Sampling and analysis of reactions by trapping reaction components on a sorbent

Abstract

Methods and devices for rapidly analyzing groups of reactions are disclosed. The method includes the steps of contacting a fluid sample from one of the reaction mixtures with a sorbent, trapping at least one component of the fluid sample on the sorbent, and detecting the at least one component of the fluid sample trapped on the sorbent. The contacting step, the trapping step, and the detecting step are carried out at least once for each of the reaction mixtures in rapid serial or parallel fashion. The present invention is useful for screening combinatorial libraries, especially libraries of catalysts made through parallel synthesis, but the disclosed methods and devices can be used to analyze a broad spectrum of chemical transformations.

What is claimed is:  
     
         1 . A method of analyzing reaction mixtures comprising the steps of: 
 contacting a fluid sample from one of the reaction mixtures with a sorbent;    trapping at least one component of the fluid sample on the sorbent; and    detecting the at least one component of the fluid sample trapped on the sorbent;    wherein the contacting step, the trapping step, and the detecting step are carried out at least once for each of the reaction mixtures.    
     
     
         2 . The method of  claim 1 , wherein the at least one component is a reaction product.  
     
     
         3 . The method of  claim 1 , wherein the contacting step is carried out for at least two of the reaction mixtures simultaneously.  
     
     
         4 . The method of  claim 1 , wherein the detecting step is carried out for at least two of the reaction mixtures simultaneously.  
     
     
         5 . The method of  claim 1 , wherein the fluid sample from each of the reaction mixtures is in contact with the sorbent for about the same amount of time.  
     
     
         6 . The method of  claim 1 , wherein the fluid sample in the contacting step is a vapor.  
     
     
         7 . The method of  claim 6 , wherein the contacting step further comprises the step of vaporizing a portion of each of the reaction mixtures.  
     
     
         8 . The method of  claim 7 , wherein the vaporizing step comprises heating each of the reaction mixtures.  
     
     
         9 . The method of  claim 6 , further comprising the steps of: 
 confining the reaction mixtures in wells formed in a surface of a reaction block; and    disposing a layer of the sorbent on the surface of the reaction block, so that the vapor from each of the reaction mixtures contacts discrete areas of the layer during the contacting step.    
     
     
         10 . The method of  claim 9 , wherein the layer of the sorbent is supported on a solid layer.  
     
     
         11 . The method of  claim 10 , wherein the solid layer is gas permeable.  
     
     
         12 . The method of  claim 11 , wherein the contacting step further comprises the steps of: 
 pressurizing at least one of the wells; and    venting the vapor from the at least one of the wells through the solid layer.    
     
     
         13 . The method of  claim 10 , wherein the layer of the sorbent on the solid layer is discontinuous.  
     
     
         14 . The method of  claim 6 , further comprising the steps of: 
 confining the reaction mixtures in vessels; and    providing fluid communication between the vapor from each of the reaction mixtures and the sorbent.    
     
     
         15 . The method of  claim 14 , further comprising the step of placing the sorbent in one end of each of the vessels, so that the vapor from each of the reaction mixtures contacts the sorbent during the contacting step.  
     
     
         16 . The method of  claim 14 , wherein the contacting step further comprises the steps of: 
 pressurizing at least one of the vessels; and    venting at least one of the vessels so that the vapor flows through the sorbent.    
     
     
         17 . The method of  claim 1 , wherein the fluid sample in the contacting step is a liquid.  
     
     
         18 . The method of  claim 17 , wherein the contacting step further comprises the steps of: 
 withdrawing a predetermined amount of the fluid sample from one of the reaction mixtures; and    applying the predetermined amount of the fluid sample on the sorbent.    
     
     
         19  The method of  claim 1 , wherein the detecting step further comprises the step of obtaining an absorption spectrum of the sorbent in order to detect the presence of the at least one component trapped on the sorbent.  
     
     
         20 . The method of  claim 19 , wherein the absorption spectrum is obtained from an infrared region of the spectrum, an ultraviolet region of the spectrum, or a visible region of the spectrum.  
     
