Thin Film-Based Assemblies

JP2024526697A5Pending Publication Date: 2025-07-11VITROTEM BV
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Patent Information

Application Number
JP2024501206
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2021-07-08
Filing Date
2022-07-08
Publication Date
2025-07-11

AI Technical Summary

Technical Problem

Existing thin film-based assemblies, such as graphene liquid cells, face challenges in achieving consistent and controlled spacing between the thin film and the support base due to the delicate handling of thin films less than 10 nm thick, leading to variable and low density of suitable graphene liquid cells, which affects analysis precision.

Method used

Incorporating spherical nanoparticles as spacers between the thin film and the support base to control the spacing, allowing for a more uniform and higher density of graphene liquid cells with tailored dimensions suitable for the sample being analyzed.

Benefits of technology

The use of spherical nanoparticles enables the formation of graphene liquid cells with controlled thickness and larger lateral dimensions, enhancing the yield and suitability of the cells for high-resolution imaging and dynamic process observation.

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Abstract

The thin film-based assembly (100) includes a support base (101) and a thin film (102) disposed on the support base (101). The thin film (102) has a thickness of less than 10 nm, such as a graphene film. Between the thin film (102) and the support base (101) are included one or more spherical nanoparticles (106). The spherical nanoparticles (106) functionally constitute spacers between the thin film (102) and the support base (101).
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Description

[Technical field]

[0001] One aspect of the invention relates to a thin film-based assembly that includes a thin film disposed on a support base. The thin film-based assembly may be, for example, a preparation of a graphene liquid cell. Other aspects of the invention relate to uses of the thin film-based assembly and methods of forming the thin film-based assembly. [Background technology]

[0002] Thin films with a thickness of less than 10 nm, such as graphene films, are used in a wide range of applications. The thin film is placed on a support base to form a thin film assembly. The thin film and the support base jointly define a space, which may encapsulate a substance or have another function. The thin film provides a relatively high degree of transparency, allowing a relatively precise analysis of what is inside this space and what is happening inside the space. The support base may itself be composed of a thin film. This allows a relatively precise analysis of radiation that crosses the space through one thin film and the other. The thin film has a relatively weak effect on this crossing radiation.

[0003] The preparation of a graphene liquid cell is an example of a thin-film-based assembly as described hereinbefore. Such a preparation can be obtained using a TEM support as the main base. The TEM support is usually in the form of a metal plate with a grid with relatively small openings. The metal plate has a thickness of a few millimeters. The grid spacing is usually between 0.01 μm and 0.5 μm. Alternatively, the TEM support can comprise a silicon oxide or silicon nitride disk with an opening or an array of openings. The TEM support is provided with a lower graphene membrane. The TEM support may be coated with a porous thin film that supports the lower graphene membrane. A liquid containing one or more samples to be analyzed is deposited on the lower graphene layer present on the TEM support.

[0004] The upper graphene membrane is placed on top of the lower graphene membrane present on the TEM support. The liquid containing the sample or samples is thereby sandwiched between these graphene membranes. Excess liquid can be removed, for example, by an absorbent sheet. The upper graphene membrane is in contact with the lower graphene membrane. Nanoscale liquid pockets are formed, and a nanoscale volume of liquid containing the sample or samples to be analyzed is tightly enclosed between the two aforementioned graphene membranes. Such liquid pockets are graphene liquid cells, which can be formed over a significant area of ​​the TEM support. Typically, hundreds of graphene liquid cells can be formed on a TEM support. The size of the graphene liquid cells can vary, and typically lie between 0.01 μm and 5 μm in the lateral dimensions of length and width, and between 1 nanometer and 100 nanometers in thickness.

[0005] The graphene liquid cell preparation thus obtained can be used to image the sample contained therein using a transmission electron microscope. The liquid containing the sample to be imaged is tightly enclosed between the two graphene membranes, so that the graphene liquid cell preparation can be inserted into the vacuum column of a transmission electron microscope. The graphene liquid cell is thin, allowing high-resolution imaging of the sample. The electron beam can traverse the graphene liquid cell through an opening in the TEM support. The two graphene membranes are so thin that the electron beam is not significantly affected by the graphene membranes.

[0006] WO 2021 / 123458 describes the preparation of a thin film liquid cell suitable for transmission electron microscopy at room temperature as follows: A thin film suspended in a liquid is prepared. A droplet of the liquid on which the thin film is suspended is transferred to a support using a loop. During this transfer, the loop carries the droplet, which in turn carries the thin film. A sufficient amount of liquid is removed from the droplet on the support to form a thin film liquid cell. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2021 / 123458 Summary of the Invention

[0008] What is needed is a membrane-based assembly in which the space between the membrane and the support base can better approximate the desired properties.

