Method and system for preparing synthetic multicomponent biotechnological and chemical process samples

A biotechnology and multi-component technology, applied in the field of synthesizing multi-component samples, can solve the problems of insufficient sensor calibration, poor calibration results of spectral sensors, etc.

Active Publication Date: 2017-02-22
F HOFFMANN LA ROCHE & CO AG
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These designs ensure that all experiments are independent and meet the above requirements, but generally yield poorly calibrated results for spectral sensors
Also, these designs typically only have 3-5 steps of variation, which is often insufficient for calibration of these sensors
Moreover, these orthogonal methods are only applicable for known and measurable variations, which is not the case when considering the presence of a considerable number of process samples with unknown, non-measurable variations

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method and system for preparing synthetic multicomponent biotechnological and chemical process samples
  • Method and system for preparing synthetic multicomponent biotechnological and chemical process samples
  • Method and system for preparing synthetic multicomponent biotechnological and chemical process samples

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0138] Example 1 concerns the synthesis of multicomponent fermentation samples. This example is intended to show step-by-step the implementation of parts of the invention in a multi-component (several analyte) complex system without limiting its use in other systems not covered by this example.

[0139]A good example of the application of the present invention is its use to simulate fed-batch fermentation, eg, Chinese Hamster Ovary (CHO) mammalian cell culture. Such fed-batch fermentations contain multi-component complex matrix analytes that are dependent on cell activity and imposed process conditions such as feed, feed rate, pH and temperature profile, among others.

[0140] The complex nature of these systems, the need to monitor them has long been an integral part of industrial processes, as this allows for increased automation and the introduction of advanced control schemes. In recent years, Process Analytical Technology (PAT) has emerged as a driving force to overcome ...

example 2

[0170] Example 2 involves increasing the number of synthetic multicomponent fermentation samples in order to better capture process dynamics.

[0171] One of the disadvantages of off-line measurements in a dynamic process is the small amount of sample available for measurement when compared to the variation of a specific analyte. This is important when dealing with in-line sensors such as near- and mid-infrared spectrometers in particular. Therefore, the current example uses parts of the solution provided in Example 1 to increase the number of samples that can be used to simulate process steps. This is useful if very deterministic distribution curves are required in some parts of the process, in particular it is useful to increase the number of samples in undersampled process stages. A good example of this kind of undersampling can be found in figure 1 The GTF distribution curve in . As can be seen, for the first data subset interval (from 0.06 to 0.35 time units), the majo...

example 3

[0180] Example 3 involves generating data samples to make the calibration model more accurate and robust.

[0181] The examples presented so far represent process dynamics and thus have the same behavior as process samples. The fermentation profile naturally preserves the metabolically introduced concentration dependence between the cell substrate and metabolites. Indeed, analysis of the correlations of the analytes presented in the offline data (Table 1) showed that these correlations were significant. Since the data generated in Examples 1 and 2 closely modeled the fermentation profile, it is also expected that the correlation would still hold for those synthetic multicomponent samples. As can be seen from Table 8, some analytes and culture parameters showed high correlation (0.8<|R|<1), moderate correlation (0.6<|R|<0.8) or slight correlation (0.5 <|R|<0.6), while the other analytes and culture parameters did not show any correlation at all (|R|<0.5). Among them, highly ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The present invention describes a method that is comprised of creating a set of synthetic samples that mimic a dynamic process or a specific process step or a variation thereof, to be used to develop multivariate monitoring calibrations and process supervisory control systems. In order to enhance calibration models accuracy and robustness the introduction of randomly spiked, programed spiked, random mixing and orthogonal experimental designed samples is also described. The new method works by using prior knowledge of dynamic processes expressed by their available data and quality control data and using such data to build mixtures profiles that can be used to build synthetic samples that mimic the process dynamics. A novel methodology to overcome calibration developments drawbacks of the prior art can be provided comprising designed synthetic multicomponent samples that mimic dynamic processes and using orthogonal design of experiments or random spikes or programed spikes or random mixing to enhance calibration models performance. With such multicomponent synthetic-samples which approximate accurately the matrix main components composition of real-samples we have demonstrated a novel use of PAT monitoring tools to estimate the dynamic process state (process supervision). The capability to derive multivariate process trajectories with multiparametric analysis of synthetic-samples prepared to span the multivariate design-space of a process allows for process supervisory control strategies to be established during process development and optimization.

Description

technical field [0001] The present invention relates to a method for the preparation of synthetic multicomponent samples of powders, liquids and liquids with suspended components capable of simulating dynamic processes, in particular multicomponent mixing, crystallization, distillation, chemical reactions and fermentation, for use in The multivariate calibration and multivariate supervision systems used in the development of the described process. In particular, the present invention relates to methods of developing multivariate calibration and / or supervisory systems, and more particularly, to computer programs and systems for operating such methods. Background technique [0002] Monitoring, monitoring and controlling industrial processes is often difficult and time-consuming because these systems have complex multi-component matrices that require laboratory chemical and physical analysis by benchmark methods. Furthermore, these assays typically have a lower acquisition fre...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): G06F19/00G01N21/27G01N35/00
CPCG01N21/278G01N21/359G01N35/00693G01N2035/0097G01N21/65G01N2201/129G16C20/70G16C20/20
Inventor J·卡多苏-曼内斯S·布泽尔P·费里萨多
Owner F HOFFMANN LA ROCHE & CO AG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap