CN106061599B

CN106061599B - The manufacture of annular microfluid probe

Info

Publication number: CN106061599B
Application number: CN201580011253.1A
Authority: CN
Inventors: M·博格; E·德拉马尔什; G·凯加拉; R·洛芙奇克
Original assignee: International Business Machines Corp
Current assignee: International Business Machines Corp
Priority date: 2014-03-07
Filing date: 2015-02-13
Publication date: 2017-09-12
Anticipated expiration: 2035-02-13
Also published as: DE112015000711B4; CN106061599A; GB2523825A; WO2015132686A1; GB201404041D0; GB2544614B; JP6482569B2; DE112015000711T5; GB2544614A; JP2017516666A

Abstract

There is provided a kind of method of manufacture miniature probe (100), methods described includes：Set that (S16) n microfluid probe is laid out (14) is provided on the identical bi-layer substrate (10,10a) including two layers (11,12), the layout is annularly disposed on the bi-layer substrate, and each layout in wherein described layout includes：First layer (110), a part for its one (11) corresponding in described two layers (11,12) of the bi-layer substrate；And the second layer (120), a part for its another (12) for corresponding in described two layers (11,12) of the bi-layer substrate；And at least one microchannel (123,124) that a part for lower surface (110l) of the second layer including being limited by unlimited groove on the upper surface of the second layer (120) (120u) and by the first layer (110) is closed；Substantially portal (16) in the center machining (S20) of the bi-layer substrate (10), so as to produce the cylindrical wall (18) for defining the hole and blocking each microchannel being laid out at least one microchannel of (14) so that at least one described microchannel (123,124) of each layout in the layout extends up at least one corresponding aperture (121,122) that the end for being in the groove in the cylindrical wall (18) is formed；And it is last, each layout of segmentation (S30) the n layout pops one's head in (100) to obtain n microfluid.Therefore the MFP probes obtained are also provided.

Description

The manufacture of annular microfluid probe

Technical field

Present invention relates in general to the manufacture of microfluid probe and resulting device.Especially, the present invention relates to perpendicular The manufacture of straight microfluid probe.

Background technology

Microfluidic device is generally referred to as micro manufacturing device, and it is used to pump, sample, mix, analyze and quantify to liquor charging Body.Its prominent features are derived from the special behavior that liquid is showed on micrometer length scales.The stream of liquid in microfluidic device Dynamic can be typically stratiform.Volume far below a millilambda can be by manufacturing with the lateral dimensions in micrometer range Structure and obtain.The reaction being restricted in large scale (by the diffusion of reactant) therefore can be accelerated.Microfluidizer Part thus be accordingly used in various applications.

Many microfluidic devices have user's chip interface and closure flow path.Closure flow path is easy to Functional Unit Part (for example, heater, blender, pump, UV-detector, valve etc.) is incorporated into a device, while making and leaking and evaporate Related the problem of, minimizes.

It has recently been introduced MFP novelty and generic concept：Vertical MFP (being also referred to as vMFP in the literature), referring to G.Kaigala et al., Langmuir, 27 (9), the 5686-5693 pages, 2011 (http://pubs.acs.org/doi/abs/ 10.1021/la2003639).Vertical MFP probes are with the microfluidic features manufactured in the planes with basal layer.It is such to visit Head is vertically oriented in operation, and probe summit (processing surface) is parallel to processed surface.

The content of the invention

According in a first aspect, the present invention is embodied as a kind of method for manufacturing microfluid probe, methods described includes：

The set of n microfluid probe layout, the layout annular are provided on the identical bi-layer substrate including two layers Ground is distributed on the bi-layer substrate, and each layout in wherein described layout includes：

First layer, its part of one corresponded in described two layers of the bi-layer substrate；And

The second layer, its

Corresponding to another the part in described two layers of the bi-layer substrate；And

Groove including being opened wide on the upper surface in the second layer is limited and by the lower surface of the first layer At least one microchannel of part closure；

Substantially in the center machining holes of the bi-layer substrate, define the hole so as to produce and block the cloth The cylindrical wall of each microchannel at least one described microchannel of office so that the institute of each layout in the layout State at least one microchannel extend up to formed at the cylindrical wall in the end of the groove at least one is corresponding Aperture；And

Each layout in the n layout is partitioned into obtain n microfluid probe.

In embodiment, methods described also includes, before it is split, the step of polishing the cylindrical wall.

Preferably, methods described also includes：Before mechanical machining, with such as including wax, polymer or photoresist Material etc the ductile material filling probe layout microchannel the step of；And remove after machining described Ductile material, preferably after the step of polishing the cylindrical wall, and is more preferably being partitioned into the every of the n layout The removal of ductile material is performed after one layout.

In a preferred embodiment, methods described also includes, before the layout is provided, and manufactures the n microfluid and visits The set of head layout, it is included on another the upper surface in described two layers in the n layout of slotting out At least one described microchannel of each layout.

