U.S. patent application number 10/474420 was filed with the patent office on 2004-06-17 for mixing deivce and mixing method for mixing small amounts of liquid.
Invention is credited to Gauer, Christoph, Wixforth, Achim.
Application Number | 20040115097 10/474420 |
Document ID | / |
Family ID | 7681016 |
Filed Date | 2004-06-17 |
United States Patent
Application |
20040115097 |
Kind Code |
A1 |
Wixforth, Achim ; et
al. |
June 17, 2004 |
Mixing deivce and mixing method for mixing small amounts of
liquid
Abstract
The invention relates to a mixing method for mixing at least one
small quantity of liquid, in which a quantity of liquid is applied
in a reaction region and at least one surface sound wave is reacted
with the quantity of liquid. The invention relates further to a
mixing device for mixing at least one quantity of liquid for
performing the method of the present invention, a use of the
device, and a method of analysis for bond strengths on
surfaces.
Inventors: |
Wixforth, Achim; (Munchen,
DE) ; Gauer, Christoph; (Munchen, DE) |
Correspondence
Address: |
Rocco S Barrese
Dilworth & Barrese
333 Earle Ovington Boulevard
Uniondale
NY
11553
US
|
Family ID: |
7681016 |
Appl. No.: |
10/474420 |
Filed: |
October 9, 2003 |
PCT Filed: |
March 22, 2002 |
PCT NO: |
PCT/EP02/03257 |
Current U.S.
Class: |
422/400 ;
436/180 |
Current CPC
Class: |
B01F 35/71815 20220101;
B01L 2400/0433 20130101; B01F 31/87 20220101; B01F 2101/23
20220101; B01L 2400/0496 20130101; B01F 31/86 20220101; B01L
3/502792 20130101; Y10T 436/25 20150115; B01F 35/71 20220101; G01N
1/40 20130101; B01F 33/30 20220101; B01L 2400/0436 20130101; Y10T
436/2575 20150115; B01L 2300/089 20130101; B01L 2300/0816 20130101;
G01N 29/222 20130101 |
Class at
Publication: |
422/100 ;
436/180 |
International
Class: |
G01N 001/10 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 9, 2001 |
DE |
101 17 772.0 |
Claims
1. A mixing method for mixing at least a small quantity of liquid,
in which at least one quantity of liquid (53) is applied to a
reaction region (3, 23, 43, 63, 83, 93, 103, 204) of a solid body
surface, preferably of a chip, and at least one surface sound wave
is brought into a reaction with the at least one quantity of liquid
(53, 73), in order to mix it.
2. The mixing method according to claim 1, in which the at least
one quantity of liquid (53) is applied to a part (23, 43, 103) of
the surface, on which a production device (25, 45, 105) for the at
least one surface sound-wave is located.
3. The mixing method according to one of claims 1 or 2, in which
the at least one quantity of liquid is applied in a depression (3,
23, 204) in the solid body surface.
4. The mixing method according to one of claims 1 through 3, in
which the at least one quantity of liquid (53, 73) is applied on a
part (43, 63, 83, 93, 103) of the surface, which has different
wetting characteristics than its lateral surrounding area, such
that the liquid preferably is retained thereon.
5. The mixing method according to one of claims 1 through 4, in
which the surface sound wave is pulsed.
6. The mixing method according to claim 5, in which the pulse
frequency of the surface sound wave is selected, such that it is in
resonance with an eigenfrequency of the small quantity of liquid
(53) on the reaction region (3, 23, 43, 63, 83, 93, 103, 204).
7. The mixing method according to one of claims 1 through 6, in
which the at least one surface sound wave is sent decentralized
onto the quantity of liquid (73).
8. The mixing method according to one of claims 1 through 7, in
which at least two surface sound waves are sent onto the quantity
of liquid (73), whose phase displacement (.DELTA..PHI.) is unequal
by a multitude to its wave length (.lambda.), preferably is equal
to half the wave length.
9. The mixing method according to one of claims 1 through 8, in
which the at least one surface sound wave is produced with an
interdigital transducer (5, 25, 45, 65, 66, 67, 68, 85, 95, 105,
206).
10. The mixing method according to one of claims 1 through 9, in
which the at least one surface sound wave is produced with a
surface sound wave generating device with a preferably
biocompatible coating.
11. The mixing method according to claim 10, in which an insulating
coating of the surface sound wave generating device is used.
12. The mixing method according to one of claims 10 or 11, in which
a coating is used with a higher dielectrical constant on the
surface sound wave generating device.
13. The mixing method according to one of claims 1 through 12, in
which the quantity of liquid is disposed in an area, in which a
resonator (86) for a surface sound wave is located, which is sent
out from a surface sound generating device (85) spaced from the
resonator region.
14. The mixing method according to one of claims 1 through 13, in
which the quantity of liquid is located in a region, in which
interference elements (101, 104) are located for generating
turbulence in the quantity of liquid.
15. The mixing method according to one of claims 1 through 14, in
which multiple quantities of liquid are applied for mixing on the
reaction region (3, 23, 43, 63, 83, 93, 103, 204).
16. The mixing method according to one of claims 1 through 14, in
which a material to be released on the reaction region (3, 23, 43,
63, 83, 93, 103, 204) is brought into contact with a liquid and by
action of a surface sound wave, is released into the liquid.
17. The mixing method according to one of claims 1 through 16, in
which the at least one quantity of liquid (53, 73) additionally is
headed.
18. The mixing device for mixing at least one small quantity of
liquid by performing a method according to claim 1, with a t least
one surface sound wave generating device (5, 25, 45, 65, 66, 67,
68, 85, 95, 105, 206) on a solid body surface and a reaction region
(3, 23, 43, 63, 83, 93, 103, 204), which is arranged to the at
least one surface sound wave generating device, such that it is
deformed in operation of the at least one surface sound wave
generating device from the generated surface sound wave.
19. The mixing device according to claim 18, in which the reaction
region is formed as a depression (3, 23, 204) and the depth of this
depression is small relative to the wave length of a surface sound
wave, which can be produced with the surface sound wave generating
device (5, 206).
20. The mixing device according to claim 18, in which the reaction
region (23) is designed as a depression and the at least one
surface sound wave generating device (25) is arranged at least
partially in the depression.
21. The mixing device according to one of claims 19 or 20, in which
the depression includes a recess (204) in a coating (202) on a
solid body.
22. The mixing device according to claim 21, in which the coating
(202) includes silicon dioxide.
23. The mixing device according to claim 18, in which the reaction
region includes preferably a holding region (43, 63, 83, 93, 103)
on the solid body surface, whose wetting characteristics differ
from its lateral surrounding area, such that the quantity of liquid
preferably is retained thereon.
