U.S. patent application number 12/326723 was filed with the patent office on 2009-03-19 for micro fluidics manifold apparatus.
This patent application is currently assigned to INNOVADYNE TECHNOLOGIES, INC.. Invention is credited to Mitchel J. Doktycz, James E. Johnson, Neil R. Picha.
Application Number | 20090074625 12/326723 |
Document ID | / |
Family ID | 24768948 |
Filed Date | 2009-03-19 |
United States Patent
Application |
20090074625 |
Kind Code |
A1 |
Johnson; James E. ; et
al. |
March 19, 2009 |
MICRO FLUIDICS MANIFOLD APPARATUS
Abstract
A manifold device is provided for use with a valve assembly, an
aspiration source and a dispensing source to transfer fluid from at
least one of a plurality of fluid reservoirs to at least one test
site on a substrate surface. The manifold device includes a
manifold body that defines a plurality of fluid aspiration
conduits, for fluid aspiration in an aspiration position, and a
plurality of fluid dispensing conduits to selectively dispense at
least one droplet of the corresponding liquid sample slug, in a
dispensing position. In the aspiration position, the respective
sample paths are out of fluid communication with the dispensing
source and, in the dispensing position, the respective sample paths
are out of fluid communication with the aspiration source.
Inventors: |
Johnson; James E.;
(Sebastopol, CA) ; Picha; Neil R.; (Petaluma,
CA) ; Doktycz; Mitchel J.; (Knoxville, TN) |
Correspondence
Address: |
Weaver Austin Villeneuve & Sampson LLP
P.O. BOX 70250
OAKLAND
CA
94612-0250
US
|
Assignee: |
INNOVADYNE TECHNOLOGIES,
INC.
Santa Rosa
CA
|
Family ID: |
24768948 |
Appl. No.: |
12/326723 |
Filed: |
December 2, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11034389 |
Jan 11, 2005 |
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12326723 |
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09689548 |
Oct 11, 2000 |
6852291 |
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11034389 |
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Current U.S.
Class: |
422/400 |
Current CPC
Class: |
F16K 11/0743 20130101;
Y10T 436/2575 20150115; G01N 2035/1041 20130101; Y10T 137/86863
20150401; B01J 2219/00605 20130101; F16K 99/0013 20130101; B01J
2219/00659 20130101; B01J 2219/00394 20130101; Y10T 137/87249
20150401; G01N 1/14 20130101; B01J 2219/00412 20130101; F16K
2099/0084 20130101; B01J 2219/00315 20130101; F16K 99/0001
20130101; G01N 35/1097 20130101; C40B 60/14 20130101; B01J 19/0046
20130101; F16K 99/0028 20130101 |
Class at
Publication: |
422/100 |
International
Class: |
B01L 3/02 20060101
B01L003/02 |
Claims
1. A manifold device for use with a valve assembly, an aspiration
source and a dispensing source to transfer fluid from at least one
of a plurality of fluid reservoirs to at least one test site on a
substrate surface, said valve assembly including a rotor face
defining a plurality of discrete communication channels each
movable as a unit between an aspiration condition and a dispensing
condition as the valve assembly rotates relative its rotational
axis, said manifold device comprising: a manifold body defining a
plurality of fluid aspiration conduits each having a first
aspiration port in fluid communication with the aspiration source,
and a second aspiration port in selective fluid communication with
a corresponding communication channel of the valve assembly to
aspirate a respective liquid sample slug from a corresponding
reservoir of sample fluid into discrete sample paths when the valve
assembly is in the aspiration condition, said manifold body further
defining a plurality of fluid dispensing conduits each having a
respective first dispensing port in fluid communication with the
dispensing source, and a second dispensing port in selective fluid
communication with a corresponding communication channel of the
valve assembly to selectively dispense at least one droplet of the
corresponding liquid sample slug from the corresponding sample path
when the valve assembly is in the dispensing condition, wherein, in
the aspiration condition, said respective sample paths are out of
fluid communication with the dispensing source and, in the
dispensing condition, said respective sample paths are out of fluid
communication with the aspiration source.
2. The manifold device as defined by claim 1, wherein said manifold
body includes a stator face containing the second aspiration ports
and the second dispensing ports, and formed for rotational sliding
contact with the rotor face at a rotor-stator interface for sliding
sealed contact between the aspiration condition, fluidly coupling
the corresponding second aspiration port to the corresponding
sample path, and the dispensing condition, fluidly coupling the
corresponding second dispensing port to the corresponding sample
path.
3. The manifold device as defined by claim 2, wherein said stator
face is substantially planar.
4. The manifold device as defined by claim 2, wherein said manifold
body includes a plurality of primary passages each having an upper
communication port terminating at the stator face such that said
respective communication channel fluidly couples the corresponding
primary passage to the aspiration source in the aspiration
condition, and fluidly couples the respective primary passage to
the dispensing source in the dispensing condition.
5. The manifold device as defined by claim 4, further including: a
plurality of removable nozzle members mounted to said manifold
body, and each having one end fluidly coupled to a corresponding
primary passage and an opposite end terminating at a dispensing
orifice configured to dispense a respective droplet.
6. The manifold device as defined by claim 1, wherein said manifold
body includes at least two plate members fixedly mounted together
in a manner cooperatively defining at least one of said aspiration
conduits and said dispensing conduits.
7. The manifold device as defined by claim 6, wherein said at least
two plate members includes a first plate member having a bottomside
surface and a second plate member having an opposed topside surface
fixedly joined therebetween at a first interface, at least one of
said bottomside surface and said topside surface defining a
plurality of first grooves which cooperate with the other of the
topside surface of the second plate member and the bottomside
surface of the first plate member to define at least one of the
aspiration conduits or the dispensing conduits.
8. The manifold device as defined by claim 7, wherein each said
second aspiration port and said second dispensing port terminates
at a stator face of the first plate member which is oriented
opposite the bottomside surface thereof, said stator face being
configured for rotational sliding contact with the rotor face at a
rotor-stator interface.
9. The manifold device as defined by claim 8, wherein said manifold
body includes a plurality of primary passages each having an upper
communication port terminating at the stator face such that said
respective sample channel fluidly couples the corresponding primary
passage to the aspiration source in the aspiration condition, and
fluidly couples the respective primary passage to the dispensing
source in the dispensing condition.
10. The manifold device as defined by claim 7, wherein said topside
surface and said bottomside surface are substantially planar.
11. The manifold device as defined by claim 7, wherein, said second
plate member includes a bottomside surface positioned opposite said
topside surface thereof, and further including: a third plate
member having a topside fixedly joined to the bottomside surface of
the second plate member at a second interface, at least one of said
bottomside surface of the second plate member and the topside
surface of the third plate member defining a plurality of second
grooves which cooperate with the other of the topside surface of
the third plate member and the bottomside surface of the second
plate member to define at least the other of the aspiration
conduits or the dispensing conduits.
