U.S. patent application number 10/799070 was filed with the patent office on 2004-10-28 for high throughput viscometer and method of using game.
This patent application is currently assigned to Symyx Technologies, Inc.. Invention is credited to Hajduk, Damian, Mansky, Paul.
Application Number | 20040211247 10/799070 |
Document ID | / |
Family ID | 24315174 |
Filed Date | 2004-10-28 |
United States Patent
Application |
20040211247 |
Kind Code |
A1 |
Hajduk, Damian ; et
al. |
October 28, 2004 |
High throughput viscometer and method of using game
Abstract
An apparatus and method for measuring viscosity or related
properties of fluid samples in parallel is disclosed. The apparatus
includes a plurality of tubes and reservoirs in fluid communication
with the tubes. The tubes provide flow paths for the fluid samples,
which are initially contained within the reservoirs. The apparatus
also includes a mechanism for filling the reservoirs with the fluid
samples, and a device for determining volumetric flow rates of
fluid samples flowing from the reservoirs through the plurality of
tubes simultaneously. The disclosed apparatus is capable of
measuring viscosity or related properties of at least five fluid
samples simultaneously. Useful reservoirs and tubes include
syringes.
Inventors: |
Hajduk, Damian; (San Jose,
CA) ; Mansky, Paul; (San Francisco, CA) |
Correspondence
Address: |
DOBRUSIN & THENNISCH PC
401 S OLD WOODWARD AVE
SUITE 311
BIRMINGHAM
MI
48009
US
|
Assignee: |
Symyx Technologies, Inc.
|
Family ID: |
24315174 |
Appl. No.: |
10/799070 |
Filed: |
March 12, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10799070 |
Mar 12, 2004 |
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10104203 |
Mar 22, 2002 |
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6732574 |
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10104203 |
Mar 22, 2002 |
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09578997 |
May 25, 2000 |
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6393898 |
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Current U.S.
Class: |
73/54.07 ;
73/54.06 |
Current CPC
Class: |
G01N 11/06 20130101 |
Class at
Publication: |
073/054.07 ;
073/054.06 |
International
Class: |
G01N 011/06; G01N
011/08 |
Claims
We claim:
1. An apparatus for measuring viscosity or related properties of a
plurality of fluid samples, the apparatus comprising: a three axis
robot; at least one tube providing a flow path for the plurality of
fluid samples, the tube having a pre-defined length and a
substantially uniform inner diameter over at least a portion of the
pre-defined length, the at least one tube being translatable by the
three axis robot; at least one reservoir for containing the fluid
samples associated with each tube via a hub, the reservoir in fluid
communication with the tube; and a device for determining the
volumetric flow rate as the fluid sample flows out of the reservoir
and through the tube.
2. The apparatus of claim 1, further comprising a mechanism for
filling the at least one reservoir selected from a vacuum source, a
single or multiple-channel pipette, or combinations thereof.
3. The apparatus of claim 1, wherein the device for determining the
volumetric flow rate comprises sensors locate at upstream and
downstream positions along each reservoir.
4. The apparatus of claim 3, wherein the sensors comprise a light
source and a light detector, the light detector generating a signal
in response to a momentary interruption of light form the light
source.
5. The apparatus of claim 1, wherein the hub is a luer hub.
6. A method of screening fluid samples comprising: a) providing a
plurality of fluid samples in a plurality of wells; b) locating a
tube in fluid communication with a first fluid sample with a three
axis robot, wherein the tube is associated via a hub with a
reservoir that is in fluid communication with the tube; c) filling
the reservoir with the first fluid sample; d) flowing the first
fluid sample out of the reservoir through the tube; e) determining
the volumetric flow rate as the first fluid sample is flowed out of
the reservoir; f) relating the volumetric flow rate to viscosity or
other property for the first fluid sample; and g) repeating steps
(b) through (f) for each of the plurality of fluid samples.
7. The method of claim 6, wherein the determining step comprises
measuring the times required for a meniscus in each reservoir to
travel a predetermined distance.
8. The method of claim 7, further comprising computing viscosities
of each of the fluid samples from the meniscus travel times.
9. The method of claim 7, further comprising estimating molecular
weights of the fluid samples from the meniscus travel times.
10. The method of claim 6, wherein an upstream and a downstream
detector are utilized to determine the volumetric flow rate.
11. An apparatus for measuring viscosity of a plurality of fluid
samples, the apparatus comprising: a three-axis robot adapted for
translation between the plurality of fluid samples; at least one
tube providing a flow path for each of the plurality of fluid
samples, the tube having a pre-defined length and a substantially
uniform inner diameter over at least a portion of the pre-defined
length, the at least one tube being translatable by the three axis
robot; at least one reservoir for containing the fluid samples
associate with each tube via a hub, the reservoir in fluid
communication with the tube; a mechanism for transferring each of
the plurality of fluid samples to the reservoir; and a pressure
sensor in the reservoir for determining pressure in the reservoir
as the fluid sample flows out of the reservoir.
12. The apparatus of claim 11, wherein the hub is a luer hub.
13. The apparatus of claim 11, wherein the three axis robot
comprises at least two arms capable of working in parallel.
14. A method for measuring viscosity of a plurality of fluid
samples, comprising the steps of: a) locating at least one tube in
fluid communication with a first fluid sample with a three axis
robot, wherein the tube is associated with a reservoir that is in
fluid communication with the at least one tube; b) filling the
reservoir with a first fluid sample; c) flowing the first fluid
sample out of the reservoir; d) determining the pressure in the
reservoir as the first fluid sample is flowed out of the reservoir;
e) calculating viscosity or related property for the first fluid
sample; and f) repeating steps (c) through (e) for each of the
plurality of fluid samples.
15. The method of claim 14, further comprising measuring the
molecular weight of each fluid sample.
16. The method of claim 14, wherein the fluid samples include a
polymer.
Description
BACKGROUND
[0001] 1. Technical Field
[0002] The present invention relates to a device and technique for
measuring viscosity and related properties of multiple samples, in
some embodiments simultaneously, and is particularly useful for
rapidly screening and characterizing a combinatorial library of
materials.
[0003] 2. Discussion
[0004] Combinatorial chemistry generally refers to methods and
materials for creating collections of diverse materials or
compounds--commonly known as libraries--and to techniques and
instruments for evaluating or screening libraries for desirable
properties. Combinatorial chemistry has revolutionized the process
of drug discovery, and has enabled researchers to rapidly discover
and optimize useful materials.
[0005] One useful screening criterion is viscosity, .eta., which is
a physical property that characterizes a fluid's resistance to
flow. For laminar flow of Newtonian fluids, including gases and
simple liquids, viscosity is proportional to the tangential
component of stress (shear force) divided by the local velocity
gradient. Although complex fluids such as pastes, slurries, and
high polymers do not follow the simple relationship between
tangential stress and local velocity gradient, viscosity and its
analogs nevertheless can serve as useful screening criteria. For
example, one can use viscosity measurements to estimate molecular
weights of polymers in solution.