Preferably, the microchannel of slotting out is held by using the micro manufacturing of photoetching or micromachined etc OK, and the step of preferably include wet etching or dry ecthing each microchannel.

In embodiment, methods described is directed at and combined described two layers after being additionally included in each microchannel of slotting out Step.

Preferably, the manufacture also includes each layout in being laid out for described n, is machined into vertically connecting At least one through hole of at least one microchannel is connected to, at least one described through hole is preferably passed through in described two layers Described another is machined.

In a preferred embodiment：Each of described two layers has substantially disc-shape；The bi-layer substrate it is described It is one in two layers：With another small average diameter described in described two layers than the bi-layer substrate, And relative to another alignment described in described two layers so as to described in leaving in described two layers another not by The exterior section of one covering in described two layers, and methods described preferably includes, in the identical bilayer Before the set that the microfluid probe layout is provided on substrate：Metallize at least in part described another in described two layers Individual another at least described exterior section caused in described two layers is metallized.

Preferably, methods described also includes：Before mechanical machining, probe layout is provided on corresponding bi-layer substrate Some set；And corresponding bi-layer substrate is superimposed, wherein the step of machining is including substantially in the double of the superposition The center of layer substrate, the substrate machining through all superpositions are portalled, so as to produce the bi-layer substrate for blocking the superposition Each bi-layer substrate in the layout at least one microchannel each microchannel hole cylindrical wall, and Wherein it is preferred to, methods described also includes polishing resulting hole cylindrical wall.

In embodiment, the offer, which is included in provide on identical bi-layer substrate, includes at least the two of interior set and outer set Each set of individual annular concentric set, the interior set and the outer set is gathered accordingly including being annularly disposed at it In probe layout, methods described includes two steps portalling of machining, wherein：It is machined into the first hole and is cut with producing First cylindrical wall of the microchannel of the disconnected interior set, and by by one of the bi-layer substrate including the interior set Point it is machined into the second hole from the separation of the remainder of the bi-layer substrate and blocks the microchannel of the outer set to produce The second cylindrical wall.

According on the other hand, the present invention is embodied as a kind of any one method in above example and obtained Microfluid probe, wherein it is described probe include：First layer；And the second layer, the second layer includes：By in the upper of the second layer At least one microchannel that a part for the groove restriction opened wide on surface and the lower surface by the first layer is closed；And The edge of the second layer, at least one microchannel end at least one aperture, it is described edge limited The part on the processing surface of the probe.

In a preferred embodiment, the machining in the hole in the manufacture method popped one's head in due to the microfluid, it is described At least a portion for handling surface is recessed.

Preferably, the microfluid probe also has into the angle of 2 π/n ± π/10 and preferably into 2 π/n ± pi/2s 0 Two side edge portions at angle.

In embodiment, the microfluid probe also includes at least two microchannels, and preferably also includes correspondingly It is attached perpendicularly at least two through holes of at least two microchannel.

Preferably, the exterior section relative with the edge on the processing surface of the restriction probe is metallized.

By non-limitative example and specific implementation apparatus and method of the present invention will be described with reference to the drawings now.In figure Shown technical characteristic is not necessarily drawn to.

Brief description of the drawings

It is various that the manufacture method that Fig. 1 is schematically depicted in microfluid probe according to an embodiment of the invention includes Step；

Fig. 2 is flow chart the step of showing the manufacture method of microfluid probe according to an embodiment of the invention；

Fig. 3 is shown schematically in the microfluid probe cloth on the identical bi-layer substrate that embodiments of the invention include Office；

Fig. 4 shows Fig. 3 modification；

Fig. 5 is shown in the geometry specification for the layout for example shown in Fig. 3 that embodiment includes；

Fig. 6 schematically shows the step in the manufacture method of the layout of two annular concentric set of use according to embodiment Suddenly；

Fig. 7 schematically shows the step in the manufacture method according to embodiment, wherein before machining center hole It is superimposed some bi-layer substrates；

Fig. 8 is the 3D views for simplifying expression of microfluid probe according to an embodiment of the invention；And

Fig. 9 shows the surface treatment of the progress of being popped one's head in by microfluid according to embodiment (2D views simplify and represented).

Embodiment

As mentioned in the Introduction, vertical MFP probes have some advantages.Such probe is by micro manufacturing.In manufacturing step At least some (including polishings) need individually (that is, to repeat) or carry out in groups with 3-4 probe for each unit.Can be with It is the conditioning step in the extensive manufacture of MFP probes to recognize such manufacturing step.The polishing of probe (and is more generally visited The preparation on the processing surface of head) it is especially labour-intensive and so significantly increases manufacturing cost.In addition, there is production problems (for example, directional polish or excessive), polishing tool has significant floor space and costliness.Finally, popped one's head in during polishing Misalignment can cause different summit sizes.The present invention is by introducing new manufacture concept, dependent on annular spread MFP probe layouts are solved at least some (some embodiments are addressed all of these issues) in these problems.This method with so far Untill for vMFP layout and known method is contrasted, vMFP layout in pop one's head in from probe layout two-dimensional array cut Cut.

