Modeling, optimization, and sensitivity analysis of a continuous multi-segment crystallizer for production of active pharmaceutical ingredients

We have investigated the simulation-based, steady-state optimization of a new type of crystallizer for the production of pharmaceuticals. The multi-segment, multi-addition plug-flow crystallizer (MSMA-PFC) offers better control over supersaturation in one dimension compared to a batch or stirred-tank crystallizer. Through use of a population balance framework, we have written the governing model equations of population balance and mass balance on the crystallizer segments. The solution of these equations was accomplished through either the method of moments or the finite volume method. The goal was to optimize the performance of the crystallizer with respect to certain quantities, such as maximizing the mean crystal size, minimizing the coefficient of variation, or minimizing the sum of the squared errors when attempting to hit a target distribution. Such optimizations are all highly nonconvex, necessitating the use of the genetic algorithm. Our results for the optimization of a process for crystallizing flufenamic acid showed improvement in crystal size over prior literature results. Through the use of a novel simultaneous design and control (SDC) methodology, we have further optimized the flowrates and crystallizer geometry in tandem.^ We have further investigated the robustness of this process and observe significant sensitivity to error in antisolvent flowrate, as well as the kinetic parameters of crystallization. We have lastly performed a parametric study on the use of the MSMA-PFC for in-situ dissolution of fine crystals back into solution. Fine crystals are a known processing difficulty in drug manufacture, thus motivating the development of a process that can eliminate them efficiently. Prior results for cooling crystallization indicated this to be possible. However, our results show little to no dissolution is used after optimizing the crystallizer, indicating the negative impact of adding pure solvent to the process (reduced concentration via dilution, and decreased residence time) outweighs the positive benefits of dissolving fines. The prior results for cooling crystallization did not possess this coupling between flowrate, residence time, and concentration, thus making fines dissolution significantly more beneficial for that process. We conclude that the success observed in hitting the target distribution has more to do with using multiple segments and having finer control over supersaturation than with the ability to go below solubility. Our results showed that excessive nucleation still overwhelms the MSMA-PFC for in-situ fines dissolution when nucleation is too high

