U.S. patent application number 11/252821 was filed with the patent office on 2006-05-04 for device including a dissolvable structure for flow control.
This patent application is currently assigned to Applera Corporation. Invention is credited to Debjyoti Banerjee, Konrad Faulstich, Aldrich N. K. Lau, Umberto Ulmanella, Jun Xie.
Application Number | 20060093528 11/252821 |
Document ID | / |
Family ID | 36203645 |
Filed Date | 2006-05-04 |
United States Patent
Application |
20060093528 |
Kind Code |
A1 |
Banerjee; Debjyoti ; et
al. |
May 4, 2006 |
Device including a dissolvable structure for flow control
Abstract
A diagnostic device is provided that includes a plurality of
retainment regions, with the retainment regions that are separated
by at least one dissolvable barrier. The retainment regions can be
interconnected through at least one fluid processing passageway. A
retainment region can include a container such as a retainment
region, well, chamber, or other receptacle, or a retainment region
such as a surface on which the material is retained. The retainment
regions can include a reaction retainment region, one or more
reagent retainment regions, each containing unreacted reagents, and
a sample retainment region. A pressure-actuated valve can be
positioned in each fluid processing passageway interconnecting the
one or more reagent retainment regions with the respective
intermediate retainment regions interposed between each of the one
or more reagent retainment regions and the reaction retainment
region. The dissolvable barrier can be a fluid flow modulator in
the at least one fluid processing passageway.
Inventors: |
Banerjee; Debjyoti;
(Fremont, CA) ; Faulstich; Konrad; (San Jose,
CA) ; Lau; Aldrich N. K.; (Palo Alto, CA) ;
Ulmanella; Umberto; (San Mateo, CA) ; Xie; Jun;
(Pasadena, CA) |
Correspondence
Address: |
KILYK & BOWERSOX, P.L.L.C.
3603 CHAIN BRIDGE ROAD
SUITE E
FAIRFAX
VA
22030
US
|
Assignee: |
Applera Corporation
Foster City
CA
|
Family ID: |
36203645 |
Appl. No.: |
11/252821 |
Filed: |
October 18, 2005 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
60619731 |
Oct 18, 2004 |
|
|
|
60619677 |
Oct 18, 2004 |
|
|
|
60619623 |
Oct 18, 2004 |
|
|
|
Current U.S.
Class: |
422/400 ;
251/12 |
Current CPC
Class: |
B01L 2300/0864 20130101;
B01L 2400/0481 20130101; B01L 2400/0655 20130101; Y10S 422/901
20130101; Y10T 137/1624 20150401; Y10T 137/85978 20150401; B01L
2400/082 20130101; B01L 3/502746 20130101; B01L 2200/0621 20130101;
B01L 2400/0661 20130101; Y10T 137/8376 20150401; B01L 2400/086
20130101; B01L 2300/0816 20130101; B01L 2400/0487 20130101; F16K
99/0057 20130101; Y10T 436/2575 20150115; B01L 2300/087 20130101;
F16K 99/0036 20130101; Y10T 436/143333 20150115; B01L 2400/0406
20130101; B01L 2300/0867 20130101; F16K 2099/0084 20130101; Y10T
137/8593 20150401; F16K 99/003 20130101; B01L 2400/0683 20130101;
B01L 3/502738 20130101; F16K 99/0001 20130101; Y10T 137/0324
20150401; B01L 2400/0415 20130101; B01L 2400/084 20130101; Y10T
137/1812 20150401; Y10T 137/0318 20150401; B01L 2400/0677 20130101;
Y10T 137/2191 20150401 |
Class at
Publication: |
422/103 ;
251/012 |
International
Class: |
B01L 3/00 20060101
B01L003/00 |
Claims
1. A fluid processing device comprising: a fluid processing
passageway; a plurality of retainment regions, at least two of the
retainment regions each being in fluid communication with the fluid
processing passageway; and at least one fluid flow modulator
arranged in the fluid processing passageway and being adapted to
open to form, or to increase in size, a fluid communication between
the at least two retainment regions, the fluid flow modulator
comprising at least one of a polyethylene glycol material, a
derivative of a polyethylene glycol material, and a combination
thereof, and being adapted to dissolve when contacted with water at
room temperature.
2. The fluid processing device of claim 1, wherein at least one of
the plurality of retainment regions comprises aqueous fluid
retained therein.
3. The fluid processing device of claim 1, wherein the at least one
fluid flow modulator comprises at least one of a polyethylene
glycol material and a derivative of a polyethylene glycol material,
having a melting point of from about 35.degree. C. and about
65.degree. C.
4. The fluid processing device of claim 1, wherein the fluid
processing passageway is dimensioned sufficient to cause capillary
flow of a fluid from at least one of the at least two retainment
regions through the fluid processing passageway.
5. The fluid processing device of claim 1, wherein the fluid
processing passageway is dimensioned sufficient to cause
electrokinetic migration of charged components in a fluid, from at
least one of the at least two retainment regions through the fluid
processing passageway.
6. The fluid processing device of claim 5, further comprising at
least two electrodes disposed in the device with the fluid
processing passageway therebetween.
7. The fluid processing device of claim 1, further comprising: at
least one additional retainment region; at least one additional
fluid processing passageway; and at least one valve comprising one
or more of a pressure-actuatable valve and a heat-actuatable valve
arranged in the at least one additional fluid processing
passageway, wherein the at least one additional fluid processing
passageway is in fluid communication with the at least one
additional retainment region and at least one of the plurality of
retainment regions.
8. A system comprising the fluid processing device of claim 1, and
a pump, wherein the pump is arranged in fluid communication with at
least one of the fluid processing passageway and one or more of the
plurality of retainment regions.
9. A system comprising the fluid processing device of claim 6, a
power source, and at least two electrical leads forming electrical
connections, respectively, between the power source and the at
least two electrodes.
10. The fluid processing device of claim 1, wherein the at least
one fluid flow modulator comprises a material having the formula:
R.sub.1--Q-(--CH.sub.2--).sub.p-(--OCH.sub.2CH.sub.2--).sub.m-(--CH.sub.2-
--).sub.q-G--R.sub.2 Formula 1 wherein G and Q are each
independently a single bond, O, N, ##STR8## R.sub.1 and R.sub.2 are
each independently H, OH, NH.sub.2, O(C.sub.nH.sub.2n+1),
O(C.sub.nH.sub.2n-1), CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, R.sub.9, R.sub.10,
R.sub.11, R.sub.12, R.sub.13, and R.sub.14, are each independently
O, S, or NH, p and q are each independently 0, 1, 2, or 3, m is an
integer from 0 to about 10,00, at least one of p, q, and m is an
integer greater than 0, g is an integer from 2 to about 20, and n
is an integer from 1 to about 20; ##STR9## R.sub.4, R.sub.5, and
R.sub.6 are each independently H, OH, NH.sub.2,
O(C.sub.nH.sub.2n+1), O(C.sub.nH.sub.2n-1), CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, u is an integer from 0 to
about 10,000, g is an integer from 2 to about 20, n is an integer
from 1 to about 20, t, v, and z are each independently an integer
from 0 to about 10,000, and at least one of t, u, and v, is an
integer greater than 0;
[R.sub.7-(--CH.sub.2CH.sub.2O--).sub.x-(--CH.sub.2CH.sub.2--).sub.r-]a-A--
-R.sub.3--B-[-(--CH.sub.2CH.sub.2--).sub.s-(--CH.sub.2CH.sub.2O--).sub.y---
R.sub.8].sub.b Formula 3 wherein A and B are each independently a
single bond, O, N, ##STR10## R.sub.7 and R.sub.8 are each
independently H, OH, NH.sub.2, O(C.sub.nH.sub.2+1),
O(C.sub.nH.sub.2n-1), CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, R.sub.3 is
C.sub.nH.sub.2n, C.sub.nH.sub.2n-2, or CH.sub.2CH(CH.sub.3)O,
R.sub.9, R.sub.10, R.sub.11, R.sub.12, R.sub.13, and R.sub.14, can
each independently be O, S, or NH, a, b, r, and s are each
independently 0, 1, 2, or 3, x and y are each independently an
integer from 1 to about 10,000, g is an integer from 2 to about 20,
and n is an integer from 1 to about 20; or ##STR11## wherein: A, G,
and Q are each independently a single bond, O, N, ##STR12##
R.sub.1, R.sub.2, R.sub.4, and R.sub.5 are each independently H,
OH, NH.sub.2, O(C.sub.nH.sub.2n+1), O(C.sub.nH.sub.2n-1),
CH.sub.2OH, -(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, R.sub.9, R.sub.10,
R.sub.11, R.sub.12, R.sub.13, and R.sub.14, are each independently
O, S, or NH, f is an integer from 1 to about 10,000, p and q are
each independently 0, 1, 2, or 3, m is an integer from 0 to about
10,000, at least one of p, q, and m is an integer greater than 0, g
is an integer from 2 to about 20, and n is an integer from 1 to
about 20.
