FLUIDIC BRIDGE DEVICE AND
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority to U.S. Provisional Application No.
62/142,063 filed April 2, 2015, the entire contents of which are incorporated herein by reference.
[0002] This application is generally related to U.S. Patent No. 6,374,684 entitled "Fluid
Control and Processing System," filed August 25, 2000; and U.S. Patent No. 8,048,386 entitled
"Fluid Processing and Control," filed February 25, 2002, each of which the entire contents are
incorporated herein by reference for all purposes.
BACKGROUND OF THE INVENTION
[0003] The present invention relates generally to fluid manipulation and, more particularly, to
a device, system and method for transporting a fluid sample between sample processing devices.
[0004] The analysis of fluids such as clinical or environmental fluids generally involves a
series of processing steps, which can include chemical, optical, electrical, mechanical, thermal,
or acoustical processing of the fluid samples. Whether incorporated into a bench-top instrument,
a portable analyzer, a disposable cartridge, or a combination thereof, such processing typically
involves complex fluidic assemblies and processing algorithms.
[0005] Conventional systems for processing fluid samples employ a series of regions or
chambers each configured for subjecting the fluid sample to a specific processing step. As the
fluid sample flows through the system sequentially from region or chamber to a subsequent
region or chamber, the fluid sample undergoes the processing steps according to a specific
protocol. Because different protocols require different configurations, conventional systems
employing such sequential processing arrangements are not versatile or easily adaptable to
different protocols or processing and analysis systems. A single device may not provide the
functionality needed to perform all the processing steps that analysis of a sample may require.
As a result, a user may need to utilize different devices in processing a sample.
BRIEF SUMMARY OF THE INVENTION
[0006] The present invention provides an apparatus, system and method for manipulating
fluid samples, in particular, for transporting a fluid sample between a first and a second sample
processing device. In some aspects of the invention, the first sample processing device relates to
sample preparation and the second sample processing device relates to analysis of the prepared
sample and/or further processing of the sample.
[0007] Some embodiments of the invention include methods, systems and devices that
facilitate transport of a fluid sample prepared, at least in part, by a first sample processing device
to a second sample processing device for further processing or analysis, such as detection of a
target within the fluid sample. In some aspects, the invention provides a fluidic bridge device
through which the prepared sample can be transported from the sample preparation device to the
processing and/or analysis device. In some embodiments, the fluidic bridge is an elongate
member having one or more fluid flow conduits extending between fluid-tight couplings on
opposing ends of the bridge. The fluid-tight couplings are adapted for coupling with each of the
first and second sample processing devices at a fluid tight junction so as to fluidly couple the
first and second processing devices.
[0008] In some embodiments, the first sample processing device is a sample preparation
apparatus that employs a rotary valve configuration to control fluidic movement within a
cartridge that allows fluidic communication between a fluid sample processing region selectively
with a plurality of chambers in the cartridge. Non-limiting exemplary chambers can include, a
sample chamber, a reagent chamber, a waste chamber, a wash chamber, a lysate chamber, an
amplification chamber, and a reaction chamber. The fluid flow among the fluid sample
processing region and the chambers is controlled by adjusting the position of the rotary valve. In
this way, the metering and distribution of fluids in the apparatus can be varied depending on the
specific protocol, which allows sample preparation to be adaptable to different protocols such as
may be associated with a sample or different types of samples. For example, the first sample
processing apparatus can include a means for cell lysis, e.g., a somcation means so that bacteria
and cells in a fluid sample to be analyzed can be lysed. Additional lysis means suitable for use
with the instant invention are well known to persons of skill in the art, and can include, chemical
lysis, mechanical lysis, and thermal lysis. In some embodiments, the sample includes bacteria,
eukaryotic cells, prokaryotic cells, or viral particles.
[0009] In one aspect, sample processing comprises sample processing steps that are performed
from initial sample preparation steps, intermediate processing steps, and/or further processing
steps to facilitate a final reaction for detection of a target analyte in the fluid sample. For
example, sample processing can include preliminary preparation steps, such as filtering,
grinding, mincing, concentrating, trapping debris or purifying a rough sample, or steps for
fragmenting of DNA or RNA of the target analyte, such as by sonication or other mechanical or
chemical means. Sample processing may include various intermediate processing steps, such as
filtering, amplification, or further processing of nucleic acids in the sample, including but not
limited to bisulfite treatment, reverse transcription, or fragmentation of DNA or RNA. Sample
processing may further include final processing and analyte detection steps, such as final
amplification, filtering and mixing with reagents for a reaction to detect the target analyte, which
detection can include optical, chemical and/or electrical detection. In some embodiments, the
first sample processing device is configured to perform initial and/or intermediate processing
steps, while the second sample processing device is configured to perform intermediate and/or
final processing, such as any of those described herein or as would be known to one of skill in
the art of target analyte detection. In some embodiments, the first sample processing device is
configured to perform at least a first step in the overall sample processing and transport of the
fluid sample to the second sample processing device to perform at least a subsequent step in the
process, which can include detection of the target analyte. In another embodiment, the fluid
sample can be transported from the second sample processing device back to the first sample
processing device for additional processing a d detection of analytes.
[0010] I some embodiments, the first sample processing device can be a fluid control and
processing system for controlling fluid flow among a plurality of chambers within a cartridge,
the cartridge comprising a housing including a valve body having a fluid sample processing
region continuously coupled fluidicly with a fluid displacement chamber. The fluid
displacement chamber is depressurizable to draw fluid into the fluid displacement chamber and
pressunzable to expel fluid from the fluid displacement chamber. The fluid sample processing
region includes a plurality of fluid processing ports each fluidicly coupled with one of a plurality
of external ports of the valve body. The fluid displacement chamber is fluidicly coupled with at
least one of the external ports. The valve body is adjustable with respect to the plurality of
chambers within the housing to allow the external ports to be placed selectively in fluidic
communication with the plurality of chambers. In some embodiments, the valve body is
adjustable with respect to the housing comprising the plurality of chambers, to place one external
port at a time in fluidic communication with one of the plurality of chambers.
[0011] In some embodiments of the cartridge, the fluid sample processing region can be
disposed between the fluid displacement chamber and at least one fluid port. The term "fluid
processing region" refers to a region in which a fluid is subject to processing including, without
limitation, chemical, optical, electrical, mechanical, thermal, or acoustical processing. For
example, chemical processing may include a catalyst; optical processing may include UV
activation; electrical processing may include electroperation or electrophoresis or isoelectric
focusing; mechanical processing may include mixing, filtering, pressurization, and cell
disruption; thermal processing may include heating or cooling; and acoustical processing may
include the use of ultrasound. In some embodiments, the fluid processing region may include an
active member, such as a filter, to facilitate processing of the fluid. Non-limiting exemplary
active members that are suitable for use with the instant invention include a microfluidic chip, a
solid phase material, a filter or a filter stack, an affinity matrix, a magnetic separation matrix, a
size exclusion column, a capillary tube, or the like. Suitable solid phase materials include,
without limitation, beads, fibers, membranes, filter paper, lysis paper impregnated with a lysing
agent, glass wool, polymers, or gels. In some embodiments, the fluid processing region is used
to prepare a sample for further processing, for instance, in a second fluid processing device
fluidly coupled with the first fluid sample processing device through the fluidic bridge.
Additional active members suitable for use with the instant invention are well known to persons
of skill in the art. In some embodiments, an energy transmitting member is operatively coupled
with the fluid sample processing region for transmitting energy thereto to process fluid contained
therein. In some embodiments, the valve body includes a crossover channel, and the valve body
is adjustable with respect to the plurality of chambers to place the crossover channel in fluidic
communication with two of the chambers concurrently. The cartridge housing can include one
or more branches that extend to one or more transfer ports to which a reaction vessel can be
attached so as to facilitate transfer of fluid sample from a chamber of the cartridge into the
reaction vessel. In some embodiments, the reaction vessel extends from the housing of the
cartridge. These aspects can be understood further by referring to U.S. Patent No. 8,048,386. It
is understood that in some embodiments, fluid may flow in either direction into or out of the
transfer ports such that fluid flow is not limited in any particular direction. For example, in an
embodiment having a pair of transfer ports, air may be pumped into or evacuated from one of the
pair of transfer ports to facilitate flow of the fluid sample into a conduit of the reaction vessel
through the transfer port.
