of the first controlled scale.,Development Steps constrain the culture to achieve reproducible results.,Well plates,,Shake Flasks,,STBRs
10、,Large Flasks / Spinners,Traditional Process Flow,Upstream process development steps typically rely on antiquated technologies. These technologies have questionable scalability.,?,,,?,?,Better Tools, Better Decisions, Earlier,-Flasks,Sensored -Flasks,STBRs,Improved consistency, monitoring and contro
11、l permit better quality experiments. Improved experiment quality upstream of STBRs allows better decisions. -Flasks, SDR, SFR, AFS and The RAM make your existing work more predictive.,,,,,AFM, The RAM,,Consistency, Monitoring and Control,-Flasks,Test Tubes, Shake flasks. Increased aeration. Reduced
12、evaporative loss. Solid support , Re-useable / Autoclavable. May be used with the SensorDish Reader.,-Flasks are Shake Flasks,-Flasks Scale to Shake Flasks,-Flask ConfigurationsFrom 100ul to 4.0ml,,Applikon Small-Scale A big STEP AHEAD with a small footprint.,-Flasks,The SDR and SFR,Predictive Resul
13、ts, Earlier,-Flask: Replaces well plate lids, test tubes and shake flasks Works with all shaker-incubators SensorDish Reader + SensorFlask Reader Add Sensors to well plates and Shake Flasks Compatible with - flask closures Collect data from hundreds of parallel cultures,SensorDish Reader , SDR,Senso
14、rDish Reader , SDR,Non-invasive, online. pH or Dissolved Oxygen. No Calibration Required.,6-well,24-well,Expandable,Additional SDRs link into the Basic Set. Up to 10 SDRs on one Laptop. No additional software required for expansion.,SDRs Integrate with -Flasks,,,-Flasks Integrate with the SensorDish
15、Reader,Eliminate Well-plate inconsistency. Reduce and equalize evaporative losses across well-plates. Obtain online pH or dissolved oxygen data for all wells.,DO profiles (all 24 for each well-plate),,,,,Polystyrene,u-Flask,SensorFlaskReader , SFR,The SensorFlask Reader, SFR,Shaker-mounting blue-too
16、th sensor platform. Shake Flasks with DO and pH sensors. (also single DO or pH if desired) Multiple volumes (125/250/500/1000 ml). Up to 9 flasks on the platform at one time.,Microbial and Mammalian Applications,Microbial Applications: Monitor pH and DO levels. Ensure aerobic growth. Follow carbon s
17、ource utilization and exhaustion. Adjust orbiter speeds to maintain DO levels for better scalability.,Mammalian Applications: Accurately monitor pH /pCO2 levels. Adjust bicarbonate levels more accurately. Monitor DO levels, adjust orbiter speeds for better scalability.,Software,Individual Flask Cali
18、bration,Complete Hardware,Hardware Includes: Platform. Batteries. Bluetooth adapter. Software. Clamps. Bluetooth range of 15ft. Battery life 3 months on a single charge. (platform can operate on single battery),Predictive Results, Earlier,-Flask: Replaces well plate lids, test tubes and shake flasks Works with all shaker-incubators SensorDish Reader + SensorFlask Reader Add Sensors to well plates and Shake Flasks Compatible with - flask closures Collect data from hundreds of parallel cultures,Questions?,,
生物反應器課件Bioreactorselection.ppt
