Fluid handling – Systems – With flow control means for branched passages
Reexamination Certificate
2001-11-01
2004-03-02
Fox, John (Department: 3753)
Fluid handling
Systems
With flow control means for branched passages
C251S061100
Reexamination Certificate
active
06698454
ABSTRACT:
TECHNICAL FIELD
The present invention relates to valves associated with microfluidic assemblies, and more specifically, to valves integrally associated with microfluidic assemblies adapted to transport liquid samples for analytical purposes.
BACKGROUND OF THE INVENTION
A variety of analytical instruments are used to characterize liquid samples containing an analyte of interest, particularly in the context of assays directed to real-time detection of biomolecular interactions. For example, the study of real-time biomolecular interactions through use of “biosensors” are now of fundamental importance in many fields, including biology, immunology and pharmacology. In this context, many biosensor-based analytical instruments include “microfluidic structures” adapted to transport one or more liquid samples through an interaction or a detection zone. Such microfluidic structures generally include a block unit that has multiple internal channels, inlet and outlet ports, pumps and valves; all of which operate in concert to flow small volumes of liquid sample and various other buffers and reagents through one or more interaction and/or detection zones.
An exemplary microfluidic structure for such liquid handling may be illustrated in the context of biosensors that use surface plasmon resonance (SPR) to monitor the interactions between an analyte and a ligand bound to a solid support. In this regard, a representative class of biosensor instrumentation is sold by Biacore AB (Uppsala, Sweden) under the trade name BIAcore® (hereinafter referred to as “the BIAcore instrument”). The BIAcore instrument includes a light emitting diode, a sensor chip covered with a thin gold film, an integrated microfluidic cartridge and photo detector. Incoming light from the diode is reflected in the gold film and detected by the photo detector. At a certain angle of incidence (“the SPR angle”), a surface plasmon wave is set up in the gold layer, which is detected as an intensity loss or “dip” in the reflected light. The theoretical basis behind the BIAcore instrument has been fully described in the literature (see, e.g., Jönsson, U. et al.,
Biotechniques
11:620-627, 1991).
More specifically, and as best shown in
FIG. 1
(prior art), a representative BIAcore instrument
100
comprises a source of light
102
, first lens means
104
for directing a transversely extending convergent beam
106
toward a prism
108
whereby the beam is focused in the bottom surface of the prism
108
to thus form a streak
110
of light. Rays of light reflected from the sensitized surfaces are imaged via an anamorphic lens system
112
on a two-dimensional photodetector device
114
. The electronic signals created by the photodetectors are processed in an evaluation device
116
in the form of a computer.
By means of the prism
108
and an opto-interface
118
light from streak
110
is directed to a sensor unit
120
which lies in contact with a number of parallel, upwardly open portions
122
A-D of flow channels
124
A-D, respectively; only one of which,
124
A, is shown. The flow channels form part of a block unit
126
for liquid handling, this block unit is shown with schematically indicated inlet connection tubes
128
and
130
and outlet connection tubes
132
and
134
. A more complete description of this representative BIAcore instrument including its microfluidic block unit for flowing solutions therein may be found in U.S. Pat. No. 5,313,264, which is incorporated herein by reference in its entirety.
As more fully described in U.S. Pat. No. 5,313,264, and as also best seen in
FIG. 1
(prior art), the upwardly open portions
122
A-D of flow channels
124
A-D (only flow channel
124
A is shown) correspond to a first layer
136
of a sealing elastomer material (e.g., silicone rubber or the like) that has a number of cuts or slits extending therethrough. The first layer
136
has been cast onto a plateau
138
which is integral with a base plate
140
. The base plate
140
is preferably a solid member made of, for example, plastic, metal, ceramics, or the like.
As best seen in corresponding
FIGS. 1A and 1B
, a second layer
142
of an elastomer material (e.g., silicone rubber or the like) has been applied by, for example, casting to the underside of base plate
140
. The second layer
142
is provided with a system of flow channels or conduits formed by casting. A third layer
144
, preferably of the same material as that of second layer
142
, has been cast onto a support plate
146
made of a solid material (preferably made of the same material as that of base plate
140
).
In view of the foregoing description, it will be readily understood that when the BIAcore instrument
100
is in an operable configuration such that the sensor unit
120
is pressed against first layer
136
by the opto-interface
118
, the upwardly open portions
122
A-D in first layer
136
will be sealed in liquid-tight relationship against sensor unit
120
and form four flow cells. For sake of simplicity, these four flow cells are also designated
122
A-D.
Moreover, in operation, a liquid sample is made to flow through one or more of the flow cells
122
A-D. More specifically, a pump (not shown) pumps the liquid sample to inlet tube
128
, through an inlet channel
148
, through an open valve
150
, and then through a primary channel
152
having a fixed and well-defined volume, until it reaches a closed valve
154
. The closed valve
154
directs the liquid sample into a waste channel
156
communicating via outlet connecting tube
134
with a disposal receptacle
158
.
Next, a valve (not shown) at the upstream end of waste channel
156
is closed, and at the same time valve
150
is also closed. The liquid sample in the primary volume is now ready to be pumped into the flow cell
122
A. This is done with the aid of an eluent solution
160
which is pumped by a pump
162
through inlet tube
130
to an eluent conduit
164
ending in a valve (not shown) which is now opened together with valve
154
. Continued pumping of the eluent solution
160
causes the advancing eluent solution to press forward against the primary volume of the liquid sample and force it to advance upwardly through a riser duct
166
in the plateau
138
, and then into flow cell
122
A, and then down through a second riser duct
168
and out through an exhaust duct
170
and an outlet tube
132
. From the outlet tube
132
, the sample liquid followed by the eluent solution is directed to a waste disposal receptacle
172
. When the sample liquid, which has a predetermined volume and/or flow rate, is flowing along flow cell
122
A, the chemical interaction between the sample liquid and the sensing surface of the sensor unit
120
is optically detected and analyzed.
One aspect associated with the above-described microfluidic structure, however, lies with the second elastomeric layer
142
(FIGS.
1
A and
1
B), which elastomeric layer forms part of the valves. In general, the elastomeric layer has low chemical resistance, and may have high permeability with respect to certain gases and small molecules. Both of these attributes are less than optimal in certain embodiments. Accordingly, there is a need in the art for improved microfluidic structures adapted to transport liquid samples for analytical purposes. The present invention fulfills these needs, and provides for further related advantages.
SUMMARY OF THE INVENTION
The present invention discloses a valve integrally associated with a microfluidic transport assembly that is useful for regulating the flow of a liquid sample through an analytical instrument such as, for example, a biosensor. The valve integrally associated with a microfluidic liquid transport assembly includes: a first rigid layer having substantially planar and opposing first and second surfaces; a second rigid layer having substantially planar and opposing third and fourth surfaces, the third surface of the second rigid layer being substantially coplanar and integrally bonded to the second surface of the first rigid layer; a first passageway defined by a
Hansson Thord
Sjölander Stefan
Biacore AB
Fox John
Seed IP Law Group PLLC
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