US6001311A — Apparatus for diverse chemical synthesis using tw…

Claim 1

Independent Claim 225 words

A chemical synthesis apparatus for building chemical compounds by sequentially adding chemical units in a liquid reagent, said apparatus comprising: a frame assembly; a base assembly movably mounted to said frame assembly for movement in a first direction and including an array of reaction wells aligned in a plurality of spaced-apart reaction well rows and reaction well columns, each reaction well having at least one respective upper orifice extending into said well; a head assembly mounted to said frame assembly and having an array of nozzles aligned in a plurality of nozzle rows and nozzle columns spaced apart by a distance substantially similar to the spacing between said well rows and well columns for alignment therebetween, each nozzle being coupled to a different reservoir of liquid reagent for controlled delivery therethrough; said nozzle columns being independently movable in a second direction perpendicular to the first direction; and a plurality of seals positioned between said head assembly and said nozzle columns to form a seal therebetween; whereby repositioning of a nozzle column in the second direction allows delivery of any liquid reagent from the reservoirs coupled to the nozzle columns to any of the rows of reaction wells and movement of the base assembly in the first direction allows delivery of any liquid reagent to any of the reaction wells in a column of reaction wells.

Claim 2

Dependent Claim 225 words

A chemical synthesis apparatus for building chemical compounds by sequentially adding chemical units in a liquid reagent, said apparatus comprising: a frame assembly; a base assembly movably mounted to said frame assembly for movement in a first direction and including an array of reaction wells aligned in a plurality of spaced-apart reaction well rows and reaction well columns, each reaction well having at least one respective upper orifice extending into said well; a head assembly mounted to said frame assembly and having an array of nozzles aligned in a plurality of nozzle rows and nozzle columns spaced apart by a distance substantially similar to the spacing between said well rows and well columns for alignment therebetween, each nozzle being coupled to a different reservoir of liquid reagent for controlled delivery therethrough; said nozzle columns being independently movable in a second direction perpendicular to the first direction; and a plurality of seals positioned between said head assembly and said nozzle columns to form a seal therebetween; whereby repositioning of a nozzle column in the second direction allows delivery of any liquid reagent from the reservoirs coupled to the nozzle columns to any of the rows of reaction wells and movement of the base assembly in the first direction allows delivery of any liquid reagent to any of the reaction wells in a column of reaction wells.

Claim 3

Dependent Claim 65 words

The chemical synthesis apparatus as defined in claim 1 wherein, said base assembly moves relative said head assembly along a path substantially perpendicular to said nozzle columns to position at least one well column in depository alignment with at least one of said nozzles in a selected nozzle column for simultaneous deposition of a liquid reagent into selected reaction wells for synthesis of chemical compounds.

Claim 4

Dependent Claim 61 words

The chemical synthesis apparatus as defined in claim 1 wherein, said nozzle columns move independently relative to said base assembly, along a path substantially parallel to said reaction well columns for moving said nozzle columns to position at least one nozzle column for deposition of a liquid reagent into at least one of said reaction wells for synthesis of chemical compounds.

Claim 5

Dependent Claim 140 words

The chemical synthesis apparatus as defined in claim 1 further comprising: a transport mechanism coupled to said base assembly for moving said head assembly, along a path substantially perpendicular to said nozzle columns to position at least one well column of reaction wells in depository alignment with at least one of said nozzles in a selected nozzle column for simultaneous deposition of a liquid reagent into at least one selected reaction well for synthesis of at least one chemical compound, and a plurality of independently controlled sliders for individual moving support of the nozzle columns along a path substantially parallel to said reaction well columns for moving said nozzle columns to position at least one nozzle of said nozzle columns for deposition of a liquid reagent into at least one of said selected reaction wells for synthesis of chemical compounds.

Claim 6

Dependent Claim 169 words

The chemical synthesis apparatus as defined in claim 4 further comprising: a first sliding seal positioned between said head assembly and said base assembly, and enclosing all said reaction wells and all said nozzles therein to seal a common chamber; and a plurality of second sliding seals positioned between said head assembly and said sliders, and enclosing all said reaction wells and all said nozzles therein to seal a common chamber; each said well additionally having a lower orifice being of a size and dimension to form a capillary liquid seal to retain said deposited liquid reagent in said selected wells to enable chemical compound synthesis therein when a pressure differential between a first gas pressure in said common chamber and a second gas pressure exerted on each lower orifice is less than a predetermined amount; and a pressure regulating device for controlling said pressure differential such that upon said pressure differential exceeding said predetermined amount, said liquid reagent being expelled from respective wells through the respective lower orifices.

Claim 7

Dependent Claim 47 words

The chemical synthesis apparatus as defined in claim 5 wherein, said first sliding seal is provided by a balloon seal having one end affixed to a bottom surface of said head assembly, and an opposite end in sliding contact with a top surface of said base assembly.

Claim 8

Dependent Claim 51 words

The chemical synthesis apparatus as defined in claim 5 wherein, said plurality of second sliding seals are provided by a plurality of balloon seals each having one end affixed to a bottom surface of said sliders and an opposite end in sliding contact with a top surface of said head assembly.

