AQU@Sense MB
Artikelnummer: P06170006
- Fully Automated In-Process Control: Seamlessly integrates into water purification systems for automated, real-time monitoring.
- Trend Monitoring: Early detection of deviations or adverse trends in water purification systems allows for proactive intervention.
- Rapid Pharmaceutical Water Release: Enables PW or WFI systems to be released within 2-3 hours post-sanitization.
- Primary Validated Instrument: Thoroughly validated according to European Pharmacopeia, USP and PDA TR33
- Proven Technology: Utilizes Flow Cytometry with integrated dyeing, to reliably detect intact microorganisms.
The Future of Microbial Monitoring: AQU@Sense MB
Fully automated In-Process Control for enumeration of microorganisms is available today.
Gain comprehensive insights into PW and WFI systems through regular measurements and trend monitoring. Results are delivered within 20 minutes, facilitating rapid decision-making and early trend detection. Enhance product quality and process efficiency with an fully automated instrument tool for microbiological monitoring.
ICC instead of CFU: A new measurement
Intact Cell count is significantly higher than Colony forming Units
Comparison of different methods to detect microorganisms has shown that the number of individual cells is by far higher than the results of HPC. Scan RDI and fluorescence microscopy have shown, that one colony on the plate typically origins from many individual cells.
Seamless Integration
Mechanical Integration:
Single Sampling Point
Multi Point with up to 4 Sampling points
The AQU@Sense MB can be combined with a valve system that can connect up to four sampling points to one AQU@Sense MB. The control of the measurement sequence is done by the control unit of the water system.
Measurement Modes:
- Manual: The measurement can be started manually with a minimum sampling interval of 30 minutes
- Automatic: An automatic measurement interval between 30 minutes and 6 hours can be programmed in the AQU@Sense MB
- Remote controlled: The measurement can be triggered via digital input signals with a minimum sampling interval of 30 minutes.
Data transfer:
- 4 to 20 mA
- Modbus
Technical Details
| Technical Details | |
| Product Id | P06170006 |
| Dimensions (W x D x H): | 350x270x373mm |
| Weight: | 14 kg |
| Degree of Protection: | IP65 |
| Operating Environment: | Indoor, +5°C - +35°C, 10% - 90% RH |
| Measurement Principle: | Flow Cytometry with DNA specific staining Side Scatter and 2 Fluorescence Signals |
| Sample Volume: | 90 µl |
| Sampling: | Online, offline single measurement or offline with sample manager for up to 30 samples |
| Analysis Time: | 30 minutes (Time to result ~20 minutes) |
| Measuring interval: |
min 30 minutes (manual, automatic or triggered with digital input) |
| Sanitizable: |
Ozone up to 100 ppb / hot water up to 85 °C |
| Power Supply: | 18 VDC, 1.4A, 20W |
| Communication Output: |
2x4 ... 20mA analog outputs (freely configurable) 4 digital outputs Modbus TCP/IP |
| Communication Input: | 3 digital inputs (start-, stop-, abort measurement) |
| Data storage: | Memory card 32GB |
| Data Export: | USB 2.0, Ethernet |
| Electronic Documentation: | 21 CFR Part 11 compliant electronic documentation Audit Trail Logbook User management with 4 user levels |
| Compliance and Certification: | CE Certification, Factory Validation Certificate |
| Standard scope of delivery | Item | Article No. P06170006 |
|
AQU@Sense MB Cartridge Online Sampling Device Manual Sampling Device Power Supply / Cable |
What are the differences between Heterotrophic Plate Count (HPC) and AQU@Sense MB?
| Heterotrophic Plate Count | AQU@Sense MB | |
| Technology | Growth based, dependent on culture medium | Fluorescence analysis after DNA-specific staining |
| Sampling | Manual | Automatic |
| Measuring unit | Colony Forming Unit (CFU) | Intact Cell Count (ICC) |
| Time to result | 3-7 Days | 20 Minutes (30 Minutes measurement interval) |
| LOD | 1 Colony | 1 ICC |
| Range | 1-300 colonies per sample |
1-1 000 000 ICC per sample |
| Identification |
Colonies |
Individual Cells Dot-plot / fingerprint of a population Interpretation of the results according to different events (trend monitoring) |
| Enumeration | Visual counting by humans | Automatic |
| Sample size | 100 or 200ml | 90µl |
How can the AQU@Sense MB differentiate intact and damaged/dead cells in one sample?
