MICROFLUIDIC CELL AND METHOD FOR THE PRODUCTION THEREOF
20190329252 ยท 2019-10-31
Assignee
Inventors
- Hauke Esemann (Woerrstadt, DE)
- Stephanie Mangold (Klein - Winternheim, DE)
- Andreas Roters (Mainz, DE)
- Andreas ORTNER (Gau-Algesheim, DE)
- Markus Heiss-Chouquet (Bischofsheim, DE)
- Fabian Wagner (Mainz, DE)
- Vanessa Hiller (Mainz, DE)
- Laura Brueckbauer (Dorn-Duerkheim, DE)
Cpc classification
B81C1/00119
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/12
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502707
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502715
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/12
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
A method for the production of microfluidic cells using a disc-shaped glass element is provided. The disc-shaped glass element has a thickness of at most 700 micrometers is structured in such a way that it has at least one opening. The opening connects the two opposite-lying, parallel side faces of the glass element. The side faces are attached to a glass part so that the opening is sealed by the two glass parts to form a microfluidic cell having a cavity enclosed therein. The cavity is suitable for the conveyance of fluids. The attachment of the glass element to at least one of the two glass parts is produced by an adhesive that is applied onto the side face of the glass element. During application of the adhesive, the at least one opening in the glass element is left free of adhesive.
Claims
1. A method for the production of a microfluidic cell, comprising: structuring a glass element that has a thickness of at most 700 micrometers to have an opening that connects two opposite-lying parallel side faces of the glass element; and attaching a first glass part to a first face of the two side faces and a second glass part to a second face of the two side faces to seal the opening so that a cavity that is enclosed between the two glass parts, wherein the cavity is configured to convey fluids, wherein the step of attaching at least one of the first and second glass parts comprises using an adhesive in such a manner that the opening is left free of the adhesive.
2. The method of claim 1, wherein the step of using the adhesive comprises applying the adhesive to at least one of the two faces of the glass element so that the opening is left free of adhesive.
3. The method of claim 1, wherein the step of structuring glass element to have the opening comprises structuring an elongated opening so that the cavity is a fluid-carrying channel.
4. The method of claim 3, wherein the step of using the adhesive comprises printing onto at least one of the two side faces, leaving out a region extending over the elongated opening, wherein the region is larger than the opening so that an edge of the adhesive is set back from an edge of the opening.
5. The method of claim 1, wherein the step of using the adhesive comprises applying the adhesive so that an edge of the opening remains free of adhesive.
6. The method of claim 1, wherein the step of structuring glass element to have the opening comprises: directing a laser beam of an ultrashort-pulse laser onto one of the two side faces and concentrating the laser beam using a focusing optics to form an elongated focus in the glass element so that a filament-shaped damage insertion is produced in the glass element, wherein the filament-shaped damage insertion has a longitudinal direction that extends perpendicularly between the two side faces; and exposing, after forming the filament-shaped damage insertion, the glass element to an etching medium to remove glass from the glass element at a removal rate of less than 8 m per hour to widens the filament-shaped damage insertion to form the opening.
7. The method of claim 6, wherein the etching medium inserts rounded dome-shaped depressions in walls of the opening.
8. The method of claim 6, further comprising repeating the step of directing the laser beam to produce a plurality of filament-shaped damage insertions adjacent to one another, wherein the step of exposing the glass element to the etching medium comprises etching the plurality of filament-shaped damage insertions until adjacent insertions are joined together to form the opening.
9. The method of claim 8, wherein ridges remain between the plurality of filament-shaped damage insertions after the exposing step, the ridges extending parallel to the longitudinal direction.
10. The method of claim 1, further comprising: directing a laser beam of an ultrashort-pulse laser onto one of the two side faces and concentrating the laser beam using a focusing optics to form an elongated focus in the glass element so that a filament-shaped damage insertion is produced in the glass element, wherein the filament-shaped damage insertion has a longitudinal direction that extends perpendicularly from one of the two side faces and terminates in the glass element; repeating the step of directing the laser beam to produce a plurality of filament-shaped damage insertions adjacent to one another; and exposing, after forming the plurality of filament-shaped damage insertions, the glass element to an etching medium to remove glass from the glass element at a removal rate of less than 8 m per hour until adjacent insertions are joined together to form a recess that is sealed on one side by the glass element.
11. The method of claim 10, wherein ridges remain between the plurality of filament-shaped damage insertions after the exposing step, the ridges extending parallel to the longitudinal direction.
12. The method of claim 1, wherein at least one of the first and second glass parts comprises a second opening, wherein the first and second glass parts are attached to the glass element in such a way that the second opening is in fluid communication with the opening.
13. The method of claim 1, wherein the step of structuring the glass element to have the opening comprises structuring to have at least two adjacently extending openings, the at least two openings being separated from each other by a crosspiece, wherein the cross piece has a minimum width of at most 400 m, and wherein the crosspiece is bonded with the adhesive to the at least one of the first and second glass parts.
14. The method of claim 1, wherein the adhesive is a photocurable adhesive, the step of attaching further comprising irradiating the adhesive through one of the first and second glass parts to harden the adhesive.
