U.S. patent number RE38,281 [Application Number 09/897,788] was granted by the patent office on 2003-10-21 for dispensing apparatus having improved dynamic range.
This patent grant is currently assigned to Biodot, Inc.. Invention is credited to Thomas C. Tisone.
United States Patent |
RE38,281 |
Tisone |
October 21, 2003 |
**Please see images for:
( Certificate of Correction ) ** |
Dispensing apparatus having improved dynamic range
Abstract
A method and apparatus for dispensing precise quantities of
reagents is disclosed including a positive displacement syringe
pump in series with a dispenser, such as an aerosol dispenser or
solenoid valve dispenser. The pump is controlled by a stepper motor
or the like to provide an incremental quantity or continuous flow
of reagent to the dispenser. The pump and dispenser are operated in
cooperation with one another such that the quantity and/or flow
rate of liquid dispensed by the dispenser can be precisely metered
substantially independently of the particular operating parameters
of said dispenser to attain a desired flow rate, droplet size or
mist quality, droplet frequency and/or droplet velocity.
Inventors: |
Tisone; Thomas C. (Orange,
CA) |
Assignee: |
Biodot, Inc. (Irvine,
CA)
|
Family
ID: |
28795240 |
Appl.
No.: |
09/897,788 |
Filed: |
June 29, 2001 |
Related U.S. Patent Documents
|
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
|
687712 |
Jul 26, 1996 |
5743960 |
|
|
|
686957 |
Jul 26, 1996 |
5741554 |
|
|
|
687711 |
Jul 26, 1996 |
5738728 |
|
|
Reissue of: |
899325 |
Jul 23, 1997 |
05916524 |
Jun 29, 1999 |
|
|
Current U.S.
Class: |
422/521; 118/305;
118/683; 239/368; 239/369; 239/371; 422/537; 422/81; 436/180;
436/46; 436/54; 73/864.15; 73/864.24; 73/864.25 |
Current CPC
Class: |
B01L
3/0265 (20130101); B01L 3/0268 (20130101); B05B
1/3053 (20130101); B05B 7/066 (20130101); B05B
9/0413 (20130101); B05B 12/06 (20130101); B05B
17/0607 (20130101); B05B 7/2489 (20130101); G01N
2035/1023 (20130101); G01N 2035/1034 (20130101); G01N
2035/1041 (20130101); Y10T 436/2575 (20150115); Y10T
436/112499 (20150115); Y10T 436/119163 (20150115) |
Current International
Class: |
B05B
7/06 (20060101); B01L 3/02 (20060101); B05B
17/04 (20060101); B05B 7/02 (20060101); B05B
17/06 (20060101); B05B 9/04 (20060101); B05B
12/00 (20060101); B05B 1/30 (20060101); B05B
12/06 (20060101); B05B 7/24 (20060101); G01N
35/10 (20060101); G01N 035/10 () |
Field of
Search: |
;422/63-67,81,100,103
;436/180,43,46,49,54,174,179 ;73/864.15,864.24,864.25 ;118/683,305
;269/368,369,371 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
0 268 237 |
|
May 1988 |
|
EP |
|
0 326 510 |
|
Aug 1989 |
|
EP |
|
0 007 252 |
|
Jan 1980 |
|
FR |
|
Other References
IBC's 2.sup.nd Annual Conference on "MicroFabrication &
Microfluidic Technologies. Advances in the Miniaturization of
Bioanalytical Devices." Aug. 7-8, 1997. Renaissance Stanford Court
Hotel, San Francisco, CA. .
"IsoFlow" Linear Reagent Dispenser--Brochure by Imagene Technology.
.
Bio-Dot, Inc. Product Catalog. .
Series XY-3000 Brochure--Aug. 1994. .
BioJet Specification--Sep. 1995. .
Series MD-1000 Brochure--Aug. 1994. .
Bio-Dot AirJet-2000 Specification--Aug. 1994. .
CV1000 Syringe Pump Dispenser--Aug. 1994. .
BioDot, Inc. Brochure--Sep. 1995. .
Series RR-3000 BioDot "Reel-To-Reel Membrane Handling Module with
Dispensing Platform"--Not dated..
|
Primary Examiner: Ludlow; Jan
Attorney, Agent or Firm: Knobbe, Martens, Olson & Bear
LLP
Parent Case Text
.Iadd.This application is a continuation-in-part of U.S.
application Ser. No. 08/687,712, filed Jul. 26, 1996, now U.S. Pat.
No. 5,743,960, U.S. application Ser. No. 08/686,957, filed Jul. 26,
1996, now U.S. Pat. No. 5,741,554, and U.S. application Ser. No.
08/687,711, filed Jul. 26, 1996, now U.S. Pat. No. 5,738,728.
.Iaddend.
Claims
What is claimed is:
1. An apparatus for dispensing predetermined quantities of liquid
onto a substrate, comprising: a dispenser having an inlet and an
outlet and being adapted to form droplets of said liquid having a
size in the range of about 1-4 nanoliters to one microliter which
are deposited onto said substrate; and a metering pump
hydraulically arranged in series with the inlet of said dispenser
for metering predetermined quantities of said liquid to said
dispenser; whereby the quantity and/or flow rate of liquid
dispensed by said dispenser is metered substantially independently
of operating parameters of the dispenser.
2. The apparatus of claim 1 wherein the quantity and/or flow rate
of liquid dispensed by said dispenser is precisely metered
substantially independently of the droplet size or quality of said
liquid being dispensed.
3. The apparatus of claim 1 wherein said dispenser comprises an
aerosol dispenser having an outlet comprising an air passage
terminating in a nozzle and an inlet comprising a liquid passage
terminating in a venturi orifice for mixing said liquid with a flow
of air to form an aerosol mist proximate said substrate.
4. The apparatus of claim 3 wherein said aerosol dispenser
comprises an adjustable needle valve for adjusting the size of an
orifice through which said liquid is dispersed.
5. The apparatus of claim 1 wherein said dispenser comprises a
valve adapted to be opened and closed at a predetermined frequency
and duty cycle to form droplets of said liquid which are deposited
onto said substrate.
6. The apparatus of claim 5 wherein said valve is actuated by an
electric solenoid.
7. The apparatus of claim 5 wherein said valve is actuated by a
piezoelectric constrictor device.
8. The apparatus of claim 5 wherein the frequency and duty cycle of
said valve can each be adjusted substantially independently for a
given quantity or flow rate of liquid to produce droplets of a
desired size, frequency and/or exit velocity.
9. The apparatus of claim 1 in combination with a carriage adapted
for X, X-Y or X-Y-Z motion relative to said dispenser for movably
transporting said substrate and wherein said dispenser is mounted
in juxtaposition with said carriage.
10. The combination of claim 9 further comprising a controller in
communication with said metering pump and said carriage for
coordinating the output of said pump with the motion of said
carriage so that said liquid may be dispensed in precise quantities
of flow per unit length and such flow is precisely metered
substantially without being affected by the
.[.particular-operating.]. .Iadd.operating .Iaddend.parameters of
said dispenser.
11. The combination of claim 9 further comprising an array of
dispensers and metering pumps, the outlets of said dispensers being
arranged in a desired pattern suitable for attaining a desired
print matrix or dot pattern.
12. The apparatus of claim 1 wherein said liquid comprises a
chemical reagent.
13. The apparatus of claim 1 wherein said liquid comprises a
chemical reagent and said substrate comprises a diagnostic test
strip membrane.
14. The apparatus of claim 1 wherein said metering pump comprises a
syringe pump.
15. The apparatus of claim 14 wherein said syringe pump comprises a
syringe housing, a plunger axially displaceable within said syringe
housing and plunger shaft having a lead screw formed thereon.
