WO2010072861A1

WO2010072861A1 - Procedure for manufacturing nanochannels

Info

Publication number: WO2010072861A1
Application number: PCT/ES2009/000587
Authority: WO
Inventors: Aleix GARCIA GÜELL; Fausto Sanz Carrasco
Original assignee: Universidad De Barcelona
Priority date: 2008-12-22
Filing date: 2009-12-21
Publication date: 2010-07-01

Abstract

It comprises the following steps: (i) Depositing on glass a nickel electrode layer; (ii) depositing a layer of photosensitive material (photoresist) on the electrode layer; (iii) conferring a pattern on the photoresist having photolithographic form, covering it with a pattern mask and exposing it to light; (iv) lifting off the exposed portion of the nickel layer, forming in this manner a pattern of grooves; (v) filling such grooves with palladium by electrodeposition; (vi) removing the residual layer of photoresist and the residual layer of nickel, obtaining in this manner a master having a projecting pattern; (vii) transferring the pattern of the master to polydimethylsiloxane to obtain a moulded part; (viii) separating the moulded part and (ix) joining it to the planar covering part to cover the empty grooves. It is useful for manufacturing nanochannels having complicated and well-defined patterns of independently-controlled width and height.

Description

Nanochannel Manufacturing Procedure

The present invention is related to the field of technology known as nanofluidics. It refers specifically to the manufacture of nanochannels, i.e. channels with at least one dimension in the nanoscale, which are used in this field of technology.

STATE OF THE TECHNIQUE

Nanofluidics has emerged as a discipline of science and engineering, where a fluid flows in structures with at least one transverse dimension close to the nanometric range. Although the phenomena of fluid transport in the nanoscale have already been studied in the past, the nanofluidic terminology has been appearing and becoming popular only in recent years. This growing interest comes from the new opportunities offered by micro- and nanotechnologies. While materials known as zeolites naturally include a random pore network, the new technologies allow the fabrication of well-defined nanochannel networks (cf. P. Abgrall et al., "Nanofluidic Devices and Their Applications", Analvtical Chemistrv 2008 , vol. 80, pp. 2326-2341).

The nanochannels (also called nanofluidic channels) are channels with at least one dimension in the nanoscale, this usually being defined as the range between 1 and 100 nm, while the submicrometer term is used for objects in the range between 100 nm and 1,000 nm (= 1 μm). An important parameter of a nanochannel is its aspect ratio (AR) between the height and width of its section. Many nanofluidic devices are based on flat or low AR nanochannels. Square nanochannels have AR close to 1. Nanochannel patterns can occur in two types of networks, called 1 D (one-dimensional, when there are only connections between nanochannels and deposits) and 2D (two-dimensional, including connections between the nano-channels themselves). The article by P. Abgrall et al. cited above provides an updated review of the preparation techniques used for the manufacture of nanochannels. For the simplest case, ie that of flat nanochannels, several techniques are described, being classified as bond-based techniques ("bonding-based techniques") or as sacrificial techniques. For 2D and 3D networks of square nanochannels, several of the so-called top-down techniques of nanometric pattern formation are known, being classified among photolithography, serial pattern techniques and replication techniques. This document mentions that the replication by molding ("casting") of poly (dimethylsiloxane) (referred to as "PDMS" in the following) is widely used, obtaining channels with sections as small as 200 nm by 200 nm, but that these structures They suffer from collapses as dimensions and ARs decrease.

Apart from the risk of collapse and the relatively high cost, several nanochannel manufacturing techniques suffer from difficulties in the precise definition / drawing of the pattern, and / or the lack of independent control of the height and / or the width of the channel . Thus, it is desirable to have new nanochannel manufacturing processes, both flat and square, that allow for small dimensions and high quality, at a relatively low cost.

EXPLANATION OF THE INVENTION

According to the present invention, there is provided a method (method) for the manufacture (manufacture, preparation) of nanochannels, comprising the following steps (i) - (ix):

(i) Deposit a layer of metallic electrode on an insulating substrate. In particular embodiments the insulating substrate is glass, silicon or a polyimide (eg a Kapton® polyimide film manufactured by DuPont), with glass being preferred. In particular embodiments, the metal electrode layer is made of nickel, silver or chrome, with nickel being preferred. Nickel can be deposited on glass by physical vapor deposition (PVD). The height of the metal electrode layer is directly related to the salient characteristic of the master, and consequently with the height of the nanochannel (10-200 nm can be easily reached).