15. A microfluidic cell, comprising: a disc-shaped glass element with a thickness of at most 700 micrometers and an opening that connects two opposite-lying, parallel side faces of the glass element; a first glass part attached to a first face of the two side faces; a second glass part attached to a second face of the two side faces; a cavity defined by the opening being sealed by the first and second glass parts, the cavity being suitable for fluid conveyance; and dome shaped depressions in at least part of a wall the opening.
16. The microfluidic cell of claim 15, further comprising: an adhesive attaching at least one of the first and second glass parts to the glass element; and a region that is left free of the adhesive around the opening so that a part of the cavity is formed by the first and second glass parts.
17. The microfluidic cell of claim 15, wherein the dome shaped depressions have a depth, on average, of less than 5 m and/or have a transverse measurement, on average, of 5 m to 20 m.
18. The microfluidic cell of claim 15, wherein the opening has an edge that comprises a plurality of parallel, adjacently extending, laterally open channels with a ridge that extends parallel to the longitudinal direction between adjacent open channels.
19. The microfluidic cell of claim 15, further comprising a second opening and a crosspiece, the crosspiece being between the opening and the second opening, the crosspiece having a minimum width of less than 1 mm and having a parameter G of at least 10 mm.sup.1/3 and of at most 400 mm.sup.1/3, wherein the parameter G is specified by:
20. The microfluidic cell of claim 15, further comprising a recess in one of the glass element, the first glass part, and the second glass part, wherein the recess is open on one side and is in fluid communication with the cavity.
21. A microfluidic cell, comprising a stack of at least two disc-shaped glass elements that are attached to each other and two glass parts that are attached to the stack and between which the stack is arranged, wherein the glass elements each have an opening that is sealed by attachment of the bordering glass element or the glass parts to form a cavity configured to convey fluids, wherein the openings in the glass elements communicate with one another, and wherein the glass elements and the glass parts are attached to one another by adhesive layers that leave the openings free of adhesive.
22. The microfluidic cell of claim 21, further comprising dome shaped depressions in at least part of a wall the opening and/or an edge of the opening that comprises a plurality of parallel, adjacently extending, laterally open channels with a ridge that extends parallel to the longitudinal direction between adjacent open channels.
23. An intermediate product for producing a microfluidic cell, comprising: a disc-shaped glass element with a thickness of at most 700 micrometers and an opening that connects two opposite-lying, parallel side faces of the glass element; and adhesive on each of the two side faces, the opening being free of the adhesive.
24. The intermediate product of claim 23, further comprising dome shaped depressions in at least part of a wall the opening and/or an edge of the opening that comprises a plurality of parallel, adjacently extending, laterally open channels with a ridge that extends parallel to the longitudinal direction between adjacent open channels.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] The invention will be explained below in detail and with reference to the appended drawings.
[0035]
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DETAILED DESCRIPTION
[0055]
[0056] As can be seen in the illustration, the disc-shaped glass element 3 has a plurality of adjacently lying elongated openings 10. The latter are separated from one another in part by narrow webs or crosspieces 19, respectively. If the glass parts 5, 7 are attached to the disc-shaped glass element 3, then the elongated openings 10 are sealed by the two glass parts 5, 7, and cavities are formed that particularly form elongated channels corresponding to the shape of the openings 10 running in the direction along the side faces of the glass element 3.
[0057] Even very thin crosspieces 19 can be printed with the adhesive. In one embodiment of the invention, it is provided that a glass element 3 having at least two adjacently extending openings 10 are provided, which are separated from each other by a crosspiece 19 that has a minimum width of at most 400 m, wherein the crosspiece of the glass element 3 is attached to the glass part 5 or 7 by using an adhesive. In the illustrated example, a group of openings 10 has been produced, which are separated by crosspieces 19 with a crosspiece width of 300 m. In order to further ensure a tight attachment and in order to prevent or at least to reduce any entry of adhesive onto the wall of the cavity formed from the opening, a minimum width of the crosspiece of at least 50 m is preferred.
[0058] In order to attach the glass parts 5, 7 to the disc-shaped glass element 3, it is then provided that adhesive is applied onto the surfaces to be attached. Preferably, the application of adhesive is produced, at least for the attachment to one of the glass parts 5, 7, on the disc-shaped glass element 3. However, the application of adhesive can also be made on a corresponding surface of the glass part 5 or 7 that is to be attached.
[0059] As can be further seen on the basis of
[0060] In an enhancement of the invention, without any limitation to the illustrated example, it is therefore provided that, in at least one of the glass parts, an opening 40 is present or is inserted into the glass part 5, 7, wherein the glass part 5, 7 is combined with the glass element in such a way that the opening 40 produces a connection to the opening 10 in the glass element 3 and hence produces a fluid-carrying connection in the cavity that is produced in the glass element 3 from the opening 10 when it is sealed to the two glass parts 5, 7. For example, the opening 10 in elongated shape can form a cavity 9 in the form of a thin channel, along which a fluid that is provided at the opening 40 in the glass part 5, 7 is conveyed. In one exemplary embodiment, as the glass element 3, an interposer with a thickness of 80 micrometers was adhesively bonded to a glass element 5 with a thickness of 0.7 millimeter as a cover and to a glass element 7 as a bottom with a thickness of 0.3 millimeter.
