Engineering Commons^™

Use Of An Automated, Integrated Laboratory Environment To Enable Predictive Modeling Approaches For Identifying Critical Process Parameters And Controlling Key Quality Attributes, Brandon Downey, John Schmitt, Jeffrey Breit, Brian Russell, Justin Beller, Liz Herman, Anthony Quach, David Lyon

Cell Culture Engineering XV

An essential part of ensuring a high quality medicine is being able to reliably control Critical Quality Attributes (CQA’s). In the cell culture process, bioreactor conditions, feeds, cell state are some of the many variables that affect CQA’s. Out of this very large set of possible variables, the small subset of these (i.e., critical process parameters, or CPP’s) that have a large effect on the CQA’s must be identified and understood such that those CPP’s can be controlled to ensure quality product. Here, we demonstrate the use of predictive modeling techniques to supplement experimental bioreactor studies when defining critical process …

Evolution Of An Integrated Continuous Antibody Manufacturing Process, Christopher Kistler

Cell Culture Engineering XV

Efforts continue to reduce the timeline and cost of progressing biologics from discovery through preclinical development to product launch. Integrated processes, those that link upstream and downstream processing with control of product quality are an attractive way to achieve meaningful reductions in the overall cost of ownership of a biologics manufacturing process.

To start along this path, an integrated continuous processing laboratory, the PROLab (Protein Refinery Operations Lab) was built to pilot the concepts of an integrated continuous antibody manufacturing process under automated control. A perfusion process was developed capable of operating for >30 days using either TFF (Spectrum KrosFlo® …

Protein Refinery Operations Lab (Pro Lab): A Sandbox For Continuous Protein Production & Advanced Process Control, Mark Brower, David Pollard, Finn Hung

Integrated Continuous Biomanufacturing II

Significant strides towards implementation of continuous bioprocessing are being made at an ever increasing rate. Advances in technology for traditional unit operations such as cell-retention devices in perfusion cell culture, continuous multi-column chromatography (CMCC) and single-pass tangential flow filtration have led to demonstrations of both semi-continuous and fully-continuous protein production processes operating at periodic steady states at the pilot-scale. Previous proof of concept work at Merck & Co., Inc. has shown an automated (DeltaV) and single-use monoclonal antibody (mAb) purification scheme through Protein A CMCC and pH viral inactivation with minimal human interaction for 30 days fed from a perfusion …

Hierarchical Optimal Force-Position-Contour Control Of Machining Processes. Part Ii. Illustrative Example, Yan Tang, Robert G. Landers, S. N. Balakrishnan

Mechanical and Aerospace Engineering Faculty Research & Creative Works

There has been a tremendous amount of research in machine tool servomechanism control, contour control, and machining force control; however, to date these technologies have not been tightly integrated. This paper develops a hierarchical optimal control methodology for the simultaneous regulation of servomechanism positions, contour error, and machining forces. The contour error and machining force process reside in the top level of the hierarchy where the goals are to 1) drive the contour error to zero to maximize quality and 2) maintain a constant cutting force to maximize productivity. These goals are systematically propagated to the bottom level, via aggregation …

Hierarchical Optimal Force-Position-Contour Control Of Machining Processes. Part I. Controller Methodology, Yan Tang, Robert G. Landers, S. N. Balakrishnan

Mechanical and Aerospace Engineering Faculty Research & Creative Works

There has been a tremendous amount of research in machine tool servomechanism control, contour control, and machining force control; however, to date these technologies have not been tightly integrated. This paper develops a hierarchical optimal control methodology for the simultaneous regulation of servomechanism positions, contour error, and machining forces. The contour error and machining force process reside in the top level of the hierarchy where the goals are to 1) drive the contour error to zero to maximize quality and 2) maintain a constant cutting force to maximize productivity. These goals are systematically propagated to the bottom level, via aggregation …

Trends In Process Control Systems Security, Ann K. Miller

Electrical and Computer Engineering Faculty Research & Creative Works

The protection of critical infrastructure systems is a hotly debated topic. The very label "critical infrastructure" implies that these systems are important, and they are: they support our everyday lives, from the water and food in our homes to our physical and financial welfare. This article explores the recent evolution of programmable logic controllers (PCSs) and their environments, explains the need for improved security in these systems, and describes some of the emerging research areas that offer promise in PCS security.