11. A fluid processing device comprising: a fluid processing
passageway; and at least one fluid flow modulator arranged in the
fluid processing passageway and being adapted to open to form, or
increase the size of, a fluid communication through the fluid
processing passageway, the at least one fluid flow modulator being
adapted to dissolve when contacted with water at room temperature,
and having the formula:
R.sub.1--Q-(--CH.sub.2--).sub.p-(--OCH.sub.2CH.sub.2--).sub.m-(--CH.sub.2-
--).sub.q-G--R.sub.2 Formula 1 wherein G and Q are each
independently a single bond, O, N, ##STR13## R.sub.1 and R.sub.2
are each independently H, OH, NH.sub.2, O(C.sub.nH.sub.2n+1),
O(C.sub.nH.sub.2n-1), CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, R.sub.9, R.sub.10,
R.sub.11, R.sub.12, R.sub.13, and R.sub.14, are each independently
O, S, or NH, p and q are each independently 0, 1, 2, or 3, m is an
integer from 0 to about 10,000, at least one of p, q, and m is an
integer greater than 0, g is an integer from 2 to about 20, and n
is an integer from 1 to about 20; ##STR14## wherein R.sub.4,
R.sub.5, and R.sub.6 are each independently H, OH, NH.sub.2,
O(C.sub.nH.sub.2n+1), O(C.sub.nH.sub.2n-1), CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, u is an integer from 0 to
about 10,000, g is an integer from 2 to about 20, n is an integer
from 1 to about 20, t, v, and z are each independently an integer
from 0 to about 10,000, and at least one of t, u, and v, is an
integer greater than 0;
[R.sub.7-(--CH.sub.2CH.sub.2O--).sub.x-(--CH.sub.2CH.sub.2--).sub.r-].sub-
.a-A--R.sub.3--B-[-(--CH.sub.2CH.sub.2--).sub.s-(--CH.sub.2CH.sub.2O--).su-
b.y--R.sub.8].sub.b Formula 3 wherein A and B are each
independently a single bond, O, N, ##STR15## R.sub.7 and R.sub.8
are each independently H, OH, NH.sub.2, O(C.sub.nH.sub.2n+1),
O(C.sub.nH.sub.2n-1), CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, R.sub.3 is
C.sub.nH.sub.2n, C.sub.nH.sub.2n-2, or CH.sub.2CH(CH.sub.3)O,
R.sub.9, R.sub.10, R.sub.11, R.sub.12, R.sub.13, and R.sub.14, can
each independently be O, S, or NH, a, b, r, and s are each
independently 0, 1, 2, or 3, x and y are each independently an
integer from 1 to about 10,000, g is an integer from 2 to about 20,
and n is an integer from 1 to about 20; or ##STR16## wherein A, G,
and Q are each independently a single bond, O, N, ##STR17##
R.sub.1, R.sub.2, R.sub.4, and R.sub.5 are each independently H,
OH, NH.sub.2, O(C.sub.nH.sub.2n+1), O(C.sub.nH.sub.2n-1),
CH.sub.2OH, -(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, C.sub.nH.sub.2n+1,
(C.sub.nH.sub.2n+1)(CN).sub.2C, or SO.sub.4H; R.sub.9, R.sub.10,
R.sub.11, R.sub.12, R.sub.13, and R.sub.14, are each independently
O, S, or NH, f is an integer from 1 to about 10,000, p and q are
each independently 0, 1, 2, or 3, m is an integer from 0 to about
10,000, at least one of p, q, and m is an integer greater than 0, g
is an integer from 2 to about 20, and n is an integer from 1 to
about 20.
12. A fluid processing device comprising: a substrate; a plurality
of retainment regions formed in or on the substrate, comprising at
least a first retainment region and a second retainment region; and
a barrier at least partially separating the first retainment region
from the second retainment region, wherein said barrier comprises
at least one of a polyethylene glycol material, a derivative of a
polyethylene glycol material, and a combination thereof, and being
adapted to dissolve when contacted with water at room
temperature.
13. The fluid processing device claim 12, wherein said barrier
completely separates the first retainment region from fluid
communication with the second retainment region.
14. The fluid processing device claim 12, wherein the barrier
comprises at least one of a polyethylene glycol material and a
derivative of a polyethylene glycol material, having a molecular
weight of from about 500 Daltons to about 5,000,000 Daltons.
15. The fluid processing device of claim 12, further comprising: at
least one additional retainment region; at least one fluid
processing passageway; and at least one valve comprising a
pressure-actuatable valve or a heat-actuatable valve arranged in
the at least one fluid processing passageway, wherein the at least
one fluid processing passageway is in fluid communication with the
at least one additional retainment region and at least one of the
plurality of retainment regions.
16. The fluid processing device of claim 15, wherein the at least
one valve comprises at least one pressure-actuatable valve
comprising a burstable valve that is adapted to open and establish
fluid communication only upon receiving pressure of at least about
1 psig from a fluid in the at least one additional retainment
region.
17. The fluid processing device of claim 12, wherein the barrier
comprises one or more of a substituted polyethylene glycol
material, a polyethylene glycol derivative, and a branched
polyethylene glycol, a derivative of a branched polyethylene
glycol, and a combination thereof.
18. The fluid processing device of claim 12, wherein the barrier
comprises a material having the formula:
R.sub.1--Q-(--CH.sub.2--).sub.p-(--OCH.sub.2CH.sub.2--).sub.m-(--CH.sub.2-
--).sub.q-G--R.sub.2 Formula 1 wherein G and Q are each
independently a single bond, O, N, ##STR18## R.sub.1 and R.sub.2
are each independently H, OH, NH.sub.2, CH.sub.3, C.sub.2H.sub.5,
OCH.sub.3, OC.sub.2H.sub.5, CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, R.sub.9, R.sub.10,
R.sub.11, R.sub.12, R.sub.13, and R.sub.14, are each independently
O, S, or NH, p and q are each independently 0, 1, 2, or 3, m is an
integer from 0 to about 10,000; at least one of p, q, and m is an
integer greater than 0, g is an integer from 2 to about 20, and n
is an integer from 1 to about 20; ##STR19## wherein R.sub.4,
R.sub.5, and R.sub.6 are each independently H, OH, NH.sub.2,
CH.sub.3, C.sub.2H.sub.5, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, u is an integer from 0 to
about 10,000, g is an integer from 2 to about 20, n is an integer
from 1 to about 20, t, v, and z are each independently an integer
from 0 to about 10,000, and at least one of t, u, and v, is an
integer greater than 0;
[R.sub.7-(--CH.sub.2CH.sub.2O--).sub.x-(--CH.sub.2CH.sub.2--).sub.r-].sub-
.a-A--R.sub.3--B-[-(--CH.sub.2CH.sub.2--).sub.s-(--CH.sub.2CH.sub.2O--).su-
b.y--R.sub.8].sub.b Formula 3 wherein A and B are each
independently a single bond, O, N, ##STR20## R.sub.7 and R.sub.8
are each independently H, OH, NH.sub.2, CH.sub.3, C.sub.2H.sub.5,
OCH.sub.3, OC.sub.2H.sub.5, CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, R.sub.3 is
C.sub.nH.sub.2n, C.sub.nH.sub.2n-2, or CH.sub.2CH(CH.sub.3)O,
R.sub.9, R.sub.10, R.sub.11, R.sub.12, R.sub.13, and R.sub.14, can
each independently be O, S, or NH, a, b, r, and s are each
independently 0, 1, 2, or 3, x and y are each independently an
integer from 1 to about 10,000, g is an integer from 2 to about 20,
and n is an integer from 1 to about 20; or ##STR21## wherein: A, G,
and Q are each independently a single bond, O, N, ##STR22##
R.sub.1, R.sub.2, R.sub.4, and R.sub.5 are each independently H,
OH, NH.sub.2, CH.sub.3, C.sub.2H.sub.5, OCH.sub.3, OC.sub.2H.sub.5,
CH.sub.2OH, -(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1, R.sub.9, R.sub.10,
R.sub.11, R.sub.12, R.sub.13, and R.sub.14, are each independently
O, S, or NH, f is an integer from 1 to about 10,000, p and q are
each independently 0, 1, 2, or 3 m is an integer from 0 to about
10,000, at least one of p, q, and m is an integer greater than 0, g
is an integer from 2 to about 20, and n is an integer from 1 to
about 20.
19. A method comprising: providing a fluid processing device
comprising at least a first retainment region and a second
retainment region, and a barrier arranged between the first
retainment region and the second retainment region, wherein at
least one of the first and second retainment regions retains an
aqueous solution, the barrier comprises at least one of a
polyethylene glycol material, a derivative of a polyethylene glycol
material, and a combination thereof, and the barrier is adapted to
dissolve when contacted with the aqueous solution; and contacting
the barrier with the aqueous solution to dissolve at least a
portion of the barrier and form, or increase the size of, a fluid
communication between the first retainment region and the second
retainment region.
20. A method of performing a set of predetermined assays,
comprising: providing a plurality of retainment regions in a
closed, disposable cuvette, the retainment regions interconnected
by fluid processing passageways but closed to fluid flow to or from
locations outside of the cuvette, the cuvette including: first
retainment regions; second retainment regions; first fluid
processing passageways interconnecting the first retainment regions
from the second retainment regions, wherein the first retainment
regions are selectively closed-off from fluid communication with
the second retainment regions by pressure-actuated valves
positioned in the first fluid processing passageways; one or more
third retainment regions interconnected by second fluid processing
passageways with at least the second retainment regions; and fluid
flow modulators positioned in the second fluid processing
passageways; applying pressure to the pressure actuated valves in
the first fluid processing passageways sufficient to provide fluid
communication between the first and second retainment regions;
introducing a sample for testing or other processing into the one
or more third retainment regions; and establishing fluid
communication between the second retainment regions and the one or
more third retainment regions at a controlled rate that is a
function of characteristics of at least one of the sample in the
one or more third retainment regions and a fluid within the second
retainment regions.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims benefit under 35 U.S.C. Section
119(e) from earlier U.S. Provisional Patent Applications Nos.