[0061]
[0062] The attachment of the glass element 3 to the two glass parts 5, 7 is produced by an applied adhesive 12. During application of the adhesive 12, the openings 10 in the glass element 3 are left free. It is thereby prevented that the adhesive reaches the edges 11 of the openings 10 and, as a result, after completed fabrication of the cell, is present in the cavities 9 formed from the openings. The adhesive 12 is applied as a thin adhesive layer 15. In the illustrated example, the application is produced on both sides of the glass element 3. However, it is also conceivable to apply the adhesive for one or both joints onto a glass part 5, 7. In any case, however, the adhesive is applied in such a way that the edge of the opening 10 that later forms the side wall of a cavity produced using the opening 10 remains free of adhesive.
[0063] The adhesive layer 15 can also be applied as an adhering filmfor example, as a film furnished with a pressure-sensitive adhesive.
[0064] In general, it may be desirable to prefabricate the glass element 3 with the adhesive layers 15 and to join the glass parts 5, 7 thereto only at a later point in time. This is the case, for example, when one or both of the glass parts 5, 7 is or are furnished with biomarkers or, in general, biofunctional molecules, which, after the attachment thereof, can then adhere to the wall of the cavity 9 and react with constituents of an added fluid. Thus created, in general, is a microfluidic cell 1 for which the glass element 3 is attached to at least one of the glass parts 5, 7 by an adhesive layer 15, whereby the adhesive layer 15 has a region 13 that remains free of adhesive around the at least one opening 10, so that the part of the wall of the cavity 9 formed by the glass part 5, 7 is left free of the adhesive layer 15, and whereby at least this part of the wall of the cavity 9 is furnished with adhering biofunctional molecules, in particular biomarkers. If the biofunctional molecules are applied over the entire surface, then they are also situated in the adhesively bonded region, where, of course, however, they cannot come into contact with the fluid that is to be treated.
[0065] In order to be able to perform such a later adhesive bonding with individually furnished glass parts 5, 7, for example, the invention also relates to an intermediate product for producing a microfluidic cell 1 having a disc-shaped glass element 3 with a thickness of at most 700 micrometers, which is structured in such a way that it has at least one opening 10, which connects the two opposite-lying parallel side faces 30, 31 of the glass element 3, wherein each of the two side faces 30, 31 is furnished with an adhesive layer 15 in order to attach the side faces 30, 31 to the glass parts 5, 7, so that the opening 10 is sealed, and a microfluidic cell 1 having a cavity 9 that is suitable for the conveyance of fluids is formed, wherein the adhesive layer 15 leaves free the at least one opening 10 in the glass element 3.
[0066] As can be seen on the basis of
[0067] In general, thin adhesive layers 15 are preferred. In accordance with one embodiment of the invention, it is preferred that the adhesive 12 is applied with a thickness of at most 50 m, preferably at most 20 m. As mentioned above, however, it is favorable when the adhesive layer thickness is at least of the magnitude of the variation in thickness of the glass. In general, it is preferred that the thickness of the applied adhesive layer is at least 2 m.
[0068]
[0069] As illustrated, the region 13 can be kept larger than the opening 10, so that the edge of the left-free region is spaced apart somewhat from the edge 11 of the opening 10. In addition to the embodiment with an ink-jet printing head, it is also possible for other methods to be used. Other printing methods are pad printing, screen printing, stencil printing, roll coating or roll-to-roll coating, dispensing, and stamp transfer. Suitable especially for larger unit numbers are printing methods such as pad printing and screen printing. In an exemplary embodiment, for the production of a structure of a microfluidic cell such as that shown in
[0070] The viscosity of the adhesive can generally also be adjusted to the printing method. Thus, for pad printing, lower viscositiesfor example, in the range around 300 mPa.Math.sare preferred. In the inkjet method, illustrated by way of example in
[0071] A preferred embodiment of the invention provides the application of a photocurable, preferably UV-curable, adhesive 12. The adhesive 12 can then be irradiated with light, preferably UV light, through one of the glass parts 5, 7, so that the adhesive is hardened and the glass part, or, in the case of two-sided application, both glass parts 5, 7 are firmly adhesively bonded to the glass element 3. Suitable adhesives, which can also be UV-curable, are silicone-containing adhesives, epoxy resins, and acrylates.
[0072] Described below is a preferred embodiment of the structuring of the glass element 3 in order to introduce one elongated opening or a plurality of elongated openings 10. The opening 10 in the glass element 3 is produced in that the laser beam 27 of an ultrashort-pulse laser 29 is directed onto one of the side faces 30, 31 of the glass element 3 and, by using a focusing optics 23, is concentrated to an elongated focus in the glass element 3, whereby, through the irradiated energy of the laser beam 27, filament-shaped damage 32 is produced in the volume of the glass element 3, the longitudinal direction of which extends transversely to the side faces 30, 31, in particular perpendicularly to the side faces 30, 31, and, for the creation of filament-shaped damage by the ultrashort-pulse laser 29, one pulse or a pulse packet containing at least two laser pulses following one another is or are radiated and whereby, after inserting the filament-shaped damage 32; the glass element 3 is exposed to an etching medium, which removes the glass of the glass element 3 at a removal rate of preferably less than 8 m per hour; and widens the filament-shaped damage 32 to form a channel 35; and introduces rounded, dome-shaped depressions into the walls of the channel.
