The present invention refers to a device or an instrument respectively for sampling, transporting or dispensing of fluid media according the introduction of claim 1, a microstructure comprising at least a device or facility, the use of the device or the structure as well as a method for the production of a device or structure respectively.
For sampling or dispensing respectively of fluid samples, such as in particular of fluids in the analytical field such as in particular medical or pharmaceutical field among others so called pipettes or capillaries or multiple pipette microstructures are used. In the course of increasing the efficiency in analytical laboratories, the economization and due to smaller sample amounts in this field also the used instruments such as in particular pipettes or multiple pipette structures are getting finer and more complex. For this purpose e.g. from the firms Zymark or Caliper multiple pipette structures are offered comprising up to 384 so called pipette tips for sampling amounts in the range of 2 to 100 nI.
In the EP 1 388 369 micro fluidic systems are proposed, which can be used in micro array systems including channel spring probes, that include at least one capillary channel. The proposed spring beams with incorporated channels as e.g. stressy metal beams curve away from a substrate when released. The channel spring probes are arranged onto a substrate by using specific production steps by covering the substrate with a plurality of layer coatings, so that the spring properties are achieved.
The subject of the present invention consists in proposing further refinement or increase of capacity and the possibility of increased automation in micro-technical process steps by using Nano- or Microsystems as in particular in analyses, the execution of test series, sampling, sample dispensing, at capillary-electro phoresis, capillary-chromatography, etc., etc.
According the present invention it is proposed, that instead of a “straight” device, a planar 2D-structure or channel spring probes arranged onto a substrate as proposed within the EP 1 388 369, in the nI or μl-range, a bent or arcuate fluidic device or a corresponding fluidic instrument respectively or a 3D-structure is used. E.g. an out of plane sampling device for sampling, transporting and/or disposal of fluid media is proposed, comprising within a substrate plane at least one longitudinal extending strip like portion, comprising a liquid channel, such as a pipette or a capillary tube or needle respectively for sampling or dispensing, which is bent or arcuate designed at least at one location extending out of the plane of the substrate.
“Bent” in the sense of the present invention means that out of an initially, essentially plane substrate, e.g. a substrate pre-structured by etching a three-dimensional structure has been produced by a specific bending action, the bent parts of the initially plane substrate project out of the plane of the substrate. In particular capillary channels or grooves can be produced which either are running into the substrate plane or also out of the substrate plane.
Surprisingly and against any assumption it could be proved in experiments that the flow in e.g. so called capillary grooves and in particular in open fluid channels also works “around the corner” in the μl and nano liter range. The open channel or the open channels can be inside as well as 10 outside of the radius of curvature at the location of the bending.
The same of course is valid for structures, which consist of a plurality of devices or instruments respectively including liquid channels in the micro liter or nano liter range comprising at least one bent location or structure respectively as proposed above.
It goes without saying that the flow characteristic of the fluid within the capillary grooves or fluid channels is dependent on the geometry and the surface finish or coating of the inner wall surface. In case of a water based solution or a fluid the surface is preferably hydrophilic and case of a more oily fluid the surface characteristic is preferably more hydrophobic like. As a general comment, one can say, that the contact angle between the fluid and the surface should be small.
Within the prior art so called 3D-structures are known, where capillaries for sampling are bonded into and/or arranged onto a so called “out-of-plane” structure as e.g. the channel spring probes as proposed in the EP 1 388 369.
For these structures the production costs are very high and also the production method is complicated and error-prone. In addition with some of such structures closed liquid channels have to be used which means within the prior art often so called closed capillaries are proposed. In addition for the spring probes as proposed within the EP 1 388 369 multi structures have to be applied onto a substrate to achieve the spring properties.
In contrast to the today usually used materials for the production of pipettes or capillaries i.e. for the production of the devices proposed according the present invention or structures comprising a plurality of devices or instruments respectively preferably plastically formable material as metals, at least partially plastic polymers and the same are used usually comprising only one layer.
On one side the production of the inventively proposed elements or instruments such as pipettes and capillaries or of whole structures is very simple, as the elements or instruments comprising the fluid channels usually consist only of one layer and can be bent in a simple manner. In addition a metal band can be used as a basis, which can be treated by using well-known lithography processes such as e.g. by means of etching to produce the liquid channels. It is possible e.g. to produce open channels on one side or both sides of a small metal band and further more closed channels can be produced by covering the open channels using a film. The possible production processes for the production of the inventive elements or devices respectively like i.e. etching, punching, bending, etc. shall be explained later on with reference to the attached drawings.