60/619,731, 60/619,677, and 60/619,623, all of which were filed
Oct. 18, 2004, and all of which are incorporated herein in their
entireties by reference.
INTRODUCTION
[0002] The present teachings relate to a diagnostic device and
method providing automatically controlled interconnection between a
plurality of retainment regions.
[0003] A portable or nonportable diagnostic device or method can
perform a set of predetermined assays by providing for controlled
interaction between various fluids initially present in separate
retainment regions. A device and method compatible with nucleic
acid sequence reactions, and detecting such reactions, is
desirable.
SUMMARY
[0004] According to various embodiments, a diagnostic device is
provided that includes a plurality of retainment regions, as
exemplified below, with the retainment regions being interconnected
through a plurality of fluid communications, fluid processing
passageways, and/or channels. Herein the phrase "retainment region"
means a retainment or containment feature such as a well, a fluid
retainment region, a reservoir, a channel, a vial, a compartment,
another receptacle, a surface on which a material is retained, or
the like. The following discussion with regard to retainment
regions would be equally applicable to any of the above-mentioned
features or their equivalents.
[0005] The retainment regions can include a reaction retainment
region, one or more reagent retainment regions each containing
reagents, and a sample retainment region. A pressure-actuated valve
can be positioned in each of the fluid processing passageways
interconnecting the one or more reagent retainment regions with
respective intermediate retainment regions interposed between each
of the one or more reagent retainment regions and the reaction
retainment region. A barrier or fluid flow modulator, as
exemplified below with reference to a valve, can be provided in one
or more of the fluid processing passageways interconnecting the
reagent retainment regions with the reaction retainment region or
intermediate retainment regions, or interconnecting the
intermediate retainment regions and the reaction retainment
region.
[0006] According to various embodiments, a method of performing a
set of predetermined assays is provided. The method can include
providing a plurality of retainment regions in a closed, and if
desired, disposable cuvette, with the retainment regions being
interconnected by fluid processing passageways but closed to fluid
flow to or from locations outside of the cuvette. First retainment
regions can be selectively closed off from fluid communication with
second retainment regions with which they are interconnected by
first channels including pressure-actuated valves positioned
therein. The pressure-actuated valves can comprise a burstable or
tearable diaphragm, or other frangible seal that can rupture, tear,
break, or the like, when exposed to a change in pressure, for
example, an increase or decrease in pressure. One or more third
retainment regions can be selectively closed off from fluid
communication with at least the second retainment regions with
which they are interconnected by second channels by valves
positioned in the second channels. Pressure can be applied to the
pressure actuated valves in the first channel sufficient to provide
fluid communication between the first and second retainment
regions. A sample to be tested or otherwise processed can be
introduced into the one or more third retainment regions, and fluid
communication can be established between the second retainment
regions and the one or more third retainment regions at a
controlled rate that can be a function of any one of a number of
stimuli and/or characteristics of at least one of the sample in the
one or more third retainment regions and a fluid within the second
retainment regions. The characteristics of at least one of the
sample in the one or more third retainment regions and a fluid
within the second retainment region can include, but are not
limited to water content, pH, chemical composition, temperature,
electrical charge, magnetic properties, or the like.
[0007] The closed, and if desired, disposable cuvette, can be
provided as a substrate that is fabricated from a single piece or
more than one piece. The retainment regions, interconnecting fluid
processing passageways, and/or valves can be fabricated all in the
single piece substrate, or if desired, can be fabricated in one or
more different pieces, which can then be combined to form the
cuvette.
[0008] According to some embodiments, the device can comprise no
vent, at least one vent, or a plurality of vents, to relieve
pressure resulting from a flow of a fluid and its communication. A
vent can comprise a vent channel configured to relieve such
pressure. A vent can be provided in communication with a retainment
region, such that upon fluid flow resultant pressure is released. A
vent channel can comprise a hydrophobic vent channel that allows
air to travel through the channel but does not allow the flow of an
aqueous fluid.
[0009] According to some embodiments, a device is provided that can
comprise no vent and can be manufactured and sealed under vacuum
whereby the device can comprise a low internal gas pressure
relative to the external ambient pressure.
[0010] Additional features and advantages of various embodiments
will be set forth in part in the description that follows, and in
part will be apparent from the description, or can be learned by
practice of various embodiments. Other advantages of the various
embodiments will be realized and attained by means of the elements
and combinations exemplified in the application.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Various embodiments of the present teachings are exemplified
in the accompanying drawings. The teachings are not limited to the
embodiments depicted in the drawings, and include equivalent
structures and methods, as set forth in the following description
and as would be known to those of ordinary skill in the art in view
of the present teachings.
[0012] FIGS. 1(a), 1(b), and 1(c) schematically illustrate various
stages in the operation of a valve according to various
embodiments.
[0013] FIG. 2 is a schematic illustration of a diagnostic device
according to various embodiments.
[0014] FIG. 3 is a schematic illustration of a diagnostic device
according to various embodiments.
[0015] FIGS. 4A-4J schematically illustrate various stages in the
operation of a diagnostic device according to an embodiment.
[0016] FIGS. 5A-5J schematically illustrate various stages in the
operation of a diagnostic device according to an embodiment.
[0017] FIG. 6 illustrates the assembly of a diagnostic device from
two separate pieces.
[0018] FIG. 7 illustrates the effect of misalignment of the pieces
shown in FIG. 6 for an embodiment of the device as shown in FIG.
3.
[0019] FIG. 8 illustrates the effect of misalignment of the pieces
shown in FIG. 6 for an embodiment of the device as shown in FIG.
2.
[0020] FIG. 9 illustrates an arrangement of retainment regions and
a valve according to various embodiments.
[0021] FIG. 10 illustrates an arrangement of retainment regions and
a valve according to various embodiments.
[0022] FIG. 11 illustrates an arrangement of retainment regions and
a valve according to various embodiments.
[0023] It is to be understood that both the foregoing general
description and the following detailed description are exemplary
and explanatory only and are intended to provide a further
explanation of the various embodiments of the present
teachings.
DESCRIPTION OF VARIOUS EMBODIMENTS
[0024] According to various embodiments, a diagnostic device, that
can be either portable or nonportable, is provided to perform one
or more predetermined assays as desired, for example, in nucleic
acid sequence detection technology. For a given assay, the assay
protocol can involve a set of fluid handling steps such as mixing,
incubation, washing, and the like, which are desirably performed in
a given sequence of steps and for specified time periods for
samples and reagents in specified volumes or proportions. The
device can be miniaturized to the point that it can be used as a
handheld portable diagnostic device. As shown in the exemplary
embodiments illustrated in FIG. 2 and FIG. 3, the diagnostic device
can include a plurality of retainment regions, as exemplified
below, interconnected by fluid processing passageways. The
plurality of retainment regions can be included within a closed,
disposable cuvette such that all of the retainment regions are
closed to fluid flow to or from locations outside of the cuvette.
The plurality of retainment regions in the cuvette can include a
reaction retainment region, one or more reagent retainment regions,
each containing unreacted reagents, and a sample retainment region
that can contain or receive a sample to be reacted with the
unreacted reagents. The unreacted reagents, which can include
enzymes, buffers, catalysts, or other reaction components, can be
contained in a first set of retainment regions that are
interconnected with an intermediate set of retainment regions by
fluid processing passageways containing pressure-actuated valves.
The intermediate retainment regions can also be connected through
fluid processing passageways to a reaction retainment region, with
the fluid processing passageways that connect the intermediate
retainment regions to the reaction retainment region comprising a
material that is adapted to reduce in volume within the fluid
processing passageway when brought into contact with fluids from
the intermediate retainment regions, or when brought into contact
with a sample after the sample has been added to the sample
retainment region.
[0025] The term "fluid processing passageway" means any area, a
structure, or communication, that allows for fluid communication
between at least two retainment regions, for example, a channel
connecting two regions. One or more fluid processing passageways
according to the present teachings can be configured or adapted to
provide capillary driven flow. One or more fluid processing
passageways according to the present teachings can be configured or
adapted to provide electrokinetic driven flow. One or more of the
fluid processing passageways according to the present teachings can
be configured or adapted to control the rate and timing of fluid
flow by varying the dimensions of the fluid processing
passageway.
[0026] The terms "fluid processing passageway," "a fluid
communication," "fluid flow channel," "fluid processing
passageway," "flow channel," "flow control channel," and "flow
control passageway," are each used synonymous with the term "fluid
passageway," as herein defined.
[0027] According to various embodiments, the term "fluid" means a
gas, an aqueous fluid, a non-aqueous fluid, a vacuum, or a partial
vacuum. A gas can comprise, for example, air. Where two retainment
regions are separated by a fluid flow modulator, one retainment
region can comprise, for example, an aqueous or non-aqueous fluid
retained therein, while the other retainment region can comprise a
gas or a vacuum or partial vacuum, contained therein. In various
embodiments, the device can be manufactured to provide a vacuum on
one or more sides of a dissolvable valve, for example, to achieve a
pressure of from about 0.01 to about 0.99 atm, or from about 0.1 to
about 0.5 atm.
[0028] The term "retainment region" means any area that can
comprise a reagent or other reaction component for a reaction where
the retainment region is in fluid communication with, fully
separate from, or partially separate from, another retainment
region that can comprise another reagent or reaction component for
the reaction that is the same as or different from the first
reagent. A first retainment region can be separate from a second
retainment region, or a first retainment region can be surrounded
by a second retainment region, where the first and second
retainment regions are separated by a barrier comprising a
shaped-wall.