[0006] Combinatorial libraries routinely comprise hundreds or
thousands of individual library members. As a result, most
viscometers are unsuitable for screening purposes because they were
designed to slowly process one sample at a time. Although generally
the throughput of serial instruments and techniques can benefit
from automation, many viscometers have relatively long response
times, require time-consuming sample preparation, and exhibit
sluggish temperature control, making such instruments impractical
for use as screening tools.
[0007] The present invention overcomes, or at least mitigates, some
or all the problems discussed above.
SUMMARY OF THE INVENTION
[0008] The present invention provides an apparatus. for measuring
viscosity or related properties of fluid samples in parallel. In
some embodiments, the apparatus includes a plurality of tubes and
reservoirs in fluid communication with the tubes. Each of the tubes
has a predetermined length and a uniform inner diameter over at
least a portion of the tube's length. In addition, the tubes
provide flow paths for the fluid samples, which are initially
contained within the reservoirs. The apparatus also includes a
mechanism for filling the reservoirs with the fluid samples, and a
device for determining volumetric flow rates of fluid samples
flowing from the reservoirs through the plurality of tubes
simultaneously. The disclosed apparatus is capable of measuring
viscosity or related properties of at least five fluid samples
simultaneously.
[0009] The present invention also provides an apparatus comprised
of an array of syringes for measuring viscosity or related
properties of fluid samples in parallel. Each of the syringes
includes a barrel for containing the fluid samples, a plunger
located within the barrel for aspirating the fluid samples into the
barrel, and a hypodermic needle in fluid communication with the
barrel. The hypodermic needle, which has a substantially uniform
diameter over a majority of its length, provides a flow path for
the fluid samples. The apparatus also includes upstream and
downstream detector arrays that are located along the barrel of
each syringe. The detector arrays, which monitor volumetric flow
rates of the fluid samples through each hypodermic needle, are
capable of measuring viscosity or related properties of at least
five fluid samples simultaneously.
[0010] Additionally, the present invention includes a method of
screening fluid samples. The method comprises (1) providing fluid
samples to a plurality of reservoirs; (2) allowing the fluid
samples to flow from the reservoirs through a plurality of tubes;
and (3) detecting the volumetric flow rates of at least five of the
fluid samples through each of the tubes simultaneously.
[0011] Another embodiment of the present invention uses the same
viscometer design with upstream and downstream detectors described
above, but places at least one of those viscometers on tip of the
arm of a three axis robot, and preferably at least two viscometers
are placed on the tip of at least two arms of a three axis robot.
In this embodiment, the viscometer is operated in the same manner
described above and is moved from well to well of a sample tray or
combinatorial library of samples. Many known liquid handling
systems incorporate one or more tips and the viscometer may be
placed on as many tips as are present in the robot being used. In
addition, when multiple arm robots with multiple tips are used a
high throughput instrument for viscosity measurements is provided.
For example 8 tips on a 9 mm pitch may be provided on one or more
arms of the robot. Thus, this embodiment of the present invention
is either a rapid serial measurement or a simultaneous measurement
on multiple samples.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 is a perspective front view of a parallel
viscometer.
[0013] FIG. 2 shows a partial exploded view of one of the syringes
that comprises the parallel viscometer.
[0014] FIG. 3 shows a cross sectional view of a syringe barrel and
plunger.
[0015] FIG. 4 shows a close-up, cross-sectional view of a first end
of a syringe barrel.
[0016] FIG. 5 shows a close-up, cross-sectional view of a second
end of a syringe barrel.
[0017] FIG. 6 shows a top view of a barrel retaining plate.
[0018] FIG. 7 shows a cross sectional view of a barrel retaining
plate.
[0019] FIG. 8 shows a top view of a Luer hub capture plate.
[0020] FIG. 9 shows a cross sectional view of a Luer hub capture
plate.
[0021] FIG. 10 shows a top view of a preload block.
[0022] FIG. 11 shows a cross sectional view of a preload block.
[0023] FIG. 12 shows a top view of a needle capture assembly.
[0024] FIG. 13 shows a cross sectional view of a needle capture
assembly.
[0025] FIG. 14 shows a perspective view of a detector block
module.
[0026] FIG. 15 shows a top view of an optional needle alignment
block.
[0027] FIG. 16 shows a plot of drop time versus sample number.
[0028] FIG. 17 shows a plot of drop time versus twenty-three
samples for a single syringe.
[0029] FIG. 18 shows a plot of relative viscosity-1 versus
concentration of polyisobutylene in hexane for six narrow molecular
weight distribution polyisobutylene standards.
[0030] FIG. 19 shows a plot of intrinsic viscosity versus weight
average molecular weight for narrow molecular weight distribution
polyisobutylene standards.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0031] Overview of Parallel Viscometer
[0032] A parallel viscometer made in accordance with the present
invention generally includes two or more tubes. The tubes can be
constructed of any material, but stainless steel is particularly
useful because of its mechanical strength, high thermal
conductivity, and excellent dimensional stability and control. Each
of the tubes has a substantially uniform inner diameter, d, over at
least a portion of its length, l, which defines a viscosity
measurement region. Typically, this region is the same for each of
the tubes and coincides with their total lengths, but one can vary
the inner diameter and length of individual tubes to account for
differences in sample viscosity. In addition, the inner diameter of
the tubes may assume any value as long as the Reynolds Number, R,
which provides a measure of inertial forces to viscous forces
within a liquid sample is less than about 10.sup.3--i.e., liquid
flow within the tubes is laminar. From a practical standpoint, d
and l are usually minimized to allow viscosity measurements using
as little of the samples as possible. This is often the case when
screening combinatorial libraries because the amount of any
particular sample or library member can be as small as about
10.sup.2 .mu.l.
[0033] The parallel viscometer also includes reservoirs for holding
the liquid samples prior to their introduction in the tubes. The
reservoirs should be chemically inert, and therefore suitable
fabrication materials include glass, PTFE, aluminum, and stainless
steel. As noted below, it is often desirable to monitor the
volumetric flow rate through the tubes by detecting changes in
sample volume within the reservoir. Since optical techniques are
well suited for this task, the reservoirs are often made of a
transparent material such as glass. The reservoir may be above or
below the tube.
[0034] In addition, the parallel viscometer includes a mechanism
for filling the reservoirs with the samples. Suitable filling
mechanisms include aspiration via fluid connection to a vacuum
source; manual or automatic transfer of liquid samples using a
single-channel or multiple-channel pipette; and direct loading and
subsequent melting of solid samples. As illustrated in FIG. 1,
syringe needles and barrels can serve as the viscosity measurement
regions (tubes) and the reservoirs, respectively. When using
syringes, the reservoirs (barrels) can be aspirated by withdrawal
of the syringe plungers.