The advantage of the instruments or devices proposed according the present invention is, that sampling or dispensing of a sample is far easier by using a bent or arcuated element, such as a pipette or a capillary including instrument, as it does not have to be moved against the substrate surface in a more or less perpendicularly manner, from which substrate a sample has to be removed. It is e.g. possible to move the pipette or capillary including device from one side more or less in a parallel manner over the surface of the substrate for removing a sample. By using an inventive structure also at limited dimensional conditions at the same time a plurality of samples can be removed or dispensed in a simple manner. The various advantages of the inventively proposed devices or elements respectively as well as the structures shall be explained in more details later on with reference to the attached drawings.
Furthermore a process is described for sampling, transporting and/or dispensing of fluid media in particular by using the above mentioned devices or the above mentioned structures. According to the inventive process a pipette or capillary such as a needle or a structure, comprising a plurality of pipettes or capillaries is used and the fluid is transported along a location at sampling or dispensing a sample, which is arcuated or bent respectively.
Further preferred aspects or embodiments of the elements, devices as well as of the structures and the processes respectively are characterized in dependent claims.
The devices, instruments or structures respectively according the present invention are suitable in particular for diagnostic or analytical processes in the field of chemistry, medicine, microbiology, pharmaceutics, etc. The invention shall be explained in more details with reference to the attached drawings.
In the drawings:
a-1c show in perspective view embodiments of a bent fluidic channel,
a and 2b show in perspective view bent elements comprising a needle shaped tip-end,
a and 3b show in perspective view a bent element, comprising a tip-like end,
a and b liquid reservoirs in perspective view as well as fluidic elements for sampling,
c shows a section along line I-I of
a and 5b show in perspective view the simple immersion of a bent fluidic element into a fleece or non woven element,
a and 6b show schematically in perspective view the dispense of a fluid from a bent fluidic element in accordance with the principal of a fountain pen,
a and 8b show the sample transfer from fluidic device to fluidic device by overlapping contact of capillaries,
a-13d show an elastic flat spring like fluidic element arranged on a CD in view from the top, in a sectional view seen from the side as well as actuated by use of an actuating element for the dispense of samples,
a and 14b show an example of a mechanical transmission at flat springs for the production of a structure according the present invention,
a and 15b show a planar micro-structure produced in conventional manner as well as a bent “out-of-plane” micro-structure,
a to 16f show a possible version for the production of fluidic channels in inventive fluidic elements,
a shows a micro fluidic-device with bent distance elements, and
b a stack of a plurality of micro fluidic-devices as shown in
In the
b shows a one layer bent element 3 comprising an open “inner” channel with a bend of e.g. approximately 90 degrees.
c finally shows a one layer bent element 5, comprising an “outer” open channel and a bend 2.
a and 2b show each a bent element, which is needle-like shaped.
The bent or arcuate fluidic element can also be shaped as a tip end, as shown in the
With the use of experiments it could be shown, that the flow “around the corner” in particular also with use of open fluid channels works perfectly. It is irrelevant, if the open channel (capillary) is on the inner or the outer surface of the bent radius.
In
To ensure, that the disk or the CD grooves are always filled with fluid, it is preferred to arrange etched well reservoirs 25. These wells may be filled with conventional methods, e.g. by using pipettes. The disk can be kept static or can be rotated so that sampling is possible at any location around the circular-like grooves.
In
c shows a cross-sectional view along the line I′I from
In
In the following
The disposal of a sample may also be effected by contact of the tip-like-end of the bent fluidic elements onto a plain surface, as shown in the
To produce a N×M-array a plurality of so-called fountain-pen needles are used as schematically shown in
With reference to
In
In
In
A structure, produced out of the steel CD 41 in
In addition and as shown with reference to one specific stripe preferably in the centre-line of the strip-like sections 43 and 45 capillaries 46, preferably again by etching are produced as well as in addition so-called pots or wells 48 in the area of the outer stripes 43.
By means of a structure as shown in
In analogue manner in
In the example according
The cassette-like structures in addition have the advantage, that they can be stored or transported as e.g. stacks.
In
c shows a possible specific embodiment the flat spring 63 being combined with a bent needle-like tip 65. The combination of the bent needle-like tip enables an improved sampling of samples.
In
So that the fluidic elements or the individual flat springlike elements remain in their pre-stressed position for the production of the structure or the individual fluidic elements a material has to be used, which possesses certain elasticity or restoring force at deformation. Therefore in particular e.g. metal materials are suitable for the production of the proposed structures.
Furthermore it is also possible for actuating the fluidic elements or the flat spring-like elements to coat the metal substrate with a Piezo-substrat or a Bi-metal respectively, so that the actuation of the individual fluidic elements or flat spring-like elements can be executed by the movement of the Piezo-elements.
As already mentioned above the production of the flatspring-like elements can be achieved by etching what shall be explained in more details with reference to the attached
As shown in
In other words the pre-stress occurs as described with reference to the
In addition the element, which is pre-bent with a certain transmission ratio, again, can be coated with a Piezo-substrate or Bi-metal, so that for sample-sampling or sample-disposal the activation is possible by means of the Piezo-element or bi-metal.
