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Abstract Nascent advanced therapies, including regenerative medicine and cell and gene therapies, rely on the production of cells in bioreactors that are highly heterogeneous in both space and time. Unfortunately, advanced therapies have failed to reach a wide patient population due to unreliable manufacturing processes that result in batch variability and cost prohibitive production. This can be attributed largely to a void in existing process analytical technologies (PATs) capable of characterizing the secreted critical quality attribute (CQA) biomolecules that correlate with the final product quality. The Dynamic Sampling Platform (DSP) is a PAT for cell bioreactor monitoring that can be coupled to a suite of sensor techniques to provide real‐time feedback on spatial and temporal CQA content in situ. In this study, DSP is coupled with electrospray ionization mass spectrometry and direct‐from‐culture sampling to obtain measures of CQA content in bulk media and the cell microenvironment throughout the entire cell culture process (≈3 weeks). Post hoc analysis of this real‐time data reveals that sampling from the microenvironment enables cell state monitoring (e.g., confluence, differentiation). These results demonstrate that an effective PAT should incorporate both spatial and temporal resolution to serve as an effective input for feedback control in biomanufacturing.
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Data-Driven Intelligent 3D Surface Measurement in Smart Manufacturing: Review and Outlook
High-fidelity characterization and effective monitoring of spatial and spatiotemporal processes are crucial for high-performance quality control of many manufacturing processes and systems in the era of smart manufacturing. Although the recent development in measurement technologies has made it possible to acquire high-resolution three-dimensional (3D) surface measurement data, it is generally expensive and time-consuming to use such technologies in real-world production settings. Data-driven approaches that stem from statistics and machine learning can potentially enable intelligent, cost-effective surface measurement and thus allow manufacturers to use high-resolution surface data for better decision-making without introducing substantial production cost induced by data acquisition. Among these methods, spatial and spatiotemporal interpolation techniques can draw inferences about unmeasured locations on a surface using the measurement of other locations, thus decreasing the measurement cost and time. However, interpolation methods are very sensitive to the availability of measurement data, and their performances largely depend on the measurement scheme or the sampling design, i.e., how to allocate measurement efforts. As such, sampling design is considered to be another important field that enables intelligent surface measurement. This paper reviews and summarizes the state-of-the-art research in interpolation and sampling design for surface measurement in varied manufacturing applications. Research gaps and future research directions are also identified and can serve as a fundamental guideline to industrial practitioners and researchers for future studies in these areas.
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- Award ID(s):
- 1944345
- PAR ID:
- 10210567
- Date Published:
- Journal Name:
- Machines
- Volume:
- 9
- Issue:
- 1
- ISSN:
- 2075-1702
- Page Range / eLocation ID:
- 13
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/machines9010013
