Note: Descriptions are shown in the official language in which they were submitted.
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PRESSURE CYCLING SYSTEMS AND RELATED METHOD
CROSS REFERENCE TO RELATED APPLICATIONS
Pursuant to 35 USC 119(e), this application claims the benefit of prior U.S.
Provisional Application 60/914,926, filed Apri130, 2007 and U.S. Provisional
Application 60/886,817, filed January 26, 2007. Each of these applications is
incorporated by reference in its entirety.
TECHNICAL FIELD
This disclosure relates to controlling pressure-sensitive reactions, and more
particularly to systems and methods for controlling the timing of pressure-
sensitive
reactions.
BACKGROUND
Devices are known for providing control over timing and/or synchronization of
pressure-sensitive reactions (e.g., chemical reactions). Such devices are
known to include
one or more pressure modulated reaction vessels and means for producing
fluctuations in
pressure in the reaction vessels. Samples can be deposited in the reaction
vessels and
exposed to changes in pressure to control one or more pressure-sensitive
reactions within
or between the samples.
SUMMARY
In general, this disclosure relates to pressure cycling systems and related
methods.
The systems can be used, for example, to provide a pressure modulated
environment for
controlling pressure-sensitive events (e.g., physical, kinetic, structural,
morphological,
thermodynamic, and/or chemical reactions, e.g., enzymatic and non-enzymatic
reactions).
In one aspect, a pressure cycling system includes a reaction chamber
configured
to receive a sample and a charge pump in fluid communication with the reaction
chamber.
The charge pump is operable to convey a fluid from a fluid source toward the
reaction
chamber. The system also includes a check valve disposed between the charge
pump and
the reaction chamber. The check valve is operable to inhibit the flow of fluid
from the
reaction chamber toward the charge pump. A pressure intensifier is in fluid
communication with the reaction chamber. The pressure intensifier is
pneumatically
operable to adjust a pressure in the reaction chamber. A controller is
configured to
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control operation of the charge pump and the pressure intensifier. The
controller is
configured to pressurize the reaction chamber to a first pressure through
operation of the
charge pump. The controller is also configured to fluctuate the pressure in
the reaction
chamber between a second pressure and a third pressure through operation of
the pressure
intensifier.
In another aspect, a method of controlling timing of pressure-sensitive
reactions
includes depositing a sample in a reaction chamber and pressurizing the
reaction chamber
to a first pressure. Pressurizing the reaction chamber includes conveying a
fluid from a
fluid source to the reaction chamber through a check valve. The method also
includes
cycling a pressure level in the reaction chamber between a second pressure and
a third
pressure. Cycling the pressure level includes driving a pressure intensifier
with a
pressurized gas.
Embodiments can include one or more of the following features.
In some embodiments, the third pressure is greater than the second pressure,
and
the second pressure is greater than or equal to the first pressure.
The controller is configured to control operation of the charge pump and the
pressure intensifier based, at least in part, on user input.
In some implementations, a fluid pressure sensor is disposed between the
charge
pump and the check valve and in communication with the controller. The
controller is
configured to control operation of the charge pump and the pressure
intensifier based, at
least in part, on feedback from the fluid pressure sensor.
In some embodiments, the controller is configured to inhibit operation of the
charge pump in response to receiving feedback from the fluid pressure sensor
indicating
that the reaction chamber is pressurized to the first pressure.
In some implementations, the controller is configured to initiate operation of
the
pressure intensifier in response to receiving feedback from the fluid pressure
sensor
indicating that the reaction chamber is pressurized to the first pressure.
In some embodiments, the systems and/or methods can include a pressure
regulator operable to control a flow of a pressurized gas from a pressurized
gas source
toward the pressure intensifier. The controller can be configured to control
the operation
of the pressure regulator based on a feedback from the fluid pressure sensor.
In some implementations, the controller is configured to control operation of
the
pressure regulator based, at least in part, on user input.
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In some embodiments, a gas pressure sensor is disposed between the pressure
regulator and the pressure intensifier, and configured to provide feedback to
the
controller. The controller can be configured to control operation of the
pressure regulator
based, at least in part, on the feedback from the gas pressure sensor.
In some implementations, a directional control valve is disposed between the
pressure regulator and the pressure intensifier and operable to control the
flow of
pressurized gas between the pressure regulator and the pressure intensifier.
In some embodiments, the controller can be configured to control operation of
the
directional control valve.
In some implementations, the controller is configured to control operation of
the
directional control valve based, at least in part, on user input.
