Bioprocess Monitoring
Manufacturing Quality Control
Enhanced Bioprocess Control
Intact cell count monitoring in bioprocesses offers significant value by providing precise and rapid quantification of living cells, crucial for optimizing production efficiency and ensuring product quality. This process is essential for industries like pharmaceuticals and biotechnology, where maintaining cell viability directly impacts yield and consistency.
By accurately monitoring intact cells, companies can make timely adjustments, reduce waste, and enhance overall process control, leading to increased productivity and cost-effectiveness.
The Information Gap
Monitoring the status and dynamics of bioprocesses remains a significant challenge.
From an operational perspective, maintaining stable cultivation conditions is essential for ensuring consistent cell growth and process performance. Analytical challenges arise from the need to generate accurate, reliable, and reproducible measurements that can support informed process control decisions. In addition, regulatory requirements demand robust documentation, method validation, and data integrity throughout process development and manufacturing. Economic considerations further complicate implementation, as advanced monitoring technologies often require substantial investment in instrumentation, automation, and personnel training.
Addressing these challenges is critical for achieving effective bioprocess control and fully exploiting the potential of intact-cell monitoring approaches such as flow cytometry.
Comparing Flow Cytometry to Optical Density (OD)
While optical density remains a useful tool for routine monitoring, it cannot provide information about cell viability. Other methods, though available, are often too slow, laborious, or lack specificity for live cells.
Flow cytometry-based ICC offers a powerful alternative, delivering rapid, reliable, and specific insights into the living bacterial population in bioreactors. For modern bioprocessing, this means better control, higher yields, and improved product quality.
Implementing Intact Cell Monitoring
Our Approach
Effective bioprocess control depends on timely and reliable information about cell population dynamics. However, conventional monitoring methods such as optical density, dry cell weight, and colony-forming unit (CFU) assays often provide either indirect measurements of biomass or delayed results that limit their usefulness for real-time process decisions. As a result, critical changes in culture performance may not be detected until they have already affected productivity or product quality.
The rqmicro ICC Kit addresses this challenge by enabling rapid and direct quantification of intact cells using flow cytometry. By providing actionable information on the concentration of physiologically intact cells throughout the cultivation process, the ICC Kit supports improved process understanding, enhanced monitoring capabilities, and more informed operational decision-making.
1
Identify the Monitoring Objective
Outcome: Clear definition of the process stages, sampling points, and decision-making criteria that will benefit from intact cell measurements.
2
Establish the Baseline and Method Correlation
Outcome: Process-specific reference ranges and an understanding of how intact cell counts relate to conventional process indicators.
3
Integrate ICC Monitoring into Routine Operations
Outcome: Reliable, reproducible, and timely monitoring of culture dynamics during routine operation.
4
Utilize ICC Data for Process Optimization
Outcome: Enhanced process control, improved reproducibility, and data-driven optimization of cultivation and production performance.
Benefits for Your Operation
Early detection of population heterogeneity and subpopulations
Flow cytometry reveals distributions of physiological states (not just averages), enabling detection of subpopulations such as stressed, damaged, or non-growing cells. This allows operators to identify emerging process instability before it becomes visible in bulk measurements like OD or metabolite profiles.
Earlier and more reliable deviation detection in complex processes
Because bioprocesses are inherently heterogeneous, small shifts in subpopulations often precede measurable changes in conventional process variables. Real-time or near-real-time cytometric data enables earlier detection of process drift, contamination, or stress responses, improving control responsiveness.
Direct measurement of physiological cell states rather than proxy biomass
Unlike optical density or capacitance, flow cytometry provides single-cell resolution of viability, integrity, and physiological condition. This reduces reliance on indirect correlations that can break down under changing process conditions or morphology shifts.
Improved process understanding enabling better control strategies
Single-cell data supports deeper understanding of how process conditions affect population dynamics (e.g., stress adaptation, phase transitions). This enables more rational optimization of feeding, induction, and harvest strategies rather than purely empirical control.
Proven Performance
The rqmicro ICC Kit delivers reliable performance in both industrial and research bioprocess environments.
In biotechnology production, it supports process monitoring through rapid quantification of intact cells and provides valuable insights into cell population dynamics.