[0035] Generally, the parallel viscometer also includes a device
for monitoring the volumetric flow rate, Q, of the samples flowing
through the tubes. As described below, once the volumetric flow
rate is known, one may calculate the viscosity of the samples from
the Hagen-Poiseulle equation, which relates fluid viscosity to the
volumetric flow rate and the pressure drop, .DELTA.P, across the
viscosity measurement region of an individual tube. For
gravity-driven flows, the pressure drop comprises the product of
the sample density, the gravitational acceleration, and the length
of the viscosity measurement region. When gravity is insufficient
to induce flow--i.e., when sample viscosity or capillary forces are
large--the parallel viscometer includes a mechanism for applying
and monitoring a force (pressure) that drives the liquid samples
through the tubes. Typically, the parallel viscometer employs rams
or pistons within the reservoirs to drive the fluid samples through
the tubes.
[0036] Useful devices for monitoring the volumetric flow rate
include sensor pairs located at upstream and downstream positions
along each of the reservoirs. Each sensor may comprise a light
source and a light detector, which generates a signal in response
to a momentary interruption of light resulting from a passing
liquid meniscus, a change in liquid opacity, or a shift in
refractive index. Alternatively, each sensor may consist of a
heated wire that generates a signal in response to a change in
electrical resistance resulting from dissimilarities in heat
transfer characteristics of liquids and gases. Other useful
detector pairs include magnetic sensors that generate a signal in
response to movement of a magnet float within the sample fluid, and
conductivity sensors that respond to differences in electrical
conductivity among fluids. In any case, the two signals from the
sensor pairs delimit the time interval for a known volume of sample
to pass through the viscosity measurement region (tube), which
allows calculation of Q.
[0037] Other techniques and devices for measuring or inferring Q
include measuring the mass of discrete samples that exit the tubes
during a predetermined time interval, and monitoring changes in
electrical capacitance of an electrically conductive cylindrical
reservoir and coaxial wire. In the latter technique, the
capacitance of the system varies as the ratio of liquid sample to
air in the reservoir changes. The parallel viscometer may also
employ proximity sensors to measure the speed of rams or pistons
when screening high viscosity samples. Regardless of the detection
system employed, the parallel viscometer typically uses an A/D data
acquisition board in tandem with a computer and necessary software
to record sensor output and to determine Q.
[0038] The parallel viscometer also includes one or more
receptacles for collecting samples exiting the tubes. Since the
samples are often reused in subsequent screening experiments, the
tubes are typically supplied with separate receptacles to prevent
cross-contamination of samples. Useful receptacles include wells of
standard ninety-six well microtiter plates. Because viscosity is a
strong function of temperature, the parallel viscometer may
optionally include an environmental chamber for maintaining the
fluid samples at a constant temperature.
[0039] Overview of the Viscometer on a Robotic Arm Tip
[0040] In this embodiment of the present invention, a three-axis
robot is provided having at least one arm and at least one tip on
that at least one arm. A single viscometer as described above is
placed on a tip of the arm of the robot. For example, a syringe may
be fitted over the robotic tip with a vacuum tight seal,
effectively becoming part of the tip. The needle can be inserted
into one of the sample wells (e.g. in a 96 well plate) and liquid
aspirated into the barrel or tube by reducing the pressure in the
barrel or tube. This may be done either by retracting the plunger
on a separate syringe pump, such as provided to aspirate and
dispense liquids in an automated liquid handling system, or by
shunting the line to a vacuum source. Once a sufficient quantity of
liquid is aspirated into the barrel, the syringe is lifted above
the sample's liquid level, and the liquid is allowed or forced to
flow through the needle and back into the sample well from which it
was drawn. The flow may be monitored by any of a variety of
mechanisms described herein. When the measurement is complete, the
syringe can be cleaned automatically in a number of ways prior to
making the next measurement. Three axis robots are well known in
the art and are commercially available, such as those available
from Cavro Scientific Instruments (Sunnyvale, Calif.); see also
U.S. Pat. Nos. 5,476,358 and 5,324,163 and WO 99/51980, which are
all incorporated herein by reference. In addition, the number of
viscometers is dependent on the number of tips present in the
chosen robot. If a multi-arm, multi-tipped robot is chosen, then 2,
4, 8, 16 or more viscometers can take measurements in accord with
the disclosure herein simultaneously or in rapid serial mode.
[0041] Throughout and in accord with this specification, the number
of viscometers is a methodology and design choice those of skill in
the art can make in view of this specification. A ninety-six
parallel viscometer is detailed below, however, lower or higher
throughput requirements may serve the needs of a particular
application of this invention and thus, 8 or more, 16 or more, 24
or more or 48 or more viscometers in parallel are within the scope
of this invention. Generally, an array of materials comprises a
plurality of materials for which a viscosity measurement is a
desired measurement. In other embodiments, an array of materials
will comprise 8 or more, 16 or more, 24 or more or 48 or more
materials, each of which is different from the others. Arrays and
methods of making such arrays are described in detail, for example,
U.S. Pat. No. 6,004,617 and U.S. patent application Ser. No.
09/227,558, filed Jan. 8, 1999, both of which are incorporated
herein by reference for all purposes.
[0042] Ninety-Six Element Parallel Viscometer
[0043] FIG. 1 shows a perspective front view of a parallel
viscometer 100 that can measure viscosity of ninety-six samples
simultaneously. The viscometer 100 includes a rigid frame 102
mounted on a supporting base 104. A pair of side plates 106, which
are attached to the rigid frame 102, support a set of syringes 108
that serve as the reservoirs and tubes described in the overview
section. The viscometer 100 shown in FIG. 1 has ninety-six syringes
108 or measuring elements, although the number of syringes 108 used
can vary. Each of the syringes 108 includes a plunger 110, a barrel
112, and a hollow elongated needle or capillary tube 114. As
described below, a barrel retaining plate 116 and a needle capture
assembly 118 hold each syringes 108 in place. The barrel retaining
plate 116 and the needle capture assembly 118 are securely fastened
to the side plates 106 using threaded fasteners 119, which prevent
movement of each syringe barrel 112 and capillary tube 114 during
viscosity measurement.
[0044] As noted in FIG. 1, the parallel viscometer 100 also
includes a plunger plate 120 that provides uniform translation of
each plunger 110 in a direction parallel to its longitudinal axis.
A mounting bracket 122 connects the plunger plate 120 to a
translation block 124 located within a guide channel 126. The guide
channel 126 is attached to the rigid frame 102 and has a pair of
planar side walls 128 that are substantially parallel to the travel
direction of each plunger 110. The small clearance between the
guide channel 126 side walls 128 and the translation block 124
allow the block 124 to slide freely within the guide channel 126
with minimal lateral motion. In this way, the translation block 124
and the guide channel 126 restrict the movement of the plunger
plate 120 to a direction substantially parallel to the longitudinal
axis of each plunger 110.