In more detail, and referring to Fig. 1,2 and 6,7 and 8, the aspect of the present invention is described first, it is related to microfluid The manufacture method of probe (hereinafter referred to as MFPs) 100.

Most typically, the coming of new concept needs the set for the n MFP layouts 14 being arranged on identical bi-layer substrate 10. The bi-layer substrate include at least two layer 11,12.

Layout 14 is annularly disposed on bi-layer substrate 10.In more detail, each layout 14 includes：

First layer 110, i.e. the part of one 11 formed in the layer 11,12 of bi-layer substrate 10；And

The second layer 120, its another part corresponded in these layers 11,12.

For the sake of clarity：In the layout portion corresponding to single layout 14 (or conclusively MFP probe 100) 110th, make a distinction between 120, and layer 11,12 be initially formed bi-layer substrate 10 for manufacturing MFP probes those are bigger Layer.

Bi-layer substrate represents to include at least two layer 11,12 any suitable substrate.First and second layer 11, in 12 Each most viable ground can be disk, such as wafer disc.However, layer 11,12 is not necessarily circle：It is only necessary to be laid out 14 annular spread.Two layers 11,12 can be identical material (or not being).Preferred material is glass or silicon.Further, The material of layer 11,12 can include (for any one in layer)：Plastics, ceramics, metal and/or simultaneous with this manufacture method Any other hard material held.

At a layout 14, a layer (for example, second layer 120) should typically comprise the miniflow of structuring thereon It is most of in body characteristicses (microchannel, through hole etc.).Strictly speaking, it includes at least one microchannel 123,124, but not In the case of damaging the application, embodiment described below majority assumes two microchannels 123,124.Microchannel is by layer 120 Upper surface 120u on open wide groove limit.Groove is by it is assumed here that be another layer of " first " layer 110 (referring to Fig. 8) Lower surface 110l a part closure.

Due to the annular spread (or being circular layout) of layout, one in the functional character of each in n layout 14 Or multiple (for example, microchannel, through holes etc.) typically should be laid out the 14 annular centers limited relative to through by these Transversal symmetry axis 2 π/n rotation under be constant.Therefore, substrate 10 can be under 2 π/n rotation it is constant, it is at least right In the aspect for being related to these functional characters.Certainly, if providing different layouts, as shown in Figure 4, feelings on same substrate 10a Condition may no longer be so.

Typically, can provide 6 in same substrate 10, more than 12 or even 24 be laid out.Due to yield reason, make every effort to most The quantity n of bigization layout, for example, n=36,48 or 72.The preferred amount of layout depends on substrate dimension, the complexity of layout (it depends on expected application).Further, manufacture method described here can be used for any quantity n >=2 (example in principle Such as, n >=3,4,5,7 ...) layout.

The important step of this manufacture method be substantially bi-layer substrate 10 center machining holes 16 (referring to Fig. 1 or 2 In step S20).Machining holes produce cylindrical wall 18 (defining the hole).Layout and hole are designed so that 18 sections of cylindrical wall Relevant microchannel in disconnected layout 14.That is, aperture is produced in the end of each of these microchannels.Therefore, microchannel 123rd, the 124 corresponding aperture 121,122 (being formed when it is in machining holes 16) extended up to now at cylindrical wall 18, such as Most preferably finding in Fig. 1,3 and 8.

Machining holes 16 can include drilling, milling, cutting etc..It can also include column spinner or laser, water jet, Etching etc..It should be noted that (referring to Fig. 6) in the embodiment using concentric arrangement, same mechanical process technology can be used for machinery Process first (interior) annular ring in hole (the step S20i in Fig. 6) and for cutting inner ring so that obtain second it is (outer) enclose. In modification, different hole mechanical manufacturing technologies can be used for obtaining two circles.It then will be discussed in detail Fig. 6 embodiment.

Finally, and as shown in fig. 1, each (step S30 in Fig. 1,2) among n layout is split, therefore Obtain n MFP probe 100.Those skilled in the art is it will be appreciated that radial separation can include by using prefabricated pre-cut Secant etc. cuts, cut open or partitioning layout 14.Fig. 3 is shown can typically cutting used herein or cutting line (dotted line) Pattern.

The manufacture method specifically described herein allows the wafer-level processes on the processing surface of MFP probes, and thus solves Some problems of the manufacture of previously described vMFP probes.Using this manufacture method, some spies can be obtained in a single step The processing surface 310,320 of head (typically many).