In the R&D environment of a company developing microbiome therapeutics, the ICC Kit enables efficient monitoring of microbial cultures during process development. These applications demonstrate the versatility of the ICC Kit as a robust tool for generating actionable insights into bioprocess performance.
Example: Flow cytometry plot obtained on the rqmicro.COUNT with visible populations of live (below) and dead (above) E. coli cells
Solutions for This Application
Brief introduction explaining how the products support this application.
rqmicro.COUNT
A cartridge-based flow cytometer that rapidly quantifies total viable bacteria and specific pathogens using the rqmicro Test Kits. The instrument delivers actionable results in as little as 30 minutes. rqmicro.COUNT is designed for both laboratory and on-site use, enabling reliable microbiological monitoring.
Key Benefits
- Decentralized testing
- High-speed single-cell analysis
- Easy to use
Cloud Solution
The rqmicro Cloud Solution is a secure, browser-based platform for storing, analyzing, and sharing microbiological test results. With customizable dashboards, automated alerts, and reporting tools, it supports efficient monitoring, compliance, and data-driven decision-making across multiple sites.
Key Benefits
- Centralized Data Management
- Real-Time Monitoring & Alerts
- Simplified Reporting & Compliance
Test Kits
The rqmicro Test Kits are ready-to-use assay kits designed for rapid microbiological water analysis with rqmicro.COUNT. The Intact Cell Count (ICC), enables simple sample preparation with highly sensitive detection to deliver fast, reliable, and actionable results.
Key Benefits
- Rapid Results
- Reliable Detection
- Easy-to-Use Workflow
Frequently Asked Questions
Here are some common questions about the test method, instrumentation and user requirements.
rqmicro combines three core technologies in a single workflow:
- Microbiological Assays detection and quantification of microorganisms including immunoassays for the selective quantification of target bacteria.
- Microfluidic cartridge technology with integrated immunomagnetic separation (IMS) for automated sample processing.
- Flow Cytometry for rapid detection and quantification of bacteria, including viability assessment.
This integrated approach enables rapid microbiological testing without the need for lengthy cultivation steps.
Single-use cartridges provide several advantages:
- Ensure standardized workflows
- Reduce maintenance requirements
- Minimize the risk of cross-contamination
- Eliminate complex cleaning procedures
- Enable operation by non-specialist users
The cartridge-based design supports both laboratory and field applications.
The rqmicro platform is designed for the detection and quantification of total bioburden and also specific bacteria. Depending on the assay, users can analyze:
- Total viable bacteria (Intact Cell Count)
- Total bacteria (Total Cell Count)
- Legionella (L.p. SG 1, L.p. SG 1-15 and Legionella spp.)
- E. coli (incl. Big 6 and O157)
Traditional culture methods only detect microorganisms that grow on agar plates. Many bacteria can remain viable but fail to form colonies under cultivation conditions.
rqmicro uses cultivation-independent flow cytometry, allowing the detection of viable cells regardless of their ability to grow on culture media. This provides faster results and a more complete picture of microbial contamination.
Flow cytometry is a laser-based analytical method that measures individual cells suspended in a fluid stream.
As cells pass through the laser beam, fluorescent signals are generated and detected by the instrument. Thousands of cells can be analyzed every second, enabling rapid and highly sensitive microbiological testing.
rqmicro uses fluorescence-based flow cytometry together with viability staining. Fluorescent dyes interact differently with live and dead cells based on membrane integrity and physiological status.
The instrument analyzes these fluorescence patterns to distinguish viable cells from non-viable cells, providing rapid live/dead information within the measurement process.
Viability information helps users:
- Assess microbiological risk more accurately
- Evaluate treatment effectiveness
- Detect bacteria that may be missed by culture methods
- Monitor changes in water systems in near real time
This enables faster operational decisions and improved process control.
VBNC stands for Viable But Non-Culturable.
These bacteria are alive and may remain metabolically active, but they do not grow on standard culture media. As a result, conventional cultivation methods can underestimate the true microbial load.
Flow cytometry can detect these cells, allowing a more comprehensive assessment of water quality and microbiological risk.
qmicro.COUNT is designed for routine operation with minimal training.
Users do not need to be flow cytometry experts. The cartridge-based workflow and automated analysis reduce operator dependency and simplify routine testing.
Contact an Expert
Christophe Gutknecht
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