[0045] A DC motor (not shown), which is mounted on the rigid frame
102 between the set of syringes 108 and the back plane 130 of the
viscometer 100, drives the plunger plate 120. The translation block
124, which is connected to the plunger plate 120, is fastened to a
threaded rod or drive shaft 132, which is located within the guide
channel 126. The drive shaft 132 is mechanically connected to the
motor using appropriate gearing and extends from the motor to one
end 134 of the guide channel 126. Because the drive shaft is
stationary, the translation block 124 and the plunger plate 120
move away or toward each syringe barrel 112 when the motor rotates
the drive shaft 132. The translation direction of the plunger plate
120 depends on the rotation direction of the drive shaft 132.
Typically, a microprocessor-based motor controller (not shown)
regulates the speed and direction of the motor and hence the
translation speed and direction of the plunger plate 120.
[0046] The parallel viscometer 100 also includes an upstream
detector array 136 and a downstream detector array 138, which
monitor the volumetric flow rate, Q, of the samples flowing through
each syringe barrel 112 and capillary tube 114. The detector arrays
136, 138 are made up of twelve linear arrays 140, 142, each having
eight elements (not shown) spaced nine millimeters apart. The
resulting twelve-by-eight or ninety-six-element detector arrays
136, 138 allow the set of syringes 108 to have the same lateral
spacing as a standard ninety-six well microtiter plate. Each of the
detector elements is comprised of an infrared source such as an IR
LED, and an infrared detector, which are aligned on opposing sides
of each syringe barrel 112. As described below, for each of the
syringes 108, the upstream 136 and downstream 138 detector arrays
monitor Q by noting the time it takes for a liquid meniscus within
the syringe barrel 112 to travel between the upstream detector
element and the downstream detector element.
[0047] FIG. 2 shows a partial exploded view of one of the syringes
108. The syringe 108 includes a flat-tipped 156 stainless steel
hypodermic needle 158 having a capillary tube 114 portion that
serves as the viscosity measurement region. Although each capillary
tube 114 shown in FIG. 1 has the same dimensions, the length and
inner diameter of each capillary tube 114 can vary to accommodate
samples possessing a broad range of viscosities. One end of the
capillary tube 114 has a standard Luer hub 160, which is used to
connect the capillary tube 114 to the syringe barrel 112. The
capillary tube 114 shown in FIG. 2 has a six-inch length and a
0.040-inch inner diameter, though generally, the length and the
inner diameter of the capillary tube 114 is chosen to achieve a
reasonable viscosity measurement time. Typical measurement times
are from about ten seconds to about one minute.
[0048] Each syringe barrel 112 functions as a reservoir for a
particular measuring element of the parallel viscometer 100. The
syringe barrel 112 depicted in FIG. 2 is fabricated from glass and
has a cylindrical bore (not shown) extending throughout its length.
A PTFE Luer tip 162 is attached to one end of the syringe barrel
112 using a stainless steel end cap 164. The Luer tip 162 has the
shape of a truncated cone that mates with a slightly tapered,
cylindrical internal cavity 166 of the Luer hub 160. During
assembly of each of the syringes 108, the Luer tip 162 is press-fit
into the Luer hub 160 to create a gas-tight seal between the
capillary tube 114 and the syringe barrel 112. The syringe barrel
112 shown in FIG. 2 has a five-inch length and a 0.2-inch internal
diameter, providing a maximum reservoir volume of about 250 .mu.l.
The syringe barrel 112 also has a 0.04-inch diameter vent hole 168
bored through its wall, which allows fluid communication with the
cylindrical bore of the syringe barrel 112 and the environment. The
dimensions of the syringe barrel 112, as well as the size and the
location of the vent hole 168 can vary among syringes 108.
[0049] As noted in FIG. 2, each of the syringes 108 also includes a
plunger 110, which can be used to aspirate a liquid sample into
particular syringes 108 or to drive the sample through the
capillary tube 114. The plunger 110 includes a rigid cylindrical
rod 170 and a plunger button 172 that delimits a portion of the
plunger 110 located outside the syringe barrel 112. As described
below, the plunger button 172 connects the plunger rod 170 to the
plunger plate 126 shown in FIG. 1.
[0050] FIGS. 3, 4 and 5 provide further details of the syringes
108. FIG. 3 shows a cross-sectional view of the syringe barrel 112
and the plunger 110; FIG. 4 and FIG. 5 show, respectively, close-up
cross-sectional views of first 190 and second 192 ends of the
syringe barrel 112. As noted above, the syringe barrel 112 has a
Luer tip 162 that is attached to the first end 190 of the syringe
barrel 112 using an end cap 164. A deformable sleeve 194 is placed
between the end cap 164 and the syringe barrel 112 to provide a
gas-tight seal between the end cap 164, the Luer tip 162, and the
syringe barrel 112. The Luer tip 162 has a 0.04-inch cylindrical
through-hole 196 extending along its longitudinal axis, which
provides fluid communication between the cylindrical bore of the
syringe barrel 112 and the interior of the capillary tube 114. The
dimensions of the through-hole 196 can vary among syringes 108.
[0051] As shown in FIG. 3 and FIG. 4, the portion of the plunger
110 within the first end 190 of the syringe barrel 112 includes a
resilient plunger tip 198 attached to the plunger rod 170. The
plunger tip 198 has a cylindrical outer surface with a nominal
outer diameter slightly larger than the internal diameter of the
syringe barrel 112. In the embodiment shown in FIG. 3 and FIG. 4,
the plunger tip 198 compresses when placed within the syringe
barrel 112, providing a gas-tight seal between the cylindrical bore
of the syringe barrel 112 and the plunger tip 198, though a
gas-tight seal is sometimes unnecessary. Ordinarily, the plunger
tip 198 should be more compressible than the syringe barrel 112 and
should be made of a chemically inert material such as PTFE. The
portion of the plunger 110 located adjacent the second end 192 of
the syringe barrel 112, includes a plunger button 172 attached to
the plunger rod 170. The plunger button 172 includes a threaded
hole 200 that allows attachment of the plunger 110 to the plunger
plate 120 (FIG. 1) using threaded fasteners 202.