The AQU@Sense MB employs two specific staining agents: SYBR Green I and Propidium Iodide. SYBR Green I penetrates intact cell membranes and selectively binds to the cell’s DNA. In contrast, Propidium Iodide cannot penetrate intact membranes and binds exclusively to the DNA of compromised cells.
To determine whether only SYBR Green I or both SYBR Green I and Propidium Iodide are bound to a cell, the cells are passed through a very thin capillary and illuminated with a laser, stray light and fluorescence light from is generated and analyzed with a specific detection system. As SYBR Green I and Propidium Iodide emit fluorescence at distinct wavelengths, the system can differentiate between intact or damaged cells.
Which advantages has AQU@Sense MB compared to other RMMs?
- Primary-validated technology by independent scientists, ensuring high credibility and reliability
- Clear and unambiguous results, with differentiation between intact and damaged cells/debris
- Reproducible results
- High autonomy with a user-friendly plug-and-play setup, minimizing manual intervention
- Robust/industrial design
- No direct user contact with chemicals or waste
- Minimal maintenance requirements
- Advanced detection capabilities, identifying individual cells, even within conglomerates or biofilm fragments, enabling comprehensive trend monitoring.
What is the correlation between the two measuring units CFU and ICC?
Intact Cell Counts (ICC) and Colony Forming Units (CFU) do not exhibit a direct correlation. Primarily due to the presence of Viable but Non-Culturable Cells (VBNC), which are not detected on HPC but easily detected in flow cytometer. Secondly, due to difference in time and environmental factors between two methods. Flow cytometry provides an instantaneous snapshot of cell presence. Therefore, cells that may not thrive under HPC conditions might still be detected by flow cytometry.
Consequently, when the AQU@Sense MB is employed as a tool in Quality Control (QC), a performance qualification (PQ) is necessary at the customer's site to establish parameters, including baseline, warning, and action levels.
What are Viable But Non-Culturable (VBNC) organisms? Are they of big importance for patients’ safety?
For microorganisms, entering the VBNC (viable but non-culturable) stage is a survival strategy in response to stress conditions like unfavorable environments, nutrient depletion, and temperature fluctuations, which are main features of PW/WFI water systems.
These VBNC bacteria remain alive and metabolically active but are unable to grow in standard laboratory conditions. Recent studies have shown that the VBNC state is reversible, meaning these microorganisms can return to a multiplying state, posing a potential bioburden, and in turn, health risk. Flow cytometry helps detect VBNC microorganisms in pharmaceutical water because it uses non-growth-based methods.
These VBNC bacteria remain alive and metabolically active but are unable to grow in standard laboratory conditions. Recent studies have shown that the VBNC state is reversible, meaning these microorganisms can return to a multiplying state, posing a potential bioburden, and in turn, health risk. Flow cytometry helps detect VBNC microorganisms in pharmaceutical water because it uses non-growth-based methods.
Is it possible to identify the strain with AQU@Sense MB?
No, the AQU@Sense MB does not identify the strain. However, since flow cytometry is applied, a fingerprint of the distribution of the cells is given which can give more information about the state of the microbial population.
How to use AQU@Sense MB in daily monitoring?
There are two possible fields of application for daily routine analysis. In-Process Control (IPC) and Quality Control (QC).
For IPC it can be can be integrated into the water system as an online control system for monitoring bioburden. When operating at its maximum capacity, the AQU@Sense MB can perform batchwise continuously up to 48 measurements per day (minimum measurement interval: 30 minutes).
The measurement interval is adjustable according to the needs and standard operation of water system.
The benefits of frequent measurements are noticeable - for rapid detection of even minor changes, in contrast to the conventional plate count method. This system can be utilized not only to continuously monitor bioburden levels in the plant but also e.g., to release the water system after sanitation or maintenance for technical water release.
Is it possible to make QC releases with the AQU@Sense MB?
Yes, it is possible to perform a QC release using the AQU@Sense MB. However, to incorporate it into current QC release process, customers must conduct a performance qualification (PQ) to confirm its suitability for the intended purpose. According to regulatory guidelines, the AQU@Sense MB or any other Rapid Microbiological Method (RMM) can be validated as a QC release method. Since the AQU@Sense MB is already primary validated the performance qualification procedure is much simpler.