Claim 9

Dependent Claim 34 words

The chemical synthesis apparatus as defined in claim 4 wherein, said transport mechanism includes a stepped motor operably coupled to said base assembly for linear incremental movement of said reactions wells along said path.

Claim 10

Dependent Claim 25 words

The chemical synthesis apparatus as defined in claim 7 wherein, each balloon seal increases its seal integrity as the pressure in the common chamber increases.

Claim 11

Dependent Claim 29 words

The chemical synthesis apparatus as defined in claim 1 wherein, any nozzle in said array of nozzles is positionable in direct depository alignment over any row of reaction wells.

Claim 12

Dependent Claim 59 words

The chemical synthesis apparatus as defined in claim 9 wherein, each nozzle communicates with a reagent reservoir through a tube forming a passageway and having one end coupled to said nozzle and an opposite end terminating in said reagent reservoir, sand each tube includes a valve assembly in-line with said passageway to control passage of the reagent solution therethrough.

Claim 13

Dependent Claim 81 words

The chemical synthesis apparatus as defined in claim 5 wherein, said pressure regulating device includes an inlet into said common chamber positioned upstream from said array of nozzles, an outlet out of said common chamber positioned downstream from said array of nozzles, and a pressurized gas source coupled to said inlet for continuously streaming a gas from said gas source through said common chamber from said inlet to said outlet to sweep said common chamber of fumes emitted by said reagents.

Claim 14

Dependent Claim 51 words

The chemical synthesis apparatus as defined in claim 12 wherein, said pressure regulating device further includes a chamber valve coupled to said outlet controlling outflow of said gas from said chamber for one of raising said pressure differential above said predetermined amount and lowering said pressure differential below said predetermined amount.

Claim 15

Dependent Claim 191 words

A chemical synthesis apparatus for building chemical compounds by sequentially adding chemical units in a liquid reagent, said apparatus comprising: a head assembly having an array of nozzles comprising nozzle rows and nozzle columns, mounted thereto in generally spaced-apart relation, all nozzles being coupled to a different reservoir of liquid reagent for controlled delivery therethrough, said nozzle columns being independently movable, sliders for individual moving support of said nozzle columns; a base assembly having a plurality of reaction wells and including an upper orifice extending into each reaction well, each said reaction well additionally having a lower orifice being of size and dimension to form a capillary liquid seal to retain deposited liquids in said reaction well, the base assembly and the head assembly being movable relative to one another in a first direction, the nozzle columns being movable in a second, perpendicular direction, the relative movement of the head assembly and the base assembly and the movement of the nozzle columns allowing delivery of any liquid reagent to any reaction well, and a plurality of seals positioned between said head assembly and said nozzle columns to form a seal therebetween.

Claim 16

Dependent Claim 191 words

A chemical synthesis apparatus for building chemical compounds by sequentially adding chemical units in a liquid reagent, said apparatus comprising: a head assembly having an array of nozzles comprising nozzle rows and nozzle columns, mounted thereto in generally spaced-apart relation, all nozzles being coupled to a different reservoir of liquid reagent for controlled delivery therethrough, said nozzle columns being independently movable, sliders for individual moving support of said nozzle columns; a base assembly having a plurality of reaction wells and including an upper orifice extending into each reaction well, each said reaction well additionally having a lower orifice being of size and dimension to form a capillary liquid seal to retain deposited liquids in said reaction well, the base assembly and the head assembly being movable relative to one another in a first direction, the nozzle columns being movable in a second, perpendicular direction, the relative movement of the head assembly and the base assembly and the movement of the nozzle columns allowing delivery of any liquid reagent to any reaction well, and a plurality of seals positioned between said head assembly and said nozzle columns to form a seal therebetween.

Claim 17

Dependent Claim 123 words

The chemical synthesis apparatus as defined in claim 14 further comprising: a transport mechanism coupled to at least one of said base assembly and said head assembly to produce relative movement therebetween to position a reaction well and a selected nozzle in alignment for deposition of a liquid reagent into said reaction well for synthesis of a chemical compound; and a plurality of independently controllable sliders for individual moving support of the nozzle columns, relative to said head assembly, along a path substantially parallel to said nozzle columns for moving said nozzle columns to position at least one nozzle of a nozzle column for deposition of a liquid reagent into at least one reaction well for synthesis of one or more chemical compounds.

Claim 18

Dependent Claim 59 words

The chemical synthesis apparatus as defined in claim 14 further comprising: a pressure regulating device for controlling the pressure differential from said upper orifice to said lower orifice of said reaction well such that upon said pressure differential exceeding said predetermined amount, said reagent solution being expelled from said reaction well through said lower orifice of said reaction wells.