[0052] FIG. 6 and FIG. 7 show a top view and a cross sectional
view, respectively, of the barrel retaining plate 116. As noted in
the discussion of FIG. 1, the barrel retaining plate 116 and the
needle capture assembly 118, help secure each of the syringes 108
during viscosity measurement. The barrel retaining plate 116 is
ordinarily fabricated from a rigid material such as aluminum, and
includes a plurality of plunger through-holes 220 that extend from
an upper surface 222 of the plate 116 to a lower surface 224 of the
plate 116. Like the well spacing of a standard ninety-six well
microtiter plate, the through-holes 220 shown in FIG. 6 are arrayed
on nine-mm centers. As shown in FIG. 7, the through-holes 220 allow
passage of syringe plunger rods 170, but prevent movement of
syringe barrels 112 through the upper surface 222 of the barrel
retaining plate 116. The through-holes 220 include counter bores
226 that extend from the lower surface 224 of the plate 116
partially into the barrel retaining plate 116. The size of each of
the counter bores 226 is sufficient to receive a second end 192
(FIG. 3) of each of the syringe barrels 112. The barrel retaining
plate 116 typically includes resilient washers 228 that sit within
the counter bores 226 and cushion the syringe barrels 112 during
assembly and operation of the viscometer 100. Each of the washers
228 has an internal bore 230 at least as large as the through-holes
220 to allow movement of the plunger rods 170.
[0053] FIG. 8-FIG. 11 provide details of the needle capture
assembly 118, which comprises a Luer hub capture plate 250 and a
needle preload block 252. FIG. 8 and FIG. 9 show, respectively, top
and cross sectional views of the Luer hub capture plate 250, which
is typically fabricated from a rigid material such as aluminum. The
Luer hub capture plate 250 includes a set of channels 254 that
extend from an upper surface 256 to a lower surface 258 of the
plate 250, and from a region adjacent a front edge 260 of the plate
250 to a back edge 262 of the plate 250. Each of the channels 254
comprises an upper channel portion 264 and a lower channel portion
266 that are located adjacent the upper and lower surfaces 256, 258
of the plate 250. The upper and lower channel portions 264, 266
have generally parallel and planar side walls 268, 270 that define
uniform channel widths. As shown in FIG. 9, the width of the upper
channel portion 264 is greater than the width of the lower channel
portion 266. The Luer hub capture plate 250 includes a first group
of through-holes 272 for aligning the capture plate 250 and the
preload block 252, and a second group of through-holes 274
(threaded) for attaching the capture plate 250 to the preload block
252.
[0054] FIG. 10 and FIG. 11 show top and cross sectional views,
respectively, of the preload block 252. The preload block 252, like
the Luer hub capture plate 250, is typically fabricated from a
rigid material such as aluminum. The preload block 252 includes
through-holes 300 that extend from an upper surface 302 of the
block 252 to a lower surface 304 of the block 252. The
through-holes 300 are arrayed on nine-mm center--corresponding to
the well spacing of a standard ninety-six well microtiter
plate--and include counter bores 306 that extend from the upper
surface 302 part way into the preload block 252. The preload block
252 includes a second group of through-holes 310 for aligning the
preload block 252 and the Luer-hub capture plate 250, and a third
group of through-holes 312 for attaching the preload block 252 to
the Luer hub capture plate 250.
[0055] FIG. 12 and FIG. 13 show, respectively, top and cross
sectional views of the needle capture assembly 118, which is
comprised of the Luer hub capture plate 250 and the needle preload
block 252. The Luer hub capture plate 250 is disposed above (or on)
the needle preload block 252 such that the first and second
through-holes 272, 274 of the capture plate 250 line up,
respectively, with the second and third through-holes 310, 312 of
the preload block 252. Furthermore, each row 314 of through-holes
300 lines on the preload block 252 line up with one of the channels
254 of the capture plate 250. Since each channel 254 and row 314
can accommodate eight Luer hubs 160, and since the capture plate
250 and the preload block 252 have twelve channels 254 and twelve
rows 314, respectively, the needle capture assembly 118 can secure
up to ninety-six syringes 108 (FIG. 2).
[0056] FIG. 13 shows how the Luer hub capture plate 250 and the
needle preload block 252 cooperate to secure a set of syringes 108
(FIG. 2). For clarity, the needle capture assembly 118 shown in
FIG. 13 includes a single hypodermic needle 158, though typically
each through-hole 300 of the needle preload block will contain a
hypodermic 158 needle. The hypodermic needle 158 includes a
capillary tube 114, which serves as a viscosity measurement region,
and a Luer hub 160, which connects the capillary tube 114 to a
syringe barrel 112. As noted in the description of FIG. 2, the Luer
hub 160 has a tapered internal cavity 166 that can receive the
conical-shaped Luer tip 162 of the syringe barrel 112. The Luer hub
160 also includes generally cylindrical body 340, neck 342 and
flanged head 344 portions that in FIG. 13 are located,
respectively, within the lower 266 and upper 264 channel portions
and adjacent the upper surface 256 of the Luer hub capture plate
250. Since the diameters of the body 340 and flanged head 344
portions of the Luer hub 160 are larger than the width of the upper
portions 264 of the channels 254, the Luer hub capture plate 250
limits axial translation of the hypodermic needle 158. In addition,
each of the counter bores 306 in the needle preload block 252
typically receives a spring 346 that applies a force against the
Luer hub 160 to resist axial movement of the hypodermic needles 158
and syringes 108.
[0057] Many methods can be used to load and assemble the needle
capture assembly 118. For example, one method includes placing
springs 346 in the counter bores 306 of the needle preload block
252 and inserting the capillary tube portion 114 of the hypodermic
needles 158 through the springs 346, counter bores 306 and
through-bores 300 of the preload block 252. Once the desired
fraction of through-holes 300 contain hypodermic needles 158, the
method calls for aligning the body 340 and neck 342 portions of the
Luer hubs 160 with, respectively, the lower 266 and upper 264
channel portions along the back edge 262 of the Luer hub capture
plate 250. The method includes sliding the Luer hubs 160 into the
channels by translating the needle preload block 252 from the back
edge 262 to the front edge 260 of the Luer hub capture plate 250.
The process continues until the first and second through-holes 272,
274 of the capture plate 250 line up, respectively, with the second
and third through-holes 310, 312 of the preload block 252. After
alignment, the method concludes by attaching the preload-block 252
to the Luer hub capture plate 250 by twisting fasteners into the
third 312 and second 272 through-holes of the needle preload block
252 and the Luer hub capture plate 250. After loading the
hypodermic needles 158, the needle capture assembly 118 represents
a quick way to connect (disconnect) ninety-six hypodermic needles
158 or capillary tubes 114 and ninety-six syringe barrels 112 or
reservoirs simultaneously.
