U.S. patent application number 17/045739 was filed with the patent office on 2021-01-28 for chambers to receive fluids by negative pressures.
The applicant listed for this patent is HEWLETT-PACKARD DEVELOPMENT COMPANY, L.P.. Invention is credited to Silam J CHOY, Pavel KORNILOVICH, John LAHMANN.
Application Number | 20210023555 17/045739 |
Document ID | / |
Family ID | 1000005166076 |
Filed Date | 2021-01-28 |
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United States Patent
Application |
20210023555 |
Kind Code |
A1 |
LAHMANN; John ; et
al. |
January 28, 2021 |
CHAMBERS TO RECEIVE FLUIDS BY NEGATIVE PRESSURES
Abstract
An example device includes a chamber including a fluid inlet, a
fluid outlet, and a negative-pressure port. The negative-pressure
port is positioned relative to the fluid inlet to draw a droplet of
a fluid from the fluid inlet into the chamber when the fluid is
applied to the fluid inlet and negative pressure is applied to the
negative-pressure port. The fluid outlet is positioned relative to
the fluid inlet to collect the droplet. The example device further
includes a downstream microfluidic channel connected to the fluid
outlet of the chamber. The downstream microfluidic channel
communicates capillary action to the fluid outlet of the chamber.
The capillary action resists flow of the fluid from the fluid
outlet into the chamber induced by the negative pressure applied to
the negative-pressure port.
Inventors: |
LAHMANN; John; (Corvallis,
OR) ; CHOY; Silam J; (Corvallis, OR) ;
KORNILOVICH; Pavel; (Corvallis, OR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
HEWLETT-PACKARD DEVELOPMENT COMPANY, L.P. |
Spring |
TX |
US |
|
|
Family ID: |
1000005166076 |
Appl. No.: |
17/045739 |
Filed: |
November 21, 2018 |
PCT Filed: |
November 21, 2018 |
PCT NO: |
PCT/US2018/062347 |
371 Date: |
October 6, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
PCT/US2018/029169 |
Apr 24, 2018 |
|
|
|
17045739 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01L 2400/0406 20130101;
B01L 2300/0883 20130101; B01L 3/502715 20130101; B01L 2400/0442
20130101; B01L 3/50273 20130101 |
International
Class: |
B01L 3/00 20060101
B01L003/00 |
Claims
1. A device comprising: a chamber including a fluid inlet, a fluid
outlet, and a negative-pressure port, the negative-pressure port
positioned relative to the fluid inlet to draw a droplet of a fluid
from the fluid inlet into the chamber when the fluid is applied to
the fluid inlet and negative pressure is applied to the
negative-pressure port, the fluid outlet positioned relative to the
fluid inlet to collect the droplet; and a downstream microfluidic
channel connected to the fluid outlet of the chamber, the
downstream microfluidic channel to communicate capillary action to
the fluid outlet of the chamber, the capillary action to resist
flow of the fluid from the fluid outlet into the chamber induced by
the negative pressure applied to the negative-pressure port.
2. The device of claim 1, further comprising a droplet ejector at
an end of the downstream microfluidic channel to eject droplets to
draw fluid through the downstream microfluidic channel, the droplet
ejector further to provide the capillary action.
3. The device of claim 2, further comprising a target microfluidic
network communicating with the downstream microfluidic channel
between the chamber and the droplet ejector, the target
microfluidic network to perform a process with the fluid.
4. The device of claim 3, wherein the process comprises a nucleic
acid amplification process.
5. The device of claim 1, further comprising a droplet ejector
connected to the negative-pressure port to provide the negative
pressure.
6. The device of claim 1, further comprising a magnet at the
chamber.
7. The device of claim 1, further comprising a dried reagent in the
chamber.
8. The device of claim 1, wherein the chamber is of a mesofluidic
scale.
9. The device of claim 1, wherein a capillary break separates the
negative-pressure port from the fluid inlet or the fluid
outlet.
10. A method comprising: applying a negative pressure to a
negative-pressure port of a chamber to draw a droplet of a fluid
from a fluid inlet of the chamber into the chamber; collecting the
droplet at a fluid outlet of the chamber, the fluid outlet
positioned below the fluid inlet relative to a force of gravity;
and communicating capillary action from a downstream microfluidic
channel to the fluid outlet of the chamber, the capillary action to
resist flow of the fluid from the fluid outlet into the chamber
induced by the negative pressure applied to the negative-pressure
port.