16. The apparatus of claim 15 wherein said lead screw is sized and
positioned such that when said lead screw is rotated, said plunger
is displaced axially, causing a predetermined quantity of said
liquid to be delivered to said inlet of said dispenser.
17. The apparatus of claim 15 wherein said syringe housing has a
displacement volume of between about 25 microliters about 25
milliliters.
18. The apparatus of claim 1 wherein said metering pump comprises a
stepper motor adapted to cause said pump to dispense predetermined
incremental quantities or flow rates of said liquid to said
dispenser.
19. The apparatus of claim 18 wherein said metering pump has an
incremental displacement volume of between about 0.42 nanoliters
and 2.1 microliters.
20. The apparatus of claim 18 wherein said metering pump has an
incremental displacement volume of less than about 4.2
nanoliters.
21. The apparatus of claim 18 wherein said metering pump has a
resolution of between about 3,000 and 48,000 steps.
22. The apparatus of claim 18 wherein said metering pump has a
resolution of at least about 12,000 steps.
23. The apparatus of claim 1 further comprising a second metering
pump hydraulically coupled to said first metering pump for
providing continuous web production capability.
24. The apparatus of claim 1 wherein said dispenser and metering
pump are configured so as to provide a range of selectable droplet
sizes attainable for stable operation varying by a factor of
greater than about 250.
25. The apparatus of claim 1 wherein said dispenser and metering
pump are configured so as to provide selectable droplet sizes
ranging from less than about 4.2 nanoliters to greater than about 1
microliter.
26. An apparatus for dispensing a liquid onto a substrate,
comprising: a dispenser having an inlet and an outlet and a valve
adapted to be opened and closed at a predetermined frequency and
duty cycle to form droplets of said liquid which are deposited onto
said substrate; and a positive displacement pump hydraulically
arranged in series with the inlet of said dispenser for metering
predetermined quantities of said liquid to said dispenser;
whereby the quantity and/or flow rate of liquid dispensed by said
dispenser .[.can be.]. .Iadd.is .Iaddend.precisely metered
substantially independently of .[.the particular.]. operating
parameters of said dispenser.
27. The apparatus of claim 26 wherein the size, frequency, and
velocity of droplets dispensed by said dispenser each is adjusted
substantially independently of the quantity and/or flow rate of
liquid being dispensed.
28. The apparatus of claim 26 wherein said valve is actuated by an
electric solenoid.
29. The apparatus of claim 26 wherein said valve is actuated by a
piezoelectric constrictor device.
30. The apparatus of claim 26 wherein the frequency and duty cycle
of said valve each is adjusted substantially independently for a
given quantity or flow rate of liquid to produce droplets of a
desired size, frequency and/or exit velocity.
31. The apparatus of claim 26 wherein said positive displacement
pump comprises a syringe pump.
32. The apparatus of claim 31 wherein said syringe pump comprises a
syringe housing, a plunger axially displaceable within said syringe
housing and plunger shaft having a lead screw formed thereon.
33. The apparatus of claim 32 wherein said lead screw is sized and
positioned such that when said lead screw is rotated, said plunger
is displaced axially, causing a predetermined quantity of said
liquid to be delivered to said inlet of said dispenser.
34. The apparatus of claim 33 wherein said positive displacement
pump further comprises a stepper motor adapted to cause said pump
to dispense predetermined incremental quantities or flow rates of
said liquid to said dispenser.
35. The apparatus of claim 26 wherein said dispenser and positive
displacement pump are configured so as to provide a range of
selectable droplet sizes attainable for stable operation varying by
a factor of greater than about 250.
36. The apparatus of claim 1 wherein said dispenser and metering
pump are configured so as to provide selectable droplet sizes in
the range of about 0.54 nanoliters.
37. An apparatus for dispensing predetermined quantities of liquid
onto a substrate, comprising: a dispenser having an inlet and an
outlet and being adapted to form droplets of said liquid having a
size in the range of about 1-4 nanoliters to one microliter which
are deposited onto said substrate; and a pump hydraulically
arranged in series with the inlet of said dispenser for metering
predetermined quantities of said liquid to said dispenser; said
dispenser and pump being selected and configured so as to provide a
range of selectable droplet sizes attainable for stable operation
varying by a factor of greater than about 250 and whereby the
quantity and/or flow rate of liquid dispensed by said dispenser is
metered substantially independently of .[.the.]. operating
parameters of the dispenser.
38. The apparatus of claim 37 wherein said dispenser comprises a
valve adapted to be opened and closed at a predetermined frequency
and duty cycle to form droplets of said liquid which are deposited
onto said substrate.
39. The apparatus of claim 38 wherein said valve is actuated by an
electric solenoid.
40. The apparatus of claim 38 wherein said valve is actuated by a
piezoelectric constrictor device.
41. The apparatus of claim 38 wherein the frequency and duty cycle
of said valve .[.can each be.]. .Iadd.each is .Iaddend.adjusted
substantially independently for a given quantity or flow rate of
liquid to produce droplets of a desired size, frequency and/or exit
velocity.
42. The apparatus of claim 37 in combination with a carriage
adapted for X, X-Y or X-Y-Z motion relative to said dispenser for
movably transporting said substrate and wherein said dispenser is
mounted in juxtaposition with said carriage.
43. The combination of claim 42 further comprising a controller in
communication with said pump and said carriage for coordinating the
output of said pump with the motion of said carriage so that said
liquid may be dispensed in precise quantities of flow per unit
length and such flow is precisely metered substantially without
being affected by the .[.particular.]. operating parameters of said
dispenser.
44. The combination of claim 43 further comprising an array of
dispensers and pumps, the outlets of said dispensers being arranged
in a desired pattern suitable for attaining a desired print matrix
or dot pattern.
45. The apparatus of claim 37 wherein said pump comprises a syringe
pump.
46. The apparatus of claim 45 wherein said syringe pump comprises a
syringe housing, a plunger axially displaceable within said syringe
housing and plunger shaft having a lead screw formed thereon.
47. The apparatus of claim 45 wherein said syringe housing has a
displacement volume of between about 25 microliters about 25
milliliters.
48. The apparatus of claim 37 wherein said pump comprises a stepper
motor adapted to cause said pump to dispense predetermined
incremental quantities or flow rates of said liquid to said
dispenser.
49. The apparatus of claim 48 wherein said pump has an incremental
displacement volume of between about 0.42 nanoliters and 2.1
microliters.
50. The apparatus of claim 48 wherein said pump has an incremental
displacement volume of less than about 4.2 nanoliters.
51. The apparatus of claim 37 wherein said dispenser and pump are
configured so as to provide selectable droplet sizes ranging from
less than about 4.2 nanoliters to greater than about 1
microliter.
52. The apparatus of claim 37 wherein said dispenser and pump are
configured so as to provide selectable droplet sizes in the range
of about 0.54 nanoliters.
53. The apparatus of claim 1 wherein the dispenser is adapted to
form droplets of said liquid having a size of about 0.54
nanoliters.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to an improved method and
apparatus for dispensing chemical reagents and other liquids onto a
substrate and, in particular, to various methods and apparati
particularly adapted for dispensing precise quantities of chemical
reagents onto a receptive membrane, such as to form a diagnostic
test strip, having improved dynamic range of operation.
2. Description of the Prior Art
Clinical testing of various bodily fluids conducted by medical
personnel are well-established tools for medical diagnosis and
treatment of various diseases and medical conditions. Such tests
have become increasingly sophisticated, as medical advancements
have led to many new ways of diagnosing and treating diseases.
The routine use of clinical testing for early screening and
diagnosis of diseases or medical conditions has given rise to a
heightened interest in simplified procedures for such clinical
testing that do not require a high degree of skill or which persons
may conduct on themselves for the purpose of acquiring information
on a physiological relevant condition. Such tests may be carried
out with or without consultation with a health care professional.