Especially, probe is arranged on chip so that can be in single step before segmentation probe in such a way The middle polishing (wafer scale polishing) for performing all probes.In this respect, the embodiment of this manufacture method can also include, in segmentation Before, the step of polishing (S24 in Fig. 1,2) cylindrical wall 18.Further, polishing can together with machining holes 16 or It is performed simultaneously.Depending on the technology for machining holes 16, extra, different polishing steps is in practice likely to be unnecessary 's.Polishing therefore can be with mechanical processing steps.Now, polishing may not necessarily imply that mechanical polishing means.But, can be with Use the means of such as high pressure jer cutting.In all cases, machining and/or polishing step can allow obtain by The cleaning treatment surface 310,320 of this MFP produced probe 100, it has low surface roughness and is well suited for allusion quotation The vMFP applications of type.

Advantageously, this manufacture method can also include, before mechanical machining, and the microchannel of layout is filled with ductile material Step S18 so that during subsequent manufacturing step, particularly protect microchannel during the machining S20 in hole 16.Class As, other microfluidic features of layout can be filled with ductile material.The material can then be removed S40 (in step S20 Afterwards or then).Ductile material is preferably removed after polishing S24 (if any).It is highly preferred that it is only dividing Cut and be removed after S30, also to protect microfluidic features during splitting.

Any material that ductile material represents to can be used for filling and block microfluidic features to be protected.Typically, The ductile material can by heat and melt it, then by appropriate cleaning and rinse microfluidic features be removed.So Material can include wax, photoresist, or more generally, one or more polymer.

Photoresist is favourable, and reason is that it allows to be crosslinked resist solution by exposure and thus makes it non- Often solvable (its allow then simple remove) and cleaning passage.Preferably, ductile material should not be typically used in cutting It is solvable in liquid (for example, water is possibly used for cooling substrate 10 and probe) in operation.Photoresist is very pure and by mistake Filter；They unlikely leave any particle.More generally, photo anti-corrosion agent material can be proved to be favourable.

Low temperature (about 60-80 DEG C) wax can be used to fill and blocking channel in addition.After machining holes, wax can be by Heat and then removed using vacuum.It for example can also be dissolved using heptane.With low viscosity (for example, at 80 DEG C) Any pure cryogenic wax can be potentially suitable for this purpose.

In modification, it can also use by the dissolving of light, temperature or solvent and/or liquefied other polymer.

So far, most of basic sides of manufacture method have been described, it is assumed that the substrate of preproduction is obtainable (the step S16 in Fig. 1,2).Further, the embodiment of this manufacture method can include upstream manufacturing step (in Fig. 1,2 S8、S10、S12)。

It is interesting to note that such step can include microchannel 123,124,224 (step S12) of slotting out.In layer 11st, on the surface of one in 12, microchannel of for example being slotted out on the upper surface 120u of layer 12.In two layers which Passage of being slotted out on individual is inessential, as long as they are for example after the coupling by another layer of closure.

The microchannel S12 that slots out is preferably realized by micro manufacturing.This can include photoetching or micromachined.Groove is for example Can be by instrument engraving and/or milling directly on the upper surface of basic unit 120.It can have any suitable cross sectional shape, For example circular, square, U or V-arrangement section.Outfit can be chosen according to the material of basic unit.In modification, it is also contemplated that Laser ablation.Also advantageously, deep reactive ion etch (DRIE) is used for the manufacture of microchannel.Micro manufacturing can be wrapped typically in addition Include wet etching or the step of dry corrosion carves each of microchannel.Advantageously, because the wafer scale method proposed here, passage can To be together etched.

After the step S12 for microchannel of slotting out, manufacture can also include being directed at and combining two layers 11,12, referring to Step S14 in Fig. 1 or 2.It should be noted that in Fig. 1,120u faces the eyes of reader above layer 12, just as under layer 11 Face 110l (in Fig. 1 bottom point).However, layer 11 is overturn before S14 is combined so that below step S16, layer 11 110l 120u above the layer 12 in Fig. 1.

As first example, the thermal of glassy layer 11,12 can continue 4 hours (heating and cooling speed at 600 DEG C Rate：75 DEG C/h) and carry out.This causes the fusion (irreversible) of glass substrate.It is preferably cold when using glass substrate But speed is no more than 100 DEG C/h to avoid stress.In addition, the thermal expansion needs of chip glass are equal.

As another example, the components of two silicon wafers 11,12 can be by by~3 μm of polyimide adhesive (HD Microsystems GmbH, Neu-Isenburg, Germany) be spun in the polished side of lid chip and by being then aligned and Realized with reference to two chips.10 minutes (PRESSYS LE, Paul-Otto are continued with the progress of 2 bar pressures with reference at 320 DEG C Weber GmbH, Remshalden, Germany).Then MFP probes can be cut and store.