In some embodiments, a gas pressure sensor is disposed between the pressure
regulator and the pressure intensifier. The gas pressure sensor can be
configured to
provide feedback to the controller. The controller can be configured to
control operation
of the directional control valve based, at least in part, on feedback from the
gas pressure
sensor.
In some implementations the directional control valve comprises a 4-way
directional control valve.
In some embodiments, the pressure intensifier includes a pneumatic chamber, a
fluid chamber arranged in fluid communication with the reaction chamber, and a
piston
disposed between the pneumatic chamber and the fluid chamber. The piston is
displaceable to adjust a volume of the fluid chamber, and wherein the
controller is
configured to control displacement of the piston.
In some implementations a pressure regulator is operable to control a flow of
a
pressurized gas from a pressurized gas source toward the pneumatic chamber.
The
controller can be configured to control operation of the pressure regulator.
In some embodiments, the controller is configured to control fluid pressure in
the
reaction chamber through operation of the pressure regulator.
In some implementations, the controller is configured to control displacement
of
the piston through operation of the pressure regulator.
In some embodiments, a directional control valve is disposed between the
pressure
regulator and the pressure intensifier. The directional control valve is
operable to control
the flow of pressurized gas between the pressure regulator and the pneumatic
chamber.
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The controller can be configured to control operation of the directional
control valve, and
wherein the controller is configured to control displacement of the piston
through
operation of the pressure regulator and the directional control valve.
In some implementations, an end-of-stroke sensor is operable to detect the
presence of the piston at an end-of-stroke position, corresponding to a
minimum volume
of the fluid chamber. The end-of-stroke sensor is configured to provide
feedback to the
controller. The controller can be configured to control operation of the
charge pump
and/or the pressure intensifier in response to receiving feedback from the end-
of-stroke
sensor indicating that the reaction chamber is at the end-of-stroke position.
In some embodiments, the systems and/or methods can include a reaction vessel
defining the reaction chamber. The reaction vessel can include an aperture
extending
from the reaction chamber to a first open end and sized to allow insertion of
the sample
into the reaction chamber. The systems or methods can also include a vessel
cover
releasably connectable to the reaction vessel and operable to form a
substantially hermetic
barrier between the reaction chamber and the first open end.
In some implementations, the vessel cover includes a vent actuator (e.g., a
button)
being operable to vent gases and/or fluids from the reaction chamber during
use.
In some embodiments, the vessel cover includes a release valve being operable
to
inhibit the release of gases and/or fluids from the reaction chamber, and the
vent button is
engageable to open the release valve.
In some implementations, the vessel cover defines a flow pathway adapted to
allow the release of gases and/or fluids from the reaction chamber through the
vessel
cover.
In some embodiments, the systems and/or methods can include a drain line in
fluid communication with the flow pathway. The drain line can be disposed
between the
flow pathway and the fluid source. The drain line can be adapted to direct a
flow of gases
and/or fluids from the flow pathway toward the fluid source for recovery, or
drain for
disposal.
In some implementations, the flow pathway is adapted to direct a flow of gases
and/or fluids from the reaction chamber toward a drain region of the aperture.
In some embodiments, the reaction vessel defines a drain conduit in fluid
communication with the flow pathway and adapted to allow the release of gases
and/or
fluids from the flow pathway through the reaction vessel.
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In some implementations, the systems or devices can include a drain line
disposed
between the drain conduit and the fluid source and adapted to direct a flow of
gases
and/or fluids from the flow pathway toward the fluid source, thereby providing
for
recovery of gases and/or fluids released from the reaction chamber.
In some embodiments, a cover sensor is configured to communicate with the
controller. The cover sensor is operable to detect a connection between the
vent cover
and the reaction vessel. The controller can be configured to inhibit
pressurization of the
reaction chamber in response to receiving feedback from the cover sensor
indicating an
open connection between the vent cover and the reaction vessel.
In some implementations, the systems and/or methods can include a sample
vessel
defining a sample chamber configured to receive the sample, and including a
plunger
disposed between a first open end of the sample vessel and the sample chamber.
The
reaction chamber can be configured to receive the reaction vessel. The plunger
is
displaceable, in response to changes in pressure in the reaction chamber, to
adjust a
volume of the sample chamber, thereby to adjust a pressure exerted on the
sample.
In some embodiments, the second pressure is between about 150 psi and about
35,000 psi.
In some implementations, the third pressure is between about 3,500 psi and
about
35,000 psi.
In some embodiments, the methods can include venting the reaction chamber of
gases and/or fluids prior to pressurizing the reaction chamber to the first
pressure.