With reference to the
b shows the bent out-of-plane nI or μl-structure 87, in which the individual elements 83 are bent out, forming the out-of-plane bent element parts 88, which may have a bend or deflection in the range of approximately 90 degrees. Of course the angle can be different and can be in the range of only a few degrees up to an angle of almost 180 degrees.
The production of an individual structure element 83, comprising at least one fluidic channel 84 as described in particular with reference to the
In
The polymer layer afterwards is partially exposed to light and partially removed by washing of the exposed parts, so that channel-like longitudinal extending free areas 93 will occur, as schematically shown in
According a further embodiment it is even possible to produce a totally open passage 97 by etching of the metal, as schematically shown in
Finally the polymer 91 shall be removed, so that the channel or capillary for an inventively proposed fluidic element is produced, as shown schematically in cross-section in
It is now possible to leave open the channel, as shown e.g. at the fluidic elements in
At the same time at the production step of the channel-like capillaries by etching also transmission forces as described with reference to
Furthermore from simple planar nI or μl-structures certain parts can be bent out of the two-dimensional plane into the third dimension (out-of-plane) by bending such as by arching, forming, etc., so that the inventive structures in the nI or μl-range will occur. The planar nI or μl-structures can be produced with conventional, micro technological production methods, such as lithography or etching, as described with reference to
The bent elements can fulfill various different functions, as e.g. contacting, needle-punching, reflecting, etc. Preconditions for bending an element out of the substrate plane is the at least partial etching through the whole substrate sheet, as in particular described with reference e.g. to
The possibility of plastic deformation of the micro-structure makes it possible to include inherent into the micro-fluidic systems e.g. out-of-plane distance-producing elements, positioning holes, adjustment aids, positioning aids, stoppers, etc. as schematically shown in
Furthermore, in
As already mentioned above the present invention refers to nI and μl-structures for the transport and/or the transfer of very small amounts of liquids in the nI and μl-range. As an example for sampling blood a needle like tip having a length of e.g. 3 mm can be used, the width of the needle-shaft may be approximately 400 μm, the capillary may have a width of approximately 200 μm and the depth of the capillary may be e.g. of about 80 μm. The amount of blood to be sampled can be in the range between 2 μ1 and 100 μ1. These values are of course examples given for the better understanding of the present invention and therefore the present invention is not at all restricted to the mentioned values. It should be shown how fine or small respectively the inventively described micro structures are and witch small liquid amounts are taken into consideration in the present invention.
The big advantage of the present invention is that sampling or sample-disposal “around-the-corner” is possible with using the bent nano-or micro-structures. By using the inventive devices or elements respectively or structures sampling or sample-disposal is possible in spatial or dimensional very limited conditions, as e.g. a fluidic device can be guided or moved parallel to a substrate or object respectively, from which a sample has to be sampled, which simplifies essentially the sampling of a sample.
The fluidic elements and structures which are shown with reference to the
Number | Date | Country | Kind |
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04027634 | Nov 2004 | EP | regional |
This application is a continuation of currently U.S. patent application Ser. No. 13/439,036 filed Apr. 4, 2012, which is a continuation of U.S. Ser. No. 11/791,251, filed May 21, 2007, now U.S. Pat. No. 8,241,566, which is a National Phase Entry of International Application No. PCT/CH2005/000688 filed Nov. 22, 2005, which claims priority to EP Application 04027634.7 filed Nov. 22, 2004.
Number | Name | Date | Kind |
---|---|---|---|
1895727 | Pearce | Jan 1933 | A |
2030918 | Halpin et al. | Feb 1936 | A |
3358496 | Farmer | Dec 1967 | A |
4269197 | Gilbard | May 1981 | A |
4731335 | Brigati | Mar 1988 | A |
4789263 | Germann | Dec 1988 | A |
6116297 | Feygin | Sep 2000 | A |
6602472 | Zimmermann et al. | Aug 2003 | B1 |
7241420 | Hantschel et al. | Jul 2007 | B2 |
20030183761 | Hantschel et al. | Oct 2003 | A1 |
20030211629 | Baumgardner et al. | Nov 2003 | A1 |
20040022681 | Hantschel et al. | Feb 2004 | A1 |
Number | Date | Country |
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1 388 369 | Nov 2004 | EP |
Entry |
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T. Hantschel, L. Wong, C.L. Chua, D.K. Fork; Fabrication of highly conductive stressed-metal springs and their use as sliding-contact interconnects; Microelectronic Engineering; 67-68 (2003) pp. 690-695. |
Number | Date | Country | |
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20130183212 A1 | Jul 2013 | US |
Number | Date | Country | |
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Parent | 13439036 | Apr 2012 | US |
Child | 13800795 | US | |
Parent | 11791251 | US | |
Child | 13439036 | US |