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Computer software and algorithms for systems biologically linked to cellular phenotype

A computer, cellular technology used in the field of computer-implemented screening

Inactive Publication Date: 2007-01-03
BECTON DICKINSON & CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Finding the correct growth effector or combination of growth effectors for a given cell type to obtain a desired cell fate is therefore onerous

Method used

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  • Computer software and algorithms for systems biologically linked to cellular phenotype
  • Computer software and algorithms for systems biologically linked to cellular phenotype
  • Computer software and algorithms for systems biologically linked to cellular phenotype

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

Example 1 Binding of hyaluronic acid to amine-rich tissue culture surfaces

[0072] Becton Dickinson Labware Prepares PRIMARIA Using Oxygen / Nitrogen Plasma TM Tissue Culture Products. In particular, oxygen / nitrogen plasma is used to treat polystyrene products to allow the incorporation of oxygen and nitrogen containing functional groups such as amino and amide groups. For this experiment, carbodiimide bioconjugate chemistry is well known in the art (e.g. "Protein Immobilization: Fundamentals and Applications" Richard S. Taylor, Ed. (M. Dekker, NY, 1991) or in co-pending commonly owned U.S. application 10 / 259,797 (the application was filed on September 30, 2002), the incorporation of HA into PRIMARIA TM Amine-rich surfaces on multiwell plates.

Embodiment 2

The combination of embodiment 2ECM protein and hyaluronic acid

[0073] The ECM species was covalently attached to the HA polymer of Example 1 tethered to the culture surface. In particular, using the periodate method described in E.Junowicz and S.Charm, "The Derivatization of Oxidized Polysaccharides for Protein Immobilization and Affinity Chromotography," Biochimica et. Biophysica Acta, Vol. 428:157-165 (1976) by oxidation Generates an aldehyde group on HA. This method requires the addition of sodium periodate to a solution of HA, which activates the terminal sugars. Next, standard immobilization chemistry (such as described in "Protein Immobilization: Fundamentals and Applications" Richard F. Taylor, Ed. (M. Dekker, NY, 1991 or in co-pending co-owned U.S. application 10 / 259,797) , which was filed on September 30, 2002), binds activated HA to amine groups on ECM proteins.

Embodiment 3

Example 3 Simultaneous screening of 10 different ECM proteins using a statistically designed experiment (mixture design)

[0074] In this example, the statistical design is a mixture design. Using this design to identify factor pairs or single factors that have a positive effect on cellular responses allowed us to see the interaction between the two ECMs. In this example, 10 individual ECMs, each representing a single "factor", were used to prepare a mixture of ECMs, which were placed as Figure 7 wells of the 96-well plate shown in . The ECM is covalently attached to a biocompatible polymer (see Examples 1 and 2) on the culture surface. Note that without a statistical design of experiments, 210 (1024) single experiments, or 11 96-well plates, would be required to examine the effect of each of the 10 ECMs in combination with the others on a given cell type.

[0075] In this example, a set of 10 attachment ligands was chosen and a 96-well array was chosen as the mode of this ...

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Abstract

An automated method and system for identifying agents capable of eliciting a phenotypic change in a cell-type is provided. The method includes the steps of: providing receptacles in an array; and providing a statistical design including generic factor names, factor levels and experimental runs. The method further includes the steps of utilizing a software program to generate a computer representation of the statistical design by automatically mapping the identities of the agents to the generic factor names, by mapping the concentration or amounts of the agents to the factor levels and by mapping the locations of the receptacles within the array to the experimental runs. The method also includes placing different mixtures of single agents into receptacles in the array based on the computer representation of the statistical design; contacting the placed mixtures with cells; acquiring experimental data from the contacted cells; and utilizing a processor including an algorithm for comparing the acquired data with the statistical design to identify particular agent mixtures or single agents that cause a phenotypic change in the contacted cells.

Description

field of invention [0001] The present invention generally relates to the field of high throughput screening methods. In particular, the invention relates to computer-implemented screening methods that can be used to identify mixtures of single agents and single agents within these mixtures that elicit desired biological responses in cells. Background of the invention [0002] For cells to be used in therapies to treat or cure human disease, control over cell fate, such as cell survival, proliferation and differentiation, is required when maintaining cells in in vitro cell culture. There is therefore a need to control the interaction of receptors and ligands on the cell surface. For example, to control the interaction between cells and ligands present on an in vitro cell culture substrate, a suitable cell culture substrate such as polystyrene. This coating thus eliminates any uncontrolled adsorption of serum proteins. Biologically active ligands suitable for interacting w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G06K9/00G06Q50/00G16B20/00C12M1/34C12M3/00C40B60/14G01N33/48G01N33/50G06FG06F15/00G06F17/18G06F19/00G06G7/48G06G7/58G16B50/20
CPCB01J2219/00695B01J2219/007B01J2219/00691B01J2219/00306G06F19/28B01J2219/00743G06F19/18G06F19/20C40B60/14G16B20/00G16B25/00G16B50/00G16B50/20
Inventor P·D·哈兰M·A·海达兰
Owner BECTON DICKINSON & CO
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