12. The manifold device as defined by claim 11, wherein each said
second aspiration port and said second dispensing port terminates
at a stator face of the first plate member which is oriented
opposite the first interface surface, said stator face being
configured for rotational sliding contact with the rotor face at a
rotor-stator interface.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a divisional of prior application Ser.
No. 11/034,389 to Johnson et al., filed on Jan. 11, 2005 and titled
"HYBRID VALVE APPARATUS AND METHOD OF FLUID HANDLING, which in turn
is a divisional of prior application Ser. No. 09/689,548 to Johnson
et al., filed on Oct. 11, 2000 and titled "HYBRID VALVE APPARATUS
AND METHOD OF FLUID HANDLING, now U.S. Pat. No. 6,852,291, both of
which are incorporated by reference in their entirety.
TECHNICAL FIELD
[0002] The present invention relates to fabrication, apparatus,
system and methods for manipulating arrays of samples, reagents or
solvents from a source or reservoir to a destination substrate, and
more particularly, relates to a hybrid valve system applied to
aspirate, dispense and switch fluids during large-scale chemical or
biochemical screening assays, syntheses, arraying and plate
spotting.
BACKGROUND ART
[0003] Advances in Life Sciences, particularly in genomics and
proteomics, have greatly increased the potential number of
reactions and analyses that must be performed by the biotechnology
and pharmaceutical industries. An estimated 30 million tests are
required to screen a typical pharmaceutical company's compound
library against target receptors. The typical number of tests will
increase dramatically as information is gleaned from the sequencing
of the human genome. To meet these increasing throughput demands in
an economically feasible manner, miniaturization of tests is
imperative.
[0004] Technological advances are enabling the demonstration and
use of microscale chemical/biochemical reactions for performing
various types of analyses. Implementation of these reactions at
such smaller scales offer economies that are unmatched by
conventional approaches. Reduced volumes can lower costs by an
order of magnitude but conventional liquid-handling devices fail at
the required volumes. Parallel implementation provides even greater
advantages as demonstrated by the use of high-density plates for
screening and high-density MALDI-TOF plates for mass spectrometry
analyses of proteins. The rate-limiting hardware is low volume
liquid transfer technology that is robust and scalable for
compounds of interest. With growing demand, the development of
fluid handling devices adept at manipulating sub-microliter volumes
of multiple reagents is needed.
[0005] Current systems for handling liquid reagents often employ a
"pick and place" technique where a sample from a source plate,
usually a microtiter plate, is picked up and placed into another
reservoir known as the target plate. This technique is often
applied for replicating plates, where scale reduction between the
source and the target plates are beneficially realized. Typically,
an appropriate volume is aspirated from a source plate and
deposited to a target site on a multiple target plate. In this
arrangement, reduced sample volumes and sample spacing are required
for higher degrees of miniaturization.
[0006] In other advancements using "pick and place" distribution,
drop-on demand ink jet technology has been adopted for accurately
delivering volumes on the order of picoliters. This technology is
not only capable of volumetric precision, but also positional
accuracy as well. These ink jet systems typically employ thermal,
piezoelectric, or solenoid actuation to deliver defined volumes of
liquid sample to precise locations, increasing test site array
density.
[0007] Two of these approaches, in particular, thermal and
piezoelectric ink jet technology, utilize micromachined actuation
mechanisms and dispensing orifices which offer non-contact
dispensing from the tip without requiring capillary contact for
flow purposes. Problematic to these devices is plugging of orifices
and scalability. While this printing technology is capable of
low-volume, accurate delivery, the initial systems for dispensing
chemical reagents lack speed and efficiency due to conventional
switching technology. A syringe drive per channel is generally
employed, limiting systems to a scale that fails to provide the
required throughput. The current systems are unable to quickly
switch multiple channels between large-scale metering tasks and
subsequent micro dispensing tasks, failing to exploit the
advantages and the high speed afforded by this non-contact printing
technology.
DISCLOSURE OF INVENTION
[0008] The present invention provides a hybrid valve apparatus for
use with an aspiration actuator and a dispensing actuator to
transfer fluid from a reservoir to a test site on a substrate
surface. The hybrid valve includes a valve assembly movable between
an aspiration condition and a dispensing condition, and a manifold
device coupled to the valve assembly. The manifold device includes
a fluid aspiration conduit having a first aspiration port in fluid
communication with the aspiration actuator. On an opposite end of
the aspiration conduit is a second aspiration port in selective
fluid communication with the valve assembly to selectively aspirate
a liquid sample slug from the reservoir into a discrete sample path
when the valve assembly is in the aspiration condition. The
manifold device further includes a fluid dispensing conduit having
a first dispensing port in fluid communication with the dispensing
actuator, and a second dispensing port in selective fluid
communication with the valve assembly. When the valve assembly is
in the dispensing condition, the sample path is fluidly coupled to
the dispensing actuator to selectively dispense at least one
droplet of the liquid sample slug therefrom, while simultaneously
being out of fluid communication with the aspiration actuator. In
contrast, in the aspiration condition, the sample path is in fluid
communication with the aspiration actuator, while being out of
fluid communication with the dispensing actuator.
[0009] In one embodiment, the hybrid valve includes a plurality of
aspiration actuators and a plurality of dispensing actuators to
transfer fluid from a plurality of fluid reservoirs to a plurality
of test sites on the substrate surface. The manifold device defines
a plurality of independent fluid aspiration conduits, each of which
includes a first aspiration port in fluid communication with a
corresponding one of the plurality of aspiration actuators, and a
second aspiration port terminating at a stator face of the manifold
for selective fluid communication with the valve assembly. Thus,
when the valve assembly is in the aspiration condition, each
aspiration actuator can be operated to selectively aspirate a
respective liquid sample slug from a corresponding reservoir of
sample fluid into discrete sample paths. The manifold device
further defines a plurality of fluid dispensing conduits, each
having a respective first dispensing port in fluid communication
with a corresponding one of the plurality of dispensing actuators,
and a second dispensing port terminating at the stator face. When
the valve assembly is in the dispensing condition, each dispensing
actuator can be operated to selectively dispense at least one
droplet of the corresponding liquid sample slug from the
corresponding sample path.
[0010] Accordingly, at no time are the aspiration actuator or the
dispensing actuator both in fluid communication with the sample
path when the valve assembly is in either the aspiration or
dispensing condition. This arrangement is highly beneficial in that
contamination of the dispensing actuators can be eliminated by
isolating the aspiration paths and dispensing actuators. Moreover,
each fluid path is operatively switched between the aspiration
actuator and the dispensing actuator enabling the use of
conventional liquid handling techniques, such as air gaps, to
isolate system hydraulic fluid during aspiration, and the
subsequent low-volume, non-contact dispensing of the reagents or
sample fluid to the test site.
[0011] In the preferred embodiment, the manifold device includes a
stator face configured for rotational sliding contact with a rotor
face of the valve assembly at a rotor-stator interface. Each of the
second aspiration ports and the second dispensing ports terminate
at the stator face for communication with the valve assembly. The
manifold device further includes a plurality of primary passages
each defining at least a portion of their respective sample paths.