[0073] In
[0074] The focusing optics 23 then focus the laser beam 27 to form an elongated focus in the direction of the beam, that is, accordingly transversely and, in particular, perpendicularly to the irradiated side face 30. Such a focus can be produced, for example, with a cone-shaped lens (a so-called axicon) or with a lens having a large spherical aberration. The control of the positioning device 47 and of the ultrashort-pulse laser 30 is preferably performed by means of a computing device 45 set up to run a program. In this way, it is possible to produce predefined patterns of filament-shaped damage 32 distributed laterally along the side face 2; this is accomplished, in particular, by reading in positional data, preferably from a file or via a network.
[0075] In accordance with one exemplary embodiment, the following parameters can be used for the laser beam.
[0076] The wavelength of the laser beam is 1064 nm, which is typical for a YAG laser. A laser beam with a raw beam diameter of 12 mm is produced, which is then focused using an optics in the form of a biconvex lens with a focal length of 16 mm. The pulse length of the ultrashort-pulse laser is less than 20 ps, preferably about 10 ps. The pulses are delivered in bursts of 2 or more pulses, preferably 4 or more pulses. The burst frequency is 12-48 ns, preferably about 20 ns, the pulse energy is at least 200 microjoules, and the burst energy is correspondingly at least 400 microjoules.
[0077] Subsequently, after one filament-shaped damage insertion, or, in particular, a plurality of filament-shaped damage insertions 32, the glass element 3 is removed and placed in an etching bath, where, in a slow etching process, glass is removed along the filament-shaped damage insertions 32, so that, at the site of such a damage insertion 32, a channel is inserted into the glass element 3 in each case.
[0078] Without any limitation to special exemplary embodiments, generally a basic etching bath, with a pH value of >12, such as, for example, a KOH solution containing >4 mol/L, preferably >5 mol/L, especially preferred >6 mol/L, but <30 mol/L is preferred. The etching is performed in accordance with one embodiment of the invention, regardless of the etching medium used, at a temperature of the etching bath of >70 C., preferably >80 C., and especially preferably >90 C. The etching using a basic etching bath leads to the structure with dome-shaped depressions. However, it is also possible to perform etching using an acidic etching medium.
[0079]
[0080]
[0081] The channels 41, which are inserted next to one another along the path traveled by the laser, can then serve as desired breakage sites in order to release a part of the glass element 3 or to separate the glass element 3 along this path in order to obtain an opening 10.
[0082]
[0083] Quite generally, without any limitation to the special exemplary embodiment, a separation along one channel or a plurality of channels 41 then results in the creation of a plate-shaped glass element 3 having a channel 41, which is open on the side and forms a part of the edge 100 of the opening 10.
[0084] Furthermore, glass material was still present between the channels 41, as shown in
[0085] In order to release an inner part and/or to produce an opening 10 in a glass element 3, a variant of the above-described method is especially suitable. This embodiment of the invention is based on the fact that, as a result of the etching, the diameter of the channels 41 is enlarged to such an extent that the glass between the channels 41 is removed and the channels 41 combine.
[0086]
[0087]
[0088] Furthermore, all of these examples are based on an embodiment of the method according to the invention, in which the point of impingement 73 of the laser beam 27 on the glass element 3 is guided along a predetermined path, and a plurality of filament-shaped damage insertions 32 that lie adjacent to one another on the path, and subsequently, as a result of the etching, a plurality of adjacently lying channels 41 are inserted into the glass element 3, and the glass element 3 is then separated along the path, so that an edge 100 with laterally open channels 41 is formed.
[0089] The channels 41 have, in general, a tube-shaped, cylindrical basic shape or are tube-shaped with cylindrically formed walls. It is thereby possible for a slight tapering of the opening to be present at the side face toward the middle of the glass element 3. During the combination of the generally cylindrically formed channels 41 in the course of the widening during the etching process, ridges can form at the abutting sites. In general, without any limitation to the example of
[0090] Accordingly, these ridges or ribs extend parallel to the longitudinal direction of the channels and, in the illustration of
[0091]
[0092] In this example, the separating distance of the channels 41 is relatively large, being about 50 m. The separating distance can also be chosen to be smaller, in particular in the case when the channels 41 transition directly into one another without any flat edge sections 101. In general, the separating distance of the channels (also referred to as the pitch) is preferably in the range of 3 to 70 micrometers. This separating distance is measured here from the middle of one channel to the middle of the adjacent channel. The transverse dimension or the diameter of the channels 41 is preferably less than 100 micrometers. Preferably, the diameter lies in a range that is similar to the separating distance of the channels 41. Without any limitation to the examples described here, a diameter that lies in the range of 3 micrometers to 50 micrometers is preferred. In the example of
[0093] As can be seen on the basis of
[0094] Accordingly, without any limitation to the examples illustrated, the invention generally also relates to a microfluidic cell 1 having a disc-shaped glass element 3 with a thickness of at most 300 micrometers, which has at least one elongated opening 10 that connects the two opposite-lying parallel side faces 30, 31 of the glass element 3, wherein each of the side faces 30, 31 of the glass element 3 is attached to a glass part 5, 7, so that the elongated opening 10 through the two glass parts 5, 7 is sealed and an enclosed cavity 9 is formed between the two glass parts 5, 7 and is suitable for the conveyance of fluids, wherein the edge 100 of the opening 10 or, accordingly, only the part of the wall of the cavity that is formed by the edge 100 of the opening 10 has dome-shaped depressions 37.
