U.S. patent application number 10/882757 was filed with the patent office on 2004-12-02 for apparatus and methods for parallel processing of multiple reaction mixtures.
This patent application is currently assigned to Symyx Technologies, Inc.. Invention is credited to Chandler, William H. JR., Dales, G. Cameron, Diamond, Gary M., Frank, Trevor G., Freitag, J. Christopher, Higashihara, Kenneth S., Murphy, Vince, Troth, Jonah R..
Application Number | 20040241875 10/882757 |
Document ID | / |
Family ID | 25093920 |
Filed Date | 2004-12-02 |
United States Patent
Application |
20040241875 |
Kind Code |
A1 |
Dales, G. Cameron ; et
al. |
December 2, 2004 |
Apparatus and methods for parallel processing of multiple reaction
mixtures
Abstract
A parallel reactor system including a reactor and vessels in the
reactor for holding reaction mixtures, and a cannula for
introducing fluid reaction material into the vessels. A robot
system is operable to insert the cannula into cannula passages in
the reactor for delivery of reaction materials, including slurries,
to respective vessels, and to withdraw the cannula from the cannula
passages after delivery. Related methods are also disclosed.
Inventors: |
Dales, G. Cameron; (Palo
Alto, CA) ; Troth, Jonah R.; (Mountain View, CA)
; Higashihara, Kenneth S.; (Mountain View, CA) ;
Diamond, Gary M.; (San Jose, CA) ; Murphy, Vince;
(Campbell, CA) ; Chandler, William H. JR.;
(Milpitas, CA) ; Frank, Trevor G.; (Fremont,
CA) ; Freitag, J. Christopher; (Santa Clara,
CA) |
Correspondence
Address: |
SENNIGER POWERS LEAVITT AND ROEDEL
ONE METROPOLITAN SQUARE
16TH FLOOR
ST LOUIS
MO
63102
US
|
Assignee: |
Symyx Technologies, Inc.
|
Family ID: |
25093920 |
Appl. No.: |
10/882757 |
Filed: |
June 30, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10882757 |
Jun 30, 2004 |
|
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09772101 |
Jan 26, 2001 |
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6759014 |
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Current U.S.
Class: |
506/33 ; 422/400;
436/180 |
Current CPC
Class: |
B01J 2219/00308
20130101; B01J 19/0046 20130101; B01J 2219/00691 20130101; C40B
60/14 20130101; Y10T 436/2575 20150115; B01J 2219/00596 20130101;
C40B 40/14 20130101; B01J 2219/00585 20130101; G01N 35/0099
20130101; B01J 2219/00373 20130101; B01J 2219/00481 20130101; G01N
35/1079 20130101; G01N 2035/0406 20130101; B01J 2219/00497
20130101; B01J 2219/00466 20130101; G01N 35/1004 20130101; B01J
2219/00283 20130101; B01J 2219/00722 20130101 |
Class at
Publication: |
436/180 ;
422/100 |
International
Class: |
G01N 001/10 |
Claims
What is claimed is:
1. A method of preparing and delivering a slurry into a series of
vessels, said method comprising: (1) mixing a particulate solid
material and a liquid dispersing medium and agitating the mixture
to form a substantially homogeneous first slurry in which said
particulate solid material is suspended in the liquid; (2)
aspirating the slurry into a cannula carried by a robot system
while the slurry is substantially homogeneous; (3) operating the
robot system to insert the cannula into a vessel; (4) delivering
the slurry from the cannula into the vessel while the cannula is in
said vessel; and (5) repeating (2)-(4) for a second vessel with
said first slurry or repeating (2)-(4) for a second vessel with a
second slurry.
2. A method as set forth in claim 1 wherein said aspirating occurs
during said agitating.
3. A method as set forth in claim 1 wherein said slurry is
delivered to said vessel while the slurry is still substantially
homogenous.
4. A method as set forth in claim 3 wherein said slurry is
delivered to said vessel within 60 seconds of said aspirating.
5. A method as set forth in claim 1 wherein said agitating is
accomplished by vortexing.
6. A method as set forth in claim 1 further comprising aspirating a
barrier liquid into said cannula after aspirating said slurry and
before delivering said slurry.
7. A method as set forth in claim 1 wherein at least one of said
slurries comprises a catalyst.
8. A method as set forth in claim 7 wherein said catalyst is
supported on said particulate solid material.
9. A method as set forth in claim 1 wherein at least one of said
slurries is prepared less than 90 minutes before delivery to said
vessel.
10. A method as set forth in claim 9 wherein at least one of said
slurries is prepared not more than 45 minutes before delivery to
said vessel.
11. A method as set forth in claim 10 wherein at least one of said
slurries is prepared not more than 10 minutes before delivery to
said vessel.
12. A method as set forth in claim 11 wherein at least one of said
slurries is prepared not more than 5 minutes before delivery to
said vessel.
13. A method as set forth in claim 12 wherein at least one of said
slurries is prepared not more than 1 minute before delivery to said
vessel.
14. A method as set forth in claim 13 wherein at least one of said
slurries is prepared not more than 30 seconds before delivery to
said vessel.
15. A method as set forth in claim 1 wherein at least one of said
vessels into which one of said slurries is delivered is
pressurized.
16. A method as set forth in claim 15 wherein said one of said
slurries is delivered at a pressure of up to 500 psig or
greater.
17. A method as set forth in claim 1 wherein said first and second
slurries are of different composition.
18. A method as set forth in claim 1 further comprising controlling
at least two of said mixing, agitating, aspirating, operating, and
delivering with a system processor.
19. A method as set forth in claim 1 further comprising controlling
said mixing, agitating, aspirating, operating, and delivering with
said system processor.
20. A method of processing mixtures in a series of vessels, said
method comprising: (1) mixing a particulate solid material and a
liquid dispersing medium and agitating the mixture to form a
substantially homogeneous first slurry in which said particulate
solid material is suspended in the liquid; (2) aspirating the
slurry into a cannula carried by a robot system while the slurry is
substantially homogeneous; (3) operating the robot system to insert
the cannula into a vessel; (4) delivering the slurry from the
cannula into the vessel while the cannula is in said vessel; (5)
repeating (2)-(4) for a second vessel with said first slurry or
repeating (2)-(4) for a second vessel with a second slurry; and (6)
processing mixtures comprising said slurries in said vessels.
21. A method as set forth in claim 20 wherein at least one of said
slurries comprises a catalyst for catalyzing a reaction of reaction
materials in said mixtures and said processing comprises reacting
said reaction materials.
22. A method as set forth in claim 21 wherein said reaction
comprises a polymerization reaction.
23. A method as set forth in claim 22 further comprising evaluating
catalyst performance of said catalyst.
24. A method as set forth in claim 20 further comprising
controlling at least two of said mixing, agitating, aspirating,
operating, delivering, and processing with a system processor.
25. A method as set forth in claim 24 further comprising
controlling said mixing, agitating, aspirating, operating,
delivering, and processing with said system processor.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of U.S. patent
application Ser. No. 09/772,101, filed Jan. 26, 2001, the entire
text of which is hereby incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention relates generally to parallel
reactors, and in particular, to parallel research reactors suitable
for use in a combinatorial (i.e., high-throughput) science research
program in which chemical reactions are conducted simultaneously
using small volumes of reaction materials to efficiently and
economically screen large libraries of chemical materials.
[0003] The present invention is related to co-owned International
Application No. PCT/US 99/18358, filed Aug. 12, 1999 by Turner et
al., entitled Parallel Reactor with Internal Sensing and Method of
Using Same, published Feb. 24, 2000 (International Publication No.
WO 00/09255), and which is incorporated herein by reference for all
purposes. This PCT application claims priority from the following
co-owned, co-pending U.S. applications bearing the same title, all
of which are also incorporated by reference: Ser. No. 09/211,982,
filed Dec. 14, 1998 by Turner et al. and Ser. No. 09/177,170, filed
Oct. 22, 1998 by Dales et al., claiming the benefit of provisional
application Ser. No. 60/096,603, filed Aug. 13, 1998 by Dales et
al. The present invention is also related to co-owned, co-pending
U.S. application Ser. No. 09/548,848, filed Apr. 13, 2000 by Turner
et al., entitled Parallel Reactor with Internal Sensing and Method
of Using Same, claiming priority from the aforementioned PCT
application; U.S. application Ser. No. 09/239,223, filed Jan. 29,
1999 by Wang et al., entitled Analysis and Control of Parallel
Chemical Reactions; U.S. Application Ser. No. 60/209,142, filed
Jun. 2, 2000, by Nielsen et al., entitled Parallel Semicontinuous
or Continuous Stirred Reactors; and U.S. Application Ser. No.
60/255,716, filed Dec. 14, 2000, by Nielsen et al., entitled
Parallel Semicontinuous Stirred Reactors, all of which are hereby
incorporated by reference for all purposes. These applications
disclose a number of embodiments for parallel research reactors
suitable for use, for example, in combinatorial chemistry
applications such as polymer research and catalyst research.
However, these embodiments are not especially suited for processing
certain slurry materials, such as those containing small particle
solids (e.g., silica or alumina particles used as catalyst
supports) which can cause excessive wear and/or impede proper
operation of reactor equipment, or slurries having aggressive
bonding characteristics, which may make them difficult to handle
and to clean from reactor equipment. There is a need, therefore,
for a system capable of handling such materials.
SUMMARY OF THE INVENTION
[0004] In view of the foregoing, the objectives of this invention
include the provision of a parallel reactor and related methods
which overcome deficiencies of known parallel reactors, especially
parallel research reactors and methods; the provision of such a
parallel reactor and methods which allow for the efficient handling
of slurry reactant materials, including slurries containing small
particles of solid material, such as silica, and slurries which are
especially "sticky" and thus difficult to handle; the provision of
such a reactor and methods which provide for the delivery of
precise quantities of reactant products, including slurries, to the
reaction vessels of a parallel reactor; and the provision of such a
reactor and methods which provide for the delivery of slurry and
other reaction materials under pressure and/or temperature to one
or more reaction chambers of the reactor.
[0005] In general, apparatus of the present invention is operable
for processing multiple reaction mixtures in parallel. In one
aspect, the apparatus comprises a reactor having an exterior
surface, and vessels in the reactor for holding the reaction
mixtures, each vessel having a central longitudinal axis. A cannula
is used for introducing fluid reaction material into the vessels.
The cannula has a longitudinal axis, a distal end, and a port
generally adjacent said distal end for delivery of reaction
material from the cannula. Cannula passages in the reactor extend
between the exterior surface of the reactor and the vessels. Each
passage extends at an angle relative to the central longitudinal
axis of a respective vessel. A robot system is operable to insert
the cannula through a selected cannula passage and into a
respective vessel for the delivery of the reaction material from
the cannula to the respective vessel, and to withdraw the cannula
from the selected cannula passage and respective vessel.