In some implementation, the pressure intensifier includes a pneumatic chamber,
a
fluid chamber arranged in fluid communication with the reaction chamber, and a
piston
disposed between the pneumatic chamber and the fluid chamber. Cycling the
pressure in
the reaction chamber can include displacing the piston relative to the fluid
chamber.
In some implementations, displacing the piston relative to the fluid chamber
includes directing a flow of pressurized gas towards a first surface of the
piston, to cause
the piston to move in a first direction relative to the fluid chamber; and
redirecting the
flow of pressurized gas towards a second surface of the piston, opposite the
first surface,
to cause the piston to move in a second direction, opposite the first
direction.
In some embodiments, the methods can include maintaining the reaction chamber
at a temperature of between about -40 C and about 100 C.
Embodiments can include one or more of the following advantages.
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In some embodiments, the systems provide for relatively small and light weight
pressure cycling.
In some implements, the systems and methods provide for portable pressure
cycling.
In some embodiments, the systems and methods provide for time, pressure and/or
temperature regulated control of pressure sensitive reactions.
In some implementations, the systems and methods can be used to conduct
reactions including one or more pressure-sensitive steps. These reactions can
include, for
example, anti-body binding, DNA binding, lysis, activation (germination),
inactivation,
structural modification, permeation/diffusion, dissolution, bond breaking and
bond
formation, e.g., covalent and/or non-covalent bond breaking and formation;
hydrophobic
or hydrophilic interactions; and structural conformations, e.g., folding, and
formation of
helices and sheets.
Other aspects, features, and advantages are in the description, drawings, and
claims.
DESCRIPTION OF DRAWINGS
FIG. 1 is a block diagram of a pressure cycling system.
FIGS. 2A through 2C are perspective, side, and cross-sectional views of a
reaction
vessel.
FIG. 2D is a detailed cross-section view of a cover attachment for the
reaction
vessel of FIGS. 2A through 2C.
FIGS. 3A and 3B are perspective and cross-sectional views of a sample vessel.
FIGS. 4A through 4C are perspective, side, and cross-sectional views of a
pressure
intensifier.
FIGS. 5A and 5B are perspective and cross-sectional views of a pressure
intensifier and reaction vessel assembly.
FIG. 5C is a detailed cross-sectional view of a check-valve tee of the
intensifier
and reaction vessel assembly of FIGS. 5A and 5B.
FIG. 6 is a schematic view of a pressure cycling system.
FIG. 7 is a graph illustrating a pressure-time profile of a pressure cycle of
a
pressure cycling system.
FIG. 8 is a display showing a pressure-time profile of a pressure cycling
system in
graphical format.
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FIGS. 9A and 9B are orthogonal front and side views of a reaction vessel and
vessel cover assembly.
FIGS. 9C and 9D are cross-sectional views of the reaction vessel and vessel
cover
assembly of FIGS, 9A and 9B.
FIG. 10 is a cross-sectional view of a reaction vessel with a thermally
regulated
fluid jacket.
DETAILED DESCRIPTION
Referring to FIG. 1, a pressure cycling system 10 includes a reaction vessel
11, a
pre-charge circuit 40, a pressure intensifier 60, and a control circuit 100.
Reaction vessel
11 receives and retains a sample 31 (see, e.g., FIG. 2C) for exposure to
pressure cycling
(e.g., for inhibiting and/or inducing chemical reactions of the sample). The
pre-charge
circuit 40 is in fluid communication with the reaction vessel 11 and is
configured to
deliver fluid (e.g., water) from a fluid source 42 (e.g., fluid reservoir) to
the reaction
vessel 11. The volume of fluid provided by the pre-charge system 40 determines
a
minimum pressure level within the reaction vessel 11 during pressure cycling.
The pressure cycling system 10 also includes a pressure intensifier 60 in
fluid
communication with the reaction vessel 11. The pressure intensifier 60 is
operable to
adjust the pressure level within the reaction vessel 11. Pressure generated by
the pressure
intensifier 60 determines a high pressure level within the reaction vessel 11.
The control circuit 100 communicates with the pre-charge circuit 40 and the
pressure intensifier 60 to control a pressure level within the reaction vessel
11 based on
both sensed system data and user input. The control circuit 100 includes a
controller 101
configured to communicate with the pre-charge system 40 for controlling the
flow of
fluid toward the reaction vessel 11. The control circuit 100 also includes a
electronic
pressure regulator 102 and a directional control valve 103. Controller 101
operates in
cooperation with the electronic pressure regulator 102 and the directional
control valve
103 to control a flow of pressurized gas (e.g., pressurized C02, air, an inert
gas, e.g.,
argon, nitrogen, etc.) from a pressurized gas source 61 (e.g., an air
compressor,
compressed gas bottle, lab line air, etc.) toward the pressure intensifier 60,
i.e., for driving
the pressure intensifier 60.