(ii) Deposit a layer of photosensitive material (referred to as photoresist in the following) on the metal electrode layer. A photoresist, well known to those skilled in the art, it is a light sensitive material and used in various industrial processes, such as photolithography and photo-recording, to form a patterned coating on a surface. In a particular embodiment the photoresist is a positive photoresist, ie of the type in which the portion of the photoresist that is exposed to the light is soluble to the developer, and the portion of the photoresist that is not exposed remains insoluble to the developer. The photoresist can be deposited by spin-coating, following the recommended procedure for the photoresist in question.

(iii) Photolithographically confer a pattern to the photoresist layer, covering it with a pattern mask and exposing it to light, preferably to ultraviolet light. The pattern mask is directly related to the final two-dimensional arrangement of the nanochannels.

(iv) Start the exposed portion of the metal electrode layer, thus forming a pattern of trenches. In a particular embodiment, the start-up is carried out by electrooxidation, i.e. by electrochemical or potentiostatic start-up. In another particular embodiment, the start-up is carried out by chemical attack, for example by immersion in a solution of nitric acid, which is especially suitable when the metal electrode layer is made of nickel. The electrochemical start-up implies a counter-electrode (eg a platinum sheet or wire), and a reference electrode with respect to which the potential applied to the sample refers (eg a silver-chloride reference electrode of silver, or one of calomelanos).

(v) Fill the ditches with a metal by electrodeposition. In particular embodiments the metal used to fill the ditches is palladium, platinum, gold, cadmium or bismuth, with palladium being preferred.

(vi) Remove the remaining photoresist layer and the remaining metal electrode layer, thus obtaining a master with an outgoing pattern. The conditions are selected according to the nature of the photoresist and the metal electrode layer, as is known in the art.

(vii) Transfer the master's pattern to a moldable material, thus obtaining a molded part ("cast moiety"). In particular embodiments the material Castable is a prepolymer that forms a polymer in situ. The polymer can be formed in situ from a mixture of prepolymer and catalyst, with PDMS being a preferred polymer. A 10: 1 weight ratio of PDMS prepolymer to catalyst is preferred. Preferably, the formation of air bubbles is avoided, eg by vacuum treatment. In a particular embodiment, the surface of the master is previously coated with a non-stick layer to facilitate the separation step (viii). A preferred nonstick is trichloroperfluorooctylsilane, which is deposited as a monolayer by gas phase deposition ("gas-phase deposition").

(viii) Separate the molded part from the master, where this molded part comprises empty ditches. The separation by mechanical means is favored when the surface of the master was previously coated with a non-stick layer.

(ix) Join the molded part to the flat covering part ("capping moiety") that covers the empty ditches, thus obtaining the nanochannels corresponding to the pattern mask. In a particular embodiment the flat covering part is made of glass, silicon, PDMS or a thermoplastic, the glass being preferred. In another particular embodiment, the molded part is made of PDMS, and the flat covering part is another molded part of PDMS, both parts having their respective molded surfaces facing each other to form multidimensional nanochannels.

An advantage of PDMS is that it can be sealed with itself, or with other surfaces such as glass, reversibly or irreversibly, and without distortion of the channels. It is preferable to join the PDMS with the glass irreversibly, since this provides more consistent yields, reproducible results, a higher success rate and a lower probability of leakage during handling. In a preferred embodiment, the molded surface of the molded part made of PDMS and the flat covering part are glued with the aid of an oxygen plasma. This treatment generates silanol groups on the surface of the PDMS by oxidation of methyl groups. The oxidized surface PDMS can bind itself, glass, silicon or other thermoplastics.

Due to the dimensions of the characteristics of the master with outgoing pattern and of the nanochannels created in the PDMS replica, it is used Normally, the atomic force microscopy (AFM) for the characterization of the substrates.

The method of manufacturing nanochannels of the present invention has several advantages over those known in the art. Thus, the manufacturing steps of the masters with salient pattern that are desired, illustrated in Example 1, have the possibility of creating patterns of nanostructured characteristics through traditional UV photolithography techniques in several possible substrates, such as silicon oxide, glass or polyimide surfaces (eg DuPont Kapton® polyimide film). In addition, the nanostructure of the master with protruding pattern can be made of various materials, such as gold, palladium or platinum, and with a high and independent control of its width (from 20 to 1,000 nm) and its height (from 10 to 200 nm) . In the accompanying examples, palladium has been used as metal, but other metals can also be used, since only the shape of the nanostructure matters and not the material from which it is made.