[0006] Another aspect of the present invention involves a method of
loading fluid reaction material into a series of vessels in a
reactor, each vessel having a central longitudinal axis. The method
comprises, in sequence, (1) inserting a cannula through a cannula
passage in the reactor to a position in which the cannula extends
at an angle relative to the central longitudinal axis of a first
vessel of the series of vessels, and in which a distal end of the
cannula is disposed in the vessel, (2) delivering a fluid reaction
material from the cannula into the vessel, (3) withdrawing the
cannula from said passage, and repeating 1-3 for a second
vessel.
[0007] The present invention is also directed to a cannula for use
in aspirating reactant materials and delivering such materials to
reaction vessels for the parallel processing of such materials. The
cannula comprises a tubular metal reservoir having a longitudinal
axis, an inside diameter defining a hollow interior for containing
said reactant materials, an outside diameter, a proximal end and a
distal end. The cannula also includes a long straight thin needle
formed from metal tubing and coaxial with the reservoir. The needle
has an outside diameter substantially less than the outside
diameter of the reservoir and an inside diameter defining a flow
passage through the needle. The needle further has a proximal end,
a distal end, and a port adjacent the distal end for aspirating
reactant materials into the needle and delivering reactant
materials from the needle. A metal transition joins the proximal
end of the needle to the distal end of the reservoir so that the
hollow of the interior of the reservoir is in fluid communication
with the flow passage of the needle.
[0008] Another aspect of the present invention involves vessels
designed for placement in a series of vertical cylindric wells in a
parallel reactor of the type having cannula passages extending at
an angle off vertical from an exterior surface of the reactor to
the wells, each cannula passage being adapted for the passage
therethrough of a cannula containing reaction material to be
delivered to a respective vessel. Each vessel has a bottom and a
cylindric side wall extending up from the bottom and terminating in
a rim defining an open upper end of the vessel. The cylindric side
wall has an inside diameter in the range of 0.5-2.5 in. The vessel
has a volume in the range of 5-200 ml. and an overall height in the
range of 1.0-4.0 in., such that when the vessel is placed in a well
of the reactor, the open upper end of the vessel is disposed at an
elevation below the cannula passage where the cannula passage
enters the well and is positioned for entry of the cannula down
through the open upper end of the vessel to a position below the
rim of the vessel for the delivery of reactant materials into the
vessel.
[0009] In yet another aspect, the present invention involves a
method of preparing and delivering a slurry reaction material into
a series of vessels in a reactor. The method comprises (1) mixing a
particulate solid material and a liquid to form a substantially
homogeneous first slurry in which the particulate solid material is
suspended in the liquid, (2) aspirating the first slurry into a
cannula carried by a robot system while the slurry is substantially
homogeneous, (3) operating the robot system to insert the cannula
into the reactor, (4) delivering the slurry from the cannula into
the vessel while the cannula is in said cannula passage, and (5)
repeating 2-4 for a second vessel and optionally a second
slurry.
[0010] Other objects and features will be in part apparent and in
part pointed out hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a perspective of a parallel reactor of the present
invention;
[0012] FIG. 2 is a schematic diagram showing key components of the
reactor for delivering a slurry fluid to a number of reactor
modules;
[0013] FIG. 3 is an enlarged portion of FIG. 1 showing, among other
things, a modular reactor and a robot system for servicing the
reactor;
[0014] FIG. 4 is an enlarged portion of FIG. 3 showing a shaker and
hot and ambient wash towers;
[0015] FIG. 5 is an enlarged portion of FIG. 3 showing several
reactor modules mounted on a series of interconnected carriage
plates:
[0016] FIG. 6 is a perspective of a heated wash tower of the
present invention;
[0017] FIG. 7 is a top view of the heated wash tower;
[0018] FIG. 8 is a vertical section on lines 8--8 of FIG. 7;
[0019] FIG. 9 is a top view of a reactor module showing a cannula
immediately prior to the delivery of fluid to a vessel in the
module;
[0020] FIG. 10 is a vertical section along lines 10--10 of FIG. 9
showing the construction of a reactor module and cannula for
delivering fluid (e.g., in slurry form) to a vessel in the reactor
module;
[0021] FIG. 11 is a vertical section on line 11-11 of FIG. 9 in a
plane through the central axis of the vessel;
[0022] FIGS. 12-14 are sequential views illustrating various steps
in the procedure for delivering fluid to a vessel via the
cannula;
[0023] FIG. 15 is a perspective of key components of the robot
system, showing the cannula in a travel position with the head of
the support in a lowered position down on the needle of the
cannula;
[0024] FIG. 16 is a view similar to FIG. 15 showing the cannula in
a fluid delivery position, with the head of the support in a raised
position up on the needle;
[0025] FIG. 17 is a perspective showing a mechanism for rotating
the right robot arm about its axis, the mechanism being shown in a
flat or non-rotated position;
[0026] FIG. 18 is a view similar to FIG. 17 showing the mechanism
in a rotated position;
[0027] FIG. 19 is a view similar to FIG. 18 but showing the
mechanism as viewed from an opposite end of the mechanism;
[0028] FIG. 20 is a perspective showing a mechanism for rotating
the left robot arm about its axis, the mechanism being shown in a
flat or non-rotated position;
[0029] FIG. 21 is a view similar to FIG. 20 showing the mechanism
in a rotated position;
[0030] FIG. 22 is a view similar to FIG. 20 but showing the
mechanism as viewed from below;
[0031] FIG. 23 is a side elevation of the cannula, with part of the
cannula being shown in section to illustrate details;
[0032] FIG. 23A is an enlarged view showing details of the
construction of the cannula of FIG. 23;
[0033] FIG. 24 is an enlarged view of a port of the cannula;
[0034] FIG. 25 is a section taken on line 25--25 of FIG. 24;
[0035] FIG. 26 is a front elevation of a mount for mounting the
cannula on the robot system, and a support for supporting a needle
of the cannula;
[0036] FIG. 27 is a vertical section taken on lines 27--27 of FIG.
26; and
[0037] FIG. 28 is an enlarged portion of FIG. 27 showing a head of
the support.
[0038] Corresponding parts are designated by corresponding
references numbers throughout the drawings.
DESCRIPTION OF PREFERRED EMBODIMENTS
[0039] Referring now to the drawings, and more particularly to FIG.
1, apparatus for parallel processing of multiple reaction mixtures
is indicated in its entirety by the reference numeral 1. (As used
herein, the term "parallel" means that two or more of the multiple
reaction mixtures are processed either simultaneously or at least
during overlapping time periods.) The apparatus 1, which may be
referred to as a parallel reactor system, is similar in certain
respects to the parallel reactor system described in the
aforementioned publications and applications, including U.S.
application Ser. No. 09/548,848.
[0040] In general, the apparatus 1 comprises an enclosure 3 having
a floor 4, a rail system generally designated 5 on the floor 4, and
a carriage generally designated 7 slidable on the rail system. A
modular reactor 9 comprising a number of reactor modules, each
generally designated 9M, are mounted side-by-side on the carriage.
Six such reactor modules 9M are shown in FIGS. 1-3, but this number
may vary from one to six or more. Further, the reactor need not be
modular, but rather it could be a single monolithic reactor. The
reactor 9 is preferably a research reactor, but could also be a
relatively small-volume production reactor. Two orbital shakers 13
are provided on the carriage 7 for shaking fluid reactants or other
reaction materials in mixing vials 15 held by racks 17 mounted on
the shakers (FIG. 4). The reaction materials may be in slurry form
comprising solid particles, such as silica or alumina particles
supporting a catalyst, suspended in a carrier fluid. The apparatus
1 further includes a pair of cannulas, each generally designated
21, and a four-axis robot system, generally indicated at 23, for
moving the cannulas to aspirate fluid reaction materials from the
vials into the cannulas, and then to move the cannulas into
position for delivery of the fluid materials to the reactor modules
9M, as will be described. Alternatively, a single cannula or more
than two cannulas could be used to service the reactor modules.
Apparatus, generally designated 25, for cleaning the cannulas is
also provided on the carriage adjacent each orbital shaker.
[0041] In the preferred embodiment, the robot system 23, carriage
7, rail system 5 and various components on the carriage are all
enclosed by the enclosure 3, which is a tubular enclosure supported
by legs. (For convenience of illustrating the equipment inside the
enclosure, certain portions of the top and side walls of the
enclosure are omitted in FIG. 1.) The enclosure is preferably what
is referred to as a "dry box" or a "glove box" having gloves 33
affixed to the periphery of openings 35 in the side walls of the
enclosure to allow an operator to manipulate items inside the
enclosure and reduce possible contamination. The enclosure 3 can be
gas-tight or filled with a pressurized inert gas (e.g., argon or
nitrogen). In either case, the environment is controlled to
eliminate contaminants or other material which might interfere with
the parallel reaction processes being conducted in the enclosure.
Conventional antechambers (air locks) 37 on the enclosure provide
access to the interior of the enclosure. Glove box enclosures
suitable for use in the present invention are available from, among
others, Vacuum Atmospheres Company of Hawthorne, Calif., and M.
Braun Inc. of Newburyport, Mass. Other types of enclosures may also
be used, such as a purge box which is movable between a
non-enclosing position and an enclosing position and purged of
contaminants with a pressurized inert gas.
[0042] Also disposed within the enclosure 3 is suitable pumping
equipment 41 for servicing the two cannulas 21, as schematically
shown in FIG. 2. This equipment is of conventional design and may
comprise, for example, positive displacement pumps, preferably
adapted for small volume increments. Exemplary pumps include four
syringe pumps 43 in a housing 45, each syringe pump comprising a
pump and associated syringe. In this embodiment, one set of two
syringe pumps 43 services one cannula 21 and the other set of two
syringe pumps 43 services the other cannula 21. Preferably, one
syringe pump 43a of each two-pump set is operable to pump a larger
(but still relatively small) volume of fluid, e.g., 5 ml to 25 ml,
and the other syringe pump 43b of the two-pump set is operable to
pump a smaller volume, e.g.,100 .mu.l to 1 ml. The amount of fluid
pumped for any given reaction preferably will vary from about 5
.mu.l to about 500 ml, more preferably from about 1 ml to about 500
ml, still more preferably from about 1 ml to about 100 ml, yet more
preferably from about 2 ml to about 50 ml, still more preferably
from about 2 ml to about 25 ml, and most preferably from about 5 ml
to about 15 ml. The two pumps of each two-pump set are connected to
a supply 49 of working fluid (e.g., solvent) by a flow line 51. The
construction and operation of the syringe pumps 43 is conventional,
such pumps being commercially available from Cavro Scientific
Instruments of Sunnyvale, Calif., pump part No. 730367 and syringe
part No. 730320. Accordingly, a detailed description of these
syringe pumps is unnecessary. Suffice it to say that they are
operable in two modes, the first being an intake mode to aspirate
measured quantities of fluid reaction material into the cannulas
21, and the second being an output mode to pump measured volumes of
working fluid to the cannulas 21 to force corresponding volumes of
reaction material from the cannulas for delivery to the reactors
9M. Generally speaking, the smaller volume syringe pump 43b is used
to pump smaller volumes of fluid, and the larger volume syringe
pump 43a is used to pump larger volumes of process material. In the
event fluid must be supplied under pressure to a reactor module 9M,
the smaller volume syringe pump 43b is preferably used, since it is
operable to supply fluids at pressures up to 500 psig. or more.