24. The mixing device according to claim 23, in which the at least
one surface sound wave generating device (45, 105) and the
preferred holding region (23, 103) overlap at least partially.
25. The mixing device according to one of claims 23 or 24, in which
the surrounding area of the preferred holding region (43, 63, 83,
93, 103) is silanisized.
26. The mixing device according to one of claims 18 through 25, in
which the reaction region (63) and the at least one surface sound
wave generating device (65, 66, 67, 68) are arranged relative to
one another, such that a surface sound wave, which is generated
with the at least one surface sound wave generating device (65, 66,
67, 68) acts decentrally on the reaction region (63).
27. The mixing device according to one of claims 18 through 26,
with at least two surface sound wave generating devices (65, 66,
67, 68) for producing surface sound waves, which are
phase-displaced to one another in the reaction region (63).
28. The mixing device according to one of claims 18 through 27,
with interference elements (101, 104) in the reaction region (93,
103).
29. The mixing device according to claim 28, in which the
interference elements (101) include etched regions in a non-etched
or only minimally etched surrounding area or non-etched or only
minimally etched regions in an etched surrounding area.
30. The mixing device according to claim 28, in which the
interference elements (101) include regions, which are coated
differently from its surrounding area.
31. The mixing device according to claim 28, in which the
interference elements are formed by a non-uniform definition (104)
of the reaction region (103).
32. The mixing device according to one of claims 18 through 31,
with a preferably biocompatible coating (33, 43) on the surface
sound wave generating device (25, 45).
33. The mixing device according to claim 32, in which the coating
(33, 43) has different wetting characteristics from its lateral
surrounding area, such that the liquid preferably stops
thereon.
34. The mixing device according to one of claims 18 through 33, in
which the at least one surface sound wave generating device (5, 25,
45, 64, 66, 67, 68, 85, 95, 105, 206) includes an interdigital
transducer.
35. The mixing device according to one of claims 18 through 34,
with a resonator (86) in the reaction region (83), which is
designed, such that a surface sound wave, which is produced with
the at least one surface sound wave generating device (85),
resonates.
36. The mixing device according to claims 34 and 35, in which the
resonator (86) includes periodically arranged metal coatings, whose
distance corresponds to the finger distance of the interdigital
transducer (85).
37. The mixing device according to one of claims 35 or 36, with a
coating on the resonator.
38. The mixing device according to one of claims 18 through 37,
with a coating on the at least one surface sound wave generating
device.
39. The mixing device according to one of claims 37 and 38, in
which the coating is insulating.
40. The mixing device according to one of claims 37 through 39, in
which the coating has a high dialectric constant.
41. The mixing device according to one of claims 37 through 40,
with a thickness, which is smaller or essentially the same as the
wave length of the surface sound wave produced by the at least one
surface sound wave generating device.
42. The mixing device according to one of claims 18 through 41,
with a heating device in the region of the reaction region (2, 23,
43, 63, 83, 93, 103, 204).
43. A use of a device according to one of claims 18 through 42 as a
cell adhesion assay.
44. A method of analysis for analyzing the bond strength of objects
on surfaces using a method according to one of claims 1 through 17,
in which as the quantity of liquid, a solution with microscopically
small objects is used and during or after the reaction of the
surface sound wave with the quantity of liquid in dependence on the
current produced by the surface sound wave in the quantity of
liquid, the objects adhered to the quantity on the surface is
analyzed.
45. The method of analysis according to claim 44, in which, as the
solution, a nutritive solution is used and the objects are
biological objects, in particular, cells or bacteria.
46. The method of analysis according to one of claims 44 or 45, in
which the surface is functionalized in at least one sub-area.
Description
[0001] The invention relates to a mixing method, a mixing device
for mixing at least one small quantity of liquid, a use for the
device and an analytical method for bond strengths on surfaces.
[0002] The term liquid includes thereby other pure liquids, mixes,
dispersions, and suspensions, as well as liquids, in which solid
parts, for example, biological materials are located.
[0003] In microanalysis, small quantities of liquid must be mixed
or stirred. R. M. Moroney et al describe in Appl. Phys. Letters 59,
pages 774 and on (1991) the mixing of liquid in a 250 .mu.m deep
cavity with the use of an ultrasonic lambda wave, which disperses
in a thin, flexible membrane, which closes off the cavity on one
side.
[0004] Mixing processes for the smallest quantities of liquid were
of value for specialized "lab-on-chip" technology since the
earliest time point, which can be performed on a chip. The size of
the quantity of liquid is in the range of pico- to milliliters. The
relevant surfaces on the chip are in the millimeter, micrometer, or
submicrometer range.
[0005] The mixing process of small quantities of liquid is
essentially diffusion-driven. Since the typical reaction times of
many chemical or biological process are very short, the necessary
time for the chemical/biological process on the chip is determined
essentially by the time of the mixing of the reactants.
[0006] For acceleration of the mixing, James B. Knight et al
proposed in "Physical Review Letters" 1998, pages 3863 and on of
driving a quantity of liquid with high speed on a chip in a 10
.mu.m deep channel through a narrow point in a buffer solution.
With a thin liquid jet produced in this manner, mixing is
accelerated.
[0007] Also in the border region of such a laminar liquid stream,
the mixing occurs, however, always still by diffusion.
[0008] Thus, it is desirable if homogenous reaction conditions can
be produced in a quick manner, for example, concentration and
temperature. Also, this can be achieved by mixing.
[0009] The object of the present invention is to provide a method
and device with which mixing of one or more small quantities of
liquid can be performed simply, cost-effectively, and effectively
on the smallest space, for example, on a chip.
[0010] This object is resolved with a method with the features of
claim 1 and a device with the features of claim 18. The respective
dependent claims relates to advantageous forms. An analytical
method for analyzing the bond strength on the surface with the use
of the method of the present invention or an advantageous use of
the device of the present invention are the subject matter of
claims 44 or 43.
[0011] With the mixing method of the present invention, one or more
small quantities of liquid are brought into a reaction region of a
solid body surface, for example, a chip. There, it is brought to a
reaction with at least one surface sound wave by mixing.
[0012] The size of the reaction region is in the range of
millimeters, micrometers, or submicrometers. The amount of the
liquid is adapted to this size.
[0013] The quantity of liquid and the sound path can completely
overlap for maximum reaction effect. A partial overlapping makes
possible the production of additional turbulence.
[0014] The surface sound wave transmits an impulse onto the
quantity of liquid. This impulse transmission is achieved either by
the mechanical deformation of the solid body surface by the surface
sound wave and/or by the electrical field, which conducts the
mechanical deformation with the use of piezoelectric
substrates.