11. The method of claim 10, further comprising ejecting droplets
using a droplet ejector at an end of the downstream microfluidic
channel to draw fluid through the downstream microfluidic
channel.
12. The method of claim 11, further comprising performing a process
with the fluid at a target microfluidic network communicating with
the downstream microfluidic channel between the chamber and the
droplet ejector.
13. The method of claim 12, comprising performing a nucleic acid
amplification process with the fluid at the target microfluidic
network.
14. The method of claim 10, further comprising ejecting droplets
using a droplet ejector connected to the negative-pressure port to
apply the negative pressure to the negative-pressure port.
15. A device comprising: a housing; a chamber defined by the
housing, the chamber including a fluid inlet, a fluid outlet, and a
negative-pressure port; a downstream microfluidic channel connected
to the fluid outlet of the chamber, the downstream microfluidic
channel to resist backflow of fluid from the fluid outlet into the
chamber induced by negative pressure applied to the
negative-pressure port; a feature at the housing, the feature
shaped to position the fluid outlet below the fluid inlet relative
to a force of gravity when the feature is mated with a
complementary feature at an analysis device; and a signal interface
to receive a signal from the analysis device to apply the negative
pressure to the negative-pressure port to draw a droplet of fluid
from the fluid inlet into the chamber.
Description
BACKGROUND
[0001] Microfluidic systems may be used to perform a variety of
chemical, biological, and biochemical processes, such as nucleic
acid testing. Delivery of reagents to a process site may be
accomplished in a variety of ways.
BRIEF DESCRIPTION OF THE DRAWINGS
[0002] FIG. 1 is a side cross-sectional view of an example device
including a chamber that may receive fluid by application of a
negative pressure to a negative pressure port.
[0003] FIG. 2 is a side cross-sectional view of an example device
including a chamber that may receive fluid by application of a
negative pressure using a droplet ejector.
[0004] FIG. 3 is a flowchart of an example method to provide fluid
to a chamber by application of a negative pressure to a negative
pressure port.
[0005] FIG. 4 is a side cross-sectional view of an example device
including a chamber containing a magnet to interact with fluid
drawn into the chamber by application of a negative pressure using
a droplet ejector.
[0006] FIG. 5 is a side cross-sectional view of an example device
including a chamber that may receive fluid by application of a
negative pressure using a droplet ejector unit primed with drive
fluid.
[0007] FIG. 6 is a side cross-sectional view of an example device
including a chamber that may receive fluid by application of a
negative pressure using a droplet ejector and that may provide
fluid to several target microfluidic networks.
[0008] FIG. 7 is a side cross-sectional view of example vertically
arranged devices, each including a chamber that may receive fluid
by application of a negative pressure to a negative pressure
port.
[0009] FIG. 8 is a schematic diagram of an example cartridge
including a chamber that may receive fluid by application of a
negative pressure to a negative pressure port.
[0010] FIG. 9 is a schematic diagram of an example device including
a chamber that may receive fluid by application of a negative
pressure to a negative pressure port, the example device being
provided to a centrifuge.
DETAILED DESCRIPTION
[0011] A filter flask or Buchner Flask is typically not used in a
microfluidic system, as such a flask is large scale and required
human intervention to remove collected material, even when a bottom
drain is provided. Further, known filter flasks are generally not
suited for microfluidic applications, such as nucleic acid testing
using a target microfluidic network.
[0012] This disclosure provides a mesofluidic chamber into which
upstream fluid may be drawn when downstream microfluidic output of
the chamber is stopped. This may facilitate performing mixing,
reaction, concentration, or other manipulation within the
chamber.
[0013] The chamber has a fluid inlet and a fluid outlet. The fluid
inlet may be positioned above the fluid outlet and separated from
the fluid outlet by a distance to form a capillary break. A
negative pressure port is provided to the chamber to apply low
pressure to the air or other gas within the chamber. The low
pressure draws fluid into the chamber via the fluid inlet. The
fluid inlet may be shaped to form droplets of incoming fluid.
Droplets may collect near the fluid outlet at the bottom of the
chamber.
[0014] The fluid outlet of the chamber is connected to a downstream
microfluidic channel that provides resistance to flow via capillary
action. The downstream microfluidic channel may feed a target
microfluidic network for a given application, such as thermocycling
for a polymerase chain reaction (PCR) process. A thermal inkjet
(TIJ) or piezo ejector array may be provided to draw fluid through
the downstream microfluidic channel. The resistance provided by the
downstream microfluidic channel and any downstream microfluidic
components provided holds fluid at the outlet against the low
pressure used to draw droplets into the chamber.
