WO2008148917A2

WO2008148917A2 - Production method for a micrometric fluid focusing device

Info

Publication number: WO2008148917A2
Application number: PCT/ES2008/000413
Authority: WO
Inventors: Antonio Luque Estepa; José Manuel QUERO REBOUL; Francisco Antonio PERDIGONES SÁNCHEZ; Alfonso Miguel GAÑÁN CALVO
Original assignee: Universidad De Sevilla
Priority date: 2007-06-06
Filing date: 2008-06-05
Publication date: 2008-12-11
Also published as: ES2310967B2; WO2008148917A3; ES2310967A1

Abstract

The invention relates to a production method for a device intended to disperse or 'focus' a fluid in a precise, controlled manner at a micrometer scale, using the flow focusing technique and devices produced in accordance with said method. According to the invention, the method enables the simple production of a device that can produce coaxial flows of fluids (three-dimensional encapsulation). The production process, which is based on standard techniques used in microsystem technology (microelectromechanical systems or MEMS), enables the low-cost mass production of dispersion devices having micrometer precision and a very reduced size. The device produced can be easily built into two-dimensional matrices and coaxial flows can be created in the direction perpendicular to the matrix

Description

TITLE

MANUFACTURING METHOD FOR MICROMETRIC SCALE FLUID FOCUSING DEVICE

OBJECT OF THE INVENTION

The object of the present invention is a manufacturing process for a device intended for the dispersion of a fluid, called focusing, in another or others, called focusing, precisely and controlled on a micrometric scale by means of the technique known as "flow focusing "and devices manufactured according to that procedure

The method object of the present invention allows in a simple way the manufacture of a device capable of producing coaxial currents of fluids (three-dimensional encapsulation). The manufacturing process, based on standard techniques in microsystem technology (microelectromechanical systems or MEMS, Micro Electro Mechanical Systems), allows the mass production of dispersion devices with micrometric precision, at low cost, and with a very small size.

The manufactured device can be easily integrated into two-dimensional matrices, coaxial flows can be created in the direction perpendicular to the device matrix.

STATE OF THE TECHNIQUE

The technique known as Flow-Focusing, or fluid focusing, is a mechanical method for the production of very small diameter jets. According to the method of application of the method, a stable jet can be achieved, or it can be forced to break into micro-droplets of controlled size. The technique is based on wrapping the liquid jet with another immiscible fluid with the former, so that it flows coaxially with said immiscible (or focusing) fluid. It is also possible to use a liquid as the surrounding fluid and that the focused fluid is a gas.

The main applications of fluid encapsulation are the following:

1. Generation of aerosols. By means of the dispersion of a liquid within the air it is possible to generate drops with very controlled and homogeneous sizes. The diameters of

SUBSTITUTE SHEET (RULE 26) The drops generated can vary between hundreds of microns and tens of nanometers.

2. Bubble generation. If the focused fluid is a gas and the focusing fluid is a liquid, then bubbles are generated, the size of which is perfectly uniform and can be controlled.

3. Generation of foams and emulsions. By applying the two methods described in the previous sections, highly efficient production of emulsions and foams is possible.

4. Production of complex particles. If the technique of coaxial jets of immiscible fluids is applied two or more times successively, and its rupture in drops is caused, the production of fluid drops containing other drops inside it can be achieved. These particles find application in the dispensing of medicines, whose active principle would be inside, and would be surrounded by a protective material that would dissolve, releasing said active principle in a controlled manner.

6. Particle analysis. A particle analyzer is able to measure the spectrum-photometric properties of the circulating particles. To achieve a linear flow of particles, it is usual to force the fluid that contains them to flow surrounded by another coaxial current. In this way, a highly stable jet of predetermined dimensions is achieved.

7. Flow cytometry. In the event that the particles analyzed according to the method described in the previous section are cells of an animal or plant organism, the technique is called flow cytometry.

There are several known techniques and devices for two-dimensional fluid focusing (see, for example, US20040043506, inventors Haussecker and Sundarajan). The manufacturing techniques commonly used for these devices allow linear groupings thereof, but make it extremely difficult to make a two-dimensional array of devices.