[0012] In some embodiments, the fluidic bridge includes an elongated bridge having one or
more fluid channels extending between one or more fluid-tight couplings on opposing ends of
the elongate bridge. The one or more fluid-tight couplings on a first end of the elongated bridge
are adapted for coupling with a first sample processing device at a fluid tight junction, the one or
more fluid-tight couplings on a second end of the elongate bri dge opposite the first end adapted
for coupling with a second sample processing device. In some embodiments, the one or more
fluid-tight coupling on the first end are included within a fluid interface adapted to couple with
one or more transfer ports of a sample processing cartridge of the first sample processing device
that are also suited for coupling with a reaction vessel, such as that described above, thereby
allowing a particular configuration of sample cartridge to be used with either a reaction vessel or
the fluidic bridge. In some embodiments, the fluidic bridge includes an elongated bridge having
one or more fluid channels not including a sample preparation chamber. The elongated bridge
can be defined by a planar frame supporting the one or more fluid-tight couplings on each end.
In one aspect, the planar frame comprises a material sufficiently stiff so as to support the bridge
when attached to the first sample processing device at one end. The fluidic bridge may be
formed of a polymer- based material or any suitable material for transporting a fluid sample.
[0013] In some embodiments, the one or more fluid channels have a cross-sectional lumen area
that does not substantially vary across the length of the fluid channel between respective fluidtight
couplings at the opposing ends of the fluidic bridge. The cross-sectional area of each of the
one or more fluid channels remains a substantially constant size and shape between respective
fluid-tight couplings. In some embodiments, the one or more fluid channels include two spaced
apart fluid channels that are spaced apart and dimensioned so as to be fittingly received within
two corresponding transfer ports in a sample processing cartridge housing. In some
embodiments, the bridge can include a supporting web structure separating the at least two
channels. In some embodiments, the bridge can be configured so that the volume of each of the
at least two channels between the first and second ends, does not substantially differ. In some
embodiments, the bridge can be configured so that the volume of at least one of the at least two
channels has a substantially different volume between the first and second ends of the fluidic
bridge.
[0014] In some embodiments, the one or more fluid channels can be adapted without a sample
preparation region within the fluidic bridge, meaning that the fluid channels do not include a
portion configured for initial sample preparation steps, such as initial filtering of debris from the
fluid sample, initial mixing with reagents, and/or initial fragmentation of the DNA of the target
analyte, such as a sonication chamber or sharp edges adapted for adapted for breaking or
fragmenting cells or DNA strands. In some embodiments, the one or more fluid channels can
include one or more regions adapted for providing controlled flow of the fluid sample, such as
may be used for transitive storage or collection of the fluid sample, which can be useful for
mixing, amplification or to facilitate control of the temperature of the fluid sample.
[0015] In some aspects, the fluid-tight couplings at the first end of the bridge comprise a stub
dimensioned to be fittingly received within one or more corresponding ports in the first sample
processing device so as to fluidly couple the one or more channels with the first sample
processing device. The stubs can be dimensioned to be fluidly coupled by a friction fit within
the corresponding ports in the first sample processing device, or a cartridge housing that is
inserted into the first sample processing device. In some embodiments, the bridge comprises at
least two fluid channels fed by two inlet stubs at the first end of the bridge that are fittingly
received within at least two transfer ports on the cartridge housing. The fluid-tight couplings at
the second end can also include stubs dimensioned to be fittingly received within one or more
corresponding ports in the second sample processing device or can interface with an adapter to
facilitate fluidic coupling with the second device. In some embodiments, the second device can
be a container or receptacle.
[0016] In some embodiments, the fluidic bridge includes a flange from which the inlet stubs
extend, the flange being engageable with a retaining member of the first sample processing
device so as to maintain the fluid tight coupling and position of the fluidic bridge when coupled
to the first sample processing device or cartridge that is inserted into the first sample processing
device. The first sample processing device or cartridge can also include a gasket surrounding the
plurality of transfer ports, the gasket being of a formabie material, such as an elastomeric
material, so that when the inlet portions of the first end of the fluidic bridge are fluidly coupled
with the at least two transfer ports the gasket member engages a proximal facing surface of the
flange so as to ensure a fluid-tight coupling. The distal end of the fluidic bridge can be of a
similar or identical structure so as to form fluid-tight couplings with similar transfer ports of a
second processing device, or alternatively, the distal end can be configured differently for
attachment to various differing devices. In some embodiments, the fluid tight couplings at
opposite ends of the fluidic bridge are substantially similar or identical and the first and/or
second sample processing device can include one or more adapters or attachments that facilitate
attachment of the distal end of the fluidic bridge to various differing sample processing devices.
[0017] In some embodiments, the fluidic bridge can include one or more features for further
processing of the fluid sample during transport there through. In some embodiments, the fluidic
bri dge can include at least one processing region in fluid communication with at least one of the
fluid channels, wherein the processing region is not a sample preparation chamber. In some
embodiments, at least a portion of the fluidic bridge is at least partly translucent or transparent so
as to allow optical detection/interrogation of fluid transported through the one or more fluid
channels or to allow confirmation that the fluid sample is passing through the bridge by visual
observation. In some embodiments, the bridge can include one or more features that can provide
an additional process step, for example, a chamber for chemical treatment, such as bisulfite
treatment, a pre-amplification chamber or filter, or features that facilitate passage of the fluid
sample through the bridge, for example, a gas permeable vent or a bubble trap.
[0018] In some embodiments, the fluidic bridge s formed, entirely or partly, of an opaque
material or includes an opaque coating on all or part of the device. This aspect may serve to
protect the device, or at least an interior of a portion of a fluid conduit therein, from ambient
light. In some embodiments, the fluidic bridge is substantially opaque and includes a window
portion that s transparent or semi-transparent so as to allow optical detection in a select portion
of the device.
[0019] In some embodiments of the invention, the fluidic bridge is of sufficient length and
dimension that when coupled with a cartridge mounted within a cartridge receiver of a first
sample processing device having a passageway, the elongated bridge extends through the
passageway and outside of the cartridge receiver of the first sample processing device to
facilitate transport of the prepared sample from the cartridge to a second sample processing
device positioned near the first sample processing device. In some embodiments, the fluidic
bridge includes a planar frame supporting and defining the one or more channels. The planar
frame comprises a sufficiently stiff material, typically a polymer-based material, so as to support
the one or more fluidic channels so that the bridge extends outside of the cartridge receiver so
that a user can readily attach the opposite end of the bridge to a desired second fluid sample
processing device. This configuration allows various differing types of devices to be used for the
second sample processing device, so long as the devices can be connected to the bridge member.
In some aspects, the bridge member can be directly connected to the second sample processing
device, or one or more adapters can be utilized to facilitate the connection.
[0020] Methods of transporting a fluid sample between a first and second sample processing
device are provided herein. A non-limiting exemplary method includes fluidly coupling first and
second sample processing devices by coupling an elongate fluidic bridge having one or more
fluid channels; and effecting flow of the fluid sample through the fluidic bridge by transmission
of an electronic instruction to the first and/or second device. In some aspects, fluid flow through
the o e or more channels ca be effected through pressurization/depressurization or by
displacement of the fluid sample by the first or second sample processing devices. It is
appreciated that the instruction for transport of the fluid sample through the bridge could be
received by either or both of the first and second sample processing device(s). For example, in
some embodiments, the fluid channel is depressurized from the second processing device. In
some embodiments the motive force can be pressure from first sample processing device and
depressurization from the second processing device. It is appreciated that various alternative
configurations may be used in providing motive force for transfer of the fluid sample through the
bridge with one or both of the first and second sample processing device(s).