[0058] FIG. 14 shows a perspective view of a detector block module
370 for holding linear arrays 140, 142 that comprise the upstream
136 and downstream 138 detector arrays, respectively. The detector
block module 370, which is typically fabricated from a rigid
material such as aluminum, has generally planar and parallel top
372 and bottom 374 surfaces and generally planar and parallel first
376 and second 378 sides. As noted in the description of FIG. 1,
the upstream 136 and downstream 138 detector arrays monitor the
volumetric flow rate of samples flowing through each syringe barrel
112 and capillary tube 114. The detector arrays 136, 138 are made
up of twelve linear arrays 140, 142, each having eight detector
elements spaced nine millimeters apart. The resulting
twelve-by-eight or ninety-six-element detector arrays 136, 138
allow the set of syringes 108 to have the same lateral spacing as a
standard ninety-six well microtiter plate. Each of the detector
elements is comprised of an infrared emitter and an infrared
detector, which are aligned on opposing sides of each syringe
barrel 112. A useful IR emitter and detector include an IR LED and
an IR-sensitive phototransistor, respectively. Note that the use of
an infrared emitter and detector helps reduce interference from
ambient visible light.
[0059] Thus, as shown in FIG. 14, the detector block module 370
includes eight through-bores 380 that extend from the top surface
372 to the bottom surface 374 of the block module 370. Each of the
through-bores 380 has a diameter large enough to accommodate a
syringe barrel 112. The detector block module 370 also includes
pairs of rectangular notches 382, 384 cut into the first 376 and
second 378 sides of the block 370. The pairs of rectangular notches
382, 384 are sized to contain components of a detector array
element 386, which as noted above, comprise an infrared detector
388 and an infrared emitter 390. Each pair of rectangular notches
382, 384 includes first 392 and second 394 apertures that provide a
line of sight between the IR detector 388 and IR emitter 390,
respectively. In addition, the detector block module 370 includes
clearance holes 396 that are located adjacent to the front 398 and
rear 400 ends of the module 370. Each of the clearance holes 396
extends from the first 376 side to the second 378 side of the
detector block module 370 and has a diameter large enough to allow
a support rod (not shown) to pass through. To form each of the
ninety-six element detector arrays 136, 138, twelve of the detector
block modules 370 are stacked on support rods inserted through the
clearance holes 396.
[0060] A suitable IR emitter 390 and an IR detector 388 are
available from Honeywell under the trade designations SEP8706 and
SDP8371, respectively. Since commercially available infrared
emitters and detectors often emit or detect light over a larger
range of angles than is desirable for detection of the liquid
meniscus, this angular range may be reduced by partially blocking
the entrance and exit apertures of these devices through the
application of an opaque coating such as an enamel paint containing
colloidal silver particles, or by the placement of an appropriately
sized metal washer over the aperture.
[0061] As noted in the description of FIG. 1, the upstream 136 and
downstream 138 detector arrays monitor the volumetric flow rate of
fluid samples. The detector arrays 136, 138 measure the time
necessary for a liquid meniscus within the syringe barrel 112 to
travel between the detector arrays 136, 138, which can be
accomplished by noting changes in voltages generated by the
detector arrays 136, 138 in response to fluid characteristics. For
example, in the absence of liquid in the barrel 112, infrared light
from the emitter 390 exits the second aperture 394 of the detector
block module 370, travels through the syringe barrel 112, enters
the first aperture 392, and strikes the infrared detector 388. This
results in a voltage, V.sub.S, at the output of the detector 388.
When the boundary between the fluid sample and air within the
syringe barrel 112 passes the detector array element 386, V.sub.S
changes relative to some reference voltage, V.sub.REF. If the fluid
sample is substantially transparent to infrared light, the change
is brief and results from disruption of the infrared light beam by
the sample meniscus. If, however, the fluid sample is opaque,
V.sub.S exhibits a step change--an increase or decrease relative to
V.sub.REF--upon passage of the meniscus depending on the electrical
response of the detector 388 to an increase in light level.
[0062] In a closely related embodiment, the apertures 392, 394 are
not necessarily aligned. Infrared light from the emitter 390 exits
the second aperture 394 of the detector block module 370, and
enters the syringe barrel 112 interior. When the angular
distribution of light from the emitter 390 is sufficiently broad, a
portion of this light will reflect back into the barrel 112 at the
interfaces between the barrel 112 and either the ambient air or
barrel 112 contents. The reflected light will then travel around
the barrel 112 interior, undergoing multiple reflections at its
internal and external surfaces. Some fraction of light will escape
from the barrel 112 each time the light is partially reflected from
these surfaces. For reflections occurring near the first aperture
392, light escaping the barrel 112 will strike the infrared
detector 388, producing voltage V.sub.S at the output of the
detector 388. The fraction of light escaping the barrel 112 depends
on the relative refractive index of the syringe barrel 112 and its
contents, and therefore the magnitude of V.sub.S will depend on
whether sample fluid coats the inner surface of the barrel 112
adjacent the detector array element 386. Therefore, the detector
338 output voltage, V.sub.S, will exhibit a significant change
relative to V.sub.REF upon passage of the fluid meniscus.
[0063] Although one can detect the transition in V.sub.S directly,
the viscometer 100 typically employs either a standard comparator
circuit or a Schmitt trigger circuit to detect a rise (or fall) in
V.sub.S. With a standard comparator, the comparator output,
V.sub.O, saturates at V.sub.CC for V.sub.S greater than V.sub.REF
and saturates at -V.sub.EE for V.sub.S less than V.sub.REF. Thus,
when using the standard comparator, the momentary drop in V.sub.S
results in a sharp decrease in V.sub.O from V.sub.CC to -V.sub.EE
and a sharp increase in V.sub.O from -V.sub.EE to V.sub.CC as the
meniscus passes the detector array element 386. The standard
comparator usually works well unless V.sub.S is "noisy." Sources of
noise include gas occlusions, voids, and other impurities in the
fluid sample, which can perturb the IR light and result in spurious
beam interruptions.
[0064] The Schmitt trigger circuit can detect the transition even
for "noisy" V.sub.S. It uses a comparator whose reference voltage,
V.sub.REF, is derived from a voltage divider across the output
(i.e., positive feedback). V.sub.REF changes when the output
switches state: V.sub.REF=.beta.V.sub.CC for V.sub.O>0 and
-.beta.V.sub.EE for V.sub.O<0, where .beta. is called the
feedback factor and is a positive number less than unity. Thus,
when V.sub.S rises through V.sub.REF=.beta.V.sub.CC, V.sub.O is at
V.sub.CC and switches to -V.sub.EE, and when V.sub.S falls through
V.sub.REF=.beta.V.sub.EE, V.sub.O is at -V.sub.EE and switches to
V.sub.CC. As a result, the Schmitt trigger will not respond to
input noise having a magnitude less than the differences between
the two threshold voltages, V.sub.N<.beta.(V.sub.CC+V.sub.EE).
Note that one may implement the standard comparator and Schmitt
trigger circuits in hardware or software.