Claim 19

Dependent Claim 74 words

The chemical synthesis apparatus as defined in claim 14 further comprising: a first sliding seal positioned between said head assembly and said base assembly, and enclosing all upper orifices of said reaction wells and all said nozzles therein to seal a common chamber; and a plurality of second sliding seals positioned between said head assembly and said sliders, and enclosing all said reaction wells and all said nozzles therein to seal said common chamber.

Claim 20

Dependent Claim 34 words

A chemical synthesis apparatus for building chemical compounds as defined in claim 17, wherein said second sliding seals are balloon seals that increase their seal integrity as the pressure in the common chamber increases.

Claim 21

Dependent Claim 77 words

The chemical synthesis apparatus as defined in claim 16 wherein, said pressure regulating device includes an inlet into said common chamber positioned upstream from said nozzles, and an outlet out of said common chamber positioned downstream from said nozzles, and a pressurized gas source coupled to said inlet for continuously streaming a gas from said gas source through said common chamber from said inlet to said outlet to sweep said chamber of fumes emitted by said reagents.

Claim 22

Dependent Claim 52 words

The chemical synthesis apparatus as defined in claim 19 wherein, said pressure regulating device further includes a chamber valve coupled to said outlet controlling outflow of said gas from said common chamber for one of raising said pressure differential above said predetermined amount and lowering said pressure differential below said predetermined amount.

Claim 23

Dependent Claim 21 words

The chemical synthesis apparatus as defined in claim 19 wherein, said inlet and said outlet are part of said head assembly.

Claim 24

Dependent Claim 102 words

The chemical synthesis apparatus as defined in claim 16 wherein, said base assembly includes a top surface defining said upper orifice of said wells, and an opposite facing bottom surface, each said lower orifice extending from said bottom surface toward said top surface and into a reaction well, and said synthesis apparatus further including: a bottom chamber mechanism cooperating with said base bottom surface to form a bottom chamber enclosing each said lower orifice therein, said pressure regulating device communicating with said bottom chamber to form a vacuum for regulation of said pressure differential from said top surface to said bottom surface.

Claim 25

Dependent Claim 33 words

The chemical synthesis apparatus as defined in claim 14 wherein, any nozzle in said array of nozzles is positionable in direct depository alignment over any reaction well in said array of reaction wells.

Claim 26

Dependent Claim 189 words

A chemical synthesis apparatus for building a chemical compound by sequentially adding chemical units in a reagent solution, said apparatus comprising: a base assembly defining a plurality of reaction wells aligned in an array of spaced-apart reaction well rows and reaction well columns; a head assembly having an array of nozzles aligned in a plurality of nozzle rows and nozzle columns, spaced apart by a distance substantially similar to the spacing between said reaction well rows and reaction well columns for alignment therebetween, said nozzle columns being independently movable to reposition their nozzles over different rows of reaction wells, each nozzle being coupled to one reservoir of a plurality of independent reagent reservoirs each including a different liquid reagent for selective, sequential and controlled delivery to and reaction well in a predetermined manner through a respective nozzle, and a plurality of sliders for individual moving support of said nozzle columns, the head assembly and base assembly being relatively movable so that each nozzle can be aligned with any reaction well, and a plurality of seals positioned between said head assembly and said nozzle columns to form a seal therebetween.

Claim 27

Dependent Claim 189 words

A chemical synthesis apparatus for building a chemical compound by sequentially adding chemical units in a reagent solution, said apparatus comprising: a base assembly defining a plurality of reaction wells aligned in an array of spaced-apart reaction well rows and reaction well columns; a head assembly having an array of nozzles aligned in a plurality of nozzle rows and nozzle columns, spaced apart by a distance substantially similar to the spacing between said reaction well rows and reaction well columns for alignment therebetween, said nozzle columns being independently movable to reposition their nozzles over different rows of reaction wells, each nozzle being coupled to one reservoir of a plurality of independent reagent reservoirs each including a different liquid reagent for selective, sequential and controlled delivery to and reaction well in a predetermined manner through a respective nozzle, and a plurality of sliders for individual moving support of said nozzle columns, the head assembly and base assembly being relatively movable so that each nozzle can be aligned with any reaction well, and a plurality of seals positioned between said head assembly and said nozzle columns to form a seal therebetween.

Claim 28

Dependent Claim 71 words

The chemical synthesis apparatus as defined in claim 24 further comprising: a transport mechanism coupled to at least one of said head assembly and said base assembly to produce relative movement substantially perpendicular to said nozzle columns to align any one selected nozzle with any one reaction well for deposition of a liquid reagent into said one reaction well for synthesis of a chemical compound using any of the liquid reagents.

Claim 29

Dependent Claim 55 words

The chemical synthesis apparatus as defined in claim 24 wherein: the sliders are coupled to said nozzle columns for movement substantially perpendicular to said reaction well rows to align any one selected nozzle with any one reaction well for deposition of a liquid reagent into said one reaction well for synthesis of a chemical compound.