Referring to FIGS. 2A-2D, the reaction vessel 11 defines a reaction chamber 12
for receiving a sample vesse130 containing a sample 31. The reaction vessel 11
also
defines a first fluid port 13, which permits the flow of fluids into and out
of the reaction
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chamber 12. An aperture 14 extending between the reaction chamber 12 and an
outer
surface of the reaction vessel 11 allows for the placement of the sample
vesse130 into the
reaction chamber 12.
A removable cover 15 forms a releasable connection with the aperture 14 and
provides a hermetic barrier between the reaction chamber 12 and atmospheric
pressure.
As shown, for example, in FIGS. 2C and 2D, the cover 15 includes an o-ring 16
which
provides an air and fluid tight seal between the cover 15 and the wall of the
reaction
chamber 12. The cover 15 also includes a venting button 17 which is actuable
to
evacuate gas and/or fluid from the reaction chamber 12 through a venting bore
18 (i.e.,
for relief of pressure within the reaction chamber 12). More specifically, the
cover 15
defines a vent chamber 19, which is in fluid communication with the venting
bore 18.
The cover 15 also defines a vent conduit 20, which is in fluid communication
with the
vent chamber 19. When the cover 15 is disposed within the aperture 14 (as
shown in
FIG. 2C), the vent conduit 20 and the vent chamber 19 provide a flow pathway
allowing
for the flow of fluids and/or gases from the reaction chamber 12 to the
venting bore 18.
The venting button 17 is connected (i.e., via a stem 21) to a guide bearing
22, which is
slidably disposed in the vent chamber 19. The guide bearing 22 is connected to
a first end
of a push rod 23. The push rod 23 extends from the guide bearing 22, in the
vent
chamber 19, through the vent conduit 20 and terminates at a ball stop 24. When
the
venting button 17 is in a first position (shown in hidden lines in FIG. 2C),
the ball stop 24
engages a first end 25 of the vent conduit 20 thereby forming a check valve
that inhibits
the flow of fluids and/or gases between the first end 25 of the vent conduit
20 and the
venting bore 18. When the venting button 17 is actuated or pressed (e.g., as
indicated by
arrow 26) the ball stop 24 is displaced away from first end 25 of the venting
conduit 20,
thereby allowing fluids and/or gases to flow from the reaction chamber 21 to
the vent
chamber 19 and out of the venting bore 18. A drain line 27 (e.g., a flexible
hose) can be
provided between the venting bore 18 and the fluid reservoir 42 to allow for
the recovery
of fluids evacuated from the reaction chamber 21.
The cover 17 is held in place within the aperture 14 with the aid of dowel
pins
28a, which are held together by a dowel handle 28b. The dowel pins 28a engage
corresponding holes 29a, 29b in the cover 15 and reaction vessel 11. Cover 15
can be
removed from the reaction vessel 11 to allow access to the reaction chamber 12
(i.e., for
insertion and removal of the sample vesse130).
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Referring to FIGS. 3A and 3B, the sample vesse130 defines a sample chamber 32
to receive the sample 31. Sample vesse130 includes a removable cap 33 that
provides
access to the sample chamber 32 for insertion and removal of the sample 31.
The sample
vesse130 also includes a plunger 35. The plunger 35 is displaceable (as
indicated by
arrow 119) under pressure to adjust the volume, and as a result, the pressure,
of the
sample chamber 32. Suitable sample vessels 30 are available commercially under
the
trade name PULSEr'T' Tubes from Pressure BioSciences Inc. of West Bridgewater,
MA.
Referring to FIGS. 4A-4C, the pressure intensifier 60 includes a pneumatic
cylinder 62 and a fluid cylinder 72, which are fastened to each other through
a truss 80.
The pneumatic cylinder 62 is secured between first and second mounting plates
81a, 81b,
which are fastened together with first fastener elements 82. A first flange
83a of the truss
80 is mounted to the first mounting plate 81a with second fastener elements
83. The
reaction vessel 11 is secured between a second flange 83b of the truss 80 and
a third
mounting plate 81c with third fastener elements 84.
