U.S. patent application number 10/948014 was filed with the patent office on 2005-02-17 for droplet dispensing system.
This patent application is currently assigned to Cytonome, Inc.. Invention is credited to Gilbert, John.
Application Number | 20050036920 10/948014 |
Document ID | / |
Family ID | 26704545 |
Filed Date | 2005-02-17 |
United States Patent
Application |
20050036920 |
Kind Code |
A1 |
Gilbert, John |
February 17, 2005 |
Droplet dispensing system
Abstract
A droplet dispensing system for forming and dispensing droplets
of a liquid sample is provided. The droplet dispensing system is
fabricated on the tip of a dispensing pin. The tip of the
dispensing pin includes a droplet ejection nozzle, a filling
channel, a chamber and an actuator for ejecting droplets on demand.
The system further includes a holder for mounting the dispensing
pin. The holder also contains a control circuit for activating the
actuator.
Inventors: |
Gilbert, John; (Brookline,
MA) |
Correspondence
Address: |
LAHIVE & COCKFIELD, LLP.
28 STATE STREET
BOSTON
MA
02109
US
|
Assignee: |
Cytonome, Inc.
Watertown
MA
|
Family ID: |
26704545 |
Appl. No.: |
10/948014 |
Filed: |
September 23, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10948014 |
Sep 23, 2004 |
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10029108 |
Dec 21, 2001 |
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6808683 |
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60325040 |
Sep 25, 2001 |
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Current U.S.
Class: |
422/400 |
Current CPC
Class: |
B01L 2200/147 20130101;
C12Q 1/00 20130101; G01N 27/447 20130101; B01L 2200/143 20130101;
B01L 3/0268 20130101; B01L 2400/0439 20130101; B01L 3/0244
20130101; G01N 2035/1037 20130101; Y10T 436/119163 20150115; Y10T
436/2575 20150115; B01L 3/0248 20130101 |
Class at
Publication: |
422/100 |
International
Class: |
B01L 003/02 |
Claims
1. A droplet dispensing system, comprising: a first pin having a
tip; and a dispensing pin having a tip and spaced adjacent to the
first pin so as to form a sample filling channel between the first
and second pin, the dispensing pin tip having a sample chamber
located in fluid communication with the sample filling channel, an
ejection nozzle for ejecting a droplet from the sample chamber, and
an actuator for triggering formation and ejection of a droplet from
the ejection nozzle.
2. The droplet dispensing system of claim 1, wherein the first pin
and the second pin are movable relative to each other, so as to
vary the size of the sample filling channel.
3. The sample dispensing system of claim 1, wherein the first pin
tip and the dispensing pin tip have a diameter between about 0.5
millimeters and about 5 millimeters.
4. The sample dispensing system of claim 3, wherein the dispensing
pin tip diameter is about 1.0 millimeters.
5. The sample dispensing system of claim 1, further comprising a
holder for mounting the first pin and the dispensing pin.
6. The sample dispensing system of claim 5, wherein the holder
contains a control circuit for activating the actuator.
7. The sample dispensing system of claim 6, further comprising an
electrical connector for providing an electrical connection between
the control circuit and the actuator.
8. The sample dispensing system of claim 1, wherein the first pin
and the dispensing pin are formed from a silicon wafer.
9. The sample dispensing system of claim 1, wherein the filling
channel includes a filling nozzle for introducing a liquid sample
to the filling channel.
10. The sample dispensing system of claim 9, wherein the filling
nozzle extends beyond the ejection nozzle, such that when the first
pin tip and the dispensing pin tip are dipped into a reservoir, the
filling nozzle is immersed in a liquid supply without immersing the
ejection nozzle of the dispensing tip.
11. The sample dispensing system of claim 1, wherein the droplet
ejection nozzle has an ejection port, said ejection port having a
diameter between about thirty and about fifty microns.
12. The sample dispensing system of claim 1, wherein the actuator
comprises a piezoelectric film affixed to a side wall of the sample
chamber.
13. The sample dispensing system of claim 1, wherein the actuator
comprises an electromechanical assembly for effecting ejection of a
droplet from the ejection nozzle.
14. The sample dispensing system of claim 1, wherein the actuator
comprises a magnetic assembly for effecting ejection of a droplet
from the ejection nozzle.