[0015] By the impulse transmission and by the restoring force
determined by the surface tension of the liquid, a substantial
turbulent flow is released into the liquid, which permits the
chemical reaction to run substantially more quickly than in a pure
diffusion situation.
[0016] Particular advantages of the impulse transmission by means
of surface sound waves for manipulation of small quantities of
liquid are:
[0017] 1. The intensity of the action of force on the small
quantity of liquid can be adjusted in a wide region via the
amplitude of the surface wave.
[0018] 2. Different temporal distributions of the force can be
electronically defined in a simple manner, such as, for example,
pulses of different lengths.
[0019] 3. The exposure to sound waves of the solid body surface
with the surface wave affects an automatic cleaning of the areas
contacted.
[0020] 4. A control via corresponding software is possible in a
simple manner.
[0021] The surface sound wave can be produced with the assistance
of a surface wave generating device, which is located in a known
distance to the region in which the liquid is located on the solid
body surface. The mixing is particularly efficient if the surface
wave generating device is located directly in the region on which
the liquid is applied. By the corresponding deformation of the
surface or the force effect by means of the electrical field
assisting the deformation, the liquid can be effectively and
directly mixed.
[0022] With one form of the method of the present invention, the
liquid quantity or quantities are applied in a depression of the
solid body surface, which is small relative to the wave length of
the surface wave. Such a depression makes possible the accurate
localization of the quantity of liquid on the solid body
surface.
[0023] With another form of the method of the present invention,
the liquid is applied in a region of the surface, whose wetting
characteristics are different from its lateral surrounding area,
such that the liquid preferably is stopped there. With such a form,
it is not necessary that the liquid is brought into a depression.
On the surface region with the different wetting characteristics
than its lateral surrounding area, the liquid quantity is retained,
based on its surface tension. The liquid is located on this
preferred holding region, for example, in the form of drops. Thus,
it is particularly advantageous that in spite of the defined
holding region of the liquid, which is achieved by modulation of
the wetting characteristics, no trenches, corners, or edges are
necessary, which could at least locally affect the mixing process.
By means of the essentially planar surface, the application as well
as the removal of the liquid is markedly simplified before and
after the process. Also, cleaning of the surface is more simply
performed than in the case of a depression.
[0024] With action of too large of an outer force, the quantity of
liquid does not leave the depression or the preferred holding
region based on its surface tension. First, with the effect of a
sufficiently large force, the liquid is driven out from the region.
With the method of the present invention, then, first with a
minimal intensity of the surface sound wave, a blending of the
liquid on the preferred holding region is can be achieved. Should
the liquid leave this region, then, the intensity of the surface
sound wave can be increases until the liquid leaves the preferred
holding region.
[0025] The surface sound wave can be produced on the piezoelectric
substrate or substrates with piezoelectric regions, for example,
piezoelectric coatings. Thus, it can be achieved than the substrate
or corresponding coatings are present only in the region in which
the surface wave generating device is located.
[0026] The surface wave can be continuously emitted, in order to
provoke the mixing process. It is particularly effective, however,
when the surface sound wave is pulsed.
[0027] If, in addition, the pulse frequency of the surface sound
wave is selected, such that it is the same as a eigenfrequency of a
small quantity of liquid, a resonance excess occurs, which still
further intensifies the mixing. The pulse frequency suited for this
purpose is based on the quantity of liquid or its volume and its
surface tension and amounts typically to a few HZ up to a few
kHz.
[0028] The surface sound wave can be emitted, for example, such
that the quantity of liquid is uniformly exposed to sound waves.
Beneath the quantity of liquid, the solid body surface deforms by
the permeating surface sound wave and thus forms a mechanical
deformation. This mechanical deformation or the electrical field
assisting it acts on the quantity of liquid in the border region
between the quantity of liquid and the solid body surface. The
running surface wave moves with the lower part of the quantity of
liquid. Based on the surface tension, with a sufficiently minimal
intensity of the surface sound wave, the quantity of liquid
nevertheless does not leave the preferred holding region or the
depression. In order to produce a volume equalization within the
quantity of liquid, a counter flow forms in the upper area of the
quantity of liquid, which is removed from the solid body surface.
In this manner, a movement in the quantity of liquid is produced
and a stirring or blending is achieved.
[0029] With another embodiment, the surface sound wave is sent
decentrally onto the quantity of liquid. The quantity of liquid is
impinged then only in a partial area and begins to rotate, for
example.
[0030] A similar effect can be achieved when the surface sound wave
is generated by a surface wave generating device, which is located
in the preferred holding region or in the depression, however not
symmetrical thereto.
[0031] With another embodiment of the method of the present
invention, at least two surface sound waves are sent onto the
quantity of liquid, which are phase-displaced in the region of the
quantity of liquid. For example, two parallel surface sound waves
with a phase-displacement of a half wavelength can be sent onto the
quantity of liquid. The impulse transmission, which is transmitted
by the "wave peaks" of the surface sound wave onto the quantity of
liquid, is then likewise phase-displaced, so that a formation of
vortices in the quantity of liquid occurs, which affects a very
effective stirring or blending.
[0032] The phase-displacement can achieve that two parallel
arranged surface wave generating devices with a corresponding
phase-displaced frequency are controlled. Likewise, the surface
wave generating devices can have a different distance from the
reaction region, which does not correspond to the whole-number
multiple of a wave length.
[0033] With a further advantageous form of the method of the
present invention, the liquid is brought into a surface region, in
which a resonator for a surface sound wave is located, which, for
example, is produced with a spaced surface wave generating device.
Such a resonator can be produced, for example, by a periodically
etch structure or periodically applied coating, preferably made of
metal. A surface sound wave, which runs in this region, is
amplified locally, in order to stimulate the mixing process in the
liquid.
[0034] For effective production of turbulences, in the preferred
holding region or in the depression, in which the liquid is located
when performing the method of the present invention, interference
elements can be applied, which stimulate the formation of
turbulences.
[0035] For production of the surface wave, with one advantageous
form, a known interdigital transducer is used. Such an interdigital
transducer, for example, has two electrodes, which engage in one
another in the manner of fingers, for example, at distances of a
few .mu.m. By application of a high frequency alternating field,
for example, in the dimension of a few MHz up to a few 100 MHz, a
surface sound wave is stimulated in a piezoelectric substrate or in
a piezoelectric region of the substrate, when the resonance
condition at least is approximately fulfilled that the frequency is
the same as the quotient from the surface speed and the finger
distance of an electrode. The dispersion direction is perpendicular
to the engaged finger electrode structures. Of course, also other
interdigital transducer geometries can be used, such as those known
from the technology of surface wave filters. With the assistance of
an interdigital transducer, a very defined surface sound wave can
be produced in a very simple manner. The manufacture of an
interdigital transducer is cost-effective and simple with known
lithographic methods and coating technologies. Interdigital
transducers can be wirelessly controlled, for example, by radiation
of an electromagnetic alternating field in an antenna device
connected with the interdigital transducer.