Claim 30

Dependent Claim 153 words

The chemical synthesis apparatus as defined in claim 24 further comprising: a first sliding seal positioned between said head assembly and said base assembly, and enclosing all said reaction wells and all said nozzles therein to seal a common chamber; a plurality of second sliding seals positioned between said head assembly and said sliders, and enclosing all said reaction wells and all said nozzles therein to seal said common chamber; and each reaction well including at least one respective orifice extending into a respective well, each orifice having an entrance into said well and an exit, said exit being of a size and dimension to form a capillary liquid seal to retain the deposited liquid reagent in selected wells to enable chemical compound synthesis therein when a pressure differential between a first gas pressure in said chamber and a second gas pressure exerted at each orifice exit is less than a predetermined amount.

Claim 31

Dependent Claim 27 words

The chemical synthesis apparatus as defined in claim 24 wherein, any nozzle in said array of nozzles is positionable in direct depository alignment over any reaction well.

Claim 32

Dependent Claim 44 words

The chemical synthesis apparatus as defined in claim 27 further including, a pressure regulating device for controlling said pressure differential such that upon said pressure differential exceeding said predetermined amount, said reagent solution is expelled from said well through the exit of said orifice.

Claim 33

Dependent Claim 86 words

The chemical synthesis apparatus as defined in claim 29 wherein, said pressure regulating device includes an inlet into said common chamber positioned upstream from said array of nozzles, an outlet out of said common chamber positioned downstream from said array of nozzles, and a pressure gas source coupled to said inlet for continuously streaming a gas from said gas source through said common chamber from said chamber inlet to said chamber outlet and out said outlet to sweep said chamber of fumes emitted by said reagents.

Claim 34

Dependent Claim 51 words

The chemical synthesis apparatus as defined in claim 30 wherein, said pressure regulating device further includes a chamber valve coupled to said outlet controlling outflow of said gas from said chamber for one of raising said pressure differential above said predetermined amount and lowering said pressure differential below said predetermined amount.

Claim 35

Dependent Claim 21 words

The chemical synthesis apparatus as defined in claim 31 wherein, said inlet and said outlet are defined by said head assembly.

Claim 36

Dependent Claim 40 words

The chemical synthesis apparatus as defined in claim 32 wherein, said inlet is provided by an inlet slot extending substantially transversely across said common chamber such that said continuous stream is substantially laminar during passage by said array of nozzles.

Claim 37

Dependent Claim 29 words

The chemical synthesis apparatus as defined in claim 27 wherein, said second sliding seals are balloon seals that increase their seal integrity as pressure in the common chamber increases.

Claim 38

Dependent Claim 130 words

A chemical synthesis apparatus for building chemical compounds by sequentially adding chemical units in a liquid reagent, said apparatus comprising: a head assembly having a substantially planar bottom surface and an array of nozzles comprising nozzle rows and nozzle columns, mounted thereto in generally spaced-apart relation, said nozzle columns being independently movable, all nozzles being coupled to a different reservoir of liquid reagent, and having a nozzle tip portion formed and dimensioned for controlled droplet formation and delivery in a substantially vertical direction therethrough; a base assembly having a plurality of reaction wells, the base assembly and head assembly being relatively movable to reposition columns of nozzles over different reaction wells, and a plurality of seals positioned between said head assembly and said nozzle columns to form a seal therebetween.

Claim 39

Dependent Claim 130 words

A chemical synthesis apparatus for building chemical compounds by sequentially adding chemical units in a liquid reagent, said apparatus comprising: a head assembly having a substantially planar bottom surface and an array of nozzles comprising nozzle rows and nozzle columns, mounted thereto in generally spaced-apart relation, said nozzle columns being independently movable, all nozzles being coupled to a different reservoir of liquid reagent, and having a nozzle tip portion formed and dimensioned for controlled droplet formation and delivery in a substantially vertical direction therethrough; a base assembly having a plurality of reaction wells, the base assembly and head assembly being relatively movable to reposition columns of nozzles over different reaction wells, and a plurality of seals positioned between said head assembly and said nozzle columns to form a seal therebetween.

Claim 40

Dependent Claim 118 words

The chemical synthesis apparatus as defined in claim 35 further comprising: a transport mechanism coupled to at least one of said base assembly and said head assembly to produce relative movement therebetween to position a reaction well and a selected one nozzle in alignment for deposition of a liquid reagent into said reaction wells for synthesis of a chemical compound; and a plurality of independently controllable sliders for individual moving support, relative said head assembly, along a path substantially parallel to said nozzle columns for moving said nozzle columns to position at least one nozzle of said nozzle columns for deposition of a liquid reagent into at least one of said reaction wells for synthesis of chemical compounds.

Claim 41

Dependent Claim 80 words

The chemical synthesis apparatus as defined in claim 35 further comprising: a first sliding seal positioned between said head assembly bottom surface and said base assembly to form a common chamber for enclosing both said reaction wells and said nozzles therein; sliders for individual moving support of said nozzle columns; and a plurality of second sliding seals positioned between said head assembly and said sliders to form a common chamber for enclosing both said reaction well and said nozzles therein.

Claim 42

Dependent Claim 28 words

The chemical synthesis apparatus as defined in claim 35 wherein, any nozzle in said array of moveable nozzles is positionable in direct depository alignment over any reaction well.

