U.S. patent application number 14/127341 was filed with the patent office on 2014-08-14 for microfluidic structure having recesses.
This patent application is currently assigned to BOEHRINGER INGELHEIM MICROPARTS GMBH. The applicant listed for this patent is Dirk Kurowski, Oliver Paul. Invention is credited to Dirk Kurowski, Oliver Paul.
Application Number | 20140227148 14/127341 |
Document ID | / |
Family ID | 44773214 |
Filed Date | 2014-08-14 |
United States Patent
Application |
20140227148 |
Kind Code |
A1 |
Kurowski; Dirk ; et
al. |
August 14, 2014 |
Microfluidic Structure Having Recesses
Abstract
The invention relates to a microfluidic structure (1),
comprising at least one cavity (10) having at least one inlet
opening (11) and at least one outlet opening (12), wherein the
cavity (10) can be filled with a liquid or a liquid can flow
through the cavity and at least one element (13) is provided inside
the cavity (10), which element stops the flow of the liquid at
least temporarily and/or diverts the flow of the liquid at least in
some regions within the cavity (10). According to the invention,
the at least one element (13) is formed by a recess (13) introduced
into a wall of the cavity (10), which recess (13) has at least one
first region (14) at which the liquid stops at least temporarily
and/or is diverted at least in some regions and at least one second
region (15) at which the liquid preferably flows into the recess
(13). Such a microfluidic structure makes it possible to fill the
cavity (10) without air inclusions. Thereby, the useful volume of
the cavity (10) is not limited, and the production costs of a
microfluidic component (2) having such a microfluidic structure (1)
can be kept low.
Inventors: |
Kurowski; Dirk; (Gevelsberg,
DE) ; Paul; Oliver; (Gelsenkirchen, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Kurowski; Dirk
Paul; Oliver |
Gevelsberg
Gelsenkirchen |
|
DE
DE |
|
|
Assignee: |
BOEHRINGER INGELHEIM MICROPARTS
GMBH
Dortmund
DE
|
Family ID: |
44773214 |
Appl. No.: |
14/127341 |
Filed: |
July 2, 2012 |
PCT Filed: |
July 2, 2012 |
PCT NO: |
PCT/EP2012/062863 |
371 Date: |
April 28, 2014 |
Current U.S.
Class: |
422/502 |
Current CPC
Class: |
B01L 3/502723 20130101;
B01L 2400/0406 20130101; B01L 2300/0858 20130101; B01L 2400/084
20130101; B01L 2300/0809 20130101; B01L 2400/086 20130101; B01L
2200/0684 20130101; B01L 2200/0642 20130101; B01L 3/502738
20130101; B01L 3/502746 20130101; B01L 3/5027 20130101; B01L
3/502753 20130101; B01L 2300/0864 20130101 |
Class at
Publication: |
422/502 |
International
Class: |
B01L 3/00 20060101
B01L003/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 5, 2011 |
EP |
11172775.6 |
Claims
1. Microfluidic structure (1, 3, 5), comprising at least one cavity
(10, 30, 40) with at least one inlet opening (11) and at least one
outlet opening (12), the cavity (10, 30, 40) being adapted to be
filled with a liquid F or have such a liquid flow through it and
within the cavity (10, 30, 40) at least one element (13, 31, 41)
being provided which at least temporarily stops and/or at least
partially deflects the liquid (F) as it flows (S) within the cavity
(10, 30, 40), characterised in that the at least one element (13,
31, 41) is formed by a recess (13, 31, 41) provided in a wall (19)
of the cavity (10, 30, 40), said recess (13, 31, 41) comprising at
least one first region (14, 32, 42) at which the liquid (F) is at
least temporarily stopped and/or is at least partly deflected and
at least one second region (15, 15', 5'', 15''', 33, 43), at which
the liquid (F) preferably flows into the recess (13, 31, 41).
2. Microfluidic structure (1, 3, 5) according to claim 1,
characterised in that the second region (15, 33, 43) is formed by a
ramp-like transition (R) which, starting from a base level (19) of
the cavity (10), extends to a base level (20) of the recess
(13).
