JP6482569B2 - Fabrication of annular microfluidic probe head - Google Patents

Description

  The present invention relates generally to fabrication of microfluidic probe heads and resulting devices. Specifically, the present invention relates to the fabrication of vertical microfluidic probe heads.

Microfluidics generally refers to microfabricated devices that are used to pump, sample, mix, analyze, and dosing liquids. The prominent features of these devices originate from the unique properties that liquids exhibit on a micrometer length scale.
The liquid flow in the microfluidics can usually be laminar. By making structures with lateral dimensions in the micrometer range, quantities much smaller than 1 nanoliter can be obtained. This can accelerate reactions that are limited on large scales (due to diffusion of reactants). For this reason, microfluidics is used for various purposes.

  Many microfluidic devices have a user chip interface and a closed channel. The closed flow path facilitates the incorporation of functional elements (eg, heaters, mixers, pumps, UV detectors, valves, etc.) into a single device while minimizing problems with leakage and evaporation.

  Recently, a vertical MFP (also referred to as vMFP (vertical MFP) in the paper), which is a new and general concept of microfluidic probe (MFP), has been introduced. See Non-Patent Document 1. A vertical MFP head has microfluidic features created in-plane using a base layer. During operation, such a head is oriented vertically with the head top (processing plane) parallel to the surface to be processed.

G. Kaigala et al., Langmuir, 27 (9), pp. 5686-5893, 2011 (http://pubs.acs.org/doi/abs/10.1021/la2003639).

  A method of making an annular microfluidic probe head is provided.

According to a first aspect, the present invention is embodied as a method of making a microfluidic probe head, the method comprising:
Providing a set of n microfluidic probe head layouts on the same bilayer substrate comprising two layers;
The layout is arranged in a ring on a two-layer substrate, and each layout is
A first layer corresponding to a portion of one of the two layers of the two-layer substrate, and a second layer corresponding to a portion of the other layer of the two layers of the two-layer substrate, the upper portion of the second layer A second layer comprising at least one microchannel open to the surface and defined by a groove closed by a portion of the lower surface of the first layer;
Machining a hole approximately in the center of the two-layer substrate, creating a cylinder wall that delimits the hole and blocks each of the at least one microchannel of the layout; Machining so that at least one microchannel extends to at least one respective opening formed at the end of the groove at the level of the cylinder wall;
singulating each of the n layouts to obtain n microfluidic probe heads;
including.

  In embodiments, the method further includes polishing the cylinder wall prior to singulating.

  Preferably, the method includes the step of filling the microchannel of the probe head layout with a malleable material including wax, polymer or photoresist prior to the machining step. After the step, removing the malleable material, the removal of the malleable material is preferably after the step of polishing the cylinder wall, more preferably after each of the n layouts. And the removing step performed after the singulation step.

  In preferred embodiments, the method includes grooving at least one microchannel of each of the n layouts on the top surface of the other of the two layers prior to providing the layout. Creating the set of n microfluidic probe head layouts.

  Preferably, the step of grooving the microchannel is performed by micromachining, such as using photolithography or micromachining, and preferably includes wet or dry etching each microchannel.

  In embodiments, the method further includes aligning and bonding the two layers after each microchannel grooving step.

  Preferably, the step of creating a set of layouts is machining at least one via vertically connected to at least one microchannel for each of the n layouts, wherein the at least one via is Preferably machined through the other of the two layers.

  In preferred embodiments, each of the two layers has a generally disk shape, and one layer of the two layers of the two-layer substrate has a smaller average diameter than the other layer of the two layers of the two-layer substrate. Having the outer side of the other layer of the two layers, which is not covered by one layer of the two layers, and is aligned with respect to the other layer, Prior to the step of providing a set of microfluidic probe head layouts, at least partially metallize the other layer of the two layers such that at least the outer portion of the other layer of the two layers is metallized. Steps are preferably further included.

  Preferably, the method comprises the steps of providing several sets of probe head layouts on each layer of the two-layer substrate prior to the machining step, and superimposing each layer of the two-layer substrate. A machining step passes through all the stacked substrates to produce a bore cylinder wall that blocks each of the at least one microchannel of the layout in each layer of the stacked bilayer substrate; Preferably, the method further comprises the step of polishing the hole cylinder wall obtained, the method further comprising the step of machining, comprising the step of machining the hole in approximately the center of the superimposed bilayer substrate.