An equivalence testing must be conducted using appropriate parameters, followed by statistical analysis, since it indicates a new measuring unit (Intact Cell Counts, ICC) instead of Colony Forming Units (CFU). The results of the testing must demonstrate that the results of the AQU@Sense MB allow for an unequivocal decision regarding compliance with the standards outlined in the monographs, even when compared to the conventional HPC.
Is AQU@Sense MB acknowledged by the authorities (EMA, USP, FDA etc.)?
The AQU@Sense MB, along with other RMM devices (Status November 2023), is not specifically authorized by name by any regulatory body. However, it can be validated and qualified as a QC release method, since the EU GMP Annex I strongly recommend to incorporate RMM’s.
At BWT, we are working on obtaining authorization for the applied method (flow cytometry).
Downloads
Scientific Publications
Seamless Integration
Mechanical Integration:
Single Sampling Point
Multi Point with up to 4 Sampling points
The AQU@Sense MB can be combined with a valve system that can connect up to four sampling points to one AQU@Sense MB. The control of the measurement sequence is done by the control unit of the water system.
Measurement Modes:
- Manual: The measurement can be started manually with a minimum sampling interval of 30 minutes
- Automatic: An automatic measurement interval between 30 minutes and 6 hours can be programmed in the AQU@Sense MB
- Remote controlled: The measurement can be triggered via digital input signals with a minimum sampling interval of 30 minutes.
Data transfer:
- 4 to 20 mA
- Modbus
Technical Details
| Technical Details | |
| Product Id | P06170006 |
| Dimensions (W x D x H): | 350x270x373mm |
| Weight: | 14 kg |
| Degree of Protection: | IP65 |
| Operating Environment: | Indoor, +5°C - +35°C, 10% - 90% RH |
| Measurement Principle: | Flow Cytometry with DNA specific staining Side Scatter and 2 Fluorescence Signals |
| Sample Volume: | 90 µl |
| Sampling: | Online, offline single measurement or offline with sample manager for up to 30 samples |
| Analysis Time: | 30 minutes (Time to result ~20 minutes) |
| Measuring interval: |
min 30 minutes (manual, automatic or triggered with digital input) |
| Sanitizable: |
Ozone up to 100 ppb / hot water up to 85 °C |
| Power Supply: | 18 VDC, 1.4A, 20W |
| Communication Output: |
2x4 ... 20mA analog outputs (freely configurable) 4 digital outputs Modbus TCP/IP |
| Communication Input: | 3 digital inputs (start-, stop-, abort measurement) |
| Data storage: | Memory card 32GB |
| Data Export: | USB 2.0, Ethernet |
| Electronic Documentation: | 21 CFR Part 11 compliant electronic documentation Audit Trail Logbook User management with 4 user levels |
| Compliance and Certification: | CE Certification, Factory Validation Certificate |
| Standard scope of delivery | Item | Article No. P06170006 |
|
AQU@Sense MB Cartridge Online Sampling Device Manual Sampling Device Power Supply / Cable |
What are the differences between Heterotrophic Plate Count (HPC) and AQU@Sense MB?
| Heterotrophic Plate Count | AQU@Sense MB | |
| Technology | Growth based, dependent on culture medium | Fluorescence analysis after DNA-specific staining |
| Sampling | Manual | Automatic |
| Measuring unit | Colony Forming Unit (CFU) | Intact Cell Count (ICC) |
| Time to result | 3-7 Days | 20 Minutes (30 Minutes measurement interval) |
| LOD | 1 Colony | 1 ICC |
| Range | 1-300 colonies per sample |
1-1 000 000 ICC per sample |
| Identification |
Colonies |
Individual Cells Dot-plot / fingerprint of a population Interpretation of the results according to different events (trend monitoring) |
| Enumeration | Visual counting by humans | Automatic |
| Sample size | 100 or 200ml | 90µl |
How can the AQU@Sense MB differentiate intact and damaged/dead cells in one sample?
The AQU@Sense MB employs two specific staining agents: SYBR Green I and Propidium Iodide. SYBR Green I penetrates intact cell membranes and selectively binds to the cell’s DNA. In contrast, Propidium Iodide cannot penetrate intact membranes and binds exclusively to the DNA of compromised cells.
To determine whether only SYBR Green I or both SYBR Green I and Propidium Iodide are bound to a cell, the cells are passed through a very thin capillary and illuminated with a laser, stray light and fluorescence light from is generated and analyzed with a specific detection system. As SYBR Green I and Propidium Iodide emit fluorescence at distinct wavelengths, the system can differentiate between intact or damaged cells.