As shown in FIG. 4B and 4C, the pneumatic cylinder 62 defines a pneumatic
chamber 63 which houses a piston 64. The piston 64 includes a first extension
rod 65
which extends through a first washer 66, disposed between the pneumatic
cylinder 62 and
the first mounting plate 81a, and into the truss 80. Truss 80 defines a truss
chamber 85
which receives the first extension rod 65 from the pneumatic cylinder 62. A
second
extend rod 67 is mounted to a distal end 68 of the first extension rod 65
within the truss
chamber 85. A distal end 69 of the second extension rod 67 extends into the
fluid
cylinder 72 through washer assembly 71. Washer assembly 71 provides a fluid
seal
between the second extension rod 67 and the fluid cylinder 72.
The first and second mounting plates 81a, 81b define first and second cylinder
ports 70a, 70b, respectively, which are in communication with the pneumatic
chamber 63.
The first and second cylinder ports 70a, 70b provide a conduit for the flow of
pressurized
gas into and out of the pneumatic chamber 63 (i.e., to control displacement of
the piston
64).
The fluid cylinder 72 defines a fluid chamber 73 which receives the second
extension rod 67. A bearing 74 is provided to guide and support the second
extension rod
67 within the fluid chamber 73. The fluid cylinder 72 also defines a second
fluid port 75,
which permits the flow of fluids into and out of the fluid chamber 73. The
piston 64 is
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displaceable along the pneumatic chamber 63 (as indicated by arrows 120) to
adjust the
volume the fluid chamber 73.
As shown in FIGS.5A-5C, the reaction vessel 11 is connected the pressure
intensifier 60 through a check-valve tee 90. A first pipe section 91 is
fastened between
the reaction vessel 11 and the check-valve tee 90. The first pipe section 91
provides a
first fluid conduit 92 between the first fluid port 29 and a first fluid
pathway 93 of the
check-valve tee 90. A second pipe section 94 is fastened between the pressure
intensifier
60 and the check-valve tee 90. The second pipe section 94 provides a second
fluid
conduit 95 between the second fluid port 75 and the first fluid pathway 93 of
the check-
valve tee 90. Together, the first pipe section 91, the check-valve tee 90, and
the second
pipe section 94 allow for the transfer of fluid between the pressure
intensifier 60 and the
reaction vessel 11. The check-valve tee 90 also includes a second fluid
pathway 96 which
extends between an inlet port 97 and the first fluid pathway 93. A check-valve
98 (shown
schematically in FIG. 5C) is disposed within the second fluid pathway 96. The
check-
valve 98 allows for the flow of fluid from the inlet port 97 toward the first
fluid pathway
93, while, at the same time, inhibits flow in the opposite direction (i.e.,
from the first fluid
pathway 93 toward the inlet port 97. Thus, fluid flowing from an external
source (as
indicated by arrow 122) is allowed to enter the reaction chamber 12 and the
fluid chamber
73 through inlet port 97, but will be inhibited from escape causing pressure
to build in the
fluid region between the reaction chamber 12 and the fluid chamber 73.
Referring to FIG. 6, the pre-charge circuit 40 delivers fluid to the reaction
vessel
11 through the check-valve tee 90. The pre-charge circuit 40 includes a charge
pump 41
driven by relay 43, a fluid reservoir 42, and a pressure sensor 44.
The controller 101 controls operation of the charge pump 41, which, in turn,
controls the flow of fluid from the fluid reservoir 42 to the check-valve tee
90. The
pressure sensor 44, together with the controller 101, monitors fluid pressure
in the flow
line 45 between the charge pump 41 and the check-valve tee 90. The fluid
pressure will
increase as the reaction vessel 11 is filled with fluid. Once the pressure
sensor 44 detects
a line pressure indicating that the reaction vessel 11 is charged to the
predetermined
minimum (pre-charge) pressure level (e.g., between about 150 and 200 psi), the
controller
101 will discontinue operation of the charge pump 41 to inhibit further flow
to the
reaction vessel 11.
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The controller 101 also controls operation of the electronic pressure
regulator 102.
Once the pressure sensor 44 detects that the reaction vessel 11 is pre-charged
to the
minimum pressure level, the controller 101 will command the electronic
pressure
regulator 102 to allow for the flow of compressed gas from an external
pressure source 61
(e.g., compressed gas, e.g., C02, at 90 psi or greater, e.g., 800 psi) to the
pressure
intensifier 60. Pressurized gas from supply 118 is delivered through a first
pressure
regulator 142 toward the electronic pressure regulator 102. The first pressure
regulator
142 drops the pressure down to a level that the electronic pressure regulator
102, and
other system components, can handle. Pressurized gas flows from the electronic
pressure
regulator 102 to the pressure intensifier 60 through directional control valve
103, which is
also controlled by the controller 101.