[0095] In the case of microfluidic cells, this structure of the cavity 9 has the special advantage that the dome-shaped depressions at the side walls improve the wettability for fluids. This ensures an improved ability to fill the cell.
[0096] This embodiment is independent of the way in which the glass element 3 is attached to the glass parts 5, 7. The above-described adhesive bonding is preferred, but other methods of attachment, such as, for instance, anodic bonding or direct bonding as well as also welding or soldering using glass solder, are possible. In accordance with an enhancement of the invention, therefore, without any limitation to special exemplary embodiments or to the figures, the glass element 3 is attached to at least one of the glass parts 5, 7 through an adhesive bond or an anodic bond or a direct bond or a weld or a glass solder. In the case of adhesive bonding, the above-explained structured coating with an adhesive layer 15 is preferred.
[0097] In accordance herewith, in an enhancement of the invention, it is provided that the glass element 3 is attached to at least one of the glass parts 5, 7 through an adhesive layer 15, wherein the adhesive layer 15 has a region 13 that is left free of adhesive around the at least one opening 10, so that the part 91 of the wall of the cavity 9 formed by the glass part 5, 7 is left free of the adhesive layer. In particular, therefore, this part 91 of the wall can thereby be formed by the surface material of the glass part 5, 7. The regions 91 are marked in
[0098] The depth of the dome-shaped depressions 37 is typically, that is, on average, less than 5 m; for transverse measurements, on average, 5-20 m. In accordance with an enhancement of the invention, the etching is thus carried out in such a way that at least one of the aforementioned features of the dome-shaped depressions is obtained.
[0099] It can be seen that, not only owing to the depressions 37, but especially owing to the channels 41, the surface of the edge 100 is larger than the surface of a flat edge. This fine structure, too, improves the wettability of the cavity 9.
[0100] In accordance with one aspect of the invention, therefore, a microfluidic cell 1 having a glass element 3 with two opposite-lying side faces 30, 31 and an elongated opening 10, which is delimited by an edge 100, is provided, wherein, at the side faces 30, 31, the glass parts 5, 7 are fastened, so that the opening 10 forms a cavity 9 between the glass parts 5, 7, wherein the edge 100 of the opening has a plurality of parallel, adjacently extending, laterally open channels 41 with rounded walls 54 and with a transverse dimension of less than 200 m, the longitudinal direction 51 of which extends transversely, preferably perpendicularly, to the side faces 30, 31 of the glass element 3, and these channels preferably also end at the side faces 30, 31 or open into them. As such, this embodiment is also independent of the kind of attachment of the glass element 3 to the glass parts 5, 7 and, furthermore, is also independent of whether dome-shaped depressions are created by the etching. Preferably present, however, are both the depressions 37 and an adhesive layer 15 for attachment to the glass part or glass parts 5, 7.
[0101] If the channels 41 directly bordered one another and had an exactly semicircular cross section, then the length of the edge line parallel to the side faces 30, 31 would be larger than the edge line of a smooth edge by a factor of /2. The enlargements of the surface area that can be achieved using the method according to the invention are, in general, somewhat smaller and typically lie in the range of 10 to 40 percent. Correspondingly, in an enhancement of the invention, it is provided that the surface of the edge 100, due to the channels 41, is enlarged by a factor of 1.1 to 1.4 in comparison to a smooth edge surface area without channels 41.
[0102] This enlargement of the surface affords, as a further side effect, an edge that is relatively resistant to breakage under bending loads. This is surprising insofar as, normally, the probability of breakage is scaled to the surface area. The structures that protrude with respect to the rounded channel likely lead to the fact that defects are not able to propagate at these protruding structures (ridges or flat edge sections). As a result of the structuring of the edge 11, the propagation of cracks is thus suppressed. The microfluidic cell 1 is thus also more stable mechanically.
[0103] On the basis of
[0104] Furthermore, it can be seen that, in a top view of the depressions 37, the ridges 70 form polygonal boundary lines 71 of the depressions 37. In this case, the mean number of corners 72 of the boundary lines 71 of the depressions 7 is preferably also less than eight, preferably less than seven. The latter feature results when the regions occupied by most of the dome-shaped depressions are convex in the mathematical sense.
[0105] In one embodiment of the invention, therefore, a microfluidic cell 1 is provided, for which the dome-shaped depressions 37 in the edge 100 of the opening 10 border one another and the concave roundings of the depressions 37 that are in abutting contact with one another create ridges 70. In an enhancement of this embodiment, it is further provided that, in a top view of the depressions 37, the ridges 70 form polygonal boundary lines 71 of the depressions 37.