Devices and their corresponding manufacturing processes have also been previously designed to achieve three-dimensional fluid encapsulation (see Sundarajan et al., IEEE J. Microelectromech. Syst, vol. 13, no. 4, pp. 559-567). Until now, the manufacturing processes and materials used for these devices do not allow the grouping of several forming a two-dimensional matrix.

SUBSTITUTE SHEET (RULE 26) The integration of the fluid encapsulation devices in matrices offers the advantage of allowing a greater production in the unit of time, increasing the efficiency of the global system.

Other manufacturing processes for encapsulation devices integrable in matrices have been previously published (for example, patent ES2199048, inventor Gañán-Calvo), but they are complex and the level of integration achieved is small, given the difficulty of small-scale machining the materials on which they are based, mainly metals.

The high number of patents and scientific publications oriented towards the achievement of a flow focusing device that can be easily manufactured on a small scale and can be integrated into matrices demonstrates the usefulness of said device.

As for the manufacturing processes of micrometer devices, these are classified as machining, engraving and molding. Traditional machining techniques are usually not suitable for the construction of a device like the one described, since they lack the necessary precision, and also do not have the economy of scale necessary to manufacture large quantities at low cost. Molding processes are used to manufacture complex geometry devices using moldable materials, but they are not currently as widely used to make microsystems as engraving processes. The engraving processes, which are used in the manufacturing method object of the present invention, evolve from the techniques of manufacturing integrated microelectronic circuits, and are based on chemical reactions that remove material from a substrate. They can be classified as surface engraving or volume, depending on the geometry of the material to be engraved. In turn, volume etching techniques are divided into wet etching (when the reagent that removes the material is in the liquid phase) and dry etching (when it is in any other phase, usually gas).

DESCRIPTION OF THE INVENTION

The manufacturing method described is intended for the manufacture of a device that has two fluid inlets and a single outlet, whereby both inlet fluids will go outside. The internal geometric configuration allows the realization of the technique known as "flow-focusing", in which one of the fluids, called focusing, completely surrounds the other fluid, called focusing, so that it is dragged concentrically by the focuser in form of a micro-jet

SUBSTITUTE SHEET (RULE 26) capillary or microscopic drops, the size of these being determined by the flow conditions (flow rate) of both focusing and focused fluids.

This device has uses in sectors of the technique such as the pharmaceutical industry (drug encapsulation), the science and engineering of materials, the food industry, the chemical industry, the biotechnology, and the scientific instrumentation.

Some of the applications of the device are the generation of microsprays, microdrops, and foams, as well as the creation of complex particles, and the analysis of particles or cells.

The advantages of the method object of the present invention with respect to other previous inventions are:

- It allows in a simple way the manufacture of a device capable of producing coaxial currents of fluids (three-dimensional focusing), which other methods previously developed are not capable of performing.

- The manufacturing process, based on standard techniques in microsystem technology, allows the mass production of the dispersion devices with a low cost, and with a very small size (the dimensions being in the order of the microns).

- The manufactured device can be easily integrated into two-dimensional matrices, and coaxial flows can also be created in the direction perpendicular to the device matrix.

The device object of the invention consists of two wafers that have been machined and joined for the encapsulation of fluids, as shown in Figure 2. In the wafer (1) there is a hole (4) through which the focused fluid ascends. The focusing fluid is supplied through the duct (6) until reaching the cylindrical structure (5) responsible for conducting the focused fluid. This geometry guarantees the encapsulation of the focused fluid by the focusing fluid. Both fluids leave through the discharge port (3) of the upper wafer (2).

The manufacturing process of the invention is as follows (see figure 5):

1. Engraving is performed on a silicon wafer (wafer # 1) by means of an RIE reactor (Reactive Ion Etching), to make distribution channels of the focusing fluid. He

SUBSTITUTE SHEET (RULE 26) Engraving is done starting from an A side of the wafer. To define the form to be recorded, a photolithography stage is first performed on the same face A, using a mask that contains the shape of the channels, and by means of which the areas that do not wish to record are protected. 2. Using the same mask as in step 1, photolithography is performed on face B of wafer # 1, and the unprotected areas are recorded, creating a mirror image of the existing channels on face B, with a lower depth . This image will be used later for the alignment between masks in other photolithography stages. 3. From the B-side of wafer # 1 another photolithography stage is performed again, aligning the mask with the copy of the channels made in step 2, and subsequently the wafer is recorded in its entire thickness using RIE. This creates the necessary step for the focused fluid.