[0065] One can use many different methods to determine the drop
time, .DELTA.t, which is the time it takes for a liquid meniscus to
travel between the detector arrays 136, 138. In a first method, the
upstream and down stream detectors of a particular syringe barrel
112 are separately connected to an A/D board, which records V.sub.O
(or V.sub.S) at a predetermined sampling rate, r. A computer can
search the recorded data streams for V.sub.O transitions (pulses)
that indicate the passing of the meniscus. Assuming that r is the
same for the upstream and downstream detectors, the computer can
then calculate .DELTA.t by dividing the number of data points
acquired between the two pulses by the data acquisition rate. In a
second method, the upstream and down stream detectors are connected
to the A/D board, which records the voltage drop across both
detectors in a single channel. Again, a computer can search the
recorded data stream for the V.sub.O (V.sub.S) transitions and
calculate .DELTA.t. Alternatively, one can employ a timer on the
A/D board, which is triggered by V.sub.O transitions, to measure
the elapsed time directly.
[0066] FIG. 15 shows a top view of an optional needle alignment
block 420. The needle alignment block 420 is typically fabricated
from a rigid material such as aluminum, and can be attached to the
rigid frame 102 that supports the parallel viscometer 100 (FIG. 1).
The needle alignment block 420 includes through-holes 422 that
extend from an upper surface 424 of the block 420 to a lower
surface (not shown) of the block 420. The through-holes 422 are
arrayed on nine-mm centers corresponding to the well spacing of a
standard ninety-six well microtiter plate, and have diameters that
allow passage of the capillary tube 114 portion of the syringe
needles 158 (FIG. 2). Placing the needle alignment block 420
adjacent the tips 156 of the capillary tubes 114 ensures that the
tubes 114 have uniform lateral spacing throughout their
lengths.
[0067] Viscosity Measurement
[0068] To perform a measurement with the parallel viscometer 100
(FIG. 1), a DC motor (not shown) drives the plunger plate 120
towards the barrel retaining plate 116 until the tip 198 of each
plunger 110 rests against the Luer tip 162 of each syringe barrel
112 (FIG. 3). A laboratory jack located adjacent the viscometer
base 104 positions a ninety-six well microtiter plate (or similar
vessel array) below the syringes 108 so that the tip 156 of each
capillary tube 114 is immersed in a fluid sample within a
particular well or vessel. The DC motor then drives the plunger
plate 120 away from the barrel retaining plate 116, generating a
vacuum between the plunger tip 198 and the capillary tip 156, which
aspirates fluid sample into each syringe barrel 112. Once the
plunger tip 198 passes the vent hole 168, the interior of each
syringe barrel 112 returns to atmospheric pressure and fluid sample
begins to drain from the barrel 112 through the capillary tube 114.
As noted when describing FIG. 14, the upstream 136 and downstream
138 detector arrays monitor the volumetric flow rate of the fluid
samples by measuring the time it takes for the liquid meniscus
within each syringe barrel 112 to travel between the detector
arrays 136, 138. When the boundary between the fluid sample and air
within each syringe barrel 112 passes a detector array element 386,
the meniscus disrupts the beam from the IR emitter 390, which
produces a brief signal at the IR detector 388. Generally, the
length and diameter of the capillary tube 114 are chosen to achieve
a reasonable drop time for the fluid samples, typically from about
ten to sixty seconds. In addition, each plunger 110 is withdrawn
from the syringe barrel 112 at a rate such that the meniscus is
above the upstream 136 detector array element 386 by the time the
plunger tip 198 passes the vent hole 168.
[0069] As noted in the overview section, one can calculate
viscosity, .eta., from the volumetric flow rate, Q. of samples
flowing through the capillary tubes 114 using the Hagen-Poiseulle
equation: 1 Q = d 4 P 128 l I
[0070] where d and l are the inner diameter and length of the
capillary tube 114, and .DELTA.P is the pressure drop across l. For
gravity-driven flows, the pressure drop is the product of the fluid
sample density, the gravitational acceleration, and l. Q can be
calculated from the expression: 2 Q = D 2 L / 4 t II
[0071] where D is the inner diameter of the syringe barrel 112, L
is the distance between the upstream 136 and downstream 138
detector arrays and At is the measured drop time.
[0072] In another embodiment, the viscometers described above can
be operated by creating a vacuum in the reservoirs (e.g., the
barrels). The vacuum can be created by a pump or by rapidly
withdrawing the plunger through the barrel. A pressure sensor can
be used to monitor the pressure of the vacuum created. The flow of
the fluid to be measured into the viscometer can be monitored by
monitoring the pressure. For example if the plunger is pulled back
a fixed distance extremely rapidly, the time for the liquid to flow
into the line may be monitored. The pressure may initially drops
rapidly as the dead volume is expanded, and recovers as liquid
flows into the tube and reduces the dead volume. Information on the
fluid flow rate and viscosity can be derived from the pressure vs.
time curves for the fluid. One method for using this embodiment
comprises a method for rapidly determining the viscosity of liquids
comprising filling at least a part of the reservoir and/or tube
with a compressible fluid (e.g. air); inserting the tube into the
material to be sampled; retracting the syringe plunger at a
specified rate for a specified time; measuring the pressure in the
line during and after the retraction of the syringe pump plunger;
calculating the trapped air volume between the rising liquid
meniscus in the tube and/or reservoir and the syringe pump plunger,
as a function of time, from the measured pressure within this
volume as sensed by the pressure sensor; calculating the volume of
liquid which has been aspirated into the pipette tip and line, as a
function of time, from the calculated trapped air volume and
knowledge of the displacement of the syringe pump plunger; and
calculating a viscosity of the liquid from the observed liquid flow
rate in response to the measured pressure. Those of skill in the
art will appreciate that this is only one method for using this
embodiment and other methods will be evident upon review of this
specification.
[0073] Molecular Weight Measurement
[0074] One can use viscosity measurements to estimate molecular
weights of polymers in solution. For a polymer dissolved in a
solvent, the ratio of the polymer solution viscosity, .eta., to the
solvent viscosity, .eta..sub.S, is proportional to the
concentration of the polymer, C, as the concentration approaches
infinite dilution (limit of C equals zero):
.eta./.eta..sub.S=1+C[.eta.] (III)
[0075] In equation III, [.eta.] is the intrinsic viscosity, which
exhibits a power-law dependence on polymer molecular weight given
by the Mark-Houwink-Sakurada (MHS) relation,
[.eta.]=[.eta..sub.O]M.sub.a (IV)
[0076] where the constants [.eta..sub.O] and .alpha. depend on the
polymer, solvent, and temperature. Correction factors are available
in the literature for solutions containing a distribution of
polymer molecular weights.