[0106] The ridges 70 of the channel 41 shown in
[0107] The glass element 3 in the example of
TABLE-US-00001 Composition (wt %) SiO.sub.2 63-83 Al.sub.2O.sub.3 0-7 B.sub.2O.sub.3 5-18 Li.sub.2O + Na.sub.2O + K.sub.2O 4-14 MgO + CaO + SrO + BaO + ZnO 0-10 TiO.sub.2 + ZrO.sub.2 0-3 P.sub.2O.sub.5 0-2
[0108] This glass can also be used for the glass parts 5, 7.
[0109]
[0110] Yet another glass from the class of low-alkali silicate glasses that is well suited for the production of a microfluidic cell 1 according to the invention is an alkali-free aluminosilicate glass. Preferred here is a glass with the following composition:
TABLE-US-00002 Composition (wt %) SiO.sub.2 50-75 Al.sub.2O.sub.3 7-25 B.sub.2O.sub.3 0-20 Li.sub.2O + Na.sub.2O + K.sub.2O 0-0.1 MgO + CaO + SrO + BaO + ZnO 5-25 TiO.sub.2 + ZrO.sub.2 0-10 P.sub.2O.sub.5 0-5
[0111] In general, it is favorable, without any limitation to the above-mentioned compositions, to use glasses with basicities in the range of 0.45 to 0.55, preferably in the range of 0.48 to 0.54. This makes the glasses especially suitable for a slow, controlled etching using basic etching media, whereby, however, an etching with acidic etching media is also still possible. This glass offers itself then for use in each case not only for the glass element 3, but also for the glass parts 5, 7.
[0112] In accordance with yet another embodiment of the invention, a glass with a very low auto-fluorescence is used. The glass can be used for the glass element 3 and/or for at least one of the glass parts 5, 7, preferably for all of these component parts of the microfluidic cell. The intensity of the auto-fluorescence is influenced by the optical basicity. A low optical basicity is associated, in general, with a reduced fluorescence, which is of advantage for biotechnological applications of the microfluidic cell. For instance, the fluorescence markers or labels Cy3 and Cy5 are often used for biotechnological applications. These labels fluoresce at wavelengths of 570 nm and 670 nm, at which many glasses also exhibit auto-fluorescence. The auto-fluorescence degrades the signal-to-noise ratio in optical detection processes. A glass used in accordance with one embodiment of the invention for at least one component part of the microfluidic cell has a ratio of auto-fluorescence emission to excitation of less than 1% at 488 nm. For this purpose, the glass has an optical basicity A of less than 0.6, preferably less than 0.55, especially preferred less than 0.53. In particular, optical basicities of less than 0.52, preferably less than 0.51, is used for at least one of the glass component parts, in particular both for the glass element 3 and for the two glass parts 5, 7. In accordance with one embodiment, a glass of low optical basicity and low auto-fluorescence that contains the following glass constituents is used:
TABLE-US-00003 SiO.sub.2 >60 to 90 mol % Al.sub.2O.sub.3 >0 to 15 mol % B.sub.2O.sub.3 >4 to 25 mol %, preferably >5 to 25 mol %, R.sub.2O >0 to <20 mol % RO 0 to <20 mol %
[0113] Here, R.sub.2O is the sum of the contents of the alkali oxides Li.sub.2O, Na.sub.2O, and K.sub.2O. RO is the sum of the contents of ZnO and the alkaline-earth oxides MgO, CaO, SrO, and BaO.
[0114] In a special embodiment, the glass contains the following glass constituents:
TABLE-US-00004 SiO.sub.2 >80 to <85 mol % Al.sub.2O.sub.3 >0.5 to <3 mol % B.sub.2O.sub.3 >8 to 15 mol % R.sub.2O >0 to <5 mol % RO 0 to <5 mol %
[0115] In accordance with yet another enhancement of the embodiment with a glass of low auto-fluorescence and low optical basicity, for the quantitative ratio x.sub.B3+/x.sub.Al3+, the molar contents of boron to aluminum are
preferably
[0116] On the other hand, the ratio is preferably
in particular
[0117] Some components of glasses also have a negative influence on the UV transmission. For especially suitable glasses, the contents of these components are limited. Thus, in accordance with yet another alternative or additional embodiment of the invention, the contents of SnO.sub.2, Sb.sub.2O.sub.3, CeO.sub.2, TiO.sub.2, and/or Fe.sub.2O.sub.3 are each in the range of 0 to 0.5 mol %, preferably less than 0.01 mol %.