[0029] A retainment region can comprise any area, structure, or
form, capable of retaining a volume of fluid. A retainment region
can be used, for example, to retain, process, react, store,
incubate, transfer, purify, or the like, a fluid sample. A
retainment region can comprise a surface area, an area, a recess, a
reservoir, a chamber, a depression, a well, a space, or the like.
According to some embodiments, a retainment region can comprise,
for example, a flat surfaces with hydrophobic regions surrounding
hydrophilic loci for receiving, containing, retaining, or binding a
sample. A retainment region can comprise any shape, for example,
round, teardrop, square, polygon, star, irregular, ovoid,
rectangular, or the like. A retainment region or fluid processing
passageway can comprise any cross-section configuration, for
example, square, round, ovoid, irregular, trapezoid, or the
like.
[0030] The terms "reservoir," "retainment region," and "region,"
are used synonymously herein.
[0031] The term "reagent for reaction," means one or more reagents
or components necessary or desirable for use in one or more
reactions or processes, for example, one or more components that in
any way affect how a desired reaction can proceed. The reagent for
reaction can comprise a reactive component. However, it is not
necessary that the reagent participate in the reaction. The reagent
for reaction can comprise a non-reactive component. The reagent for
reaction can comprise a recoverable component comprising for
example, a solvent and/or a catalyst. The reagent for reaction can
comprise a promoter, accelerant, or retardant that is not necessary
for a reaction but affects the reaction, for example, affects the
rate of the reaction. The reagent for reaction can comprise one or
more of a solid reagent for reaction and a fluid reagent for
reaction. The term "reaction component" is used synonymous with the
term "reagent for reaction," as herein defined. The reagent for
reaction can comprise one or more of a fluid and a solid. A
retainment region can be pre-loaded with one or more reagents for
reaction.
[0032] The term "vent" means any configuration or structure that
relieves vacuum and/or back pressure, or equalizes pressure in a
fluid processing device. A vent can comprise a channel or a
microchannel. A vent can comprise a non-flow through vent in which
gas that is displaced by a fluid can collect. A non-flow through
vent can comprise, for example, a hydrophobic vent.
[0033] According to various embodiments, suitable reactions or
processes can comprise one or more of a sample preparation process,
a washing process, a sample purification process, a
pre-amplification process, a pre-amplified product purification
process, an amplification process, an amplified product
purification process, a separation process, a sequencing process, a
sequencing product purification process, a labeling process, a
detecting process, or the like. Processing components can comprise
sample preparation components, purification components,
pre-amplification reaction components, amplification reaction
components, sequencing reaction components, or the like. The
skilled artisan can readily select and employ suitable components
for a desired reaction or process, without undue
experimentation.
[0034] According to some embodiments, processing or reaction
components can be disposed in one or more retainment regions,
channels, or fluid processing passageways, using any methods known
in the art. For example, components can be sprayed and dried,
delivered using a diluent, injected using a capillary, a pipette,
and/or a robotic pipette, or otherwise disposed in the regions or
fluid processing passageways.
[0035] According to various embodiments, a fluid processing device
is provided that can comprise one or more fluid processing
passageways that can comprise one or more elements, for example,
one or more of a channel, a branch channel, a valve, a flow
splitter, a vent, a port, an access area, a via, a bead, a reagent
containing bead, a cover layer, a reaction component, any
combination thereof, and the like. Any element can be in fluid
communication with another element.
[0036] The term "fluid communication" means either direct fluid
communication, for example, two regions can be in fluid
communication with each other via an unobstructed fluid processing
passageway connecting the two regions or can be capable of being in
fluid communication, for example, two regions can be capable of
fluid communication with each other when they are connected via a
fluid processing passageway that can comprise a valve disposed
therein, wherein fluid communication can be established between the
two regions upon actuating the valve, for example, by dissolving a
dissolvable valve disposed in the fluid processing passageway.
[0037] The term "in fluid communication" refers to in direct fluid
communication and/or capable of direct fluid communication, unless
otherwise expressly stated. The term "in valved fluid
communication" refers to elements wherein a valve is disposed
between the elements, such that upon opening or actuating the
valve, fluid communication between the elements is established.
[0038] According to some embodiments, the term "capillary flow"
means passive flow resulting from a capillary potential gradient or
a surface potential gradient, created during device fabrication
that can direct the flow of liquid via capillary effect (surface
tension).
[0039] According to some embodiments a fluid processing device is
provided. The device can comprise a substrate that can comprise,
for example, a top or a first surface, and one or more fluid
processing passageways that can be provided in communication with
and/or can be defined by, for example, at least a portion of the
top or first surface of the substrate. The one or more fluid
processing passageways can be provided, for example, in a top or
first surface of a substrate, on a top or first surface of a
substrate, in a substrate, in a bottom or second surface of a
substrate, on a bottom or second surface of a substrate, in an edge
of a substrate, on an edge of a substrate, or any combination
thereof. A fluid processing device can comprise different levels
and layers of fluid processing passageways that can comprise, for
example, different levels and layers of fluid processing
passageways and regions. For example, a tiered, multi-channel
device can comprise one or more fluid processing passageways that
traverse different heights or levels in the substrate.
[0040] Throughout the application, descriptions of various
embodiments use "comprising" language; however, it will be
understood by one of skill in the art, that in some specific
instances, an embodiment can alternatively be described using the
language "consisting essentially of" or "consisting of."
[0041] For purposes of better understanding the present teachings
and in no way limiting the scope of the teachings, it will be clear
to one of skill in the art that the use of the singular includes
the plural unless specifically stated otherwise. Therefore, the
terms "a," "an" and "at least one" are used interchangeably in this
application.
[0042] Unless otherwise indicated, all numbers expressing
quantities, percentages or proportions, and other numerical values
used in the specification and claims, are to be understood as being
modified in all instances by the term "about." Accordingly, unless
indicated to the contrary, the numerical parameters set forth in
the following specification and attached claims are approximations
that may vary depending upon the desired properties sought to be
obtained. In some instances, "about" can be understood to mean a
given value .+-.5%. Therefore, for example, about 100 nl, could
mean 95-105 nl. At the very least, each numerical parameter should
at least be construed in light of the number of reported
significant digits and by applying ordinary rounding
techniques.
[0043] As used herein, the term "plurality" means "two or more."
Herein, the term "two or more" is used synonymously with the term
"plurality."
[0044] A user can operate the diagnostic device by injecting a
sample into the sample retainment region, prior to, at the same
time as, or subsequent to pushing a button or otherwise applying
pressure to the retainment regions that contain unreacted reagents.
For example, a user can inject a sample and then push a button or
other feature or area of the device. As an example of an assay
performed with a device according to various embodiments, a typical
ligation assay for detection of oligo-nucleotides can include
constituents comprising the sample, a ligation oligomer, ligation
reagent which can be a mixture of enzyme and buffer, a wash buffer,
and extension and detection reagents. The sample, the ligation
oligomer, and the ligation reagent can be allowed to mix and react
along with wash buffers and the extension and detection reagents in
an automatically controlled process. The process can occur after a
user has injected the sample into the sample retainment region and
has released the reagents from the unreacted reagent retainment
regions by applying pressure to those retainment regions.
[0045] According to various embodiments, a diagnostic device can be
provided that uses capillary driven flow for fluid actuation. The
flow cross-section of the fluid processing passageways
interconnecting the various retainment regions can contribute to
the rate at which the reagents and sample are mixed in the reaction
retainment region. Valves placed within the flow control fluid
processing passageways interconnecting the retainment regions can
provide automatic flow control and timing of the fluid
actuation.
[0046] According to various embodiments, a fluid flow modulator, as
exemplified below with reference to a valve in a flow control
passageway interconnecting retainment regions, can comprise a
material that dissolves when brought into contact with a fluid
having desired characteristics. Herein, the phrase "dissolvable
valve" will be used interchangeably with the phrase "solute bridge
valve." The solute bridge valve can automatically control flow
through the fluid processing passageway interconnecting the
retainment regions and control the timing of fluid actuation by
exploiting the time it takes to dissolve, melt, or otherwise
wash-away or reduce the volume of the material making up the solute
bridge valve.
[0047] According to various embodiments, the fluid processing
device can comprise a fluid processing passageway, a plurality of
retainment regions with at least two of the retainment regions each
being in fluid communication with the fluid processing passageway,
and a fluid flow modulator arranged in the fluid processing
passageway and adapted to open and form, or to increase in size, a
fluid communication between the at least two retainment regions.
The fluid flow modulator can comprise at least one of a
polyethylene glycol material, a derivative of a polyethylene glycol
material, or a combination thereof. The fluid flow modulator can
comprise a material that is adapted to dissolve when contacted with
water at room temperature. At least one of the plurality of
retainment regions can comprise an aqueous fluid retained
therein.
[0048] According to various embodiments, the fluid processing
device comprises a fluid flow modulator in the form of a valve. The
valve can block fluid flow through a fluid processing
passageway.
[0049] The fluid flow modulator can be in the form of a valve that
only partially blocks fluid flow through the fluid processing
passageway.
[0050] According to various embodiments, the fluid flow modulator
can comprise at least one of a polyethylene glycol material and a
derivative of a polyethylene glycol material, having a molecular
weight of from about 500 Daltons to about 5,000,000 Daltons. The
fluid flow modulator can comprise at least one of a polyethylene
glycol material and a derivative of a polyethylene glycol material,
having a melting point of from about 35.degree. C. and about
65.degree. C.
[0051] According to various embodiments, the fluid processing
device comprises a fluid processing passageway dimensioned so that
a flow of fluid from at least one of two or more retainment regions
and through the fluid processing passageway, can occur by capillary
action. One or more maximum dimensions of about 5 millimeter or
less, for example, about 2 millimeters or less, or about 1
millimeter or less.