Claim 43

Dependent Claim 29 words

The chemical synthesis apparatus as defined in claim 37 wherein, said second sliding seals are balloon seals that increase their seal integrity as pressure increases in the common chamber.

Claim 44

Dependent Claim 154 words

The chemical synthesis apparatus as defined in claim 37 wherein, each said nozzle tip portion extends past the bottom surface of said head assembly partially defining said common chamber, and terminates at a position such that said nozzle tip portion is free of contact with said head assembly to substantially prevent contact of said liquid reagent with said head assembly during said droplet formation and delivery, the distal end of each nozzle is positioned proximate the substantially planar bottom surface of said head assembly, and said base assembly includes a substantially planar top surface in opposed relation to said head assembly bottom surface, and said first sliding seal is provided by a balloon seal having one end affixed to one of said head assembly bottom surface and said base assembly top surface, and an opposite end in sliding contact with the other of said base assembly top surface and said head assembly bottom surface.

Claim 45

Dependent Claim 59 words

The chemical synthesis apparatus as defined in claim 40 wherein, said opposite end tapers radially inwardly toward an interior portion of said chamber in a manner such that upon increase in pressure in said chamber, the balloon seal integrity between said opposite end and the other of said base assembly top surface and said head assembly bottom surface increases.

Claim 46

Dependent Claim 39 words

The chemical synthesis apparatus as defined in claim 41 wherein, said balloon seal of one end is mounted to said base assembly bottom surface, and said seal opposite end is in sliding contact with said base assembly top surface.

Claim 47

Dependent Claim 38 words

The chemical synthesis apparatus as defined in claim 40 wherein, said opposite end includes a substantially stick-free coating or layer in sliding contact with the other of said base assembly top surface and said head assembly bottom surface.

Claim 48

Dependent Claim 17 words

The chemical synthesis apparatus as defined in claim 43 wherein, said coating or layer comprises polyfluoroolefin resin.

Claim 49

Dependent Claim 40 words

The chemical synthesis apparatus as defined in claim 40 wherein, the other of said base assembly top surface and said head assembly bottom surface is in sliding contact with said opposite end including a substantially stick-free coating or layer therebetween.

Claim 50

Dependent Claim 17 words

The chemical synthesis apparatus as defined in claim 45 wherein, said coating or layer comprises polyfluoroolefin resin.

Claim 51

Dependent Claim 38 words

The chemical synthesis apparatus as defined in claim 39 wherein, the bottom surface of said head assembly includes at least one slot defined by said lower surface upon which each said nozzles tip portions terminate and extend into.

Claim 52

Dependent Claim 33 words

The chemical synthesis apparatus as defined in claim 36 wherein, said transport mechanism includes a stepped motor operably coupled to one of the head assembly and the base assembly for incremental movement thereof.

Claim 53

Dependent Claim 23 words

The chemical synthesis apparatus as defined in claim 36 wherein, said transport mechanism is operably coupled to said base assembly for movement thereof.

Claim 54

Dependent Claim 31 words

The chemical synthesis apparatus as defined in claim 49 wherein, said transport mechanism includes a stepped motor operably coupled to the base assembly for incremental substantially linear movement relative said nozzles.

Claim 55

Dependent Claim 80 words

The chemical synthesis apparatus as defined in claim 37 wherein, each well having an entrance into said well and an exit, said exit being a lower orifice of a size and dimension to form a capillary liquid seal to retain said liquid reagent in said well to enable chemical compound synthesis therein when a pressure differential between a first gas pressure in said common chamber and a second gas pressure exerted on said exit is less than a predetermined amount.

Claim 56

Dependent Claim 41 words

The chemical synthesis apparatus as defined in claim 51, further including, a pressure regulating device for controlling said pressure differential such that upon said pressure differential exceeding said predetermined amount, said reagent solution is expelled from said well through said exit.

Claim 57

Dependent Claim 76 words

The chemical synthesis apparatus as defined in claim 52 wherein, at least one solid support disposed in said well for synthesizing and immobilizing said chemical compound thereon; said liquid reagent in said well in contact with said solid support and at least one chemical unit of said chemical compound affixed to said solid support; and a retainer assembly positioned in said well, and formed and dimensioned to substantially prevent passage of solid support through said orifice.

Claim 58

Dependent Claim 29 words

The chemical synthesis apparatus as defined in claim 53 wherein, said retainer assembly comprises a filter member disposed in said well between said one orifice and said solid support.

Claim 59

Dependent Claim 68 words

The chemical synthesis apparatus as defined in claim 52 wherein, said pressure regulating device includes an inlet into said common chamber positioned upstream from said nozzles, an outlet out of said common chamber positioned downstream from said nozzles, and a pressurized gas source coupled to said inlet for continuously streaming a gas from said inlet to said outlet to sweep said chamber of fumes emitted by said reagents.