Contemporary procedures of this type include blood glucose tests,
ovulation tests, blood cholesterol tests and tests for the presence
of human chorionic gonadotropin in urine, the basis of modern home
pregnancy tests.
One of the most frequently used devices in clinical chemistry is
the test strip or dip stick. These devices are characterized by
their low cost and simplicity of use. Essentially, the test strip
is placed in contact with a sample of the body fluid to be tested.
Various reagents incorporated on the test strip react with one or
more analytes present in the sample to provide a detectable
signal.
Most test strips are chromogenic whereby a predetermined soluble
constituent of the sample interacts with a particular reagent
either to form a uniquely colored compound, as a qualitative
indication of the presence or absence of the constituent, or to
form a colored compound of variable color intensity, as a
quantitative indication of the amount of the constituent present.
These signals may be measured or detected either visually or via a
specially calibrated machine.
For example, test strips for determining the presence or
concentration of leukocyte cells, esterase or protease in a urine
sample utilize chromogenetic esters which produce an alcohol
product as a result of hydrolysis by esterase or protease. The
intact chromogenetic ester has a color different from the alcohol
hydrolysis product. The color change generated by hydrolysis of the
chromogenetic ester, therefore provides a method of detecting the
presence or concentration of esterase or protease, which in turn,
is correlated to the presence or concentration of leukocyte cells.
The degree and intensity of the color transition is proportional to
the amount of leukocyte esterase or HLE detected in the urine. See
U.S. Pat. No. 5,464,739.
The emergence and acceptance of such diagnostic test strips as a
component of clinical testing and health care in general has led to
the development of a number of quality diagnostic test strip
products. Moreover, the range and availability of such products is
likely to increase substantially in the future.
Because test strips are used to provide both quantitative and
qualitative measurements, it is extremely important to provide
uniformity in distribution of the reagents on the test strip
substrate. The chemistry is often quite sensitive and medical
practice requires that the testing system be extremely accurate.
When automated systems are used, it is particularly important to
ensure that the test strips are reliable and that the measurements
taken are quantitatively accurate.
Application of one or more reagents to a test strip substrate is a
highly difficult task. The viscosities and other flow properties of
the reagents, their reactiveness with the substrate or other
reagents vary from reagent to reagent, and even from lot to lot of
the same reagent. It is also sometimes necessary or desirable to
provide precise patterns of reagent on the test strip having
predetermined reagent concentrations. For example, some test strips
provide multiple test areas that are serially arranged so that
multiple tests may be performed using a single test strip. U.S.
Pat. No. 5,183,742, for instance, discloses a test strip having
multiple side-by-side detection regions or zones for simultaneously
performing various tests upon a sample of body fluid. Such test
strip may be used to determine, for example, levels of glucose,
protein, and the pH of a single blood sample. It is often
difficult, however, to form sharp lines or other geometric shapes
having uniform concentrations of reagent.
For several years the industry has been developing dispensing
methods based on the use of either air brush dispensers or solenoid
valve dispensers. Air brushes use pressurized air flowing across a
needle valve opening to atomize the reagent into a mist which is
then deposited onto the test strip substrate. The quality of the
mist, reagent dispersion pattern and the amount of reagent flow
onto the substrate is controlled by adjusting the needle valve
opening and/or the pressure of the atomizing air flow. Solenoid
valve dispensers generally comprise a small solenoid-activated
valve which can be opened and closed electronically at high speeds.
The solenoid valve is connected to a pressurized vessel or
reservoir containing the fluid to be dispensed. In operation, the
solenoid is energized by a pulse of electrical current, which opens
the valve for a predetermined duty-cycle or open time. This allows
a small volume of liquid to be forced through the nozzle forming a
droplet which is then ejected from the valve onto the target
substrate. The size and frequency of the droplets and the amount of
reagent flow onto the substrate is typically controlled by
adjusting the frequency and pulse-width of energizing current
provided to the solenoid valve and/or by adjusting the pressure of
the reservoir.
Currently available dispensing methods, however, are limited in the
flexibility they have to independently adjust and regulate the
output of the dispenser in terms of droplet size or mist quality,
droplet velocity and flow rates of dispensed reagent. Flow rates
can often drift due to changes in temperature or the viscosity of
the reagent. This can cause undesirable lot to lot variances of
reagent coating concentrations or coating patterns. Many reagents
that are used for diagnostic testing are so reactive with the
receptive membrane or substrate that large droplets can form
impressions on the membrane surface at the point of initial contact
before the droplets flow together to form the desired pattern. As a
result, it is sometimes desirable to dispense a fine mist or very
small droplets of reagent onto the substrate. Often, however, a
desired droplet size or mist quality is simply not attainable for a
desired production flow rate. It is sometimes necessary, therefore,
to perform production runs of test strips at slower than optimal
speeds in order to ensure adequate results. This can increases the
cost of production significantly. Certain dispensers, such as
solenoid valves, are also susceptible to clogging by small air or
gas bubbles forming in the valve itself or in the lines or conduits
which supply reagent or other liquids to the dispenser. This is a
major reliability problem with many conventional solenoid valve
dispensers.
While some of these problems can be controlled or mitigated by
adding surfactants or various other chemical additives to modify
the surface tension or other flow characteristics of the droplets,
compatible chemistry is not available for all reagents. Also the
use of surfactants and other chemicals can often lead to other
problems either in the test strip itself or in the dispensing
apparatus or production processes.
SUMMARY OF THE INVENTION
The reagent dispensing method and apparatus in accordance with the
present invention can dispense desired quantities of chemical
reagents or other liquids onto a substrate, such as a receptive
membrane, while advantageously providing the ability to
independently and precisely adjust droplet size or mist quality,
droplet velocity and reagent flow rates, both in terms of per unit
time or per unit distance. Thus, the present invention provides new
devices and methods of dispensing precise quantities of liquids
having improved performance and dynamic range of operation.
In accordance with one preferred embodiment the present invention
comprises an improved apparatus for dispensing precise quantities
of liquid onto a substrate. The apparatus comprises a dispenser
having an inlet and an outlet and being adapted to form droplets of
liquid having a predetermined size and/or quality. The droplets are
emitted by the dispenser so as to be deposited onto a receptive
substrate. A positive displacement pump is provided in series with
the inlet of the dispenser for metering predetermined quantities of
liquid provided to the dispenser. In this manner, the quantity
and/or flow rate of liquid dispensed by the dispenser can be
precisely metered substantially independently of the particular
operating parameters of the dispenser.
In accordance with another preferred embodiment the present
invention comprises a method or apparatus for dispensing a reagent
onto a substrate. A positive displacement syringe pump is provided
in series with a reagent dispenser. The pump is controlled via a
stepper motor or the like to provide precision incremental or
continuous flow of reagent to the dispenser. The dispenser is
selectively operated to form droplets or a mist of droplets of a
predetermined droplet size and/or quality which are then deposited
onto the target substrate. Advantageously, the droplet size, mist
quality, droplet velocity and/or flow rate of the reagent can be
precisely controlled independently of the particular system
operating parameters of the dispenser.
In accordance with another preferred embodiment the present
invention comprises an apparatus for dispensing a liquid onto a
substrate, comprising a dispenser having an inlet and an outlet and
a valve adapted to be opened and closed at a predetermined
frequency and duty cycle to form droplets which are deposited onto
the substrate. A positive displacement pump, such as a
stepper-motor-operated syringe pump, is hydraulically arranged in
series with the inlet of the dispenser for metering predetermined
quantities of liquid to the dispenser. The pump and dispenser are
operated in cooperation with one another such that the quantity
and/or flow rate of liquid dispensed by the dispenser can be
precisely metered substantially independently of the particular
operating parameters of said dispenser. In this manner, the size,
frequency, and velocity of droplets dispensed by said dispenser can
each be adjusted substantially independently of the quantity and/or
flow rate of liquid being dispensed.