[0015] Holding fluid at the outlet allows for mixing, reaction,
concentration, or other manipulation to be performed within the
chamber. When the process is complete, the low pressure may be
removed and fluid may be flowed through the outlet and into the
downstream microfluidic channel and any downstream fluid components
that it feeds.
[0016] The mesofluidic chamber allows for fluid manipulations at
microfluidic scale, and such manipulations may be controlled by
droplet ejectors as opposed to human intervention.
[0017] In the examples, a device includes a chamber and a
downstream microfluidic channel. The chamber includes a fluid
inlet, a fluid outlet, and a negative-pressure port. The
negative-pressure port is positioned relative to the fluid inlet to
draw a droplet of a fluid from the fluid inlet into the chamber
when the fluid is applied to the fluid inlet and negative pressure
is applied to the negative-pressure port. The fluid outlet is
positioned relative to the fluid inlet to collect the droplet.
[0018] The downstream microfluidic channel is connected to the
fluid outlet of the chamber. The downstream microfluidic channel is
to communicate capillary action to the fluid outlet of the chamber.
The capillary action is to resist flow of the fluid from the fluid
outlet into the chamber induced by the negative pressure applied to
the negative-pressure port.
[0019] The device can further include a droplet ejector at an end
of the downstream microfluidic channel to eject droplets to draw
fluid through the downstream microfluidic channel. The droplet
ejector can further to provide the capillary action.
[0020] The device can further include a target microfluidic network
communicating with the downstream microfluidic channel between the
chamber and the droplet ejector. The target microfluidic network is
to perform a process with the fluid.
[0021] The process can include a nucleic acid amplification
process.
[0022] The device can further include a droplet ejector connected
to the negative-pressure port to provide the negative pressure.
[0023] The device can further include a magnet at the chamber.
[0024] The device can further include a dried reagent in the
chamber.
[0025] The chamber can be of a mesofluidic scale.
[0026] A capillary break can separate the negative-pressure port
from the fluid inlet or the fluid outlet.
[0027] In some examples, a device includes a housing; a chamber
defined by the housing; a downstream microfluidic channel; a
feature at the housing; and a signal interface. The chamber
includes a fluid inlet, a fluid outlet, and a negative-pressure
port. The downstream microfluidic channel is connected to the fluid
outlet of the chamber. The downstream microfluidic channel is to
resist backflow of fluid from the fluid outlet into the chamber
induced by negative pressure applied to the negative-pressure port.
The feature is shaped to position the fluid outlet below the fluid
inlet relative to a force of gravity when the feature is mated with
a complementary feature at an analysis device. The signal interface
is to receive a signal from the analysis device to apply the
negative pressure to the negative-pressure port to draw a droplet
of fluid from the fluid inlet into the chamber.
[0028] With reference to FIG. 1, an example device 100 includes a
chamber 102 and a downstream microfluidic channel 104.
[0029] The chamber 102 includes a fluid inlet 106, a fluid outlet
108, and a negative-pressure port 110. The chamber 102 may be
funnel shaped and may be oriented such that the chamber 102 narrows
in the direction of gravity G or other force. That is, the chamber
102 may be shaped and oriented with respect to gravity to collect
fluid 112 at the fluid outlet 108.
[0030] The fluid inlet 106 may be located at the end of an inlet
channel 114 that extends into the chamber 102. Such a channel may
have a tube or conduit structure that extends into the chamber 102.
A fluid or a constituent thereof may be provided to the chamber 102
via the fluid inlet 106. A constituent provided via the fluid inlet
106 may include a fluid that reacts, mixes, or otherwise cooperates
with a material present the chamber 102, such as a dry reagent
(e.g., solid, powder, etc.), magnet, or similar, to generate a
fluid that is to be drawn through the fluid outlet 108.
[0031] The fluid outlet 108 may be an opening that is positioned
relative to the fluid inlet 106 to collect incoming droplets of
fluid. The fluid outlet 108 may be located at or near the bottom of
the chamber 102. Fluid may be outputted from the chamber 102 via
the fluid outlet 108. The fluid outlet 108 communicates with the
downstream microfluidic channel 104 to feed fluid from the chamber
102 into the downstream microfluidic channel 104.