3. Microfluidic structure (1, 3, 5) according to claim 1,
characterised in that the ramp-like transition (R), starting from a
boundary edge (23) of the recess (13), forms an angle .alpha. of
approximately 10.degree. to 60.degree., particularly preferably
about 45.degree., with the base plane (19) of the cavity (10).
4. Microfluidic structure (1, 3, 5) according to claim 1,
characterised in that the first region (14, 32, 42) is formed by a
boundary edge (22) of the recess (13), at which the convergent
walls forming the boundary edge (22) form an angle .beta. which is
less than 120.degree., particularly preferably about
90.degree..
5. Microfluidic structure (1, 3, 5) according to claim 1,
characterised in that the at least one recess (13, 31, 41) is of
elongate formation, the at least one first region (14, 32, 42)
facing an incoming liquid (F) and the at least one second region
(15, 33, 43) being remote from an incoming liquid (F).
6. Microfluidic structure (1, 3) according to claim 1,
characterised in that a plurality of recesses (13, 31, 41) are
provided which are arranged alternately, starting from side walls
of the cavity (10, 30, 40).
7. Microfluidic structure (1, 5) according to claim 1,
characterised in that the at least one first region (14, 32, 42)
extends over substantially the entire length (L) of a longitudinal
side of the at least one recess (13, 31, 41) and the at least one
second region (15, 33, 43) extends over only part of the length (L)
of another longitudinal side.
8. Microfluidic platform (2, 4, 6) having at least one microfluidic
structure (1, 3, 5) comprising at least one cavity (10, 30, 40)
with at least one inlet opening (11) and at least one outlet
opening (12), the cavity (10, 30, 40) being adapted to be filled
with a liquid F or have such a liquid flow through it and within
the cavity (10, 30, 40) at least one element (13, 31, 41) being
provided which at least temporarily stops and/or at least partially
deflects the liquid (F) as it flows (S) within the cavity (10, 30,
40), characterised in that the at least one element (13, 31, 41) is
formed by a recess (13, 31, 41) provided in a wall (19) of the
cavity (10, 30, 40), said recess (13, 31, 41) comprising at least
one first region (14, 32, 42) at which the liquid (F) is at least
temporarily stopped and/or is at least partly deflected and at
least one second region (15, 15', 5'', 15''', 33, 43), at which the
liquid (F) preferably flows into the recess (13, 31, 41).
Description
[0001] The invention relates to a microfluidic structure comprising
at least one cavity with at least one inlet opening and at least
one outlet opening, the cavity being adapted to be filled with a
liquid or have a liquid flow through it, and at least one element
being provided within the cavity which at least temporarily stops
and/or at least partly diverts the liquid as it flows within the
cavity.
[0002] Microfluidic structures are components of microfluidic
platforms or microfluidic components and essentially comprise
cavities and/or channels in which sample liquids that are to be
investigated or manipulated can be held and transported by suitable
means (e.g. by capillary forces, pressure differences created) to
reaction sites provided accordingly.
[0003] In particular, the present invention encompasses
microfluidic platforms such as for example sample carriers, test
strips, biosensors or the like which may be used for carrying out
individual tests or measurements. For example, biological liquids
(e.g. blood, urine or saliva) may be investigated, on the one hand,
for pathogens and incompatibilities but also, on the other hand,
for their content of for example glucose (blood sugar) or
cholesterol (blood fat). For this purpose corresponding detection
reactions or entire reaction cascades take place on the
microfluidic platforms.
[0004] For this it is necessary for the biological sample liquid to
be transported by suitable means to the reaction site or sites
provided for this purpose. This transporting of the sample liquid
may be carried out for example by passive capillary forces (using
corresponding capillary systems or microchannels) or by means of
active actuating elements. Injection or membrane pumps, for
example, may be used as the active actuating elements and may be
located outside the microfluidic platform or on the platform and
produce a corresponding pressure within a microfluidic structure
consisting in particular of microchannels and microcavities.
[0005] In general, microfluidic platforms comprise a sample input
region of the order of a few millimetres in size for introducing a
quantity of sample liquid of the order of a few microlitres, while
the sample liquid (such as blood) has to be transported through a
microchannel or through a microchannel system to corresponding
cavities containing for example chemical reagents in dried
form.
