Real-Time Monitoring of Bioprocesses by Mid-Infrared Spectroscopy
Monipa focuses on simplified bioprocess monitoring: our measurement system is based on MIR spectroscopy which makes it possible to monitor multiple bioprocesses online at the same time. There are applications for the instrument in both upstream bioprocessing; in metabolite monitoring and control, as well as in downstream bioprocessing to aid in aggregation studies, contaminant detection or monitoring of target proteins and excipients.
Our ATR Crystals
The single use flow cell is mounted to Monipa with an easy-click mechanism. This allows the replacement after each monitored process, reducing contamination risk. The flow cell contains our single use silicon ATR crystal, making it suitable as a disposable unit. By connecting the flow cell with a loop to f.e. the bioreactor, different parameters can be monitored online without sampling. The flow cell is mounted outside of the bioreactor, which results in stable measurement conditions. This prevents disturbances of the measurements by gas bubbles or by the stirrer which both can occur inside the bioreactor.
MONIPA OVERVIEW
Calibration Model Building
Calibration model building is an important step for spectroscopy. The spectra depend on the molecules in the measured samples. Different cell lines, cell culture media, metabolite or nutrient concentration leads to changes in the spectra. Therefore, calibration models are built by correlating the spectroscopic measurements to the reference method.
IRUBIS solution offers beside the standard method two innovative approaches to solve the time extensive and costly calibration model building. On one hand, it is possible to do an offline calibration with archived samples. On the other hand, IRUBIS software offers a relative measurement where only known start-values of the parameter need to be measured.
Monitoring and Control in Bioreactors
The use of mid-infrared (MIR) spectroscopy for online measurement of glucose and lactate in mammalian cell cultures has already been demonstrated in recent studies (Sandor et al., 2013; Wu et al., 2015). Drawbacks are high equipment costs and low robustness of the ATR probes. IRUBIS has managed to solve many of these teething issues with our Monipa system.
Benefits in Upstream Processing
Why is our system suited to USP?
- 24/7 online monitoring of metabolites and nutrients as well as glucose control
- Real-time data and glucose control (closed loop)
- Single use flow cell decreases contamination risk
- Parallel monitoring of up to 4 bioreactors
- Increased robustness compared to other spectroscopic methods
- Reduced calibration time
Our Monipa system is suited to a variety of different cell types; from CHO mammalian cells, to microorganisms such as bacteria.
Monipa in USP: Schematic Overview
Monitoring Protein Concentration, Aggregation, and Excipients
There are a variety of different applications of Monipa in downstream processing, especially taking into account its fast acquisition time of less than 1 second per spectra. Applications include protein concentration and aggregation monitoring as well as monitoring of antibody conjugates and excipients. If you’re an expert in the field, do feel free to get in touch to see if we can help.
Benefits in Downstream Processing
How Does Monipa work in DSP?
How does MIR Assist DSP?
MIR Spectroscopy in Ultrafiltration and Diafiltration
A few studies using MIR Spectroscopy have been done in the field, for example to measure the concentration of excipients and comparing it to the current UV-Vis and HPLC methods. The publication has shown that there is less than a 5% deviation between using MIR or UV-Vis /UPLC for Dia and ultrafiltration uses.
Wasalathanthri et.al, Journal of Biotechnology and Bioengineering (2020)
Protein Secondary Structure
MIR enables differentiation of protein secondary structure such as alpha helices, beta sheets and random coil structures. A distinct feature of protein aggregation is the increase of crossed β-sheet structures. Hence, IR Spectroscopy is a useful tool to analyze secondary structures of proteins, and their aggregation in complex samples.
Wang et al (2015), Anal Bioanal Chem 407: 4015-21
Ángela I. López-Lorente , I, A & Mizaikoff, B (2016), Anal Bioanal Chem 408: 2875–89
Real-Time Monitoring of Bioprocesses by Mid-Infrared Spectroscopy
Monipa focuses on simplified bioprocess monitoring: our measurement system is based on MIR spectroscopy which makes it possible to monitor multiple bioprocesses online at the same time. There are applications for the instrument in both upstream bioprocessing; in metabolite monitoring and control, as well as in downstream bioprocessing to aid in aggregation studies, contaminant detection or monitoring of target proteins and excipients.
Our ATR Crystals
The single use flow cell is mounted to Monipa with an easy-click mechanism. This allows the replacement after each monitored process, reducing contamination risk. The flow cell contains our single use silicon ATR crystal, making it suitable as a disposable unit. By connecting the flow cell with a loop to f.e. the bioreactor, different parameters can be monitored online without sampling. The flow cell is mounted outside of the bioreactor, which results in stable measurement conditions. This prevents disturbances of the measurements by gas bubbles or by the stirrer which both can occur inside the bioreactor.
MONIPA OVERVIEW
Calibration Model Building
Calibration model building is an important step for spectroscopy. The spectra depend on the molecules in the measured samples. Different cell lines, cell culture media, metabolite or nutrient concentration leads to changes in the spectra. Therefore, calibration models are built by correlating the spectroscopic measurements to the reference method.
IRUBIS solution offers beside the standard method two innovative approaches to solve the time extensive and costly calibration model building. On one hand, it is possible to do an offline calibration with archived samples. On the other hand, IRUBIS software offers a relative measurement where only known start-values of the parameter need to be measured.
Monitoring and Control in Bioreactors
The use of mid-infrared (MIR) spectroscopy for online measurement of glucose and lactate in mammalian cell cultures has already been demonstrated in recent studies (Sandor et al., 2013; Wu et al., 2015). Drawbacks are high equipment costs and low robustness of the ATR probes. IRUBIS has managed to solve many of these teething issues with our Monipa system.
Benefits in Upstream Processing
Why is our system suited to USP?
- 24/7 online monitoring of metabolites and nutrients as well as glucose control
- Real-time data and glucose control (closed loop)
- Single use flow cell decreases contamination risk
- Parallel monitoring of up to 4 bioreactors
- Increased robustness compared to other spectroscopic methods
- Reduced calibration time
Our Monipa system is suited to a variety of different cell types; from CHO mammalian cells, to microorganisms such as bacteria.
Monipa in USP: Schematic Overview
Monitoring Protein Concentration, Aggregation, and Excipients
There are a variety of different applications of Monipa in downstream processing, especially taking into account its fast acquisition time of less than 1 second per spectra. Applications include protein concentration and aggregation monitoring as well as monitoring of antibody conjugates and excipients. If you’re an expert in the field, do feel free to get in touch to see if we can help.
Benefits in Downstream Processing
Monipa in DSP
MIR in DSP
MIR Spectroscopy in Ultrafiltration and Diafiltration
A few studies using MIR Spectroscopy have been done in the field, for example to measure the concentration of excipients and comparing it to the current UV-Vis and HPLC methods. The publication has shown that there is less than a 5% deviation between using MIR or UV-Vis /UPLC for Dia and ultrafiltration uses.
Wasalathanthri et.al, Journal of Biotechnology and Bioengineering (2020)
Protein Secondary Structure
MIR enables differentiation of protein secondary structure such as alpha helices, beta sheets and random coil structures. A distinct feature of protein aggregation is the increase of crossed β-sheet structures. Hence, IR Spectroscopy is a useful tool to analyze secondary structures of proteins, and their aggregation in complex samples.
Wang et al (2015), Anal Bioanal Chem 407: 4015-21
Ángela I. López-Lorente , I, A & Mizaikoff, B (2016), Anal Bioanal Chem 408: 2875–89
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