Respiration rate (RR) and respiration patterns (RP) are considered early indicators of physiological conditions and cardiorespiratory diseases. In this study, we addressed the problem of contactless estimation of RR and classification of RP of one person or two persons in a confined space under realistic conditions. We used three impulse radio ultrawideband (IR-UWB) radars and a 3D depth camera (Kinect) to avoid any blind spot in the room and to ensure that at least one of the radars covers the monitored subjects. This article proposes a subject localization and radar selection algorithm using a Kinect camera to allow the measurement of the respiration of multiple people placed at random locations. Several different experiments were conducted to verify the algorithms proposed in this work. The mean absolute error (MAE) between the estimated RR and reference RR of one-subject and two-subjects RR estimation are 0.61±0.53 breaths/min and 0.68±0.24 breaths/min, respectively. A respiratory pattern classification algorithm combining feature-based random forest classifier and pattern discrimination algorithm was developed to classify different respiration patterns including eupnea, Cheyne-Stokes respiration, Kussmaul respiration and apnea. The overall classification accuracy of 90% was achieved on a test dataset. Finally, a real-time system showing RR and RP classification on a graphical user interface (GUI) was implemented for monitoring two subjects.

The recombinant adeno-associated virus (rAAV) is a viral vector technology for gene therapy that is considered the safest and most effective way to repair single-gene abnormalities in non-dividing cells. However, improving the viral titer productivity in rAAV production remains challenging. The first step to this end is to effectively monitor the process state variables (cell density, GLC, GLN, LAC, AMM, and rAAV viral titer) to improve the control performance for an enhanced productivity. However, the current approaches to monitoring are expensive, laborious, and time-consuming. This paper presents an extended Kalman filter (EKF) approach used to monitor the rAAV production using the online viable cell density measurements and estimating the other state variables measured at a low frequency. The proposed EKF uses an unstructured mechanistic kinetic model applicable in the upstream process. Three datasets were used for parameter estimation, calibration, and testing, and the data were collected from the production of rAAV through a triple-plasmid transfection of HEK293SF-3F6 cells. Overall, the proposed approach accurately estimated metabolite concentrations and the rAAV production yield. Therefore, the approach has a high potential to be extended to an online soft sensor and to be classified as a cost-effective and fast approach to the monitoring of rAAV production.

Recombinant adeno-associated virus (rAAV) is the most effective viral vector technology for directly translating the genomic revolution into medicinal therapies. However, the manufacturing of rAAV viral vectors remains challenging in the upstream processing with low rAAV yield in large-scale production and high cost, limiting the generalization of rAAV-based treatments. This situation can be improved by real-time monitoring of critical process parameters (CPP) that affect critical quality attributes (CQA). To achieve this aim, soft sensing combined with predictive modeling is an important strategy that can be used for optimizing the upstream process of rAAV production by monitoring critical process variables in real time. However, the development of soft sensors for rAAV production as a fast and low-cost monitoring approach is not an easy task. This review article describes four challenges and critically discusses the possible solutions that can enable the application of soft sensors for rAAV production monitoring. The challenges from a data scientist’s perspective are (i) a predictor variable (soft-sensor inputs) set without AAV viral titer, (ii) multi-step forecasting, (iii) multiple process phases, and (iv) soft-sensor development composed of the mechanistic model.