A cell culturing system includes an enzyme sensor that detects a concentration of a predetermined component of a culture medium used for culturing of cells, a sensor flow path in which the enzyme sensor is disposed, and a bioreactor that performs culturing of cells while causing the culture medium to flow through the sensor flow path, and further includes a deterioration index calculation unit that determines a deterioration index of the enzyme sensor, based on a detected concentration value of the enzyme sensor, and a detection period during which the detected concentration value is detected, and a lifespan determination unit that detects whether or not an integrated value of the deterioration index has reached a threshold value, and thereby determines the lifespan of the enzyme sensor.

A bioreactor includes a culture medium vessel housing culture medium. The culture medium vessel further includes a first side surface including a first transparent optical window; and a second side surface parallel to the first surface and including one or more sensor adapters to fix optical sensors. A cell retention vessel is disposed underneath and connected to the culture medium vessel, the cell retention vessel housing biological cells and having: a top surface that intersects a base of the culture medium vessel, and a second transparent optical window indented into the top surface at a first corner of the top surface. A semipermeable membrane is disposed at a bottom of the cell retention vessel, and a frame comprising a grid is disposed underneath the semipermeable membrane.

A cell screening device including a bottom plate, a cell placement membrane, a pair of fluid injection parts, and a flow channel, the flow channel being formed between the bottom plate and the cell placement membrane and extending in such a manner that the flow channel end parts respectively reach the fluid injection parts. In the cell placement membrane, a plurality of wells, each having a size capable of housing a single cell, and through holes are formed. In the back side of each lid, i.e., the ceiling face of the flow channel end part, a debubbling surface, which rises in an inclined or step-like manner as getting closer to a fluid injection hole, is formed.

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.

The subject invention provides standardized, high concentration inocula in solid form for use as seed cultures in scaled-up cultivation. Further embodiments include methods of producing standardized inocula, as well as methods of preserving and storing the inocula for convenient use over extended periods of time.

Example embodiments include a cell culture apparatus, methods for cell cultivation by using the cell culture apparatus, and a cell culture incubator comprising the cell culture apparatus. The cell culture apparatus comprises a plurality of cell culture modules arranged adjacent to each other. Each cell culture module comprises two or more culture medium reservoirs connected by two or more flow channels that go through a basal chamber arranged under an apical chamber. The apical and basal chambers are separated by a porous membrane. The basal chamber has a bottom part arranged higher than a bottom part of each of the culture medium reservoirs. The culture model comprises further a cavity under at least the bottom part of the basal chamber and at least one means for capturing at least one image from a bottom and/or top of the at least one cell culture module.

Methods for determining ethylene concentration in an ethylene oligomerization reactor using an ultrasonic flow meter are described, and these methods are integrated into ethylene oligomerization processes and related oligomerization reactor systems.

A method for monitoring a biotechnological process, wherein starting materials are converted into products via a biomass and important process parameters for monitoring are identified during the process, where during the process, a current concentration of the biomass utilized in the process is recurrently estimated, current measurement values of measurable process parameters are then recurrently determined on a recurring basis and current values for additional process parameters are identified therefrom, where the current measurement values of the measurable process parameters and the current determined values of the additional process parameters are based on the respective temporally correlating concentration of biomass and where, from a combination of the current concentration of biomass and the current measurement values of the measurable process parameters and the identified current values of the additional process parameters, current, cell-specific metabolic indicators are then derived which are then used in conjunction with a deterministic process model.

In one aspect, a method for automated analysis of samples from a bioreactor is provided herein, the method including: drawing at least one sample from a bioreactor; pressurizing the drawn at least one sample into a sample flow; purifying at least one target protein in the sample flow using a first liquid chromatography apparatus to create a purified sample flow; splitting the purified sample flow into a purified sample fraction flow and an effluent flow; and, analyzing the at least one target protein in the purified sample fraction flow using a second liquid chromatography apparatus. Advantageously, the subject invention provides for an automated two-step liquid chromatography process utilizing first dimension liquid chromatography for purification and second dimension liquid chromatography for analysis.

A three-dimensional (3D) microelectrode array device for in vitro electrophysiological applications includes a substrate and micro vias extending from the bottom face to the top face of the substrate. A microneedle at each micro via extends from the bottom face upward beyond the top face and forms a hypodermic microneedle array on the top face. Metallic traces on the bottom face interconnect the hypodermic microneedles to form the 3D microelectrode array. A microheater is positioned on the bottom face of the substrate. Microfluidic ports may be formed at the substrate. Interdigitated electrodes may be formed at the substrate.