Upstream manufacturing step can also relate to other microfluidic features, for example, they can especially include machining S10 through holes 111,112.That is, and for each among n layout 14, at least one through hole 111,112 can be provided To be attached perpendicularly to corresponding microchannel 123,124.For simplicity, through hole is preferably machined as insertion layer 12 Through hole so that they easily can be closed by the identical layer 11 of sealed passage 123,124.Other equipment (pipe Road port and pipe) the relative side connection of side 120u from layer 12 can be provided to, so as to simply allow probe 100 It is vertically operating.

Other manufacturing steps can particularly produce (the correspondingly step of alignment hole 21,22 in each layer 11,12 S8, S6), to be directed at layer before bonding.

Fig. 5 provides the example of the set for the geometry specification for being particularly suitable for drilling to glassy layer 11,12.The alignment of two layers Hole 21,22 can be drilled together.For the purpose, layer 11,12 for example can be combined together in advance with wax.Alignment hole 21, 22, which may then pass through two layers 11,22, is drilled.On through hole 111,112：The interface drilled between two layers 11,12 Stop so that only one layer 12 includes through hole 111,112.

When using chip glass, suitable retainer may be advantageously used with exact glass drilling, such as in computer In digital control (CNC) machine.

It is, for example, possible to use SchottBorosilicate glass wafer, it has 500 μm of crystalline substance Piece thickness and 4 inches of wafer size.It is preferred that a diameter of 0.25mm of minimum aperture.Drilling parameter preferred in this case is：

- aperture (0.4mm)：30mm/min@30'000rpm；And

- alignment hole (1.5mm)：25mm/min@25'000rpm.

Preferably drilling is performed in water cooling liquid.Diamond-coated drill can be used.

Standard milling machine and diamond bit can be used manually to get out centre bore (20mm diameters).Polishing pad can be used With the polishing in 1 micron diamond Mo Gao implementation centers hole.Standard cutting can be then performed to split probe.

Layout 14 among identical set need not be all identical, as shown in Figure 4, wherein substrate 10a four layouts There are Additional microchannels compared to residue layout.Herein, microchannel will be again with them with that will be drilled and throw in subsequent stage The intersecting mode of the centre bore of light is arranged, so as to eventually form aperture.For the layout, wafer size is 100mm and will bored A diameter of 20mm of the centre bore gone out.

, it is necessary to design electrode at probe in some MFP applications.In that respect, this manufacture method can be fitted preferably It should metallize.Metallization is performed on one preferably only in layer 11,12.Pt/Ti patterns are constructed for example on glass is It is known.Electrode can be advantageously carried out being used for heating, electrochemical sensing etc..

In this respect, this method allows simply to manufacture external electrical pole plate (pad).For example, it is assumed that two layers 11,12 is every One has substantially disc-shape, and layer 11 can carry the average diameter smaller than layer 12.When being directed at two layers, layer 12 Therefore exterior section covers tegillum 11.This allows to provide additional functionality features at the exterior section.Especially, can be with The upside 120u of metallization (at least in part, or selectivity) layer 12, for example, at least partly outside of metal layer 12 Part.Typically selectivity metallization is performed on whole larger layer.

Therefore the micro-structural of such as heating arrangement or electrochemical electrode etc can be obtained, it can be by being located at outside portion Metallization pole plate on point is connected.Less chip ensures contact pole plate freely close to electrode.Again, when passage 123, When 124 manufacture is unrelated with metallization process, passage 123,124 can be provided in any one in layer 11,12.

At present, the improvement for allowing the yield of this manufacture method to double is discussed, and this refers to Fig. 6 and 7.

A kind of mode of increase manufacture yield is to optimize wafer surface by using the concentric ring (Fig. 6) of layout.For example may be used To provide two (or more) annular concentric set (interior set and outer set) of layout 14 on identical bi-layer substrate 10.It is interior Each of set and outer set include probe layout 14i, the 14o being annularly disposed in its corresponding set.It is then possible to machine Tool processes the first hole (step S20i) to produce the first cylindrical wall of the microchannel for blocking interior set.Then, can be by that will serve as a contrast The part including interior set 14i at bottom 10 separates with the remainder of substrate 10 and is machined (step S20o) second hole.This Produce the second cylindrical wall of the microchannel for blocking outer set 14o.As it was earlier mentioned, same or analogous mechanical manufacturing technology can be with For producing the first and second cylindrical walls.

The another way of increase manufacture yield is the disk for example by providing superposition before the hole that machining runs through And the 3rd size (that is, perpendicular to wafer surface) is opened up, referring to Fig. 7.For example, in step S16, can be in corresponding bi-layer substrate Some set of probe layout 14 are provided on 10.Then, in step S19, institute is passed through in the center of generally superimposed substrate 10 Have before the substrate machining S20 holes of superposition, substrate 10 can be superimposed.This causes to produce hole 16, and the wall 18 in the hole is blocked Microchannel in each of the substrate 10 of superposition.If necessary, the cylindrical wall in resulting hole 16 is polished, such as previous institute State.

Fig. 6 and 7 embodiment can be combined.Manufacture the yield substrate multiplication overlapping as the quantity of concentric ring is multiplied by.