  In embodiments, providing the set of layouts includes providing a probe head layout in which each of the inner set and the outer set are annularly arranged in the respective set, the inner set on the same bilayer substrate. Providing at least two concentric annular sets, including the set and the outer set, wherein the method creates a first cylinder wall that blocks the inner set of microchannels, so that the first bore is machined The second hole is machined by separating the portion of the bilayer substrate containing the inner set from the remaining portion of the bilayer substrate to produce a second cylinder wall that blocks the microchannel of the outer set. It includes two steps of machining the hole to be machined.

  According to another aspect, the invention is embodied as a microfluidic probe head obtained by a method according to any one of the previous embodiments, the head comprising a first layer and a second layer. The second layer is open at its upper surface and is defined by a groove closed by a portion of the lower surface of the first layer, and at the end of the at least one microchannel, the second layer At least one opening at the level of the edge of the layer, the edge including at least one opening defining a portion of the processing surface of the head.

  In preferred embodiments, due to a hole machining step in the microfluidic probe head fabrication method, at least a portion of the treated surface is concave.

  The microfluidic probe head further presents two side edges that form an angle of 2π / n ± π / 10, preferably 2π / n ± π / 20.

  In embodiments, the microfluidic probe head further includes at least two microfluidic channels, and preferably further includes at least two vias that are each vertically coupled to the at least two microchannels.

  Desirably, the outer portion opposite the edge defining the processing surface of the head is metallized.

  In the following, devices and methods embodying the present invention will be described using non-limiting examples and with reference to the accompanying drawings. The technical features represented in the drawings are not necessarily drawn to scale.

Fig. 4 schematically illustrates various steps involved in a method of making a microfluidic probe head according to embodiments of the invention. 6 is a flowchart illustrating steps of a method of making a microfluidic probe head according to embodiments of the invention. Fig. 4 schematically illustrates a microfluidic probe head layout on the same bilayer substrate according to embodiments of the present invention. Fig. 4 shows a variant of Fig. 3. FIG. 4 illustrates a geometric specification for a layout, such as that depicted in FIG. 3, according to embodiments. Fig. 6 schematically illustrates steps in a fabrication method using two concentric annular sets of layouts according to embodiments. FIG. 6 schematically illustrates steps in a fabrication method in which several bilayer substrates are superimposed before machining the central hole, according to embodiments. 3 is a 3D view of a simplified representation of a microfluidic probe head, according to embodiments of the invention. FIG. Fig. 3 illustrates surface treatment with a microfluidic probe head according to embodiments (2D view, simplified representation).

  As mentioned in the introduction, the vertical MFP head has several advantages. Such a head is micromachined. At least some of the fabrication steps (including polishing) need to be performed individually (ie, repeated for each unit) or in groups of 3-4 heads. In mass production of MFP heads, it can be understood that such a production step is a restrictive step. The polishing of the head (more generally, the preparation of the treated surface of the head) is particularly labor intensive and therefore has a significant impact on the production costs. In addition, there are yield problems (eg, insufficient or excessive polishing), and polishing tools require significant footprint and are expensive. Finally, head misalignment during the polishing process can result in different peaks. The present invention solves at least some of these problems by introducing a new fabrication concept that utilizes an annularly arranged MFP head layout (some embodiments address all of these problems). deal with). This approach contrasts with previously known approaches to vMFP layout where the head is diced from a bidirectional array of head layouts.

  More particularly, with reference to FIGS. 1, 2, and 6, 7 and 8, some aspects of the invention will first be described, which relates to a method of making a microfluidic probe head 100.

  Most commonly, this new fabrication concept requires a set of n MFP layouts 14 that are placed on the same bilayer substrate 10. This two-layer substrate comprises at least two layers 11, 12.

The layout 14 is annularly arranged on the two-layer substrate 10. More specifically, each layout 14 is
A first layer 110, i.e. one part 11 of the layers 11, 12 forming the two-layer substrate 10;
A second layer 120 corresponding to another part 12 of these layers 11, 12;
including.

  For clarity, the distinction between layer portions 110, 120 corresponding to a single layout 14 (or ultimately one MFP head 100) is described, but layers 11, 12 are the fabrication of the MFP head. This is a larger layer that initially forms the two-layer substrate 10.

