Rapid Method For Targeted Cell (Line) Selection

Abstract

The present invention relates to a process for the prediction of cell culture performance data of sample cells, a process for the isolation of said cells and a device for the prediction of cell culture performance data of sample cells.

What is claimed is: 
     
         1 . A process for the prediction of cell culture performance data of at least one sample cell, the process comprising:
 (a) providing a sample of the at least one sample cell, cell culture performance data from a standard cell and raw standard MS (mass spectrometric) data from the standard cell,   (b) subjecting the sample of the at least one sample cell to a MS analysis to obtain raw sample MS data thereof,   (c) subjecting the raw standard and the raw sample MS data to at least one first MS signal processing method to obtain pre-treated standard and sample MS profiles and   (d) subjecting the cell culture performance data from the standard cell of (a) and the pre-treated standard and sample MS profiles obtained in (c) to a second MS signal processing method including a PLS-DA (partial least squares discriminant analysis) based comparative evaluation so as to predict the cell culture performance data of the at least one sample cell, wherein the cell culture performance data are cell specific productivity, integral viable cell count or cell product concentration data.   
     
     
         2 . The process according to  claim 1 , wherein the cell is selected from a group consisting of human cell lines, animal cell lines, plant cell lines, cells from fungi, cells from bacteria, cells from yeast and stem cells. 
     
     
         3 . The process according to  claim 1 , wherein the cell is a CHO cell line or a CHO-K1 cell line. 
     
     
         4 . The process according to  claim 1 , wherein the MS analysis in (b) is MALDI-TOF. 
     
     
         5 . The process according to  claim 1 , wherein the sample of the sample cells subjected to (b) comprises from 0.015×106 to 0.0625×106 cells. 
     
     
         6 . The process according to  claim 1 , wherein the raw sample MS data obtained in (b) and the raw standard MS data provided in (a) are signal processed by an operation selected from the group consisting of baseline correction, normalisation, alignment, filtering and cropping. 
     
     
         7 . The process according to  claim 1 , wherein the pre-treated standard and sample MS profiles obtained in (c) are optically analysed. 
     
     
         8 . The process according to  claim 1 , wherein the sample cell with the predicted cell culture performance data evaluated in (d) is cultivated in a cell culture so as to verify its cell culture performance data. 
     
     
         9 . The process according to  claim 8 , wherein the raw sample MS profiles obtained in (b) and the verified cell culture performance data of the sample cell are used in (a) as standard MS data and cell culture performance data from a standard cell. 
     
     
         10 . A method of isolating a cell with desired cell culture performance data comprising: predicting cell culture performance data of at least one sample cell with the process of claim  13 ; and
 isolating a desired cell having a desired cell culture performance data.   
     
     
         11 . A cell isolated by the process according to  claim 10 , wherein the cell has a protein productivity of at least 10 g/l/h. 
     
     
         12 . A device that is adapted to provide a prediction of cell culture performance data when supplied with a sample of at least one sample cell, the device comprising the:
 (a) means adapted for subjecting a sample of the at least one sample cell to a MS (mass spectrometric) analysis to obtain a raw sample MS data thereof;   (b) means adapted for subjecting a raw standard and the raw sample MS data to at least one first MS signal processing method to obtain pre-treated standard and sample MS profiles; and   (c) means adapted for subjecting cell culture performance data from a standard cell and the pre-treated sample and standard MS profiles to a second MS signal processing method including a PLS-DA (partial least square discriminant analysis) based comparative evaluation so as to predict the cell culture performance data of the sample cell, wherein the cell culture performance data are cell specific productivity, integral viable cell count or cell product concentration data.