[0118]
[0119]
[0120] As can be seen further in the example of
[0121] Owing to the high stability and strength of the edges of an opening 10 in the glass element 3 that are produced in accordance with the invention, the invention is especially suitable for complex and fragile structures that cannot be produced using other methods. Symmetrical sections with thin and/or long crosspieces are also included here. It was also found, however, that the stability of the glass element 3 is greatly dependent on the geometry. More precisely, it was found that it is favorable for a structure that is held in openings in the glass element by one crosspiece or by a plurality of crosspieces to comply with a specific geometric specification. This specification ensures an adequate stability and handling. Provided in particular, for this purpose, is a glass element 3 that has at least two openings 10 in such a way that, between the openings 10, a structure with at least one crosspiece 19 is formed. In this case, the structure can be assigned a parameter G, which is given by the following relation:
[0122] Glass elements 3 according to the invention in microfluidic cells can further be created here with good mechanical stability when the parameter G is at least 10 mm.sup.1/3, preferably at least 50 mm.sup.1/3, especially preferred at least 100 mm.sup.1/3. Conversely, it is sufficient when the parameter is at most 400 mm.sup.1/3, preferably at most 300 mm.sup.1/3, and especially preferred at most 200 mm.sup.1/3.
[0123] The variable h in the above relation refers to the thickness of the glass element 3, that is, a thickness of at most 300 micrometers.
[0124] For clarification of the parameters of the relation,
[0125] In the above relation, l.sub.1 refers to the longest edge length between two adjacent contact points or contact regions 44, which lie along the edge of the structure, of one crosspiece or of two different crosspieces 19 and the glass element 3. This measure thus refers to the arc length of the longest edge between two adjacent contact regions 44. Depending on the shaping, the edges 46, 47 of the crosspiece 19 can have different lengths, as also shown in the example of
[0126] The length 12 refers to the shortest rectilinear separating distance between two contact regions 44 at the ends of the crosspiece 19. For both lengths 11 and 12, the separating distance from edge to edge of the circularly shaped contact regions 44 is decisive. In the case of more than two contact regions 44, the paths of lengths l.sub.1 and l.sub.2 do not necessarily need to extend between the same contact regions 44. The double arrow inscribed in
[0127] Finally, the parameter b refers to the smallest separating distance between the openings 10 with respect to one another along the crosspiece 19 or, in other words, the minimum crosspiece width.
[0128] A geometry of this kind, as was described above, is advantageous in regard to strength and handling in connection with the formation of the edge in accordance with the invention, that is, with dome-shaped depressions. However, a geometry of this kind can also be used with differently formed edges.
[0129] In the illustrated example, only a single crosspiece 19 is present. However, a plurality of structures is also possible, which are supported by more than one crosspiece. In this case, it is important that, for a plurality of crosspieces, the paths l.sub.1 and l.sub.2 can extend between different contact regions 44. For evaluation of the stability of a design, G thus sets the longest possible path between two contact regions l.sub.1 in relation to the shortest possible connection l.sub.2 of two contact points. As stated, these can also be different contact regions. For the number N of contact regions 44, N2 fundamentally applies.
[0130] For further clarification,
[0131] On the basis of the two top structures 39, it can be seen that the separating distance 12 and the arc length l.sub.1 between the contact regions 44 at different crosspieces can be calculated. For the parameter G, the longest edge length l.sub.1 between two contact points 44 that lie adjacently along the edge of the structure is decisive. This is inscribed for both structures 39 in each case. In particular, in the example of the topmost circularly shaped structure 39, this results in a shortest separating distance l.sub.2 between two contact regions 44 and a longest edge length l.sub.1 between two other adjacent contact regions 44.
[0132] In accordance therewith, in one embodiment of the invention, also regardless of the morphology of the edges, a microfluidic cell 1 having a plate-shaped glass element 3 with a thickness of at most 700 micrometers, preferably at most 300 micrometers, and two opposite-lying side faces 30, 31 is provided, whereby, in the glass element 3, at least two openings 10 are inserted in such a way that the region of the glass element 3 between the openings forms a structure 39 having at least one crosspiece 19, the minimum width of which is less than 1 mm, whereby, for the structure, a parameter G that is specified by the above-given relation is defined, where the parameter G has a value of at least 10 mm.sup.1/3 and of at most 400 mm.sup.1/3, where l.sub.1 is the longest edge length between two adjacent contact regions 44 along the edge of one of the openings 13 and l.sub.2 is the length of the shortest possible rectilinear connection between two contact regions 44, and whereby a contact region 44 of a crosspiece 19 is defined in each case as a circularly shaped region of the glass element 3 with a diameter of 1 m, which is arranged at the crosspiece 19 in such a way that the edge thereof touches the edges of both openings 10, the intermediate region of which forms the crosspiece 19, at least at one point in each case, and where b is the minimum crosspiece width, h is the thickness of the glass element 1, and N is the number of contact regions 44. For this embodiment, crosspieces with a minimum width of not less than 300 m are preferred.