Each primary passage has a upper communication port which also
terminates at the stator face. The upper communication port remains
in fluid communication with the respective sample channel when in
the aspiration condition and the dispensing condition. Thus, the
primary passage is fluidly coupled to the respective aspiration
actuator in the aspiration condition, and fluidly coupled to the
respective dispensing actuator in the dispensing condition.
[0012] The hybrid valve may include a plurality of removable nozzle
members mounted to the manifold device to dispense the respective
droplet. Each nozzle includes one end fluidly coupled to a
corresponding primary passage and an opposite end terminating at a
dispensing orifice.
[0013] In another aspect of the present invention, the manifold
device may be by a plurality of laminated plate members which
collectively define the body of the manifold. At least two plate
members are fixedly mounted together in a manner cooperatively
defining at least one of the aspiration conduits and the dispensing
conduits. The two plate members include a first plate member having
a first interface surface and a second plate member having an
opposed second interface surface fixedly joined therebetween at a
first interface. This first interface surface defines a plurality
of first grooves which cooperate with the second interface surface
of the second plate member to define at least the aspiration
conduits or the dispensing conduits.
[0014] The dispensing actuators may include drop-on demand ink-jet
printing valving in the form of a thermal ink-jet valve, a solenoid
ink-jet valve, or a piezoelectric ink-jet valve. The aspiration
actuators, on the other hand, may include a syringe-type metering
device.
[0015] In still another aspect of the present invention, a method
may be provided for transferring liquid sample from a fluid
reservoir to a test site on a target substrate. The method includes
providing a fluid manifold device defining a fluid aspiration
conduit having a first aspiration port in fluid communication with
an aspiration actuator and a second aspiration port in fluid
communication with the valve assembly. The manifold device further
defines a fluid dispensing conduit having a first dispensing port
in fluid communication with the dispensing actuator and a second
dispensing port in fluid communication with the valve assembly. The
method includes positioning the valve assembly in an aspiration
condition, fluidly coupling the aspiration actuator to a discrete
sample path, and fluidly decoupling the dispensing actuator from
the sample path; and actuating the aspiration actuator to aspirate
a liquid sample slug from a sample reservoir into the sample path.
The method further includes positioning the valve assembly in a
dispensing condition, fluidly coupling the dispensing actuator to
the sample path, and fluidly decoupling the aspiration actuator
from the same path.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The assembly of the present invention has other objects and
features of advantage which will be more readily apparent from the
following description of the best mode of carrying out the
invention and the appended claims, when taken in conjunction with
the accompanying drawing, in which:
[0017] FIG. 1 is a top perspective view of the hybrid valve
apparatus constructed in accordance with the present invention.
[0018] FIG. 2 is an exploded top perspective view of the hybrid
valve apparatus of FIG. 1.
[0019] FIG. 3 is a schematic illustration of an assembly
incorporating the hybrid valve apparatus of FIG. 1.
[0020] FIG. 4A is a top perspective view of a manifold device of
the hybrid valve apparatus of FIG. 1, and illustrating the stator
face interface.
[0021] FIG. 4B is a bottom perspective view illustrating the lower
communication ports of the manifold device of FIG. 4A.
[0022] FIG. 5 is an enlarged, exploded bottom perspective view of
one fluid path of the hybrid valve apparatus in the aspiration
condition.
[0023] FIG. 6 is an enlarged, exploded bottom perspective view of
one fluid path of the hybrid valve apparatus in the dispensing
condition.
[0024] FIG. 7 is an enlarged, top plan view of a stator face of a
stator element of the manifold device.
[0025] FIG. 8 is an enlarged, bottom plan view of a rotor face of a
rotor element of the valve assembly.
[0026] FIG. 9 is a top plan view of the manifold device with the
rotor face superimposed over the stator face at a rotor/stator
interface in the aspiration condition.
[0027] FIG. 10 is an enlarged top plan view of the rotor/stator
interface of FIG. 9, in the aspiration condition.
[0028] FIG. 11 is a top plan view of the manifold device of FIG. 9
in the dispensing condition.
[0029] FIG. 12 is an enlarged top plan view of the rotor/stator
interface of FIG. 11, in the dispensing condition.
[0030] FIG. 13 is an exploded, enlarged bottom plan view of the
manifold device of FIG. 4B, illustrating the channels and grooves
of the individual plate members.
[0031] FIG. 14 is an enlarged, fragmentary, illustration of the
exploded bottom plan view of FIG. 13.
[0032] FIG. 15 is an exploded bottom perspective view of one fluid
path of an alternative embodiment hybrid valve apparatus in the
aspiration condition.
[0033] FIG. 16 is an exploded bottom perspective view of one fluid
path of the alternative embodiment hybrid valve apparatus of FIG.
15, in the dispensing condition.
[0034] FIG. 17 is an enlarged top plan view of the rotor/stator
interface of FIG. 15, in the aspiration condition.
[0035] FIG. 18 is an enlarged top plan view of the rotor/stator
interface of FIG. 16, in the dispensing condition.
[0036] FIG. 19 is an enlarged, bottom plan view of the rotor face
of the alternative embodiment rotor element.
[0037] FIG. 20 is an enlarged, top plan view of the stator face of
the stator element of the alternative embodiment rotor element.
BEST MODE OF CARRYING OUT THE INVENTION
[0038] While the present invention will be described with reference
to a few specific embodiments, the description is illustrative of
the invention and is not to be construed as limiting the invention.
Various modifications to the present invention can be made to the
preferred embodiments by those skilled in the art without departing
from the true spirit and scope of the invention as defined by the
appended claims. It will be noted here that for a better
understanding, like components are designated by like reference
numerals throughout the various figures.
[0039] Referring now to FIGS. 1-6, 15 and 16, a hybrid valve
apparatus, generally designated 20, is provided for use with an
aspiration source 21 and a dispensing source 22 to transfer sample
or reagent fluid from a reservoir 23 to a test site 25 on a
substrate surface 26. Broadly, the hybrid valve apparatus 20
includes a valve assembly 27 (FIGS. 15 and 16) movable between an
aspiration condition (FIGS. 5, 9 and 10) and a dispensing condition
(FIGS. 6, 11 and 12), and a manifold device 28 coupled to the valve
assembly. The manifold device 28 includes a fluid aspiration
conduit 30 having a first aspiration port 31 in fluid communication
with the aspiration source 21. On an opposite end of the aspiration
conduit 30 is a second aspiration port 32 in selective fluid
communication with the valve assembly 27 to selectively aspirate a
liquid sample slug from the reservoir 23 into a discrete sample
path 33 when the valve assembly 27 is in the aspiration condition.
The manifold device 28 further includes a fluid dispensing conduit
35 having a first dispensing port 36 in fluid communication with
the dispensing source 22, and a second dispensing port 37 in
selective fluid communication with the valve assembly 27. When the
valve assembly 27 is oriented in the dispensing condition (FIGS. 6,
11 and 12), the sample path 33 is fluidly coupled to the dispensing
source 22 to selectively dispense at least one droplet 34 of the
liquid sample slug therefrom. Importantly, in this orientation, the
valve assembly 27 also fluidly decouples the sample path 33 from
the aspiration source 21. In contrast, in the aspiration condition
(FIGS. 5, 9 and 10), the valve assembly 27 fluidly couples the
sample path 33 to the aspiration source 21, while simultaneously
being out of fluid communication with the dispensing source 22.