15. The sample dispensing system of claim 1, wherein the actuator
comprises a thermoelectric assembly for effecting ejection of a
droplet from the ejection nozzle.
16. The sample dispensing system of claim 1, wherein the filling
channel and the sample chamber have a combined volume of between
about 1 nanoliter and about 10 nanoliters.
17. A method of forming and dispensing droplets of a liquid sample,
comprising: providing a droplet dispensing system comprising a pin
having a tip, said tip forming a filling channel for filling the
tip with a predetermined volume of liquid sample, a sample chamber
for holding a predetermined volume of liquid sample, an ejection
nozzle and an actuator for effecting formation of a droplet from
said volume of liquid sample; and activating the actuator to
produce a droplet of liquid sample at the sample ejection
nozzle.
18. The method of claim 17, further comprising the step of filling
the tip with a liquid sample prior to the step of activating the
actuator.
19. The method of claim 18, wherein the step of filling the tip
comprises the step of immersing the tip in a reservoir containing a
supply of liquid sample.
20. The method of claim 19, wherein the step of immersing comprises
immersing an intake port of the filling channel without immersing
the ejection nozzle.
21. The method of claim 19, wherein the step of filling comprises
activating the actuator to pump a liquid sample into the filling
channel.
22. The method of claim 17, wherein the step of activating the
actuator comprises transmitting a droplet ejection signal to the
actuator from a control circuit.
23. The method of claim 17, further comprising the step of
directing the droplet of liquid sample to a fluid interface
port.
24. A sample dispensing system, comprising: a dispensing pin having
a tip; a substantially U-shaped fluid path formed in the tip of the
dispensing pin for conveying a liquid sample; and an actuator
coupled to a portion of the fluid path for forming a droplet of the
liquid sample upon activation of the actuator.
25. The sample dispensing system of claim 24, wherein said fluid
path comprises: a sample chamber for holding a predetermined volume
of sample, a sample filling channel in fluid communication with the
sample chamber for loading a liquid sample into the sample chamber;
and a droplet ejection port in fluid communication with the sample
chamber for ejecting a droplet of the liquid sample from the sample
chamber.
26. The sample dispensing system of claim 25, wherein the droplet
ejection port forms a nozzle.
27. A sample dispensing system, comprising: a holder; and a
dispensing pin having a first end coupled to the holder and a
second end forming a tip, wherein the tip includes a sample chamber
formed in the tip for holding a predetermined volume of sample, a
sample filling channel in fluid communication with the sample
chamber for loading a liquid sample into the sample chamber, and a
droplet ejection nozzle in fluid communication with the sample
chamber for ejecting a droplet of the liquid sample from the sample
chamber.
Description
REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional application of U.S.
application Ser. No. 10/029,108, which claims priority to U.S.
Provisional Patent Application No. 60/325,040, entitled "Droplet
Dispensing System" filed Sep. 25, 2001, and is related to U.S.
patent application Ser. No. 10/028,852, entitled "Microfluidic
System Including a Virtual Wall Fluid Interface Port for
Interfacing Fluids with the Microfluidic System", filed Jun. 20,
2002, U.S. patent application Ser. No. 10/027,484, entitled
"Microfluidic System Including a Virtual Wall Fluid Interface Port
for Interfacing Fluids with the Microfluidic System", filed Jun.
20, 2002, U.S. patent application Ser. No. 10/027,516, entitled
"Microfluidic System Including a Virtual Wall Fluid Interface Port
for Interfacing Fluids with the Microfluidic System", filed Jun.
20, 2002; U.S. patent application Ser. No. 10/027,171, entitled
"Microfabricated Two-Pin Liquid Sample Dispensing System", filed
Jun. 20, 2002; and U.S. patent application Ser. No. 10/027,922,
entitled "Small Molecule Substrate Based Enzyme Activity Assays",
filed Jun. 20, 2002. The contents of the foregoing patent
applications are herein incorporated by reference. The contents of
all references, issued patents, or published patent applications
cited herein are expressly incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to a liquid dispensing system
for forming and dispensing droplets of a liquid sample.