[0021] In some embodiments, methods include introducing a fluid sample into a fluid
sampling device having a fluidic bridge coupled thereto at a first end of the fluidic bridge;
selecting a second sample processing device from a plurality of devices; and coupling the second
end of the fluidic bridge opposite the first end to the second sample processing device. Such
methods can further include performing a first sample processing step in the first sample
processing device; transporting the fluid sample from the first sample processing device to the
second sample processing device through the fluidic bridge coupled there-between; and
performing a second sample processing step within the second sample processing device. In
some embodiments, an analysis of the fluid sample can be performed within the second device or
the fluid can be transported back to the first sample processing device through the fluidic bridge
or transported to yet another device. In some embodiments, the method can include performing
an additional sample processing step and/or a sample analysis step while the fluid is transported
through or contained within the fluidic bridge. In some embodiments, the fluidic bridge can
include one or more sample processing features, such as a filter or pre~amplification chamber. In
some embodiments, the fluidic bridge can include, for example, a sample analysis feature, such
as a micro-well array, an isoelectric focusing region, or an optical detection window.
[0022] In some embodiments, method for processing an unprepared sample can include steps
of: receiving a sample processing cartridge at a cartridge receiver, the sample processing
cartridge comprising a unprepared fluidic sample to be analyzed, a plurality of processing
chambers fluidically interconnected by a moveable valve body; receiving an electronic
instruction to process the unprepared sample into a prepared sample from an assay processing
device coupled to the cartridge receiver; performing a sample preparation method to process the
unprepared sample into the prepared sample. In some embodiments, moving the sample can
include steps of: moving a cartridge interface unit to move the valve body to change fluidic
interconnections between the plurality of sample processing chambers; applying pressure to a
pressure interface unit to move fluid between the plurality of processing chambers according to
position of the valve body; and fluidically moving the prepared sample into an elongated fluidic
bridge that extends from the sample processing cartridge and fluidically interfaces with the assay
processing device to provide the prepared sample to the assay processing device.
[0023] In some embodiments, the system comprises a first sample processing device, a second
sample processing device, and a fluidic bridge coupleable with each of the first and second
sample processing devices so as to facilitate transport of a fluid sample between the first and
second sample processing device when coupled therebetween. n some embodiments, the second
sample processing device is included within a plurality of sample processing devices selectable
by a user, the fluidic bridge being interchangeable between plurality of the sample processing
devices. In some aspects, the plurality of sample processing devices, from which the second
sample processing device is selected, includes sample processing devices of differing types.
[0024] In some embodiments, a system comprises a first sample processing device, a second
sample processing device, and a fluidic bridge that includes an elongated bridge and one or more
fluid-tight coupling on opposite ends thereof fluidically coupleable with each of the first and
second sample processing devices. In some aspects, the elongated bridge includes one or more
channels extending between a first end and a second end of the elongated bridge. In some
embodiments, the one or more channels do not include a sample preparation chamber. The one
or more fluid-tight couplings on either end are adapted for fluidly coupling the one or more fluid
channels with the first sample processing device and second sample processing devices at a fluid
tight junction so that the first and second sample processing devices are in fluid communication
through the one or more channels when the fluidi c bri dge is coupled to each of the first and
second sample processing devices so as to facilitate transport of a fluid sample between the first
and second sample processmg devices.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 is an overview of a fluidic bridge device extending between a fi rs sample
processmg device and a second sample processing/analysis device to facilitate transport of a
prepared sample there-between, in accordance with aspects and embodiments of the invention.
[0026] FIGS 2A-2D illustrates an exemplar sample processing cartridge and an associated
reaction vessel for analysis within a conventional sample processing device.
[27] FIGS. 3A-3C illustrate a fluidic bridge for use with a sample processing cartridge to
allow transport of the fluid sample from the first sample processing device to a selected second
sample processing device, in accordance with aspects and embodiments of the invention.
[0028] FIGS. 4A-4D illustrates exemplary fluidic bridge devices, in accordance with aspects
and embodiments of the invention.
[0029] FIGS. 5A-5B illustrates an exemplary fluid-tight coupling between a fluidic bridge and
a sample processing cartridge system according to an embodiment of the present invention.
[0030] FIG. 6 illustrates a sample processing device adapted for use with a sample cartridge
and the fluidic bridge to facilitate transport of a fluid sample to an external processing and/or
analysis device, in accordance with aspects and embodiments of the invention.
[0031] FIGS. 7A-7B illustrates an exemplary sample cartridge and use of the cartridge within
the sample preparation and analysis device in FIG. 6, respectively.
[0032] FIGS. 8A-8B illustrates an exemplary sample processing cartridge with a fluidic bridge
to facilitate transport of a fluid sample prepared in the cartridge to a second sample processing
device, in accordance with aspects and embodiments of the invention.
[0033] FIGS. 9- 0 depict methods of transporting a fluid sample between a first sample
processing device and a second sample processing device, in accordance with aspects and
embodiments of the invention
[0034] FIGS. 11A-l IE depict alternative embodiments of a fluidic bridge device in accordance
with aspects and embodiments of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0035] The present invention relates generally to system, device and methods for fluid
manipulation, in particular, for transport of a fluid sample from a first sample processing device
to a second sample processing device by way of a fluidic bridge.
I. Exemplary System Overview
[0036] In one aspect, the invention relates to a fluidic bridge having one or more fluid conduits
that are fluidly coupleable with each of a first and second fluid sampling device to facilitate
transport of a fluid sample through the one or more fluid conduits between the first and second
devices. In some embodiments, the first sampling device includes a sample processing cartridge
for preparation and/or analysis of a fluid sample and the fluidic bridge fluidly couples with the
sample processing cartridge so as to facilitate transport of the prepared fluid sample to the
second processing device, which can be any of various devices desired for analyzing biological
samples or further processing thereof. In some embodiments, the one or more conduits do not
include a sample preparation region. In some embodiments, the fluidic bridge can include a
variety of features, such as one or more specific regions, where each region is adapted for a
sample processing procedure or a sample analysis procedure. Non-limiting exemplar}' sample
processing procedures can include, filtration, concentration, incubation, chemical treatment and
amplification. Additional sample processing procedures suitable for use with the invention are
well known to persons of skill in the art. Non-limiting exemplary sample analysis procedures
can include, hybridization, optical interrogation, iso-electric focusing, antibody binding and
detection (e.g. ELISA), sequencing, chromatography, and lateral flow chromatography.
Additional sample analysis procedures suitable for use with the invention are well known to
persons of skill in the art. The fluidic bridge can further include one or more features, including
filters, traps, membranes, ports and windows, to allow additional processing steps during
transport of the fluid sample to the second sample processing device.
A. First Sample Processing Deviee
[0037] The first sample processing device can be any device configured to perform a process
step relating to the preparation and/or analysis of a fluid sample according to any of the methods
described herein. In some embodiments, the first sample processing device is a sample
preparation device configured to prepare a sample for analysis, such as detection of a nucleic
acid target in a nucleic acid amplification test (NAAT), e.g.. Polymerase Cham Reaction (PCR)
assay. Preparation of a fluid sample generally involves a series of processing steps, which can
include chemical, electrical, mechanical, thermal, optical or acoustical processing steps
according to a specific protocol. Such steps can be used to perform various sample preparation
functions, such as cell capture, cell lysis, binding of analyte, and binding of unwanted material.
Such a sample preparation device can employ a sample processing cartridge that includes one or
more chambers suited to perform the sample preparation steps, such a cartridge s shown and
described in U.S. Patent No. 6,374,684, entitled "Fluid Control and Processing System" filed
August 25, 2000, and U.S. Patent No, 8,048,386, entitled "Fluid Processing and Control," filed
February 25, 2002, and are incorporated herein by reference in their entirety for all purposes.