[0052] According to various embodiments, the fluid processing
device comprises a fluid processing passageway dimensioned so that
a migration of charged components in a fluid, from at least one of
the retainment regions through the fluid processing passageway, is
capable of migration by electrokinetic action. One or more maximum
dimensions of about 5 millimeter or less, for example, about 2
millimeters or less, or about 1 millimeter or less.
[0053] According to various embodiments, the fluid processing
device can comprise at least two electrodes disposed in the device
with a fluid processing passageway therebetween. A system can be
provided that includes electrical leads that can be electrically
connected to the electrodes.
[0054] According to various embodiments, the fluid processing
device can further comprise at least one additional retainment
region, at least one additional fluid processing passageway, and at
least one pressure-actuatable valve arranged in the at least one
additional fluid processing passageway. The additional fluid
processing passageway can be in fluid communication with the
additional retainment region and one or more other retainment
regions. The pressure-actuatable valve can comprise a frangible
diaphragm. The frangible diaphragm can comprise a material that is
insoluble in water at room temperature. The pressure-actuatable
valve can comprise a burstable valve that is adapted to open and
establish fluid communication only upon receiving pressure of at
least about 0.1 psig, for example, at least about 0.5 psig, at
least about 1 psig, or at least about 3 psig from a fluid in at
least one additional retainment region. The device cam comprise a
liquid retained in at least one additional retainment region.
[0055] According to various embodiments, the fluid processing
device can comprise at least one heat-actuatable valve arranged in
at least one additional fluid processing passageway. The at least
one additional fluid processing passageway can be in fluid
communication with at least one additional retainment region and at
least one of the plurality of retainment regions. The
heat-actuatable valve can comprise at least one material selected
from a rubber, a plastic, a wax, a paraffin, a polyethylene glycol
material, a derivative of a polyethylene glycol material, a
polysaccharide, a derivative of polysaccharide, and combinations
thereof. The heat-actuatable valve can comprise a material that is
insoluble in water at room temperature. The heat-actuatable valve
can comprise a material that has a melting point of from about
35.degree. C. to about 95.degree. C., for example, from about
35.degree. C. to about 70.degree. C., from about 35.degree. C. to
about 65.degree. C., or from about 35.degree. C. to about
50.degree. C.
[0056] According to various embodiments, the fluid processing
device can comprise a liquid retained in at least one retainment
region. The fluid processing device can comprise a first reagent
for a reaction, retained in at least a first one of the plurality
of retainment regions. The fluid processing device can comprise a
second reagent for the reaction retained in at least a second one
of the plurality of retainment regions. The second reagent can be
the same as, or can differ from, the first reagent.
[0057] According to various embodiments, the fluid processing
device comprises a fluid flow modulator that comprises a
substituted polyethylene glycol material. An exemplary substituted
polyethylene glycol comprises poly (ethylene glycol) methyl ether.
The fluid flow modulator comprises a polyethylene glycol
derivative. An exemplary polyethylene glycol derivative can
comprise a triblock copolymer of polyethylene oxide and
polypropylene oxide. The fluid flow modulator can comprise a
branched polyethylene glycol or derivative thereof. Exemplary
substituted polyethylene glycol materials are shown in Table 1
below: TABLE-US-00001 TABLE 1 Examples for Substituted
Poly(ethylene glycol)s ##STR1## Trade mp (.degree. Ca. M.sub.n #
Name Chemical Name R.sub.1 R.sub.2 G Q m p q C.) (Da) HLB Supplier
1 Brij .RTM. poly(ethyleneglycol) cetyl ether C.sub.16H.sub.33 H O
O -- zero zero 32- 683 12.9 ICl 56 34 Americas, Norwich, NY 2 Brij
.RTM. poly(ethyleneglycol) cetyl ether C.sub.16H.sub.33 H O O --
zero zero 38- 1124 15.7 ICl 58 43 Americas, Norwich, NY 3 Brij
.RTM. poly(ethyleneglycol) stearyl ether C.sub.18H.sub.37 H O O --
zero zero 37- 711 12.4 ICl 76 39 Americas, Norwich, NY 4 Brij .RTM.
poly(ethyleneglycol) stearyl ether C.sub.18H.sub.37 H O O -- zero
zero 44- 1152 15.3 ICl 78 66 Americas, Norwich, NY 5 Brij .RTM.
poly(ethyleneglycol) stearyl ether C.sub.18H.sub.37 H O O -- zero
zero 51- 4670 18.8 ICl 700 54 Americas, Norwich, NY 6 --
Poly(ethylene glycol) disterate C.sub.17H.sub.35CO OCC.sub.17 O O
-- 2 2 35- 930 -- Aldrich H.sub.35 37 Chemical, Milwaukee, WI 7 --
Poly(ethylene glycol) disterate C.sub.17H.sub.35CO OCC.sub.17 O O
-- 2 2 52- 12500 -- Polysciences, H.sub.35 57 Warrington, PA 8 --
Poly(ehtylene glycol) bis(3- H.sub.2N(CH.sub.2).sub.3 H.sub.2N( O
single .about.34 zero zero 49 -- -- Aldrich aminopropyl) ehter
CH.sub.2).sub.3 bond Chemical, Milwaukee, WI 9 -- Poly(ethylene
glycol) HO.sub.2CCH.sub.2 CH.sub.2 O single -- zero zero -- 600 --
Aldrich bis(carboymethyl) ether CO.sub.2H bond Chemical, Milwaukee,
WI 10 -- Poly(ethylene glycol) methyl ether CH.sub.3 H O O -- zero
zero 20 550 -- Aldrich Chemical Milwaukee, WI 11 -- Poly(ethylene
glycol) methyl ether CH.sub.3 H O O -- zero zero 30 750 -- Aldrich
Chemical, Milwaukee, WI 12 -- Poly(ethylene glycol) methyl ether
CH.sub.3 H O O -- zero zero 52 2000 -- Aldrich Chemical, Milwaukee,
WI 13 -- Poly(ethylene glycol) methyl ether CH.sub.3 H O O -- zero
zero 59 5000 -- Aldrich Chemical Milwaukee, WI 14 -- Poly(ethylene
glycol) methyl ether CH.sub.3 CH.sub.3 O O -- zero zero 42 1000 --
Aldrich Chemical, Milwaukee, WI
[0058] Exemplary derivatives of PEG can include those shown in the
Table 2 below: TABLE-US-00002 TABLE 2 Derivatives of PEG* ##STR2##
Average Molecular Melting Pt Trade name Weight (.degree. C.) HLB
Pluronic .RTM.F38 4700 48 >24 Pluronic .RTM.F77 6600 48 >24
Pluronic .RTM.F87 7700 49 >24 Pluronic .RTM.F68 8400 52 >24
Pluronic .RTM.F88 11400 54 >24 Pluronic .RTM.F127 12600 56 18-23
Pluronic .RTM.F108 14600 57 >24 Pluronic .RTM.F98 13000 58
>24 *Triblock copolymers of PEO and PPO (BASF, Mount Olive,
NJ)
[0059] The fluid processing device can comprise a plurality of
fluid flow modulators, wherein each fluid flow modulator comprises
at least one of a polyethylene glycol material, a derivative of a
polyethylene glycol material, and a combination thereof. Each of
the plurality of fluid flow modulators can be adapted to dissolve
when contacted with water at room temperature.
[0060] According to various embodiments, a barrier or fluid flow
modulator can comprise a material having the formula:
R.sub.1--Q-(--CH.sub.2--).sub.p-(--OCH.sub.2CH.sub.2--).sub.m-(--CH.sub.2-
--).sub.q-G--R.sub.2 Formula 1 wherein: G and Q are each
independently a single bond, O, N, ##STR3## R.sub.1 and R.sub.2 are
each independently H, OH, NH.sub.2, O(C.sub.nH.sub.2n+1),
O(C.sub.nH.sub.2n-1), CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1; R.sub.9, R.sub.10,
R.sub.11, R.sub.12, R.sub.13, and R.sub.14, are each independently
O, S, or NH; p and q are each independently 0, 1, 2; or 3, m is an
integer from 0 to about 10,000; at least one of p, q, and m is an
integer greater than 0; g is an integer from 2 to about 20; and n
is an integer from 1 to about 20. The barrier or fluid flow
modulator can comprise a material having the formula: ##STR4##
wherein: R.sub.4, R.sub.5, and R.sub.6 are each independently H,
OH, NH.sub.2, O(C.sub.nH.sub.2n+1), O(C.sub.nH.sub.2n-1),
CH.sub.2OH, -(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1; u is an integer from 0 to
about 10,000; g is an integer from 2 to about 20; n is an integer
from 1 to about 20; t, v, and z are each independently an integer
from 0 to about 10,000; and at least one of t, u, and v, is an
integer greater than 0. The barrier or fluid flow modulator can
comprise a material having the formula:
[R.sub.7-(--CH.sub.2CH.sub.2O--).sub.x-(--CH.sub.2CH.sub.2--).sub.r-].sub-
.a-A--R.sub.3--B-[-(--CH.sub.2CH.sub.2--).sub.s-(--CH.sub.2CH.sub.2--).sub-
.y--R.sub.8].sub.b Formula 3 wherein: A and B are each
independently a single bond, O, N, ##STR5## R.sub.7 and R.sub.8 are
each independently H, OH, NH.sub.2, O(C.sub.nH.sub.2n+1),
O(C.sub.nH.sub.2n-1), CH.sub.2OH -(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, or C.sub.nH.sub.2n+1; R.sub.3 is
C.sub.nH.sub.2n, C.sub.nH.sub.2n-2, or CH.sub.2CH(CH.sub.3)O;
R.sub.9, R.sub.10, R.sub.11, R.sub.12, R.sub.13 and R.sub.14, can
each independently be O, S, or NH; a, b, r, and s are each
independently 0, 1, 2; or 3, x and y are each independently an
integer from 1 to about 10,000; g is an integer from 2 to about 20;
and n is an integer from 1 to about 20. The barrier or fluid flow
modulator can comprise a material having the formula: ##STR6##
wherein: A, G, and Q are each independently a single bond, O, N,
##STR7## R.sub.1, R.sub.2, R.sub.4, and R.sub.5 are each
independently H, OH, NH.sub.2, O(C.sub.nH.sub.2n+1),
O(C.sub.nH.sub.2n-1), CH.sub.2OH,
-(--CH.sub.2CH.sub.2O--).sub.n--H,
CH.sub.2CH.sub.2CH.sub.2NH.sub.2, CH.sub.2CO.sub.2H,
C.sub.gH.sub.2g-1, C.sub.nH.sub.2n+1,
(C.sub.nH.sub.2n+1)(CN).sub.2C, or SO.sub.4H; R.sub.9, R.sub.10,
R.sub.11, R.sub.12, R.sub.13, and R.sub.14, are each independently
O, S, or NH; f is an integer from 1 to about 10,000; p and q are
each independently 0, 1, 2, or 3; m is an integer from 0 to about
10,000; at least one of p, q, and m is an integer greater than 0; g
is an integer from 2 to about 20; and n is an integer from 1 to
about 20.