Hierarchical Optimal Force-Position Control Of A Turning Process, B. Pandurangan, Robert G. Landers, S. N. Balakrishnan

Mechanical and Aerospace Engineering Faculty Research & Creative Works

Machining process control technologies are currently not well integrated into machine tool controllers and, thus, servomechanism dynamics are often ignored when designing and implementing process controllers. In this brief, a hierarchical controller is developed that simultaneously regulates the servomechanism motions and cutting forces in a turning operation. The force process and servomechanism system are separated into high and low levels, respectively, in the hierarchy. The high-level goal is to maintain a constant cutting force to maximize productivity while not violating a spindle power constraint. This goal is systematically propagated to the lower level and combined with the low-level goal to …

Hierarchical Optimal Control Of A Turning Process - Linearization Approach, Anand Dasgupta, B. Pandurangan, Robert G. Landers, S. N. Balakrishnan

Mechanical and Aerospace Engineering Faculty Research & Creative Works

Machining process control technologies are currently not well integrated into machine tool controllers and, thus, servomechanism dynamics are often ignored when designing and implementing process controllers. In this paper, a hierarchical controller is developed that simultaneously regulates the servomechanism positions and cutting forces in a lathing operation. The force process and servomechanism system are separated into high and low levels, respectively, in the hierarchy. The high level goal is to maintain a constant cutting force to maximize productivity while not violating a spindle power constraint. This goal is systematically propagated to the lower level and combined with the low level …

Output Feedback Force Control For A Parallel Turning Operation, Raghusimha Sudhakara, Robert G. Landers

Mechanical and Aerospace Engineering Faculty Research & Creative Works

Parallel machine tools (i.e., machine tools capable of cutting a part with multiple tools simultaneously but independently) are being utilized more and more to increase operation productivity, decrease setups, and reduce floor space. Process control is the utilization of real-time process sensor information to automatically adjust process parameters (e.g., feed, spindle speed) to increase operation productivity and quality. To date, however, these two technologies have not been combined. This paper describes the design of an output feedback controller for a parallel turning operation that accounts for the inherent nonlinearities in the force process. An analysis of the process equilibriums explains …

Approximate Dynamic Programming Based Optimal Neurocontrol Synthesis Of A Chemical Reactor Process Using Proper Orthogonal Decomposition, Radhakant Padhi, S. N. Balakrishnan

Mechanical and Aerospace Engineering Faculty Research & Creative Works

The concept of approximate dynamic programming and adaptive critic neural network based optimal controller is extended in this study to include systems governed by partial differential equations. An optimal controller is synthesized for a dispersion type tubular chemical reactor, which is governed by two coupled nonlinear partial differential equations. It consists of three steps: First, empirical basis functions are designed using the "Proper Orthogonal Decomposition" technique and a low-order lumped parameter system to represent the infinite-dimensional system is obtained by carrying out a Galerkin projection. Second, approximate dynamic programming technique is applied in a discrete time framework, followed by the …

Dynamic Re-Optimization Of A Fed-Batch Fermentor Using Adaptive Critic Designs, Donald C. Wunsch, M. S. Iyer

Electrical and Computer Engineering Faculty Research & Creative Works

Traditionally, fed-batch biochemical process optimization and control uses complicated off-line optimizers, with no online model adaptation or re-optimization. This study demonstrates the applicability of a class of adaptive critic designs for online re-optimization and control of an aerobic fed-batch fermentor. Specifically, the performance of an entire class of adaptive critic designs, viz., heuristic dynamic programming, dual heuristic programming and generalized dual heuristic programming, was demonstrated to be superior to that of a heuristic random optimizer, on optimization of a fed-batch fermentor operation producing monoclonal antibodies

Dynamic Re-Optimization Of A Fed-Batch Fermentor Using Heuristic Dynamic Programming, Donald C. Wunsch, M. S. Iyer

Electrical and Computer Engineering Faculty Research & Creative Works

Traditionally, fed-batch biochemical process optimization and control uses complicated theoretical off-line optimizers, with no online model adaptation or re-optimization. This study demonstrates the applicability, effectiveness, and economic potential of a simple phenomenological model for modeling, and an adaptive critic design, heuristic dynamic programming, for online re-optimization and control of an aerobic fed-batch fermentor. The results are compared with those obtained using a heuristic random optimizer

Fed-Batch Dynamic Optimization Using Generalized Dual Heuristic Programming, Donald C. Wunsch, M. S. Iyer

Electrical and Computer Engineering Faculty Research & Creative Works

Traditionally fed-batch biochemical process optimization and control uses complicated theoretical off-line optimizers, with no online model adaptation or re-optimization. This study demonstrates the applicability, effectiveness, and economic potential of a simple phenomenological model for modeling, and an adaptive critic design, generalized dual heuristic programming, for online re-optimization and control of an aerobic fed-batch fermentor. The results are compared with those obtained using a heuristic random optimizer