BACKGROUND OF THE INVENTION
[0003] Many chemical, biomedical, bioscience and pharmaceutical
industries require chemical operations, such as reactions,
separations and subsequent detection steps, to be performed on
samples. It is generally desirable to introduce these samples into
a sample handling system, such as a microfluidic system capable of
handling and analyzing chemical and biological specimens, quickly,
efficiently and in a highly controllable manner.
[0004] Many methods have been described for the interfacing of
fluids, e.g., samples, analytes, reagents, precursors for synthesis
and buffers, towards, within or between microfluidic systems.
Generally, introduction of a liquid sample to a microfluidic system
is accomplished through sample channels or sample wells. To
introduce a liquid sample to the microfluidic system, a capillary
tube may be provided, which dispenses a liquid sample to a sample
well, sample channel or other sample introduction port. A
significant drawback of using a capillary tube concerns the low
injection efficiency inherent to capillary tubes, that is, the
ratio between the volume of liquid required for a particular
chemical operation in a part of the microfluidic system, and the
total volume of liquid required for the introductory operation.
Moreover, it is generally difficult to control the precise volume
of dispensed sample using capillary tubes. Furthermore, capillary
tubes are subject to contamination, because the same port used to
fill the tube is also used to eject the liquid sample.
[0005] U.S. Pat. No. 6,101,946 of Martinsky describes a pin-based
system for printing microarrays of biochemical substances. The
microarray printing system comprises a printing pin having a sample
channel and a flat tip. The pin applies a biochemical substance by
filling the sample channel and subsequently directly contacting a
printing substrate, to deliver the sample from the sample channel
to the printing substrate. A drawback of the pin-based system
described in the '946 patent concerns the ability to control the
amount of delivered sample. The pin-based system is subject to
contamination and breakage, because it requires direct contact
between the pin tip and the printing substrate. Another drawback
concerns the difficulty of precisely positioning the tip of the pin
to provide sufficient contact to result in delivery of a
sample.
[0006] U.S. Pat. No. 6,110,426 of Shalon et al., the contents of
which are herein incorporated by reference, describes a capillary
dispenser for forming microarrays of biological samples. The
capillary dispenser comprises an elongate open capillary channel
adapted to hold a liquid sample. The channel is formed by a pair of
spaced-apart, coextensive, elongate members, which are tapered
toward one another and converge at a tip region at the lower end of
the channel. The elongate members are fixed relative to each other
and the capillary channel is limited to a fixed volume.
Furthermore, it is difficult to control the amount of sample that
is acquired and dispensed from the capillary dispenser of the '246
patent.
SUMMARY OF THE INVENTION
[0007] The present invention provides a droplet dispensing system
which forms and dispenses droplets of a liquid sample on demand.
The droplet dispensing system comprises a holder and one or more
dispensing pins. Each dispensing pin has a tip for forming and
ejecting droplets of a liquid sample from a supply of liquid sample
stored in the tip. The tip of each dispensing pin includes a
droplet ejection nozzle for controllably and selectively ejecting a
droplet of liquid from the tip of the dispensing pin. Each
dispensing pin tip includes a sample chamber in fluid communication
with the ejection nozzle for holding a supply of a liquid sample.
The tip further includes a filling channel in fluid communication
with the sample chamber for filling the tip with a predetermined
volume of liquid sample from a reservoir. An actuator is located on
the tip adjacent to the ejection nozzle and communicates with the
sample chamber. The droplet dispensing system forms and ejects
droplets through the ejection nozzle by activating the
actuator.
[0008] A method of manufacturing a dispensing system is also
provided. According to the illustrative embodiment, the droplet
dispensing system is fabricated from a silicon wafer. A
photolithography process is utilized to etch the filling channel,
sample chamber and ejection nozzle in the tip of a dispensing pin.
A suitable actuator is attached to the tip to provide for formation
and ejection of droplets from the ejection nozzle.
[0009] The droplet dispensing system provides fast and flexible
filling of a predetermined amount of liquid sample in the
dispensing system via the tip of a dispensing pin. The droplet
dispensing system provides efficient and rapid dispensing of the
liquid sample from the tip of a dispensing pin in the form of
droplets having a precisely controlled volume. The droplet
dispensing system enhances liquid sample application by improving
efficiency, speed and controllability, while reducing waste and
contamination.