[0036] The method of the, present invention is suited for the
stirring of a quantity of liquid, in order to provoke a reaction
therein and/or to create homogenous conditions, for example. The
term "mixing", then, also should include a stirring in the sense of
an agitation process. Likewise, the method of the present invention
can be used to mix two or more liquids with one another. Also, in
this case, the speed of the mixing or the reaction is not limited
by diffusion.
[0037] The method of the present invention likewise can be used
advantageously in order to release solids, such as a powder-type
material into a liquid. The powder first is applied onto the
reaction region of the solid body surface. In this connection, a
liquid is applied and with the assistance of the surface sound
wave, a turbulent movement is produced. Thus, the release of the
powder-type material is accelerated and a mixing can take place
very quickly.
[0038] A further advantageous form of the method contemplates that
during the mixing process, additionally at least locally heat is
applied, in order to intensify the mixing process and the
production of the turbulence current further.
[0039] The mixing device of the present invention for performing a
method of the present invention includes at least one reaction
region on a solid body surface and at least one surface wave
generating device, which is arranged on the reaction region such
that energy of a surface sound wave generated by it is transmitted
to the quantity of liquid, which is located in the reaction
region.
[0040] With the term solid body surface, in the frame of the
subject matter of the present invention, either the surface of a
solid body, for example, of a chip, such as those known from
semi-conductor technology, is intended or a coating on a solid body
surface, for example, a metallic coating or an insulating coating.
Likewise, for example, a quartz layer on a solid body should be
understood as a solid body surface. Likewise, the invention
includes embodiments, in which a part of a solid body surface, for
example, of a piezoelectric lithium niobate crystal, is provided
with a coating, for example, quartz.
[0041] With one form of the device of the present invention, a
depression is provided on the solid body surface. A surface wave
generating deice is arranged on the solid body surface, such that
it can produced a surface sound wave, which can impinged with a
liquid into the depression in a reaction. The lateral extension of
the depression is determined according to the quantity to be
manipulated. Typically, amounts here are a few micrometers to
millimeters.
[0042] If the surface wave generating device is arranged outside of
the depression, then the depression should be small relative to the
wave length, which can be generated with the surface wave
generating device. Typically, this is a few micrometers. With a
deeper depression, a surface wave, which is produced by a surface
wave generating device outside of the depression, cannot overcome
the step for entry into the depression.
[0043] With another form of the present invention, the surface wave
generating device is provided within the region of the depression
itself, so that no limitation for the depth of the surface wave
generating device is necessary. Such an arrangement makes possible
also the effective mixing of a liquid within the depression, since
the surface wave can be directly reacted with the quantity of
liquid.
[0044] If necessary, the surface sound wave generating device is
provided with a coating, in the vent the material of the surface
wave generating device for the liquid to be analyzed or the
material located therein could be damaging. This coating is
selected, such that the surface sound wave still can affect on the
liquid. The thickness of the coating in the reaction region must be
smaller than the surface sound wave length.
[0045] With another form of the device of the present invention, in
the region of the surface wave generating device, the surface
characteristic of the solid body surface is selected, such that the
wetting characteristics of this region differ from the lateral
surrounding area, in that the quantity of liquid preferably is
retained or stopped there. Also, with such a form of the present
invention, the surface sound wave generating device is arranged in
the region of the preferred holding region, in order to most
effectively form the reaction between the surface sound wave and
the quantity of liquid on the preferred holding region. Depending
on the material of the surface sound wave generating device and a
possible coating for the preferred holding region, again a
sufficiently thin additional protective layer can be provided
between these elements or on these elements, in order to separate
the liquid from these elements.
[0046] For modulation of the wetting characteristics, for example,
hydrophilic or hydrophobic regions can be used. Should aqueous
solution be manipulated, the preferred holding region is selected,
for example, such that it is more hydrophilic than the surrounding
solid body surface. This can be achieved either by a hydrophilic
coating of the preferred holding region or by a hydrophobic
surrounding area. A hydrophobic surrounding area, for example, with
a preferred form of the invention can be realized through a
silanization of the surface.
[0047] Depending on the use, the solid body surface surrounding the
holding region can be hydrophilic, lipophobic, or lipophilic in
comparison to the surface of the holding region. For manipulation
of a non-aqueous solution, for example, it can be advantageous if
the preferred holding region is lipophilic in comparison to the
surrounding area.
[0048] The modulation of the wetting characteristics can be
achieved, for example, by a corresponding coating.
[0049] The definition of the preferred holding region, in which the
liquid is more intensely wetted than in its surrounding area, also
can take place or be supported by a flat etching of the surface in
this area, whereby the etching depth is small relative to the
lateral extension of the preferred holding region, for example,
one-tenth of its lateral extension. Thus, for example, in the case
of an aqueous solution, the preferred holding region is defined, in
that the surface surrounding the preferred holding region is coated
hydrophobically and etched in a few nanometers to a few micrometers
in the surface in the area of the holding region itself. In this
manner, the contrast with reference to the wetting angle of contact
is increased. Nevertheless, the surface macroscopically is planar.
Such a flat etching, in addition, is very simply and definitely
manufacturable in production technology, without the known problems
of deep etching occurring. The wetting characteristics can be
further modulated by micro-structuring, such as is the case with
the so-called Lotus effect; which contacts on the different
roughnesses of the surfaces. This can be obtained, for example, by
micro-structuring of the corresponding surface regions, for
example, by chemical treatment or ion radiation. The making of
regions with different wetting characteristics is simply and
cost-effectively performed, then, with the aid of already known
lithographic methods and coating technologies.
[0050] The surface wave generating device can be located on the
region with modulated wetting characteristics or on the surface of
the depression. In particular, it is advantageous when a coating is
provided above the surface wave generating device, which, for
example, is biocompatible. With the assistance of such a coating,
an influence on the liquid by the material of the surface wave
generating device can be prevented or damage of the surface wave
generating device by the liquid can be prevented, when it operates,
for example, as an etching liquid.
[0051] With the choice of a biocompatible coating, for example,
biological materials are analyzed in a buffer solution, without an
impending adverse effect or damage of the material or negative
affecting the reaction conditions. A possible material for a
biocompatible coating is silicon dioxide, for example.
