Compartmentalised screening by microfluidic control

Abstract

The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalising the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.

1 . A method for identifying a compound or compounds in a repertoire of compounds, which compound or compound(s) possess(es) a desired activity, comprising the steps of: 
 a) compartmentalising the compounds into microcapsules, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and    b) identifying the compounds which possess the desired activity,    wherein one or both of steps a) and b) is performed under microfluidic control.    
     
     
         2 . A method for preparing a compound, comprising the steps of: 
 (a) compartmentalising the compounds into microcapsules, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule;    (b) identifying the compounds which possess the desired activity.    (c) identifying and producing the compound having the desired activity,    wherein one or more of steps a, b and c is performed under microfluidic control.    
     
     
         3 . A method for preparing a compound, comprising the steps of: 
 (a) compartmentalising the compounds into microcapsules, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule;    (b) identifying and, optionally, sorting the microcapsules which have contain the compound(s) having the desired activity using a change in their optical properties; and    (c) identifying and producing the compound having the desired activity.    
     
     
         4 . A method for screening a compound or compounds capable of modulating the activity of a target, comprising the steps of: 
 (a) compartmentalising the compounds into microcapsules, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule;    (b) identifying and, optionally, sorting the microcapsules which contain the compound(s) having the desired activity using a change in their optical properties; and    (c) contacting a target having a desired activity with the compound or compounds and monitoring the modulation of an activity of the target by the compound or compounds,    wherein one or more of steps a, b and c is performed under microfluidic control.    
     
     
         5 . A method for preparing a target comprising the steps of: 
 (a) providing a synthesis protocol for a target wherein at least one step is facilitated by a compound;    (b) preparing variants of the compound which facilitates this step;    (c) compartmentalising the compounds into microcapsules, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule;    (d) identifying and, optionally, sorting the microcapsules which contain the compound(s) having the desired activity using a change in their optical properties; and    (e) preparing the target using the compound identified in (d) to facilitate the relevant step of the synthesis,    wherein one or more of steps a to e is performed under microfluidic control.