[0038] A sample processing cartridge suitable for use with the invention, can include one or
more transfer ports through which the prepared fluid sample can be transported into a reaction
1
vessel for analysis. FIGS. 2A-2D illustrate an exemplary sample processing cartridge 0 and
associated reaction vessel 8 to allow sample preparation and analysis within a sample
processing device 100 that performs both sample preparation and analysis. As can be seen in
FIG. 2A, the sample processing cartridge 110 includes various components including a ma
housing having one or more chambers for sample preparation to which a reaction vessel 18, for
sample analysis, is attached. After the sample processing cartridge 110 and the reaction vessel
8 are assembled (as shown in FIG. 2B), a fluid sample is deposited within a chamber of the
cartridge and the cartridge is inserted into the sample processing device shown in FIG. 2D. The
device then performs the processing steps needed to perform sample preparation and the
prepared sample is transfer through one of a pair of transfer ports into fluid conduit of a reaction
vessel attached to the cartridge housing. The prepared fluid sample is transported into a
chamber of the reaction vessel 8 (see FIG. 2C) while an excitation means and an optical
detection means of the device 110 are used to detect optical emissions that indicate the presence
or absence of a target nucleic acid analyte of interest, e.g., a bacteria, a virus, a pathogen, a toxin,
or other target. It is appreciated that such a reaction vessel could include various differing
chambers, conduits, or micro-well arrays for use in detecting the target analyte. An exemplary
use of such a reaction vessel for analyzing a fluid sample s described in commonly assigned
U.S. Patent Application No. 6,818,185, entitled "Cartridge for Conducting a Chemical
Reaction," filed May 30, 2000, the entire contents of which are incorporate herein by reference
for all purposes.
. Fluidic Bridge
[0039] In some embodiments, the invention includes a fluidic bridge that can be fluidically
coupled to one or more transfer ports of a sample processing cartridge housing associated with a
f rst sample processing device for use in transporting a prepared fluid sample to a second sample
processing device external to the first device. This allows for improved versatility of analysis of
the sample as compared to confining processing and analysis of the sample to the functionality
associated with a single device. For example, a user may wish to utilize a different device to
analyze or perform further processing from the first sample processing device. However,
preparation of the sample can be a time consuming and laborious process to perform by hand
such that it would be advantageous to perform sample preparation within the first sample
preparation device, which can perform the sample preparation steps according to an automated
process. This expedites the sample preparation process and allows for high volumes of samples
to be prepared. By utilizing a fluidic bridge device instead of the reaction vessel, as shown in
FIGS. 3A-3B, the user can utilize the first sample processing device to prepare the sample in a
sample processing cartridge 0 and then subsequently transport the prepared sample through the
attached fluidic bridge 10 to a selected second device, which can be any of a number of
processing devices 200, 200', 200", as shown in FIG. 3B. Such devices can be configured to
couple directly to a distal end of the fluidic bridge 10 or can utilize one or more adapters to
facilitate fluid-tight coupling between the assay or processing devices and the fluidic bridge 0 .
[0040] In some embodiments, the fluidic bridge is coupled to each of the first and second
sample processing devices at the same time, such that the first device can facilitate transport of
the fluid sample through the bridge to the second device. In some embodiments, the fluidic
bridge device can be coupled to the first and second devices at different times. For example, a
sample cartridge having a fluidic bridge attached thereto can be placed in a sample processing
device for preparation of the sample and then removing the sample cartridge, with the fluidic
bridge attached, from the first sample processing device, and then attaching the open end of the
fluidic bridge to the second sample processing device. Alternatively, the fluidic bridge can be
attached to the second processing device and not the first processing device. In such an
embodiment, a cartridge containing a prepared sample from the first sample processing device
can be removed from the first device and connected to the fluidic bridge which is already
attached to the second device. In such embodiments, the second device can be configured to
facilitate transport from the cartridge device into the second device.
C. Second Sample Processing Device
[0041] The second sample processing device can be any device configured to perform a
process step relating to preparation and/or analysis of a fluid sample according to any of the
methods described herein, or known to a person of ordinary skill in the art. In some
embodiments, the second sample processing device can be internal to or located within a
common housing with the first sample processing device. For example, the first and second
sample processing devices can be separate and independent modules that are both contained in a
larger housing. In some embodiments, the second sample processing device can be a second
sample processing cartridge that is configured to perform sample analysis on the prepared
sample. In such embodiments, the sample processing cartridge contains the reaction vessel for
conducting an analysis on the prepared sample. As above, this system configuration can be used
to expedite the processing of a sample from which separate aliquots can be delivered to separate
analysis cartridges for interrogating the sample for the presence or absence of different analytes
of interest. In some embodiments, the prepared sample can be aliquoted between a second
sample preparation device and a third, fourth, fifth, etc. sample preparation device. As above,
each of the subsequent devices can be external to the first device, or they can be internal to or
located within a common housing with the first device. In some embodiments, the second device
is an analysis cartridge to be processed within the first device. In some cases, the prepared
sample can be interrogated for nucleic acid, as well as protein. Such analysis would require
aiiquoting the sample to at least 2 subsequent devices which can each be a sample cartridge. In
some embodiments, it can be desirable to determine the presence of a protein and the extent of
glycosylation of the protein. In some embodiments, it can be desirable to configure the assay for
detection or analysis of a nucleic acid (including methylation status), a protein, a carbohydrate,
and or a lipid.
[0042] In some embodiments, the second sample processing device is a device that performs
sample analysis, such as nucleic acid amplification. Non-limiting exemplary nucleic acid
amplification methods suitable for use with the invention include, polymerase chain reaction
(PGR), reverse-transcnptase PGR (RT-PCR), Ligase chain reaction, transcription mediated
amplification (TMA), and Nucleic Acid Sequence Based Amplification (NASBA). Additional
nucleic acid tests suitable for use with the instant invention are well known to persons of skill in
the art. Analysis of a fluid sample generally involves a series of steps, which can include optical
or chemical detection according to a particular protocol in some embodiments, the second
sample processing device can be used to perform any of the aspects relating to analysis and
detection of a target described in U.S. Patent Application No. 6,818,185, cited previously and
incorporated herein by reference in its entirety.
[0043] In some embodiments, the fluidic bridge is an elongated structure having one or more
fluid channels or conduits extending between opposite ends to allow a fluid sample to flow
distally from a proximal end fluidly coupled with the first sample processing device to the distal
end ffuidly coupled with the second sample processing device. In some embodiments, the one or
more fluid channels have a cross-sectional area that does not substantially vary across the length
of the fluid channel between the respective fluid-tight couplings. This allows for more
consistent, predictable flow of fluid sample through the channel to allow more control of the
fluid transport through the bridge. Fluid transport through the bridge is effected by receiving an
electronic instruction by the system, which can include either the first and/or the second sample
processing device, to transport the fluid sample after processing with the first sample processing
device is complete. Transport of the fluid sample through the one or more fluid channels can be
effected by pressurization/depressurization of the channel or by displacement of the fluid. In
some embodiments, displacement of the fluid can be effected by displacing air such that
displacement of a volume of air results in displacement of an amount of fluid sample. In some
embodiments, the amount of fluid displaced is equal to the amount of air displaced. In some
embodiments, the amount of fluid displaced is less than the amount of air displaced. For
example, in a bridge having at least two fluid channels, feeding air into or evacuating air from
one fluid channel can result in transport of the fluid sample into or through the other fluid
channel. In some embodiments a bridge member having at least two channels, each of the at
least two channels can have a volume that does not substantially differ in some embodiments,
the volumes of the at least two channels can substantially differ according to a pre-determined
amount. In some embodiments, configuring the fluid flow channels to be of similar flow
dimensions as the fluid channels with the reaction vessel noted above (see U.S. Patent No.
6,374,684), the same mechanisms by which transport of fluid sample through a reaction vessel
can be used to transport fluid sample into the fiuidic bridge for transport to a second sample
processing device. A person of skill in the art will appreciate that transport of the fluid sample
through the bridge can be effected in any number of ways that would be suitable for use with the
instant invention.