4. On a wafer # 2 an RIE engraving is made from its face B, previously defining the shape by photolithography. The depth of this engraving determines the separation between the upper end of the cylindrical surface (5) and the upper wafer (2).

5. The two wafers are joined by a physical or chemical process of hermetic bonding, for example silicon fusion bonding, or anodic bonding. 6. In wafer # 2 an area on its upper face is defined by photolithography, and through RIE a through hole is made that communicates the outside with the cavity created inside the two wafers. This hole must be aligned with the through hole inside the cylindrical structure (5) and will allow the outflow of the focused and focusing fluids once the encapsulation has occurred. 7. Additionally, in step 6, wafer # 2 can be machined to make the discharge nozzle (9) of Figure 3, or to reduce its thickness. 8. Likewise, it is possible to machine the # 1 wafer on its underside to define by means of photolithography a network of distribution channels of the focused fluid, which leads to it until the entrance of the internal hole to the cylindrical structure.

DESCRIPTION OF THE FIGURES

Figure 1. Fluid focusing concept

In the figure, (7) is the focusing fluid and (8) the focused fluid.

Figure 2. Device section

The device consists of two wafers: lower # 1 (1) and upper # 2 (2), which have been micromachined and joined. In the lower wafer (1) a cylindrical surface (5) and a backwater chamber that surrounds it from the upper face has been carved. From the lower face

SUBSTITUTE SHEET (RULE 26) of the wafer (1) two inlet holes have been opened for the focused fluid (4) and focusing fluid (6). In the upper wafer (2) an outlet opening (3) has been opened that is aligned with the focused fluid inlet hole (4). The focused fluid enters through (4) while the focusing fluid enters through (6). The cylindrical shape in (5) causes the focusing fluid to wrap the focused fluid and both exit through the hole (3).

Figure 3. Device section, with alternative geometry for the output

The discharge hole may have different output geometries. Figure 3 shows a conical output (9). Other profiles in the discharge nozzle are possible.

Figure 4. Arrangement of several integrated devices forming an array

This figure shows how the devices can be manufactured from the same substrate, distributed in a plane, and with the outlet of the encapsulated fluid perpendicular to said plane.

Figure 5. Manufacturing process

The drawing (a) shows the recess made initially in a bottom wafer # 1 to create the cylindrical surface and the backwater chamber. The drawing (b) shows the engraving from the lower face to finish the inner hole to the cylindrical surface (through which the focused fluid will circulate) and the inlet hole of the focusing fluid. The drawing (c) shows the recess made in the upper wafer # 2, and which determines the separation between the cylindrical surface and the cover. Drawing (d) shows the union of the two machined wafers so far. The drawing (e) shows the final device, after making the exit hole in the upper wafer.

EMBODIMENT OF THE INVENTION

In the following, an example of embodiment of the present invention is explained, which is not intended to be neither exhaustive nor to limit the field covered by the present invention, and is only included by way of illustration, the field being limited only by the claims that are Expose at the end.

The manufacturing method is similar to that described above. As these are standard microsystem manufacturing techniques, the optimal dimensions for this manufacturing method range from a few micrometers to tens or hundreds. The manufacturing process of a typical device consists of:

SUBSTITUTE SHEET (RULE 26) 1st. Photolithography of a silicon bottom wafer 380 micrometers thick, defining a network of distribution channels of variable-width fluid ranging from 100 to 400 micrometers.

1 B. RIE engraving of the wafer, with a depth of 180 micrometers (um) in the areas defined by the previous photolithography.

2nd. Photolithography on the opposite (lower) side of the same wafer using the same mask as in step 1a.

2b Engraving of the wafer on the underside, with a depth of 5um to use as an alignment pattern.