Now referring to Fig. 1,3-5,8 and 9, another aspect of the present invention will now be described, it is related to according to this manufacturer The MFPs that method is obtained.With above-mentioned manufacture method as one man, such MFP should include：First layer 110 and the second layer 120.Afterwards Person has one or more microchannels 123,124, and the microchannel is corresponding by what is opened wide on the upper surface 120u of the second layer 120 Groove limit and a part of lower surface 110l by first layer 110 is closed, most preferably finding in such as Fig. 8.It is additionally, since Mechanical processing technique S20, S24, aperture 121 is limited in the end of microchannel, and this enters at the edge 320 of layer 120 OK, slotted out in layer 120 passage.Edge surface 320 forms the edge surface of each layer 110,120 by popping one's head in 310th, the part on the 320 processing surfaces limited.Certainly, and as it was earlier mentioned, such MFP probe can include it is other micro- Characteristic of fluid, for example, be connected to the through hole 111,112 of microchannel.

It should be noted that the MFP probes obtained are necessarily influenceed by previously described manufacture method：

- first, and Fig. 9 is referred more especially to, due to the processing of mechanical processing steps S20, the MFP probe 100 in hole 16 Surface 310,320 be probably it is recessed (if without additional, significant Surface Machining to remove concavity)；

- secondly, with reference now to Fig. 5,8 and 9, the overall shape of probe 100 can further reflect the initial ring of layout 14 Shape is distributed.For example, probe can have lateral margin (or its at least part), it is into the angle close to 2 π/n, with such as ± π/10 Tolerance.Intervallum (referring to the dotted line in Fig. 1 or 3) and the cutting techniques used that tolerance is depended between the probe in layout. However, resulting edge should typically have the angle of 2 π/n ± pi/2s 0, it is assumed that careful enough during segmentation step.

- probe 100 can also have the further feature of this manufacturing technology, for example：

Zero due to the different technologies (that is, the machining/drilling/polishing on the segmentation contrast processing surface of lateral margin) used, The fine surface state of lateral margin is different from processing surface；And

The fan-shaped shape (sector for being similar to pie chart) of zero probe 100 and more generally, the initial loop of layout is divided Other situations in the hole 16 of cloth, the symmetry of layout and machining to produce processing surface etc., can be by this manufacturing technology Produce.

Now, upon splitting, probe 100 can be by subsequent processing or processing so that they may not necessarily keep Above-mentioned all manufacturing features.

As it was earlier mentioned, MFP exemplary embodiments include at least two microchannels 123,124, and as one man, correspondingly hang down Directly it is connected at least two through holes 111,112 of microchannel.Moreover, the exterior section of one in layer 11,12 can part Ground metallizes, so as to provide battery lead plate.The exterior section is relative with processing surface 310,320.

In addition to microchannel 123,124, side path 224 can also be provided, as shown in Figure 9.Enjoyably, Ke Yili With segmentation step aperture 222 is limited in the end of side path.

Fig. 8 shows the view of the processing end of the double-deck MFP probes 100 obtained according to the embodiment of this manufacture method.Probe 100 have basic unit 120, and wherein treatment liquid microchannel 123,124 and steeping liq microchannel 224 is provided (herein together Only describe one in side path).Each passage is in fluid communication with corresponding aperture 121,122,222 and in the example In each aperture be located on the face of basic unit 120.Cap rock 110 closes at the passage opened wide above basic unit 120 on 120u.Aperture Formed at the edge surface 320 of basic unit 120.Due to manufacturing process, processing surface 310,320 should be typically sharp, and this permits Perhaps the compact liquid deposition in relevant surfaces 200, and be easy optical monitoring leaving space.The concavity on summit is in fig. 8 It is invisible.

Probe can also carry pipe end (not shown), so that allow (can not in Fig. 8,9 with through hole 111 and 112 See) fluidly connect.Through hole and port should be configured to allow for by corresponding through hole from port flow be communicated to aperture 121, 122、222。

As the example of application, when moving about probe on surface 200, schematically shown in Figure 9, treatment liquid PL can be distributed by aperture 121, and it (may will be provided, it is not in Fig. 9 with steeping liq IL via the lateral orifice of probe Middle display) combination.It should be noted that size is less in proportion, the particularly size in aperture, it is purposely exaggerated in order to clear.Dress 100 are put to be preferably configured to obtain laminar flow.The size in aperture can essentially be such as tens microns.They are typically Tens to hundreds of microns of interval.When being used herein paired treatment channel/aperture, treatment liquid PL can be in aperture 122 Place is sucked together with some steeping liqs IL.Flow path between aperture 121 and 122 can be overturned, i.e., treatment liquid can To be injected from aperture 122, and aperture 121 can be with pumping liquid.Treatment liquid is located substantially on aperture 121 and 122 in operation Near, and surrounded by can generally be merely present in the steeping liq near probe 100.