[0052] In this connection, also a biocompatible coating, for
example, made from silicon dioxide, can be provided on the solid
body surface, in which a depression is etched, which should receive
the liquid. The surface sound wave generating device can be
arranged in a region of the surface, on which no silicon dioxide is
located. The surface sound wave disperses from the surface sound
wave generating device to the solid body surface also in the region
in which the silicon dioxide is located. Such a silicon dioxide
layer can be very easily etched, in order to produce a defined
depression. Thus, the surface sound wave can be reacted with the
liquid in the depression, should the thickness of the biocompatible
coating in the area of the depression be small relative to the wave
length of the surface sound wave.
[0053] It is particularly simple if the coating is selected, such
that it also has wetting characteristics, which differ from the
lateral surrounding area, such that the liquid preferably is
stopped or retained there.
[0054] With an advantageous further embodiment of the mixing device
of the present invention, interference elements are provided in the
reaction region. With one form with a preferred holding region,
these interference elements, for example, exist in an irregular
definition of this holding region. A liquid, which moves onto the
holding region based on the action of a surface sound wave, is
displaced by the reaction with the irregular edge into turbulence.
A similar effect can be produced by an irregular depression.
[0055] Also within the reaction region, turbulence-producing
interference elements can be provided. With an embodiment with a
depression, these interference elements can be produced, for
example, by vertical elements, which have been left with the
etching process for production of the depression. With an
embodiment with a preferred holding region, which is defined by the
different wetting characteristics, such interference elements can
be defined by regions within the preferred holding region, which
have wetting characteristics that are selected, such that the
liquid does not wet as well with the surface of the interference
elements as with the surrounding preferred holding region.
[0056] A simple embodiment of the device of the present invention
includes one or more interdigital transducers for production of the
surface sound waves.
[0057] In order to make possible an additional heating of the
liquid to be mixed, a heating device, for example, a resistance
heating, can be provided in the region of the depression or in the
preferred holding region defined by the modulation of the wetting
characteristics.
[0058] A resonance excess can be achieved, when a resonator is
located within the depression or the preferred holding region,
which is positioned, such that s surface sound wave, which is
produced with the surface wave generating device of the device of
the present invention, resonates. With an embodiment with an
interdigital transducer as the surface sound wave generating
device, such a resonator can comprise, for example, periodic
metallic strips, whose distance is commensurable with the finger
arrangement of the interdigital transducer for production of the
surface waves. With another embodiment, such a resonator can have
etched strips, for example, or other coatings in the corresponding
geometry.
[0059] As a special feature for the application for conductive
quantities of liquid, a coating of the resonators and/or surface
wave generating devices is advantageous. If a conductive medium is
located in a distance to the surface wave generating device, which
is smaller or the same as the wave length of the surface sound
waves, then the electrodes of the surface wave generating device
are capacitively coupled, whereby the efficiency with which the
surface wave generating device converts electrical energy into
acoustic energy, and with it, also the mixing efficiency, is
reduced. If one provides the surface wave generating device and/or
the resonators with an insulating layer, the mixing, efficiency can
be increased, since the evanescent, electrical field exponentially
drops. In particular, a coating with a high dielectric constant is
advantageous, since then the electrical field drops out
particularly quickly. With a particular form, the layer is selected
to be so thin that its thickness is smaller or approximately the
same as the wave length of the surface sound waves produced with
the surface sound wave generating device. A thicker coating would
intensely dampen the surface sound waves mechanically and again
reduce the mixing efficiency. The coating can be organic, for
example, made from photoresist, or inorganic, for example, silicon
dioxide or silicon nitride. The coating can be applied with known
methods, such as by spraying or spinning. For biological
applications, the coatings again preferably are biocompatible.
Further, the coatings can be laterally structured.
[0060] The device of the present invention can be part of a total
system. For example, multiple "mixing chambers" of such a type can
be provided on a single solid body chip, in order to perform
multiple processes at the same time. Likewise, a mixing device of
the present invention can be part of a complex system with multiple
analytical or synthesis devices, which makes possible other
analytical or synthesis steps. In a simple manner, a
"lab-on-a-chip" can be realized, on which multiple, different
processes can be performed simultaneously. For production of the
surface sound waves for a mixing device, one or more surface wave
generating devices can be provided at the same time, which, for
example, can be operated with different intensities.
[0061] Filling of the mixing device for performing the method of
the present invention can take place with the aid of a pipette
robotics, for example. Likewise, it can be provided that channels
or lines are provided, which have wetting characteristics similar
to the preferred holding region, which differ from its lateral
surrounding area, such that the liquid preferably stops thereon. A
quantity of liquid can be moved along such a line, for example, by
impulse transmission of a surface sound wave.
[0062] The invention is not limited to individual, free solid body
surfaces. Likewise, the invention can be realized in arrangements,
in which two solid body surfaces face one another, between which a
quantity of liquid is located. With such an embodiment, the
depression defining the reaction region or the preferred holding
region defining the reaction region can be located on one surface
and the surface wave generating device can be located on the
opposite surface. With such an arrangement, likewise the
advantageous effects of the present invention can be achieved, when
the small quantity of liquid comes into contact with both surfaces.
With such an arrangement, the preparation steps for making the
surface wave generating device and the preferred holding region or
the depression can be performed independently from one another,
before the surfaces are arranged opposite one another.
[0063] An analytical method of the present invention for analyzing
the bond strength of objects is the subject matter of claim 44. The
above-described mixing method of the present invention for mixing
small quantities of liquid is used with a solution with
microscopically small objects. During or after the reaction of this
solution with the surface sound wave, depending on the current,
which is produced by the surface sound wave, the amount or number
of the objects adhered to the surface is analyzed or counted. The
mixing device of the present invention, then, is also used in order
to produce turbulent currents, for example.
[0064] After the solution drop is placed on the surface, where it
is held together by its surface tension, the microscopically small
objects sink onto the surface. There, they can adhere either by a
specific or non-specific bond or adhesion. The solution drop is
displaced into movement with the surface sound wave according to
the mixing device of the present invention. Depending on the
current speed or strength of the surface sound wave, the
microscopically small objects located on the surface can be carried
away and thus removed. If the quantity of the objects adhered to
the surface depending on the current speed or strength is
determined, a conclusion about the bond strength can be arrived at.
A particular advantage of the use of surface sound waves is that
the amplitude or the current speed can be adjusted in further
regions, in particular, when interdigital transducers are used for
production of the surface sound waves.
[0065] Particularly advantageously, this method can be used when a
nutritive solution is used as the quantity of liquid and biological
objects, in particular, cells or bacteria, are analyzed. If
necessary, the surface can be functionalized totally or in partial
regions, in order to analyze the bond strength on different
functionalized surfaces.
[0066] The functionalizing can include, for example, cellular
mono-layers or a coating with adhesion molecules. The cellular
coating, for example, can comprise endothelial cells. The adhesion
molecules, for example, can be isolated from endothelial cells or
extra-cellular matrix proteins, such as fibronectin.