     
         21 . The method of  claim 1 , wherein the detecting step further comprises the steps of: 
 removing the at least one component trapped on the sorbent; and    identifying the at least one component removed from the sorbent by gas chromatography, liquid chromatography, mass spectroscopy, nuclear magnetic resonance spectroscopy, or absorption spectroscopy.    
     
     
         22 . The method of  claim 21 , wherein the removing step further comprises the step of heating the sorbent.  
     
     
         23 . The method of  claim 22 , wherein the removing step further comprises the step of washing the sorbent with a solvent.  
     
     
         24 . The method of  claim 1 , wherein the detecting step further comprises the steps of: 
 exposing the sorbent to an indicator reagent; and    observing a change in appearance of the sorbent resulting from an interaction of the indicator reagent with the at least one component.    
     
     
         25 . The method of  claim 24 , wherein the interaction of the indicator reagent with the at least one component results in a change in color of the sorbent.  
     
     
         26 . The method of  claim 24 , wherein the detecting step further comprises the step of irradiating the sorbent with ultraviolet light; 
 wherein the interaction of the indicator reagent with the at least one component results in a change in fluorescence of the sorbent during exposure to the ultraviolet light.    
     
     
         27 . The method of  claim 24 , wherein the observing step further comprises the steps of: 
 obtaining a signal that is a measure of the appearance of the sorbent; and    comparing the signal to a calibration curve that relates the signal to an amount of the at least one component trapped on the sorbent.    
     
     
         28 . The method of  claim 24 , wherein the observing step comprises the steps of: 
 obtaining a first signal that is a measure of the appearance of the sorbent resulting from the interaction of the indicator reagent with the at least one component; and    comparing the first signal to a second signal that is a measure of the appearance of the sorbent resulting from the interaction of the reagent with a known amount of the at least one component.    
     
     
         29 . A method of screening a group of catalysts comprising the steps of: 
 combining each of the catalysts with at least one reactant so as to form a plurality of reaction mixtures;    contacting a fluid sample from one of the reaction mixtures with a sorbent;    trapping at least one component of the fluid sample on the sorbent; and    detecting the at least one component of the fluid sample on the sorbent;    wherein the contacting step, the trapping step, and the detecting step are carried out at least once for each of the reaction mixtures.    
     
     
         30 . The method of  claim 29 , wherein the at least one component is a reaction product.  
     
     
         31 . The method of  claim 29 , wherein the combining step is carried out for at least two of the reaction mixtures simultaneously.  
     
     
         32 . The method of  claim 29 , wherein the contacting step is carried out for at least two of the reaction mixtures simultaneously.  
     
     
         33 . The method of  claim 29 , wherein the detecting step is carried out for at least two of the reaction mixtures simultaneously.  
     
     
         34 . The method of  claim 29 , wherein the fluid sample from each of the reaction mixtures is in contact with the sorbent for about the same amount of time.  
     
     
         35 . The method of  claim 29 , wherein the at least one reactant is the same for each of the reaction mixtures formed in the combining step.  
     
     
         36 . The method of  claim 29 , wherein the fluid sample in the contacting step is a vapor.  
     
     
         37 . The method of  claim 36 , wherein the contacting step further comprises the step of vaporizing a portion of each of the reaction mixtures.  
     
     
         38 . The method of  claim 37 , wherein the vaporizing step comprises heating each of the reaction mixtures.  
     
     
         39 . The method of  claim 36 , wherein the combining step further comprises the step of confining each of the catalysts and the at least one reactant in wells formed in a surface of a reaction block so as to form the plurality of reaction mixtures.  
     
     
         40 . The method of  claim 39 , further comprising the step of disposing a layer of the sorbent on the surface of the reaction block, so that the vapor from each of the reaction mixtures contacts discrete areas of the layer during the contacting step.  
     
     
         41 . The method of  claim 40 , wherein the layer of the sorbent is supported on a solid layer.  
     
     
         42 . The method of  claim 41 , wherein the solid layer is gas permeable.  
     
     
         43 . The method of  claim 42 , wherein the contacting step further comprises the steps of: 
 pressurizing at least one of the wells; and    venting the vapor from the at least one of the wells through the solid layer.    
     
     
         44 . The method of  claim 41 , wherein the layer of the sorbent on the solid layer is discontinuous.  
     