[0040] Accordingly, the hybrid valve apparatus provides a switching
system which regulates fluid communication of the aspiration
actuator and the dispensing actuator with the sample path
containing the sample or reagent fluid. Whether the hybrid valve
apparatus is in the aspiration condition or the dispensing
condition, at no time will the valve assembly allow the sample path
be in fluid communication with both the aspiration actuator and the
dispensing actuator, simultaneously. This arrangement is beneficial
in that the dispensing source can not be contaminated by the
sampled fluid due to the isolating of the dispensing source from
the sample path during the aspiration of the fluid into the sample
path. Moreover, each sample path is operatively switched between
the aspiration actuator and the dispensing actuator enabling the
micro-metered, non-contact parallel distribution of the reagents or
sample fluid to the test site.
[0041] As best viewed in the schematic representation of FIG. 3,
the present invention is particularly suitable for transferring
chemical or biochemical samples or reagents from an array of
reservoir wells 38 of a conventional microtiter plate 40, i.e. 96
or 384 wells, to an array of higher-density test sites 25, i.e. a
1536-well microtiter plate, or for fabrication of a chip-based
biological sensor (commonly referred to as a "microarray") used for
performing gene expression or other screening experiments. Briefly,
the hybrid valve apparatus is adaptable for printing arrays wherein
the distance between adjacent test sites 25, or test site pitch, is
in the range of about 1 micron (.mu.m) to about 10,000 microns
(.mu.m).
[0042] Thus, in the preferred embodiment, the manifold device 28
includes a plurality of fluid aspiration conduits 30, corresponding
fluid dispensing conduits 35 and corresponding sample paths 33,
which cooperate for the parallel transfer of fluid from the fluid
reservoir 23 to the corresponding test sites 25 (FIGS. 3, 4, 13 and
14). Briefly, each fluid aspiration conduit 30 includes a first
aspiration port 31 in fluid communication with a corresponding
aspiration source or actuator, and an opposite second aspiration
port 32 terminating at a stator face surface 41 of the manifold
device 28. Moreover, each fluid dispensing conduit 35 includes a
first dispensing port 36 in fluid communication with a
corresponding dispensing actuator 22, and an opposite second
dispensing port 37 also terminating at the manifold stator face 41
as well.
[0043] When oriented in the aspiration condition (FIGS. 5, 9 and
10), the valve actuator assembly 27 permits selective fluid
communication of the sample paths 33 with the corresponding second
aspiration ports 32 of the aspiration conduits 30 at the stator
face 41, while simultaneously preventing fluid communication with
the corresponding second dispensing ports 37 of the dispensing
conduits 35. Conversely, when the valve assembly is oriented in the
dispensing condition (FIGS. 6, 11 and 12), the sample paths 33 are
moved into selective fluid communication with the corresponding
second dispensing ports 37 at the stator face, while simultaneously
being moved out of fluid communication with the second aspiration
ports 32.
[0044] Preferably, the present invention includes twelve (12)
independent aspiration conduits 30, and dispensing conduits 35
communicating with corresponding sample paths 33. Thus, inherently,
the hybrid valve apparatus 20 may simultaneously deliver sample or
reagent fluid to twelve test sites. Other configurations,
containing greater of lesser number of independent conduits are
possible. It will be appreciated, however, that the system can be
configured for a one-to-one transfer of fluid, i.e., from each
reagent reservoir to a designated test site. Such flexibility also
lends itself to numerous variations of the preferred use. In
particular, the hybrid valve apparatus can be configured for
transferring sample or reagent fluids from a given number of
reservoirs to a different number of test sites. For instance, the
switching technology of the hybrid valve manifold device 28 can be
designed such that fluid samples from multiple aspiration
reservoirs 23 are dispensed on a single test site. Conversely, this
manifolding can be adapted for depositing fluid from a single
reservoir 23 to multiple test sites.
[0045] Briefly, as shown in FIGS. 1 and 2, the manifold device 28
is preferably sandwiched between a lower stator cover 42 and an
upper stator ring 43 for stable support thereof. This assembly
cooperates with a track or transport mechanism (not shown) which
effects the relative movement between manifold device 28, the fluid
reservoirs 23 and the test sites 25 (FIGS. 1 and 3). Preferably,
the entire hybrid valve apparatus 20 is transported between the
microtiter plates 40 and the array of test sites 25.
[0046] Although the hybrid valve apparatus 20 is adapted for
simultaneously transferring multiple volumes of fluid sample or
reagent to multiple chip test sites, a better understanding of the
invention can be gained through a description of the operation
thereof with respect to the transfer of the fluids from a single
sample path 33 in the manifold device 28. In this description,
briefly, the aspiration actuator 21 will be fluidly coupled to the
manifold sample path 33, via the valve assembly 27, to aspirate
sample fluid from the single reservoir 23 into the sample path.
Subsequently, the sample path 33 will be switched, in fluid
communication, to the dispensing conduit 35 for finely controlled
dispensing of the sample fluid contained in the sample path 33.
Accordingly, FIGS. 5, 6 and 9-12 intentionally depict a single set
of fluid transfer elements.
[0047] Referring back to FIGS. 5 and 6, in this embodiment, each
sample path 33 includes a primary passage portion 45 thereof
defined by the manifold device 28. This primary passage portion 45
extends substantially vertically therethrough in a direction
substantially parallel to an axis 44 of the hybrid valve apparatus
20. Further, each primary passage 45 includes an upper
communication port 46 terminating at the stator face 41, and a
lower communication port 47.
[0048] Preferably, as best illustrated in FIGS. 5 and 6, each
primary passage 45 includes a corresponding nozzle member 48
extending outwardly from one of the lower communication ports 47.
As will be described in greater detail below, each nozzle member is
removably mounted to the manifold device 28 which enables
individual aspiration of the sample fluid therein (in the
aspiration condition) or individual dispensing of the sample fluid
therefrom (in the dispensing condition). Moreover, a nozzle passage
50 extends longitudinally through the nozzle member 48 which
inherently increases the volumetric capacity of the corresponding
sample path 33.
[0049] In accordance with the present invention, each of the
aspiration conduits 30, the dispensing conduits 35 and the primary
passages 45 include a respective port 32, 37 and 46 which
terminates at the stator face 41 (FIG. 7) for fluid communication
with a rotor face 51 of a rotor element 52 of the valve assembly
(FIG. 8). In the preferred embodiment, each of the upper
communication ports 46 of the primary passages 45 are equidistant
from one another and are radially spaced about a rotational axis of
the rotor element 52. Similarly, each of the second aspiration
ports 32 and each of the second dispensing ports 37 is also
equidistant from one another and radially spaced about the
rotational axis 44. FIG. 7 best illustrates, however, that each of
the second aspiration ports 32, which incidentally permit fluid
communication with the corresponding aspiration actuator 21, are
positioned at a radius from the rotation axis 44 smaller than that
of the upper communication ports 46, while each of the second
dispensing ports 37 are positioned at a radius larger than that of
the upper communication ports. Finally, the upper communication
ports 46, their corresponding second aspiration ports 32 and
dispensing ports 37 are preferably collinearly aligned with a
radial line intersecting the rotational axis 44.