[0043] The enclosure 3 is provided with fittings 55 for attachment
of lines 57 which service the reactor modules. These lines 57 are
typically used for the delivery of process gases (e.g., reactant
and quenching gases) to the reactor modules 9M, as needed, and also
to vent the modules, as will be described hereinafter. The gas
lines 57 communicate with suitable sources of gas (not shown) under
pressure. The pressure of the gas in the lines 57 is controlled by
regulators indicated at 59 in FIG. 1.
[0044] Referring to FIG. 3, the rail system 5 comprises a pair of
guide rails 61 (e.g., linear guide rails of the type available from
Thomson Industries, Port Washington, N.Y.) mounted on the table.
Slide bushings 63 mounted on the underside of the carriage allow
the carriage 7 to slide back and forth on the rails.
[0045] The carriage 7 itself (FIGS. 3 and 5) comprises a plurality
of interconnected carriage plates 67, including two end plates 67a
carrying the orbital shakers 13, cleaning apparatus 25 and other
components, and a plurality of intermediate plates 67b, each of
which carries a single reactor module 9M. Adjacent carriage plates
67 are connected by rabbet joints 71 comprising overlapping
recessed edge margins releasably secured in precise position
relative to one another by quick-connect/disconnect devices 75,
each of which extends down through aligned holes in the plates. The
device may comprise, for example, a vertical shaft 77 having one or
more detents (not shown) at its lower end spring-biased to an
extended position for reception in corresponding recesses in the
lower of the two overlapping edge margins (see FIG. 5), and a
manually-operated button 79 at the upper end of the shaft for
retracting the detents to allow the shaft to be withdrawn from the
holes to disconnect the two carriage plates 67. Upon disconnection,
the carriage plates 67 can be moved together as a unit or relative
to one another on the rails 61 to facilitate maintenance and repair
of the equipment on the carriage as well as to vary the number of
carriage plates and reactor modules in the reactor matrix. The
carriage 7 is held in a fixed, predetermined home position on the
floor 4 by a "master" interlock 81 (similar to the quick
connect/disconnect devices) connecting a rigid extension 83
projecting from the carriage to a stationary fixture 85 affixed to
the floor (FIG. 3). In the preferred embodiment, disconnection of
the "master" interlock 81 to disconnect the carriage 7 from the
fixture 85 triggers a shut-off switch which prevents operation of
the robot system 23 until the interlock is reinstalled to reconnect
the carriage extension 83 to the fixture 85 at the home position.
Such re-connection requires precise alignment of holes in the
extension and the fixture, which in turn requires that all carriage
plates 67 be properly connected and positioned relative to one
another. Thus, the robot system 23 cannot be operated until the
carriage plates 67 (and all of the components fixedly attached
thereon) are precisely located on the floor 4.
[0046] As shown in FIG. 4, each vial rack 17 is releasably held in
a frame 91 mounted in fixed position on its respective shaker 13.
Spring clamps, quick-acting detents 93 or other connectors on the
frame 91 may be used for this purpose. The fit between the rack 17
and the frame 91 is a relatively close, tight fit so that the
position of each vial in the rack is set for purposes of the
computer controlled robot system 23. The rack 17 itself is modular
in design, comprising a plurality of horizontal panels 95 held in
vertically spaced relation by spacers 97 fastened to the panels.
The panels have vertically aligned openings 99 therein for
receiving and holding the vials. The modular nature of the
construction facilitates different rack configurations, all of
which can fit in the same frame 91. For example, the configuration
of the rack can be readily changed to accommodate vials of
different sizes, or different numbers of vials, or vials arranged
in different arrays. Also, the use of relatively thin panels 95
(which may be stamped metal parts) and spacers reduces the weight
of the assembly.
[0047] Referring again to FIG. 4, the cleaning apparatus 25
comprises a conventional wash tower 101 having a cavity or well 103
therein for receiving a cannula 21 to be washed and rinsed.
Suitable cleaning solution (e.g., solvent) at ambient temperature
is pumped through the cannula to flush its interior surfaces.
Solution exiting the cannula 21 is directed by the walls of the
cavity up along the outside of the cannula to clean its exterior
surfaces. Waste solution is directed to a drain 107 for disposal
(FIG. 2). A wash tower 101 suitable for use in the system is
available from Cavro Scientific Instruments of Sunnyvale, Calif.,
Model No. 727545.
[0048] In the event there is a need for more aggressive washing of
a cannula, as when slurry reaction materials containing small
particulate solids (e.g., solution phase supported catalysts) that
tend to adhere to process equipment are being used, the cleaning
apparatus 25 may include an ultrasonic bath (not shown) and/or a
separate heated wash tower generally indicated at 111. The
construction of the heated wash tower is illustrated in FIGS. 6-8.
As shown, the tower 111 comprises an upright generally
channel-shaped housing 113 on a base 115 secured to an end carriage
plate 67a, and a cylindric block 117 of metal supported within the
housing having a flanged and recessed upper end 119 and two bores
121, 123 extending down into the block 117 from the recessed upper
end 119. The first bore 121 forms a washing well and is relatively
narrow in diameter, being only slightly larger in diameter (e.g.,
0.035 in. larger) than the outside diameter of the needle of a
cannula 21 to be washed. The second bore 123 is larger in diameter
and functions as a drain. Intersecting countersinks 121a, 123a at
the upper ends of the two bores 121, 123 provide for overflow of
wash solution from the washing well 121 into the drain bore 123,
the lower end of which is connected via a fitting 127 (e.g., a
SWAGELOK.RTM. fitting). The cylindric block 117 of the wash tower
101 is surrounded by a jacket 133 containing resistance heating
coils (not shown) connected to a source of electric power by a
connection 135. The heating coils transfer heat to the cylindric
block 117 to heat the block and wash solution in the washing well
121, as will be described later. The solution should be heated to a
suitable temperature (e.g., about 170.degree.-200.degree. C.), such
as temperature sufficient to remove any coagulated reaction
materials on the needle of the cannula 21. As shown in FIG. 2, the
drain lines 107, 129 from the wash towers 101, 111 are connected to
a suitable drain system including flasks 137 for collecting waste.
Valves 138 in the waste lines can be closed to permit disconnection
and emptying of the flasks 137. After reconnection of the flasks,
valves 139 are opened to permit evacuation of any remaining vapor
in the flasks by a means of a vacuum pump 140, following which
valves 139 are closed and valves 138 opened to reestablish fluid
communication between the flasks and their respective cleaning
towers 101, 111 without contaminating the inert environment within
the enclosure 3.
[0049] In the preferred embodiment, the cleaning apparatus 25 also
includes an ultrasonic device 141 (FIG. 3) having a central recess
143 for receiving a cannula 21. This device generates ultrasonic
waves which mechanically vibrate the cannula as it is flushed with
solvent to provide an additional mechanism, if needed, for removing
slurry particles on the interior and exterior surfaces of the
needle of the cannula. The ultrasonic device 141 can be used alone
or in combination with one of the wash towers 101, 111. A suitable
ultrasonic device 141 is manufactured by Branson Ultrasonics
Corporation of Danbury, Conn., part number B3-R, and distributed by
Cole-Parmer Instrument Company of Vernon Hills, Ill., under part
number P-08849-00.
[0050] Referring now to FIGS. 9-11, each reactor module 9M
comprises a reactor block 151 of suitable metal mounted on a pair
of legs 153 secured to a base 155 which is fastened to a respective
carriage plate 67b. The reactor block 151 is preferably mounted in
a position spaced above the base so that it is thermally isolated
from the base. Each reactor block 151 has two or more (e.g., eight)
vessels therein formed by wells 163 each of which extends down from
an upper surface of the reactor block and each of which has a
central longitudinal axis A1 which is typically (but not
necessarily) generally vertical. In the preferred embodiment, each
well has a removable liner in the form of a reaction vial 165 for
holding a reaction mixture to be processed. The reaction vial 165
may be of glass or other suitably chemically inert material capable
of withstanding high-temperature chemical reactions. As used
herein, the term "vessel" broadly means any structure for confining
reaction materials in the reactor, including the walls defining the
well 163, and/or the vial 165 or other liner in the well containing
the reaction materials. In the embodiment shown in FIG. 10, the
reaction vial 165 has a height substantially less than the height
of the well 163, forming a head space 167 within the well above the
vial, the head space and interior of the vial combining to form
what may be referred to as a reaction chamber. This chamber is
sealed closed by a header plate 169 releasably secured by suitable
fasteners to the reactor block 151.
[0051] A stirrer mechanism, generally designated 171 in FIGS. 10
and 11, is provided for stirring the contents of each vessel. This
mechanism preferably comprises a stirrer in the form of a shaft 175
having a mixing blade or paddle 177 thereon engageable with the
contents of the vessel, and a magnetic drive 179 of the type
described in the aforementioned U.S. application Ser. No.
09/548,848 for rotating the stirrer at speeds in the range of 0 to
about 3000 rpm, and preferably at a speed in the range of about
200-2000, and most preferably at a speed in the range of about
1000-2000. The drive mechanism 179 is releasably coupled to the
shaft 175 by a quick-acting coupling, generally designated 181,
which may be of the type disclosed in the aforementioned U.S.
application Ser. No. 09/548,848, or in the aforementioned co-owned,
pending application Ser. No. 60/255,716, filed Dec. 14, 2000. The
magnetic drives 179 of the various stirrer mechanisms 171 of the
reactor modules 9M are powered by a drive system comprising a gear
train 185 (FIG. 11) releasably coupled to a stepper motor 187 by
means of a key and shaft slip connection 189, as best illustrated
in FIG. 5. The motor 187, in turn, is supported by brackets 191
fastened to the legs 153 extending up from the base on opposite
sides of the reactor block 151. The gear train 185 and drive
mechanisms 179 are enclosed by a cover 195 releasably secured to
the header plate 169 on the reactor block 151. The arrangement is
such that the stepper motor 187 rotates the gears of the gear train
185 to drive the magnetic drives 179 to rotate the stir shafts 175
in the vessels of the reactor module.