[0032] The negative-pressure port 110 is positioned above the fluid
outlet 108, with respective to gravity G, and relative to the fluid
inlet 106 to draw a droplet 116 of a fluid from the fluid inlet 106
into the chamber 102. The negative-pressure port 110 may be
positioned a minimum distance D from the fluid inlet 106 to prevent
a fluid droplet 116 from being drawn into the negative-pressure
port 110 by wicking, air/gas movement, or similar. The minimum
distance D may define a capillary break. The negative-pressure port
110 and chamber 102 are mutually arranged to prevent the droplet
116 from coming into contact with a surface that may wick the
droplet 116 to the negative-pressure port 110. For example, a
channel 118 that communicates with the negative-pressure port 110
may have a tube or conduit structure that extends into the chamber
102 to provide a capillary break.
[0033] A capillary break may be provided to separate the
negative-pressure port 110 from the fluid input 106 and fluid
output 108 to prevent wicking of fluid to the negative-pressure
port 110 by selected geometry (such as depicted), a surface energy
attribute of the fluid inlet 106 or fluid outlet 108, or a
combination of such.
[0034] The chamber 102 may be mesofluidic in scale relative to the
fluid outlet 108 and the downstream microfluidic channel 104.
Mesofluidic scale may be a scale that includes features having
characteristic sizes of between approximately 0.1 mm and
approximately 10 mm. The chamber 102 is not vented to atmosphere.
Openings in the chamber 102 may be limited to a fluid inlet 106, a
fluid outlet 108, and a negative-pressure port 110.
[0035] The downstream microfluidic channel 104 is connected to the
fluid outlet 108 and communicates capillary action to the fluid
outlet 108. Such capillary action is substantial enough to resist
flow of fluid from the fluid outlet 108 into the chamber 102 as may
be induced by negative pressure applied to the negative-pressure
port 110. Such capillary action may be provided by the microfluidic
channel 104, particularly if it is relatively narrow with respect
to the properties of the fluid. Sufficient capillary action may
additionally or alternatively be provided by a downstream
microfluidic component, such as a microfluidic network or droplet
ejector.
[0036] In operation, fluid may be applied to the fluid inlet 106
from an upstream source, such as a vented fluid reservoir. Negative
pressure may be applied to the negative-pressure port 110. When
negative pressure is applied to the negative-pressure port 110, the
resulting reduced pressure in the chamber 102 draws fluid through
the inlet channel 114 and causes a droplet 116 of fluid to form at
the fluid inlet 106. The droplet 116 remains at the fluid inlet 106
until detachment, as may be determined by surface tension, contact
angle, liquid mass, gravity, or similar factor. The droplet 116
breaks free and falls towards the lower portion of the chamber 102.
Droplets 116 may collect as bulk fluid 112 at the bottom of the
chamber 102. At the same time, capillary action provided by the
downstream microfluidic channel 104 and any other downstream
microfluidic component communicating with the channel 104 reduces
the effect of the negative pressure on the bulk fluid 112 at the
bottom of the chamber 102 to reduce the risk that fluid 112 is
drawn into the negative-pressure port 110.
[0037] FIG. 2 shows an example device 200. Features and aspects of
the other devices and systems described herein may be used with the
device 200 and vice versa. Like reference numerals denote like
elements and description of like elements is not repeated here.
[0038] The device 200 includes a chamber 102, a downstream
microfluidic channel 104, and a fluid inlet 106, a fluid outlet
108, and a negative-pressure port 110 provided to the chamber 102,
as described elsewhere herein.
[0039] The device 200 further includes a first droplet ejector 202
at an end of the downstream microfluidic channel 104. An array of
droplet ejectors 202 may be provided. The first droplet ejector 202
is to eject fluid droplets to draw fluid through the downstream
microfluidic channel 104. Further, the first droplet ejector 202
provides capillary action to reduce the tendency for fluid 112 in
the chamber 102 to be drawn towards to the negative-pressure port
110.
[0040] The device 200 further includes a target microfluidic
network 204 that communicates with the downstream microfluidic
channel 104. The target microfluidic network 204 is situated
between the chamber 102 and the first droplet ejector 202. The
target microfluidic network 204 performs a process with fluid drawn
through the microfluidic channel 104 by action of the first droplet
ejector 202.