II. Example Fiuidic Bridge Device Constructions
[0044] FIGS. 4A-4D depicts exemplary fiuidic bridge devices in accordance with
embodiments of the invention. As can be seen in FIG. 4A, the fiuidic bridge member 0
includes two fluid channels or conduits 1 spaced apart spaced apart from each other and
extending the length of the bridge member between opposite ends. The channels are separated
and supported by a supporting web structure 4 . The fluidic bridge can be fabricated from any
material suitable for transport of a fluid sample such that it would not interfere with processing
or analysis of the sample, typically an inert plastic or polymer-based material can be used. In
some embodiments, the material used to fabricate the fluidic bridge is a transparent or partly
translucent material to allow visual observation of sample transport and/or optical
detection/monitoring of the fluidic channel through the material.
[0045] In some embodiments, each of the one or more channels are through lumens extending
from a first fluid-tight coupling at one end and a second fluid-tight coupling at an opposite end of
the bridge. The fluidic bridge is only limited in length by the volume of air that can be displaced
by the first and/or second sample processing devices to effect fluid transport through the bridge.
In some embodiments, the fluidic bridge is or more feet in length. In some embodiments, the
length of the fluidic bridge is less than 10 feet in length, for example, the fluidic bridge can have
a length of up to 10 feet, 9 feet, 8 feet, 7 feet, 6 feet, 5 feet, 4 feet, 3 feet, 2 feet, or 1 foot. In
some embodiments, the length of the fluidic bridge is less than 1 foot. For example, the fluidic
bridge can have a length between the stubs of about 30 cm, 29 cm, 28 cm, 27 cm, 26 cm, 25 cm,
24 cm , 23 cm, 22 cm, 2 1 cm, 20 cm, 19 cm, 18 cm, 17 cm, 16 cm, 15 cm, 14 cm, 13 cm, 12 cm,
cm, 0 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, or 1 cm in length.
[0046] In some embodiments, the bridge has a length between 3 to 5 cm, such as about 4 cm
between flanges, and the fluid channels extend in parallel and are separated by about 1 cm. This
configuration allows for substantially fluid-tight couplings at each end that are of substantially
the same construction, such as that shown in FIG. 4A. The fluid-tight couplings of each channel
are defined by a stub 2, each stub being dimensioned to be fittingly received in a corresponding
external port of the first or second devices so as to facilitate a fluid-tight coupling of the fluid
channels 1 with corresponding fluid channels of the respective devices. For example, stubs 2 at
the proximal end of the fluidic bridge 10 serve as inlet stubs for flow of the prepared fluid
sample into the bridge, while the stubs 2 at the distal end serve as outlet stubs for flow of the
fluid sample out from the bridge into the second sample processing device. In some
embodiments, the inlet stubs can have an outside diameter between 2- 0 mm, for example, the
outside diameter can be 2, 3, 4, 5, 6, 7, 8, 9, or 10 mm. Typically , the outside diameter of the
stub s about 3 mm, and extends from the flange 3 a distance of about 2-5 mm, such as about 3
mm, so as to facilitate fluid-tight coupling with a sample processing cartridge, such as that
shown in FIG. 2A. The inside diameter of each of the one or more channels can he within a
range of 1mm to 5 mm.
[0047] In some embodiments, each of the one or more fluid channels is open at each end when
the bridge is unattached from the first and second device. In some embodiments, the one or
more channels extend directly between the fluid-tight coupling at each end of the fluidic bridge,
there being no other inlet or exit port there between, such that fluid flowing into an inlet stub in
one side exits the outlet stub on the opposite side. In some embodiments, where each of the one
or more fluid channels are open at each end when unattached, the channels lack any sample
preparation means, such as any pre-existing reagents or means for binding an analyte of interest
contained therein. In some embodiments, the one or more channels extend between fluid-tight
couplings without any chambers, valves or ports between the proximal and distal ends. In some
embodiments, the fluidic bridge comprises one or more valves, or ports between the proximal
and distal ends. In some embodiments, the one or more channels can include one or more
chambers or regions, which can be used to process or analyze the fluidic sample. For example,
the fluidic bridge can comprise one or more chambers or regions for thermal amplification of
nucleic acid in the sample, filtration of the sample, including lateral flow chromatography,
hybridization, and or incubation of the sample with one or more assay reagents. In some
embodiments where the one or more channels are open to external environment at one end can
cause the one or more channels that include one or more chambers unsuitable for use as sample
preparation chambers since such sample preparation means cannot be suitably contained within
open channels. In some embodiments, each of the one or more fluid channels are closed (sealed)
to the external environment through a film seal over the fluid-tight couplings when unattached to
the first or second sampling processing devices. In such embodiments, any sample preparation
means or assay reagents will be securely contamed within the fluidic bridge until attached to the
first and/or second processing device, whereby the film seals are broken or removed at the time
of connecting the fluidic bridge to said devices.
[0048] In some embodiments, the bridge is provided pre-attached to a cartridge of the first
device such that the fluid-tight couplings are coupled with one or more corresponding fluid
transfer ports of the cartridge while the fluid-tight couplings on the opposite end of the bridge
remain open. In some embodiments, the bridge is attached to cartridge of the first device with
fluid-tight couplings coupled with one or more corresponding fluid transfer ports of the cartridge
while the fluid-tight couplings on the opposite end of the bridge are sealed. In some
embodiments, a reagent, means for virus lysis, or means for binding an analyte of interest (e.g.
reagent beads) as can be used for sample preparation can be contained within one or more
chambers of the cartridge or first device. The bridge allows a user to selectively couple the
cartridge or first device to a second sample processing device as desired, which can include
various other reagents or various other means of performing additional sample processing. In
some embodiments, the fluidic bridge can contain reagents for sample processing and each of the
ends are sealed until connected to the respective first and second sample processing devices.
[0049] In some embodiments, each conduit of the fluidic bridge can include a flange 3 at
one or both ends that extends circumferentially about the bridge for use in attaching the fluidic
bridge to the sample processing cartridge and or the second sample processing device. While the
fluid tight coupling shown in FIG 5A includes stubs 2 extending from a flange 3, it is appreciated
that various other fluid-tight couplings suitable for use with the invention can be devised and that
the fluid-tight couplings at each end can differ from one another as needed to fluidly couple with
particular types of devices. Non-limiting exemplar}' fluid type couplings suitable for use with
the invention, include, Luer-!ock connections, snap-fit connections, friction fittings, click-fit
connections, and screw-on connections. Additional types of fluid tight couplings suitable for use
with the invention are well known to persons of skill in the art. In some embodiments, the
fluidic bridge can include one or more adapters that facilitate connection of the fluidic bridge
having a first type of fluid-tight coupling with a fluid sample processing device having another
type of fluid-tight coupling. A non-limiting exemplary adapter to facilitate connection of the
fluidic bridge is shown in FIG 4A.
[0050] In some embodiments, the fluidic bridge 10 can include one or more processing
features in fluid communication with one or more of the fluid flow channels, e.g. as shown in
FIG. 4B. In some embodiments, the fluidic bridge can include one or more processing features,
including one or more chambers, filters, traps, membranes, ports and windows, to allow
additional processing steps during transport of the fluid sample to the second sample processing
device. For example, as shown in FIG. 4B, the fluidic bridge can include a chamber 5, which
can be used, e.g., as an amplification chamber to perform nucleic acid amplification. Additional
uses for chamber 5 will be apparent to one of ordinary skill in the art, and can include filtration,
chromatography, hybridization, incubation, chemical treatment, e.g., bisulfite treatment and the
like. The chamber 5 allows for accumulation of a portion of the fluid sample for further
processing or analysis as needed for a particular protocol. In some embodiments, the chamber
comprises a window that is at least partly transparent, such as the transparent microarray reaction
chamber shown in FIG. 4C, which allows for optical detection of an analyte of interest in the
fluid sample through the chamber during transport of the fluid sample through the bridge. This
feature is particularly advantageous when screening for the presence or absence of multiple
analytes, or for an analysis that may require several detection steps or require further processing
and/or analysis of the fluid sample after detection of a particular target or analyte of interest.