불확실성 하에서 시스템의 유지 보수 최적화 및 수명 주기 예측

학위논문 (박사)-- 서울대학교 대학원 : 공과대학 화학생물공학부, 2019. 2. 이원보.The equipment and energy systems of most chemical plants have undergone repetitive physical and chemical changes and lead to equipment failure through aging process. Replacement and maintenance management at an appropriate point in time is an important issue in terms of safety, reliability and performance. However, it is difficult to find an optimal solution because there is a trade-off between maintenance cost and system performance. In many cases, operation companies follow expert opinions based on long-term industry experience or forced government policy. For cost-effective management, a quantitative state estimation method and management methodology of the target system is needed. Various monitoring technologies have been introduced from the field, and quantifiable methodologies have been introduced. This can be used to diagnose the current state and to predict the life span. It is useful for decision making of system management. This thesis propose a methodology for lifetime prediction and management optimization in energy storage system and underground piping environment. First part is about online state of health estimation algorithm for energy storage system. Lithium-ion batteries are widely used from portable electronics to auxiliary power supplies for vehicle and renewable power generation. In order for the battery to play a key role as an energy storage device, the state estimation, represented by state of charge and state of health, must be well established. Accurate rigorous dynamic models are essential for predicting the state-of health. There are various models from the first principle partial differential model to the equivalent circuit model for electrochemical phenomena of battery charge / discharge. It is important to simulate the battery dynamic behavior to estimate system state. However, there is a limitation on the calculation load, therefore an equivalent circuit model is widely used for state estimation. Author presents a state of health estimation algorithm for energy storage system. The proposed methodology is intended for state of health estimation under various operating conditions including changes in temperature, current and voltage. Using a recursive estimator, this method estimate the current battery state variable related to battery cell life. State of health estimation algorithm uses estimated capacity as a cell life-time indicator. Adaptive parameters are calibrated by a least sum square error estimation method based on nonlinear programming. The proposed state-of health estimation methodology is validated with cell experimental lithium ion battery pack data under typical operation schedules and demonstration site operating data. The presented results show that the proposed method is appropriate for state of health estimation under various conditions. The suitability of algorithm is demonstrated with on and off line monitoring of new and aged cells using cyclic degradation experiments. The results from diverse experimental data and data of demonstration sites show the appropriateness of the accuracy, robustness. Second part is structural reliability model for quantification about underground pipeline risk. Since the long term usage and irregular inspection activities about detection of corrosion defect, catastrophic accidents have been increasing in underground pipelines. Underground pipeline network is a complex infrastructure system that has significant impact on the economic, environmental and social aspects of modern societies. Reliability based quantitative risk assessment model is useful for underground pipeline involving uncertainties. Firstly, main pipeline failure threats and failure modes are defined. External corrosion is time-dependent factor and equipment impact is time-independent factor. The limit state function for each failure cause is defined and the accident probability is calculated by Monte Carlo simulation. Simplified consequence model is used for quantification about expected failure cost. It is applied to an existing underground pipeline for several fluids in Ulsan industrial complex. This study would contribute to introduce quantitative results to prioritize pipeline management with relative risk comparisons Third part is maintenance optimization about aged underground pipeline system. In order to detect and respond to faults causing major accidents, high resolution devices such as ILI(Inline inspection), Hydrostatic Testing, and External Corrosion Direct Assessment(ECDA) can be used. The proposed method demonstrates the structural adequacy of a pipeline by making an explicit estimate of its reliability and comparing it to a specified reliability target. Structural reliability analysis is obtaining wider acceptance as a basis for evaluating pipeline integrity and these methods are ideally suited to managing metal corrosion damage as identified risk reduction strategies. The essence of this approach is to combine deterministic failure models with maintenance data and the pipeline attributes, experimental corrosion growth rate database, and the uncertainties inherent in this information. The calculated failure probability suggests the basis for informed decisions on which defects to repair, when to repair them and when to re-inspect or replace them. This work could contribute to state estimation and control of the lithium ion battery for the energy storage system. Also, maintenance optimization model helps pipeline decision-maker determine which integrity action is better option based on total cost and risk.