     
         45 . The method of  claim 36 , wherein the combining step further comprises the steps of: 
 confining each of the catalysts and the at least one reactant in vessels so as to form the plurality of reaction mixtures; and    providing fluid communication between the vapor from each of the reaction mixtures and the sorbent.    
     
     
         46 . The method of  claim 45 , further comprising the step of placing the sorbent in one end of each of the vessels, so that the vapor from each of the reaction mixtures contacts the sorbent during the contacting step.  
     
     
         47 . The method of  claim 45 , wherein the contacting step further comprises the steps of: 
 pressurizing at least one of the vessels; and    venting the at least one of the vessels so that the vapor from each of the reaction mixtures flows through the sorbent.    
     
     
         48 . The method of  claim 29 , wherein the fluid sample in the contacting step is a liquid.  
     
     
         49 . The method of  claim 48 , wherein the contacting step further comprises the steps of: 
 withdrawing a predetermined amount of the fluid sample from one of the reaction mixtures; and    applying the predetermined amount of the fluid sample on the sorbent.    
     
     
         50 . The method of  claim 29 , wherein the detecting step further comprises the step of obtaining an absorption spectrum of the sorbent in order to detect the presence of the at least one component trapped on the sorbent.  
     
     
         51 . The method of  claim 50 , wherein the absorption spectrum is obtained from an infrared region of the spectrum, an ultraviolet region of the spectrum, or a visible region of the spectrum.  
     
     
         52 . The method of  claim 29 , wherein the detecting step further comprises the steps of: 
 removing the at least one component trapped on the sorbent; and    identifying the at least one component removed from the sorbent by gas chromatography, liquid chromatography, mass spectrometry, nuclear magnetic resonance spectrometry, or absorption spectrometry.    
     
     
         53 . The method of  claim 52 , wherein the removing step further comprises the step of heating the sorbent.  
     
     
         54 . The method of  claim 52 , wherein the removing step further comprises the step of washing the sorbent with a solvent.  
     
     
         55 . The method of  claim 29 , wherein the detecting step further comprises the steps of: 
 exposing the sorbent to an indicator reagent; and    observing a change in appearance of the sorbent resulting from an interaction of the indicator reagent with the at least one component.    
     
     
         56 . The method of  claim 55 , wherein the interaction of the indicator reagent with the at least one component results in a change in color of the sorbent.  
     
     
         57 . The method of  claim 55 , wherein the detecting step further comprises the step of irradiating the sorbent with ultraviolet light; 
 wherein the interaction of the indicator reagent with the at least one component results in a change in fluorescence of the sorbent during exposure to the ultraviolet light.    
     
     
         58 . The method of  claim 55 , wherein the observing step further comprises the steps of: 
 obtaining a signal that is a measure of the appearance of the sorbent; and    comparing the signal to a calibration curve that relates the signal to an amount of the at least one component trapped on the sorbent.    
     
     
         59 . The method of  claim 55 , wherein the observing step comprises the steps of: 
 obtaining a first signal that is a measure of the appearance of the sorbent resulting from the interaction of the indicator reagent with the at least one component; and    comparing the first signal to a second signal that is a measure of the appearance of the sorbent resulting from the interaction of the reagent with a known amount of the at least one component.    
     
     
         60 . An apparatus for analyzing reaction mixtures comprising: 
 a reaction block having wells formed along an upper surface;    a sorbent layer disposed above the upper surface of the reaction block such that the wells and the sorbent layer define vessels for containing the reaction mixtures;    wherein the sorbent layer is adapted to trap at least one fluid component of the reaction mixtures.    
     
     
         62 . The apparatus of  claim 60 , wherein the reaction block further comprises heating elements.  
     
     
         61 . The apparatus of  claim 60 , wherein the reaction block further comprises a system for regulating temperature of the reaction mixtures.  
     
     
         63 . The apparatus of  claim 60 , wherein the wells each contain a removable lining.  
     
     
         64 . The apparatus of  claim 60 , wherein the sorbent layer is supported on a solid layer.  
     
     
         65 . The apparatus of  claim 64 , wherein the sorbent layer and the solid layer comprise a thin layer chromatography plate.  
     