[0051] In some embodiments, one or more additional features can be incorporated into the
fluidic bridge. Non-limiting exemplar}' additional features that can be incorporated into the
fluidic bridge are shown in FIG. 4D. These features can include a filter 7, a bubble trap or gas
permeable vent 8, and an external port 9 . In some embodiments, a solid phase material, e.g., a
filter 7 can be positioned to capture components (e.g., cells, spores, microorganisms, viruses,
nucleic acids, proteins, lipids, carbohydrates, or the like) from the fluid sample as it passes there
through. The solid phase material can be formed of a screen, mesh, membrane, or comprised of
a chromatography column, or other structure suitable for use in filtering or concentrating the
sample. A bubble trap or gas permeable vent 8 can be used to substantially eliminate any gas or
air bubbles that may form in the fluid channel during transport of the fluid sample. The external
port 9 on the fluidic bridge can be used to access the fluid flow channel as needed, for example,
the external port can be used to deposit a substance within the fluid flow channel or within a
chamber of the fluidic bridge as needed for a particular protocol In some embodiments, the
external port of the fluidic bridge can be used to remove an aliquot of the processed sample as it
flows through the bridge. The external port can also be used to facilitate flow of the fluid sample
along various other paths, for example, another bridge can be connected to the external port 9 so
that the fluid sample can be concurrently directed along multiple paths to differing devices to
facilitate analysis for different targets at the same time. In some embodiments, this approach can
be employed by using a fluidic bridge in which one or more of the fluid flow paths split into
multiple fluid flow channels. In some embodiments, a valve is added as an additional feature. It
is appreciated that each of the features illustrated in FIGS. 4A-4D can be used in any number or
combination within a fluidic bridge device 0 in accordance with the invention described herein.
. Fluidic Interface Between Fluidic Bridge and Processing Devices
[0052] Various aspects of the sample processing cartridge 110 shown in FIGS. 2A-2D and 3A-
3C can be further understood by referring to U.S. Patent No. 6,374,684, which described certain
aspects of a sample processing cartridge in greater detail. Such cartridge devices include a fluid
control device, such as a rotary fluid control valve that is connected to the chambers of the
cartridge. Rotation of the rotary fluid control valve permits fluidic communication between
chambers and the valve so as to control flow of a sample deposited in the cartridge into different
chambers in which various compounds can be provided according to a particular protocol as
needed to prepare the sample for analysis. To operate the rotary valve, a motor such as a stepper
motor is typically coupled to a drive train that engages with a feature of the valve to control
movement of the valve and resulting movement of the fluid sample according to the desired
sample preparation protocol. The fluid metering and distribution function of the rotary valve
according to a particular sample preparation protocol s demonstrated in U.S. Patent No.
6,374,684, which is incorporated herein for all purposes.
[0053] In some embodiments, the sample processing cartridge 110 includes two transfer ports
to facilitate flow of the fluid sample through the reaction vessel 18. In the embodiment shown in
FIG. 5A, the fluidic bridge includes two fluid flow channels having corresponding inlet stubs 2
that are dimensioned and spaced apart so as to be fittingly received within the two transfer ports
1 2 of the sample processing cartridge. A sealing gasket 113 can surround the transfer ports
1 2, one or both of which can be formed of an elastomeric material so as to facilitate fluid-tight
sealing of the inlet stubs 2 within the transfer ports. The flange 3 may be dimensioned so that a
proximal facing surface of the flange engages a gasket 3 extending about the transfer ports of
the first sample processing device while a retaining member 130 of the first sample processing
device engages a distal facing surface of the flange, thereby ensuring a fluid-tight coupling of
each of the one or more fluid channels with the first and/or second sample processing device. In
some embodiments, such as shown in FIG. 5A-5B, the retaining member 30 is incorporated into
a base 131 of the sample processing cartridge on which the main body cartridge is mounted, such
that the fluidic bridge 10 can be attached and fluidly coupled to the sample processing cartridge
1
during assembly and provided to a user in an assembled condition, as shown in FIG. 5B. In
some embodiments, the sample processing cartridge includes at least two transfer ports 112 to
which the fluidic bridge device 10 fluidly couples for transport of the processed sample from the
cartridge system 0 to a second fluid processing device. In some embodiments, the sample
processing cartridge can have only one external transfer port, in which case, the corresponding
fluidic bridge for use with said cartridge will comprise a single fluid channel.
[0054] In some embodiments, the fluidic bridge comprises a sample preparation device having
the sample processing cartridge described above. In some embodiments, the fluidic bridge is
configured according to the particulars of various other types of sample processing devices in
any number of ways to provide the advantageous aspects of the fluidic bridge member described
herein. For example, the distal end of the fiuidic bridge that connects to the second sample
processing device can be specifically configured to interface with a particular device. Such
particular features can include the number of transfer ports that the bridge interfaces with, the
shape and/or size of the stub, the type of connection, and the like.
[0055] In some embodiments, the invention can include a first sample processing device tha is
modified to allow sampling preparation and analysis within the firs sample processing device or
sample preparation with the device and transport of the prepared fluid sample to a second device
through the fluidic bridge while the sample processing cartridge is mounted in the first device.
An example of such a modified first sample processing device is shown in FIG. 6 . The first
sample processing device 300 includes a mechanism 3 0 that engages with a valve of the sample
processing cartridge to facilitate processing by moving the fluid sample into the various
chambers of the mam body of the cartridge according to the protocol desired for preparation of
the sample. The device can further include an optical interrogation means for interrogating the
sample as to the presence or absence of a particular analyte.
[0056] In some embodiments, the optical interrogation means involve an optical excitation
means 320, typically an LED device, to excite fluorescent moieties on probes hybridized to the
target of interest, and a detection means 322 for detecting fluorescence emitted from said probe
when bound to target being indicative of the presence of the target for which the sample is being
analyzed. While in FIG. 6, the optical excitation means 320 and detection means 322 are shown
as being disposed on a sidewall of the passage 315 in which the sample cartridge resides, it s
understood that these elements can be positioned in various other locations so long as the fluid
sample is sufficiently accessible to the excitation means and detections means to allow excitation
and detection of the analyte. For example, the excitation means and detection means could be
incorporate into a bottom surface or upper surface of the passage 315, or may be included in an
entirely different component that is separate from, detachable or movable relative an external
housing of the first sample processing device. These features allow for analysis of a sample in a
conventional sample processing cartridge with a conventional reaction vessel 8 or preparation
of the sample in the first modified processing device 300 and subsequent transport to a second
processing device using the fluidic bridge 10. In such embodiments, it may be necessary to
relocate the transfer ports on the sample processing cartridge to accommodate both the reaction
vessel and the fluidic bridge. In some embodiments, upon completion of the preparation and
analysis in the first device, the sample can be drawn back from the reaction vessel into one of the
chambers of the cartridge, then the reaction vessel can be replaced with the fluidic bridge and
then the sample can be transferred to the second sample processing device as described herein.
[0057] FIGS. 7A-7B and 8A-8B illustrate use of an alternative sample processing cartridge
device 300 shown in FIG. 6 with a sample processing cartridge having a reaction vessel 8 as
well as use of the device 300 with a sample processing cartridge having a fluidic bridge attached,
such as that shown in FIG. 4A. The device 300 includes a passageway or pass-through to allow
the fluidic bridge 10 to extend outside the device 300 to facilitate coupling with a second device
and transport thereto. As shown in FIG. 7A, the modified sample processing device allows a
conventional sample processing cartridge device to be insert and processed from sample
preparation to analysis. As shown in FIG. 7B, the modified device 300 when used with a sample
processing cartridge having a fluidic bridge device 0 attached thereto, allows the first device
300 to be used for only sample preparation, if a user desired, and transport to a second device for
processing and analysis. Towards these ends, it is desirable for the fluidic bridge to have a
length of at least two centimeters, preferably at least four centimeters in length, although various
other lengths beyond four centimeters could be realized within the scope of the invention.