3rd. Photolithography from the lower face using a new mask and aligning it with the patterns made in step 2b, defining holes of 50um in diameter, which will be used as channels for the focused fluid. 3b Deep engraving (Deep RIE) of the wafer from the lower face in the areas defined by the photolithography performed in 3rd. The depth of the engraving is necessary to completely cross the entire thickness of the wafer, in this case 380um.

4th. In a new superior silicon wafer 380um thick, a photolithography is performed on the lower face, defining the areas in which the focusing fluid meets the focused one. These areas have a diameter of 600um. 4b Engraving of the wafer in the areas defined in the previous photolithography, with a depth of 20um.

5. Union by fusion of the two silicon wafers, with the second wafer on top of the first.

6. Reduction by machining the thickness of the second wafer, until the resulting thickness is 20um.

7a. Photolithography on the upper face of the set formed by the two wafers, defining the exit holes, with a diameter of 50um.

7b Deep engraving of the second wafer from its upper face in the areas defined by the previous photolithography, with the depth necessary to drill the wafer in its entirety (in this case 20um).

SUBSTITUTE SHEET (RULE 26)

Claims

1. Method of manufacturing a fogging device by means of capillary fluid focusing consisting of n discharge mouths, through which a focused fluid exits, located in one or several backwater chambers and facing outflow holes through which the focused fluid and one or several focusing fluids leave, characterized in that it comprises the following threads in the order indicated or in any other: a. a etching or chemical attack is carried out on the A-side of a # 1 wafer that, in one or several stages, defines one or several backwater chambers within which n discharge mouths are defined, n being greater or equal that one; to define the form to be recorded, a photolithography stage is first performed; b. a etching or chemical attack is carried out on the # 1 wafer that, in one or several stages, defines (i) one or several focusing fluid inlets that directly or indirectly feed all the backwater chambers and (ii) n fluid inlets focused that feed the n discharge mouths; to define the form to be recorded, a photolithography stage is first performed; C. a etching or chemical attack is carried out on the A-side of the # 1 wafer that, in one or several stages, defines one or several channels that allow the focusing fluid to be distributed from the or the focusing inputs to each of the backwater chambers where are the n discharge mouths; to define the form to be recorded, a photolithography stage is first performed; d. a etching or chemical attack is carried out on the face B of the # 1 wafer that, in one or several stages, defines a distribution network with or without channels that allow the focused fluid to be distributed to each of the n focused fluid inlets from one or more general entries; It is considered a particular case of this network of channels that there is a general input for each focusing input; to define the form to be recorded, a photolithography stage is first performed; and. an etching or chemical attack is carried out on a # 2 wafer that, in one or several stages, defines the exit holes of the device; to define the form to be recorded, a photolithography stage is first performed; F. a etching or chemical attack is carried out on the face B of the wafer # 2 which, in one or several stages, reduces the thickness of the plate in the vicinity of the exit holes by an equal amount or

SUBSTITUTE SHEET (RULE 26) greater than Omm; to define the form to be recorded, a photolithography stage is first performed; g. a physical or chemical method is used to join face A of wafer # 1 to

The B face of the wafer # 2, so that the n discharge mouths are aligned with the n exit holes, being separated by a distance determined by the recess of the B face of the wafer # 2 and the height of the mouth Wafer discharge # 1.

2. Method of manufacturing a fogging device by capillary fluid focusing consisting of n discharge mouths through which a focused fluid exits, located in one or more backwater chambers and facing outflow holes through the which the focused fluid and one or several focusing fluids, according to claim 1, characterized in that it comprises the following threads in the order indicated or in any other: a. a chemical etching is carried out by means of an RIE reactor (reactive ion etching) on the A side of a # 1 silicon wafer that, in one or several stages, defines on its surface one or several backwater chambers within which n discharge mouths, being n greater than or equal to one; To define the form to be recorded, a photolithography stage is first performed using the necessary masks; b. previously defining the shape and alignment by photolithography, a chemical etching is carried out by means of the RIE reactor on the # 1 wafer that, in one or several stages, defines (i) one or more focusing fluid inlets that directly or indirectly feed all the chambers backwater and (ii) n focused fluid inlets that feed the n discharge mouths; C. previously defining the shape and alignment by photolithography, a chemical etching is carried out by means of the RIE reactor on the A-side of the wafer # 1 which, in one or several stages, defines one or several channels that allow the focusing fluid to be distributed from the or the entrances focusing on each of the backwater chambers where the n discharge mouths are located; d. previously defining the shape and alignment by photolithography, a chemical etching is carried out by means of the RIE reactor on the face B of the wafer # 1 which, in one or several stages, defines a distribution network with or without channels that allow the focused fluid to be distributed to each of the n fluid inlets focused from one or more general inlets; It is considered a particular case of this network of channels that there is a general input for each focusing input;