  Bilayer substrate refers to any suitable substrate comprising at least two layers 11, 12. Each of the first and second layers 11 and 12 is most practically a disk, that is, a wafer disk. However, the layers 11 and 12 do not have to be circular, the only requirement is an annular placement of the layout 14. These two layers 11, 12 may be (or may not be) the same material. A preferred material is glass or silicon. It will be appreciated that the material of layers 11 and 12 (for any layer) may include plastic, ceramic, metal, or any other hard material that is compatible with the fabrication method, or combinations thereof.

  At the level of one layout 14, it is typically assumed that one layer (eg, second layer 120) includes most of the microfluidic features (microchannels, vias, etc.) built on the layer. Although most of the embodiments described below assume two microchannels 123, 124, strictly speaking, the layer includes at least one microchannel 123, 124 without prejudice. The microchannel is defined by a groove opening in the upper surface 120 u of the layer 120. This groove is closed by a portion of the lower surface 110l of the other layer, which is assumed herein to be the “first” layer 110 (see FIG. 8).

  Because of the annular placement (or ring arrangement) of the layout, one or more of the functional features of each of the n layouts 14 (eg, microchannels, vias, etc.) are typically centered in the annular shape defined by the layout 14. Must be invariant with a rotational symmetry of 2π / n with respect to the transverse symmetry axis passing through. Thus, the substrate 10 can be an invariant having a rotational symmetry of 2π / n for at least these functional features. Of course, this is not the case when different layouts are provided on the same substrate 10a as shown in FIG.

  Typically, 6, 12, and in some cases more than 24 layouts can be provided on the same two-layer substrate 10. For yield reasons, it may be desired to maximize the number of layouts n, for example n = 36, 48, or 72. The preferred number of layouts depends on the size of the substrate and the complexity of the layout (which depends on the intended application). Even so, the fabrication methods described herein can, in principle, implement any number of layouts n ≧ 2 (eg, n ≧ 3, 4, 5, 7,...). .

  An important step of the manufacturing method is a step of machining the hole 16 (see step S20 in FIG. 1 or 2) in the approximate center of the double-layer substrate 10. Machining this hole creates a cylinder wall 18 (which delimits the hole). The layout and this hole are designed so that the cylinder wall 18 blocks the microchannels that are the subject of the layout 14. That is, an opening is created at the end of each of these microchannels. Thus, at this time, the microchannels 123, 124 are opened in respective openings 121, 122 at the level of the cylinder wall 18 (these are the holes 16 machined, as best seen in FIGS. 1, 3 and 8. To be formed).

  Machining the hole 16 may include drilling, milling, cutting, and the like. This step may further include cylinder or laser rotation, water jet, etching, and the like. In an embodiment where a concentric layout is used (see FIG. 6), to machine the hole in the first (inner) annular ring (step S20i in FIG. 6) and to obtain the second (outer) ring. The same machining technique can be used to cut the inner ring of the. Alternatively, it is possible to use different hole machining techniques to obtain these two rings. The embodiment of FIG. 6 will be described in detail later.

  Finally, as shown in FIG. 1, each of the n layouts is singulated to obtain n MFP heads 100 as a result (step S30 in FIGS. 1 and 2). As will be appreciated by those skilled in the art, radial separation may require dicing, splitting or singulating the layout 14 using pre-machined cut lines. FIG. 3 shows a pattern of dies or cutting lines (dotted lines) that can be generally used in this context.

  The fabrication method described herein enables wafer level processing of the processing surface of the MFP head, thereby solving some of the previously described vMFP head fabrication problems. Using this fabrication method, several head (generally many) processing surfaces 310, 320 can be obtained in a single step.

  Specifically, the heads are placed on the wafer so that all heads can be polished in a single step (wafer level polishing) before the heads are singulated. In this regard, the embodiment of the manufacturing method may further include a step of polishing the cylinder wall 18 (S24 in FIGS. 1 and 2) before the singulation step. Nevertheless, it is also possible to carry out the polishing step together with or in the course of machining the hole 16. Depending on the technique used to machine the hole 16, an additional separate polishing step may actually be unnecessary. Thus, the polishing step can be associated with the machining step. In this case, the polishing step does not necessarily mean a mechanical polishing means. Instead, means such as high-pressure water-jet cutting may be used. In all cases, the machining and / or polishing steps result in a clean treated surface 310, 320 for the finished MFP head 100 that has a low surface roughness and is well suited for typical vMFP applications. Enable.

  Advantageously, the fabrication method allows the layout microchannels to be protected before the machining step, in order to protect the microchannels during the subsequent fabrication steps, especially during the machining S20 step of the hole 16. A step S18 of filling with a malleable material can be further included. Similarly, other microfluidic features of the layout can be filled with a malleable material. This material can be removed S40 later (step S20 or thereafter). If used, the malleable material is preferably removed after the polishing step S24. More preferably, in order to protect the microfluidic features even in the singulation process, the material is removed only after the step S30 of singulation.

  A malleable material refers to any material that can be used to fill and plug microfluidic features for protection. Typically, this malleable material can be removed by heating and melting it followed by appropriate washing and rinsing of the microfluidic features. Such materials may include wax, photoresist, or more generally one or more polymers.

  Photoresists are advantageous in that the channel can be cleaned because exposure exposes un-crosslinks of the resist, thereby making it very soluble, which facilitates subsequent easy removal. Desirably, the malleable material should be insoluble in liquids commonly used in dicing operations (eg, water may be used to cool the substrate 10 and head). Photoresists are very clean and filtered, and they are unlikely to leave any particulate matter. More generally, it can be said that photoreactive materials have been found to have advantages.

  Alternatively, low temperature (about 60-80 ° C.) wax may be used to fill and plug the channel. After machining the holes, the wax can be heated and then removed using a vacuum. It is also possible to dissolve using, for example, heptane. Any clean low temperature wax having a low viscosity (eg, at 80 ° C.) may potentially be suitable for this purpose.

  Alternatively, other polymers can be used, which can be dissolved or liquefied by light, temperature, or solvent, or both.

  Up to this point, the most basic aspect of the manufacturing method has been described on the assumption that a pre-processed substrate has been available (step S16 in FIGS. 1 and 2). Needless to say, the embodiment of the manufacturing method may include a upstream manufacturing step (S8, S10, and S12 in FIGS. 1 and 2).

  In particular, such a step may include a step of grooving microchannels 123, 124, 224 (S12). A microchannel is grooved on the surface of one of the layers 11, 12, for example on the upper surface 120 u of the layer 12. As long as these layers are closed, for example after bonding, by the other layer, it does not matter in principle on which of the two layers the channel is grooved.

  Step S12 for grooving the microchannel is preferably performed by micromachining. This can include photolithography or micromachining. Grooves can be made, for example, by tooling, engraving and / or milling directly on the top surface of the base layer 120. The groove may have any suitable cross-sectional shape, such as a circular, square, U, or V cross section. The necessary tool may be selected according to the material of the base layer. Alternatively, laser ablation can be considered. More advantageously, deep reactive ion etching (DRIE) is used for the fabrication of the microchannel. In addition to the above, the microfabrication can also typically include wet or dry etching each of the microchannels. Advantageously, the group of channels can be etched all at once by the wafer level approach proposed herein.

The fabrication can further include aligning and bonding the two layers 11, 12 after step S12 of grooving the microchannel, see step S14 in FIG.
In FIG. 1, the upper surface 120u of the layer 12 faces the reader's eyes, like the lower surface 110l of the layer 11 (the lowermost portion in FIG. 1). However, the layer 11 is inverted before the bonding step S14 so that the lower surface 110l of the layer 11 faces the upper surface 120u of the layer 12 in step S16 in FIG.

  As a first example, the glass layers 11 and 12 can be thermally bonded at 600 ° C. for 4 hours (heating and cooling rate: 75 ° C./hour). This results in melt adhesion (irreversible) of the glass substrate. When a glass substrate is used, it is desirable that the cooling rate does not exceed 100 ° C./hour in order to avoid stress. Furthermore, the thermal expansion of the glass wafer must be equal.

  As another example, the assembly of the two Si wafers 11, 12 is a spin coating of approximately 3 μm polyimide adhesive (HD Microsystems® GmbH, Neu-Isenburg, Germany) onto the polishing side of the lid wafer. And subsequent alignment and bonding of both wafers. Adhesion is carried out at 320 ° C. and a pressure of 2 bar (approx. 2.0 MPa) for 10 minutes (PRESSSYS LE, Paul-Ototo Weber® GmbH, Remshalden, Germany). Thereafter, the MFP head can be diced and stored.