In accordance with another preferred embodiment the present
invention comprises an apparatus as described above in combination
with a carriage adapted for X, X-Y or X-Y-Z motion relative to the
dispenser. The dispenser and carriage are arranged and controlled
in a coordinated manner to form droplets of reagent, ink, liquid
toner or other liquid in accordance with a predetermined desired
matrix or pattern. If desired, an array of dispensers and
associated positive displacement pumps may be provided and the
outlets of the dispensers being arranged in a desired pattern
suitable for attaining a desired print matrix or dot pattern.
These and other embodiments and modes of carrying out the present
invention will be readily ascertainable from the following detailed
description of the preferred modes, having reference to the
attached drawings, the invention not being limited to any
particular preferred embodiment.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A is a schematic drawing of a precision metered dispensing
apparatus having features in accordance with the present
invention;
FIG. 1B is a schematic drawing of an alternative embodiment of a
precision metered dispensing apparatus particularly adapted for
continuous web production operation and having features in
accordance with the present invention;
FIGS. 2A and 2B are cross-sectional and detail views, respectfully,
of an air brush dispenser having features in accordance with the
present invention;
FIG. 2C is a graphical representation of the test strip substrate
of FIG. 2B illustrating surface concentration of dispensed reagent
and the resulting concentration gradients of the absorbed
reagent;
FIG. 3 is a cross-sectional view of a solenoid valve dispenser
having features in accordance with the present invention;
FIG. 4 is a cross-sectional view of an optional piezoelectric
dispenser having features in accordance with the present
invention;
FIG. 5 is a cross-sectional detail view of the syringe pump of FIG.
1;
FIG. 6 is a graph comparatively illustrating the range of flow
rates attainable with a precision metered aerosol dispensing
apparatus constructed and operated in accordance with the present
invention;
FIG. 7 is a schematic drawing illustrating two possible modes of
operation of a solenoid valve dispenser constructed and operated in
accordance with the present invention;
FIG. 8 is a schematic view of an electrostatic printer for use in
accordance with one embodiment of the present invention; and
FIG. 9 is a front elevational view of an optional dispenser
platform and multi-head dispenser for use in accordance with one
embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1A is a schematic drawing of a precision metered dispensing
apparatus 10 having features in accordance with the present
invention. The dispensing apparatus 10 generally comprises a
dispenser 12 for dispensing reagent 14 from a reservoir 16 and a
positive displacement syringe pump 22 intermediate the reservoir 16
and the dispenser 12 for precisely metering the volume and/or flow
rate of reagent dispensed. The dispenser 12 is operated to provide
individual droplets or a spray of reagent, as desired, at the
predetermined incremental quantity or flow rate.
FIG. 1B is a schematic drawing of an alternative embodiment of a
precision metered dispensing apparatus 10' particularly adapted for
continuous web production operation and having features in
accordance with the present invention. For convenience of
description and ease of understanding like reference numerals are
used to refer to like components previously identified and
described in FIG. 1A. The dispensing apparatus 10' generally
comprises a dispenser 12' for dispensing reagent 14' from a
reservoir 16'. As described above, the dispenser 12' can be
selectively operated to provide individual droplets or a spray
pattern of reagent, as desired, at the predetermined incremental
quantity or metered flow rate.
In this case, however, tandem positive displacement syringe pumps
22a, 22b are disposed intermediate the reservoir 16' and the
dispenser 12' for precisely and continuously metering the volume
and/or flow rate of reagent dispensed. The pumps 22a, 22b are
preferably connected in parallel, as shown, and are isolated from
one another by appropriate check valves 24' such that each syringe
pump 22a, 22b is capable of independently metering a volume and/or
flow rate of reagent to be dispensed. This particular dispensing
apparatus configuration has significant advantages for continuous
web production applications since the syringe pumps 22a, 22b can be
operated in alternating succession while allowing the
non-dispensing syringe pump to draw additional reagent 14' from the
reservoir 16'. In this manner, continuous web production is
facilitated without interruption. Of course, one or more additional
syringe pumps may also be used in a similar manner, if desired,
such as for dispensing a wash fluid or other suitable reagents or
fluids. Alternatively, if desired, one or more continuous positive
displacement pumps, such as a peristaltic pump, may be used for
continuous web production.
The dispensers 12 and 12', described above, may comprise any one of
a number of suitable dispensers well known in the art for
dispensing a liquid, such as an air brush dispenser, a solenoid
valve dispenser or a piezoelectric dispenser. Several particularly
preferred examples are described below for illustrative purposes.
Those skilled in the art will readily appreciate that a wide
variety of other suitable dispensers may also be used to achieve
the benefits and advantages taught herein.
Air Brush Dispenser
FIGS. 2A and 2B are cross-sectional and detail views, respectfully,
of an air brush dispenser 12a, for use in accordance with one
embodiment of the present invention. The dispenser 12a generally
comprises a nozzle portion .[.32.]. .Iadd.32a .Iaddend.and a
manifold portion .[.34.]. .Iadd.34a.Iaddend.. The manifold .[.34.].
.Iadd.34a .Iaddend.allows compressed air to enter into a first
annular chamber .[.36.]. .Iadd.36a .Iaddend.and allows reagent to
enter into a second annular chamber .[.38.]. .Iadd.38a
.Iaddend.formed between a needle valve .[.40.]. .Iadd.40a
.Iaddend.and a corresponding orifice .[.42.]. .Iadd.42a.Iaddend..
The needle valve .[.40.]. .Iadd.40a .Iaddend.is fitted within and
extends through the orifice .[.42.]. .Iadd.42a.Iaddend., as shown.
It is preferably axially adjustable in accordance with well-known
needle valve adjustment techniques. The position of the needle
valve .[.40.]. .Iadd.40a .Iaddend.relative to the orifice .[.42.].
.Iadd.42a .Iaddend.determines the effective size of the resulting
needle valve opening 43, and thus the amount of reagent flow for a
given pressure differential.
Pressurized air flows over the needle valve opening 43 creating a
venturi effect which draws reagent through the orifice .[.42.].
.Iadd.42a .Iaddend.onto the tip of the needle valve .[.40.].
.Iadd.40a.Iaddend.. The pressurized air accelerates past the
orifice .[.42.]. .Iadd.42a .Iaddend.and the needle valve opening 43
over the tip of the needle .[.40.]. .Iadd.40a.Iaddend.. The
resulting high velocity air atomizes the reagent 14 flowing down
the needle .[.40.]. .Iadd.40a.Iaddend.. This creates an aerosol
mist 45 which is ejected from the nozzle .[.32.]. .Iadd.32a
.Iaddend.along with the excess airflow. In a conventional air brush
dispenser, the volume of reagent dispensed by the nozzle .[.32.].
.Iadd.32a .Iaddend.is determined by the pressure differential of
the compressed air source relative to atmospheric pressure, the
size of the needle valve opening 43, and the viscosity and other
flow characteristics of the reagent 14.
In accordance with one embodiment of the present invention,
however, a positive displacement pump 22 is provided in series
between the reservoir 16 and the air brush 12a as shown in FIG. 1.
The orifice .[.42.]. .Iadd.42a .Iaddend.now admits a flow of
reagent as determined solely by the positive displacement pump 22.
The reagent is ejected out of the orifice opening .[.42.].
.Iadd.42a .Iaddend.and mixes with the pressurized air flowing out
of the nozzle .[.32.]. .Iadd.32a.Iaddend.. Advantageously, in
accordance with the present invention absolute volume or flow rate
is an input parameter controlled by the metering pump, rather than
an output parameter which must be calibrated by trial and error
adjustment. Thus, the air brush can be used to deliver precise
quantities and flow rates of reagent onto a test strip substrate.