[0050] It will be appreciated, however, that the corresponding
ports can be alternatively spaced and oriented without departing
from the true spirit and nature of the present invention. For
example, while the collinear alignment between the corresponding
ports 32, 37 and 46 is preferred, it is not a requirement for
functionality of the manifold device, as will be apparent. Further,
whether the second dispensing ports 37 and the second aspiration
ports 32 are at a radial distance less than or greater than the
radial distance of the upper communication ports 46 of the primary
passages 45 from the rotational axis 44 is not determinative.
[0051] In accordance with the present invention, the valve assembly
27 and manifold device 28 are particularly suitable to the
application of shear valve or flat face valve technology even
though a rotary plug, a bank of 3-way solenoid valves, or MEMS
device could be used. Thus, turning now to FIGS. 2, 5, 6 and 8, the
valve assembly 27 is illustrated having rotor element 52 which
provides the contact or rotor face 51 in opposed sliding contact
with the stator face 41 at a rotor-stator interface. This high
pressure sliding contact between the stator face 41 and the rotor
face 51 provide a selective switching function between each of the
sample paths 33 (i.e., the primary passage 45 and nozzle passage
50) and the corresponding aspiration actuators 21 or dispensing
actuators 22, depending upon whether the rotor element 52 of the
valve assembly 27 is in the aspiration condition or the dispensing
condition.
[0052] Briefly, both the rotor element 52 and the stator face
element 53 are composed of conventional shear valve or flat face
valve materials which are adapted to support the high pressure
contact at the stator-rotor interface. Typical of these materials
include ceramic and synthetic composition, many of which are
proprietary in nature. The rotor element 52 is rotatably mounted to
a shaft which in turn is connected to a gear reduction inside the
actuator body 54. The gear reduction is then coupled to the motor
shaft 55 of a conventional electric motor 56 applied in shear valve
or flat face valve technology.
[0053] As best shown in FIG. 8, the rotor element 52 of the valve
assembly 27 provides a plurality of spaced-apart aspiration
channels 57 and dispensing channels 58 which are slotted in the
substantially planar rotor face 51 thereof. Each aspiration channel
57 and each dispensing channel 58 is elongated in shape, and
extends generally along a radial line intersecting the rotational
axis 44 of the rotor face 51. Further, the aspiration channels 57
and the dispensing channels 58 are equally spaced and are oriented
in an alternating manner, relative one another. Accordingly, at the
rotor-stator interface (i.e., the high pressure sliding contact
between the stator face 41 and the rotor face 51), the rotor
element 52 either reciprocates or rotates in one direction
clockwise or counter clockwise to orient the valve assembly in the
aspiration condition or the dispensing condition.
[0054] When the rotor element 52 rotates about the rotational axis
44 to the aspiration condition, the aspiration channels 57 slotted
into the rotor face 51 are rotated into alignment with the
corresponding upper communication port 46 of the primary passages
45 and the second aspiration ports 32 of the aspiration conduits 30
of the stator face 41 to provide a fluid communication path
therebetween (FIGS. 5, 9 and 10). Consequently, a fluid path is
created by the aspiration channel 57 between the corresponding
sample path 33 and the corresponding aspiration actuator 21. This
permits selective aspiration of the fluid sample or reagent, via
the aspiration actuator 21, from the sample reservoir 23 into the
sample path 33 through the nozzle member. Simultaneously, in the
aspiration condition, the second dispensing ports 37 of the
dispensing conduits 35 are dead-ended into the rotor face 51 of the
rotor element 52. Thus, the dispensing actuators 22 are out of
fluid communication with the corresponding sample paths 33.
[0055] Subsequently, as FIGS. 6, 11 and 12 illustrates, the rotor
element 52 can be selectively rotated about rotational axis 44 to
the dispensing condition. The radially extending dispensing
channels 58, also slotted into the rotor face 51, are consequently
rotated into collinear alignment with the corresponding upper
communication ports 46 and the second dispensing ports 37 of the
dispensing conduits 35 to provide a fluid communication path
therebetween. The dispensing channels 58, thus, complete the fluid
path between the corresponding sample path 33 and the corresponding
dispensing actuator 22 to permit selective dispensing, via the
dispensing actuator 22, of the fluid sample or reagent contained in
the respective sample path 33. Similarly, in the dispensing
condition, the second aspiration ports 32 of the dispensing
conduits 35 are dead-ended into the rotor face 51 of the rotor
element 52. Thus, the aspiration actuators 21 are out of fluid
communication with their corresponding sample paths 33. Further, it
will be appreciated that all twelve, or any number of sample paths
33 can be simultaneously aspirated or dispensed.
[0056] Accordingly, the shear valve and manifold device arrangement
of the present invention provides an accurate switching
functionality between the aspiration actuators and the dispensing
actuators. As above-indicated, such switching capability is
beneficial in that the full potential of the high speed, precision
ink-jet style dispensing actuators can be exploited to dispense the
sample fluids or reagents from the sample paths. Moreover, the
modular parallelism of system facilitates fabrication of
non-contact devices, e.g. 24, 48, 96-tip, suitable to the expanding
needs of the market.
[0057] It will be understood that while the valving functionality
of the present invention is particularly adaptable for flat face or
shear valves, other valve technologies are suitable such as
solenoid valves, pinch valves and micro-machined valves, actuated
by mechanical, electrical or pneumatic means.
[0058] Moreover, each dispensing conduit 35 includes an independent
dispensing source 22 fluidly coupled to its corresponding first
dispensing port 36 thereof. As best illustrated in FIGS. 1 and 2,
the dispensing actuators 22 are preferably mounted to a
corresponding dispensing actuator manifold device 28. These two
opposed dispensing actuator manifolds separate and align the
individual dispensing actuators into two sets of six actuators
releasably mounted to the stator manifold device 28 as a unit. Each
dispensing actuator 22 includes a delivery orifice 60 which is
fluidly coupled to a corresponding first dispensing port 36 of the
dispensing conduit 35.
[0059] In the preferred embodiment, each dispensing actuator 22
typically delivers a metered pressure pulse using a pressure
ranging from about 6.9(10).sup.3 N/m.sup.2 to about 138(10).sup.3
N/m.sup.2, and having a duration ranging from about (10).sup.-6
seconds to about 10 seconds. Preferably, the dispensing actuator 22
is provided by a conventional ink-jet style printing valve or pump
designed for drop-on-demand printing. Ink-jet style printing
valves/pumps for drop-on-demand printing, including thermal,
solenoid and piezoelectric types, are commercially available and
well known in the art. For instance, the Lee Company of Essex,
Conn. manufactures a solenoid-based ink-jet valve (Model No.