IV. Methods of Use
[0058] In one aspect, methods of transporting a fluid sample between a first sample processing
device and a second sample processing device by use of a fluidic bridge are provided herein.
Such a fluidic bridge can be configured according to various dimensions and length so as to
faciliate transport of a fluid sample from a first sample processing device, such as the sample
processing cartridge described herein, to a selected second sample processing device, which can
include various different types of processing and/or analysis devices. In certain assays where no
sample processing is required beyond that provided by the first sample processing device, an
assay analysis device can be coupled (directly or indirectly) to the end of the bridge opposite of
the end attached to the first sample processing device. For example, a reaction vessel, a microarray
device, or a biosensor device could be attached to the second end of the bridge. In certain
other assays, it may be desired to perform additional processing steps (e.g. amplification,
filtering, etc.) or to perform an analysis provided by a second sample processing device that is
more extensive or complex than that provided by a typical reaction vessel.
[0059] FIGS. 9-10 depict exemplary methods in accordance with embodiments of the
invention. The method illustrated in FIG. 9 includes steps of: coupling a first end of a fluidic
bridge with a first sample processing device, the bridge member comprising one or more fluid
channels extending between fluid-tight couplings at opposing ends 800; coupling the opposing
end of the flui dic bridge with a second sample processing device, thereby creating a fluid tight
coupling between the first sample processing device and the second sample processing device
802; receiving an electronic instruction to move a processed sample from the first device to the
second device 804; and fluidically moving the processed sample through the elongated bridge
extending between the first sample processing device and the second sample processing device
806. In some embodiments, the first sample processing device comprises a sample preparation
device while the second device may be used to perform analysis of the sample to detect a desired
target or for further processing of the prepared sample.
[0060] In some embodiments, fluidically moving the processed sample through the elongated
bridge is effected by either or both of the first and second sample processing device, typically,
upon receiving an electronic instruction to transport the processed sample. Transport of the
sample may be effected by pressurization or de-pressurization of at least one of the one or more
channels so as to effect fluid flow of the sample from the first processing device through a fluid
channel of the bridge and to the second sample processing device. For example, in a bridge
member having a pair of fluidic channels that form a fluid circuit when attached to
corresponding fluid transfer ports of the first and second sample processing device, air can be
withdrawn from one fluid channel of the bridge by the first or second device, thereby causing
fluid sample to be drawn from a chamber of the first sample processing device and through the
other fluid channel of the bridge before flowing into the second sample processing device.
[0061] The exemplary method as illustrated in FIG. 9 includes steps of: coupling a first end of
an elongate fluidic bridge with a first sample processing device, the elongated bridge member
comprising one or more fluid channels extending between fluid-tight couplings at opposing ends
900; coupling the opposing end of the elongate fluidic bridge with a selected second sample
processing device, thereby creating a fluid tight coupling between the first sample processing
device and the second sample processing device 902; effecting processing of the sample
according to a sample preparation protocol using the first sample processing device 904;
effecting transport of the fluid sample prepared with the first device through the fluidic bridge
into the second sample processing device 906; optionally further processing the prepared sample
using one or more features of the fluidic bridge during transport there through 908; and effecting
analysis of the prepared sample received through the fluidic bridge in the second sample
processing device for detection of a desired target 910. Further processing of the prepared
sample by one or more features in the bridge can include filtering or concentrating utilizing a
filter or other suitable solid phase material or membrane, amplification using one or more
amplification chambers, chemical treatment utilizing one or more chambers or regions, or
removal of accumulated gas or air through a gas permeable membrane or a bubble trap.
[0062] FIGS. A-l IE depict alternative embodiments of a fluidic bridge device in accordance
with various aspects of the invention. FIG. A illustrates fluidic bridge 10' in which one fluid
conduit or channel 1 splits into two fluid channels. As can be seen, upper inlet stub 2 feeds a
fluid channel that splits into two separate channels I feeding two separate outlet stubs 2 . The
lower channel 1 remains a single channel extending between inlet stud 2 to outlet stub 2 . It is
appreciated that the split channels could also be configured to extend to two different interfaces
so as to be attachable to a second and third device concurrently. FIG. 1IB illustrates fluidic
channel device 10" which includes a single fluid channel 1 extending between inlet stub 2 to
outlet stub 2 . Such an embodiment could include an additional feature, such as a faux upper
stub, to allow the fluidic bridge 10" to be secured to a conventional device having two
interfacing ports. F dic bridge 10" further includes structural webbing 4 to maintain rigidity of
such an embodiment. FIG. 11C illustrates an embodiment having more than two fluid channels.
As can be seen, fiuidic bridge 10"' includes three separate fluid channels 1 extending between
corresponding let and outlet stubs 2 . FIG. 1 D illustrates fiuidic bridge 10"" in which two
separate inlet stubs 2 feed two fluid channels that combine into a single fluid channel 1 that exits
at outlet stub 2 . FIG. 1 E illustrates fiuidic bridge 10""' which includes fluid channels 1 that
vary in diameter between the inlet and outlet stubs 2 . As can be seen, upper channel 1 increases
in cross-section from inlet stub 2 before exiting at outlet stub 2 . In this embodiment, outlet stub
2 is larger than let stub 2, but in other embodiments, outlet stub 2 can be the same size as inlet
stub 2 . Lower channel 1 also varies in size, the cross-sectional area decreasing between inlet
stub 2 to a smaller outlet stub 2 . Similarly, inlet and outlet stubs in lower channel 1 can be the
same or differing sizes. These features can be used to change the speed at which the fluid
sample exits the outlet stubs of the fiuidic bridge. In some embodiments, the increase in
diameter of one channel can correspond to the decrease in diameter of the other channel such that
that the total fluid exchange remains substantially the same as in a fiuidic bridge device having
fluid channels of the same non-variable diameter. It is appreciated that any of the features
described herein could be modified and/or combined in a fiuidic bridge device according to
various other combinations as desired for a particular application.
[0063] In the foregoing specification, the invention is described with reference to specific
embodiments thereof, but those skilled in the art will recognize that the invention is not limited
thereto. Various features, embodiments and aspects of the above-described invention can be
used individually or jointly. Further, the invention can be utilized in any number of
environments and applications beyond those described herein without departing from the broader
spirit and scope of the specification. The specification and drawings are, accordingly, to be
regarded as illustrative rather than restrictive. It will be recognized that the terms "comprising,"
"including," and "having," as used herein, are specifically intended to be read as open-ended
terms of art.
WHAT IS CLAIMED IS:
1. A fiuidic bridge for transporting fluids between sample processing
devices, the fiuidic bridge comprising:
an elongated bridge having one or more fluid channels not including a sample
preparation chamber, the one or more channels extending between a first end of the elongated
bridge and a second end opposite the first end;
one or more fluid-tight couplings on the first end adapted for fluidiy coupling the
one or more fluid channels with a first sample processing device at a fluid tight junction, and
one or more fluid-tight couplings on the second end of the elongate bridge
adapted for fluidiy coupling the one or more channels with a second sample processing device so
that the first and second sample processing devices are in fluid communication through the one
or more channels when the fiuidic bridge is coupled to each of the first and second sample
processing devices.
The bridge of claim 1 further comprising at least one chamber in fluid
communication with at least one of the fluid channels, wherein the chamber is not a sample
preparation chamber.
3 . The bridge of claim 1 wherein the one or more fluid channels are open to
an external environment when the fluid-tight couplings between which the one or more fluid
channels are unattached to the first or second sample processing device.
4 . The bridge of claim 1, wherein the first sample processing device is a
sample preparation device.
5. The bridge of claim I , wherein the elongated bridge comprises a material
that is at least partly translucent or transparent so as to allow optical detection of fluid
transported through the one or more fluid channels.
6 . The bridge of claim 1, wherein at least one of the fluid channels includes
both of a gas permeable vent and a bubble trap.