[0006] In order that a sample liquid can undergo a satisfactory
detection reaction with the reagents in a cavity, it is essential
that the cavity is filled as completely and uniformly as
possible.
[0007] When filling large cavities, particularly those that are
broad and irregularly shaped, for example with lengths and/or width
dimensions of several millimetres and a resulting volume range from
for example 10 .mu.l to about 10 ml, there is the problem that the
cavity does not fill uniformly and thus air inclusions or air
bubbles may form in the cavity. As a result, the whole of the
volume of the cavity is not available for the sample liquid. Dry
substances stored in such a cavity, for example, are thus not
sufficiently dissolved and the formation of clumps may occur, thus
adversely affecting a desired detection reaction.
[0008] According to the prior art, a remedy is offered by providing
bar-like elements in the cavity arranged in such a way that the
liquid in the cavity has to flow in a meandering direction.
[0009] However, a disadvantage of this structure is that the
bar-like elements take up space within the cavity which is actually
needed.
[0010] Therefore, to compensate, more space has to be provided on
the microfluidic platform or microfluidic component. This should be
avoided in particular for microfluidic platforms, on account of the
associated increase in manufacturing costs.
[0011] A microfluidic structure or a microfluidic platform for
filling without any air bubbles is known from DE 103 60 220 A1.
Specifically, a cavity is provided having an inlet opening and an
outlet opening. In the region of the inlet opening the cavity
comprises microstructural elements in the form of pillars. This
region forms an area of increased capillary force. The increased
capillary force initially causes total wetting, free from air
bubbles, of the entry region of the cavity with the sample liquid.
The part of the cavity facing the outlet opening is only wetted
subsequently.
[0012] In order to accelerate the transporting of liquid, a ramp is
provided in the cavity which raises the level of the cavity base to
the level of the outlet opening.
[0013] An arrangement of this kind is unsatisfactory for filling
cavities that are large, particularly broad (at right angles to the
direction of inflow or throughflow of the liquid) and irregularly
shaped.
[0014] The invention is therefore based on the problem of improving
a microfluidic structure according to the preamble of claim 1 so as
to allow improved filling, particularly of large cavities,
particularly substantially free from air bubbles.
[0015] The problem is solved with the charactering features of
claim 1. Advantageous further features of the invention can be
found in the subclaims.
[0016] The invention therefore starts from a microfluidic structure
comprising at least one cavity having at least one inlet opening
and at least one outlet opening, the cavity being adapted to be
filled with a liquid or have such a liquid flow through it and
within the cavity is provided at least one element which at least
temporarily stops and/or at least partially deflects the liquid as
it flows within the cavity.
[0017] According to the invention it is envisaged that the at least
one element is formed by a recess provided in a wall of the cavity,
which has at least one first region at which the liquid is at least
temporarily stopped and/or at least partially deflected and at
least one second region at which the liquid preferably flows into
the recess.
[0018] On reaching the second region the liquid flows immediately,
i.e. without any appreciable stop, into the recess and, beyond a
specified fill level of the recess, also draws the liquid that has
initially stopped in the first region of the recess into the recess
with it.
[0019] In this way the liquid in the cavity can be controlled such
that the cavity is filled uniformly and substantially free from air
bubbles. This is possible even with cavities that are large,
particularly wide and irregular in shape which have, for example, a
fill volume of the order of about 10 .mu.l to 10 ml.
[0020] It should be noted that the above-mentioned wall of the
cavity may be, for example, a base of the cavity. However, any
other walls of the cavity are also conceivable. Thus, in a suitable
configuration of a lid closing of the cavity, the wall may also be
formed by the latter, for example. A combination of these two
possibilities is also possible, for example.
[0021] According to a further feature of the invention, it is
envisaged that the second region is formed by a ramp-like
transition which starts from a base level of the cavity and extends
to a base level of the recess.
[0022] This ramp-like transition ensures, in a simple manner, that
the sample liquid flows into the recess at this point, without
stopping, and fills the recess.
[0023] It has proved advantageous if the ramp-like transition,
starting from a boundary edge of the recess, forms an angle of
about 10.degree. to 60.degree., most preferably about 45.degree.,
with a base plane of the cavity. Tests have shown that the desired
flow characteristics of the liquid can best be achieved by such a
choice of geometric parameters.