INKX0502600AB) which is suitable for use with the present
invention. Alternatively, conventional syringe pumps may be
employed for metering as well.
[0060] The incorporation of ink-jet drop-on-demand printing
technology into the dispense assembly of the present invention
provides significant advantages vis-a-vis known systems for
printing microarrays. In particular, the ability to deliver
independent, short-duration, pressure pulses associated with
ink-jet print valves enables the non-contact tunable delivery of
reagent sample volumes in the range of about (10).sup.10 to about
(10).sup.-12 liters. Upon application of a pressure pulse, at least
one droplet of sample or reagent fluid is ejected from the manifold
sample path through the corresponding nozzle member 48 onto
substrate surface 26. As used herein, the term "non-contact" refers
to the lack of contact between the dispense manifold and nozzles,
and the target substrate during deposition. Typically, in these
designs, the fluid is communicated through channels micromachined
into an ink-jet style printhead--such as those commonly used in
desktop and industrial printers.
[0061] Preferably, these ink-jet drop-on-demand dispensing
actuators are coupled to digitally regulated hydraulic pressure
systems (not shown). These systems enable precise manipulation of
hydraulic pressure supplied to the dispensing actuators expanding
the dynamic range of the system. An added benefit is the ability to
quickly change the pressure range to compensate for differences in
samples due to particulates or viscosity.
[0062] The aspiration source 21, on the other hand, are preferably
provided by individual aspiration actuators 21 fluidly coupled to a
corresponding first aspiration port 31 through tubing 61. These
tubes 61, which are preferably inert plastic or the like having an
inner diameter in the range of 0.2 mm to about 3.0 mm, are also
separated into two banks of six units and each have a distal end
coupled to a tubing array manifold 62. In turn, these opposed
tubing array manifolds 62 are mounted to the stator manifold device
28 as a unit.
[0063] It will be appreciated that more than one or all of the
aspiration conduits 30 can be fluidly coupled to a single
aspiration actuator 21. In the preferred form, the aspiration
actuator 21 is provided by an external metering device such as a
syringe-type pump or a diaphragm pump, or by a pressurized source
delivering a positive or negative pressure to the aspiration
conduits 30. Typical of these aspiration devices is Model # 2009D
provided by Innovadyne Technologies, Inc., Rohnert Park, Calif.
[0064] In another aspect of the present invention, the manifold
device 28 is comprised of a plurality of stacked plate members
63-66 which collectively cooperate to channel the sample fluids
from the reservoir wells to the designated test sites 25, via the
valve assembly 27. As above-indicated, the manifold device 28
defines a plurality of primary passages 45, aspiration conduits 30
and dispensing conduits 35 each of which includes a communication
port terminating at the stator face for communication with the
valve assembly 27.
[0065] Since these individual conduits are independent of one
another, fabrication is difficult for such a small scale.
Typically, the diameter of these fluid passages is on the order of
about 0.001 mm to about 1.0 mm. Moreover, these conduits and
passages must be capable of accommodating the relatively high
pressure pulses of the dispensing actuators 22 which as mentioned
have a range from about 6.9(10).sup.3 N/m.sup.2 to about
138(10).sup.3 N/m.sup.2, and have a duration in the range from
about (10).sup.-6 seconds to about (10).sup.1 seconds.
[0066] The plate members 63-66 (FIGS. 4 and 13) are preferably
rectangular in shape, each having a substantially planar topside
and an opposed bottom side. More particularly, the manifold device
28 includes a first plate member 63 having a topside surface 67
upon which the disk-shaped stator face element 53, defining the
stator face 41, is supported. On an opposite side of the topside
surface 67 of the first plate member 63 is a bottomside surface 68
upon which a plurality of horizontally extending dispensing grooves
70 are formed. These grooves are preferably about 0.3 mm in width
and are about 1.0 mm deep into the bottomside surface 68, depending
upon the particular application. A corresponding first dispensing
port 36 extends vertically into the first plate member 63 from the
topside surface 67 to the bottomside surface 68 where it intersects
one end of a corresponding dispensing groove 70. Similarly, a
corresponding second dispensing port 37 extends vertically into the
stator face element 53 and first plate member 63 from the stator
face 41 to the bottomside surface 68 where it intersects an
opposite end of a corresponding dispensing groove 70.
[0067] In accordance with this aspect of the present invention, a
substantially planar topside surface 71 of the second plate member
64 is affixedly lamination or diffusion bonded to the bottomside
surface 68 of the first plate member 63 at a first plate/second
plate interface. Hence, the diffusion bonded second plate member
topside surface 71 effectively seals the dispensing grooves 70
extending into the bottomside surface 68 of the first plate member
63 to form the corresponding dispensing conduits 35.
[0068] It will be appreciated that the groove formation forming the
horizontal portions of the dispensing conduits 35 could be provided
by both the bottomside surface 68 of the first plate member 63 and
the topside surface 71 of the second plate member 64, or
alternatively, only by the second plate topside surface. It will
further be understood that the alignment and orientation of first
dispensing ports 36 can be positioned at a plurality of locations
along the topside surface of the first plate member without
departing from the true spirit and nature of the present
invention.
[0069] Applying a similar technique, the aspiration conduits 30
could also have been defined at the first plate/second plate
interface. However, to assure sufficient spacing between adjacent
conduits to accommodate high pressure nature of the fluid delivery,
the aspiration conduits 30 are preferably formed at a separate
second plate/third plate interface between the second plate member
64 and a third plate member 65. Thus, the bottomside surface 72 of
the second plate member preferably incorporates a plurality of
horizontally extending aspiration grooves 73 (FIGS. 13 and 14)
which are preferably about 0.5 mm in width and are about 0.25 mm
deep.
[0070] A corresponding first aspiration port 31 extends vertically
into the second plate member 64 from the topside surface 71 to the
bottomside surface 72 thereof where it intersects one end of a
corresponding aspiration grooves 73. It will be appreciated that
the second plate member includes a pair of opposed wing portions 75
which extend beyond the peripheral edge of the first plate member
63. Briefly, these wing portions 75 are adapted to accommodate the
mounting of the tubing array manifolds 62 thereto. Regarding the
second dispensing ports 37, however, these aligned vertical
passages extend from the stator face 41 of the stator face element
53 through both the first plate member 63 and the second plate
member 64 to the bottomside surface 72 thereof where it intersects
an opposite end of a corresponding aspiration groove 73.
[0071] Similar to the formation of the dispensing conduits 35, a
substantially planar topside surface 76 of the third plate member
65 is affixedly coupled to the bottomside surface 72 of the second
plate member 64 at the second plate/third plate interface. Again,
applying conventional lamination or diffusion bonding techniques,
the third plate topside surface 76 can be laminated to the second
plate bottomside surface 72 to effectively seal the aspiration
grooves 73 to form the corresponding aspiration conduits 30.