This substrate is preferably a receptive membrane adapted to bond
with the reagent so as to form a diagnostic test strip. However,
the substrate 30 may also be paper, celluous, plastic or any wet or
dry surface capable of receiving a dispensed reagent or other
liquid.
As discussed in more detail below, a reagent dispensing apparatus
and method using the combination of an air brush dispenser and a
metering pump provides a new dimension of control which provides
additional production capabilities not achievable with conventional
air brush dispensers. Unlike conventional methods of operating an
air brush dispenser, which typically provide only a single stable
operating point for a given input air pressure and needle valve
opening, the method and apparatus of the present invention provides
a wide range of metered flow rates for achieving a stable
dispersion pattern. The limits of this range can be determined
experimentally. An even wider range of production flow rates can be
achieved using a single pressure setting and a series of adjustable
orifice openings as illustrated in FIG. 6, discussed later.
FIG. 2C is a graphical representation of the test strip membrane 30
of FIG. 2B, illustrating surface concentration 46 of dispensed and
the resulting concentration gradients 48 of the absorbed reagent in
the membrane 30. For stable dispersion patterns, the surface
reagent concentration 46 assumes a standard Gausian distribution,
as shown. The width or standard deviation of the distribution
pattern will depend upon the shape of the dispersion pattern
created by the nozzle .[.32.]. .Iadd.32a .Iaddend.(FIG. 2B). This
is dependent primarily on the shape of the exit nozzle .[.32.].
.Iadd.32a.Iaddend., the needle valve .[.40.]. .Iadd.40a
.Iaddend.and the input air pressure. Higher input pressures will
generally result in wider dispersion patterns.
Solenoid Valve Dispenser
FIG. 3 is a cross-sectional view of a solenoid valve dispenser 12b
for use in accordance with another embodiment of the present
invention. Solenoid valve dispensers of this type are commonly used
for ink-jet printing and are commercially available from sources
such as The Lee Company of Westbrook, Conn. The dispenser 12b
generally comprises a solenoid portion .[.32.]. .Iadd.32b
.Iaddend.and a valve portion .[.34.]. .Iadd.34b.Iaddend.. The
solenoid portion .[.32.]. .Iadd.32b .Iaddend.comprises an
electromagnetic coil or winding .[.36.]. .Iadd.36b.Iaddend., a
static core .[.38.]. .Iadd.38b .Iaddend.and a movable plunger
.[.40.]. .Iadd.40b.Iaddend.. The static core .[.38.]. .Iadd.38b
.Iaddend.and movable plunger .[.40.]. .Iadd.40b .Iaddend.are
disposed within a hollow cylindrical sleeve 41 and are preferably
spaced at least slightly away from the inner walls of the sleeve 41
so as to form an annular passage .[.42.]. .Iadd.42b
.Iaddend.through which the reagent or other liquid to be dispensed
may flow. The static core .[.38.]. .Iadd.38b .Iaddend.and movable
plunger .[.40.]. .Iadd.40b .Iaddend.are preferably formed of a
ferrous or magnetic material, such as iron, and are separated by a
small gap 44. Those skilled in the art. will appreciate that when
the solenoid coil .[.36.]. .Iadd.36b .Iaddend.is energized a
magnetic field is created which draws the plunger .[.40.].
.Iadd.40b .Iaddend.upward toward the static core .[.38.].
.Iadd.38b.Iaddend., closing the gap 44 and opening the valve
.[.34.]. .Iadd.34b.Iaddend..
The valve portion .[.34.]. .Iadd.34b .Iaddend.comprises a valve
seat 52, having an orifice opening 54, and a stopper 56 having a
valve face 58 adapted to seal against the valve seat 52. The
stopper 56 is in mechanical communication with the plunger .[.40.].
.Iadd.40b .Iaddend.and is spring biased toward the valve seat 52
via coil spring 60. Again, those skilled in the art will readily
appreciate that as the plunger .[.40.]. .Iadd.40b .Iaddend.moves up
and down, the valve .[.34.]. .Iadd.34b .Iaddend.will open and
close, accordingly. Moreover, each time the valve .[.34.].
.Iadd.34b .Iaddend.opens and closes, a volume of liquid is forced
through the valve orifice 54 to form a pulse or pressure wave which
ejects a droplet of liquid from the exit orifice 61 of the nozzle
tip 59.
Conventionally, a pressurized reservoir (not shown) having a
predetermined constant pressure is used to force liquid reagent or
other liquid through the valve orifice 54 during the time interval
in which the valve .[.34.]. .Iadd.34b .Iaddend.is open. Under
controlled conditions, such dispensers may have a repeatability of
.+-.2% with a minimum drop size of about 30-35 nanoliters. The size
of the droplet will be determined by system operating parameters
such as the reservoir pressure, valve open time or duty-cycle, and
the viscosity and other flow characteristics of the particular
reagent or liquid being dispensed. Of course, certain fixed
parameters, such the size and shape of the nozzle 59, will also
play an important role in the operational characteristics of the
valve in terms of droplet size and repeatability. In general,
however, droplet size will increase with increasing reservoir
pressure and valve open time.
In accordance with the present invention, however, a positive
displacement pump 22 is provided in series between the supply
reservoir 16 and the solenoid valve dispenser 12b, as shown in FIG.
1. For a given range of flow rates the valve orifice 54 (FIG. 3)
now admits a quantity and/or flow rate of reagent as determined
solely by the positive displacement pump 22. For example, the flow
rate could be set to deliver 1 microliter per second of reagent.
The pump 22 will then deliver a steady flow of reagent to the
solenoid valve dispenser 12b at the programmed rate. As the
solenoid valve is opened and closed, a series of droplets will be
formed at the desired volume flow rate and ejected onto the target
substrate 30. This substrate is preferably a receptive membrane
adapted to bond with the reagent so as to form a diagnostic test
strip. Alternatively, the substrate 30 may be paper, celluous,
plastic or any other wet or dry surface capable of receiving a
dispensed reagent or other liquid.
Advantageously, within a certain operating range the size of the
droplets can be adjusted without affecting the flow rate of reagent
simply by changing the frequency of the energizing pulses 13
provided to the solenoid valve dispenser 12b. Of course, there are
physical limitations of valve open time or duty-cycle necessary to
achieve stable droplet formation. If the open time is too short
relative to the flow rate provided by the metering pump 22, the
pressure will increase and possibly prevent the valve from opening
or functioning properly. If the open time is too long relative to
the flow rate, then drop formation may not be uniform for each
open/close cycle. Nevertheless, for a given flow rate of reagent
provided by the pump 22 there will be a range of compatible
frequencies and/or valve open times or duty-cycles in which stable
dispensing operations may be achieved at the desired flow rate and
droplet size. This range may be determined experimentally for a
given production set up.
Another significant advantage of the present invention is that the
velocity of individual droplets can be independently adjusted
without affecting the flow rate of reagent or droplet size. This
can be accomplished, for example, by varying the duty cycle of the
energizing pulses 13 provided to the solenoid valve dispenser
12b.
For example, at a drop volume of 83.3 nL the drop can be formed by
using 20 syringe steps with 1 valve opening using a 100 uL syringe
with a 24,000 step resolution. Using an open time of 5% will result
in a higher drop velocity than using an open time of 7%. This is
because with the shorter open time the pressure build up in the
hydraulic line is greater than 7%.
Again, there are physical limitations posed by the length of
duty-cycle necessary to achieve stable droplet formation, as noted
above. Nevertheless, for a given flow rate and droplet size there
will be a range of compatible duty-cycles in which stable
dispensing operations may be achieved at the desired flow rate,
droplet size and velocity. Again, this range may be determined
experimentally for a given production set up.