Directional control valve 103 controls the direction of the flow of the
pressurized
gas into the pneumatic cylinder 61, alternating between fist and second
cylinder ports
70a, 70b. At start-up, e.g., prior to pre-charge, directional control valve
103, under the
direction of the controller 101, is set to an intensifier retract position
connecting the
electronic pressure regulator 102 to the first cylinder port 70a and connects
the second
cylinder port 70b to a drain line 110. The controller 101 sets the electronic
pressure
regulator 102 to a nominal pressure value (e.g., 10 psi) to force pressurized
gas toward a
first surface 64a of the piston 64, to cause piston 64 to move to a fully
retracted position
(i.e., a position coincident with a maximum volume of the fluid chamber 73
(see, e.g.,
FIG. 4C)). Once the reaction vessel 11 reaches the pre-charge pressure, the
controller
101 readjusts the directional control valve 103 to an intensifier extend
position connecting
the electronic pressure regulator 102 to the second cylinder port 70b and
connecting the
first cylinder port 70a to the drain line 110 allowing the pressurized gas to
drain through
muffler 104. Then, the controller 101 will control the flow of pressurized gas
through the
electronic pressure regulator 102 to force pressurized gas towards a second
surface 64b of
the piston 64 to cause the piston 64 to move toward an extended position
decreasing the
available fluid volume of the fluid chamber 73 (FIG. 4C), and, as a result,
causing
pressure within the reaction chamber 12 to increase. The controller 101 sets
the output of
the electronic pressure regulator 102 to a calculated output pressure applied
to the
pressure intensifier 60.
By maintaining a controlled gas pressure on the pneumatic cylinder 62, a
controlled high pressure is generated in the reaction chamber 12. For pressure
cycling,
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the pressure applied to the pneumatic cylinder 62 can be varied over time to
cause the
pressure within the reaction chamber 12 to cycle between the low and high
pressure
levels.
As shown in FIG. 5, the control circuit 100 can include a cover safety sensor
106
for sensing the presence of the cover 15 (see, e.g., FIG. 2D) in the proper
position in the
reaction vessel 11. The controller 101 can be configured to inhibit operation
of the
system components in response to feedback from the cover safety sensor 106
indicating
that the cover 15 is not in proper position for pressurization of the reaction
chamber 12.
The control circuit 100 can also include an end-of-stroke (EOS) sensor 107.
The end-of-
stroke sensor 107 detects an end-of-stroke condition, indicating that the
piston 64 has
reached a position of maximum forward displacement without achieving the high
pressure level within the reaction chamber 12. The controller 101 can be
configured to
inhibit operation of the system components in response to feedback from the
EOS sensor
107 indicating that the piston 65 has reached the end-of-stroke position.
As shown in FIG. 6, the control circuit 100 includes a user input 108, and a
display 109 for showing system performance. The user input 108 allows a user
to enter
process parameters into the controller 101. Referring to FIG. 7, the process
parameters
can include one or more of the following:
= Target pressures:
o Target high pressure value P1, e.g., with a range of between about
3,500 psi and about 35,000 psi; and
o Target low pressure value P2, e.g., with a range of between about
150 psi and about 35,000 psi;
= Linear pressure ramp time: t1 and t3, e.g., with a range of between about
0.1 seconds and about 199 seconds;
= Static pressure hold time: t2 and t4 (i.e., the dwell time (t2) at the high
pressure value after the pressure is pulsed from the low pressure value and
the dwell time (t4) at the low pressure value after the pressure is pulsed
from the high pressure value, e.g., with a range of between about 5
seconds and about 100 hours (e.g., to incubate the growth of deep sea
microorganisms);
= Ambient pressure hold time between cycles, e.g., with a range of between
about 1 second and about 100 hours; and/or
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= Number of cycles (N), e.g., with a range of between 1 and 99 cycles.
The inputs may be reaction specific. In one example, P1 can be lower than P2
to
germinate bacterial spores followed by higher pressure lysis. In this example,
t1 can be
relatively long to allow germination and t2 could be shorter. In another
example, P1 can
be relatively high to thermodynamically change the structure of proteins and
generate
metastable morphologies and t3 can be relatively long to preserve these
morphologies as
a lower pressure P2 is reached.
As illustrated in FIG. 8, for example, the display 109 can be used to show the
pressure profile of the system in graphical format. Referring to FIG. 8, the
solid line 130
represents an intended pressure profile, as determined from user input (i.e.,
user entered
process parameters) and/or default system settings, while the dashed line 132
represents
an actual profile achieved. The two profiles may not be exactly identical due
to the
power capacity of the compressed gas system used and the maximum pressure
available.