Claim 60

Dependent Claim 51 words

The chemical synthesis apparatus as defined in claim 55 wherein, said pressure regulating device further includes a chamber valve coupled to said outlet controlling outflow of said gas from said chamber for one of raising said pressure differential above said predetermined amount and lowering said pressure differential below said predetermined amount.

Claim 61

Dependent Claim 21 words

The chemical synthesis apparatus as defined in claim 55 wherein, said inlet and said outlet are defined by said head assembly.

Claim 62

Dependent Claim 91 words

The chemical synthesis apparatus as defined in claim 52 wherein, said base assembly and a bottom surface defining said well, and an opposite facing bottom surface, said lower orifice extending from said bottom surface and an under orifice extending from said top surface into said well, and said synthesis apparatus further including: a bottom chamber mechanism cooperating with said base bottom surface to form a bottom chamber enclosing said lower orifice therein, said pressure regulating device communicating with said bottom chamber to form a vacuum for regulation of said pressure differential.

Claim 63

Dependent Claim 91 words

The chemical synthesis apparatus as defined in claim 37 wherein, each of said nozzles terminates proximate a substantially planar bottom surface of said head assembly, said base assembly includes a substantially planar top surface in opposed relation to said head bottom surface, and said first sliding seal is provided by a balloon seal having one end affixed to one of said head bottom surface and said base top surface, and an opposite end in sliding contact with the other of said base assembly top surface and said head assembly bottom surface.

Claim 64

Dependent Claim 59 words

The chemical synthesis apparatus as defined in claim 59 wherein, said opposite end appears radially inwardly toward an interior portion of said chamber in a manner such that upon an increase in pressure in said chamber, the seal integrity between said opposite end and the other of said base assembly top surface and said head assembly bottom surface increases.

Claim 65

Dependent Claim 96 words

The chemical synthesis apparatus as defined in claim 37 wherein, said reservoir, coupled to each said nozzle, comprises a plurality of independent reagent reservoirs each including a different reagent to be selectively and sequentially deposited in said well in a predetermined manner through a respective nozzle, and a transport mechanism coupled to at least one of said base assembly and said head assembly to produce relative movement therebetween to position a reaction well and a selected one nozzle in alignment for deposition of a liquid reagent into said reaction wells for synthesis of a chemical compound.

Claim 66

Dependent Claim 40 words

The chemical synthesis apparatus as defined in claim 61 wherein, said transport mechanism includes a stepped motor operably coupled to said base assembly for incremental movement and alignment of said wells with said nozzles for deposition of the selected reagent.

Claim 67

Dependent Claim 45 words

The chemical synthesis apparatus as defined in claim 61 wherein, each nozzle communicates with a different reservoir through a tube having a passageway communicably coupled therebetween, and each tube includes a valve assembly in-line with said passageway to control passage of the liquid reagent therethrough.

Claim 68

Dependent Claim 42 words

The chemical synthesis apparatus as defined in claim 63 wherein, a controller assembly operably coupled to said transport mechanism and each valve assembly for controlled sequential movement of said wells relative each said nozzle and for deposition of said reagent solution therein.

Claim 69

Dependent Claim 68 words

The chemical synthesis apparatus as defined in claim 61 wherein, including an inlet into said common chamber positioned upstream from said nozzles; an outlet out of said common chamber positioned downstream from said nozzles; and a pressurized gas source coupled to said inlet for continuously streaming a gas through a common chamber from said inlet to said outlet to sweep said chamber of fumes emitted by said reagents.

Claim 70

Dependent Claim 36 words

The chemical synthesis apparatus as defined in claim 65 wherein, said inlet is positioned upstream of said nozzles by a sufficient distance such that said streaming through said common chamber is substantially laminar during passage thereby.

Claim 71

Dependent Claim 34 words

The chemical synthesis apparatus as defined in claim 66 wherein, said independent reagent reservoirs are coupled to said nozzles in a manner aligning said reagents with increasing toxicity from said inlet to said outlet.

Claim 72

Dependent Claim 31 words

The chemical synthesis apparatus as defined in claim 35 wherein, a droplet of said liquid reagent expelled from any of said nozzles can be directed gravitationally to any of said wells.

Claim 73

Dependent Claim 40 words

The chemical synthesis apparatus as defined in claim 35 wherein, each said tip portion having a sufficient transverse cross-sectional dimension cooperating with a predetermined quantity of liquid reagent collected at said tip to produce said controlled droplet formation and delivery.

Claim 74

Dependent Claim 38 words

The chemical synthesis apparatus as defined in claim 37 wherein, said base assembly including a plurality of wells closely aligned in an array, and said first sliding seal enclosing said wells and said nozzles in said common chamber.

Claim 75

Dependent Claim 74 words

The chemical synthesis apparatus as defined in claim 70 wherein, said array is provided by a plurality of spaced-apart reaction well rows and reaction well columns, and said nozzles are aligned in an array having nozzle rows and nozzle columns spaced-apart by a distance substantially similar to the spacing between said spaced-apart reaction well rows and reaction well columns for alignment therebetween such that selected reaction wells may have simultaneously deposited therein selected reagent.