7 . The bridge of claim 1, wherein at least one of the one or more fluid
channels has a cross-sectional lumen area that does not substantially vary across the length of the
fluid channel between respective fluid-tight couplings.
8. The bridge of claim 7, wherein the cross-sectional area of each of the one
or more fluid channels remains a substantially constant size and shape between respective fluidtight
couplings.
9 . The bridge of claim 1, wherein the one or more channels comprise at least
two channels, each of the at least two channels extending between fluid-tight couplings of the
first and second ends.
10. The bridge of claim 1, wherein the one or more channels are fluidly sealed
by the fluid-tight couplings of the first and second ends when coupled to the first and second
sample processing devices and are open to an external environment through the fluid-tight
coupling when unattached to the first or second sample processing device.
11. The bridge of claim 9, wherein the volume of each of the at least two
channels between the first and second ends, does not substantially differ.
12 The bridge of claim 9, wherein the volume of each of the at least two
channels comprises a volume that s substantially different.
13 . The bridge of claim 9, wherein the bridge further comprises a supporting
web structure separating the at least two channels.
14. The bridge of claim 1, wherein each of the one or more fluid-tight
couplings at the first end comprises a stub dimensioned to be fittingly received within one or
more corresponding ports in the first sample processing device so as to fluidly couple the one or
more channels with the first sample processing device.
15. The bridge of claim 14, wherein each of the stubs are dimensioned to be
fluidly coupled with the first sample processing device by a friction fit when fittingly received
within the one or more corresponding ports of the first sample processing device.
The bridge of claim 4, further comprises a flange at or near the first end
that extends at least partly about the first end, the flange being adapted for securing the bridge
when fluidly coupled with the first sample processing device by interfacing with a retaining
component of the first sample processing device.
17. The bridge of claim 4, wherein the one or more fluid-tight couplings at
the second end comprise stubs dimensioned to be fittingly received within one or more
corresponding ports in the second sample processing device so as to fluidly couple the one or
more channels with the second sample processing device.
18. The bridge of claim 7, wherein the elongate bridge further comprises a
flange at or near the second end that extends at least partly about the second end, the flange
being adapted for securing the bridge when fluidly coupled with the second sample processing
device by interfacing with a retaining component of the second sample processing device.
19. A disposable cartridge for processing a sample, the cartridge comprising:
a plurality of chambers contained within a housing, the chambers being fluidicaily
interconnected by a moveable valve body comprising one or more fluid processing regions; and
an elongated bridge extending from the housing of the cartridge and having fluidtight
couplings on both opposing ends for forming a fluid tight junction with the cartridge and
another device, the elongated bridge having one or more fluid channels adapted for transport of
fluid into or out of the cartridge,
wherein at least one of the fluid processing regions is configured for sample
preparation.
20. The cartridge of claim 19, wherein the elongated bridge is of sufficient
length and dimension such that when coupled with the cartridge, when the cartridge is disposed
within a cartridge receiver during sample preparation, the elongated bridge extends through a
passageway of the cartridge receiver to facilitate transport of the prepared sample from the
cartridge to an assay processing device or an associated component.
21. The cartridge of claim 19, wherein the elongated bridge comprises at least
two fluid channels separated by a supporting web structure or ribs.
22. The cartridge of claim 19, wherein the elongated bridge further comprises
at least one sample processing chambers including an amplification chamber.
23. A module for performing sample preparation, the module comprising:
a sample processing cartridge configured to hold an unprepared sample, the sample
processing cartridge comprising a plurality of processing chambers fluidically interconnected by
a moveable valve body;
a cartridge receiver adapted to receive and removably couple with the sample processing
cartridge and interface with an assay processing device, wherein the cartridge receiver includes:
a cartridge interface unit configured for moving the valve body to change fluidic
interconnections between the plurality of sample processing chambers,
a pressure interface unit for applying pressure to move fluid among the plurality
of processing chambers according to position of the valve body, and
a sample preparation controller configured to electronically communicate with the
assay processing device and configured to control the cartridge interface unit and
pressure interface unit to process the unprepared sample into a prepared sample within
the sample processing cartridge; and
an elongated bridge coupleable with the sample processing cartridge, the
elongated bridge having one or more fluid channels through which the sample processing
cartridge and assay processing device are fluidly coupled to facilitate transport of the prepared
sample to the assay processing device.
24. The module of claim 23, wherein the cartridge receiver includes a
passageway through which the elongated bridge extends when coupled with the sample
processing cartridge when coupled within the cartridge receiver to facilitate transport of the
prepared sample from the cartridge receiver to the assay processing device.
25. The module of claim 23, wherein the elongated bridge comprises at least
two fluid channels separated by a supporting web structure or ribs.
26. The module of claim 23, wherein the elongated bridge is greater than two
inches in length so as to extend a distance away from the cartridge receiver.
27. A method for transporting a processed fluid sample, the method
comprising:
coupling a first end of an elongate fluidic bridge with a first sample processing
device, the elongated bridge member comprising one or more fluid channels extending between
fluid-tight couplings at opposing ends;
coupling the opposing end of the elongate fluidic bridge with a second sample
processing device, thereby creating a fluid tight coupling between the first sample processing
device and the second sample processing device;
processing of the fluid sample with the first sample processing device; and
fluidicaliy moving the processed sample through the elongated bridge member
extending between the first sample processing device and the second sample processing device.
28. The method of claim 27, wherein fluidicaliy moving the processed sample
through the elongated bridge member comprises receiving an electronic instruction, with the first
and/or the second processing device, to move a processed sample from the first device to the
second device.
29. The method of claim 28, wherein fluidicaliy moving the processed sample
through the elongated bridge member comprises pressurizing and/or depressunzing at least one
of the one or more fluid channels with the first samples processing device and/or the second
sample processing device in response to the electronic instruction.
30. The method of claim 27, wherein the first sample processing device
comprises a sample preparation device.
3 . The method of claim 27, wherein the second sample processing device
comprises an assay processing device.
32. A method for processing an unprepared sample, the method comprising:
receiving a sample processing cartridge at a cartridge receiver, the sample
processing cartridge comprising a plurality of processing chambers fluidicaliy interconnected by
a moveable valve body;
receiving an electronic instruction to process the unprepared sample into a
prepared sample from an assay processing device coupled to the cartridge receiver;
performing a sample preparation method to process the unprepared sample into
the prepared sample, the method comprising:
moving a cartridge interface unit to move the valve body to change fluidic
interconnections between the plurality of sample processing chambers;
applying pressure to a pressure interface unit to move fluid between the
plurality of processing chambers according to position of the valve body; and
fluidcally moving the prepared sample into an elongated bridge that extends from
the sample processing cartridge and fluidieaily interfaces with the assay processing device to
provide the prepared sample to the assay processing device
33. A system comprising:
a first sample processing device;
a second sample processing device; and
a fluidic bridge coupleable with each of the first and second sample processing
device so as to facilitate transport of a fluid sample between the first and second sample
processing device when coupled therebetween
34. The system of claim 33, further comprising a plurality of sample
processing devices that include the second sample processing device, and wherein the fluidic
bridge is configured to fluidieaily couple with any of the sample processing devices such that the
second sample processing device is selectable from the plurality of sample processing devices.
35. The system of claim 34, wherein the plurality of sample processing
devices includes differing types of sample processing devices.
36. The system of claim 33, wherein the fluidic bridge comprises:
an elongated bridge having one or more fluid channels not including a sample
preparation chamber, the one or more channels extending between a first end of the elongated
bridge and a second end opposite the first end;
one or more fluid-tight couplings on the first end adapted for fluidly coupling the
one or more fluid channels with a first sample processing device a a fluid tight junction, and
one or more fluid-tight couplings on the second end of the elongate bridge
adapted for fluidly coupling the one or more channels with a second sample processing device so
that the first and second sample processing devices are in fluid communication through the one
or more channels when the fluidic bridge is coupled to each of the first and second sample
processing devices.