[0024] However, instead of a ramp-like configuration, other
configurations of the second region would also be possible. Thus
the second region could also be formed by a "soft" transition, for
example by a convex or concave rounded portion. A notch-like
structure (looking at the recess in plan view) is also
conceivable.
[0025] The first region, by contrast, is expediently formed by a
boundary edge of the recess at which the convergent walls that form
the boundary edge enclose an angle of less than 120.degree.,
preferably approximately between 95.degree. and 70.degree., most
preferably about 90.degree..
[0026] In this way the first region reliably forms a capillary stop
at which the inflowing liquid is initially stopped or
deflected.
[0027] It has also proved highly advantageous in tests if the at
least one recess is of elongate configuration, the at least one
first region facing an incoming liquid and the at least one second
region being remote from an incoming liquid. Thus the incoming
liquid can be controlled so that initially it reaches the first
region, is stopped there, deflected and on reaching the second
region preferably runs into the recess (without any appreciable
stop) and fills it. With a corresponding arrangement of a plurality
of recesses with one another, the desired control of the liquid can
be adapted to the specific length of a cavity.
[0028] The recess may be approximately rectangular, for example, in
plan view. However, it may also be of a different shape in plan
view, for example arcuate. This may be expedient, for example, when
the cavity that is to be filled is also of arcuate configuration in
its longitudinal extent.
[0029] According to another expedient embodiment of the inventive
concept, a plurality of recesses are provided which are arranged
alternately, starting from the side walls of the cavity.
[0030] In this way it is possible to create a meandering flow path
for the liquid with the recesses in the cavity that is to be
filled.
[0031] It has also proved advantageous if the at least one first
region extends substantially over the entire length of a
longitudinal side of the at least one recess and the at least one
second region extends over only part of the length of another
longitudinal side.
[0032] In this way it is possible on the one hand to ensure a
capillary stop over a wide front while on the other hand ensuring a
time-delayed inflow of liquid into the recess, while additional
volume can be obtained at the point where the second region is not
formed.
[0033] However, the invention also relates to a microfluidic
platform having at least one microfluidic structure according to at
least one of claims 1 to 7. A microfluidic platform thus configured
can be manufactured cheaply and meets high demands for a reliable,
particularly bubble-free filling of the cavities present.
[0034] Further advantages and embodiments of the invention will
become clear from embodiments by way of example, as will be
explained with the aid of the accompanying drawings, wherein:
[0035] FIG. 1 shows a microfluidic structure according to a first
preferred embodiment in plan view, in schematic form,
[0036] FIG. 2 is a sectional view of the microfluidic structure
along section line II in FIG. 1,
[0037] FIG. 3 is a detailed view III from FIG. 2,
[0038] FIGS. 4a to 4f show different stages of filling the
microfluidic structure according to FIG. 1 with a liquid,
[0039] FIG. 5 shows a microfluidic structure in plan view according
to a second embodiment, in schematic form,
[0040] FIG. 6 shows a microfluidic structure in plan view according
to a third embodiment, in schematic form,
[0041] FIG. 7 shows a microfluidic structure according to the prior
art and
[0042] FIG. 8 shows a sectional view along section line VIII in
FIG. 7.
[0043] First of all, reference will be made to FIGS. 1 to 3.
[0044] These figures show a microfluidic structure 1 introduced
into a microfluidic component 2. The microfluidic structure 1
comprises a cavity 10 which has a fill volume of about 15 .mu.l.
The cavity 10 is irregularly shaped and is provided with an inlet
opening 11 which connects the cavity 10 to a fill channel 16. The
fill channel 16 itself may be connected to a fill opening (for
example a sample input region) which is not specifically
designated.
[0045] On the other side the cavity 10 is provided with an outlet
opening 12 which for example opens up the fluidic connection to a
venting channel 17. In the region of the outlet opening 12 a
capillary stop 24 is also provided in conventional manner.
[0046] Additionally or alternatively the cavity 10 may be connected
through an outlet opening with another microchannel 18 (shown by
dashed lines) if a liquid is to be transported through the cavity
10 into another cavity, for example (not shown).