[0010] According to one aspect a droplet dispensing system
comprising a dispensing pin is provided. The sample dispensing
system comprises a dispensing pin having a tip. The tip includes a
sample chamber, a sample filling channel formed in the tip and in
fluid communication with the sample chamber for loading a liquid
sample into the sample chamber, a droplet ejection nozzle in fluid
communication with the sample chamber for ejecting a droplet of the
liquid sample from the sample chamber and an actuator located
adjacent to the sample chamber for forming the droplet.
[0011] According to another aspect, a droplet dispensing system
comprises two interacting pins is provided. The two-pin droplet
dispensing system comprises a first pin and a dispensing pin
positioned in proximity to each other to form a filling channel
therebetween. The dispensing pin has a tip further comprising a
sample chamber located in fluid communication with the sample
filling channel, an ejection nozzle for ejecting a droplet from the
sample chamber and an actuator for triggering formation and
ejection of a droplet from the ejection nozzle.
[0012] According to yet another aspect, a method of dispensing a
liquid sample is provided. The method of dispensing a liquid sample
comprises providing a droplet dispensing system comprising a pin
having a tip including filling channel for filling the tip with a
predetermined volume of liquid sample, a sample chamber, an
ejection nozzle and an actuator for effecting formation of a
droplet. The method further comprises the step of activating the
actuator to produce a droplet of liquid sample at the sample
ejection nozzle.
[0013] According to another aspect, a liquid sample dispensing
system, comprising a holder and an array of dispensing pins
connected to the holder is provided. Each dispensing pin in the
array has a tip and a sample chamber formed in the tip for holding
a predetermined volume of sample, a sample filling channel formed
in the tip and in fluid communication with the sample chamber for
loading a liquid sample into the sample chamber and a droplet
ejection nozzle in fluid communication with the sample chamber for
ejecting a droplet of the liquid sample from the sample chamber.
The liquid sample dispensing system further includes an actuator
coupled to the sample chamber of one or more of the dispensing pins
for forming one or more droplets upon activation of the
actuator.
BRIEF DESCRIPTION OF THE FIGURES
[0014] FIG. 1 is a schematic view of a droplet dispensing system
according to the teachings of the present invention.
[0015] FIG. 2 is a perspective view of a droplet dispensing system
according to the teachings of the present invention, comprising an
array of dispensing pins connected to a holder.
[0016] FIG. 3 is an exploded perspective view of the tip of the
dispensing pin employed in the droplet dispensing system of FIG.
1.
[0017] FIG. 4 is a cross-sectional view of tip of the dispensing
pin of FIG. 3.
[0018] FIG. 5 is an exploded detailed view of an alternate
embodiment of the droplet dispensing system, where the filling
channel is formed by two interacting pin structures.
DETAILED DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENT
[0019] The present invention provides a droplet dispensing system
for forming and dispensing liquid droplets of a sample for fluidic
systems. The droplet dispensing system of the present invention
provides precise sample uptake and delivery of a liquid sample to a
sample handling system in the form of sub-micron-sized droplets.
The droplet dispensing system is suitable for use in a basic
research or a commercial environment. The droplet dispensing system
significantly improves sample introduction into a sample handling
system by increasing the efficiency, speed and controllability of
forming and dispensing droplets while significantly reducing waste
and contamination. Those skilled in the art will appreciate that
the present invention may be implemented in a number of different
applications and embodiments and is not specifically limited in its
application to the particular embodiment depicted herein.
[0020] The droplet dispensing system of the present invention
provides significant improvements over prior pin-based dispensing
systems, which require direct contact to dispense a sample, and
capillary-based dispensing systems. Capillary-based dispensing that
produce droplets by means of air pressure or a remote actuator are
limited to formation of large-sized droplets in the range of ten
nanoliters to one microliter. Other capillary-based systems that
include actuators near the tips are filled from behind the tip and
generally take a long time, between ten and thirty minutes, to
fill. In contrast, the droplet dispensing system of the present
invention includes a filling channel and a droplet ejection
actuator co-located on the end of a dispensing pin. In this manner,
filling of the dispensing system is accomplished rapidly.
Furthermore, the dispensing system of the present invention is
capable of forming small, sub-nanoliter sized droplets.