[0052] It will be understood that the stirrer mechanisms 171 may be
rotated by other types of drive mechanisms. Also, each stirrer
mechanism can be rotated by an independent drive system so that the
rotational speed of the stirrer can be varied independent of the
speed of the other stirrer mechanisms.
[0053] Referring to FIG. 11, a burst manifold 201 is secured to a
spacer plate 203 attached to the bottom of the reactor block 151.
The manifold 201 houses a series of disks 205, each of which is
mounted in a passage 207 communicating with a respective well 163.
In the event the pressure in a reaction chamber exceeds a
predetermined pressure, the disk 205 is designed to rupture, which
allows the chamber to vent into a vent passage 209 in the manifold
communicating with a suitable vent system. The rupture pressure
should be somewhat above maximum expected reaction pressures. In
preferred embodiments, the reaction pressures are greater than
atmospheric, preferably at least about 15 psig, more preferably at
least about 50-100 psig, and yet more preferably up to about 500
psig or more.
[0054] In accordance with one aspect of the present invention, each
reactor module 9M has a plurality of cannula passages 215 therein
extending between an exterior surface of the reactor block 151 and
the wells 163 formed in the reactor block, preferably one cannula
passage 215 for each well. In the preferred embodiment shown in
FIGS. 10 and 12, each cannula passage is straight and extends at an
angle from a location adjacent the upper end of the reactor block
151 at one side thereof to a respective well 163 in the block,
intersecting the side wall of the well in the head space 167 above
the upper end of the mixing vial 165 in the well or, in the event a
vial is not used, above the level of any liquid and/or solid
reaction components in the well. The central longitudinal axis A2
of the passage 215 is at an appropriate angle .theta. relative to
the central longitudinal axis A1 of the vessel, e.g., at a 25
degree angle off vertical, assuming the axis of the vessel is
vertical (although it is not necessarily so). While the passage 215
shown in the drawings is straight, it will be understood that the
passage need not be absolutely straight. For example, if the
portion of the cannula 21 to be inserted into the passage is
flexible or somewhat non-linear, the cannula passage 215 could also
assume non-linear configurations (e.g., an arcuate configuration).
However, in the preferred embodiment, the cannula passage is at
least substantially straight, meaning that it is sufficiently
straight to accommodate a cannula needle of the type to be
described later in this specification.
[0055] The passage 215 is positioned so that when a respective
cannula 21 is inserted into and through the passage 215, the distal
end of the cannula is positioned inside the vessel, preferably
inside the reaction vial 165 if one is used, for delivery of
reaction material from the cannula at an elevation above any
liquids and/or solids in the vial, and in a generally downward
direction so that the reaction material exiting the cannula is
delivered into the vial without contacting any surface of the vial,
as will be discussed later. The size and cross-sectional shape of
the cannula passage 215 is not critical. By way of example,
however, which is not intended to be limiting in any respect, the
passage can be formed by a circular bore having a diameter which
exceeds the outside diameter of cannula 21 by about 0.032 in. The
angle e of the cannula passage 215 may also vary, depending on the
spacing between adjacent reactor modules 9M, the height of the
reactor module, the size of the vessels, and other factors. In the
preferred embodiment, all cannula passages 215 extend from an
exterior surface of the reactor block 151 on the same side of the
block, but it will be understood that the cannula passages for
different wells 163 could extend from different sides of the
reactor block without departing from the scope of this
invention.
[0056] A sealing mechanism, generally designated 221 in FIG. 12, is
provided in each cannula passage 215 for maintaining the reaction
vessel sealed against ambient conditions when the cannula is
inserted into and withdrawn from the cannula passage, thus
preventing any substantial pressure losses if the pressure in the
reaction vessel is positive, or any pressure gains if the pressure
in the reaction vessel is negative with respect to ambient
pressure. As shown best in FIGS. 12-14, the sealing mechanism 221
is located in the passage 215 adjacent its upper end at the entry
port thereof which is enlarged by a counterbore 225 to accept the
mechanism. The mechanism 221 includes a valve 227 movable between a
closed position for closing the cannula passage 215 and an open
position permitting movement of the cannula through the passage,
and a seal 229 in the passage sealingly engageable with the cannula
21 when the valve 227 is in its open position. The valve 227 and
seal 229 may be separate elements or formed as a single unit. In
the preferred embodiment, the valve and seal are fabricated as a
single assembly of the type described in U.S. Pat. No. 4,954,149,
incorporated herein by reference, owned by Merlin Instrument
Company of Half Moon Bay, Calif. In this (FIG. 12) embodiment, the
valve 227 has a body 231 molded from suitable material (e.g.,
Viton.RTM. fluorocarbon rubber) received in a counterbore 233 in
the reactor body 151, a sealing ridge 235 extending
circumferentially around the body 231 for sealing against the
reactor body, a central passage 237 through the body forming part
of the cannula passage 215, a duckbill valve comprising a pair of
duckbill lips 241 formed integrally with the valve body 231, and a
metal spring 243 (e.g., of hardened stainless steel) which biases
the lips 241 together to close the passage 237. The lips 241 are
forced open against the bias of the spring by the distal end of the
cannula 21 as it is inserted through the passage 237 in the valve
body (FIG. 13). The lips 241 have a sliding fit against the cannula
as it is so inserted. The first-mentioned seal 229 is an annular
seal on the body immediately above the valve formed by the duckbill
lips 241 on the side of the valve opposite the vial 165 in the
well. The annular seal 229 is sized for sliding sealing engagement
with the cannula 21 as the cannula is withdrawn from the reactor,
since it may take some very small period of time for the lips 241
of the duckbill valve to close after the cannula is pulled past the
lips. The sealing mechanism 221 is held in place by a nut 251
threaded in the counterbore 225 in the reactor block 151 into
engagement with a circular sealing ridge (not shown) on the upper
face of the valve body 231. As shown in FIG. 12, the nut 251 has a
central bore 253 therethrough aligned with the passage 237 through
the valve body 231. The upper end of this bore which constitutes
the entry port of the cannula passage 25, is tapered to provide a
lead-in 255 for the cannula.
[0057] A wiper assembly, generally indicated at 261, is provided
adjacent the upper (inlet) end of each cannula passage 215 (see
FIGS. 9 and 12). The assembly 261 comprises a wiper frame 263
mounted on the reactor module 9M immediately above the inlets of
the cannula passages 215, a wiper member 265 overlying a leg 267 of
the frame having one or more openings 269 therein in registry with
the upper entry end of the cannula passages 215, a clamp member 271
overlying the wiper member 265, and fasteners 275 (only one shown
in FIG. 12) for tightening the clamp member 271 on the frame 263 to
clamp the wiper member 265 in place. The wiper member is of a
material capable of being penetrated by the distal end of the
needle of the cannula 21 and then wiping reaction material off the
exterior surface of the needle as it is moved down into the cannula
passage 215. The removal of reactant material before entry of the
cannula into the cannula passages is important, especially when
handling slurries containing small solid particles, since such
particles could interfere with the sealing mechanisms 221 in the
passages 215. One material found to be suitable as a wiper member
is an expanded Teflon.RTM. gasket material sold by W.L. Gore &
Associates, Inc. Other materials (e.g., silicone rubber) may also
be used. Preferably, the wiper member 265 comprises a single strip
of material which extends the length of the reactor block 151 at
one side of the block and overlies the openings 269 at the upper
ends of all cannula passages 215 in the block (see FIGS. 9 and 12).
Alternatively, the wiper member 265 can comprise separate pieces
for the separate cannula passages 215. The wiper frame 263 is
removably mounted on the reactor block 215 so the wiper member 265
can be easily replaced after each run. In the preferred embodiment,
the frame 263 sits on pins (not shown) on the reactor block 151 and
is easily removed simply by lifting the frame off the pins.
[0058] Gas manifolds 281 extend along opposite sides of the reactor
block 151, as shown in FIGS. 9 and 10. Process gas lines 57
extending from fittings 55 on the enclosure 31 communicate with one
manifold (the right manifold as shown in FIG. 10) to provide for
the delivery of process gas (e.g., reactant gas such as ethylene or
propylene) to the vessels in the reactor module 9M. Lines 57
extending from the fittings 55 on the enclosure to the other (left)
manifold 281 provide for the delivery of quenching or inert gas
(e.g., carbon dioxide) to the vessels to terminate a reaction
and/or to vent the gaseous contents of the vessel. Flow through the
lines 57 to the manifolds 281 is controlled by solenoid valves 285
mounted on the bore 155 immediately adjacent the reactor module
(FIG. 4).
[0059] In general, the robot system 23 is a conventional three-axis
system providing translational movement along X, Y and Z axes (see
FIGS. 15 and 16), except that the system is modified as described
hereinafter to provide for rotational movement about a fourth axis
R, which may intersect axis Z. The conventional three-axis system
referred to may be a system commercially available from Cavro
Scientific Instruments of Sunnyvale, Calif., Model No. 727633.
Referring to FIG. 3, the robot system 23 in one embodiment
comprises a horizontal track 301 mounted on the enclosure 3 by
brackets 303, left and right carriages 305b, 305a mounted on the
track for linear movement along the X axis, and left and right
robot arms 307L, 307R extending from respective carriages. (As
referred to herein, left and right is as viewed in FIGS. 1, 3, 15
and 16.) An elongate rack 311 on each arm 307L, 307R carries a
respective cannula 21. The rack 311 is mounted for movement in a
slot 313 in the robot arm along the Y axis, and is also engageable
with a drive pinion (not shown) in the arm for movement along the Z
axis. In accordance with another aspect of this invention, the
carriage 305L, 305R associated with each robot arm 307L, 307R is
modified to provide for rotation of the arm about axis R. Since the
left and right carriages may be of somewhat different construction,
both will be described.
[0060] The construction of the right carriage 305R is shown in
FIGS. 17-19. The carriage comprises a slider 317 engageable in
conventional fashion with the track 301, a base 319 affixed to the
slider, a shaft 321 mounted on the base having a longitudinal axis
A3 corresponding to axis R, and a pivot block 325 mounted on the
shaft for rotation on axis R. The pivot block 325 carries the right
robot arm 307R and is rotatable by a power actuator which, in the
preferred embodiment, is a double-acting pneumatic cylinder 329R.