화학공장 내 장치 및 에너지 시스템은 반복적인 사용으로 물리화학적 변화를 겪으며 노후화되고 설계 수명에 가까워지게 된다. 적절한 시점에 장비 교체와 보수 관리는 안전과 신뢰도, 전체 시스템 성능을 좌우하는 중요한 문제이다. 그러나, 보수 비용과 시스템 성능을 유지하는 것 사이에는 트레이드 오프가 존재하기 때문에 이에 대한 최적점을 찾는 것은 어려운 문제이다. 많은 경우에 운영회사에서는 경험에 기반한 전문가 의견을 따르거나, 정부차원의 안전관리 정책 최소 기준에 맞추어 진행한다. 비용효율적 관리를 위하여 정량적인 상태 추정 기법이나 유지보수 관리 방법론은 필요하다. 많은 모니터링 기술이 개발되어지고 있고 점차 실시간 측정 방법이나 센서 기술이 발달 하고 있다. 그러나, 여전히 직접 측정 및 검사 이전 장비의 수명 예측과 시스템 관리에 대한 의사결정을 도울 방법론은 부족한 실정이다. 본 논문에서는 리튬 이온 배터리의 수명예측 방법론과 지하매설배관의 관리 최적화 문제를 다룬다. 첫 장에서는 에너지 저장시스템 운전패턴에 적합한 배터리 SOH 추정 방법론에 대한 것이다. 리튬 이온 배터리는 이동가능 전자장치에서부터 자동차 및 신재생발전 등의 보조 전력 저장장치로서 활용이 이루어지고 있다. 배터리가 정상적인 역할을 하기 위하여 SOC와 SOH의 정확한 추정이 중요하다. 정확한 동적 모델은 SOH 예측을 위하여 필수적이다. BMS에는 계산 로드에 한계가 있기 때문에 상태 추정을 위하여 계산 부하가 비교적 적은 등가회로 모델이 사용된다. 본 논문에서는 SOH 예측 알고리즘을 제시하고, 셀 및 실증 사이트 데이터로 검증한다. 반복 예측기와 관측기 기법을 활용하여 SOH를 추정을 통하여 현재의 배터리 상태를 제시한다. SOH 예측 알고리즘은 용량을 중요 상태변수로 하여 예측된다. 제안 알고리즘에서는 SOH를 정확히 추정하기 위하여 확장칼만필터를 도입하여 배터리 상태변수들을 정확히 예측하고 이를 기반으로 SOH를 추정하는 알고리즘을 제안한다. 두번째 장은 구조 신뢰도 분석을 통하여 지하배관의 정량적 위험성 모델을 수립한다. 배관의 장기 사용과 불규칙한 검사/보수 활동에 대한 불확실성은 지하배관 안전 사고의 위험성을 증대시키는 요인이다. 산업단지 내의 지하배관 네트워크는 복잡한 인프라를 갖추고 있기 때문에 사고 발생시 경제적, 환경적, 사회적으로 큰 위협요소가 된다. 신뢰도 기반 정량적 위험도 모델은 지하배관의 큰 불확실성 요소를 고려하는데 유용한 방법론이다. 배관 사고 위협요인과 사고 모드를 정의하고, 부식과 타공사에 이르는 시간 의존적, 비의존적 요소를 고려하여 한계상태함수를 결정한다. 몬테카를로 시뮬레이션을 통하여 연간 사고확률이 유추되며 사고 영향거리 및 누출량 계산 모델과 합하여 정량적 위험성 분석을 할 수 있다. 배관에 존재하는 다양한 물질들에 대하여 케이스 스터디를 진행하여 정량화된 위험도에 근거하여 배관관리 우선순위를 정하는 의사결정에 반영할 수 있다. 세번째 장은 노후화된 배관 시스템의 관리 최적화에 대한 내용이다. 사고의 위험성을 미연에 방지하기 위하여 다양한 검사, 보수 방법론이 사용된다. 그러나, 이에 대한 효과가 위험성과 어떻게 관련되어서 나타나는지 알기 어렵다. 대부분 경험적으로 혹은 제도적인 방안을 통하여 보수적인 안전관리를 진행하는 한계성이 있다. 제안된 방법론을 토대로 하여 안전관리 방법에 대한 실제적인 부식 관리에 영향 정도를 정량화 한다. 신뢰도 목표와 제안 되어진 예산 등을 제한조건으로 하는 최적화를 실시하여 최적의 검사 주기, 최적의 검사 방법론을 확인한다. 위 연구를 토대로 개선된 리튬이온 배터리의 온라인 상태추정 알고리즘 제시하고 위험도 환산 비용을 결합한 구조 신뢰도 모델로 지하배관 관리 최적화 방법론을 제시한다.Abstract i Contents vi List of Figures ix List of Tables xii CHAPTER 1. Introduction 14 1.1. Research motivation 14 1.2. Research objectives 19 1.3. Outline of the thesis 20 CHAPTER 2. Lithium ion battery modeling and state of health Estimation 21 2.1. Background 21 2.2. Literature Review 22 2.2.1. Battery model 23 2.2.2. Qualitative comparative review of state of health estimation algorithm 29 2.3. Previous estimation algorithm 32 2.3.1. Nonlinear State estimation method 32 2.3.2. Sliding mode observer 35 2.3.3. Proposed Algorithm 37 2.3.4. Uncertainty Factors for SOH estimation in ESS 42 2.4. Data acquisition 44 2.4.1. Lithium ion battery specification 45 2.4.2. ESS Experimental setup 47 2.4.3. Sensitivity Analysis for Model Parameter 54 2.5. Result and Discussion 59 2.5.1. Estimation results of battery model 59 2.5.2. Estimation results of proposed method 63 2.6. Conclusion 68 CHAPTER 3. Reliability estimation modeling for quantitative risk assessment about underground pipeline 69 3.1. Introduction 69 3.2. Uncertainties in underground pipeline system 72 3.3. Probabilistic based Quantitative Risk Assessment Model 73 3.3.1. Structural Reliability Assessment 73 3.3.2. Failure mode 75 3.3.3. Limit state function and variables 79 3.3.4. Reliability Target 86 3.3.5. Failure frequency modeling 90 3.3.6. Consequence modeling 95 3.3.7. Simulation method 101 3.4. Case study 103 3.4.1. Statistical review of Industrial complex underground pipeline 103 3.5. Result and discussion 107 3.5.1. Estimation result of failure probability 107 3.5.1. Estimation result validation 118 CHAPTER 4. Maintenance optimization methodology for cost effective underground pipeline management 120 4.1. Introduction 120 4.2. Problem Definition 124 4.3. Maintenance scenario analysis modeling 126 4.3.1. Methodology description 128 4.3.2. Cost modeling 129 4.3.3. Maintenance mitigation model 132 4.4. Case study 136 4.5. Results 138 4.5.1. Result of optimal re-inspection period 138 4.5.2. Result of optimal maintenance actions 144 CHAPTER 5. Concluding Remarks 145 References 147Docto

Efficient Algorithms for Large-Scale Image Analysis

This work develops highly efficient algorithms for analyzing large images. Applications include object-based change detection and screening. The algorithms are 10-100 times as fast as existing software, sometimes even outperforming FGPA/GPU hardware, because they are designed to suit the computer architecture. This thesis describes the implementation details and the underlying algorithm engineering methodology, so that both may also be applied to other applications

Imaging Sensors and Applications

In past decades, various sensor technologies have been used in all areas of our lives, thus improving our quality of life. In particular, imaging sensors have been widely applied in the development of various imaging approaches such as optical imaging, ultrasound imaging, X-ray imaging, and nuclear imaging, and contributed to achieve high sensitivity, miniaturization, and real-time imaging. These advanced image sensing technologies play an important role not only in the medical field but also in the industrial field. This Special Issue covers broad topics on imaging sensors and applications. The scope range of imaging sensors can be extended to novel imaging sensors and diverse imaging systems, including hardware and software advancements. Additionally, biomedical and nondestructive sensing applications are welcome