[0061] According to various embodiments, a fluid processing device
can comprise a substrate, a plurality of retainment regions formed
in or on the substrate, and a barrier at least partially separating
a first retainment region from a second retainment region. The
barrier can comprise at least one of a polyethylene glycol
material, a derivative of a polyethylene glycol material, and a
combination thereof, as described above with reference to the fluid
flow modulator. The barrier can be adapted to dissolve when
contacted with water at room temperature. The barrier can be
included in a device as described above with reference to devices
including a fluid flow modulator, in place of, or in addition to
one or more fluid flow modulators. The barrier can be in the form
of a fluid flow modulator.
[0062] According to various embodiments, a method is provided that
comprises processing a fluid processing device that comprises at
least a first retainment region and a second retainment region, and
a barrier arranged between them. At least one of the first and
second retainment regions retains an aqueous solution. The barrier
can comprise at least one of a polyethylene glycol material, a
derivative of a polyethylene glycol material, and a combination
thereof. The barrier is adapted to dissolve when contacted with the
aqueous solution. According to various embodiments, the method
includes contacting the barrier with the aqueous solution to
dissolve at least a portion of the barrier and form, or increase
the size of, a fluid communication between the first retainment
region and the second retainment region. The fluid processing
device can comprise at least one additional retainment region, at
least one fluid processing passageway, and at least one
pressure-actuatable valve arranged in the at least one fluid
processing passageway. The at least one fluid processing passageway
can be in fluid communication with the at least one additional
retainment region and at least one of the first retainment region
and the second retainment region. The method can comprise opening
the pressure-actuatable valve. The pressure-actuatable valve can
comprise a diaphragm and the method can comprise bursting the
diaphragm by applying pressure to the diaphragm. A heat-actuatable
valve can be actuated instead of, or in addition to, actuation of a
pressure-actuatable valve.
[0063] According to various embodiments, the method can comprise
migrating charged components in a sample from at least one of the
at least two retainment regions, through the fluid processing
passageway, by electrokinetic motion. Migration of the charged
components can be accomplished by creating an electric field in the
device. A system can be provided that includes an electric field
generator.
[0064] According to various embodiments, a method can comprise
creating a pressure differential between a first retainment region
and a second retainment region, and moving, with the pressure
differential, a fluid from one of the first retainment region and
the second retainment region into the other of the first retainment
region and the second retainment region. The pressure differential
can be generated by activating a pump. The pressure differential
can comprise a positive-pressure differential or negative-pressure
differential. A positive pressure means a pressure at or greater
than atmospheric pressure, i.e., 1 atm. A negative pressure means a
pressure less than atmospheric pressure, i.e. less than 1 atm.
[0065] According to various embodiments, the method can comprise
creating a magnetic field across a first retainment region and a
second retainment region, and moving, with the magnetic field,
magnetically attractable materials from one of the retainment
regions toward the other retainment region.
[0066] According to various embodiments, the method can comprise
performing a set of predetermined assays in a plurality of
retainment regions, for example, retainment regions, in a closed,
disposable device. An exemplary device is a cuvette. The retainment
regions can be interconnected by fluid processing passageways but
closed to fluid flow to or from locations outside of the cuvette.
The first retainment regions can be selectively closed-off from
fluid communication with second retainment regions through first
channels that interconnect them. Selective closing-off can be
provided by pressure-actuated valves positioned in the first
channels. The second retainment regions can be interconnected to
third retainment regions by second channels. Flow through the
second channels can be controlled by fluid flow modulators
positioned in the second channels, which can also provide selective
closing-off. The method can comprise applying pressure to a
pressure-actuated valve in a first channel sufficient to break the
valve and provide fluid communication between the first and second
retainment regions. Such a method can be used to introduce a sample
for testing or other processing into one or more third retainment
regions and/or establishing fluid communication between the second
retainment regions and one or more third retainment regions, at a
controlled rate. The controlled rate can be a function of
characteristics of at least one of, a fluid in a third retainment
region and a fluid within the second retainment regions.
[0067] According to various embodiments, a system is provided that
comprises a fluid processing device as described herein, and a
pump, wherein the pump is arranged in fluid communication with at
least one of a fluid processing passageway and one or more
retainment regions.
[0068] A system can be provided that comprises a fluid processing
device as described herein, a power source, and at least two
electrical leads forming electrical connections, respectively,
between the power source and the at least two electrodes. A system
can be provided that comprises a fluid processing device as
described herein, and a magnet, wherein the magnet generates a
magnetic field and the fluid processing device is arranged at least
partially within the magnetic field.
[0069] Exemplary devices and methods according to various
embodiments are described below with reference to the drawings. The
present teachings are not limited to the embodiments depicted in
the drawings.
[0070] Referring to FIGS. 1(a)-1(c), a schematic illustration of
the process by which a solute bridge valve establishes fluid
communication between two passageways, according to various
embodiments, is shown. FIG. 1(a) shows two retainment regions 20,
24 containing fluids 30, 32, respectively, with the two retainment
regions 20, 24 being interconnected through a fluid processing
passageway 26. A solute bridge valve 22 can consist of a plug of
material that completely or partially blocks the flow fluid
processing passageway 26 and separates the fluids, e.g. solvents,
reagents or other materials, in the respective retainment regions
20, 24. In some embodiments, one or both of fluids 30 or 32, can,
at least initially, comprise a gas, a vacuum, a partial vacuum,
and/or a pressurized fluid.
[0071] FIG. 1(b) shows the size of the solute bridge valve 22
decreasing as the material that makes up the solute bridge valve
gradually dissolves into one or both of the fluids 30, 32 in
retainment regions 20, 24. FIG. 1(c) shows that the fluids 30, 32
have come into contact with each other when the material making up
solute bridge valve 22 has completely dissolved. The time required
to completely dissolve the solute bridge valve 22 can be determined
by the cross-sectional area and/or shape of the capillary flow
passage 26 and the length and dissolvability of the solute bridge
valve 22. By controlling the material and/or size of the solute
bridge valve 22, it is also possible to control the length of the
time elapsed before the solute bridge valve has completely
dissolved to allow mixing of the fluids 30, 32.
[0072] It is desirable for the material that makes up the solute
bridge valve 22 to be a material that dissolves into the fluids 30,
32. The material of the solute bridge valve also is desirably
compatible with the assay to be conducted, and would not adversely
affect the assay condition. The solute bridge valve material could
also be an active ingredient that might catalyze or react with
constituents of the assay. Examples of material that can be used to
make up the solute bridge valve 22 include polyethyleneglycol (PEG)
and derivatives of polyethyleneglycol, together referred to herein
as PEG. PEG has desirable properties and some PEG materials can
dissolve in aqueous liquids, such as those typically used in many
biological assays. PEG is generally inert and generally does not
affect biological assays. PEG is easy to pattern using
microfabrication techniques. PEG can be formulated that melts at
relatively low temperatures, i.e. 35-50.degree. C., and can be used
as a thermal "wax." PEG solutions are known to prevent non-specific
binding and precipitation of proteins and peptides on walls of the
fluid processing passageways. PEG is hygroscopic and stabilizes
proteins in solutions.
[0073] According to various embodiments, the solute bridge valve 22
can be made from a material that partially or completely separates
the retainment regions 20, 24 in the diagnostic device. Flow
control through the fluid processing passageway 26 can be affected
by the change in the open cross-sectional area of the fluid
processing passageway between the two retainment regions,
subsequent to the change in volume of the material. The actuation
of the solute bridge valve 22 can comprise the volumetric change of
the material resulting from contact with the solution or solutions
in the retainment regions 20, 24. A change in volume of the
material can result from other characteristics of the solution or
solutions, such as temperature, water content, chemical
composition, electrical charge, magnetic properties, or the like.
If the material making up the solute bridge valve 22 completely
blocks the fluid processing passageway 26, the two retainment
regions 20, 24 are completely separated and the valve is
closed.
