Gain Critical Insights from Advanced Cell Models with Real-Time Analysis - 11

Cell Culture Quality Control Assays

Real-time Monitoring and Analysis of Cell Culture Conditions and Techniques

A

large number of variables exist that alter the growth and function of cells in
culture. Many sources of variability are largely uncontrollable because they
are inherent to the stochastic processes in biological systems. Other factors
can be identified and controlled. Some key controllable factors include:

*	 Poor CO2 incubator performance due to lack of calibration and stability of temperature, humidity and CO2 over time.
*	 Non-quantitative and/or inconsistent procedures for feeding and splitting cell
cultures prior to running cell-based assays including inconsistent limits of cell
density and feeding schedules, inconsistent cell density at the time of assay and
changes to cell morphology.
*	 Alterations in media components due to lot-to-lot differences and alteration of
concentrations over time due to degradation.
*	 Differences in cell culture growth surfaces such as variability among suppliers,
vessel surface treatments and lot-to-lot variability.
*	 Biological issues resulting from growing cells in continuous culture for extended
periods of time which in turn increases the risk of phenotypic drift, contamination by infectious agents and cross contamination with other cell types.
*	 Each of these controllable variables can adversely affect the results and interpretation of data obtained from downstream assays leading to lost time and a waste
of valuable, and at times, costly reagents. A key element in controlling adverse
variables is to standardize on objective metrics, thereby eliminating human subjectivity and interpretation.
Advantages of performing quality control of cell cultures via
continuous monitoring
The IncuCyte® real-time live-cell analysis system provides a label-free, non-invasive
method for monitoring cells directly in the incubator. In sharp contrast to manual
monitoring of cell culture processes, quality control monitoring with real-time livecell analysis automates data capture and cell assessment (Figure 1). Cells can be
monitored around-the-clock and at precise, regularly scheduled sampling intervals. In addition to supporting decisions for current culture processes,
historical information can be retrieved months or years later for comparison of cell
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| January, 2019

Manual Cell Culture Monitoring

Initial cell density- subjective
Seed vessel

Initial cell density-
measured for every
well

Live-Cell Analysis

Assessments made at
random locations with
variable frequencies-
qualitative and operator
dependent

Cell utilization decisions including timing- subjective

Monitor growth

Utilize cells

Assessments made at
precise locations with
scheduled sampling intervals-objective growth
curves and morphology
data support decisions

Split, treatment, harvest or assay decisions
based on review of
both morphology and
quantitative confluence measurements

TIME

Figure 1. Comparison of cell culture monitoring methods: Vertical arrows represent interaction
points with the cell culture using manual methods and real-time live-cell analysis. Subjective
decisions made during manual monitoring result in variability for cell-based assays.
Gain Critical Insights from Advanced Cell Models with Real-Time Analysis

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