[0067] If different functionalizings are provided in different
regions on a surface, different bonds can be analyzed in parallel
on one surface. In addition, different local examples of current
can be realized on one chip, for example, by different transducers,
in order to selectively control different functionalized regions,
for example.
[0068] A particularly advantageous use of the mixing device
provides for a cell adhesion assay, which serves for analysis of
the bonding of cells on functionalized surfaces. Since cells sink
in a nutritive solution and adhere non-specifially to the substrate
surface, it is important to distinguish specific bonds from
non-specific.
[0069] With the mixing device of the present invention, the cells
can be flowed against with a surface sound wave and again are
analyzed, if individual cells break away as a function of the
current speed. In this manner, the bond strength can be analyzed as
a function of the current speed.
[0070] Cells with diameters of 10 to 100 .mu.m, for example, sit
counter to the current induced with the surface sound wave in the
event, for example, of a non-specific bond on the surface of a
sufficient resistance, such that the bond between the surface and
object can be broken by the current.
[0071] The invention will be described in detail with reference to
the accompanying figures. The figures show schematic drawings,
which are not necessarily drawn to scale. In the figures:
[0072] FIG. 1a shows a cut-out of an embodiment of the device of
the present invention for performing the method of the present
invention in plan view;
[0073] FIG. 1b shows a lateral sectional view of the embodiment of
FIG. 1a;
[0074] FIG. 2a shows a cut-out of a further embodiment of a device
of the present invention for performing a method of the present
invention in plan view;
[0075] FIG. 2b shows a lateral sectional view of the embodiment of
FIG. 2a;
[0076] FIG. 3a shows a cut-out of a third embodiment of the device
of the present invention for performing a method of the present
invention in plan view;
[0077] FIG. 3b shows a lateral sectional view of the embodiment of
FIG. 3a;
[0078] FIG. 4 shows a cut-out of a fourth embodiment of the device
of the present invention for performing the method of the present
invention in plan view;
[0079] FIG. 5a shows a cut-out of a fifth embodiment of a device of
the present invention for performing the method of the present
invention in plan view;
[0080] FIG. 5b shows a modification of the form shown in FIG. 5a of
the method of the present invention;
[0081] FIG. 6 shows a cut-out of a sixth embodiment of the device
of the present invention for performing the method of the present
invention in plan view;
[0082] FIG. 7a shows a cut-out of a seventh embodiment of the
device of the present invention for performing the method of the
present invention in plan view;
[0083] FIG. 7b shows a cut-out of an eight embodiment of the device
of the present invention for performing the method of the present
invention in plan view; and
[0084] FIG. 8 shows a sectional view of a ninth embodiment of the
device of the present invention for performing the method of the
present invention.
[0085] FIG. 1 shows in plan view (FIG. 1a) and in schematic
sectional view (FIG. 1b), one embodiment of the device of the
present invention. The shown cut-out from a chip surface has the
order of magnitude of a few millimeters. On a solid body surface,
whose cut-out in FIG. 1a is visible, a depression 3 that is a few
micrometers deep is provided. An interdigital transducer 5 is
adjacent thereto on the solid body 1. The interdigital transducer 5
includes in the known manner electrodes 9 and 7, which include
finger-type appendages 11, which engage in one another in distances
of a few micrometers. The solid body 1 is a piezoelectric crystal,
for example, lithium niobate. Alternatively, a non-piezoelectric
solid body with a piezoelectric coating, for example, zinc oxide,
can be provided.
[0086] The interdigital transducer 5 of the shown embodiment
comprises electrodes 7 and 9 with finger-type electrode structures
11 engaging in one another. The finger-type electrode structures
and the electrodes 7 and 9 can be lithographically defined, for
example, and could be damped as a metallic coating. The layer
thickness amounts, for example, to several 100 nanometers up to
several micrometers. The thicknesses are shown in FIG. 1b, as well
as in the other figures, as not true to scale. In the figures, the
finger-type electrode structures engaged in one another are only
shown schematically. Actually, a transducer includes, if necessary,
a much larger number of finger electrodes engaged in one
another.
[0087] With application of an alternating current on the electrodes
of the interdigital transducer 5, a surface sound wave is produced,
whose frequency is provided as the quotient from the surface sound
wave speed and the finger distance. The wave length corresponds
thereby in a known manner to the finger distance between two
adjacent fingers of an electrode. The radiation direction of the
surface sound wave is perpendicular to the connection line between
the electrodes 7 and 9. The radiation of interest here is
designated with 10. The electrical alternating field can either be
applied over supply lines (not shown) to the electrodes 7 and 9, or
with the assistance of an antenna device connected to the
electrodes, can be radiated wirelessly.
[0088] Such a device of the present invention is used as
follows:
[0089] A liquid to be mixed or the liquids to be mixed are, for
example, applied with a pipette robotic into the depression 3. With
the assistance of the interdigital transducer 5, a surface sound
wave with the radiation direction 10 is generated. This surface
sound wave acts on the quantity of liquid in the depression 3 and
produces there a turbulent movement by means of the deformation of
the solid body surface, which leads to mixing. With charged or
polarizable material in the liquid, additionally an impulse
transmission of the surface wave is produced by the electrical
field, which accompanies the mechanical deformation of the surface
in the piezoelectric crystal.
[0090] FIG. 2 show a further embodiment of the present invention.
Again, FIG. 2a shows a plan view and FIG. 2b shows a schematic
sectional view.
[0091] On the surface of the depression 23, an interdigital
transducer 25 with electrodes 29 and 27 is located, which have
finger-type appendages 31. The finger-type appendages extend into
the depression 23, while the electrodes 27 and 29 are arranged
outside of the depression with the shown embodiment. Reference
numeral 21 designates in the figure, again, the piezoelectric
substrate.
[0092] Above the interdigital transducer 31, a coating 33, for
example, of silicon dioxide, is provided at least in this region,
which, for example, represents a biocompatible protective
layer.
[0093] Also, with the embodiment of FIG. 2, the liquid to be mixed
is applied in the depression 23. The biocompatible protective layer
33 prevents the liquid from coming directly into contact with the
metallic electrode structure of the interdigital transducer 25. If
the liquid operates as a liquid with biological material, damage to
the biological material is prevented by the silicon dioxide.
[0094] In this connection, as with the above-illustrated first
embodiment, an electrical alternating field of a few MHz to a few
100 MHz is applied to the interdigital transducer 25, in order to
produce a surface sound wave for deforming the surface. In the
region of the interdigital transducer 25, the intensity of the
surface sound wave is very intense and leads in this manner again
to an effective mixing via the deformation of the solid boy or via
the electrical action of force on charged or polarizable
material.