[0074] FIG. 2 shows an embodiment of an assay device that uses
capillary driven flow and solute bridge valves to control a
specific sequence of fluid actuation steps. The device shown in
FIG. 2 can be constructed as a microfluidic chip manufactured using
microfabrication techniques. According to various embodiments, the
chip can comprise a set of fluid retainment regions and
microchannels for housing different liquids such as reagents,
samples, etc., and for mixing and reacting the various liquids.
FIG. 2 shows a device according to various embodiments having a
sample fluid retainment region 90 connected through a fluid flow
passage 80 to a reaction retainment region 48. An intermediate
retainment region or retainment regions is/are connected through a
fluid processing passageway 170 containing a valve 70 to the
reaction retainment region 48. A second intermediate retainment
region 46 is connected through a fluid processing passageway 172
containing a valve 72 to the reaction retainment region 48. A first
reagent retainment region 40 for containing unreacted reagents 120
can be connected through a fluid flow passage 160 containing a
valve 60 to one intermediate retainment region 44, while a second
reagent retainment region 42 containing unreacted reagents 124 can
be connected through a fluid flow passage 162 containing a valve 62
to the second intermediate retainment region 46. The reaction
retainment region 48 is connected through a fluid processing
passageway 174 containing a valve 74 to a first waste retainment
region 50. The waste retainment region 50 can also be connected,
through another fluid processing passageway 176 containing a valve
76, to a second waste retainment region 52.
[0075] Reagent retainment regions 40, 42 can be selectively
separated from the intermediate retainment regions 44, 46 by the
pressure actuated valves 60, 62 placed within the fluid flow
passages 160, 162. According to various embodiments, the pressure
actuated valves 60, 62 within fluid processing passageways 160, 162
can be diaphragms that are burstable upon pressure being applied to
the reagent retainment regions 40, 42.
[0076] The intermediate retainment regions 44, 46 can be in turn
connected through the fluid flow passages 170, 172 containing
valves 70, 72 to the reaction retainment region 48. Fluid
communication through the fluid flow passages 170, 172 containing
valves 70, 72 can be controlled by the fluid flow cross-sectional
area of the passages 170, 172 as well as the positioning of solute
bridge valves 70, 72 as discussed above, within the fluid flow
passages 170, 172. The solute bridge valves 70, 72 contained within
the fluid flow passages 170, 172 can provide automatic control of
the fluid communication between the intermediate retainment regions
44, 46 and the reaction retainment region 48 as a result of their
responsiveness to stimuli such as the chemical composition of the
fluids within retainment regions 44, 46 and within reaction
retainment region 48. Each of regions 90, 48, 40, 42, 50, and 52,
can optionally comprise a vent 91, 49, 41, 43, 51, and 53,
respectively.
[0077] FIG. 3 illustrates an embodiment wherein the retainment
regions and fluid processing passageways are arranged such that
solute bridge valves 70a, 72a, 74a, 76a corresponding to solute
bridge valves 70, 72, 74, 76 of the embodiment shown in FIG. 2, are
arranged in a line for ease of manufacture. Each of regions 90a,
48a, 40a, 42a, 50a, and 52a, can optionally comprise a vent 91a,
49a, 41a, 43a, 51a, and 53a, respectively.
[0078] FIGS. 4A-4J illustrate a sequence of events that can occur
during operation of a diagnostic device according to various
embodiments, such as exemplified in FIG. 2. FIGS. 4A-4J are
explained in greater detail below. Each of regions 90, 48, 40, 42,
50, and 52, can optionally comprise a vent 91, 49, 41, 43, 51, and
53, respectively.
[0079] FIGS. 5A-5J illustrate a sequence of events that can occur
during operation of a diagnostic device according to various
embodiments, such as exemplified in FIG. 3. FIGS. 5A-5J are
explained in greater detail below. Each of regions 90a, 48a, 40a,
42a, 50a, and 52a, can optionally comprise a vent 91a, 49a, 41a,
43a, 51a, and 53a, respectively.
[0080] In FIG. 4A a diagnostic device according to various
embodiments is provided with retainment regions 40, 42 prefilled
with, for example, a wash buffer 124 in retainment region 42 and a
detection reagent 120 within retainment region 40. Pressure
actuated valves 60, 62, such as burstable or tearable diaphragms,
can be provided within the fluid flow passages 160, 162 separating
retainment regions 40, 42 from intermediate retainment regions 44,
46.
[0081] In FIG. 4B a user can apply pressure to the retainment
regions 40, 42, thereby actuating or bursting the valves 60, 62
within fluid flow passages 160, 162. Bursting valves 60, 62 can
cause a flow of the buffers and/or reagents within the retainment
regions 40, 42 into intermediate retainment regions 44, 46.
[0082] As shown in FIG. 4C a user can then inject a sample 126 into
the sample retainment region 90, which is connected to the reaction
retainment region 48 through a fluid flow passage 80. Sample
injection could alternatively occur before or at the same time as
bursting the valves. Fluid flow passages 170, 172 and 80 can be
provided with fluid flow modulators, exemplified below with
reference to a solute bridge valve, such as a plug of material that
can change volume when exposed to certain stimuli. The solute
bridge valves can control the fluid communication between
intermediate retainment regions 44, 46 and reaction retainment
region 48, as well as the fluid communication between the sample
retainment region 90 and the reaction retainment region 48. Fluid
flow of the sample from sample retainment region 90 into reaction
retainment region 48 can also be automatically controlled as a
result of the dimensions of the fluid flow passage 80. For example,
the fluid flow passage 80 can be provided as a capillary passage
such that the sample material from sample retainment region 90
gradually wicks into the reaction retainment region 48, without the
need for a solute bridge valve to control this flow through fluid
flow passage 80. Pressure can be relieved or equalized via vent 91
and/or 49.
[0083] As shown in FIG. 4D, the sample material that is now in
reaction retainment region 48 contacts the solute bridge valve 72
on one side of the valve 72 in fluid flow passage 172, while the
reagent in intermediate retainment region 46 contacts the solute
bridge valve 72 from the opposite side of the valve. One or more of
the reagent in retainment region 46 and/or the sample in reaction
retainment region 48 begin to dissolve or otherwise affect the
volume of the material making up the solute bridge valve 72. After
a certain amount of time that is automatically controlled by at
least one of the flow cross-section of passage 172, or the volume
or composition of material at least partially making-up the solute
bridge valve 72, the solute bridge valve 72 no longer prevents the
reagent in retainment region 46 from gradually diffusing into the
sample 126 in reaction retainment region 48, as shown in FIG. 4E.
Pressure can be relieved and/or equalized via vent 43.
[0084] The flow passage 174 leading from the reaction retainment
region 48 into waste retainment region 50 can also be provided with
dimensions that allow for capillary action, and a solute bridge
valve 74 that will gradually dissolve or otherwise change volume as
a result of contact with the fluid from reaction retainment region
48. As shown in FIG. 4F, the effect of the fluid within reaction
retainment region 48 on the solute bridge valve 74 within flow
passage 174 gradually opens the flow passage 174 within which the
valve 74 is positioned to allow fluid communication between the
reaction retainment region 48 and the first waste retainment region
50. The flow of fluid from reaction region 48 into waste region 50
through fluid processing passageway 174 contributes to a capillary
flow of more reagent from reagent region 42 through fluid
processing passageway 162 and intermediate region 46 into reaction
region 48. Pressure resulting from such flow can be relieved via
vent 43 and/or vent 49. Flow of fluid from reaction region 48 into
waste region 50, as shown in FIG. 4G, can also cause more of sample
126 to flow from sample region 90 into reaction region 48. Pressure
resulting from the flow of fluid from reaction region 48 into waste
region 50, can be relieved via vent 49 and/or vent 51. According to
various embodiments, the relative dimensions of the flow passages
such as flow passage 80 leading from sample retainment region 90
into reaction retainment region 48, and the flow passage 172 within
which valve 72 is positioned leading from intermediate retainment
region 46 into reaction retainment region 48, can be selected in
order to contribute to a preferential flow of fluid from the
intermediate retainment region 46 into reaction retainment region
48. A smaller flow cross-section through passage 80 than the flow
cross-section through passage 172 would result in more fluid
flowing from the reagent retainment region 42 and intermediate
retainment region 46 into reaction retainment region 48 than the
amount of sample flowing from sample retainment region 90 into the
reaction retainment region 48.
[0085] After a predetermined amount of time, solute bridge valve 70
provided in the flow passage 170 between intermediate retainment
region 44 and reaction retainment region 48 can also begin to
dissolve, melt, or otherwise change in volume such that reagent 120
flows from reagent retainment region 40 through intermediate
retainment region 44 and into the reaction retainment region 48, as
shown in FIG. 4H. The relative cross-sectional flow areas of the
various flow passages connecting retainment regions as well as the
amount of material provided in the solute bridge valves within the
flow passages can be varied in order to control the amount of time
it takes for the reagents and other fluids within the retainment
regions to move from one retainment region to the next, thereby
providing a control of the fluid handling steps.
[0086] After more time has passed, solute bridge valve 76 in flow
passage 176 leading to a second waste retainment region 52 can
begin to dissolve, melt, or otherwise change in volume such that
fluid can flow from waste retainment region 50 into second waste
retainment region 52, as shown in FIGS. 4I and 4J. This flow can
cause more of the reagents and sample to flow from regions 44, 46
and 90 into reaction region 48. Pressure can be relieved via vent
49 and/or vent 91.