[0021] FIG. 1 illustrates the droplet dispensing system 10 of the
illustrative embodiment. The droplet dispensing system comprises a
dispensing pin 11 mounted in a holder 12. The droplet dispensing
system 10 forms and dispenses droplets of a selected liquid sample
to allow a controlled introduction of a fluid sample to a sample
handling system. The sample droplets are formed and propelled
ballistically from the tip 13 of the dispensing pin 11, the details
of which are described below. The holder 12 can include electronics
15 comprising a control circuit for supplying a droplet ejection
signal to an actuator for triggering formation and ejection of a
droplet of a liquid sample from the tip 13. An electrical connector
16 provides an electrical connection between the electronics 15 and
the actuator for transmitting the droplet ejection signal between
the control circuit and the actuator. The details regarding the
formation and ejection of droplets from the tip 13 under the
control of the electronics 15 are described below. As used herein,
the term holder is intended to include any structure suitable for
holding or retaining in a fixed or removable and replaceable manner
one or more dispensing pins.
[0022] The pin 11 of the illustrative embodiment comprises an
elongated structure having a tip 13 with a diameter of about one
millimeter. According to the illustrative embodiment, sample
loading is accomplished by immersing the tip 13 of the dispensing
pin 11 into a reservoir 14 containing the desired liquid sample.
One skilled in the art will recognize that the tip 13 may have any
diameter, for example, up to several millimeters, suitable for
dipping into a reservoir of liquid and for holding liquid there
within.
[0023] The tip 13 of the dispensing pin 11 contains a sample
chamber that holds a predetermined volume of biological or chemical
sample, a filling channel for filling the sample chamber, an
actuator and an ejection nozzle. The tip 13 is immersed in a
biochemical sample such that a predefined volume of sample fills
the filling channel and the sample chamber of each pin. The droplet
dispensing system 10 is then moved in proximity to a fluid
interface port of a sample handling system, such as a microfluidic
system or a printing substrate. An actuator disposed within the
chamber is selectively activated to form and dispense droplets of
the sample from the pin tip, which forms an ejection nozzle. The
droplet dispensing system 10 propels droplets at a predetermined
and if desired controllable velocity, and along a selected path, to
introduce the liquid sample into a microfluidic system.
[0024] According to an alternate embodiment of the invention, shown
in FIG. 2, the pin dispensing system 100 can comprise an array 110
of dispensing pins 11 arranged in a holder 120 for allowing
simultaneous formation and dispensing of a plurality of samples. In
a pin dispensing system 100 having an array of dispensing pins 11,
each dispensing pin may be individually controlled by a
corresponding control circuit 150. Alternatively, a group of
dispensing pins may be simultaneously controlled by common control
circuit. The droplet dispensing system may comprise any suitable
number of dispensing pins 11 arranged in any suitable
configuration, depending on the particular application. The array
of pin dispensing systems of an illustrative embodiment of the
present invention may be manufactured from a substrate, such a
silicon wafer, using any suitable microfabrication technique, such
as photolithography.
[0025] The droplet dispensing system 10 of the illustrative
embodiment of the present invention may be utilized as a spotting
system for printing or discharging arrays of biochemicals, such as
nucleic acid molecules or proteins, or other suitable liquid
samples to a sample handing system, such as a printing substrate,
titre plate, microfluidic system or device, and the like for use in
proteomics, genomics, screening, diagnostics and other
applications. After the pin tip 13 acquires a droplet, the pin tip
13 is moved in close proximity to a surface. The surface may
comprise a solid surface or a liquid. The surface may comprise a
porous structure, such as a porous membrane, or a non-porous
structure, such as a microscope slide. The loaded pin or pins
deposit a spot on the surface having a selected spot volume by
direct contact between the pin tip 13 and the surface. According to
the illustrative embodiment, the volume of the dispensed spot is
significantly smaller than the volume of the acquired liquid
sample, and is generally sub-nanoliter in volume, though one
skilled in the art will recognize that the invention is not limited
to this range.