In use, the system 10 is powered up and the electronic pressure regulator 102
is set
to 10 psi. The directional control valve 103 is set to the intensifier retract
position,
allowing the piston 65 to retract to a minimum pressure level position. The
desired
pressures (e.g., high pressure level and low pressure level), hold times, and
other process
parameters are entered into the controller 101 through the user input 108.
Next, sample 31 is deposited in the sample vesse130, and the sample vesse130
is
filled with fluid 36, e.g., water or silicon oil, to allow applied pressure to
be transferred to
the capsule. Fluid 36 aids the system in reaching the maximum pressure
capability of the
pressure intensifier 60. The sample vesse130 is inserted into the reaction
chamber 12
through aperture 14. Then, the cover 15 is inserted by simultaneously
depressing the
cover venting button 17 and pushing down on the cover 15. This allows for the
venting
of excess air and/or fluid from the reaction chamber 12. Once the cover 15 is
in position,
the dowel pins 28a can be inserted to lock the cover 15 in place. At this
point the
pressure in the reaction chamber 12 is about 0 psi.
With confirmation from the cover safety sensor 106 that the cover 15 is in the
proper position, the process is allowed to proceed. The charge pump 41 is
activated to fill
the reaction chamber 12 to the pre-charge pressure P2 (e.g., between about 150
and about
200 psi). The pressure sensor 44 signals the controller 101 once the reaction
chamber 12
has reached the pre-charge pressure. Then, the controller 101 turns the charge
pump 41
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off, shifts the directional control valve 103 into the intensifier forward
position, and
commands the electronic pressure regulator 102 to pressurize the pressure
intensifier 60
such that pressure within the reaction chamber 12 is elevated to the high
pressure level
P1, as defined by the process parameters. If the EOS sensor 107 detects an end-
of-stroke
condition, or, if the cover safety sensor 106 detects that the cover 15 is not
in the proper
position, the system 10 will indicate an error and depressurize the pressure
intensifier 60.
During pressure cycling, the controller 101 controls the pressure in the
reaction
chamber 12 through the electronic pressure regulator 102. Utilizing the
electronic
pressure regulator 102, the controller 101 fluctuates the pressure in the
reaction chamber
12 between the low pressure level (e.g., a reaction permissive pressure, e.g.,
between
about 150 psi and about 35,000 psi) and the high pressure level (e.g., between
about 3,500
psi and about 35,000 psi, e.g., a reaction inhibitory pressure).
Depressurization of the
pressure intensifier 60 can be achieved by setting the electronic pressure
regulator 102 to
0 pressure (i.e., 0 psi). During pressure cycling, the system pressure is
monitored by the
gas pressure sensor 105. The controller 101 scales a feedback signal from the
gas
pressure sensor 105 to calculate the pressure in the reaction chamber 12
before display.
At the end of the run, the directional control valve 103 is de-energized,
connecting
both of the first and second cylinder ports 70a, 70b to the drain line 110,
thereby allowing
the piston 64 to retract, under system pressure, to the minimum pressure level
position
(i.e., high pressure decompression). Following high pressure decompression,
the pre-
charge pressure can be released by depressing the cover venting button 17.
Fluid can also
be purged from the reaction chamber 12 by simultaneous actuating the charge
pump 41
and depressing the cover venting button 17.
Once the reaction chamber 12 has been vented to 1 atm, the cover 15 can be
removed by withdrawing the dowel pins 28a and the sample vesse130 can be
withdrawn.
While certain embodiments have been described above, other embodiments are
possible.
As an example, FIGS. 9A-9D illustrate another embodiment of a reaction vessel
11' and removable cover 15' assembly. As shown, for example, in FIGS. 9C and
9D,
rather than evacuating fluid directly out of the cover 15' (e.g., through a
venting bore),
fluid discharged from a reaction chamber 12' is redirected from a vent conduit
20'
through a flow pathway, defined by first and second draining channels 34a,
34b, toward a
drain region 37 within an aperture 14' of the reaction vessel 11'. As shown in
FIG. 9C,
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for example, the first and second draining channels 34a, 34b can include a
pair of drilled
holes. A first hole (i.e., first draining channe134a) is formed (e.g.,
drilled) which extends
from a first surface 38a of the cover 15' into the vent conduit 20'. A
blocking ball 39 is
inserted into the first hole in order to seal the hole along the first surface
of the cover 15'.
A second hole (i.e., second draining channe134b) is formed, which extends from
a second
surface 38b of the cover 15' into the first draining channe134a.