[0087] In an alternative embodiment, as exemplified in FIG. 3 and
FIGS. 5A-5J, the diagnostic device can comprise a set of retainment
regions and microchannels corresponding to the retainment regions
and microchannels of the embodiment exemplified in FIGS. 2 and
4A-4J, but with the solute bridge valves 72a, 70a, 74a, and 76a
being aligned so that they can be formed as a single, extended
length of solute bridge valve material. The length of the solute
bridge valve material can include different portions of different
respective composition. The process by which mixing of buffer
and/or reagent from retainment regions 40a, 42a, and sample from
sample retainment region 90a is controlled automatically
corresponds with the process described above for the embodiment
shown in FIG. 2 and FIGS. 4A-4J.
[0088] A sample solution can be added to sample retainment region
90a, and supplied to a reaction retainment region 48a through a
capillary flow passage 80a, as shown in FIGS. 5C and 5D. Solutions,
such as reagents and/or wash buffers, can be dispensed from
retainment regions 40a, 42a by pressing on the clear layer of film
or other flexible covering over the retainment regions to cause
pressure-actuated valves 60a, 62a in passageways 160a, 162a to
burst and allow the solutions to move into intermediate retainment
regions 44a, 46a. Solution from intermediate retainment region 46a
then begins to act on solute bridge valve 72a in fluid flow passage
172a, opening up a passageway for the solution to enter passage 80a
and reaction retainment region 48a, as shown in FIGS. 5D, 5E, 5F
and 5G. FIG. 5H illustrates solution from retainment region 44a
dissolving, or otherwise reducing the volume of solute bridge valve
70a in passageway 170a. Solute bridge valve 74a in passageway 174a
has also dissolved in FIG. 5H to allow solution from the reaction
retainment region 48a to pass to a waste retainment region 50a. As
described above with regard to the embodiment of FIG. 2, the flow
of solution from reaction region 48a to waste region 50a can create
a suction that can draw more solution from region 46a through fluid
processing passageway 172a and capillary fluid processing
passageway 80a into the reaction region 48a, as shown in FIG. 51.
Solute bridge valve 76a in fluid processing passageway 176a then
dissolves, allowing solution to flow to waste region 52a, and can
create suction that can draw solution from region 44a into reaction
region 48a, as well as drawing additional solution from region 46a
and additional sample from region 90a, as shown in FIG. 5J. For
example, vents 41 and 43 are needed in 40 and 42, respectively,
(FIG. 4A) in order to allow 120 and 124 to flow into 44 and 46,
respectively. Likewise, vent 91 is needed in communication with
region 90. A vent 49 can be provided in communication with regions
48 (FIG. 4D) such that 120, 124 and 126 can flow into it. Without a
vent, the air trapped in 48 can prevent any inflow of liquid. The
same can apply to regions 50 and 52.
[0089] The arrangement of retainment regions, passageways and
valves of the various embodiments exemplified in FIG. 3 provides
for ease of manufacturing. As shown in FIG. 3 and FIGS. 5A-5J, the
solute bridge valves 70a, 72a, 74a, and 76a can be aligned with
each other such that the solute bridge valves can be formed as one
length of material. The diagnostic device 130 shown in FIG. 6
exemplifies an embodiment wherein the solute bridge valves are
formed as one extended length of solute bridge valve material 270
in a substrate 134 separate from a substrate 132, within which
various retainment regions such as retainment regions 140 and 142
are formed. When the two substrates 132 and 134 are sandwiched
together to form the device 130, the length of solute bridge valve
material 270 can connect to passageways 260, 262, 264, and 266, as
shown in FIG. 7, which passageways are connected to various
retainment regions. As illustrated in FIG. 7, even if the two
substrates 132, 134 are not perfectly aligned, the length of solute
bridge valve material 270 will still connect with the passageways
260, 262, 264, and 266. FIG. 8 illustrates a situation wherein
separate substrates for solute bridge valves 370, 372 and
passageways 360, 362, 364, and 366, are not perfectly aligned when
forming a device as exemplified in the embodiment of FIG. 2. In
this situation the solute bridge valves 370, 372 would not connect
to passageways 360, 362, and 364, 366.
[0090] Referring to FIG. 9, and according to various embodiments,
retainment regions 444, 446, and 448 can be formed in a substrate
440, with retainment region 444 interconnected with retainment
region 448 through a passageway 470, and retainment region 446
interconnected with retainment region 448 through a passageway 472.
Solution such as reagents and/or wash buffers can be retained in
the retainment regions 444 and 446 by a flexible sheet of material
460 applied over the top surface of substrate 440 and adhered to
the top surface by an adhesive layer 462. Pressure actuated valves
470a, 472a can be positioned in the passageways 470, 472 such that
pressure applied to the solutions in retainment regions 444, 446 by
pressing down on the flexible sheet 460 over the respective
retainment regions will dispense the solutions through passages
470, 472 into the retainment region 448. A barrier 450 can define
an inner retainment region 430 and provide an automatically
controlled interaction between the solution or solutions 442 in the
retainment region 448 and a solution retained in the inner
retainment region 430. If desired, the barrier 450 can be formed
from a solute material such as PEG that will gradually dissolve and
thereby control the interaction between the solution or solutions
442 in outer retainment region 448 and a solution retained in the
inner retainment region 430.
[0091] According to various embodiments, and as exemplified by the
embodiment shown in FIG. 10, a device can be provided that
comprises a substrate 540 having a retainment region 542 formed in
the substrate and covered by a sheet 560 that is adhered to the top
surface of the substrate 540 by an adhesive 562. An inner
retainment region 530 can be defined within the retainment region
542 by a barrier 550 that can act as a fluid flow modulator between
a solution in the outer retainment region 542 and a solution or
material in the inner retainment region 530. The barrier 550 can
comprise a portion 552 made from a soluble material, and a portion
554 made from an insoluble material to provide a further degree of
automatic control of the interaction between the solutions or other
ingredients in retainment regions 542 and 530. Sample and/or
reagents can be injected into retainment regions 542 to initiate a
process. A septum (not shown) can be provided as an injection
port.
[0092] According to various embodiments, and as exemplified in the
embodiment shown in FIG. 11, the substrate 700 can be provided with
a retainment region 740 connected through a passage 770 having a
pressure actuated valve 772 to a second retainment region 742.
Similarly, another retainment region 740a can be connected through
a passage 770a having a pressure actuated valve 772a to the second
retainment region 742. A star-shaped or otherwise polygonal
retainment region 730 can be defined inside of the second
retainment region 742 by a barrier 750. All of the retainment
regions can be covered by a sheet 760 adhered to the top surface of
substrate 700 by an adhesive layer 762. A solution within
retainment region 740 can be dispensed through passage 770 by
applying pressure to the sheet 760 over the retainment region 740
to force the liquid past the pressure actuated valve 772 into the
second retainment region 742. The barrier 750 can comprise a
material such as PEG that gradually dissolves or melts in response
to a stimuli such as characteristics of the solution that has been
introduced to the second retainment region 742, thereby providing
an automatically controlled interaction between the solution in
second retainment region 742 and the solution in retainment region
730. In an exemplary device, fluid processing passageways could
interconnect with each respective point of the star shape
shown.
[0093] According to various embodiments, further control of the
fluid handling steps can be provided by including various solute
structures within the fluid processing passageways and/or the
retainment regions. The solute structures can be selected to
dissolve over a finite amount of time and change the flow
properties of the fluidic circuit. As an example, raised structures
(such as pillars of different aspect ratios) made from solute
material (such as PEG) can be fabricated by photolithography inside
the various retainment regions, retainment regions, and/or fluid
processing passageways. The incorporation of these structures can
cause the flow paths to have different capillarity and can cause
capillary suction pressures of different magnitudes in different
parts of the fluidic circuit. The structures can also introduce
additional flow resistance, with a variation in the flow resistance
depending on the dissolution of the solute structures.
[0094] In one example, an array of pillars made of PEG could be
fabricated inside of the waste retainment regions 50, 52, in the
embodiment of FIG. 2, or 50a, 52a in the embodiment of FIG. 3,
which could, for example, cause higher suction pressure in waste
retainment region 50 or 50a by capillary action as compared to the
suction pressure in reaction retainment region 48 or 48a. Over
time, the solute structures within waste retainment region 50 or
50a would dissolve in the liquid, which could result in the
capillary suction pressure into retainment region 50 or 50a
reducing over time. Subsequent dissolution of a solute within fluid
processing passageway 176 between waste retainment region 50 and
waste retainment region 52, for example, could then result in the
liquid in waste retainment region 50 being pulled into waste
retainment region 52. The pulling can be as a result of a larger
capillary suction pressure in waste retainment region 52 caused by
solute structures in retainment region 52. The PEG cannot operate
until 74 and 76 in FIG. 2 and 170a, 172a and 174a in FIG. 3 are
open. The flow of 120, 125 and 126 in FIG. 2 into 44, 46, and 48,
respectively, relies on capillary effect alone, and does not rely
on vacuum created by the PEG in 50 or 52 because neither 76 nor 74
are open. PEG can facilitate fluid flow from 48 into 50 and/or 52
without a vent. The flow of 120, 124 or 126 into 44, 46, or 48,
respectively, relies on capillary effect that requires air vents to
prevent pressure build up.
[0095] Those skilled in the art can appreciate from the foregoing
description that the present teachings can be implemented in a
variety of forms. Therefore, while these teachings have been
described in connection with particular embodiments and examples
thereof, the true scope of the present teachings should not be so
limited. Various changes and modifications can be made without
departing from the scope of the teachings herein.
* * * * *