[0026] FIG. 3 is a detailed view of the tip 13 of the dispensing
pin 11 of the droplet dispensing system 10 according to a first
embodiment of the invention. The tip 13 includes both a filling
structure for loading the droplet dispensing system with a liquid
sample and a separate droplet actuation structure for forming and
ejecting droplets of the liquid sample from the tip of the
dispensing pin. As shown in FIG. 3, a filling channel 20 is formed
in the tip 13 for uptaking sample through an intake port 22,
illustrated as a filling nozzle, from a reservoir containing a
selected liquid sample. The filling channel preferably uptakes
sample by employing capillary forces. The filling channel 20
communicates with a sample chamber 21 formed in the tip 13. The
sample chamber 21 has a tapered end forming a droplet ejection
nozzle 23. The ejection nozzle 23 includes an ejection port 25
sized and dimensioned to form droplets from a liquid sample in the
sample chamber. As shown, the ejection nozzle is positioned in
close proximity to and in fluid communication with the sample
chamber 21. The tip further includes an actuator 24 adjacent to and
contacting the sample chamber. The actuator applies a force to the
sample chamber sufficient to cause formation and ejection of a
liquid droplet through the ejection nozzle 23. The actuator 24 is
selectively activated by the electronics in the pin holder and
dispenses droplets from the ejection nozzle on demand. As
illustrated, the tip 13 forms a continuous fluid path between the
intake port 22, formed at the tip of the filling channel 20, and
the ejection port 25, formed in the droplet ejection nozzle 23.
Those of ordinary skill will readily recognize that the chamber can
have any selected shape, and can be sited and dimensioned according
to the particular application. Furthermore, the dispensing pin 11
may also include a plurality of sample chamber 21 formed in the tip
of the pin.
[0027] Filling of the pin tip with a liquid sample is accomplished
easily, flexibly and rapidly by submerging the filling nozzle 22 in
a liquid sample supply. Liquid sample is drawn up the filling
channel 20 and passes into the connected sample chamber 21.
According to the illustrative embodiment, the filling channel 20 is
sized and dimensioned so that capillary forces automatically draw
the liquid sample through the filling channel 20 and into the
sample chamber 21. According to an alternate embodiment, filling is
effected by a pumping action provided by the actuator 24. The
volume of sample that is loaded depends on the length of time that
the tip is submerged in the reservoir, the size of the filling
channel and chamber, and the force applied to the channel. The
internal volume of the filling channel 20 and the sample chamber 21
define the maximum volume of sample that can be loaded into the
tip. Those of ordinary skill will readily recognize that the intake
port 20 can be formed at a number of different locations.
[0028] The droplet dispensing system 10 is capable of dispensing
and discharging or propelling droplets rapidly and efficiently to a
sample handling system. After the tip is filled with a liquid
sample, the droplet dispensing system 10 forms and dispenses
droplet of a sample liquid from the sample chamber 21 on demand by
activating the actuator 24. According to the illustrative
embodiment, the actuator 24 comprises a piezoelectric film affixed
to a side wall of the sample chamber 21 directly adjacent to the
ejection nozzle 23. The control circuit in the holder electronics
produces a droplet ejection signal, which is applied through the
electrical connector 16 to energize the actuator 24. When a voltage
is applied to the piezoelectric film, the piezoelectric film
deflects. The deflection of the piezoelectric film generates a
force on the sample chamber 21, which produces and ejects a droplet
from the ejection nozzle 23 though the ejection port 25. One
skilled in the art will recognize that the actuator 24 is not
limited to a piezoelectric actuator and that that any suitable
actuator for ejecting a droplet from a nozzle may be utilized, such
as the variety of actuators used in ink jet printing systems. For
example, the actuator may comprise an electromechanical actuator, a
magnetic actuator, a thermoelectric actuator or any suitable
actuator for forming and ejecting a droplet from an ejection
nozzle.
[0029] According to the illustrative embodiment, the shape of the
ejection nozzle 23 and sample chamber 21, including the size and
shape of the nozzle outlet port 25, determine the size and velocity
of the formed droplet. The combined volume of the filling channel
20 and the sample chamber 21 determine the supply of liquid sample
stored in the dispensing system with each complete filling.
According to the illustrative embodiment, the interior volume of
the filling channel 20 and the sample chamber 21 is between about
one and about ten nanoliters. One skilled in the art will recognize
that the filling channel, including the intake port, and sample
chamber are not limited to the illustrated configuration and that
alterations and variations may be made without departing from the
scope of the present invention.