SUBSTITUTE SHEET (RULE 26) and. previously defining the shape and alignment by photolithography, a chemical etching is carried out by means of an RIE reactor on a silicon wafer # 2 which, in one or several stages, defines the exit holes of the device; F. previously defining the shape and alignment by photolithography, a chemical etching is carried out by means of the RIE reactor on the B face of the wafer # 2 which, in one or several stages, reduces the thickness of the plate in the vicinity of the exit holes in an amount equal to or greater than Omm; g a fusion bonding method is used to join the wafer face A

# 1 to the B face of the wafer # 2, so that the n discharge mouths are aligned with the n exit holes, being separated by a distance determined by the recess of the B face of the wafer # 2 and the height of the discharge mouth of the wafer # 1.

3. Method according to claim 1 characterized in that one or more of its stages are performed by laser ablation instead of chemical attack with photolithography stages.

4. Method according to claims 1-3, characterized in that the discharge mouth that is obtained is a tube of circular section, or a conduit of variable section with a three-dimensional geometry, including truncated conical, pyramidal, axyl-symmetrical shapes with curved generatrix or combinations of the same.

5. Method according to claims 1-3, characterized in that the outlet orifice obtained is circular in section along its entire length or has a variable section and three-dimensional geometry, including truncated conical, pyramidal, axyl-symmetrical shapes with a curved generatrix, convergent nozzles, divergent nozzles, convergent-divergent nozzles or combinations thereof.

6. Method according to claims 1-3, characterized in that the union of the two wafers is carried out by means of the chemical fusion union, anodic union, conventional adhesives, mechanical union or other procedures that ensure the fixing of the geometry and the absence of leaks interstitials

7. Method according to claims 1-3, characterized in that the wafer # 1 and / or # 2 are subjected at some time to one or more additional stages of physical or chemical processing, in particular physical-chemical milling, conventional machining, laser ablation , which allow varying the thickness of the wafer, the shape of the exit holes, the shape of the channels and / or the discharge mouths.

8. Fogging device characterized by being manufactured according to the procedures of claims 1-7.

SUBSTITUTE SHEET (RULE 26)

9. Device according to claim 8, characterized in that the base material on which the structures are formed is silicon and that the engraving techniques used on the wafers are conventional techniques in the manufacture of microsystems.

10. Device according to claim 8, characterized in that the base material on which the structures are formed is glass, composite, plastic, or any other material capable of being mechanized by chemical attack or etching according to the described procedure.

11. Device according to claim 8, characterized in that n is equal to 1 and, therefore, the device consists of a single discharge port and a single outlet opening.

12. Device according to claim 8, characterized in that the direction of the fluid focused inside the discharge mouth is essentially perpendicular to the two wafers.

13. Device according to claim 8, characterized in that the inlet of the focused fluid comes from another fluid focusing device according to claim 8, said input being therefore constituted in turn by a focused fluid and a focusing fluid. In this way, the focus of three fluids is achieved simultaneously. The complete device can be constructed by stacking two devices as described in claim 8, so that the output of the two encapsulated fluids of the lower device is connected to the inlet of the fluid or the upper device.

14. Device according to claim 8, characterized in that it consists of electrodes that allow establishing a difference in electrical potential between the outlet orifice and the discharge mouth, so that the generated electric field causes effects on the formation and breakage of the micro-focused jet.

15. Device according to claim 8, characterized in that the or the focusing fluid inlets that feed the backwater chambers or chambers are located on the B side or on the side face of the # 1 wafer.

SUBSTITUTE SHEET (RULE 26)