Now, it is possible to use by liquid is limited in by the concavity on the spontaneous processing surface 310,320 of manufacturing process It is formed in the convex space between processing surface and pending surface, schematically shown in Figure 9.However, maceration extract Body still may need hydrodynamically to limit treatment liquid, and thus avoid the scattered for the treatment of liquid.However, when device with When surface is in contact, the spill on summit has ensured some limitations of the treatment liquid flowing in recess.In this mode of operation Distance controlling is not needed.It should be noted that the curvature on summit can change with the designated volume of " design " liquid to be encapsulated.Most Afterwards, curvature limits the geometric unique flow resistance of influence flowing limitation.

All MFP probes described above particularly marked degree can be used for surface-treatment applications.Different from biologic applications, surface treatment Using including the liquid and chemicals of potential smaller pattern and wider range.Using thin silicon wafer (for example, thickness is 100 μ M) manufacture basic unit 12, for example, conventional DRIE or focused ion beam can be used to manufacture with the good of the lateral dimensions less than 10 μm The aperture shaped well, it ensures the mechanical strength of probe due to silicon lid 11 with enough thickness.It is all as described herein Multi-coating probe is also easier to use many treatment liquids, and reason is that aperture can be with small and closer to each other, and horizontal micro-channels are abundant Ground spreads out to be used to increase many ports on layer 11,12 to leave enough spaces.More generally however, this MFP technologies exist Make patterned surface, material is handled, deposits on the surface and removes biomolecule and cell, the cell on analysis surface With biomolecule, generation chemical gradient, the complex biological sample of research such as histotomy etc and generation have on the surface The structure (such as conical cavity) of peculiar profile also has possibility in terms of these.

Method specifically described herein can be used in the manufacture that MFP pops one's head in MFP chips.Resulting probe/core Piece can by manufacturer in original form (that is, as structuring bi-layer substrate and with packaged form) distribution. Chip may be mounted in single-chip package under latter event.Under any circumstance, probe and chip then can with it is other Element is integrated, and is used as the part of (a) intermediate products or (b) final products.

Refer to the attached drawing is compactly described and is adapted to many modifications above example.It is anticipated that more than Some combinations of feature.The example of such combination is provided in figure.Although with reference to the embodiment of limited quantity, modification and attached The figure description present invention, but it should be appreciated by those skilled in the art that can carry out various change and equivalent can be replaced and The scope of the present invention is not departed from.Especially, narration or the feature (device or the side that are shown in figure in embodiment, modification is specified Method) another feature can be combined or replaced with another feature in another embodiment, modification or figure, without departing from the model of the present invention Enclose.Therefore the various combinations on the feature described in any one in above example or modification are anticipated that, it still exists In the range of attached claims.Furthermore it is possible to carry out many small modifications so that particular case or material are adapted to this Scope of the teaching of invention without departing from it.So, it is contemplated that disclosed specific embodiment is unlimited to, but this hair It is bright by all embodiments including falling within the scope of the appended claims.Furthermore it is possible to expect to be different from clearly retouching above The many other modifications stated.For example, can be used for each of layer 11,12 different from other materials explicitly described herein. Similarly, passage, through hole, aperture can have different sizes.

Reference

10th, 10a bi-layer substrates

100 (one or more) micro fluidic detections (MFP) are popped one's head in

11st, 12 substrate first layers and the second layer

First (lid) layer of 110 probes 100

The lower surface of 110l first layers 11,110

111st, 112 vertical through hole

Second (base) layer of 120 probes 100

The upper surface of the 120u second layers 12,120

121st, 122 microchannel aperture

123rd, 124 microchannel

14 MFP are laid out

14i, 14o concentric probes are laid out

16 centre bores

18 define the cylindrical wall of centre bore

21st, 22 alignment hole

222 lateral microchannel apertures

224 lateral microchannels

310th, 320 probe processing surface

Claims

1. the method for one kind manufacture microfluid probe (100), methods described includes：

(S16) set of n microfluid probe layout (14) is provided on the identical bi-layer substrate including two layers (11,12), The layout is annularly disposed on the bi-layer substrate, and each in wherein described layout includes：

First layer (110), one of one (11) that first layer corresponds in described two layers (11,12) of the bi-layer substrate Point；And

The second layer (120), the one of another (12) that the second layer corresponds in described two layers (11,12) of the bi-layer substrate Part；And the second layer includes being limited and by institute by the groove opened wide on the upper surface of the second layer (120) (120u) State at least one microchannel of the part closure of the lower surface (110l) of first layer (110)；

(S20) hole (16) are machined in the center of the bi-layer substrate (10), the hole is defined so as to produce and blocks The cylindrical wall (18) of each microchannel at least one described microchannel of the layout (14) so that in the layout At least one the described microchannel of each extends up to what the end for being in the groove in the cylindrical wall (18) was formed At least one corresponding aperture；And

Each layout in segmentation (S30) the n layout pops one's head in (100) to obtain n microfluid.