[0047] The cavity 10 is a comparatively large cavity measuring
about 12 mm wide, 36 mm long and about 1.5 mm deep.
[0048] It should also be noted that there are three recesses 13
within the cavity 10. Each recess 13 is substantially rectangular
in appearance, in plan view, with a length L and a width B. The
recesses 13 are arranged alternately, starting from longitudinal
sides of the cavity 10.
[0049] It can be seen that each recess 13 comprises a first region
14 which faces an incoming liquid F (see FIG. 4) and at which the
incoming liquid F is at least temporarily stopped and/or at least
partly deflected.
[0050] Moreover, each recess 13 is provided with a second region 15
at which an incoming liquid F flows into the recess 13 without
being stopped.
[0051] The cavity 10 is closed off by a cover 21 (for example a
film attached by adhesion) and comprises a base 19. Each recess 13
comprises a base 20.
[0052] The detailed view in FIG. 3, in particular, shows that the
first region 14 (capillary) is formed by a boundary edge 22 of the
recess 13 at which the convergent walls forming the boundary edge
22 make an angle .beta. which is 90.degree.. In a departure from
the embodiment shown, other angles are naturally possible and may
be greater than or less than 90.degree..
[0053] It can also be seen that the second region 15 is formed by a
ramp-like transition R which, starting from the base level 19 of
the cavity 10, extends to a base level 20 of the recess 13.
[0054] In particular it can be seen that the ramp-like transition
R, starting from a boundary edge 23 of the recess 13, forms an
.alpha. of about 45 degrees with the base plane 19 of the cavity
10. Here, too, angles greater than or less than 45.degree. are
possible.
[0055] It should be noted that the second region 15 does not
necessarily have to be formed by a ramp-like transition but that
other embodiments are also possible. Thus, FIG. 3 shows that the
second region may for example also be formed by a "soft"
transition, for example a concave 15'' or convex 15''' rounded
portion.
[0056] With reference to FIGS. 4a to 4f it will now be described
how the flow characteristics of a liquid F flowing into the cavity
10 are controlled by the recesses 13:
[0057] Thus, the inflowing liquid F first of all flows onto the
first of the cavities 13 in a direction of flow S (FIG. 4a).
[0058] The liquid F is initially stopped and deflected at the first
region 14 or at the boundary edge 22 (FIG. 4b).
[0059] The liquid F continues on to the first region 14 of the
second recess 13 and again to the second region 15 of the first
recess 13, as a result of which the liquid F fills the first recess
13 through the second region 15 (cf. the dashed arrow in FIG.
4c).
[0060] The liquid F is then stopped and deflected again at the
first region 14 of the second recess 13 and the cavity 10 is filled
completely, initially leaving the second recess 13 free (cf. FIG.
4d).
[0061] As soon as the liquid F reaches the second region 15 of the
second recess 13, the second recess 13 is also filled through the
second region 15 (ramp-like transition (R)). The liquid front of
the liquid F then extends to the first region 14 of the last recess
13 (FIG. 4e).
[0062] At the first region 14 the liquid F is again initially
stopped and deflected until it then reaches the second region 15 of
the last recess 13 and, proceeding from that point, fills the
latter.
[0063] The filling process extends as far as the capillary stop 24
in the region of the outlet opening 12 and proceeds with
substantially no air inclusions (air bubbles) (cf. FIG. 4f).
[0064] As a result of the alternating arrangement of the recesses
13, the liquid F is directed in a substantially meandering
configuration through the cavity 10.
[0065] FIGS. 1 to 4 show that the second region 15 does not extend
over the entire length L of a recess 13 but makes up only part of
this length. Moreover, the region 15 also occupies a width which is
significantly less than the width B of the recess 13 as a whole. In
particular, the width of the region 15 is preferably less than half
the width B of the recess 13. As a result it is possible to make
good use of the volume of the recess 13 with an adequate fill
function of the region 15.
[0066] In a departure from the embodiment shown, in which the
regions 15 are positioned on the longitudinal sides of the recesses
13 remote from the incoming liquid F, it is also possible, however,
to provide such regions at least partly on the transverse sides of
the recesses 13 (cf. the dashed lines 15' in FIG. 1). It is also
possible to provide a plurality of such regions on a recess (cf.
also reference numerals 43 in FIG. 6).