The fact that the process of the present invention makes it possible to manufacture nanochannels with a well defined pattern is an advantageous feature that opens up a wide range of applications. For example, using a specific pattern mask with a spiral pattern, it is possible to manufacture a single channel of an extraordinarily large length, over a very small area, thus minimizing the total size of the device. This configuration is highly desired eg in micrometric or nanometric chromatographs.

From the observation that the flow of ions through nanochannels presents a behavior similar to electronic functions (eg rectification, field-effect or actions of bipolar transistor), a next generation of electronic devices is expected in what is called "nanofluidic computing". However, so far only very simple architectures have been studied, due to the difficulties of obtaining complex nanochannel circuits. The process of the present invention is very suitable for manufacturing real circuits for the so-called "nanofluidic computers", due to their ability to create practically all the desired nanochannel circuits. The ability to manufacture nanochannels with controllable and independent dimensions is another advantageous feature of the present invention. Several analytical applications, such as analytical separations and determination of biomolecules (proteins, DNA ...), are improved based on the similarity of sizes between the biomolecules and the nanochannels. For example, in DNA screening chips, the DNA molecules are passed through the nanochannels, making it possible to be analyzed and determine their base sequence. In these cases, high control of the nanochannel dimensions is required.

Throughout the description and the claims, the word "comprises" and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and characteristics of the invention will emerge partly from the description and partly from the practice of the invention. The following examples and drawings are provided by way of illustration, and are not intended to be limiting of the present invention. In addition, the present invention covers all possible combinations of particular and preferred embodiments indicated herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a 3D view of an atomic force microscopy (AFM) image of a master with an outgoing pattern made of palladium, used as a template for the preparation of nanochannels according to the present invention.

FIG. 2 is the profile of a section of the master of FIG. 1, illustrating its shape and dimensions (H = height).

FIG. 3 is a 3D view of an AFM image of a sample after the transfer of the pattern to PDMS, illustrating an empty ditch.

FIG. 4 is a zenith AFM image of a part of the sample of FIG. 3, illustrating the dimensions of an empty ditch. FIG. 5 is the profile of a section of the sample of FIG. 3, illustrating its shape and dimensions (H = height).

DETAILED DESCRIPTION OF PARTICULAR EMBODIMENTS

Example 1: Manufacture of a master with outgoing pattern

The manufacture of a master with an outgoing pattern was carried out following a procedure analogous to one known in the art for the preparation of nanowires ("nanowires") (cf. WO 2008/024783 A2, or C. Xiang et al., "Lithographically Pattemed Nanowire Electrodeposition: A Method for Patterning Electrically Continuous Metal Nanowires on Dielectrics ", ACS Nano 2008, vol. 2, pp. 1939-1949). As insulating substrates glass plates were used for microscopy. They were scrupulously washed with strong oxidizing agents, such as piranha solution or Nochromix®, for at least 1 hour. They were then scrupulously washed with ultra pure water to ensure complete removal of the oxidizing agents from the previous cleaning step, and finally they were dried in a high purity nitrogen stream. Then a nickel film was deposited by physical vapor deposition (PVD) on these clean glass plates, using an evaporator at speeds of 0.5-1.5 A / s. This film acted as a layer of metallic electrode, and its thickness is directly related to the height of the final projecting characteristic of the master, and consequently, to the depth or height of the nanochannel. Outgoing characteristics were synthesized satisfactorily, using nickel films of thicknesses between 10 and 200 nm.

The nickel-coated glass samples were coated with a positive photoresist layer by spin-coating, following the standard procedure recommended for the photoresist. In the present example, Shipley S1808 positive photoresist was used, at a speed of 2500 rpm for 40 s. This photoresist layer was then cured at 90 ⁰ C gently for 30 min to produce a photoresist layer thickness of about 500 nm.

After cooling to room temperature, standard lithography with a pattern mask was used to create a pattern. A beam of UV light passed through of a transparent pattern mask in contact with the photoresist coated sample tight with a quartz plate (time and light intensity and wavelength may change according to the characteristics of the photoresist used). After exposure to UV light, the sample was immersed in a developer solution and cleaned with ultra pure water. The sample was a glass plate with a layer of evaporated nickel of a certain thickness, covered by a polymer layer with pattern by photolithographic techniques. Some parts of the nickel layer were coated (ie protected) by the polymer layer, and other parts were exposed.