Claim 76

Dependent Claim 78 words

The chemical synthesis apparatus as defined in claim 36 wherein, said transport mechanism is formed to align any one nozzle with any one reaction well for simultaneous delivery of selected reagents from selected nozzles into selected reaction wells, and includes a stepped motor operably coupled to said base assembly for linear incremental movement of said wells along a path substantially perpendicular with said plurality of well columns for alignment with respective nozzles for deposition of the selected reagent.

Claim 77

Dependent Claim 22 words

The chemical synthesis apparatus as defined in claim 71 wherein, respective nozzles of each nozzle row are coupled to one reagent reservoir.

Claim 78

Dependent Claim 62 words

The chemical synthesis apparatus as defined in claim 71 wherein, each nozzle communicates with said different reservoir through a tube forming a passageway and having one end coupled to said nozzle and an opposite end terminating in one or more independent reagent reservoirs and each tube includes a valve assembly in-line with said passageway to control passage of the reagent solution therethrough.

Claim 79

Dependent Claim 32 words

The chemical synthesis apparatus as defined in claim 74 wherein, each of said independent reagent reservoirs contains a liquid reagent and is pressurized to expel said liquid reagent therefrom through respective tubes.

Claim 80

Dependent Claim 43 words

The chemical synthesis apparatus as defined in claim 74 wherein, a controller assembly operably coupled to said transport mechanism and each valve assembly for controlled sequential movement of said reaction wells relative each said nozzle and for deposition of said reagent solution therein.

Claim 81

Dependent Claim 99 words

The chemical synthesis apparatus as define in claim 71 wherein, said base assembly includes an array of reaction wells with at least one orifice extending into each reaction well, each orifice having an entrance into said reaction well and an exit, said exit being of a size and dimension to form a capillary liquid seal to retain deposited liquid reagent in selected reaction wells to enable chemical compound synthesis therein when a pressure differential between a first gas pressure in said common chamber and a second gas pressure exerted at each orifice exit is less than a predetermined amount.

Claim 82

Dependent Claim 40 words

The chemical synthesis apparatus as defined in claim 77 wherein, a pressure regulating device for controlling said pressure differential such that upon said pressure differential exceeding said predetermined amount, said reagent solution being expelled from said well through said orifice.

Claim 83

Dependent Claim 80 words

The chemical synthesis apparatus as defined in claim 78 wherein, said pressure regulating device includes an inlet into said common chamber positioned upstream from said array of nozzles, an outlet out of said common chamber positioned downstream from said array of nozzles, and a pressurized gas source coupled to said inlet for continuously streaming a gas from said gas source through said common chamber from said inlet to said outlet to sweep said chamber of fumes emitted by said reagents.

Claim 84

Dependent Claim 52 words

The chemical synthesis apparatus as defined in claim 79 wherein, said pressure regulating device further includes a chamber valve coupled to said outlet controlling outflow and said gas from said common chamber for one of raising said pressure differential above said predetermined amount and lowering said pressure differential below said predetermined amount.

Claim 85

Dependent Claim 21 words

The chemical synthesis apparatus as defined in claim 80 wherein, said inlet and said outlet are defined by said head assembly.

Claim 86

Dependent Claim 40 words

The chemical synthesis apparatus as defined in claim 81 wherein, said inlet is provided by an inlet slot extending substantially transversely across said common chamber such that said continuous stream is substantially laminar during passage by said array of nozzles.

Claim 87

Dependent Claim 25 words

The chemical synthesis apparatus as defined in claim 82 wherein, said outlet is provided by an outlet slot extending substantially transversely across said common chamber.

Claim 88

Dependent Claim 41 words

The chemical synthesis apparatus as defined in claim 36 wherein, a frame assembly upon which said head assembly is pivotally mounted between a closed position, sealing said common chamber and an open position, permitting access to said nozzles and said wells.

Claim 89

Dependent Claim 52 words

The chemical synthesis apparatus as defined in claim 84 wherein, said base assembly is movable mounted to said frame assembly, and said transport mechanism includes a stepped motor operably coupled to said base assembly for incremental movement and alignment of said well with said respective nozzle for deposition of the selected reagent.