  These upstream fabrication steps can further target other microfluidic features, for example, these can include, among other things, the machining step S10 of the vias 111,112. That is, for each of the n layouts 14, at least one via 111, 112 can be provided to connect perpendicularly to the respective microchannels 123, 124. For simplicity, the vias are preferably machined as through holes through the layer 12 so that they can be easily closed by the same layer 11 that has already sealed the channels 123, 124. Processed. Additional equipment (plumbing ports and pipes) can be provided to connect from the side opposite the 120u side in the layer 12 to allow easy vertical movement of the head 100.

  Other fabrication steps can be directed, inter alia, to the creation of alignment holes 21, 22 in each layer 11, 12 (steps S8, S6, respectively) to align the layers prior to bonding.

  FIG. 5 shows an example of a set of geometric specifications that are particularly easy to use for drilling glass layers 11, 12. The alignment holes 21 and 22 in both layers may be drilled together. For this reason, the layers 11, 12 can be bonded together beforehand, for example using wax. The alignment holes 21, 22 can then be drilled through both layers 11, 12. For vias 111, 112, drilling stops at the contact surface of both layers 11, 12 so that only one layer 12 includes vias 111, 112.

  When using glass wafers, suitable holders can advantageously be used for high precision glass drilling, for example in a computer numerical control (CNC) machine.

For example, a Schott Borofloat® 33 borosilicate glass wafer having a thickness of 500 μm and a wafer size of 4 inches (about 10 cm) may be used. A desirable minimum hole diameter is 0.25 mm. In this case, the desired drilling parameters are
-Small hole (0.4 mm): 30,000 rpm, 30 mm / min; and-Alignment hole (1.5 mm): 25,000 rpm, 25 mm / min.
It is.

  Drilling is desirably performed in an aqueous coolant. Use a diamond-coated drill.

  The central hole can be manually drilled (20 mm diameter) using a standard milling machine and diamond drill. The central hole may be polished using a polishing pad and a 1 micrometer diamond paste. A standard die cut can then be made to singulate the head.

  As shown in FIG. 4, the same set of layouts 14 need not all be identical, in which the four layouts of the substrate 10a represent the added microchannels compared to the remaining layouts. Yes. Again in this figure, the microchannels are similarly arranged so that they meet at the central hole and are drilled and polished at a later stage, eventually forming an opening. For this layout, the wafer size is 100 mm and the diameter of the central hole to be drilled is 20 mm.

  In some MFP applications, it is necessary to design the electrodes at the head level. In this respect, the present manufacturing method can completely cope with metallization. The metallization is preferably performed on only one of the layers 11, 12. For example, it is known to form a Pt / Ti pattern on glass. The electrodes can be advantageously implemented for heating, electrochemical sensing, and the like.

  In this respect, the present method allows an external electrical pad to be easily made. For example, assume that each of the two layers 11, 12 has a substantially disk shape, and that layer 11 is given a smaller average diameter than layer 12. When aligning these two layers, the outer portion of layer 12 should therefore not be covered by layer 11. This makes it possible to provide additional functional features at the level of this outer part. Specifically, the upper side 120u of layer 12 may be metallized (at least partially or selectively) such that this outer portion of layer 12 is at least partially metallized. Metallization is usually performed selectively on the entire larger layer. Thereby, a microstructure such as a heating structure or an electrochemical electrode that can be connected via a metallization pad provided on the outer portion can be obtained. Smaller wafers ensure free access to the electrode contact pads. As before, the channels 123, 124 can be provided on either of the layers 11, 12 because their fabrication is separated from the metallization process.

  Here, an improvement which makes it possible to increase the yield of the production method will be described with reference to FIGS.

  One way to increase the production yield is to use the concentric rings of the layout to make the best use of the wafer surface (see FIG. 6). For example, two (or more) concentric annular sets (inner set and outer set) of the layout 14 can be provided on the same bilayer substrate 10. Each of the inner and outer sets includes a probe head layout 14i, 14o that is annularly disposed in the respective set. Then, the first hole may be machined to generate a first cylinder wall that blocks the inner set of microchannels (step S20i). Next, the second hole can be machined by separating the portion including the inner set 14i of the substrate 10 from the remaining portion of the substrate 10 (step S20o). The hole creates a second cylinder wall that blocks the microchannels of the outer set 14o. As mentioned above, the same or homogeneous machining techniques can be used to produce the first and second cylinder walls.