Although the formation of the ditches could be carried out by dissolving the metal electrode by chemical attack ("etching"), in this example the starting of the nickel layer was carried out electrochemically or potentiostatically in a single compartment cell with three electrodes, with a solution 0.1 M of KCI and 0.1 ml_ of concentrated HCI (for 50 mL of solution). The nickel layer was dissolved, starting with the most exposed areas, and, after these were dissolved, the nickel layer that resided under the photoresist layer continued its dissolution, thus creating a ditch. Then this ditch was filled by electrodeposition of Pd, using the following electrochemical conditions: a single compartment cell with three electrodes, and a potentiostat to apply to the sample the appropriate potential to selectively electrodeposite the desired metal; Pd was deposited from a 2 mM solution of PdCI ₂ and 0.1 M of KCI, applying 0.2 V to the sample with respect to a silver-silver chloride reference electrode.

Subsequently, the photoresist layer was removed by washing the samples with acetone, ethanol and ultrapure water, respectively. Finally, the sample was dried with a nitrogen jet. The remaining nickel layer was removed by immersing the sample in diluted HNO ₃ , leaving the electrodeposited palladium with the desired shape to be used as a master for the manufacture of nanochannels. The nanometric characteristics had the height of the initial film thickness, the width proportional to the electrodeposition time, and the pattern given by the mask.

Example 2: Transfer to PDMS of the master pattern characteristics In order to improve the final separation between the PDMS mold and the master with protruding pattern, and to avoid any damage or engagement of the nanometric characteristics of Pd in the polymer, a self-assembled trichloroperfluorooctylsilane monolayer (from Aldrich) was applied first over the Ia Master surface with protruding pattern, as a non-stick layer. This monolayer was formed by gas phase deposition by placing the samples and a glass plate with a drop of this silane in a desiccator, and vacuuming for 30 min. To achieve a uniform and densely compact monolayer of fluorinated hydrocarbon with high mechanical resistance, the sample was placed in an oven for 1 h at 80 ^° C.

A mixture with a ratio of 10: 1 weight / weight of PDMS prepolymer and its catalyst was scrupulously mixed for 5 minutes in a single-use container. After mixing, the air bubbles were removed by placing the single-use container under vacuum conditions for 30 min.

The previously fabricated master pattern of Example 1 was placed in a Petri dish, and then the PDMS mixture free of air bubbles was turned over the master, paying attention to avoid trapping any air bubble around the master. To ensure that the PDMS replica was flat, the whole set was placed in a flat place for 1 day. Finally, to solidify and completely polymerize / cure the PDMS, the samples were placed in an oven for 1 h at 80 ^° C.

Once the PDMS was cured, a scalpel was used to separate the PDMS polymer from the master. Thanks to the non-stick monolayer previously used, and favored by the elasticity of the PDMS, the separation of the PDMS from the rigid master was carried out without damaging any of the parts, and thus they could be used many times. An AFM analysis showed that the nanometric characteristics of the master with an outgoing pattern had been correctly transferred to the molded part of PDMS.

Example 3: Joining a molded part of PDMS to a flat glass covering part To form the nanochannels, extremely clean glass plates were used as a flat covering part. Glass plates were washed with 95% ethanol in an ultrasonic bath for 30 min, then with ultra pure water, and then dried in a laminar flow hood. After the separation of the master, the faces with features of the molded part made of PDMS and the glass plate were placed in an oxygen plasma cleaner, with the faces facing up. The vacuum was connected until a pressure of 200 mTor was reached. At this time, the plasma was connected for 1-2 minutes at low power (<100 W). Immediately after this time, the chamber was opened and the two surfaces (the molded part and the flat covering part) were quickly contacted (in less than 1 min) after the oxidation, to avoid the reconstruction in the PDMS air rusty. Then, the devices were ready to be filled with the appropriate solutions for the desired experiments or applications. Water-filled devices could be stored in a humidified incubator for 2 or 3 days before use. The contact with water or polar organic solvents maintained the hydrophilic nature of the surface indefinitely.