Referring to FIGS. 9C and 9D, the reaction vessel 11' includes a sea146 (e.g.,
an
0-ring seal) disposed within a groove 47 in a wall of the aperture 14'. The
sea146 marks
a boundary of the drain region 37; the drain region 37 being the region within
the aperture
22' below the sea146. The sea146 creates a hermetic barrier with the first
surface 38a of
the cover 15' to inhibit the flow of discharged fluid from the drain region 37
past the seal
46. As shown in FIG. 9D, the reaction vessel 11' includes a drain bore 48 in
fluid
communication with the second draining channe134b. Fluid and/or gases exiting
the
reaction chamber 12' through the vent conduit 20' will be directed to the
drain region 37
and subsequently discharged through the draining bore 48. A drain line 27'
(e.g., a
flexible hose) can be provided between the draining bore 48 and the fluid
reservoir 42 to
allow for the recovery of fluids evacuated from the reaction chamber 12'.
Referring to FIGS. 9C and 9D, in operation, friction between the sea146 and
the
cover 15' and between the o-ring 16' and the wall of the reaction chamber 12'
can make
removal of the cover 15' forceful. With the dowel pins 28a removed, a pressure
assisted
lifting feature can be provided by utilizing the pressure within the reaction
chamber 12' to
lift the cover 15' past the o-ring 16' seal engagement zone (i.e., out of high
pressure
contact with the wall of the reaction chamber 12'). In one example, the
pressure of the
reaction chamber 12' is maintained at about 150 psi, and the seal diameter of
the o-ring
16' is about 7 inches, thereby creating a lifting force of about 57 pounds.
Once the cover
15' is lifted past the o-ring 16' engagement zone, the reaction chamber 12' is
placed in
direct fluid communication with the drain region 37 allowing fluid to drain,
thereby
causing the pressure in the reaction chamber 12' to drop. At this point, the
cover 15' will
no longer continue to move up and the sea146 is almost disengaged from contact
with the
first surface 38a of the cover 15'. Sea146 can be a relatively loose fitting
seal requiring
only hand force to remove the cover 15' from the aperture 14'.
In some embodiments, different controllers can have different capabilities.
For
example, in some embodiments, the controller allows for pressure ramping on
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pressurization and depressurization. In another example, the controller can
cycle pressure
between multiple additional distinct set points (e.g., 4, 5, or more) rather
the exemplary
three distinct pressure approach described above. In another embodiment, the
pressure
can be varied according to a computer-controlled wave form.
In some embodiments, the control circuit can include a pressure transducer
(see,
e.g., FIG. 6, item 140) arranged in fluid communication with the reaction
chamber for
direct measuring pressure within the reaction chamber.
In some implementations, the system can include a fluid drain line connecting
the
outlet port on the cover with fluid reservoir for recovery of purged fluid.
In some implementations, other combinations of equipment can be used to
implement the concepts described above. For example, in some embodiments, the
pressure intensifier and the reaction vessel can be a single unit rather than
two connected
units.
While the pressure cycling systems of the embodiments described above include
a
charge pump that is controlled by the system controller, some systems can have
a manual
override mode for manual pre-charge control.
In some embodiments, high pressure cycling (i.e., control over the flow of
pressurized gas to the pressure intensifier) can be conducted manually in
addition to or as
an alternative to the automated control described above.
In some implementations, the systems can include hand valve (see, e.g., FIG.
6,
item 144) to provide manual control over the flow of pressurize gas between
the gas
source and the electronic pressure regulator.
In some embodiments, the reaction chamber and the intensifier fluid chamber
can
be integrated into a single unit.
In some implementations, where the charge pressure is not needed, the systems
can operate without the charge pump (i.e., in some cases the charge pump can
be absent).
In some embodiments, the reaction chamber is made from or lined with a
material
(e.g., stainless steel) that is chemically compatible with the sample being
processed.
In some implementations, the systems can include temperature control for the
reaction chamber. For example, as shown in FIG. 10, in some cases the reaction
vessel
11 is surrounded by a cooling and/or heating jacket 146 to control the
temperature of the
reaction chamber. Referring to FIG. 10, jacket 146 includes inlet and outlet
ports 147,
148, respectively, which permit a temperature regulated fluid (e.g., from a
fluid reservoir
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(not shown) to be circulated into chamber 149 surrounding the reaction vessel
11. 0-rings
150, 151 provide a fluid seal for jacket 146. The temperature of reaction
chamber 12 can
be controlled within a range of about -40 C. to 100 C.
Accordingly, other embodiments are within the scope of the following claims.
17