  Another way to increase fabrication yield is to take advantage of the third dimension, i.e., normal to the wafer surface, for example by preparing a superimposed disk prior to machining a hole through the disk. (Refer to FIG. 7). For example, in step S16, several sets of probe head layouts 14 on each bilayer substrate 10 can be prepared. Next, in step S19, these substrates 10 are overlapped, and then a hole can be machined in the approximate center of these stacked substrates 10 through all the stacked substrates (S20). It is. This results in the creation of holes 16, which block the microchannels in each of the superimposed substrates 10. As described above, the cylinder wall of the obtained hole 16 is polished as necessary.

  The embodiments of FIGS. 6 and 7 can be combined. The production yield increases according to the number of concentric rings × the number of superposed substrates.

  Next, another aspect of the present invention will now be described with reference also to FIGS. 1, 3-5, 8, and 9, which relates to an MFP obtained by the present fabrication method. Similarly to the manufacturing method described above, this MFP also includes the first layer 110 and the second layer 120. The latter layer presents one or more microchannels 123, 124 that are delimited by respective grooves and open to the upper surface 120u of the second layer 120, as best seen in FIG. A part of the lower surface 110l of the first layer 110 is closed. Also, as a result of the machining processes S20, S24, an opening 121 is defined at the end of the microchannel at the level of the edge 320 of the layer 120 in which these channels are grooved. The edge surface 320 forms the portion of the processing surface that is bounded by the edge surfaces 310, 320 of each layer 110, 120 of the head. Of course, as noted above, such an MFP head may include other microfluidic features such as vias 111, 112 connecting the microchannels.

The obtained MFP head is not necessarily influenced by the manufacturing method described above.
First, referring to FIG. 9 in more detail, the processing surfaces 310, 320 of the MFP head 100 are machined in the hole 16 (unless additional substantial surface treatment has been performed to remove the concave surface). It may be concave due to the processing step S20.
Second, referring now to FIGS. 5, 8 and 9, the general shape of the head 100 may further reflect the original annular placement of the layout 14. For example, the head may have a side edge (or at least that portion) that forms an angle close to 2π / n, for example, subject to a tolerance of ± π / 10. This tolerance depends on the spacer stripes of the head in the layout (see dotted lines in FIG. 1 or 3) and the individualization technique used. However, the resulting edge should typically exhibit an angle of 2π / n ± π / 20, provided that sufficient care is taken during the individualization step.
The head 100 may further exhibit other distinct features of the fabrication technique, for example,
O The fine surface condition of the side edge is different from the condition of the treated surface due to the different techniques used (ie, individualization of the side edge, vs. machining / drilling / polishing of the treated surface). And 〇 From this fabrication technique, the fan-shaped shape of the head 100 (similar to a sector in a quadrant), and more generally, the remainder of the initial annular placement of the layout and the symmetry of the layout Properties and holes 16 machined to create a treated surface may be provided.

  Here, after the singulation, the head 100 can be subjected to subsequent processing or processing so that they cannot always retain all of the above-described distinct features of the present production.

  As previously mentioned, an exemplary embodiment of an MFP includes at least two microchannels 123, 124 and at least two vias 111, 112 aligned therewith and vertically connecting the microchannels, respectively. Including. Also, one outer portion of layers 11 and 12 can be partially metallized because it includes an electrical pad. This outer portion is on the opposite side of the processing surfaces 310, 320.

  In addition to the microchannels 123, 124, a lateral channel 224 could be provided as shown in FIG. Interestingly, it is possible to use an individualization step to partition the opening 222 at the end of the lateral channel.

  FIG. 8 shows a view of the processing end of the two-layer MFP head 100 obtained from the embodiment of the manufacturing method. The head 100 has a basal layer 120, and the processing liquid microchannels 123, 124 are provided together with the immersion liquid microchannel 224 (only one lateral channel is shown in the figure). Yes. Each channel is in fluid communication with a respective opening 121, 122, 222, and in this example, each opening is located on the surface of the base layer 120. The cover layer 110 closes a channel that opens on the upper surface 120 u of the base layer 120. The opening is formed at the level of the edge surface 320 of the base layer 120. Due to this fabrication process, the treated surfaces 310, 320 are typically sharp, which allows for compact liquid deposition on the target surface 200, leaving room for easy optical monitoring. leave. In FIG. 8, the concave surface at the top is not visible.