The cylinder 329R is mounted on a platform 331 pivotally secured at
333 in FIG. 19 to the pivot block 325 and has a rod end having a
clevis pivot connection 335 with a shaft 337 extending from the
base 319, the arrangement being such that the extension of the
cylinder rod causes the pivot block 325 to rotate in a first
(clockwise) direction from the generally horizontal "home" position
shown in FIG. 17 to the tilted position shown in FIG. 18, and
retraction of the rod causes the pivot block to rotate in the
opposite (counterclockwise) direction. During such extension and
retraction, the platform 331 pivots relative to the pivot block 325
and the clevis connection 335 rotates on the shaft 337. Extension
and retraction of the cylinder 329R is controlled by a suitable
pneumatic system, one such system being designated 341 in FIG. 2.
In this embodiment, an inert gas (e.g., argon or nitrogen) is
supplied to opposite ends of the cylinder 329R by two lines 343,
345, the first of which (343) supplies gas at a relatively high
pressure (e.g., 60 psig) to one end of the cylinder for extending
the cylinder to rotate the pivot block 325 to its angled (tilted)
position, and the second of which (345) supplies gas at a lower
pressure (e.g., 40 psig) to the opposite end of the cylinder. Both
gas lines 343, 345 are connected to a suitable source 351 of high
pressure gas (e.g., argon or other inert gas). Regulators 353 are
used to control the pressure in the lines 343, 345. A solenoid
valve 357 in line 343 controls the supply of high pressure gas to
the cylinder 329R. Both lines contain orifices 361 adjacent the
cylinder 329R to restrict the flow of gas to dampen the movement of
the cylinder, and thus the rotational movement of the pivot block
325 and robot arm 307R. When the solenoid valve 357 is open to
provide high pressure gas to the cylinder, the piston of the
cylinder extends against the lower pressure gas to rotate the pivot
block 325. When the solenoid valve 357 is closed, gas is vented
from the high-pressure end of the cylinder 329R, allowing the
piston to move in the opposite direction under the influence of the
lower pressure gas to rotate the pivot block 325 in the opposite
direction. Other pneumatic circuits may be used. Similarly, other
types of power actuators may be used for rotating the pivot block
325. Further, other damping means may be used to dampen the rate of
pivotal movement of the pivot block 325 and robot arm 307R about
axis R. For example, a suitable damping device could be positioned
between the pivot block 325 and the base 319.
[0061] The range of rotational movement of the pivot block 325 is
determined by stops (see FIGS. 17 and 18). In the preferred
embodiment, movement in the clockwise direction is determined by
the location of a first adjustable stop 365 on the base 319
engageable by a first stop 367 on the pivot block 325, and
rotational movement of the pivot block in the counterclockwise
direction is determined by the location of a second adjustable stop
369 on the base engageable with a second stop 371 on the pivot
block.
[0062] The first adjustable stop 365 comprises a damping cylinder
375 mounted on the base 319 in a generally horizontal position, and
a rod 377 (FIG. 17) extending from the cylinder having an upper end
engageable by the first stop 367 on the pivot block 325. The
cylinder 375 has a threaded connection with the base 319 so that
the cylinder may be moved along its axis to adjust the axial
position of the rod 377. A jamb nut (not shown) may be used to
secure the cylinder in adjusted position. The damping cylinder 375
contains fluid movable through an optimally adjustable orifice to
damp movement of the rod 377 as it moves to its final fixed
position, as will be understood by those skilled in the art. The
cylinder and rod are of conventional design. A suitable damping
cylinder 375 is commercially available from Humphrey of Kalamazoo,
Mich., Part No. HKSH5X8.
[0063] The second adjustable stop 369 is similar to the first
adjustable stop 365 described above except that the cylinder
(designated 381) is mounted in a generally vertical position for
engagement of its rod 383 by the second stop 371 on the pivot block
325.
[0064] It will be understood, therefore, that the range of
rotational movement of the pivot block 325 can be adjusted by
setting the location of the adjustable stops 365, 369 to the
desired locations. In the preferred embodiment, the range of motion
is through a range of about 25 degrees, preferably between a
position in which the cannula 21 is vertical and one where the
cannula is 25 degrees off vertical, although this range may vary
without departing from the scope of this invention. Whatever the
range, the pivot block 325 in its tilted position should rotate the
robot arm 307R to a position in which the cannula 21 is held at an
angle corresponding to the angle of the cannula passages 215 in the
reactors 9M so that the cannulas can be inserted through the
passages.
[0065] The range of rotational movement of the pivot block 325 can
be limited in other ways without departing from the scope of this
invention.
[0066] The left carriage 305L for the left robot arm 307L is shown
in FIGS. 20-22. The construction of the left carriage is very
similar to the construction of the right carriage 307R, and
corresponding parts are designated by the same reference numbers.
However, there are some differences between the two carriages even
though the left and right robot arms are mirror images of one
another. This is because, in the preferred embodiment shown in the
drawings (e.g., FIG. 9), the entry ports of the cannula passages
215 of the reactor modules 9M all face in the same lateral
direction, i.e., toward the left end of the dry box 3 shown in FIG.
1. Another reason for the different construction is the preference
to maintain the R-axis of rotation of each robot arm 307L, 307R in
line with the Z-axis of travel to reduce the complexity of the
motion control for the robot. In any event, the most significant
difference in construction is that, for the left carriage 305L, the
pivot shaft 321 is on the opposite side of the base 319, and the
cylinder 329 is mounted so that retraction of the cylinder causes
the pivot block 325 (and the left robot arm 307L) to rotate from
its home position shown in FIG. 20 to its angled position shown in
FIG. 21, and extension of the cylinder causes the pivot block to
rotate from its angled position back to its home position.
[0067] It will be understood that the construction of the left and
right carriages 305L, 305R could be different from that shown
without departing from the scope of this invention.
[0068] A cannula 21 used in the apparatus of the present invention
is shown in FIGS. 23-25. The cannula includes a hollow tubular
reservoir 391 having a central longitudinal axis A4, an outside
diameter, an inside diameter defining a hollow interior 375, a
proximal (upper) end 397 and a distal (lower) end 399. The cannula
also includes a long thin straight tube 401 (hereinafter referred
to as a "needle") extending coaxially with respect to the reservoir
391. The needle 401 has an outside diameter substantially less than
the outside diameter of the reservoir 391, an inside diameter which
defines a central flow passage 403 extending the length of the
needle, an open proximal (upper) end 405 which communicates with
the hollow interior 395 of the reservoir, a lower distal end 407,
and a port 409 adjacent the distal end which opens laterally (i.e.,
to the side) relative to the aforementioned axis. The upper end 405
of the needle 401 is joined to the lower end 399 of the reservoir
391 by means of a bowl-shaped metal transition, generally
designated 411, having a sloping, funnel-shaped interior side wall
413 and a bottom 415 having a hole 417 therein for snugly receiving
the upper end portion of the needle, the upper end 405 of the
needle being flush with the interior surface of the transition. The
transition is joined to the reservoir and the needle by welds
indicated at 421 in FIG. 23A. These weld areas, and the entire
interior surface of the transition and adjacent surfaces of the
reservoir and needle, are polished to a high degree of smoothness
so that the interior surfaces of the reservoir, transition and
needle form a continuous expanse of smooth surface area without
crevices or other surface discontinuities which might trap
particles or other material which could interfere with aspiration
into the needle or delivery from the needle in accurate quantities.
The exterior surfaces of the reservoir 391, transition 411 and
needle 401 should be similarly polished.
[0069] By way of example, the reservoir 391 is formed from metal,
preferably stainless steel tubing having, for example, an outside
diameter in the range of about 0.05 to 0.50 in, more preferably in
the range of about 0.05-0.25 in, and most preferably about 0.188
in.; an inside diameter in the range of about 0.02-0.45 in, and
more preferably about 0.118 in.; and a length in the range of about
1.0-6.0 in, more preferably about 2.0 in. The volume of the
reservoir 391 should be substantially greater than the largest
volume of material to be aspirated into the cannula 21 (e.g.,
preferably in the range of about 10 .mu.l-5000 .mu.l, more
preferably in the range of about 25 .mu.l-3500 .mu.l, and most
preferably about 350 .mu.l).
[0070] The needle 401 is preferably also formed from metal tubing
having, for example, an outside diameter in the range of about
0.02-0.10 in, and more preferably about 0.028 in.; an inside
diameter in the range of about 0.01-0.09 in., and more preferably
about 0.0155 in.; and a length in the range of about 1.5-5.0 in,
more preferably in the range of about 2.0-4.0, and most preferably
about 3.4 in. The port 409 of the needle, shown best in FIG. 24, is
generally oval in the shape of a racetrack and is sized to have a
minimum dimension D1 substantially larger (e.g., four times larger)
than the largest particle of material to be handled by the cannula.
For example, a port 409 having a minimum dimension of about 0.0155
has been found to be acceptable for handling slurries containing
silica particles averaging 10-100 microns in diameter. Other shapes
and dimensions may be suitable, depending on the type of material
being handled. The transition 411 is preferably of the same metal
as the needle 401 and reservoir 391, e.g., stainless steel, and has
a suitable axial length (e.g., preferably in the range of 0.10-0.50
in., and more preferably about 0.215 in.) The exact shape of the
transition is not believed to be critical, so long as the inside
surface of the transition is contoured for funneling material from
the reservoir to the needle to provide for efficient flow between
the reservoir and needle (e.g., no air pockets or other dead volume
or space). The interior surface of the transition 411 should also
be smooth to minimize any discontinuities or other surface
variations which would otherwise tend to trap material. In the
preferred embodiment, the interior wall 413 of the transition 411
is generally conical with an included angle .omega. in the range of
about 20-70 degrees, and more preferably about 30 degrees, although
other angles of inclination may also be used. The upper end of the
transition 411 is formed with an upwardly projecting annular
shoulder 425 received in a shallow counterbore 427 in the lower end
399 of the reservoir 391 to ensure proper registration between the
two members when they are secured together, as by laser welding.
The OD of the transition 411 is preferably substantially the same
as the OD of the reservoir 391, and the ID of the transition at its
upper end is preferably the same as the ID of the reservoir at its
lower end.
