Search for: All records

Abstract Magnetoelastic (ME) sensors, which can be remotely activated via magnetic fields, are an excellent choice for wireless monitoring of biological parameters due to their ability to be scaled into different sizes and have their surface functionalized for chemical or biological sensing. In this study, we present the application of a commercially available ME material (Metglas 2826 MB) to develop a sensor system that can monitor the attachment of anchorage‐dependent mammalian cells in two‐dimensional in vitro cell cultures. Results obtained with the developed sensors and detection system correlated with microscopic image analysis of cell quantification, which showed a linear relationship between the sensor response and attached fibroblast cells on the sensor surface. It was also revealed that the developed ME sensor system is capable of providing temporal profiles of cell growth corresponding to different stages of cell attachment and proliferation in real‐time. 

Abstract Large‐scale manufacturing of therapeutic cells requires bioreactor technologies with online feedback control enabled by monitoring of secreted biomolecular critical quality attributes (CQAs). Electrospray ionization mass spectrometry (ESI‐MS) is a highly sensitive label‐free method to detect and identify biomolecules, but requires extensive sample preparation before analysis, making online application of ESI‐MS challenging. We present a microfabricated, monolithically integrated device capable of continuous sample collection, treatment, and direct infusion for ESI‐MS detection of biomolecules in high‐salt solutions. The dynamic mass spectrometry probe (DMSP) uses a microfluidic mass exchanger to rapidly condition samples for online MS analysis by removing interfering salts, while concurrently introducing MS signal enhancers to the sample for sensitive biomolecular detection. Exploiting this active conditioning capability increases MS signal intensity and signal‐to‐noise ratio. As a result, sensitivity for low‐concentration biomolecules is significantly improved, and multiple proteins can be detected from chemically complex samples. Thus, the DMSP has significant potential to serve as an enabling portion of a novel analytical tool for discovery and monitoring of CQAs relevant to therapeutic cell manufacturing. 

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.