[0072] As best viewed in FIGS. 4A and 13, the circular pattern of
the upper communication port 46 extend vertically through the
stator element 53. The first plate member 63, the second plate
member 64 and the third plate member 65 also include corresponding
co-axially aligned passage components to collectively form the
primary passages 45 of the sample paths 33 when the manifold plate
members are laminated together. Typically, the transverse
cross-sectional area of primary passages 45 are on the order of
about 0.2 mm.sup.2 to about 0.8 mm.sup.2 from the stator face 41 to
a bottomside surface 77 of the third plate member 65.
[0073] To reorient the circular pattern of the upper communication
port 46 at the bottomside surface 77 of the third plate member 65
to a rectangular pattern of the lower communications ports 47,
which conforms to the spacing of the array of reservoir wells 38 of
the microtiter plate 40 and test sites 25, a fourth plate member 66
is required. As shown in FIGS. 10, 12 and 13, a fourth topside
surface 76 of the fourth plate includes a plurality of horizontally
extending repositioning grooves 79. These grooves 79 are preferably
about 0.5 mm in width and are about 0.25 mm deep into the topside
surface 76 of the fourth plate member 66. A corresponding lower
communication port 47 extends vertically into the fourth plate
member 66 from a bottomside surface 80 to the topside surface 78
thereof where it intersects one end of a corresponding
repositioning groove 79. The other end of the repositioning groove
79 is aligned with the corresponding primary passage 45 terminating
at the bottomside surface 77 of the third plate member 65. Again,
applying conventional lamination or diffusion bonding techniques,
the fourth plate topside surface 78 can be diffusion bonded to the
third plate bottomside surface 77 to effectively seal the
repositioning grooves 79 to form another portion of the sample path
33.
[0074] As above-mentioned and as illustrated in FIGS. 2, 5 and 6,
fluidly coupled to each lower communication port 47 of the primary
passage 45 is a corresponding nozzle member 48 having a nozzle
passage 50 extending therethrough. The elongated nozzle member 48
includes a distal tip portion 81 suitably dimensioned to extend
into a targeted reservoir well 38, in aspiration condition, to
aspirate sample or reagent fluid into the sample path 33. Moreover,
the 2.times.6 array of nozzles are spaced apart to conform with the
array of reservoir wells and test sites 25 for simultaneous
aspiration and dispensing. They can also be redistributed to other
formats such as 1.times.12.
[0075] In the preferred embodiment, the diameter of the nozzle 50
passages abruptly changes to a smaller diameter by means of an
orifice, such as a jeweled orifice. This change in diameter is
beneficial in that it facilitates ejection of the sample fluids
from the tip when a pressure pulse is delivered by the
corresponding dispensing actuator 22.
[0076] As shown in FIG. 3, system fluid reservoirs 82, 83,
containing conventional mobile phase fluid 85, 86, are supplied to
the aspiration actuators 21 and the dispensing actuators 22 as a
driving fluid. In the aspiration condition, when rotor element 52
of the valve assembly 27 is rotated to align the corresponding
aspiration channels 57 to the corresponding upper communication
ports 46 of the primary passages 45 of the sample paths 33 and the
second dispensing ports 37 of the aspiration conduits 30, the
aspiration actuators 21 can be first employed to purge the entire
path from the first aspiration port 31 of the aspiration conduit
all the way to the corresponding dispensing orifice of the tip 81
of the nozzle member 48. Thus, after the nozzle tips are optionally
cleaned, clean mobile phase fluid replaces any sample or reagent
fluid from previous operations.
[0077] The transport mechanism (not shown) is then operated to
position the hybrid valve assembly 27 at the reservoir wells 38
where the designated nozzle tips 81 are submersed in the targeted
reservoir wells. Operation of one or more of the syringe pumps 21
draw the sample or reagent fluids into the corresponding sample
path 33 in the manifold device 28. The volume of fluid aspirated
into the corresponding sample path 33, thus, can be accurately
metered.
[0078] Subsequently, the transport mechanism can move the hybrid
valve assembly 27 to the test sites 25, while the electric motor 56
and drive train 54 rotates the rotor element 52 from the aspiration
condition to the dispensing condition. As mentioned, the aspiration
channels 57 in the rotor face 51 are moved out of fluid coupling to
the upper communication ports 46 of the primary passages 45, while
the dispensing channels 58 in the rotor face 51 are moved to
fluidly couple the second dispensing ports 37 of the dispensing
conduits 35 with the corresponding communication ports 46.
Essentially, in the aspiration condition, the second dispensing
port 37 of the dispensing conduit 35 is dead-ended against the
rotor face 51, while in the dispensing position, the second
aspiration port 32 of the aspiration conduit 30 is dead-ended
against the rotor face 51.
[0079] The mobile phase fluid, which is preferably substantially
similar to that supplied to the aspiration actuators, is fluidly
coupled to the corresponding dispensing channels 58 in the rotor
face 51 to selectively dispense the sample fluids from the
corresponding nozzle tips 81. Accordingly, cross-contamination is
minimized to the mobile phase fluids contained in the corresponding
dispensing channels 58. This assures that the dispensing conduits
35 can be substantially maintained free of contamination of any
sample or reagent fluids.
[0080] In an alternative embodiment of the present invention, the
nozzle passages 50 and corresponding primary passages 45 may only
be employed to dispense the sample or reagent fluid from the sample
path 33. Unlike the embodiment above-mentioned, the nozzle member
48, thus, will not be utilized to aspirate the targeted fluid into
the sample path from the source plate. Accordingly, as viewed in
the embodiments of FIGS. 15 and 17, the hybrid valve assembly can
load the sample path 33 through means other than the nozzle members
48, while maintaining the isolation of the sample path from the
dispensing actuator, in the aspiration condition (FIGS. 15 and 17),
and isolation of the sample path from the aspiration actuator, in
the dispensing condition (FIGS. 16 and 18).
[0081] Briefly, the manifold body in this configuration includes a
source conduit, generally designated 87, having an upper
communication opening 88 terminating at the stator face 41, and an
opposite end in fluid communication with the source reservoir 23.
Further, as best viewed in FIGS. 15, 17 and 19, the contact or
rotor face 51 of the valve body or rotor element 52 includes a
sample channel 90 which, in the aspiration condition, fluidly
couples the second aspiration port 32 of the aspiration conduit 30
to the upper communication opening 88 of the source conduit 87.
[0082] Accordingly, in the aspiration condition, the aspiration
actuator 21 is fluidly coupled to the source reservoir through the
sample channel 90 formed in the rotor face 51. Upon activation of
the aspiration actuator, the reagent or sample fluid can be drawn
into the sample path 33 by way of the source conduit 87 in the
manifold body 28. To isolate the dispensing actuator 22 from the
sample path 33, the corresponding second dispensing port 37 of the
dispensing conduit 35 is dead-ended into the rotor face 51, and
thereby out of fluid communication with the sample path (FIG.
17).