[0071] The cannula 21 can be fabricated as follows. The needle 401
is made by bending the end of a length of straight metal tubing and
cutting the distal end of the tubing along a line A--A (FIG. 25),
parallel to the axis A4 of the tubing, to form the laterally
opening port 409. To insure that the port 409 opens substantially
downwardly when the needle is inserted in the cannula passage 215,
the angle .alpha. between the cut line A--A and the bend radius 429
should substantially correspond to the angle .theta. of inclination
of the passage 215. The proximal (upper) end 405 of the tube is
then inserted into the hole 417 in the bottom of the transition 411
and welded in position along weld lines 421 on the inside and
outside of the transition. The inside and outside surfaces of the
transition and welded areas of the needle are subjected to a
grinding/polishing procedure to provide a smooth finish in which
the upper end of the needle is flush with the inside surface of the
transition, and in which all surfaces and junctures are completely
smooth. The distal end 407 of the needle 401 at the port 409 are
also polished. The transition 411 is then welded to the tubular
reservoir 391. A final polishing operation smooths the weld areas
at the juncture between the transition 411 and the reservoir 391,
and the inside and outside surfaces of the reservoir.
[0072] The cannula 21 can be fabricated in other ways. However, it
is important that the cannula needle have a laterally opening port
so that when the needle is inserted through the cannula passage 215
and into the reaction chamber, fluid reaction material (e.g.,
slurry material) is delivered from the port in a downward direction
onto the interior bottom surface of vial 165 or the surface of the
contents in the reaction vial rather than onto the side wall of the
vial. Further, it is important that a reservoir be provided above
the needle to insure that reaction materials aspirated into the
needle are fully contained without backing up into the flow lines
of the system.
[0073] A flow line 431 (e.g., flexible plastic tubing) is secured
to the upper open end of the reservoir 391 by means of a fitting
433 having a sealing connection with the upper end of the reservoir
and the flow line (FIGS. 26 and 27). This connection is effected by
means of a compression nut 435 threadable on the fitting 433. The
nut 435 is designed so that when it is turned, it squeezes against
the flow line 431 and reservoir 391 to provide a sealing connection
of the line to the reservoir for the flow of working fluid (e.g.,
solvent) between the pump 43 and the cannula 21, as occurs during
operation of the system.
[0074] Again referring to FIGS. 26 and 27, each cannula 21 is
mounted on a respective robot arm 307R, 307L by means of a mount
comprising a bracket 441 secured at its upper end to the elongate
rack 311 extending down from the robot arm, and a cannula support
443 secured to the bracket 441 for supporting and stabilizing the
cannula as it is moved. More particularly, the cannula support 443
comprises a yoke-like body 445 which is mounted on locating pins
446 projecting forward from the bracket and secured in position to
the bracket by suitable fasteners (e.g., socket-head cap screws,
not shown). The body 445 has a vertical bore 447 through it for
receiving the reservoir 391 of the cannula therein, a pair of
recesses 449 in the front face of the body 445 exposing portions of
the reservoir, a pair of clamping plates 451 received in the
recesses and engageable with the exposed portions of the reservoir,
and clamping screws (not shown) extending through clearance holes
453 in the clamping plates and threadable into the body 445. The
clamping screws are tightened to draw the clamping plates toward
the body to clamp the reservoir in fixed position against the body.
The cannula should be secured in a position wherein the port 409 at
the distal end 407 of the needle 401 faces in a generally downward
direction when the cannula is in its fluid delivery position.
[0075] The cannula support 443 also includes a head 455 fixedly
mounted on a pair of parallel guide rods 457 which are slidable in
bushings (not shown) in bores of arms 463 extending laterally from
opposite sides of the support body 445. The head 455 has a central
bore 465 therein (FIG. 28) sized for a close clearance fit with the
needle 401 of the cannula at a position intermediate the ends of
the needle. The head 455 is movable relative to the body 445 from a
lowered position (shown in solid lines in FIG. 26 ) in which the
head is spaced from the body for engagement with a more distal
portion of the needle 401, and a raised position (shown in phantom
lines) in which the head is closer to the body for engagement with
a more proximal portion of the needle to allow for insertion of the
said more distal portion of the needle into a cannula passage 215.
The head 455 and guide rods 457 affixed thereto are biased by
gravity toward the lowered position. A retaining ring (not shown)
on at least one of the guide rods 457 is engageable with the
support body 445 for limiting the downward movement of the head.
The close clearance fit of the needle 401 in the bore 465 of the
head (FIG. 28) maintains the needle in the required precise angular
position, and also stabilizes the needle to prevent buckling of the
needle in use, as when the needle is pushed to penetrate the
sealing mechanism 221. (This mechanism may be resistant to
penetration if the pressures in the reactor chamber is large.)
Preferably, the bore 465 in the head 455 is sized to be about
0.001-0.010 in. larger than the OD of the needle 401, and more
preferably about 0.004 in. larger.
[0076] The operation of the robot system 23, the various valves for
delivering gases to and from the reactor vessels, and other
electronic components of the system are under the control of a
suitable system processor and software (or firmware). Reference may
be made to the aforementioned U.S. application Ser. No. 09/548,848
for more detail. In general, however, the robot system 23 is
operable to use the left robot arm 307L to service one bank of
reactor modules 9M (e.g., the left three modules in FIGS. 1 and 2)
and the right robot arm 307R to service the remaining modules
(e.g., the right three modules in FIGS. 1 and 2). Using multiple
robot arms to service different sections of the reactor matrix
speeds set-up of the parallel reactor system and manipulation
during the course of the reactions. Alternatively, the robot system
could have only one arm 307 to service all modules, or three robot
arms could be used. When using multiple robot arms, different arms
could be dedicated to delivering different reaction materials to
all or less than all of the reactor modules. The precise locations
of the various components of the reactor system (e.g., cannula
passage 215 entry ports, wash towers 101, 111, ultrasonic cleaners
141, vial positions in the racks 17) are programmed into the robot
system in a manner which will be understood by those skilled in the
art.
[0077] The general operation of the system will now be described.
First, vessels and stirrers are installed and the reactor covers
195 are replaced and secured. Optionally, but preferably, a set of
purge procedures is followed to purge all inlet lines, particularly
those inlet lines 57 that will contain reactant gas. These purge
procedures may not be necessary if the previous run left the
reactor in a ready or purged state. Generally, the purging is
carried out so that all lines and reactor vessels contain a desired
atmosphere or gas. In the delivery or inlet lines, typically, a
reactant gas may be used, such as ethylene gas, to ensure that no
dead volumes or other gases are in the delivery lines.
[0078] Thereafter, liquid components are added to the reactor
vessels. For example, if catalytic materials for a polymerization
reaction are to be characterized, the vessels may contain a solvent
or diluent and other liquid reagents (e.g., a liquid co-monomer,
such as 1-octene, 1-hexene or styrene, if desired). Suitable
solvents may be polar or non-polar and include toluene and hexanes.
The solvents loaded into the reactor vessels may be, but are not
necessarily, the same solvents used in other parts of the apparatus
(e.g., the working fluid used in the syringe pumps and the solvents
used in the wash towers). Thereafter, the temperature set point of
the reaction is set and the temperature is allowed to stabilize.
Then the reactors are charged with the atmospheric gas for the
reaction, which may be an inert gas or reactant gas, in order to
bring the vessels to the desired operating pressure, which is
typically in the range of from 0-500 psig. If the reaction
atmosphere is a reactant gas (e.g., a gaseous monomer, such as
ethylene), the liquid reagents are typically allowed to become
saturated with the gaseous monomer such that the reaction vessel
contents reach an equilibrium point. In the example being followed
(i.e., a catalyzed polymerization reaction), a catalyst
particle-containing fluid or slurry is then injected into the
vessels. If a catalyst is the particulate (i.e., a solid supported
catalyst) then the catalyst (e.g., including co-catalysts or
activators) and non-catalyst reagents (e.g., scavengers) are added
to the vessels. Preferably, the catalyst in slurry form is the last
component to be added to the reactor vessels.
[0079] Generally, as used herein, a slurry comprises at least two
components, including (1) a solid particulate and (2) a liquid
dispersing medium or diluent. The particulate is preferably a solid
catalyst (e.g., a zeolite) or solid supported catalyst (e.g., an
organometallic complex supported on a solid support, such as
alumina or silica). Slurries of this type are known in the art. The
amount of catalyst depends on the experimental design as discussed
herein. Typically, the slurry contains a sufficient quantity of the
liquid diluent to disperse the solid particulate in a substantially
homogenous suspension with appropriate agitation as necessary. The
diluent is typically not a solvent for the solid catalyst or solid
supported catalyst, but may be a solvent for other reaction
materials, such as monomer or scavenger. The viscosity and density
of the diluent can be selected to facilitate substantial
homogeneity of the slurry upon agitation. As used herein,
substantially homogeneous means that the particulates are dispersed
sufficiently in the diluent so that upon aspiration of a sample
from the slurry, a consistent fraction of particulate is aspirated
reproducibly to within scientifically acceptable error. This can be
judged, e.g., on the basis of polymer productivity or catalyst
efficiency. Slurry homogeneity allows for aspiration of a known
volume of slurry, from which can be determined the quantity of
catalyst that is being used in a particular reaction (e.g., being
injected into a reaction vessel according to the design of the
combinatorial or high throughput experiment). For example, 10 mg of
solid supported catalyst combined with sufficient diluent to
produce 1 ml of slurry can provide for a catalyst injection of 1 mg
for every 100 .mu.l that is aspirated into a cannula 21 from a
homogenous slurry. Thus, determination of catalyst to be injected
(on the basis of moles or mass) can be determined on the basis of
known volumes in the cannula and/or other parts of the reactor
system described herein. Also, in other words, the slurry for
injection can be adjusted (e.g., in terms of concentration of solid
supported catalyst in the slurry) to accommodate the equipment in
use (e.g., cannula volume) as well as the design of the
combinatorial or high throughput experiment.
[0080] The preparation of the slurry for injection is highly
dependent on the exact chemistry in practice. Generally, slurries
are prepared by mixing the particulate solid material and the
liquid dispersing medium or diluent and thereafter agitating,
preferably swirling or vortexing, the mixture to form a
substantially homogenous slurry in which the particulate solid
material is suspended in the liquid. If the reactor vessels are
initially charged with a liquid solvent, the same solvent may be
used as the liquid dispersing medium for slurry preparation. Many
factors can be adjusted to accommodate different chemistries,
including the timing of adding the liquid dispersing medium to the
particulate solid material to make the slurry, the ratio of the
particulate solid material to diluent, the intensity with which the
slurry mixture is agitated (e.g., the rate of swirling or
vortexing) during preparation, the rate of cannula insertion into
and out of the slurry, and the size and shape of the vial from
which the slurry is aspirated prior to injection. In the case of
catalytic slurries, some solid catalysts and some solid supports of
supported catalysts are fragile and may degrade as a result of
agitation (e.g., in terms of particle size or shape) or the time
for slurry preparation may be so long that the liquid dispersing
medium will evaporate, thereby changing the concentration of the
catalyst in the slurry from that desired by the experimental
design. Thus, in one preferred embodiment, the slurry is prepared
within a limited time prior to injection, for example less than 90
minutes prior to injection, more preferably not more than 45
minutes prior to injection, more preferably not more than 10
minutes prior to injection, still more preferably not more than 5
minutes prior to injection and especially not more than 1 minute
prior to injection. Depending on the speed set for the robots,
etc., slurry may be prepared by mixing the particulate solid
material and the liquid dispersing medium within about 30 seconds
prior to injection to the reactor vessel, as described herein.