[0095] A further embodiment of the present invention is the subject
matter of FIG. 3, in which, again, FIG. 3a shows a schematic plan
view and FIG. 3b shows a cross sectional view. This embodiment has
no depression. On the solid body 41, the interdigital transducer 45
is provided with electrodes 47 and 49, which again have
finger-type, electrode appendages 51 engaged in one another. With
the shown embodiment, a coating 43 is disposed above the
interdigital transducer, which is selected, such that the liquid to
be manipulated or the liquids to be manipulated preferably are
stopped thereon. The coating 43 is selected, such that it is more
heavily wetted by the liquid than the lateral surrounding area.
[0096] Alternatively, it can be provided that the surrounding area
of a region, in which the interdigital transducer 45 is located,
has wetting characteristics, such that the small quantity of liquid
preferably is stopped there less than on the region, in which the
interdigital transducer 51 is provided. For manipulation of aqueous
liquids, the surrounding region is hydrophobic in comparison to the
region, in which the interdigital transducer 45 is located.
Hydrophobic wetting characteristics are achieved, for example, by
silanizing of the surface.
[0097] With such an embodiment with a silanized surrounding area,
however, additionally a coating 43, for example, of silicon
dioxide, can be provided, in order to protect the interdigital
transducer or to ensure biocompatibility.
[0098] For example, aqueous liquids are applied on the region with
the interdigital transducer 45. Application of an electrical
alternating field likewise affects an impulse transmission of a
surface sound wave on the quantity of liquid 53, as with the
embodiment of FIG. 2. In this manner, also with this embodiment,
the mixing is effectively supplied.
[0099] The method of the present invention can be performed with a
device according to FIG. 1, in which the depression 3 is replaced
by a preferred holding region, whose wetting characteristics are
selected in the manner described with reference to FIG. 3, such
that the small quantity of liquid preferably is stopped or held
thereon.
[0100] In FIG. 4, an embodiment of the present invention with a
preferred holding region 63 is shown, which, for example, is
produced by the modulation of the wetting characteristics in a
manner already described. A transducer 65, which, for example,
corresponds to the above-described transducer 5, is arranged on the
solid body surface, such that the wave path 70 acts decentralized
on the preferred holding region 63 with the produced surface sound
wave.
[0101] In the preferred holding region 63, a quantity of liquid is
located, which is not shown in the figure. If a surface wave is
produced with the transducer 65, then this widens in the direction
70 and acts decentrally on the quantity of liquid. If the intensity
of the surface sound wave is sufficiently minimal, then the
quantity of liquid is not removed by the impulse of the surface
sound wave from the preferred holding region 63. By means of the
impulse transmission, however, a movement within the quantity of
liquid is produced, which leads to turbulence corresponding to the
current profile 72. Thus, an effective mixing is achieved.
[0102] With the embodiment of the present invention shown in FIG.
5a, two transducers 65 and 66 are provided, which, respectively,
have a wave path 70 or 74, which acts decentrally on the preferred
holding region 63.
[0103] Exemplary "wave peaks" of surface sound waves are designated
with 62 or 64, which are produced with the transducers 65 or 66,
when a phrase-displaced alternating current of the same frequency
is applied to this. The phase displacement between the surface
sound waves is designated with .DELTA..PHI.. Reference numeral 73
designated by way of example a quantity of liquid. The surface
waves impinge transversely on the quantity of liquid 73. By the
phase displacement, vortices are produced, which are designated by
way of example with 76 and 78.
[0104] In FIG. 5a, optional further transducers 67 and 68 are
provided, with which, respectively, a surface sound wave can be
produced, which acts counter to the surface waves of the surface
wave generating device 65 or 66. In this manner, a higher
flexibility with the application is provided. With a suitable
selection of the phase between the opposite transducers 65 and 67,
also a continual surface wave can be stimulated, which can affect
an intense mixing in the region between its nodes.
[0105] A similar effect can be achieved when the interdigital
transducers are arranged on the chip surface with different
distances to the preferred holding region. By the different running
times of the surface sound waves, in this manner, a phase
displacement between the surface waves can be achieved, which can
are produced with the interdigital transducers.
[0106] FIG. 5b shows a modification, in which, likewise, two
transducers are used in order to produce turbulence. The surface
sound waves with the wave path direction 70 or 74 produced with the
transducers 65 or 66 impinge decentrally on the preferred holding
region 63, on which one of the quantity of liquids, which is not
shown for purposes of clarity, is found. If the transducers 65 and
66 are stimulated by means of an alternating field, whose phase
correlation is such that at the location of the holding region 63,
the surface sound waves produced with the transducers 65 or 66 are
in phase, thus forming the vortices designated with 77 and 79 in a
quantity of liquid, which is located on the holding region 63 of
FIG. 5b. Also here, an effective mixing of a quantity of liquid on
the preferred holding region 63 is achieved.
[0107] In FIG. 6, an embodiment of the present invention with a
resonator is shown. Reference numeral 85 designates again an
interdigital transducer corresponding to the transducer 5 of the
embodiment of FIG. 1. Reference numeral 83 designated a preferred
holding region, which, for example, would be produced again by
modulation of the wetting characteristics relative to the
surrounding regions of the solid body. In the preferred holding
region, a resonator is arranged. This corresponds, for example, to
a finger-type metal coating with a finger distance of half the wave
length, which a surface wave has, which can be radiated in the
direction 90 from the interdigital transducer 85, when an
alternating field is applied to this. A strip of this metal coating
is designated with 86, by way of example. Alternatively, for
example, a periodic channel etching can be provided.
[0108] The resonator strips preferably are arranged at a distance
of the half wave length and form discontinuity in the acoustic
impendence of the free surface. On a piezoelectric substrate, also
a discontinuity of the electrical edge characteristics positively
occurs in addition to the discontinuity of the mass coating of the
strips. A metal as the resonator on the surface of a piezoelectric
mechanism additionally minimizes the wave speed beneath the metal,
based on the short-circuiting of the piezoelectric field.
[0109] Such a resonator increases the surface sound wave amplitude
at the location of the mixing in the preferred holding region. In
such a resonator, with the radiation of a surface sound wave, a
local, excess standing wave field is formed, which develops by
phasecorrect reflections on the individual, periodically arranged
discontinuities.
[0110] The resonator strips can be insulated from the preferred
holding region by an intermediate layer. Likewise, on the
resonator, a coating can be provided, which serves to protect the
quantity of liquid located thereon. For the sake of clarity, these
types of embodiments are now shown in FIG. 6.