[0077] To measure the molecular weight of a polymer in solution
using the parallel viscometer 100, one measures the drop time,
.DELTA.t.sub.S, for the solvent and then measures .DELTA.t for the
polymer solution. Since the drop time is inversely proportional to
the volumetric flow rate, Q, through the capillary tube 114, and Q
is inversely proportional to the viscosity of the solvent and the
polymer solution, the ratio .eta./.eta..sub.S is equal to the ratio
of the drop times, .DELTA.t/.DELTA.t.sub.S. Because corrections
associated with the dimensions of the instrument, changes in the
height of the liquid sample in the reservoir, and transitions in
flow behavior at the entrance and exit of the capillary tube 114
are similar for .DELTA.t and .DELTA.t.sub.S measurements, the
measurement of .eta./.eta..sub.S is self-normalizing. If C is
known, one can determine the intrinsic viscosity from equation III,
and the molecular weight from equation IV (MHS relation).
[0078] If the concentration of the polymer solution is initially
unknown, both the molecular weight and the concentration can be
estimated by measuring the ratio of drop times in two different
solvents. The first solvent is a good solvent for the polymer, and
typically has a constant .alpha. of 0.7 or greater. The second
solvent is a marginal solvent for the polymer, and is usually
prepared by adding a known amount of a poor solvent to the first
solvent. Ordinarily, one should maximize the difference in a
between the first (good) and second (marginal) solvents by adding
as much of the poor solvent as possible to the first solvent
without causing the polymer to precipitate. In such cases, the
marginal solvent typically has an .alpha. of about 0.5. If we then
define .mu.=.eta./.eta..sub.S-1, where .eta./.eta..sub.S is the
ratio of drop times as described above, then 3 1 2 = C 1 [ 1 ] C 2
[ 21 ] = ( C 1 C 2 ) ( O , 1 O , 2 ) M 1 - 2 V
[0079] where subscripts 1 and 2 denote measurements of polymer
solutions made using the first and second solvents, respectively,
and the second solvent is prepared by adding a known amount of a
poor solvent to the first solvent. p In equation V, the constants
[.eta..sub.O,1], [.eta..sub.O,2], .alpha..sub.1, and .alpha..sub.2
are determined by measurements of polymer standards at known
concentrations prior to measurements of the unknown solution. Since
the ratio of C.sub.1 to C.sub.2 is known, the ratio
.mu..sub.1/.mu..sub.2 depends only on the molecular weight of the
polymer. After estimating the molecular weight via this method,
either concentration (C.sub.1 or C.sub.2) can be estimated from the
MHS relation for the polymer of interest in solvent 1 or 2.
[0080] Modifications
[0081] The parallel viscometer shown in FIG. 1 can be modified to
screen high viscosity liquids such as polymer melts. A force sensor
is attached to the top of each plunger 110. After filling each
syringe barrel 112 with high viscosity liquids, the plunger 110
descends at a constant rate and the force sensor determines the
force required to maintain this motion. Assuming negligible
friction between the plunger 110 and the barrel 112, the force is
roughly proportional to the pressure inside the barrel 112; in
combination with the flow rate through the capillary tube 114, the
viscosity of each liquid can be determined using the
Hagen-Poiseulle relation (equation I). If the liquid is relatively
incompressible, the flow rate may be inferred from the rate at
which the plunger 110 descends. Thus, optical detectors 386 are not
required for measurement of flow rate, which permits the syringe
barrel 112 to be made of a strong, opaque material such as
stainless steel. In an alternate embodiment, each plunger is
independently attached to a weight, which in turn is held in place
by an electromagnet or mechanical latch. A measurement is conducted
by releasing the weight and either permitting the plunger 110 to
descend for a fixed amount of time while measuring the quantity of
material expelled from the capillary 114 (for example, by weighing
or noting the total travel distance of the plunger), or by
measuring the amount of time it takes the plunger 110 to descend a
fixed distance.
EXAMPLES
[0082] The following examples are intended to be illustrative and
non-limiting, and represent specific embodiments of the present
invention.
Example 1
Variation in Drop Time Between Syringes
[0083] A parallel viscometer similar to the apparatus depicted in
FIG. 1 was used to measure drop time, .DELTA.t, for tetrahydrofuran
(THF) samples at 20.degree. C. The drop time was measured for
ninety-six samples simultaneously, and was repeated four times for
each sample. FIG. 16 plots drop time (in seconds) versus sample
number (1-4) that were obtained for three different syringes
(channels 3, 4 and 5). Although some variation exists between
syringes (channels), drop time measurements for individual channels
are highly repeatable.
Example 2
Single Channel (Syringe) Reproducibility
[0084] The parallel viscometer of Example 1 was used to measure
drop time for toluene samples at 20.degree. C. The drop time was
measured for a series of twenty-three samples using a single
syringe (channel) having a 20-gauge hypodermic needle. FIG. 17
plots drop time (in seconds) versus sample number (1-23) for the
single channel. The average drop time for the twenty-three samples
was 3.690 s, and the standard deviation was 0.006 seconds. Note
that a filter could be used to eliminate disordant data (sample 9,
17).
Example 3
Measurement of Intrinsic Viscosity
[0085] The parallel viscometer of Example 1 and 2 was used to
determine the intrinsic viscosities of a set of commercially
available polyisobutylene standards at concentrations in hexane
from 1 to 20 mg/ml at 25.degree. C. The molecular weights of these
materials as reported by the supplier (Polymer Standards Service
USA, Silver Springs, Md.) appear in Table 1. FIG. 18 shows
.DELTA.t/.DELTA.t.sub.S-1 or .eta./.eta..sub.S-1 versus
polyisobutylene concentration, where .DELTA.t and .DELTA.t.sub.S
are the drop times for the polymer solution and for pure hexane,
respectively, and where the ratio .eta./.eta..sub.S is the relative
viscosity. Each data point represents an average of at least five
measurements. A linear least-squares fit each of these curves
yields the intrinsic viscosity, [.eta.], for each standard of
differing molecular weight. These data are summarized in Table 1
and plotted in FIG. 19. The resulting power law relation,
[.eta.].about.M.sup.0.611, indicates that hexane is a reasonable
(though not good) solvent for this polymer.
1TABLE 1 Weight-average molecular weights (M.sub.w), number-average
molecular weights (M.sub.n), and intrinsic viscosities ([.eta.])
for polyisobutylene standards M.sub.w M.sub.n [.eta.] (ml/mg)
(g/mol) (g/mol) .times.10.sup.3 2470 2200 5.65 4400 3200 8.05 24200
19600 21.0 86100 72100 53.3 134000 117000 89.0 1110000 862000
201
[0086] It is understood that the above description is intended to
be illustrative and not restrictive. Many embodiments will be
apparent to those of skill in the art upon reading the above
description. The scope of the invention should therefore be
determined not with reference to the above description, but should
instead be determined with reference to the appended claims, along
with the full scope of equivalents to which such claims are
entitled. The disclosures of all articles and references, including
patent applications and publications, are incorporated herein by
reference for all purposes.
* * * * *