As discussed in more detail below, dispensing a reagent by using a
combination of a solenoid valve dispenser and a metering pump
provides a new dimension of control which provides additional
production capabilities not achievable with conventional solenoid
valve dispensers. Unlike conventional solenoid valve dispensers,
which typically have only a single flow rate or operating point for
a given set of system operating parameters (e.g. reservoir
pressure, valve frequency and duty cycle), the present invention
provides a wide dynamic range of metered flow rates, droplet size,
droplet frequency and droplet velocity for achieving stable
dispensing operation. Moreover, because the solenoid valve
dispenser 12b is forced to deliver precise quantities and/or flow
rates of reagent, the solenoid valve dispenser is not as
susceptible to clogging due to air or gas bubbles. Rather, any air
or gas bubbles tend to be recondensed or ejected out of the
solenoid valve dispenser 12b by operation of the positive
displacement pump 22.
Piezoelectric Dispenser
FIG. 4 shows a cross-sectional view of an optional piezoelectric
dispenser 12c which may also have advantageous use in accordance
with the present invention. The piezoelectric dispenser generally
comprises a capillary tube 84 made of glass or other suitable
material and a piezoelectric constrictor 86 disposed around the
capillary tube 84, as shown. The capillary tube 84 has a nozzle
portion 88 of a reduced diameter. When the capillary tube 84 is
constricted by the piezoelectric constrictor 86, droplets 90 are
formed at the exit orifice 89 of the nozzle portion 88.
Advantageously, the dynamics of the piezoelectric dispenser 12c are
such that it is able to operate at higher frequencies and shorter
duty cycles than typical solenoid valve dispensers, resulting in
even smaller droplets 90. Operation of the piezoelectric dispenser
in terms of adjusting droplet size, frequency, velocity and flow
rates is substantially the same as that described above in
connection with the solenoid valve dispenser 12b of FIG. 3 and,
therefore, will not be repeated here.
Syringe Pump
A positive displacement pump for use in accordance with one
particular embodiment of the present invention may be any one of
several varieties of commercially available pumping devices for
metering precise quantities of liquid. A syringe-type pump 22, as
shown in FIGS. 1A and 1B, is preferred because of its convenience
and commercial availability. A wide variety of other pumps may
used, however, to achieve the benefits and advantages as disclosed
herein. These may include, without limitation, rotary pumps,
peristaltic pumps, squash-plate pumps, and the like. As illustrated
in more detail in FIG. 5, the syringe pump 22 generally comprises a
syringe housing 62 of a predetermined volume and a plunger 64 which
is sealed against the syringe housing by O-rings or the like. The
plunger 64 mechanically engages a plunger shaft 66 having a lead
screw portion 68 adapted to thread in and out of a base support
(not shown). Those skilled in the art will readily appreciate that
as the lead screw portion 68 of the plunger shaft 66 is rotated the
plunger 64 will be displaced axially, forcing reagent from the
syringe housing 62 into the exit tube 70. Any number of suitable
motors or mechanical actuators may be used to drive the lead screw
68. Preferably, a stepper motor 26 (FIG. 1) or other incremental or
continuous actuator device is used so that the amount and/or flow
rate of reagent can be precisely regulated.
Suitable syringe pumps are commercially available, such as the
Bio-Dot CV1000 Syringe Pump Dispenser, available from Bio-Dot, Inc.
of Irvine, Calif. This particular syringe pump incorporates an
electronically controlled stepper motor for providing precision
liquid handling using a variety of syringe sizes. The CV1000 is
powered by a single 24 DC volt power supply and is controlled via
an industry-standard RS232 or RS485 bus interface. The syringe pump
may have anywhere from 3,000-24,000 steps, although higher
resolution pumps having 48,000 steps or more may also be used to
enjoy the benefits of the invention herein disclosed. Higher
resolution pumps, such as piezoelectric pumps, may also be used to
provide even finer resolutions as desired. The lead screw 68 may
optionally be fitted with an optical encoder or similar device to
detect any lost steps. Alternatively, the lead screw of the
metering pump can be replaced with a piezoelectric slide to provide
both smaller volume increments and also faster
acceleration/deceleration characteristics. Multiple syringe pumps
may also be used in parallel, for example, for delivering varying
concentrations of reagent and/or other liquids to the dispenser or
for alternating dispensing operations between two or more reagents.
This could have application, for instance, to ink jet printing
using one or more colored inks or liquid toners.
The travel of the plunger 64 is preferably about 60 mm. Plunger
speeds may range from 0.8 seconds per stroke with a 10-step minimum
for low-resolution pumping or 1.5 seconds per stroke with a 20-step
minimum for high-speed resolution pumping. The stroke speed may
vary depending upon the syringe size and the tubing used. Syringes
may vary from less than 50 microliters to 25 milliliters, or more
as needed. For most reagent dispensing applications it should be
adequate to provide a syringe having a volume from about 500
microliters to about 25 milliliters. The minimum incremental
displacement volume of the pump will depend on the pump resolution
and syringe volume. For example, for a syringe housing volume of
500 ml and 12,000 step resolution pump the minimum incremental
displacement volume will be about 42 nanoliters. Minimum
incremental displacement volumes from about 2.1 nanoliters to 2.1
milliliters are preferred, although higher or lower incremental
displacement volumes may also be used while still enjoying the
benefits of the present invention.
The syringe housing 62 may be made from any one of a number of
suitable bio compatible materials such as glass, Teflon.TM. or
Kel-F. The plunger 64 is preferably formed of virgin Teflon.TM..
Referring to FIG. 1, the syringe is connected to the reservoir 16
and the dispenser 12 using a Teflon tubing 23, such as 1/4-inch
O.D. tubing provided with luer-type fittings for connection to the
syringe and dispenser. Various check valves 24 or shut-off valves
25 may also be used, as desired or needed, to direct the flow of
reagent to and from the reservoir 16, syringe pump 22 and dispenser
12c.
Reagent Reservoir
The reagent reservoir 16 may be any one of a number of suitable
receptacles capable of allowing a liquid reagent 14 to be siphoned
into pump 22. The reservoir may be pressurized, as desired, but is
preferable vented to the atmosphere, as shown, via a vent opening
15. The particular size and shape of the reservoir 16 is relatively
unimportant.
A siphon tube 17 extends downward into the reservoir 16 to a
desired depth sufficient to allow siphoning of reagent 14.
Preferably the siphon tube 17 extends as deep as possible into the
reservoir 16 without causing blockage of the lower inlet portion of
the tube 17. Optionally, the lower inlet portion of the tube 17 may
be cut at an angle or have other features as necessary to desirable
to provide consistent and reliable siphoning of reagent 14.
Operation
As indicated above, a key operational advantage achieved by the
present invention is that over a certain dynamic range the flow of
reagent, droplet size or mist quality, droplet frequency, and/or
droplet velocity may be controlled substantially independently of
one another and of the particular flow characteristics of the
reagent and operating parameters of the dispenser 12. For example,
the size of droplets formed by the dispenser can be adjusted
without affecting the flow rate of reagent metered by the pump by
changing the operating frequency (for solenoid valve or
piezoelectric dispenser) or by adjusting the exit orifice size (for
an air brush dispenser). The quantity or flow rate of reagent
dispensed is substantially unaffected because it is precisely
controlled by the positive displacement pump 22. This has
particular advantage, for example, in applications requiring the
dispensing of very small droplets or for dispensing higher
viscosity reagents, since the reagent flow can be precisely
controlled without substantial regard to the system operating
parameters otherwise required to achieve stable dispensing
operations. FIG. 6 comparatively illustrates the range of flow
rates and operating conditions for given orifice openings
attainable in accordance with the present invention using an air
brush dispenser, versus conventional dispensing methods using an
air brush dispenser.
