A method for an automatic inspection of a plurality of plate-like plastic carriers, whereby each plastic carrier is closed by a cover and has a unique identification code and a culture medium. A storage container including a multiplicity of plastic carriers is provided, and a computer-controlled handling unit including an optical inspection system is provided. While performing the automatic inspection in an inspection routine, a plastic carrier is removed from the storage container with the aid of the handling unit, the cover of the plastic carrier is subsequently removed, the plastic carrier is supplied to the inspection system, the identification code is read, and at least one image of the plastic carrier, including the surface of the culture solution is recorded. The image is evaluated for a growth of germs and/or faults in the plastic carrier and the result of the evaluation is stored for each plastic carrier.

The invention relates to a serum-free cell culture perfusion medium comprising the medium components subgrouped into at least three separate aqueous concentrated feeds and a diluent, wherein the resulting serum-free cell culture perfusion medium is pH-adjusting to neutral pH upon mixing. Also provided is a method of preparing said serum-free cell culture perfusion medium. The invention further relates to methods of culturing mammalian cells or producing a protein of interest in perfusion culture using said serum-free cell culture perfusion medium that achieve high productivity at a low cell specific perfusion rate. The invention further relates to the use of the new and improved serum-free cell culture perfusion medium to control osmolality in a perfusion cell culture, wherein increasing osmolality results in an increase in total productivity and/or cell specific productivity by suppressing cell growth during cell culture, e.g., during production phase of perfusion cell culture. Suppression of cell growth particularly reduces or eliminates the need for wasteful cell bleed.

A portable incubator system integrated to a mobile phone providing a real-time tracking of samples and data flow is provided. The portable incubator system allowing cells to be cultured, reproduced and characterized in real-time without a need for a commercial incubator and a microscope-camera system installed within the portable incubator system.

According to an aspect there is provided an illumination system for illumination of a sample in a container, such as a well of a microplate or a petri dish, the container comprising a bottom surface and side walls which together define a volume for receiving the sample, the illumination system comprising: at least one light source; a mask comprising an opaque portion, preventing light from passing through the mask, and an at least partially transparent portion, allowing light to pass through the mask; wherein the illumination system is adapted to be positioned such that the light generated by the light source, passing through the mask, illuminates the sample in the container; and wherein the light source and the mask are configured such that a shape, a size, and a position of a projection of the light passing through the mask, onto a plane of the bottom surface, match a shape, a size, and a position of the bottom surface.

A cell area extraction unit (241) extracts a cell area in a phase image that is created based on a hologram obtained by in-line holographic microscope (IHM). A background value acquisition unit (242) obtains a background value from phase values at a plurality of positions outside the cell area. An intracellular phase value acquisition unit (243) averages a plurality of phase values on a sampling line set at a position close to the periphery of a cell, while avoiding a central portion in which the phase value may be lowered in the cell area, to obtain an intracellular phase value. A phase change amount calculation unit (244) obtains the difference between the intracellular phase value and the background value. A phase change amount determination unit (245) compares the value of the difference with thresholds in two levels to determine whether the cell is in an undifferentiated state or an undifferentiation deviant state. It is thereby possible to automatically make a correct determination while removing the influence of a theoretical measurement error by IHM.

The monitoring and control of bioprocesses is provided. The present disclosure provides the ability to generate generic calibration models, independent of cell line, using inline Raman probes to monitor changes in glucose, lactate, glutamate, ammonium, viable cell concentration (VCC), total cell concentration (TCC) and product concentration. Calibration models were developed from cell culture using two different CHOK1SV GS-KO™ cell lines producing different monoclonal antibodies (mAbs). Developed predictive models, qualified using an independent CHOK1SV GS-KO™ cell line not used in calibration, measured changes in glucose, lactate, ammonium, VCC, and TCC with minor prediction errors over the course of cell culture with minimal cell line dependence. The development of these generic models allows the application of spectroscopic PAT techniques in a clinical manufacturing environment, where processes are typically run once or twice in GMP manufacturing based on a common platform process.

A method of identifying a molecular composition and a spatial position of a single cell comprised in a 3 dimensional structure comprising a plurality of cells is provided.

By moving at least one of a culture container having a plurality of wells or an imaging optical system that forms an image of an observation target in each of the wells, an observation position in the culture container is scanned to observe the observation target. In a case where an auto-focus control for each observation position is performed, a start timing of the auto-focus control for each observation position is switched on the basis of a boundary portion between the adjacent wells in a scanning direction of the observation position.

Spectral data indicating an intensity of electromagnetic waves, which have been emitted to a cell suspension including a cell and a culture solution and have been subjected to an action of the cell suspension, for each wave number or wavelength is acquired. Preprocessing is performed on the spectral data. A soft sensor, which receives processed data obtained by the preprocessing as an input and outputs state data indicating a state of the cell or the culture solution, is constructed by machine learning using a plurality of combinations of the processed data and the state data as training data. The processed data for the spectral data acquired for a cell suspension including a cell which is being cultured is input to the soft sensor, and the state data output from the soft sensor is acquired.

A bioreactor device includes a solid substrate having a first face and a second face. The solid substrate at least partially defines a perfusion channel, a plurality of chambers, a fluidic inlet, and a fluidic outlet. A first sheet disposed over the first face and a second sheet disposed over the second face. Characteristically, the combination of the solid substrate, the first sheet and the second sheet define the perfusion channel and each chamber of the plurality of chambers. The plurality of chambers are arranged in rows of chambers in which adjacent chambers are positioned at opposite side of the perfusion channel. The perfusion channel extends from the fluidic inlet and the fluidic outlet having a serpentine path along each row of chambers with each chamber being in fluid communication with the perfusion channel.