[0041] The target microfluidic network 204 may include a passive
component, such as a network of microfluidic channels, which may be
made of silicon, silicon oxide, photoresist, polydimethylsiloxane
(PDMS), cyclic olefin copolymer (COC), other plastics, glass, or
other materials that may be made using micro-fabrication
technologies. The target microfluidic network 204 may contain a
solid compound to interact with fluid delivered by the channel 104.
A solid compound may be solid in bulk, may be a powder or
particulate, may be integrated into a fibrous material, or
similar.
[0042] The target microfluidic network 204 may include an active
component. Examples of active components include a pump, sensor,
mixing chamber, channel, heater, reaction chamber, droplet ejector,
or similar component to perform further action on fluid delivered
by the channel 104.
[0043] In various examples, the target microfluidic network 204
includes microfluidic structure to implement an analytical process,
such as a nucleic acid testing process that uses nucleic acid
amplification (NAT), such as polymerase chain reaction (PCR),
real-time or quantitative polymerase chain reaction (qPCR), reverse
transcription polymerase chain reaction (RT-PCR), loop mediated
isothermal amplification (LAMP), and similar.
[0044] The device 200 further includes a second droplet ejector 206
connected to the negative-pressure port 110 to provide negative
pressure or partial vacuum to the chamber 102. An array of droplet
ejectors 206 may be provided. The second droplet ejector 206 may be
connected to the negative-pressure port 110 by a negative-pressure
channel 118. The second droplet ejector 206 is to eject fluid
droplets to draw fluid through the negative-pressure channel 118
and away from the chamber 102 to induce a negative pressure in the
chamber 102.
[0045] The first and second droplet ejectors 202, 206 may be formed
at a substrate and such a substrate may have multiple layers. The
substrate may include silicon, glass, photoresist (e.g., SU-8), or
similar materials. A droplet ejector 202, 206 may include a jet
element, such as a resistive heater, a piezoelectric element, or
similar device that may implement inkjet droplet jetting
techniques, such as thermal inkjet (TIJ) jetting. The jet element
is controllable to draw fluid from the respective channel 104, 118
to jet fluid droplets out an orifice. An array having any number of
droplet ejectors 202, 206 may be provided.
[0046] The downstream and negative pressure channels 104, 118 may
be primed with fluid. For example, the downstream microfluidic
channel 104 may be preloaded with a drive fluid or a working fluid.
A drive fluid serves to communicate negative pressure and be
ejected without being used by the analytical process implemented by
the target microfluidic network 204. Working fluid may be used by
the target microfluidic network 204. The negative pressure channel
118 may be preloaded with a drive fluid. Movement of the drive
fluid away from the negative-pressure port 110 induces negative
pressure in the chamber 102. In other examples, a channel 104, 118
is partially filled with drive fluid. Specifically, the downstream
microfluidic channel 104 may be empty of drive fluid in a segment
upstream of the target microfluidic network 204, so as to reduce
the likelihood of contamination of the target microfluidic network
204 with drive fluid. Likewise, a small segment of the channel 104
downstream of the target microfluidic network 204 may be empty of
drive fluid, so as to reduce the likelihood of contamination of the
target microfluidic network 204 in case of a small amount of
backflow.
[0047] In some examples, the devices and systems described herein
can be used with a method for providing fluid to a chamber by
application of a negative pressure. An example method includes
applying a negative pressure to a negative-pressure port of a
chamber to draw a droplet of a fluid from a fluid inlet of the
chamber into the chamber; collecting the droplet at a fluid outlet
of the chamber, in which the fluid outlet positioned below the
fluid inlet relative to a force of gravity; and communicating
capillary action from a downstream microfluidic channel to the
fluid outlet of the chamber. The capillary action is to resist flow
of the fluid from the fluid outlet into the chamber induced by the
negative pressure applied to the negative-pressure port.
[0048] The method can further include ejecting droplets using a
droplet ejector at an end of the downstream microfluidic channel to
draw fluid through the downstream microfluidic channel.
[0049] The method can further include performing a process with the
fluid at a target microfluidic network communicating with the
downstream microfluidic channel between the chamber and the droplet
ejector.
[0050] A nucleic acid amplification process can be performed with
the fluid at the target microfluidic network.
[0051] The method can further include ejecting droplets using a
droplet ejector connected to the negative-pressure port to apply
the negative pressure to the negative-pressure port.
[0052] FIG. 3 shows an example method 300. The method 300 may be
performed by any of the systems and devices described herein, such
as the device 200 which will be used as an example. The method
starts at block 302.