[0030] The tapered droplet ejection nozzle 23 formed at the end of
the sample chamber 21 is designed to accelerate and direct the flow
of liquid from the sample chamber, such that droplets are propelled
ballistically from the tip 13 of the dispensing pin 11. The
ejection nozzle 23 and ejection port are sized and dimensioned so
that liquid is generally held in by capillary forces and forced out
only on demand, by calculatingly activating the actuator 24.
According to the illustrative embodiment, the nozzle ejection port
25 has a diameter between about thirty and about fifty microns,
resulting in a droplet having a diameter of about forty-five
microns and a volume between of about thirty-five picoliters. One
skilled in the art will recognize that variations of these
dimensions are within the scope of the invention and that the
volumes and dimensions may be varied to suit a particular
application. The sample chamber 21 and filling channel 20 may be
sized and dimensioned to produce between 10 and 10,000 droplets per
filling, of any selected size, depending on the particular
application.
[0031] According to the illustrative embodiment, the droplet
ejection nozzle 23 and the intake port 22 are co-fabricated on the
dispensing tip 13 to form a continuous fluid path through the
dispensing pin tip 13 for loading a supply of a liquid sample and
dispensing the liquid sample in the form of liquid droplets. The
intake port 22 and the ejection nozzle 23 are positioned separately
on the tip, such that the intake port 22 is capable of being
immersed in a sample reservoir without requiring simultaneous
immersion of the ejection nozzle 23. As shown, both nozzles 22 and
23 are formed in the tip of the dispensing pin, but the filling
nozzle 22 extends a predetermined distance beyond the ejection
nozzle 23. In this manner, the tip 13 can be loaded with a
predetermined amount of liquid sample by immersing only the filling
nozzle, without requiring immersion and possible contamination of
the ejection nozzle as well.
[0032] FIG. 4 is a cross-sectional view of the pin tip 13 of FIG. 3
along line A-A. As illustrated, the tip 13 comprises a silicon
substrate 30. According to the illustrative embodiment, the droplet
dispensing system is fabricated from a silicon wafer using a
standard photolithography process. One skilled in the art will
recognize that alternative materials and manufacturing techniques
may be utilized. For example, the pin dispensing system may be made
out of glass, plastic or any other suitable material.
[0033] To form the droplet dispensing system of the illustrative
embodiment, a silicon substrate 30 is provided. The substrate is
etched to form the filling channel 20, the sample chamber 21 and
the ejection nozzle 23. A top layer 31 of silicon is bonded to the
substrate after formation of the filling channel 20 and sample
chamber 21 to cover and seal the etched channel and chamber. The
actuator 24 is deposited on the exterior surface of the top layer
31, adjacent to the sample chamber 21 and in proximity to the
ejection nozzle 23, such that a force produced by the actuator 24
is translated to the sample chamber 21 to form a droplet and propel
the droplet from the ejection nozzle ballistically. As discussed,
an electrical connector is provided to electrically connect the
actuator 24 to a control circuit to allow transmission of a droplet
ejection signal to the actuator 24. Those of ordinary skill will
readily recognize that the tip can be manufactured and configured
in a variety of different ways, such as by any conventional
microfabrication technique, including photolithography.
[0034] The droplet dispensing system 10 may also be utilized with a
variety of applications requiring application of a liquid sample.
Once the sample is loaded in the dispensing tip 13, the dispensing
pin 11 or dispensing pins are brought into proximity with a fluid
interface port of a sample handling system. The droplet dispensing
system of the illustrative embodiment may be utilized to form
droplets of a liquid sample and introduce droplets to a
microfluidic system. For example, the droplet dispensing system 10
may be utilized to supply droplets to a micro-chip having a virtual
wall interface port, as described in U.S. Provisional Patent
Application No. 60/299,515, entitled Methods For Forming A
Microscale Virtual Wall And Use OfSaid Wall In Microfluidic
Applications, the contents of which are incorporated by reference
herein. Briefly, U.S. Provisional Patent Application No. 60/299,515
describes a microfluidic system having a fluid interface port
comprising an aperture sized and dimensioned to form a virtual wall
in the sidewall of a microchannel. The droplet dispensing system of
the illustrative embodiment may be utilized to form and propel
droplets towards the virtual wall in order to introduce a liquid
sample to the interior of a microchannel. Alternatively, the
droplet dispensing system 10 may be utilized to introduce a liquid
sample to a sample reservoir in a microfluidic system, such as a
well. According to another application, the droplet dispensing
system may be utilized in spotting applications for printing arrays
of biochemical substances on a printing substrate, such as
described in U.S. Pat. No. 6,101,946.
