Adaptive Tracking of a Single-Rigid-Body Character in Various Environments

Since the introduction of DeepMimic [Peng et al. 2018], subsequent research has focused on expanding the repertoire of simulated motions across various scenarios. In this study, we propose an alternative approach for this goal, a deep reinforcement learning method based on the simulation of a single-rigid-body character. Using the centroidal dynamics model (CDM) to express the full-body character as a single rigid body (SRB) and training a policy to track a reference motion, we can obtain a policy that is capable of adapting to various unobserved environmental changes and controller transitions without requiring any additional learning. Due to the reduced dimension of state and action space, the learning process is sample-efficient. The final full-body motion is kinematically generated in a physically plausible way, based on the state of the simulated SRB character. The SRB simulation is formulated as a quadratic programming (QP) problem, and the policy outputs an action that allows the SRB character to follow the reference motion. We demonstrate that our policy, efficiently trained within 30 minutes on an ultraportable laptop, has the ability to cope with environments that have not been experienced during learning, such as running on uneven terrain or pushing a box, and transitions between learned policies, without any additional learning

Microfluidic Cell Retention Device for Perfusion of Mammalian Suspension Culture

Continuous production of biologics, a growing trend in the biopharmaceutical industry, requires a reliable and efficient cell retention device that also maintains cell viability. Current filtration methods, such as tangential flow filtration using hollow-fiber membranes, suffer from membrane fouling, leading to significant reliability and productivity issues such as low cell viability, product retention, and an increased contamination risk associated with filter replacement. We introduce a novel cell retention device based on inertial sorting for perfusion culture of suspended mammalian cells. The device was characterized in terms of cell retention capacity, biocompatibility, scalability, and long-term reliability. This technology was demonstrated using a high concentration ( > 20 million cells/mL) perfusion culture of an IgG 1 -producing Chinese hamster ovary (CHO) cell line for 18-25 days. The device demonstrated reliable and clog-free cell retention, high IgG 1 recovery ( > 99%) and cell viability ( > 97%). Lab-scale perfusion cultures (350 mL) were used to demonstrate the technology, which can be scaled-out with parallel devices to enable larger scale operation. The new cell retention device is thus ideal for rapid perfusion process development in a biomanufacturing workflow

Novel micro/nanofluidic system for separation and monitoring of cells and proteins in perfusion

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2019Cataloged from PDF version of thesis.Includes bibliographical references.High-quality complex biopharmaceutical products based on cells and proteins are transforming modem medicine and advancing treatments for many health conditions. Continuous biomanufacturing is one of the top technology trends in the biopharmaceutical industry to improve biological product quality and reduce manufacturing cost. This thesis introduces novel high-throughput microfluidic cell separation and nanofluidic protein quality monitoring technologies. The novel micro/nanofluidic system enables reliable and efficient microfiltration and robust online rapid product quality monitoring during continuous biomanufacturing. This technology overcomes the limitations of the current membrane-based microfiltration and quality monitoring technologies, including filter clogging, low product recovery, manual sample preparation, and off-line analysis. The first part describes the novel cell retention device for perfusion culture based on inertial sorting.Size-dependent hydrodynamic forces enabled membrane-less microfiltration for the separation of suspended mammalian cells. The device performance in terms of cell retention efficiency, long-term biocompatibility, and scalability was assessed. Long-term and small-scale perfusion culture using the device was subsequently demonstrated. Clog-free cell retention with high product recovery in this work can be utilized for long-term reliable and efficient perfusion culture. The next part describes the removal of small dead cells from bioreactor cultivation by high-throughput size-based cell separation using inertial sorting. The device parameters were studied to optimize removal of the dead cells, and high-throughput and high-concentration dead cell removal was demonstrated. Finally, continuous online purity monitoring of the proteins in the cell culture supernatant during perfusion culture was achieved with a novel nanofluidic filter array.This nanofluidic device with online sample preparation system was integrated with perfusion culture using the microfluidic cell retention device. The purity of proteins in the cell culture supernatant was monitored for more than a week in a fully automated continuous manner. As a robust online sensing technology for continuous biomanufacturing, this nanofluidic filter array could replace the existing offline analytical technologies for protein purity monitoring. In summary, this thesis presents a novel micro/nanofluidic system for separation and monitoring of cells and proteins for continuous biomanufacturing. This innovative approach can contribute to long-term reliable and efficient biomanufacturing in the future.a dissertation presented by Taehong Kwon.Ph. D.Ph.D. Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Scienc

Engineering a deformation-free plastic spiral inertial microfluidic system for CHO cell clarification in biomanufacturing

A deformation-free and mass-producible plastic spiral inertial microfluidic device was developed, which provides continuous, clogging-free, and industry-level-throughput cell manipulation

Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System

We demonstrate a new micro/nanofluidic system for continuous and automatic monitoring of protein product size and quantity directly from the culture supernatant during a high-cell-concentration CHO cell perfusion culture. A microfluidic device enables clog-free cell retention for a bench-scale (350 mL) perfusion bioreactor that continuously produces the culture supernatant containing monoclonal antibodies (IgG1). A nanofluidic device directly monitors the protein size and quantity in the culture supernatant. The continuous-flow and fully automated operation of this nanofluidic protein analytics reduces design complexity and offers more detailed information on protein products than offline and batch-mode conventional analytics. Moreover, chemical and mechanical robustness of the nanofluidic device enables continuous monitoring for several days to a week. This continuous and online protein quality monitoring could be deployed at different steps and scales of biomanufacturing to improve product quality and manufacturing efficiency.SMART Innovation Centre (Grant ING137075-BIO)SMART Innovation Centre (Grant ING1510101-BIO)U.S. Food and Drug Administration (Award 1-U01-FD006751-01

Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics

Removing nonviable cells from a cell suspension is crucial in biotechnology and biomanufacturing. Label-free microfluidic cell separation devices based on dielectrophoresis, acoustophoresis, and deterministic lateral displacement are used to remove nonviable cells. However, their volumetric throughputs and test cell concentrations are generally too low to be useful in typical bioreactors in biomanufacturing. In this study, we demonstrate the efficient removal of small (<10 μm) nonviable cells from bioreactors while maintaining viable cells using inertial microfluidic cell sorting devices and characterize their performance. Despite the size overlap between viable and nonviable cell populations, the devices demonstrated 3.5-28.0% dead cell removal efficiency with 88.3-83.6% removal purity as well as 97.8-99.8% live cell retention efficiency at 4 million cells per mL with 80% viability. Cascaded and parallel configurations increased the cell concentration capacity (10 million cells per mL) and volumetric throughput (6-8 mL min-1). The system can be used for the removal of small nonviable cells from a cell suspension during continuous perfusion cell culture operations

Label-free Neutrophil Enrichment from Patient-derived Airway Secretion Using Closed-loop Inertial Microfluidics

Airway secretions contain a large number of immune-related cells, e.g., neutrophils, macrophages, and lymphocytes, which can be used as a major resource to evaluate a variety of pulmonary diseases, both for research and clinical purposes. However, due to the heterogeneous and viscous nature of patient mucus, there is currently no reliable dissociation method that does not damage the host immune cells in the patient airway secretion. In this research, we introduce a sample preparation method that uses inertial microfluidics for the patient's immune assessment. Regardless of the heterogeneous fluidic properties of the clinical samples, the proposed method recovers more than 95% of neutrophils from airway secretion samples that are diluted 1,000-fold with milliliters of clean saline. By recirculating the concentrated output stream to the initial sample reservoir, a high concentration, recovery, and purity of the immune cells are provided; recirculation is considered a trade-off to the single-run syringe-based operation of inertial microfluidics. The closed-loop operation of spiral microfluidics provides leukocytes without physical or chemical disturbance, as demonstrated by the phorbol 12-myristate 13-acetate (PMA)-induced elastase release of sorted neutrophils. Keywords: Immunology and Infection, Issue 136, Inertial microfluidics, airway secretion, label-free cell sorting, heterogeneous biofluid, neutrophil enrichment, patient sample preparationNational Institute of Allergy and Infectious Diseases (U.S.) (R21AI119042)National Institutes of Health (U.S.) (U24-AI118656

Liquid-capped encoded microcapsules for multiplex assay

Although droplet microfludics is a promising technology for handling a number of liquids of a single type of analyte, it has limitations in handling thousands of different types of analytes for multiplex assay. Here, we present a novel ???liquid-capped encoded microcapsule???, which is applicable to various liquid format assays. Various liquid drops can be graphically encoded and arrayed without repeated dispensing processes, evaporation, and the risk of cross-contamination. Millions of nanoliter-scale liquids are encapsulated within encoded microcapsules and self-assembled in microwells in a single dispensing process. The graphical code on the microcapsule enables identification of randomly assembled microcapsules in each microwell. We conducted various liquid phase assays including enzyme inhibitor screening, virus transduction, and drug-induced apoptosis tests. The results showed that our liquid handling technology can be utilized widely for various solution phase assays

A Work-Related Musculoskeletal Disorders (WMSDs) Risk-Assessment System Using a Single-View Pose Estimation Model

Musculoskeletal disorders are an unavoidable occupational health problem. In particular, workers who perform repetitive tasks onsite in the manufacturing industry suffer from musculoskeletal problems. In this paper, we propose a system that evaluates the posture of workers in the manufacturing industry with single-view 3D human pose-estimation that can estimate the posture in 3D using an RGB camera that can easily acquire the posture of a worker in a complex workplace. The proposed system builds a Duckyang-Auto Worker Health Safety Environment (DyWHSE), a manufacturing-industry-specific dataset, to estimate the wrist pose evaluated by the Rapid Limb Upper Assessment (RULA). Additionally, we evaluate the quality of the built DyWHSE dataset using the Human3.6M dataset, and the applicability of the proposed system is verified by comparing it with the evaluation results of the experts. The proposed system provides quantitative assessment guidance for working posture risk assessment, assisting the continuous posture assessment of workers