Similarly, with a conventional solenoid valve dispenser in order to
obtain very small droplets, one must attempt to shorten the open
time or duty cycle of the valve. However, as the valve open time is
shortened, the flow rate of reagent decreases such that the cycle
frequency of the valve must be increased to compensate. At a
certain point the flow characteristics of the reagent will limit
the ability to achieve uniform formation of droplets when the valve
open time is very small. Moreover, even if stable dispensing
operation could be achieved by increasing the reservoir pressure,
such increased pressure will tend to increase the droplet size and
flow rate of reagent, necessitating even further adjustments to
achieve stable dispensing operation at the desired flow rate and
droplet size.
The present invention, however, overcomes these and other problems
of the prior art by precisely metering the quantity and/or flow
rate of the reagent. Advantageously, the amount of reagent can be
precisely regulated over a wide dynamic range without being
substantially affected by the particular operating parameters of
the dispenser. This feature enables droplet size, droplet
frequency, droplet velocity and other system parameters to be
varied dramatically from one range to another at a given flow rate.
Thus, the present invention not only provides a method for precise
metering of reagent, but also adds a new dimension of operation a
dispenser not before possible.
Another important operational advantage is that the range of
droplet sizes attainable with the present invention is much wider
than achieved with conventional solenoid valve dispensers. The
method and apparatus of the present invention using the solenoid
valve dispenser, for example, is capable of attaining minimum
stable droplet sizes in the range of 1-4 nanoliters, compared with
30-35 nanoliters for most conventional solenoid valve dispensers.
In principle, even smaller droplet sizes (on the order of 0.54
nanoliters or smaller) should be attainable in accordance with the
present invention using syringe pumps having a resolution of 48,000
steps and a syringe volume of 25 microliters. Drop formation
experiments have demonstrated the ability to dispense
4.16-nanoliter drops with very good repeatability using a nozzle 59
(FIG. 3) having an exit orifice 61 of about 175 microns in
diameter. A smaller exit orifice 61 having a diameter in the range
of 75-125 microns should provide stable formation and dispensing of
even smaller droplets in accordance with the present invention.
On the other hand, with the same setup one can program drop sizes
or volume delivered up into the range of 1 uL by pulsing the
syringe many times per valve opening and by increasing the valve
open time to allow the larger volume to flow through the open
valve. For example, for a drop size of 4.16 nL, the preferred
setting would be 1 syringe step, 1 valve opening and the open time
would be 2% or about 0.2 millisecond. For a drop size of 1,000 nL
or 1.0 uL, the preferred setting would be 240 syringe steps, 1
valve opening and the open time would be in the range of 25%-30% or
2.5 to 3.5 milliseconds. One can also deliver the larger volumes in
a high frequency burst of smaller drops. For example, one can
deliver 4.16 uL as 100 drops of 41.67 nL each using a frequency of
100 Hz and an open time of 6% or 0.6 milliseconds.
Thus, the range of droplet sizes attainable for stable dispensing
operation may vary by a factor of about 250 or more. This feature
of the present invention has particular advantage for high
production manufacturing and processing of diagnostic test strips.
In certain production applications, for example, it may be
desirable to dispense very small droplets or fine mists of reagent
to provide optimal coating characteristics. At the same time, it
may be desirable to provide high reagent flow rates for increased
production levels. With a conventional solenoid valve dispenser,
for example, to increase the output flow rate the valve frequency
or the length of the valve open time must be increased. But the
longer the valve open time is, the larger the droplets will be.
There is also an operational limit for a given valve and exit
orifice to how short the open time of the valve can be and how high
the operating frequency can be while still attaining stable
operation.
The present invention, however, allows the use of much shorter
valve open times to attain stable operation at high flow rates by
positively displacing the reagent through the valve opening. In
other words, the flow of reagent is not substantially affected by
the particular operating frequency of the valve or the length of
the open time. It is dependent only on the displacement of the
syringe pump, which acts as the forcing function for the entire
system.
Of course, as noted above, there will be a maximum range of
operation for a solenoid valve dispenser operating at given
operating frequency and valve open time. The higher limit will be
the maximum amount of reagent that can be forced through the valve
at maximum design pressure for the given operating frequency and
valve open time. The lower limit will be determined by the
stability of droplet formation. If the valve open time and/or
operating frequency are too small for a given flow rate, the
pressures in the dispenser will become too great, causing possible
rupture or malfunction of the system. If the valve open time and/or
operating frequency are too large for a given flow rate, the drop
formation may not be uniform for each open/close cycle.
Nevertheless, for a given flow rate of reagent provided by the pump
22 there will be a range of compatible frequencies and/or valve
open times for which stable operation may be achieved. This range
may be determined experimentally by adjusting the operating
frequency and open time of the valve to achieve stable droplet
formation. Similar advantages can be achieved with air brush
dispensers or other types of dispensers.
X-Y-Z Dispensing Platform
In a particularly preferred mode of operation, a dispenser may be
integrated to an X, X-Y, or X-Y-Z platform wherein the programmed
motion control can be coordinated with the metering pump to deliver
a desired volume per unit length, with the ability to also
independently control the frequency and droplet size of the reagent
being dispensed. For example, it is possible to deliver reagent at
a rate of 1 microliter per centimeter at a constant table speed
with a droplet size ranging between 4 and 100 nanoliters. The
droplet size for a given dispenser flow rate can be controlled by
adjusting the operation frequency of the solenoid valve. In this
context, there are several particularly desirable modes of
operation: (1) line or continuous dispensing; (2) spot or "dot"
dispensing; (3) aspirating; and (4) dot matrix printing. Each of
these preferred modes of operation is addressed below:
Continuous Dispensing
In the continuous dispensing mode, the metering pump is set to a
prescribed flow rate to deliver a metered volume of reagent in
volume-per-unit time. For example, the flow rate could be
programmed to deliver 1 microliter per second. The syringe will
then pump reagent to the solenoid valve 12 at the predetermined
rate. By opening and closing the valve during this flow, droplets
will be formed according to the open time and operating frequency
of the valve. Thus, in the continuous dispensing mode, the system
is not only capable of delivering precise metered flow rates of
reagent, but this can be done with independent control of table
speed, reagent concentration per unit length and droplet size.
If the solenoid valve dispenser is placed very close to the
substrate, as shown in FIG. 7 (to the left), then reagent will flow
directly onto the substrate providing a continuous line. This mode
of continuous operation may provide particular advantage where
reagent patterns having very sharp lines are necessary or
desirable. If desired, a continuous drive reagent pump may also be
used to assure a steady flow of reagent to the solenoid valve
dispenser. More commonly, however, the solenoid valve dispenser
will be spaced at least slightly away from the substrate, as shown
in FIG. 7 (to the right). In this mode, discrete droplets will be
formed which are ejected onto the substrate to form the desired
pattern. The size of each droplet will determine the effective
resolution of the resulting pattern formed on the substrate. It is
convenient to express this resolution in terms of dots per inch or
"dpi." The present invention should be capable of achieving
dispensing resolutions in the range of 300-600 dpi or higher.
Dot Dispensing
In the dot dispensing mode, individual droplets can be dispensed at
preprogrammed positions. This can be accomplished by synchronizing
the solenoid valve and displacement pump with the X, X-Y or X-Y-Z
platform. The metering pump is incremented to create a hydraulic
pressure wave. The solenoid valve is coordinated to open and close
at predetermined times relative to the pump increment. The valve
may be initially opened either be before or after the pump is
incremented. While the valve is open the pressure wave pushes a
volume of fluid down the nozzle forming a droplet at the exit
orifice at the time of peak pressure amplitude. The droplet will
have a size determined by the incremental volume provided by the
metering pump. For example, a 50-microliter syringe pump with a
12,000 step resolution will provide an incremental displacement
volume of 4.16 nanoliters.