     
         66 . The apparatus of  claim 64 , wherein the solid layer is gas permeable.  
     
     
         67 . The apparatus of  claim 66 , further comprising a cover having an upper surface and a lower surface, the lower surface of the cover disposed above the solid layer; and 
 a plurality of conduits formed in the cover that provide passageways for vapor flow between each of the vessels and the upper surface of the cover.    
     
     
         68 . An apparatus for analyzing reaction mixtures comprising: 
 vessels for containing each of the reaction mixtures; and    sorbent traps in fluid communication with the vessels;    wherein the sorbent traps are adapted to trap at least one fluid component of the reaction mixtures.    
     
     
         69 . The apparatus of  claim 68 , further comprising: 
 a reaction block having wells formed along an upper surface; and    a cover having an upper surface and a lower surface;    wherein the cover is disposed above the upper surface of the reaction block such that the wells and the lower surface of the cover define the vessels for containing each of the reaction mixtures.    
     
     
         70 . The apparatus of  claim 69 , wherein each of the vessels contain a removable lining.  
     
     
         71 . The apparatus of  claim 69 , wherein the sorbent traps are located in the vessels adjacent to the lower surface of the cover.  
     
     
         72 . The apparatus of  claim 69 , further comprising passageways formed in the cover that extend from the lower surface of the cover to the upper surface of the reaction cover.  
     
     
         73 . The apparatus of  claim 72 , wherein the sorbent traps are located in at least some of the passageways.  
     
     
         74 . The apparatus of  claim 72 , wherein the passageways further comprise inlet passageways and outlet passageways, wherein the outlet passageways contain the sorbent traps and the inlet passageways are adapted to provide a component of the reaction mixtures to each of the vessels.  
     
     
         75 . The apparatus of  claim 72 , wherein the sorbent traps are located external to the cover and communicate with the vessels through the passageways.  
     
     
         76 . The apparatus of  claim 72 , wherein the passageways further comprise inlet passageways and outlet passageways, wherein the sorbent traps communicate with the vessels through the outlet passageways, and the inlet passageways are adapted to provide a component of the reaction mixtures to each of the vessels.  
     
     
         77 . The apparatus of  claim 68 , further comprising heating elements in thermal contact with the vessels.  
     
     
         78 . The apparatus of  claim 68 , further comprising a temperature control system for regulating the temperature of the reaction mixtures.  
     
     
         79 . An apparatus for screening reaction mixtures, wherein at least one constituent of the reaction mixtures is contained in depressions located along a top surface of a planar substrate, the apparatus comprising: 
 a heating block adapted to support the planar substrate and to provide thermal contact with a bottom surface of the planar substrate;    a gas permeable sorbent layer having an upper surface and a lower surface, wherein the lower surface of the sorbent layer is disposed above the top surface of the planar substrate, and the sorbent layer is adapted to trap at least one vapor phase component of the reaction mixtures;    a cover having an upper surface and a lower surface, the lower surface of the reactor cover disposed above the upper surface of the sorbent layer; and    passageways formed in the cover that extend from the lower surface of the cover to the upper surface of the cover and provide flow paths for vapor phase components of the reaction mixtures from the upper surface of the cover to the at least one constituent of the reactive mixture.    
     
     
         80 . The apparatus of  claim 79 , wherein the heating block further comprises a system for regulating temperature of the reaction mixtures.  
     
     
         81 . The apparatus of  claim 79  further comprising a gas permeable solid layer having an upper surface and a lower surface wherein the sorbent layer is supported on one of the upper surface of the gas permeable solid layer and the lower surface of the gas permeable solid layer.  
     
     
         82 . The apparatus of claim  81 , wherein the solid layer is a frit, quartz paper, or a wire mesh.  
     
     
         83 . The apparatus of claim  82 , wherein the frit is made of glass, polyethylene, or polytetrafluoroethylene.  
     
     
         84 . The apparatus of claim  81 , wherein the sorbent layer is discontinuous.  
     
     
         85 . The apparatus of claim  84 , wherein the sorbent layer is disposed in depressions formed along one of the upper surface of the gas permeable solid layer and the lower surface of the gas permeable solid layer.