[0053] At block 304, negative pressure is applied to a
negative-pressure port 110 of a chamber 102 to draw a droplet 116
of a fluid from a fluid inlet 106 of the chamber 102 into the
chamber 102. Negative pressure may be applied at the negative
pressure port 110 by ejecting droplets using a droplet ejector 206
in fluid communication with the negative-pressure port 110.
[0054] At block 306, the droplet 116 is collected at a fluid outlet
108 of the chamber 102. The fluid outlet 108 is positioned below
the fluid inlet 106 and the droplet 116 falls from the fluid inlet
106 towards the fluid outlet 108. The droplet 116 may accumulate as
fluid 112 at the bottom of the chamber 102. A reaction or other
fluid manipulation may take place at the bottom of the chamber
102.
[0055] During this process, as shown at block 308, a force due to
capillary action is communicated from a downstream microfluidic
channel 104 to the fluid outlet 108 of the chamber 102. Capillary
action resists flow of the fluid 112 from the vicinity of the fluid
outlet 108 further back into the chamber 102, as may be induced by
the negative pressure applied to the negative-pressure port 110.
Capillary action may be provided by the downstream microfluidic
channel 104, a target microfluidic network 204 that communicates
with the downstream microfluidic channel 104, a droplet ejector 202
that terminates the downstream microfluidic channel 104, or a
combination of such. Backflow of fluid 112, such as flow into the
negative-pressure port 110, may thus be prevented.
[0056] Once the fluid 112 has undergone a sufficient amount of
accumulation, reaction, or other manipulation, then the fluid 112
may be drawn through the downstream microfluidic channel 104 and
into the target microfluidic network 204 to perform an analytical
process, at block 310. Drawing fluid in this manner may include
ceasing the negative pressure at the negative-pressure port 110 and
ejecting droplets using a droplet ejector 202 at an end of the
downstream microfluidic channel 104 to induce negative pressure in
the downstream microfluidic channel 104 and target microfluidic
network 204. The method 300 ends at block 312.
[0057] The analytical process performed at the target microfluidic
network 204 may include a nucleic acid testing process. For
example, with reference to the example device 400 shown in FIG. 4,
a biological sample, such as a DNA/RNA sample, may be concentrated
around a permanent magnet 402 located within a chamber 102 or
embedded in a wall of the chamber 102. Features and aspects of the
other devices and systems described herein may be used with the
device 400 and vice versa. Like reference numerals denote like
elements and description of like elements is not repeated here.
[0058] Fluid provided to the inlet channel 114 may include a
DNA/RNA sample mixed with paramagnetic microbeads. A microbead
surface has physical or chemical affinity to an analyte of
interest, for example, a DNA molecule or a particular protein.
Negative pressure is applied to a negative pressure port 110 to
draw droplets 116 of the fluid into the chamber 102 to interact
with the magnet 402. The magnet attracts the paramagnetic
microbeads from the other material of the sample, thus
concentrating the analyte. The fluid 112 may be provided with a
residence time near the magnet 402, enhancing concentration.
[0059] The negative pressure may be ceased once sufficient analyte
is collected. Then, the fluid 112 may be drawn from the chamber 102
by activation of a droplet ejector 202 communicating with a fluid
outlet 108 of the chamber 102.
[0060] Subsequently, another fluid may be provided to the inlet
channel 114 and brought into the chamber 102 to release the
concentrated analyte from the magnet 402. Such a fluid may include
an elution buffer that elutes the analyte and allows the analyte to
be drawn into the target microfluidic network 204 to undergo a
nucleic acid testing process implemented by the target microfluidic
network 204.
[0061] FIG. 5 shows an example device 500. Features and aspects of
the other devices and systems described herein may be used with the
device 500 and vice versa. Like reference numerals denote like
elements and description of like elements is not repeated here.
[0062] The device 500 includes a first ejection unit 502 connected
to a downstream end of a downstream microfluidic channel 104 that
communicates with a fluid outlet 108 of a chamber 102. The first
ejection unit 502 includes a fluid reservoir 504 and a droplet
ejector 506 or array thereof that is fed with fluid by the fluid
reservoir 504. The fluid reservoir 504 may be primed with a fluid
that is ejected to generate a negative pressure in the downstream
microfluidic channel 104 to draw fluid 112 from the chamber 102
through a target microfluidic network 204.