  In order to allow fluid communication with vias 111 and 112 (not visible in FIGS. 8 and 9), the head can be further provided with a piping port (not shown). The via and the port are configured so as to allow fluid communication from the port to the openings 121, 122, and 222 through the respective vias.

  As an example of the application, as schematically shown in FIG. 9, when moving the head in the vicinity of the surface 200, the processing liquid PL can be dispensed through the opening 121, which is the immersion liquid IL (perhaps the head's Supplied through the lateral opening and not shown in FIG. 9). Note that the dimensions, particularly the dimensions of the openings, are not proportional to the original dimensions, but are intentionally exaggerated for the sake of clarity. The device 100 is desirably configured to allow laminar flow. The dimensions of the openings can actually be, for example, tens of micrometers. These are usually sized to tens to hundreds of micrometers. Since the processing channel / opening pair is used in this figure, the processing liquid PL can be sucked through the opening 122 together with a part of the immersion liquid IL. The flow path may be reversed between the openings 121 and 122, that is, the processing liquid may be supplied from the opening 122, and the opening 121 may suck the liquid. During operation, the processing liquid is basically located in the immediate vicinity of the openings 121 and 122 and is usually surrounded by an immersion liquid that can exist only in the vicinity of the head 100.

  Here, as schematically shown in FIG. 9, the concave surface of the processing surfaces 310 and 320 naturally formed from the manufacturing process is formed as a convex space formed between the processing surface and the processing target surface. Can be used to confine liquids inside. However, even so, it may be necessary for the immersion liquid to hydrodynamically confine the treatment liquid, thereby avoiding the dispersion of the treatment liquid. Nevertheless, when the device is in contact with the surface, the concave shape at the top already ensures some confinement of the flow of processing liquid into the concave surface. In this mode of operation, distance control is not necessary. It should be noted that this top curvature can be altered to “design” to include a specific amount of liquid. Finally, this curvature defines the inherent flow resistance and affects the flow confinement geometry.

  The MFP head as described above is particularly useful for surface treatment applications, among others. The above applications, unlike biological applications, require potentially smaller patterns and wider ranges of liquids and chemicals. A thin Si wafer (eg, 100 μm thick) may be used to make the base layer 12, and a well-defined aperture having a lateral dimension of less than 10 μm, for example, may be made using conventional DRIE or focused ion beams. It is possible, and the mechanical strength of the head can be secured by the Si lid 11 having a sufficient thickness. The stacked head as described herein also has horizontal microchannels that fan out sufficiently to leave enough space on the layers 11 and 12 to add many ports, with small openings. And can be brought close to each other, which is more suitable for the use of many processing solutions. Furthermore, more generally, the MFP technology patterns the surface, processes the material, deposits and removes biomolecules and cells on the surface, analyzes the cells and biomolecules on the surface, It has the potential to generate chemical gradients, explore complex biological samples such as tissue sections, and generate structures with unique profiles such as tapered cavities.

  The methods described herein can be used to fabricate MFP heads and MFP chips. The produced head / chip can be distributed in raw form (ie, a structured two-layer substrate) or packaged form by the manufacturer. In the latter case, the chip may be mounted in a single chip package. In either case, the head or chip can then be incorporated with other elements as part of (a) the intermediate product or (b) the final product.

  The foregoing embodiments have been described briefly with reference to the accompanying drawings and may include many variations. Several combinations of the aforementioned features can be considered. An example of such a combination is shown in the figure. Although the present invention has been described with reference to a limited number of embodiments, alternatives, and accompanying drawings, it will be understood by those skilled in the art that various modifications can be made without departing from the scope of the invention. It can be added and can be replaced by an equivalent. In particular, features (device-like or method-like) mentioned in a given embodiment, variant, or shown in the drawings may be used in another embodiment without departing from the scope of the invention. , Alternatives, or combined with or substituted for other features in the drawings. Various combinations of the features described with respect to any of the foregoing embodiments or variations are therefore intended to remain within the scope of the appended claims. In addition, many minor modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the scope of the invention. Accordingly, the invention is not limited to the specific embodiments disclosed, but the invention is intended to embrace all embodiments that fall within the scope of the appended claims. Moreover, many other variants other than those explicitly mentioned above can be devised. For example, materials other than those explicitly described herein could be used for each of layers 11 and 12. Similarly, the channels, vias, and openings could be provided with different dimensions.