The timing and duration of each valve cycle relative to the
hydraulic pressure wave created by the pump can be determined
experimentally to achieve stable dispensing operation having the
desired droplet size. If the wavelength of the hydraulic pressure
wave is too large relative to the valve open time, the pressure
wave may actually force the valve shut. If the wavelength is about
equal to or shorter than the valve open time, then a pulse of fluid
will be displaced forming a droplet. Again, the size or volume of
the droplet will be determined primarily by the incremental
displacement volume of the syringe pump.
If the valve open time is large relative to the pressure wavelength
then several pulses or displacements may travel through the valve
during the time in which it is open. This may be acceptable or even
desirable for some applications, such as where bursts of droplets
are desired at a programmed valve frequency. For example, the
dispensing apparatus can be programmed to produce 10 drops at 100
Hz to yield a composite drop size of about 41.6 nanoliters. This
mode of operation can provide the ability to dispense drop sizes
down to less than 1 nanoliter with the appropriate nozzle design.
It will depend on the resolution of the metering pump and the
minimum valve open/close time and the size of the exit orifice. If
the valve is left open too long, however, then the system may not
maintain enough pressure to eject droplets. To achieve the most
stable dispensing operation, the valve open time should be about
consistent with the droplet volume or composite droplet volume
dispensed.
The timing, frequency and duty cycle of the solenoid valve relative
to the syringe pump and movable carriage/platform can be
coordinated or synchronized by any one of a number controllers well
known in the art. Typical controllers are microprocessor based and
provide any one of a number of output control pulses or electrical
signals of predetermined phase, pulse width and/or frequency. These
signals may be used, for example, to control and coordinate the
syringe pump, movable carriage/platform and solenoid valve
dispenser in accordance with the present invention.
There may also be some optimum phasing of the pressure pulse
relative to the open/close times of the solenoid valve. Stable
operation has been observed, for instance, when the valve open time
is adjusted to be an even multiple of the pulse width of the pump
increment, with the open/close time of the valve being synchronized
to be in phase with the resulting pressure wave. For example, with
a 50-microliter syringe pump operating at 12,000-step resolution,
the incremental displacement volume will be about 4.16 nanoliters.
Therefore, stable operation should be possible with droplet sizes
of some multiple of 4.16 nanoliters. The minimum droplet size for
stable operation may be increased or decreased accordingly by
adjusting the resolution of the pump or by increasing the size of
the syringe. For a large droplet, say 9.times.4.16 nanoliters=33.28
nanoliters, it may be preferred to open the valve longer than for
smaller droplets in order to get more uniform lines and stable
operation. Again, the range of stable operation can be readily
determined experimentally for each desired operating mode.
Aspirating
Another preferred mode of operation is aspirating ("sucking")
precise quantities of reagent or other liquids from a sample or
reservoir. This mode may be used, for example, in a "suck and spit"
operation whereby a precise quantity of fluid is aspirated from one
vial containing a sample fluid and then dispensed into another vial
or onto a diagnostic test strip for testing or further processing.
The dispenser/aspirator may be a simple nozzle or needle
("aspirating tube") or, more preferably, it may be a solenoid valve
dispenser. The metering pump and dispenser/aspirator are preferably
synchronized or coordinated with an X, X-Y or X-Y-Z movable
platform.
In operation the metering pump is filled with a wash fluid such as
distilled water. The tip of the dispenser or aspirating tube is
placed into the fluid to be aspirated and the metering pump is
decremented to draw a precise quantity of the fluid into the tip of
the dispenser or aspirating tube. It is generally desirable to only
aspirate a small volume of reagent into the tip of the solenoid
valve dispenser that does not pass into the valve. The metering
pump is then incremented to dispense a precise portion of the fluid
into a receiving receptacle or substrate. The remaining fluid is
dispensed into a waste/wash receptacle along with a predetermined
quantity of the wash. This ensures that the fluid sample does not
get diluted with the wash fluid and the sample is flushed out after
each aspirate and dispense cycle.
This mode of operation has particular advantage for dispensing high
viscosity reagents. Conventional solenoid valve dispensers
typically do not work very well with solutions having a viscosity
above about 5 centipoise. But there are many applications where it
is desirable to dispense reagents having high viscosities.
Advantageously, the present invention, when used in the
aspirate/dispense mode, provides a solution to this problem. Again,
in the aspirate/dispense mode the system will be filled with a wash
fluid such as water or a water-based solution having a low
viscosity. The reagent is first aspirated then dispensed, followed
by washing of the valve by dispensing excess wash fluid.
In the case of a viscous reagent, the present invention can
aspirate and dispense such reagents very effectively by decreasing
the speed of aspiration. This allows more time for the more viscous
fluid to flow into the tip of the solenoid valve dispenser or
aspirating tube. Because the viscous fluid will then be
hydraulically coupled to the wash fluid, it can now be dispensed
from the nozzle effectively, since the system is driven by positive
displacement and the fluids are incompressible. Using this mode,
the present invention can dispense reagents of a viscosity that
cannot typically be directly dispensed.
Printing
Another possibly desirable mode of operation may be to use the drop
dispensing capability of the present invention in conjunction with
electrostatic, dot matrix, or other printing techniques to create
printed patterns, lines and other geometric shapes on a substrate.
In this case the metering pump may be used as an internal forcing
function to control quantitatively the droplet size of each dot in
a matrix pattern. By superimposing programmed dispensing frequency
function and selective charging and deflecting of droplets, the
present invention can provide drop-on-demand printing having
extended capabilities for finer dot sizes and printing
resolution.
For example, a dispensing apparatus 10" having features of the
present invention may be in used in conjunction with an
electrostatic printing head 200, such as shown in FIG. 8 to create
a dot matrix pattern on a substrate. The dispensing apparatus can
be programmed to dispense droplets of a predetermined size and
frequency pattern. These droplets can be electrically charged such
that they may be deflected by an electric field generated between a
pair of deflector plates 210. The amount of charge put on a droplet
is variable, and thus, the amount of deflection is also variable.
The electronics may be arranged and adjusted such that droplets can
be placed in any number of predetermined positions. Selective
charging and deflecting of individual droplets may be used to form
a desired dot matrix pattern, as shown. Alternatively, multiple
dispensers and pumps may be arranged to form an array of
drop-on-demand dispensers for simple dot matrix printing
operations.
Dispensing Platforms
As noted above, the dispensing apparatus in accordance with the
present invention may also be mounted on any one of a number of
membrane placement and handling modules. For instance, a single
platform 100 may be used to mount multiple dispensers to handle one
or more reagents, as shown in FIG. 9. Such dispensing platforms may
be microprocessor-based and are preferably controlled through an
industry standard input/output I-O controller (not shown), such as
an RS232 interface. A remote programmable controller 110 may also
be used, as desired, to control the various dispensing equipment
and platforms or to program a central I/O controller. The invention
is also well suited for use with individual membrane strip handling
modules and continuous reel-to-reel handling modules. An individual
membrane strip module may incorporate an X-Y table motion for
dispensing. The reel-to-reel platform may incorporate
constant-speed membrane transport with mountings attached for
motion of one or more dispensers. A drying oven (not shown) may
also be used to increase production throughput, as desired.
It will be appreciated by those skilled in the art that the methods
and apparati disclosed in accordance with the present invention can
be used to dispense a wide variety of liquids, reagents and other
substances and a variety of substrates. Although the invention has
been disclosed in the context of certain preferred embodiments,
those skilled in the art will readily appreciate that the present
invention extends beyond the specifically disclosed embodiments to
other alternative embodiments of the invention. Thus, it is
intended that the scope of the invention should not be limited by
the particular disclosed embodiments described above, but should be
determined only by a fair reading of the claims that follow.
* * * * *