Which advantages has AQU@Sense MB compared to other RMMs?
- Primary-validated technology by independent scientists, ensuring high credibility and reliability
- Clear and unambiguous results, with differentiation between intact and damaged cells/debris
- Reproducible results
- High autonomy with a user-friendly plug-and-play setup, minimizing manual intervention
- Robust/industrial design
- No direct user contact with chemicals or waste
- Minimal maintenance requirements
- Advanced detection capabilities, identifying individual cells, even within conglomerates or biofilm fragments, enabling comprehensive trend monitoring.
What is the correlation between the two measuring units CFU and ICC?
Intact Cell Counts (ICC) and Colony Forming Units (CFU) do not exhibit a direct correlation. Primarily due to the presence of Viable but Non-Culturable Cells (VBNC), which are not detected on HPC but easily detected in flow cytometer. Secondly, due to difference in time and environmental factors between two methods. Flow cytometry provides an instantaneous snapshot of cell presence. Therefore, cells that may not thrive under HPC conditions might still be detected by flow cytometry.
Consequently, when the AQU@Sense MB is employed as a tool in Quality Control (QC), a performance qualification (PQ) is necessary at the customer's site to establish parameters, including baseline, warning, and action levels.
What are Viable But Non-Culturable (VBNC) organisms? Are they of big importance for patients’ safety?
For microorganisms, entering the VBNC (viable but non-culturable) stage is a survival strategy in response to stress conditions like unfavorable environments, nutrient depletion, and temperature fluctuations, which are main features of PW/WFI water systems.
These VBNC bacteria remain alive and metabolically active but are unable to grow in standard laboratory conditions. Recent studies have shown that the VBNC state is reversible, meaning these microorganisms can return to a multiplying state, posing a potential bioburden, and in turn, health risk. Flow cytometry helps detect VBNC microorganisms in pharmaceutical water because it uses non-growth-based methods.
These VBNC bacteria remain alive and metabolically active but are unable to grow in standard laboratory conditions. Recent studies have shown that the VBNC state is reversible, meaning these microorganisms can return to a multiplying state, posing a potential bioburden, and in turn, health risk. Flow cytometry helps detect VBNC microorganisms in pharmaceutical water because it uses non-growth-based methods.
Is it possible to identify the strain with AQU@Sense MB?
No, the AQU@Sense MB does not identify the strain. However, since flow cytometry is applied, a fingerprint of the distribution of the cells is given which can give more information about the state of the microbial population.
How to use AQU@Sense MB in daily monitoring?
There are two possible fields of application for daily routine analysis. In-Process Control (IPC) and Quality Control (QC).
For IPC it can be can be integrated into the water system as an online control system for monitoring bioburden. When operating at its maximum capacity, the AQU@Sense MB can perform batchwise continuously up to 48 measurements per day (minimum measurement interval: 30 minutes).
The measurement interval is adjustable according to the needs and standard operation of water system.
The benefits of frequent measurements are noticeable - for rapid detection of even minor changes, in contrast to the conventional plate count method. This system can be utilized not only to continuously monitor bioburden levels in the plant but also e.g., to release the water system after sanitation or maintenance for technical water release.
Is it possible to make QC releases with the AQU@Sense MB?
Yes, it is possible to perform a QC release using the AQU@Sense MB. However, to incorporate it into current QC release process, customers must conduct a performance qualification (PQ) to confirm its suitability for the intended purpose. According to regulatory guidelines, the AQU@Sense MB or any other Rapid Microbiological Method (RMM) can be validated as a QC release method. Since the AQU@Sense MB is already primary validated the performance qualification procedure is much simpler.
An equivalence testing must be conducted using appropriate parameters, followed by statistical analysis, since it indicates a new measuring unit (Intact Cell Counts, ICC) instead of Colony Forming Units (CFU). The results of the testing must demonstrate that the results of the AQU@Sense MB allow for an unequivocal decision regarding compliance with the standards outlined in the monographs, even when compared to the conventional HPC.
Is AQU@Sense MB acknowledged by the authorities (EMA, USP, FDA etc.)?
The AQU@Sense MB, along with other RMM devices (Status November 2023), is not specifically authorized by name by any regulatory body. However, it can be validated and qualified as a QC release method, since the EU GMP Annex I strongly recommend to incorporate RMM’s.
At BWT, we are working on obtaining authorization for the applied method (flow cytometry).
Downloads
Scientific Publications