2. according to the method described in claim 1, in addition to：Before it is split, the step of polishing (S24) described cylindrical wall.

3. method according to claim 1 or 2, in addition to：

Before mechanical machining, the step of microchannel of (S18) described probe layout is filled with ductile material；And

(S40) described ductile material is removed after machining.

4. method according to claim 3, wherein the ductile material is to include the material of wax, polymer or photoresist Material.

5. method according to claim 3, wherein performing ductile material after the step of polishing (S24) described cylindrical wall Removal.

6. method according to claim 3, wherein each in segmentation (S30) the n layout is held after being laid out The removal of row ductile material.

7. method according to claim 1 or 2, in addition to：Before the layout is provided, (S8, S10, S12) institute is manufactured The set of n microfluid probe layout is stated, it is included in the upper surface (120u) of another (12) in described two layers On slot out (S12) it is described n layout in each layout at least one described microchannel.

8. method according to claim 7, wherein (S12) described microchannel of slotting is carried out by micro manufacturing.

9. method according to claim 8, wherein (S12) described microchannel of slotting out is added by using photoetching or micromechanics Work is carried out.

10. method according to claim 8, wherein (S12) described microchannel of slotting out is every including wet etching or dry ecthing The step of individual microchannel.

11. method according to claim 8, is additionally included in alignment and combination (S14) institute after each microchannel of slotting out The step of stating two layers.

12. method according to claim 7, wherein the manufacture also includes each cloth in being laid out for described n Office, is machined at least one through hole that (S10) is attached perpendicularly at least one microchannel.

13. method according to claim 12, wherein at least one described through hole is passed through in described two layers (11,12) Described another (12) and be machined.

14. method according to claim 1 or 2, wherein

Each of described two layers (11,12) has disc-shape；And

One (11) in described two layers (11,12) of the bi-layer substrate：

Another (12) in described two layers (11,12) with than the bi-layer substrate small average diameter；And

Relative to another alignment described in described two layers of the bi-layer substrate so as to leaving described two layers (11,12) In another (12) not by described two layers (11,12) one (11) covering exterior section.

15. method according to claim 14, in addition to：The microfluid probe is provided on the identical bi-layer substrate Before the set for being laid out (14)：Described another (12) metallized at least in part in described two layers (11,12) cause institute At least described exterior section for stating another (12) in two layers is metallized.

16. method according to claim 1 or 2, wherein methods described also include：

Before mechanical machining, some set of (S16) probe layout are provided on corresponding bi-layer substrate；And

(S19) corresponding bi-layer substrate is superimposed,

The step of being wherein machined (S20) is included in the center of the bi-layer substrate of the superposition, the lining through all superpositions Bottom machining is portalled, so that the institute of the layout of each bi-layer substrate in producing the bi-layer substrate for blocking the superposition State the hole cylindrical wall of each microchannel of at least one microchannel.

17. method according to claim 16, in addition to polish resulting hole cylindrical wall.

18. method according to claim 1 or 2, is provided including interior wherein the offer is included on identical bi-layer substrate Set and at least two annular concentric set of outer set, each set in the interior set and the outer set include ring The probe layout in its corresponding set is distributed in shape, methods described includes two steps that machining is portalled, wherein

Machining (S20i) goes out the first hole to produce the first cylindrical wall of the microchannel for blocking the interior set, and

By by a part for the bi-layer substrate including the interior set from the separation of the remainder of the bi-layer substrate Machining (S20o) goes out the second hole to produce the second cylindrical wall of the microchannel for blocking the outer set.

19. the microfluid probe that a kind of method according to any one of preceding claims 1-18 is obtained, wherein described Microfluid probe includes：

First layer (110)；And

The second layer (120), the second layer includes：

Limited and by the first layer (110) by the groove opened wide on the upper surface of the second layer (120) (120u) At least one microchannel of the part closure of lower surface (110l)；And

Edge in the second layer (120), at least one microchannel end at least one aperture, it is described The part on the processing surface of the edge limited probe.

20. microfluid probe according to claim 19, wherein the institute in the manufacture method popped one's head in by the microfluid The machining of hole (16) is stated, at least a portion on the processing surface is recessed.

21. the microfluid probe according to claim 19 or 20, two side edge parts also with the angle into 2 π/n ± π/10 Point.

22. the microfluid probe according to claim 19 or 20, two side edge portions at the angle also with 2 π/n ± pi/2s 0.

23. the microfluid probe according to claim 19 or 20, including at least two microchannels.

24. microfluid according to claim 23 probe, in addition to be correspondingly attached perpendicularly to described at least two micro- At least two through holes of passage.

25. the microfluid probe according to claim 19 or 20, wherein with limiting described in the processing surface of the probe The relative exterior section in edge is metallized.