Claim 90

Independent Claim 357 words

A method of synthesis of a chemical compound in a synthesis apparatus by sequentially adding chemical units thereto, said synthesis apparatus including a head assembly having a plurality of nozzles mounted thereto in generally spaced-apart relation, each nozzle being coupled to a reservoir of liquid reagent for controlled delivery therethrough, a base assembly having a plurality of reaction wells, a sliding seal positioned between said head assembly and said base assembly to permit relative movement therebetween, and enclosing both said reaction well and said nozzles therein to form a common chamber, and a second sliding seal positioned between the nozzles and the head assembly, said method comprising the steps of: A) aligning a reaction well and a selected one nozzle in a lateral X-direction through a transport mechanism coupled to at least one of said head assembly and said base assembly to produce relative movement therebetween; B) aligning said reaction well and a selected one nozzle in a longitudinal Y-direction through a moveable slider holding said selected one nozzle, and coupled to said head assembly to produce relative motion between said slider and said head assembly; C) depositing a liquid reagent into said well from said reagent reservoir through said one nozzle to enable synthesis of a chemical compound; and D) purging gaseous fumes or reaction by-products, emitted by said reagents, from said common chamber through passage of a gas from a pressurized gas source, coupled to an inlet into said common chamber and positioned upstream from said nozzles, and out of said chamber through an outlet out from said common chamber and positioned downstream from said nozzles, E) expelling said deposited liquid reagent from said well through an exit orifice of said well by applying a first gas pressure to said common chamber such that a pressure differential between said first gas pressure and second gas pressure exerted on said exit of said orifice exceeds a predetermined amount necessary to overcome a capillary liquid seal formed between said liquid reagent and orifice to retain said liquid reagent in said well, and F) repeating steps A-E to form at least one chemical compound from various chemical units.

Claim 91

Independent Claim 357 words

A method of synthesis of a chemical compound in a synthesis apparatus by sequentially adding chemical units thereto, said synthesis apparatus including a head assembly having a plurality of nozzles mounted thereto in generally spaced-apart relation, each nozzle being coupled to a reservoir of liquid reagent for controlled delivery therethrough, a base assembly having a plurality of reaction wells, a sliding seal positioned between said head assembly and said base assembly to permit relative movement therebetween, and enclosing both said reaction well and said nozzles therein to form a common chamber, and a second sliding seal positioned between the nozzles and the head assembly, said method comprising the steps of: A) aligning a reaction well and a selected one nozzle in a lateral X-direction through a transport mechanism coupled to at least one of said head assembly and said base assembly to produce relative movement therebetween; B) aligning said reaction well and a selected one nozzle in a longitudinal Y-direction through a moveable slider holding said selected one nozzle, and coupled to said head assembly to produce relative motion between said slider and said head assembly; C) depositing a liquid reagent into said well from said reagent reservoir through said one nozzle to enable synthesis of a chemical compound; and D) purging gaseous fumes or reaction by-products, emitted by said reagents, from said common chamber through passage of a gas from a pressurized gas source, coupled to an inlet into said common chamber and positioned upstream from said nozzles, and out of said chamber through an outlet out from said common chamber and positioned downstream from said nozzles, E) expelling said deposited liquid reagent from said well through an exit orifice of said well by applying a first gas pressure to said common chamber such that a pressure differential between said first gas pressure and second gas pressure exerted on said exit of said orifice exceeds a predetermined amount necessary to overcome a capillary liquid seal formed between said liquid reagent and orifice to retain said liquid reagent in said well, and F) repeating steps A-E to form at least one chemical compound from various chemical units.

Claim 92

Dependent Claim 39 words

The method of synthesis of chemical compounds as described in claim 86 wherein, said expelling step is accomplished by controlling out flow of said gas through said outlet to increase said pressure, to a degree exceeding said predetermined amount.

Claim 93

Dependent Claim 36 words

The method of synthesis of chemical compounds as described in claim 87 wherein, said controlling out flow is accomplished by a chamber valve coupled to said chamber outlet for control of passage of said gas therethrough.

Claim 94

Dependent Claim 40 words

The method of synthesis of chemical compounds as described in claim 86 wherein, steps A-C are repeated before the carrying out of purging step D, enabling a plurality of liquid reagents to simultaneously react in at least one reaction well.

Claim 95

Dependent Claim 43 words

The method of synthesis of chemical compounds as described in claim 86 wherein, said chemical compound is synthesized by the sequential addition of chemical units to at least one solid support for synthesizing and immobilizing a chemical compound thereon in a liquid reagent.

Claim 96

Dependent Claim 43 words

The method of synthesis of chemical compounds as described in claim 89 wherein, said chemical compound is synthesized by the sequential addition of chemical units to at least one solid support for synthesizing and immobilizing a chemical compound thereon in a liquid reagent.

Claim 97

Dependent Claim 25 words

The method of synthesis of chemical compounds as described in claim 90 wherein, said at least one solid support comprises at least one glass bead.

Claim 98

Dependent Claim 35 words

The method of synthesis of chemical compounds as described in claim 90 further comprising the step of: E) transferring from at least one reaction well at least one solid support to a different reaction well.

Claim 99

Dependent Claim 29 words

The method of synthesis of chemical compounds as described in claim 93 further comprising the step of: F) repeating steps A-E to form chemical compounds from various chemical units.

Claim 100

Dependent Claim 31 words

The method of synthesis of chemical compounds as described in claim 86 wherein, the integrity of the second sliding seal is increased by an increase in pressure in the common chamber.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2002-12-13	2003-06-14	2003-12-14	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2006-12-13	2007-06-14	2007-12-14	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2010-12-13	2011-06-14	2011-12-14	$7700.00	Window Closed / Lapsed

Apparatus for diverse chemical synthesis using two-dimensional array

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