Other factors that can be adjusted include the intensity of
agitation of the slurry mixture. The rate of swirling or vortexing
of the slurry necessary to achieve a substantially homogeneous
slurry depends on the concentration of the particulate solid
material in the liquid dispersing medium and the volume and shape
of the mixing vial. In general, the higher the concentration of
solid particles in the slurry, then the higher the vortexing rate
necessary to ensure a substantially homogeneous slurry. Similarly,
the lower the concentration of solid particles in the slurry, the
lower the vortexing rate should be. Examples of suitable slurry
vortexing rates include from about 100 rpm to about 1300 rpm.
Mixing vial sizes include 20 ml, 8 ml, and 1 ml.
[0081] For a catalytic reaction in which the catalyst is on a solid
support, in order to prepare the slurry, the solid supported
catalyst is first weighed, with the weight being used to calculate
the amount of liquid dispersion medium that is added to the
supported catalyst to prepare the slurry for injection. The
preparation of the slurry for injection can be important with
respect to the size of the cannula, since the cannula can
accommodate only a limited amount of slurry. Thus, it is important
to calculate the concentration of the slurry, the desired catalyst
amount on the support (e.g., silica) and then the desired amount of
liquid dispersing medium.
[0082] To initiate a typical run of reactions, the orbital shakers
13 are actuated to shake the racks 17 containing the vials and
agitate the slurry materials contained therein to provide a
substantially homogeneous slurry. The robot system is then actuated
to move the cannulas to positions in which the desired quantities
of slurry material are aspirated from vials in respective racks on
the shakers, the left cannula 21 (as viewed in FIG. 1) aspirating
from one or more vials in the left rack 17 and the right cannula 21
aspirating from one or more vials in the right rack 17. During
aspiration, the cannulas are preferably in a vertical position and
the shakers are preferably in operation to agitate the slurry and
ensure that the slurry aspirated into the cannula is substantially
homogenous. When the cannula 21 is entering the vortexing slurry,
the cannula speed along the Z axis of the robot is slowed down so
that the cannula entering the vortexing slurry does not
substantially disturb the homogeneous slurry. The cannula is
preferably paused from about 1-2 sec. in the vortexing slurry prior
to aspiration in order to ensure that a substantially homogeneous
slurry is aspirated into the cannula. Also, prior to aspiration,
the speed of aspiration is slowed (e.g., by slowing the aspiration
rate of the syringe pump 43) to avoid particle selectivity or other
issues that might impact the homogeneity of the slurry that is
aspirated into the cannula. Thereafter, the desired volume of
slurry is aspirated into the cannula.
[0083] In the preferred embodiment, after aspiration of an
appropriate quantity of slurry into a cannula 21 is complete, the
robot system 23 moves the cannula to aspirate a small volume of
barrier liquid (e.g., 30-50 .mu.l of optionally the same liquid
charged to the reactor vessels) into the tip of the needle 401. The
robot system is then operated to lift the cannula along the Z-axis
of the respective robot arm 307L, 307R to a height sufficient to
clear the reactor modules 9M; the power actuator 329 is operated to
rotate the robot arm on its R-axis to tilt the cannula to its
fluid-delivery angle (e.g., 25.degree.); and the cannula is moved
along X and/or Y-axes to a position in which the needle is ready
for insertion into the cannula passage 215 leading to the first
vessel to be loaded with slurry, as shown in FIG. 12. The cannula
is held in this position for a short dwell period (e.g., 1-2
seconds) sufficient to allow any vibratory or harmonic movement of
the needle to cease, following which the angled cannula is moved
along the Z axis of the elongate rack 311 to cause the needle 401
to penetrate the wiper member 265 to wipe any slurry material off
the outside of the needle. The needle continues to advance into the
entry port of the cannula passage 215 and through the annular seal
229 to a position (FIG. 13) immediately upstream of the duckbill
valve lips 241, where the advance of the needle 401 is paused while
the robot is signaled to increase the speed of the needle 401 along
the Z-axis of the rack 311. The syringe flow rate is also
increased. Alternatively, the syringe flow could be increased after
the liquid barrier has been aspirated. In either event, after a
dwell in the position of FIG. 13, the needle is pushed forward at a
relatively high speed through the valve, forcing the lips 241 of
the duckbill valve apart, and down through the passage 215 to the
fluid delivery or dispensing position shown in FIGS. 10 and 14. As
the needle approaches its dispensing position, the head 455 of the
cannula support 443 engages the wiper member frame 263 and remains
in that position as the needle continues to advance to the position
shown in FIG. 10 where the distal end of the needle 401 is disposed
inside the vial 165 at a level above the contents of the vial, and
the port 409 in the needle faces generally downward. The high speed
of the needle 401 in combination with the small volume of barrier
liquid in the tip of the needle and high syringe flow rate helps to
avoid possible reaction from occurring in the cannula (e.g., in an
embodiment where the slurry comprises a catalyst).
[0084] With the needle 401 in its FIG. 10 delivery or dispensing
position, solvent is pumped into the cannula 21 through the solvent
line 431 to force the small volume of barrier liquid and the
predetermined quantity of slurry material from the cannula directly
into the vial 165. A predetermined quantity of chaser solvent is
also dispensed in an amount sufficient to ensure that the slurry is
effectively transferred to the vessel. Preferably, slurry
preparation and the speed with which the robot system manipulates
the cannula are controlled such that the slurry delivered to the
vial remains substantially homogenous. In an especially preferred
embodiment, the slurry is delivered to the vial within 60 seconds
of aspirating the slurry into the cannula.
[0085] Because the contents of the vessel are already under
pressure, the slurry material must be delivered from the cannula at
a pressure greater than the vessel pressure. Typical reaction
pressures vary from about ambient to 500 psig, and more preferably
from about 50-300 psig, so at least some of the syringe pumps 43
(e.g., pumps 43a) should have the capability of generating a
delivery pressure of up to 500 psig or greater. Since the port 409
at the distal end of the needle 401 is facing down, the slurry
preferably does not contact or accumulate on the side walls of the
vial 165 but rather is deposited on the surface of the contents in
the bottom of the vial where it can be properly mixed. Following
delivery of the slurry material to the vial, the robot is operable
to withdraw the distal end of the needle 401 at high speed past the
lips 241 of the duckbill valve to the position shown in FIG. 13
between the lips 241 and the seal 229. The needle is held in this
position for a short dwell period (e.g., 1-2 seconds) sufficient to
enable the lips 241 of the valve to close and for the robot speed
along the Z-axis of the rack to be reduced to a slower speed (i.e.,
the robot arm speed along the Z-axis is reset at this point to
normal). During this time the annular seal 229 is in sealing
engagement with the needle 401 to prevent any substantial leakage
past the lips while they are closing. The robot then moves the
needle at the slower speed to a position where it is completely
withdrawn from the cannula passage and the cannula is again at a
height sufficient to clear the reactor modules. As the needle 401
withdraws from the cannula passage 215, the head 455 of the cannula
support 443 returns to its needle supporting position shown in
solid lines in FIG. 26.
[0086] After each aspiration into the cannula 21 and after each
delivery from the cannula, the cannula is preferably moved to the
cleaning apparatus 25 and cleaned for several reasons. First,
cleaning avoids cross-contamination of materials. Second, small
particles (e.g., silica particles) which might otherwise interfere
with or damage the reaction equipment are removed. And third,
cleaning removes any build-up of polymer material on the needle 401
adjacent the port 409. (Some polymerization may occur in the needle
prior to dispensing, when the needle is first exposed to reactant
gas in the cannula passage.) If such build-up is not removed, it
could interfere with the delivery of material from the cannula and
subsequent aspirations into the needle. Prior to insertion of a
cannula into the appropriate wash tower 101, 111 and/or ultrasonic
cleaning device 141, the power cylinder 329 of a respective robot
is actuated to rotate the robot arm 307L, 307R to its home (or
non-tilted) position in which the needle is vertical. The needle is
then lowered for cleaning.
[0087] The robot system 23 is operated to move the cannula 21 back
to the rack 17 containing the slurry source followed by aspiration
and delivery of slurry to a second and subsequent vessels as
necessary to load the reactor. Although the same slurry can be
delivered to each of the vessels, it may be desired in some
reaction protocols to deliver a second slurry that differs in
composition from the first slurry to at least some of the remaining
vessels in the reactor. The second slurry may differ in composition
in terms of solid particulate concentration and/or the solid and
liquid components of the slurry. For a single run of the reactor,
there can be as many slurries as there are reaction vessels such
that there may be 1, 2, 8, 16, 24 or 48 of different slurry
compositions.
[0088] It will be understood that the two robot arms 307L, 307R
move independent of one another to carry out the dispensing process
in the most efficient manner. As noted previously, the left robot
arm typically services the left bank of reactor modules and the
right arm the right bank of modules. Alternatively, one robot arm
could be used to service all reactors. The speed at which the
robots move the cannulas may also vary to reduce the time needed to
load the vessels. For example, the cannula 21 may be moved at
higher speeds when larger distances are being traversed, and at
slower speeds at other times, as when the cannula is approaching
various destinations and during the initial stages of needle
insertion into a cannula passage 215.
[0089] After the vessels have been loaded, the reactions are
monitored for a desired interval of time or reaction stage or until
the reactions are considered to be finished, following which
quenching gas (e.g., CO.sub.2) is delivered to the vessels through
lines 57 to terminate the reaction. After the reaction is
completed, and prior to removing samples and vessels, appropriate
venting procedures should be followed to ensure that there is no
loss of product through the vent lines. Specifically, if venting of
the reaction vessels is too fast, the solid supported catalyst or
other particulate materials (e.g., such as polymer particles) may
vent through the vent lines 57. Venting procedures may include slow
venting (e.g., vent valve cycling) and/or inert gas purging (e.g.,
argon or nitrogen). After the appropriate venting procedures are
complete, the reactor covers 195 are removed to allow removal of
the reaction samples and replacement of the removable vials and
stirrers 175.