AFM characterization of substrates

For this characterization, an MFP-3D Stand Alone atomic force microscope (from Asylum Research, Santa Barbara, California, USA) was used. The AFM probes were silicon tips from Nanosensors Nanoworld

Innovative Technologies, with the following characteristics: SPM silicon probes arrow - NCR-W; no contact mode; 4.6 μm thickness; length of 160 μm; width of 45 μm; resonance frequency of 285 kHz and force constant of 42 N / m. AFM images were obtained in air with the acoustic AC mode (non-contact mode), depending on the working frequency of several factors, such as the type of probe used. The frequency was usually between 250 kHz and 300 kHz.

The thicknesses and widths of the characteristics of the masters and of the nanochannels were measured using AFM and operating in non-contact AFM mode. FIG. 1 provides a topographic 3D view of a master with an outgoing palladium pattern. FIG. 2 presents a profile to illustrate the form of the section and the nanometric dimensions of the structure of the pattern in the glass substrate. To ensure uniformity in height and width along the entire length with pattern, many random AFM profiles were taken along their axes, obtaining an average value.

FIG. 3 is a 3D view of an AFM image of a PDMS sample after the transfer step, which demonstrates the existence of empty trenches that reproduce the nanometric characteristics of the master with an outgoing pattern. Also shown in FIG 4. is an overhead view of a channel on an enlarged scale. A profile of a molded part of PDMS is represented in FIG. 5, showing the nanometric depth of the trench and its rectangular shape. For the correct acquisition of the images, the following instrumental parameters were set: starting amplitude ("setpoint amplitude" of 1.3 V; integral gain of 1; proportional gain of 1 and "drive amplitude" of 125 mV. As is evident for the experts in the field, all these parameters can be changed depending on the probe used, the sample, the microscope, etc. For example, the parameters for the characterization of the master may not be the same as those used for the characterization of the PDMS, because to the differences in the mechanical properties of each sample.All AFM images were processed with the MFP Igor Pro 5.05A software provided by Asylum Research.

Claims

1. Procedure for the manufacture of nanochannels comprising the steps of: (i) depositing a layer of metallic electrode on an insulating substrate;

(ii) depositing a layer of photosensitive material {photoresisf) on the metal electrode layer;

(iii) confer photolithographically a pattern to the photoresist layer, covering it with a pattern mask and exposing it to light; (iv) tear off the exposed portion of the metal electrode layer, thus forming a pattern of trenches;

(v) fill the ditches with a metal by electrodeposition;

(vi) remove the remaining photoresist layer and the remaining metal electrode layer, thus obtaining a master with protruding pattern; (vii) transfer the master's pattern to a moldable material, to obtain a molded part;

(viii) separate from the master the molded part, where this molded part comprises empty ditches, and

(ix) joining the molded part to a flat covering part to cover the empty ditches, thus obtaining the nanochannels corresponding to the pattern mask.

2. Method according to claim 1, wherein in the transfer step (vii) the moldable material is a prepolymer that forms a polymer in situ.

3. Method according to claim 2, wherein the polymer is poly (dimethylsiloxane) (PDMS).

4. Method according to any of claims 1-3, wherein in the joining step (ix), the flat covering part is made of a material selected from the group consisting of glass, silicon, PDMS and a thermoplastic.

5. Method according to claim 4, wherein the material is glass.

6. Method according to claim 5, wherein in the transfer step (vii) the surface of the master is previously coated with a layer non-stick to facilitate the separation step (viü).

7. Method according to claim 4, wherein the molded part is made of PDMS, and the flat covering part is also made of PDMS, both parts being joined with their respective molded surfaces facing each other.

8. Method according to any of claims 1-7, wherein the metal electrode layer is made of a material selected from the group consisting of nickel, silver and chromium.

9. Method according to claim 8, wherein the metal electrode layer is made of nickel.

10. Method according to any of claims 1-9, wherein the insulating substrate is a material selected from the group consisting of glass, silicon and a polyimide.

11. Method according to claim 10, wherein the insulating substrate is glass.

12. Method according to any of claims 1-11, wherein the starting step (iv) is carried out either by electrooxidation, or by chemical attack.

13. Method according to claim 12, wherein the metal used to fill the trenches in the filling step (v) is selected from the group consisting of palladium, platinum, gold, cadmium and bismuth.

14. Method according to claim 13, wherein the metal is palladium.

15. Method according to any of the preceding claims, wherein the photoresist is positive.