[0063] The device 500 includes a second ejection unit 508 connected
to a downstream end of a negative pressure channel 118 that
communicates with a negative-pressure port 110 of the chamber 102.
The second ejection unit 508 includes a fluid reservoir 510 and a
droplet ejector 512 or array thereof that is fed with fluid by the
fluid reservoir 510. The fluid reservoir 510 may be primed with a
fluid that is ejected to generate a negative pressure in the
negative pressure channel 118 to draw fluid droplets 116 into
chamber 102 via a fluid 106.
[0064] The droplet ejectors 506, 512 may be formed at the same
semiconductor substrate 514. Alternatively, the droplet ejectors
506, 512 may be formed at different semiconductor substrates that
may be physically joined by, for example, being molded into a
single flat package (e.g., semiconductor slivers that are
epoxy-molded together). Alternatively still, the droplet ejectors
506, 512 may be provided in two separate packages or
printheads.
[0065] The droplet ejectors 506, 512 may eject to a waste area 516,
such as an absorbent material.
[0066] In an example application, which also applies to the other
devices described herein, the device 500 may be used for reagent
rehydration. A dried reagent 518, such as a solid or powdered
material, may be located in the chamber 102. Rehydration fluid,
such as water, may be drawn into the chamber 102 by activating the
second ejection unit 508 to provide a negative pressure in the
chamber 102, thereby causing droplets of rehydration fluid to be
pulled into the chamber 102 from the fluid inlet 106. The
rehydration fluid collects at the bottom of the chamber 102 and
rehydrates the dried reagent 518. When rehydration is complete, the
resulting fluid reagent may be draw into the target microfluidic
network 204 by activation of the first ejection unit 502. The
second ejection unit 508 may be stopped so as to not resist fluid
movement out of the outlet 108 of the chamber 102. Alternatively,
the second ejection unit 508 may be run until its driving fluid is
completely ejected thereby releasing the partial vacuum at the
negative-pressure port 110 with no sensor or other intervention
required.
[0067] The dried reagent 518 may be a freeze-dried PCR master mix
for use at the target microfluidic network 204 that implements a
nucleic acid testing process.
[0068] FIG. 6 shows an example device 600. Features and aspects of
the other devices and systems described herein may be used with the
device 600 and vice versa. Like reference numerals denote like
elements and description of like elements is not repeated here.
[0069] A plurality of target microfluidic networks 204, 602 may be
provided downstream of a chamber 102 that is provided fluid through
vacuum induction of fluid droplets 116 by a negative-pressure port
110. The target microfluidic networks 204, 602 may be arranged in
parallel. For example, each target microfluidic networks 204, 602
may be may communicate with the chamber via a respective downstream
microfluidic channel 104, 604 that extend from a common channel 606
that connects to an outlet of the chamber 102.
[0070] Fluid may be selectively drawn through the target
microfluidic networks 204, 602 by selective activation of
respective downstream ejection units 502, 608.
[0071] In one example application, the target microfluidic networks
204, 602 may be used to perform different nucleic acid testing
processes (e.g., different heating cycle programs, etc.) to the
same sample collected at the chamber 102. In another example, the
target microfluidic networks 204, 602 may be used to perform the
same nucleic acid testing process to different fluids drawn from
the chamber 102. That is, an analyte at different concentrations
may be drawn into the target microfluidic networks 204, 602 at
different times.
[0072] FIG. 7 shows an example device 700. Features and aspects of
the other devices and systems described herein may be used with the
device 700 and vice versa. Like reference numerals denote like
elements and description of like elements is not repeated here.
[0073] A plurality of chambers 702, 704 may be vertically arranged.
Fluid may be provided to an inlet channel 706 at an upper chamber
702. Fluid droplets 708 may be drawn into the upper chamber 702
through a fluid inlet 710 by negative pressure applied to the
chamber 702 via an upper negative-pressure port 712. Droplets
collect as fluid 714 at the bottom of the upper chamber 702 near an
upper fluid outlet 716. The upper fluid outlet 716 communicates
with an inlet channel 718 at a lower chamber 704. Fluid droplets
720 may be drawn into the lower chamber 704 through a fluid inlet
722 that communicates with the inlet channel 718 by negative
pressure applied to the chamber 704 via a lower negative-pressure
port 724. Droplets collect as fluid 726 at the bottom of the lower
chamber 704 near a lower fluid outlet 728.