[0090] In a preferred embodiment, the reaction vials 165 used in
the reactor modules 9M should have a cross-sectional shape
corresponding to the cross-sectional shape of the wells 163 (e.g,
circular), a volume somewhat greater than the total volume of
reaction materials and/or products to be contained by a vessel, and
a height such that when the vial is placed in a well 163, the rim
of the vial is at an elevation below where the cannula passage 215
enters the well. Preferably, the open upper end of the reaction
vial is positioned for receiving the distal end of the needle 401
in its delivery or dispensing position, with the port 409 of the
needle located inside the vial at an elevation below the upper end
of the vial and facing downward. Thus, the height of the vial will
vary depending on various factors, including the angle of the
cannula passage 215, the reactor height, the depth of the well 163,
and other factors. In the preferred embodiment, the vial has a
rounded bottom and a cylindric side wall extending up from the
bottom and terminating in a rim defining an open upper end of the
vessel. For use in a reactor block of the type shown in FIG. 10,
the side wall of the reaction vial has an inside diameter in the
range of about 0.5-2.5 in., more preferably in the range of about
0.5-0.75 in., and most preferably about 0.609 in.; the vial has an
overall height in the range of about 1.0-4.0 in., more preferably
in the range of about 1.5-3.0 in., and most preferably about 2.15
in; and the vial defines a volume in the range of about 5-200 ml,
and preferably in the range of about 5-20 ml, and most preferably
about 10 ml.
[0091] In the event there is a need or desire to move, remove,
and/or replace one or more of the reactor modules 9M, as during a
maintenance procedure, the carriage extension 83 is disconnected
from the fixture 85 on the table 3 by disconnecting the master
locking device 81. This disconnection triggers a shut-off switch
which renders the robot system 23 inoperable. Disconnection of
device 81 allows all of the carriage plates 67 to be moved together
as a unit along the rails 61. If desired, one or more of the other
carriage plate locking devices 75 may be released to disconnect the
appropriate carriage plates 67 from one another to allow the plates
to be slidably moved relative to one another along the rails 61 and
the reactor modules 9M to be separated for convenient service or
rearrangement of the reactor matrix. After the modules are serviced
and/or rearranged, the carriage plates 67 are reconnected and the
carriage extension 83 reconnected to the table fixture 85 to render
the robot operable.
[0092] It will be observed from the foregoing that the parallel
reactor apparatus of the present invention represents an advance
over prior systems. The system can be used to deliver
hard-to-handle (e.g., "sticky") slurry materials. For example, as
discussed herein, solid supported catalyst particle size may be so
small as to be considered "catalyst fines" or other
characterizations that are typically used in industry. At these
particle sizes, reactor or equipment fouling is possible. One of
the benefits of this invention is that such fouling is minimized
while still providing for the delivery of accurate volumes to the
reactor vessels in an efficient, fully automated manner, and at
pressures other than ambient, if desired.
[0093] When introducing elements of the present invention or the
preferred embodiment(s) thereof, the articles "a", "an", "the" and
"said" are intended to mean that there are one or more of the
elements. The terms "comprising", "including" and "having" are
intended to be inclusive and mean that there may be additional
elements other than the listed elements.
[0094] The following example is simply intended to further
illustrate and explain the present invention. This invention,
therefore, should not be limited to any of the details in this
example.
EXAMPLE
[0095] In general, with the reactor modules 9M in a benign state,
and the reactor covers 195 removed, reaction vials 165 are inserted
in the reactor wells 163. Disposable stirrers 175 are attached to
the drivers 179 and checked to ensure that the coupling 181 is
engaged. Before the covers 195 are re-secured, a metal tool is used
to push each vial all the way to the bottom of the reactor well
163, ensuring the vial is not obstructing the cannula passage 215.
After the vials are verified to be in the correct position, the
reactor covers 195 are secured to the reactor modules. Purge
routines are run as defined earlier.
[0096] Experimental library design is supplied, which specifies
reactant components, quantities as well as database storage and
retrieval parameters. For a standard catalyzed polymerization
reaction, the robot system 23 is instructed to add to each reaction
vial 165 200 .mu.l of liquid co-monomer 1-octene, followed by 4500
.mu.l of hexane solvent, with the left arm 307L of the robot
servicing the left 3 modules 9M of the reactor and the right arm
307R of the robot system servicing the right 3 modules of the
reactor (see FIG. 1). While adding solvent and co-monomer, syringe
flow rates are set to initial values of:
[0097] Start Speed: 100 .mu.l/s
[0098] Top Speed: 300 .mu.l/s
[0099] Cutoff Speed: 100 .mu.l/s
[0100] For each X,Y and Z movement, there are 3 speeds for each
robot arm 307 and, in this experiment, those speeds are the same
for the right and left arms of the robot system. These speeds are
set to have the following initial values:
[0101] Start speed: X=11.17 mm/sec, Y=28.11 mm/sec., and Z=9.8
mm/sec.
[0102] End speed: X=893.6 mm/sec, Y=568.8 mm/sec., and Z=196
mm/sec.
[0103] Acceleration: X=900 mm/sec.sup.2, Y=800 mm/sec.sup.2, and
Z=500 mm/sec.sup.2.
[0104] Once these reagents are added, the temperature is set to the
specified temperature from the experimental design, which in this
case is 85.degree. C. Simultaneously, the stirrers 175 are
activated to stir at their desired RPM, which is 800 RPM. The
temperatures in the reaction chambers of the reactor modules 9M are
allowed to stabilize to their set point(s). Upon stabilization,
each reaction chamber is charged with ethylene gas at a pressure of
about 100 psig, with the uptake of ethylene being monitored. After
saturation of the solvent with ethylene (which takes an average of
about 10 minutes), non-catalyst and catalyst material can be added
to each reaction chamber. For example, 200 .mu.l of MMAO (modified
methylamumoxane) can be added as a scavenger, followed by 500 .mu.l
of additional hexane solvent acting as a chaser to flush the
cannula 21. (Note that this entire process is automated with the
robot system 23). During aspiration of the MMAO and hexane, the
initial syringe flow rates are used. During movements between the
reactor chambers and reagents, the stated initial robot arm speeds
are used. Once the cannula 21 has reached the position shown in
FIG. 12, the arm speed is slowed down to have a Z acceleration
component of 250 mm/sec.sup.2, allowing the needle 401 to pierce
the wiper member 265. This arm speed is used throughout this
portion of the addition sequence. When the cannula reaches the
fluid delivery the position shown in FIG. 14, the syringe flow rate
is changed to 100 .mu.l/s (start), 400 .mu.l/s (stop), 100 .mu.l/s
(cutoff). After the cannula is removed from the cannula passage
215, the robot arm speeds and syringe flow rates are reset to their
initial values. The cannula 21 is then cleaned at the appropriate
wash stations 101, 111 and flushes a sufficient volume of solvent
to remove any and all memory of the previous reagent, on average
1000 .mu.l per wash station.
[0105] Preparation of a slurry is initiated by adding a solid
supported catalyst to each reaction vial 165. The solid supported
catalyst is prepared as is well known in the art, as disclosed for
example in U.S. Pat. No. 5,643,847 or U.S. Pat. No. 5,712,352, each
of which is incorporated herein by reference. After the above
described wash sequence has concluded, the two robot arms 307L,
307R move at the same speed to move the cannulas 21 to their
respective orbital shakers 141. Each shaker supports a rack 17
comprising two rack panels each holding 24 individual 1.0 ml mixing
vials, spaced in an 8.times.3 array, 48 vials total. Of the 48
mixing vials 24 contain a solid supported catalyst e.g., 10 mg of
solid supported catalyst to be delivered to corresponding reactor
vials 165. The shaker is operated at a speed of 1100 RPM. The
cannula 21 aspirates diluent from a separate reagent vial
accessible to the robot system 21, following which the cannula is
moved to the first mixing vial where it dispenses 500 .mu.l of
diluent, in this case toluene. The cannula 21 is then washed at a
station 101, 111 for a sufficient period of time, during which the
solid supported catalyst particles in the mixing vial 165 are
suspended in the diluent to provide a substantially homogeneous
slurry. After washing, the cannula moves back to a position just
above the rim of the mixing vial 15 containing the slurry for the
first reaction vial 165 and pauses. This pause allows the robot arm
speed and the syringe flow rate to be decreased to the initial
values noted above, except the Z-deceleration component is set to
250 mm/sec.sup.2 and the syringe flow is changed to 50 .mu.l/sec
(start), 25 .mu.l/sec (stop) and 50 .mu.l/sec (cutoff). As
described, the lower speed allows the cannula to enter the slurry
without altering the vortexing and allows aspiration of
substantially homogeneous slurry without selectivity. While the
cannula is paused above the rim of the mixing vial, the syringe
pump is filled with 500 .mu.l of a chaser solvent (toluene) from
the same solvent reservoir. The cannula then descends into the
slurry and pauses. 100 .mu.l of slurry containing 1 mg of solid
supported catalyst is aspirated from the first mixing vial 15. The
robot arm speed and syringe flow rate are reset and the cannula 21
is moved to a vial on the same rack 17 containing solvent and
aspirates 50 .mu.l of solvent to act as a liquid barrier. The
cannula is then moved to the reactor module containing the first
reaction vial 165, and the injection sequence described earlier and
shown in FIGS. 12-14 is carried out. Prior to movement of the
cannula from the position shown in FIG. 13 to the delivery position
shown in FIG. 14, the speed of the robot arm is increased to have a
Z-acceleration component of 1450 mm/sec.sup.2. This allows the
cannula 21 to reach fluid delivery position as quickly as possible.
The syringe flow rate is also increased to 100 .mu.l/sec (start),
400 .mu.l/sec (stop), 100 .mu.l/sec (cutoff). Upon reaching the
delivery position, the syringe pump 43 forces the entire contents
of the cannula, i.e., solvent chaser, slurry, and liquid barrier,
at the highest possible flow rate. Once delivery is completed, the
cannula is withdrawn from the cannula passage 215 in the manner
previously described, the cannula moving first to the dwell
position shown in FIG. 13, where the robot arm speed and syringe
flow rate are decreased to their initial values, and then withdrawn
completely from the cannula passage 215. The cannula then goes
through the appropriate wash routine. The sequence is repeated for
each and all reaction vials 165. Upon catalyst injection to each
reaction vial, polymerization occurs, allowing catalyst performance
from a slurry to be evaluated
[0106] In view of the above, it will be seen that the several
objects of the invention are achieved and other advantageous
results attained.
[0107] As various changes could be made in the above constructions
without departing from the scope of the invention, it is intended
that all matter contained in the above description or shown in the
accompanying drawings shall be interpreted as illustrative and not
in a limiting sense.
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