10, 10a Double-layer substrate 100 Microfluidic probe (MFP) head (s)
11, 12 First and second layers of substrate 110 First (lid) layer of head 100 110l Lower surface of first layers 11, 110 111, 112 Vertical via 120 Second (base) layer of head 100 120u Second layer 12, 120 Upper surface 121, 122 Microchannel opening 123, 124 Microchannel 14 MFP layout 14i, 14o Concentric probe head layout 16 Center hole 18 Cylinder wall delimiting the center hole 21, 22 Alignment hole 222 Lateral direction Microchannel opening 224 Transverse microchannel 310, 320 Processing surface of head

Claims (10)

A method of making a microfluidic probe head, the method comprising:
Providing a set of n microfluidic probe head layouts on the same bilayer substrate comprising two layers;
The layout is annularly arranged on the two-layer substrate, and each of the layouts includes:
A first layer corresponding to a portion of one of the two layers of the two-layer substrate, and a second layer corresponding to a portion of the other of the two layers of the two-layer substrate, The second layer comprising at least one microchannel open to a top surface of the two layers and defined by a groove closed by a portion of the bottom surface of the first layer;
Machining a hole substantially in the middle of the bilayer substrate, creating a cylinder wall that delimits the hole and blocks each of the at least one microchannel of the layout; Machining such that at least one microchannel of each of the layouts extends to at least one respective opening formed at the level of a cylinder wall at the end of the groove;
singulating each of the n layouts to obtain n microfluidic probe heads;
Including methods.   The method of claim 1, further comprising polishing the cylinder wall prior to the singulation step. Filling the microchannels of the probe head layout with a malleable material including wax, polymer or photoresist prior to the machining step;
Removing the malleable material after the machining step, wherein the removal of the malleable material is preferably after the step of polishing the cylinder wall, more preferably the n pieces. The method of claim 1, further comprising the removing step performed after the step of singulating each of the layouts.   Prior to providing the layout, grooving the at least one microchannel of each of the n layouts on the top surface of the other layer of the two layers. 4. The method of any one of claims 1-3, further comprising creating the set of fluid probe head layouts.   5. The method of claim 4, wherein the step of grooving the microchannel is performed by micromachining, such as using photolithography or micromachining, and preferably comprises wet or dry etching each microchannel.   The method of claim 5, further comprising aligning and bonding the two layers after grooving the microchannel. The step of creating the set of layouts includes, for each of the n layouts,
Machining at least one via vertically coupled to the at least one microchannel, the at least one via preferably being machined through the other layer of the two layers. The method according to claim 4, 5, or 6. Each of the two layers has a generally disc shape;
The one layer of the two layers of the two-layer substrate is
Having an average diameter smaller than the other of the two layers of the two-layer substrate;
Aligned with respect to the other layer such that an outer portion of the other layer of the two layers remains uncovered by the one layer of the two layers;
The method is such that at least the outer portion of the other layer of the two layers is metallized prior to providing the set of the microfluidic probe head layout on the same bilayer substrate. Desirably further comprising metallizing the other layer of the two layers at least partially;
The method according to any one of claims 1 to 7. Providing several sets of probe head layouts on each layer of the two-layer substrate prior to the machining step;
Overlaying each layer of the two-layer substrate,
The machining step includes all of the superimposed cylinder walls to produce a hole cylinder wall that blocks each of the at least one microchannel of the layout in each layer of the superimposed bilayer substrate. And further comprising the step of machining the hole through a substrate and approximately in the center of the superimposed two-layer substrate.
Preferably, the method further comprises the step of polishing the resulting bore cylinder wall.
9. A method according to any one of claims 1-8. Providing the set of layouts includes the probe set layout in which each of the inner set and the outer set are annularly arranged in the respective set, the inner set and the outer set on the same bilayer substrate Providing at least two concentric annular sets, wherein the method includes the step of machining the first bore to produce a first cylinder wall that blocks the inner set of microchannels;
A second hole separates a portion of the bilayer substrate that includes the inner set from the rest of the bilayer substrate to create a second cylinder wall that blocks the microchannels of the outer set. Machined by,
Including two steps of machining the hole,
The method according to any one of claims 1 to 9.

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