[0111] In FIGS. 7a and 7b, two embodiments are shown by way of
example, in which interference elements are provided, which serve
to increase turbulence. In FIG. 7a, reference numeral 95 designates
again a transducer, which can emit a surface wave in the direction
100 in the manner previously described. A preferred holding region
is designated with reference numeral 93, which can be originated,
for example by modulation of the wetting characteristics. Reference
numeral 101 designates turbulence structures, whose wetting
characteristics corresponds to the wetting characteristics of the
solid body surface outside of the preferred holding region. A
liquid, which is located on the preferred holding region 93, is
inhibited by these interference elements 101 to a laminar movement.
Turbulences are generate, which are caused by the unfavorable
wetting characteristics of the interference elements 101.
[0112] With the embodiment of FIG. 7b, the preferred holding region
103 is located in the region of the finger of the transducer 105,
similar to the embodiment in FIG. 3. With the embodiment of FIG.
7b, the preferred holding region is not provided with a smooth
edge, however, rather with spikes 104. A movement, which is
produced with the help of the impulse transmission by the
interdigital transducer on a quantity of liquid on the preferred
holding region 103 is broken down by the spikes 104, so that
turbulences are produced, which assist mixing.
[0113] The inference elements shown in FIG. 7 are only to be
understood as an example. Other geometries of the interference
elements for production of turbulence on the preferred holding
region or in the depression are likewise contemplated, of course.
The turbulence structures are made, for example, by etching.
[0114] FIG. 8 show the schematic section through a different
embodiment of the device of the present invention. Here, reference
numeral 200 designates a lithium niobate crystal as the
piezoelectric solid body substrate. On a part of the crystal 200, a
coating 202 made of silicon dioxide is provided, which has an
etched region 204. An interdigital transducer, such as that
described above, is designated with reference numeral 206. The
direction 208 of a surface sound wave is designated, which can be
sent out from the interdigital transducer 206, when a corresponding
alternating field is applied to this. The surface sound wave widens
in the piezoelectric crystal also on the silicon dioxide coating.
In the etched region 204, the thickness of the silicon dioxide
layer is selected to be small enough, such that it is very small
relative to the wave length of a surface wave, which can be
produced with the interdigital transducer 206. This means that the
thickness of the coating 202 in the etched region 204 is very small
relative to the finger distance of the interdigital transducer 206.
A surface sound wave, which runs in the border region between the
piezoelectric crystal 200 and the silicon dioxide layer 202, can be
reacted with such a thin silicon dioxide layer in the etched region
204 with a quantity of liquid, which is located in the etched
region 204. Such an embodiment has the advantage that silicon
dioxide is very easy to etch and so a defined receptacle for the
quantity of liquid can be produced. Nevertheless, the metal
structure of the interdigital transducer 206 can be applied very
easily with known lithographic coating methods on the piezoelectric
crystal.
[0115] In addition, with all embodiments, a heating device, for
example, a resistance heating, can be provided, which produces an
additional mixing or temperature convection. For purposes of
clarity, none of the figures shows such an embodiment.
[0116] The liquid can be applied in the active regions, for
example, with a pipette robotic. Likewise, however, a supply line
can be supplied (not shown). This can be a channel, through which
the liquid is sent, or however, for example, with an embodiment
according to one of FIG. 3 through 7, it can be a narrower strip on
the solid body surface, which has the same wetting characteristics
as the active region 43. Via such a supply line, liquid can be
brought into the active region of the interdigital transducer 45,
also, for example, by impulse transmission of a surface sound
wave.
[0117] For the purposes of clarity, embodiments are shown in the
figures, in which only one interdigital transducer is provided.
However, multiple interdigital transducers can be provided, for
example, various finger distances. The transducer, if necessary can
be arranged about the reaction region. The interdigital transducer
need not necessarily have a constant finger distance. With an
interdigital transducer with non-constant finger distance, the wave
path also is limited in the lateral direction, since the resonance
conditions only can be fulfilled in a small region of the
transducer.
[0118] The coatings described for the embodiments above the
resonators and/or interdigital transducers are selected
advantageously with a thickness, which is small or approximately
the same as the wave length, which is sent from the interdigital
transducers. Such a coating damps the surface sound wave
mechanically not too intensely, but prevents however a capacitive
coupling of the electrodes, which would lead to a reduction of the
efficiency, with which the interdigital transducer converts
electrical energy into acoustic energy. Such a coating preferably
is insulating with a high dielectric constant, for example, made
from photoresist, silicon dioxide, or silicon nitride. Such coating
can be provided also with embodiments for which a coating is not
explicitly shown or mentioned above.
[0119] The described embodiments are only to be understood as
examples of the devices of the present invention. Of course, also
other combinations of the features of the present invention can be
provided. For example, a resonator structure, as is described with
reference to FIG. 6, also can be provided with an embodiment, which
shows a depression instead of the preferred holding region 83.
Likewise, interference elements, such as those shown with reference
to FIG. 7, also can be provided in embodiments in which the
preferred holding region 93 or 103 is replaced by a depression,
such as, for example, with the embodiments in FIGS. 1 or 2. Also,
embodiments, in which the surface sound wave does not impinge
centrally onto the quantity of liquid can have depressions instead
of the preferred holding region, as described with reference to
FIGS. 4 and 5.
[0120] The invention is also not limited to realization on a chip
surface. Likewise, two opposite solid body surfaces can be
provided, between which the liquid is located. With such an
arrangement, for example, the surface sound wave generating device
can be located on the surface and the structure limiting the
movement of the quantity of liquid, that is, the depression or the
preferred holding region, can be located on the other solid body
surface. If a small quantity of liquid contacts both surfaces, the
described effect also can be achieved with this form of the
invention.
[0121] All shown and described embodiments can be part of a larger
system, in which multiple mixing devices are arranged on a solid
body surface. On the chip surface, also other analytical or
synthesis devices can be located.
[0122] The devices and methods of the present invention are suited
for effective mixing of the smallest amounts of liquid, in order to
provoke a reaction, for example. The device of the present
invention and the method of the present invention support
effectively the formation of homogenous, thermodynamic conditions
in the quantity of liquid. Likewise, different quantities of liquid
can be quickly and effectively mixed with one another, without
being limited by diffusion. With another application of the method
of the present invention, a solid, such as a powder, for example,
can be applied in the reaction region. In this connection, a liquid
can be brought into the active region. With the assistance of the
impulse transmission of the surface sound wave, the release of the
powder can be accelerated significantly. Finally, the device and
method according to the present invention also can be used
effectively for distribution of material, for example, biological
materials, in the liquid.
[0123] Particularly advantageous, the method of the present
invention can be used for analyzing the bond strength of
microscopically small objects, for example, cells or bacteria on
functionalized surfaces, whereby a mixing device of the present
invention can be used as a cell adhesion assay.
* * * * *