[0067] FIG. 5 now shows a second embodiment 3 of a microfluidic
structure of a microfluidic component 4. In contrast to the
microfluidic structure 1 according to FIGS. 1 to 4, the
microfluidic structure 3 comprises a cavity 30 with slightly
differently configured recesses 31. Each recess 31 is in turn
provided with a first region 32 in the form of a stop edge
(capillary stop) which faces the direction of flow S of an incoming
liquid. On the longitudinal side of the recess 31 remote away from
the incoming liquid there is in turn a second region 33 in the form
of a ramp, the region 33 extending over an entire length L of the
recess 31. The width of the region 33 in turn amounts to at most
only half a width B of the recess 31. In this embodiment as well, a
meandering flow is created for an incoming liquid by the
alternating arrangement of the recesses 31.
[0068] With reference to FIG. 6, a third embodiment of the
invention will now be described. A microfluidic structure 5 on a
microfluidic component 6 is shown which (in contrast to the
preceding embodiments) has a cavity 40 which is curved, viewed in
the direction of inflow S of a liquid.
[0069] Seven recesses 41 are provided in the cavity 40, each recess
41 having a longitudinal extent L and being of a curved
configuration over this length L. Moreover it is apparent that each
recess 41 is in turn provided with a first region 42 in the form of
a stop edge (comparable with region 14 of the first embodiment)
and, at the longitudinal side remote from the incoming liquid,
comprises two regions 43 in the form of a ramp (comparable with the
region 15 in the first embodiment).
[0070] An incoming liquid is initially stopped and deflected at the
regions 42 and after reaching the regions 43 the process of filling
each recess 41 begins until the liquid runs right on to the next
recess 41. Thus the cavity 40 is filled step by step without any
appreciable air inclusions.
[0071] Finally, with reference to FIGS. 7 and 8, the prior art will
be briefly discussed.
[0072] These Figures show a microfluidic structure 7 of a
microfluidic component 8 in which, in contrast to the embodiments
according to the invention, a cavity 50 comprises not recesses but
bars 51. The bars 51 are arranged alternately, starting from
longitudinal sides of the cavity 50, and are intended to allow a
meandering flow of an incoming liquid (not shown) and hence filling
of the cavity 50 substantially free from air bubbles. The bars 51
start from a base 53 of the cavity 50 and extend to a cover 52
which closes off the cavity 50 at the top.
[0073] It is readily apparent that the inserted bars 51
significantly restrict the useful volume of the cavity 50.
LIST OF REFERENCE NUMERALS
[0074] 1 Microfluidic structure [0075] 2 Microfluidic component
[0076] 3 Microfluidic structure [0077] 4 Microfluidic component
[0078] 5 Microfluidic structure [0079] 6 Microfluidic component
[0080] 7 Microfluidic structure [0081] 8 Microfluidic component
[0082] 10 Cavity [0083] 11 Inlet opening [0084] 12 Outlet opening
[0085] 13 Recess [0086] 14 First region of the recess (stop edge)
[0087] 15 Second region of the recess (ramp) [0088] 15' Second
region of alternative design [0089] 15'' Second region of
alternative design (concave rounded portion) [0090] 15''' Second
region of alternative design (convex rounded portion) [0091] 16
Fill channel [0092] 17 Venting channel [0093] 18 Further
microchannel [0094] 19 Base of cavity [0095] 20 Base of recess
[0096] 21 Cover [0097] 22 Boundary edge of recess [0098] 23
Boundary edge of recess [0099] 24 Capillary stop [0100] 30 Cavity
[0101] 31 Recess [0102] 32 First region of recess (stop edge)
[0103] 33 Second region of recess (ramp) [0104] 40 Cavity [0105] 41
Recess [0106] 42 First region of recess (stop edge) [0107] 43
Second region of recess (ramp) [0108] 50 Cavity [0109] 51 Bar
[0110] 52 Cover [0111] 53 Base of recess [0112] .alpha. Angle
[0113] .beta. Angle [0114] B Width of recess [0115] F Liquid [0116]
L Longitudinal extent of recess [0117] R Ramp-like transition
region [0118] S Direction of flow of an incoming liquid
* * * * *