[0133] In the above-described exemplary embodiments of the invention, the microfluidic cell comprises a sandwich structure with three levels, namely, the glass parts 5, 7 and the interposed glass element 3. The terms glass element, on the one hand, and glass part, on the other hand, are chosen in the sense of the description solely to make a simple distinction between the different layers of the sandwich structure. One of the glass parts, such as, for example, the glass part 5, can then, for its part, be designed, in turn, as another glass element 3 with at least one opening 10, which is sealed by another glass part with the formation of a cavity, whereby the other glass part, in turn, can also be another glass element 3 structured with an opening, etc. If, in the above description, the outer glass elements are identified as the glass parts 5, 7 a microfluidic cell 1 with a multilayer structure is obtained. The example of
[0134] In accordance with one embodiment of the invention, there is thus provided a microfluidic cell 1 that has a stack 234 with at least two disc-shaped glass elements 2, 3, 4 attached to each other as well as two glass parts 5, 7, which are attached to the stack 234 and the stack 234 is arranged between them, whereby the glass elements 2, 3, 4 each have at least one, preferably elongated opening 10, which is sealed by being attached to the bordering glass elements 2, 3,4 or glass parts 5, 7 and thereby forms a cavity 9, which is suitable for the conveyance of fluids. Preferably, as stated, the cavities 9 in the various glass elements communicate with one another. Furthermore, the attachment of glass elements 2, 3, 4 and glass parts 5, 7 is produced, as discussed, through adhesive layers 15, which leave free the openings 10. Furthermore, it is preferred that the openings 10 are produced by the method explained here by introducing filament-shaped damage insertions and etching them to create channels 41, so that the edges 100 of the openings have dome-shaped depressions.
[0135] In the embodiments of the invention presented here, the structuring of the glass elements 2, 3, 4 and the glass parts 5, 7 are made in the form of openings, which pass through the respective glass element or glass part. However, it is also possible, by using the above-described laser-assisted etching method, to produce depressions or recesses that are open on one side. Such structures can be combined with the openings 10 or 40 in an advantageous way in order to produce fluid-carrying arrangements in the microfluidic cell 1. In general, without any limitation to the specific examples described here, it is therefore provided in one embodiment of the invention that a glass element 2, 3, 4 and/or glass part has a recess or depression that is open on one side, which is a component part of a structure that is suitable for the conveyance of fluids and, in particular, is a component part of cavities 9 formed with an opening 10 in the glass element 3 or communicates with the cavity 9.
[0136]
[0137]
[0138] The method for producing such a depression or recess 24 is based preferably on a variant of the laser-based method explained above, in which filament-shaped damage insertions introduced by an ultrashort-pulse laser are widened by etching. Without any limitation to the illustrated examples, the method is generally based on the fact that the laser beam 27 of an ultrashort-pulse laser 29 is directed onto one of the side faces 30, 31 of the glass element 3 or the glass parts 5, 7 and concentrated using a focusing optics 23 to form an elongated focus in the glass, wherein, through the irradiated energy of the laser beam 27, filament-shaped damage insertions 32 are produced in the volume of the glass, the longitudinal direction of which extends transversely to the side face 30, 31, in particular perpendicularly to the side face 30, 31, of the glass element 3 or the glass parts 5, 7, and, for the creation of filament-shaped damage by the ultrashort-pulse laser 29, one pulse or a pulse packet containing at least two laser pulses in succession is irradiated, wherein the laser beam 27 is irradiated in such a way that one end of the elongated focus lies inside the glass, so that the filament-shaped damage 32 also terminates in the glass, but extends up to a side face 31, 32; and whereby, after the insertion of the filament-shaped damage 32, the glass is exposed to an etching medium, which removes the glass of the glass element 3 at a removal rate of preferably less than 8 m per hour, and widens the filament-shaped damage 32 to form a channel 41, so that, on account of the filament-shaped damage 32 ending in the glass, the channels 41 likewise end in the glass and are sealed on one side, whereby the channels 41 are joined laterally during the etching, so that a recess 24 is produced in the glass. The lateral delimitation of the recess is accordingly defined, as in the embodiment with the creation of an opening 10, by the path of the adjacently lying points of impingement of the laser beam. The method is suitable especially for recesses with a depth of up to 5 mm. The depth can be at least 50 m, preferably at least 100 m, especially preferred, at least 200 m.
[0139]
[0140] For the creation of recesses or depressions 24 that have only one opening to one of the side faces 30, 31 of the glass element 3 or the glass parts 5, 7, the filament-shaped damage insertions 32 according to one embodiment of the invention are produced in a two-dimensional grid.
[0141]
[0142]
LIST OF REFERENCE NUMBERS
[0143]
TABLE-US-00005 1 microfluidic cell 2, 3, 4 disc-shaped glass element 5, 7 glass part 9 cavity 10 opening in 3 11 edge of 10 12 adhesive 13 left-free region 15 adhesive layer 16 edge of 15 17 printing apparatus 18 printing head 19 crosspiece 20 computer 21 laser processing device 23 focusing optics 24 recess 27 laser beam 29 ultrashort-pulse laser 30, 31 side faces of 3 32 filament-shaped damage insertion 35 channel 37 dome-shaped depression 39 structure with a plurality of openings 10 40 opening in 5, 7 43 base 41 channel 44 contact region 47 positioning device 48 positioning marker 45 computing device 51 longitudinal direction of 41 52 ridge 54 wall of 41 70 ridge 71 polygonal boundary line 72 corner of 71 73 point of impingement of the laser beam 27 90 inner part 91 part of the wall of 9 formed by 5, 7 100 edge of 10 101 flat edge section 234 stack of glass elements 2, 3, 4 320 end of 32