[0074] Control of the device 700 may be effected by selectively
applying negative pressure to the upper negative-pressure port 712,
upper fluid outlet 716, lower negative-pressure port 724, and lower
fluid outlet 728, by respective channels 730, 732, 734, 736.
Negative pressure may be applied to the channels 730, 732, 734, 736
using droplet ejectors.
[0075] For example, a DNA/RNA sample may be drawn into the upper
chamber 702 to be concentrated by providing a fluid containing the
DNA/RNA sample to the inlet channel 706 and by applying negative
pressure to the channel 730. A magnet may be provided in the upper
chamber 702 to assist in concentration, as described elsewhere
herein. The fluid may include a lysis buffer. After concentration,
the remaining fluid may be drawn through the channel 732 to waste.
The sample in the upper chamber 702 may be washed. The concentrated
sample may then be eluted from the upper chamber 702 and drawn into
the lower chamber 704 by applying a negative pressure to the
channel 734. Once accumulated in the lower chamber 704, the
prepared sample may be metered out to a target microfluidic network
connected to the channel 736 by applying a negative pressure to the
channel 736. The target microfluidic network may then be controlled
to perform a nucleic acid testing process on the sample.
[0076] FIG. 8 shows an example system 800. Features and aspects of
the other devices and systems described herein may be used with the
system 800 and vice versa. Like reference numerals denote like
elements and description of like elements is not repeated here.
[0077] The system 800 includes a cartridge 802 including a chamber
102 or arrangement of chambers, as discussed elsewhere herein,
including a negative-pressure port to receive a negative pressure
to draw droplets of fluid into the chamber 102 for use by a
downstream target microfluidic network. Such components may be
contained within a cartridge housing 804.
[0078] The cartridge 802 further includes a signal interface 806 at
the housing 804. The signal interface 806 is electrically connected
to a droplet ejector that applies a negative pressure to the
chamber 102. The signal interface 806 may include an electrical
contact.
[0079] The system 800 further includes an analysis device 808. The
analysis device 808 includes a processor 810 installed within a
housing 812. The processor 810 is connected to an interface 814
that may include an electrical contact. The interface 814 provides
for communications between the processor 810 and the signal
interface 806 of the cartridge 802. The analysis device 808 may
allow for user control of a process implemented by a cartridge 802.
The analysis device 808 may be installed at a lab or other location
in an upright orientation.
[0080] The housing 804 of the cartridge 802 includes a feature 816
shaped to position a fluid outlet of the chamber 102 below a fluid
inlet of the chamber 102 relative to a force of gravity G when the
feature 816 is mated with a complementary feature 818 at the
housing 812 of the analysis device 808. The features 816, 818 may
include a mating groove and ridge, for example.
[0081] The cartridge 802 is removably mechanically connected to the
analysis device 808 by way of the mating features 816, 818.
Further, when the analysis device 808 is upright, the mating
features 816, 818 force the cartridge 802 to be connected in the
correct orientation relative to a force of gravity G, so that the
chamber 102 may function as described herein.
[0082] When connected, the signal interface 806 of the cartridge
802 may receive a signal from the processor 810 via the interface
814 of the analysis device 808, and such signal may drive a droplet
ejector of the cartridge 802 to apply the negative pressure to the
chamber 102 to operate the chamber 102 as described elsewhere
herein.
[0083] FIG. 9 shows an example device 100 installed at a centrifuge
900. Any of the devices and systems described herein may be so
installed at a rotating disc or other rotational element of a
centrifuge 900. The device 100 is oriented so that its chamber 102
narrows in a direction of a centrifugal force F generated by
rotation of the centrifuge 900. That is, the chamber 102 may be
shaped and oriented with respect to the centrifuge 900 to collect
fluid at its fluid outlet 108 under centrifugal force F. In this
way, centrifugal force F may be used to mimic the effect of
gravity. Other features and aspects of the device 100 may be as
described elsewhere herein.
[0084] As should be apparent from the above, the techniques
described herein allow for vacuum controlled fluid manipulations at
microfluidic scale. A mesofluidic chamber is provided with a
negative pressure port that may be controlled by a microfluidic
droplet ejector without direct human intervention.
[0085] It should be recognized that features and aspects of the
various examples provided above can be combined into further
examples that also fall within the scope of the present disclosure.
In addition, the figures are not to scale and may have size and
shape exaggerated for illustrative purposes.
* * * * *