[0083] Once the reagent or sample fluid is aspirated into the
sample path 33, via the aspiration actuator 21, the valve assembly
27 can be moved to the dispense position of FIGS. 16 and 18. In the
preferred form, the rotor element 52 of the valve assembly is
rotated about rotational axis 44 for movement from the aspiration
condition to the dispense condition. The sample channel 90,
containing the reagent or sample fluid, is co-aligned with and
moved into the fluid communication with the second dispensing port
37 of the dispensing conduit 35 and the upper communication port 46
of the primary passage 45. The dispensing actuator 22 is therefore
fluidly coupled to the sample path 33 to fluidly dispense the
reagent or sample fluid out of the nozzle member 48. Moreover, to
isolate the aspiration actuator 21 from the sample path 33, the
corresponding aspiration port 32 of the aspiration conduit 30 is
dead-ended into the rotor face 51, and thereby out of fluid
communication with the sample path (FIG. 18).
[0084] In this embodiment, thus, it will be appreciated that the
dispensable volume of the sample path 33 is essentially the same as
that of the sample channel 90. When the rotor element 52 rotates to
the dispensing condition (FIGS. 16 and 18), only the sample or
reagent fluid contained in the sample channel 90 is fluidly
accessible to the dispensing actuator. It will be understood,
however, that volumetric quantities less than the full volume of
the sample channel 90 may be dispensed through precision operation
of the dispensing actuator 22.
[0085] As best shown in FIG. 19, each sample channel 90 is slotted
into the substantially planar rotor face 51 of the rotor element
52. Further, each equally spaced sample channel 90 is elongated in
shape, and extends generally along a radial line intersecting the
rotational axis 44 of the rotor face 51. Accordingly, at the
rotor-stator interface (i.e., the high pressure sliding contact
between the stator face 41 and the rotor face 51), the rotor
element 52 either reciprocates or rotates in one direction
clockwise or counter clockwise to orient the valve assembly in the
aspiration condition or the dispensing condition.
[0086] These sample channels 90 preferably have a length in the
range of about 1.0 mm to about 6.0 mm, and have a transverse
cross-sectional area of about 0.3 mm.sup.2 to about 1 mm.sup.2.
Accordingly, the volumetric capacity of the sample channel 90 is
preferably in the range of about 0.5 .mu.l to about 2.0 .mu.l. In
comparison, the primary passage 45 and the nozzle passage 50 of the
outlet preferably has a volume in the range of 0.1 .mu.l to about
2.0 .mu.l.
[0087] The separation of the aspiration duty from the nozzle member
48 has several functional advantages. One benefit is that the total
volume of sample is contained in the sample channel 90. Unused
sample or reagent may be returned to the source, during dispense
(FIG. 18) via the source path 23 significantly reducing sample and
reagent waste volumes. An added benefit is that the nozzle member
48 may be greatly reduced in length to shorten the dispense path
and pre-dispensing.
[0088] Another benefit of this design is that a spacing and order
of the source reservoir array does not need to match that of the
targeted test sites. That is, since the nozzle member 48 are not
employed for both the aspiration and dispensing functions, the
aspiration inlets (not shown), fluidly coupled to source conduits
87, can be set at one spacing and order (e.g., 96 well format),
while the nozzle members 48 can be set to a different spacing and
order (e.g., 1536 well format). Accordingly, the aspiration
versatility is substantially increased. For example, some
applications require individual manipulation of aspiration tips,
such as applications that reformat individual positive samples to
one destination plate from a multiplicity of positive and negative
samples in a source plate.
[0089] In yet another advantage of this design, the transverse
cross-sectional dimension of the aspiration and source conduits 30,
87, on the aspiration side, can be different from that of the
dispensing conduits 35 and the primary passages 45 in the manifold
device 28 and the nozzle passages 50 of the nozzle member 48, on
the dispensing side. For example, it would be desirable to provide
a large bore aspiration conduit 30 and source conduit 87 to
facilitate rapid sample aspiration into the sample channel. In
contrast, it would be desirable to provide a smaller bore for the
nozzle passages 50 to facilitate ejection of smaller discrete
volumes. Otherwise, when a smaller bore is utilized for restrictive
flow of the dispense nozzle, in the previous embodiment, effective
aspiration is compromised.
[0090] Lastly, the permissible wider cross-sectional dimension of
the aspiration inlet allows for the inclusion of filtering devices.
For example, by incorporating a filter on the inlet side, small
particulates in the reagent or sample fluid that would normally
clog, and render useless, a small bore nozzle can be removed. Such
a filter could be exchangeable and would contain a high surface
area allowing for filtering of particulates without frequent
clogging. Typical of such filtering devices include frits commonly
used in solid phase extraction or liquid chromatography
devices.
[0091] Referring back to FIGS. 15 and 16, this embodiment of the
present invention may further include a flush passage 91 in the
manifold device 28 having an upper central flush port 92
terminating at the stator face 41, and an opposite end in fluid
communication with a flush source 93. The central flush port 92 is
aligned substantially co-axial with the rotational axis 44 of the
rotor element 52 for continuous fluid communication with a flush
channel 95 slotted in the rotor face 51 (FIG. 19).
[0092] In the aspiration condition of FIGS. 15 and 17, this flush
channel 95 in the rotor element 52 is fluidly couples the flush
port 92 of the flush passage 91 to the upper communication port 46
of the corresponding primary passage 45. Thus, while the reagent or
sample fluid is being aspirated into the corresponding sample path
33, the primary passages 45 and the nozzle passages 50 may be
simultaneously flushed or cleaned with wash fluid or the like from
the wash source 93. In contrast, when the rotor element is rotated
to the dispensing condition of FIGS. 16 and 18, the flush channel
95 slotted in the rotor face fluidly couples the flush port 92 of
the flush passage 91 to the upper communication opening 88 of the
source conduit 87. Therefore, when the reagent or sample fluid is
being dispensed from the sample path 33 through the corresponding
nozzle member 48, unused sample or reagent could be returned to the
source reservoir 23 and the aspirate path flushed.
[0093] Preferably, the flush channel 95 is provided by a plurality
of equally spaced elongated slots which extend generally along a
radial line intersecting the rotational axis 44 of the rotor face
51. These radially extending flush channels intersect at the
rotational axis 44 so that the flush channels are in continuous
fluid communication with the central flush port 92. As shown in
FIG. 20, the upper communication ports 46 of the primary passages
45 and the upper communication openings 88 of the source conduits
87 are alternately spaced about the rotational axis 44.
Accordingly, each rotation movement of the rotor element 52 between
the aspiration condition (FIGS. 15 and 17) and the dispensing
condition (FIGS. 16 and 18) alternates fluid communication with the
nozzle passages 50 and the source conduits 87.
[0094] Accordingly, at the rotor-stator interface (i.e., the high
pressure sliding contact between the stator face 41 and the rotor
face 51), the rotor element 52 either reciprocates or rotates in
one direction clockwise or counter clockwise to orient the valve
assembly in the aspiration condition or the dispensing
condition.
[0095] Although only a few embodiments of the present inventions
have been described in detail, it should be understood that the
present inventions may be embodied in many other specific forms
without departing from the spirit or scope of the inventions.
* * * * *