[0035] FIG. 5 is a detailed exploded view of a droplet dispensing
system 40 according to an alternate embodiment of the invention,
where the filling and droplet actuation mechanisms are formed in
the tips of two interacting pins. As illustrated, the droplet
dispensing mechanism is formed using two separately movable pins, a
first pin 41 and a dispensing pin 42. The pins 41 and 42 are
positioned relative to each other so as to form a filling channel
43 and filling nozzle 44 between the tips of the pins. The tip of
the dispensing pin 42 includes a sample chamber 45 in fluid
communication with the filling channel 43 and further includes a
droplet ejection nozzle 46 formed in the tip of the pin 42 and an
actuator 47 for forming droplets of a liquid sample, which are
ejected from the tip of the pin 42 through an ejection port 48 in
the droplet ejection nozzle 46. The separation distance D between
the pins 41 and 42 is movable to increase or decrease the amount of
sample acquired during filling. For example, if more sample volume
per filling is desired, the separation distance is increased,
thereby increasing the volume of the filling channel 43 and
allowing a larger volume of liquid sample to be stored and
subsequently dispensed.
[0036] The droplet dispensing system 40 of the illustrative
embodiment provides significant improvements to the process of
introducing a liquid sample to a sample handling system. The
illustrative configuration limits dead volume between the filling
channel and the sample chamber to more efficiently utilize a sample
and reduce waste of the sample. The location of the actuator near
the droplet ejection nozzle ensures that small droplets are formed
thereby increasing the controllability and efficiency of the sample
dispensing process. The flow-through design of the fluid path
ensures that sample is not wasted and that the entire loaded liquid
sample in the tip is utilized.
[0037] The illustrative embodiment significantly improves and
enhances the ability to control the formation of droplets by
allowing digital control of the quantity of dispensed sample. The
droplet dispensing system forms and eject droplets on demand having
a predetermined and precisely controlled volume. The volume of
dispensed sample is easily modified by varying the number of
droplets dispensed. For example, if a larger volume of sample is
required, the actuator is activated more frequently to produce more
droplets. Furthermore, the ability to produce droplets of a liquid
sample on demand provides efficient utilization of resources.
[0038] The droplet dispensing system also allows dispensing of a
liquid sample without requiring direct contact between the sample
dispenser and a substrate or fluid interface port. The droplet
dispensing system forms, propels and directs droplets with
precision. The droplet dispensing system further provides rapid,
easy and efficient filling and ejection of a liquid sample in
controlled volumes, without requiring complicated mechanisms or
machinery.
[0039] Another advantage of the droplet dispensing system of the
present invention concerns the cleaning of the system after use.
The flow-through design of the fluid path, including a separate
intake port and ejection port, allows for cleaning solution to
flush through the system, thereby reducing contaminants
significantly. To clean the droplet dispensing system, the pin tip
is dipped into a reservoir of cleaning solution. The actuator may
be activated continuously to pump cleaning solution through the
filling channel and sample chamber and out through the ejection
nozzle. By flushing contaminants through the tip of the dispensing
pin, the illustrative droplet dispensing system provides
significant advantages over prior dispensing systems. Furthermore,
the use of silicon to form the interior fluid path allows for more
vigorous cleaning solutions to be utilizes without degrading the
system.
[0040] The present invention has been described relative to an
illustrative embodiment. Since certain changes may be made in the
above constructions without departing from the scope of the
invention, it is intended that all matter contained in the above
description or shown in the accompanying drawings be interpreted as
illustrative and not in a limiting sense.
[0041] It is also to be understood that the following claims are to
cover all generic and specific features of the invention described
herein, and all statements of the scope of the invention which, as
a matter of language, might be said to fall therebetween.
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