[0009] The present invention takes into account the following: When placing a thin film on a support base, it can be difficult to obtain a space between these two entities that has certain desired properties, or at least closely approximates these properties. This is mainly due to the fact that thin films are delicate and difficult to handle, and have a thickness of less than 10 nm.

[0010] For example, in making the graphene liquid cell preparations described above, the graphene liquid cells may vary in size relatively widely. There may be relatively few graphene liquid cells of an appropriate size for the sample to be analyzed, i.e., relatively many that are too large, too small, or both. Also, the density of graphene liquid cells of appropriate size may be relatively low, which may adversely affect the analysis of interest.

[0011] One aspect of the invention as defined in claim 1 relates to a membrane-based assembly comprising: A support base; a thin film disposed on the support base, the thin film having a thickness of less than 10 nm; The thin film-based assembly comprises: The thin film includes at least one spherical nanoparticle contained between the thin film and the support base, functionally forming a spacer between the thin film and the support base.

[0012] A further aspect of the invention as defined in claim 16 relates to the use of a thin film-based assembly as defined herein.

[0013] Yet another aspect of the invention as defined in claim 17 relates to a method for forming a thin film based assembly, the method comprising the steps of: disposing the spherical nanoparticles on a supporting base; disposing a thin film on the support base, the thin film having a thickness of less than 10 nm, the thin film being disposed on the support base such that at least one spherical nanoparticle is comprised between the thin film and the support base, whereby the at least one spherical nanoparticle functionally constitutes a spacer between the thin film and the support base.

[0014] In each of these embodiments, the spherical nanoparticles allow a space to be obtained between the support base and the thin film disposed thereon that can better approximate certain desired properties. This is because the spherical nanoparticles constitute spacers that serve to define said space. Thus, the spherical nanoparticles provide a form of control over the space formed between the support base and the thin film. This control is achieved by the appropriate size, or size distribution, and the appropriate density, or density distribution, of the spherical nanoparticles. For example, in the preparation of graphene liquid cells, nanoparticles added to the liquid containing the sample can provide a high yield of graphene liquid cells having an appropriate size for the sample to be enclosed in these cells. Furthermore, the nanoparticles also contribute to the formation of the graphene liquid cells, so that a relatively high density of graphene liquid cells can be obtained in the preparation.

[0015] When forming a thin film-based assembly according to the present invention, the spherical nanoparticles can freely assemble. If the density of the spherical nanoparticles is relatively high, this can result in close packing in certain regions. In such regions, concave triangular spaces can form between the spherical nanoparticles, with dimensions determined by their diameter. Conversely, if the density of the spherical nanoparticles is relatively low, the spherical nanoparticles are likely to be randomly distributed on the support base. This can result in "tent-like" encapsulations, each "supported" by one spherical nanoparticle. The height and lateral extent of such encapsulations are again determined by the diameter of the spherical nanoparticles.

[0016] The spherical nanoparticles are produced in bulk, dispersed in a liquid, or held free in air. Thus, the spherical nanoparticles are typically essentially unfixed to a support base, or to a thin film, prior to forming a thin film-based assembly in accordance with the present invention. When forming a thin film-based assembly, the spherical nanoparticles can be fixed within the assembly. The free movement of the spherical nanoparticles prior to being fixed facilitates the attachment of large arrays of spherical nanoparticles to a support base. As a result, a large number of cells are formed over a macroscopic area.

[0017] For purposes of illustration, certain embodiments of the invention will now be described in detail with reference to the accompanying drawings, in which additional features will be presented and in which advantages will become apparent, some of which are defined in the dependent claims. [Brief description of the drawings]

[0018] [Figure 1] FIG. 1 is a schematic cross-sectional view of a graphene liquid cell containing spherical nanoparticles that functionally constitute the spacer. [Diagram 2] FIG. 2 is a top-down photograph showing a portion of a graphene liquid cell preparation. [Diagram 3] Figure 3 shows a high magnification top-down photograph of a small portion of the graphene liquid cell preparation. [Figure 4]FIG. 4 is a schematic cross-sectional view of a graphene liquid cell supported on a microfabricated base. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] FIG. 1 shows a graphene liquid cell 100 in a schematic manner. FIG. 1 provides a schematic cross-sectional view of the graphene liquid cell 100. The graphene liquid cell 100 shown in FIG. 1 may form part of a graphene liquid cell preparation. The graphene liquid cell preparation can be used to image a sample contained therein using a transmission electron microscope. The preparation may further include a TEM support on which the graphene liquid cell 100 rests, TEM being an abbreviation for transmission electron microscope. Such a TEM support is not represented in FIG. 1 for the sake of simplicity.

[0020] The graphene liquid cell 100 includes a lower graphene film 101 and an upper graphene film 102. The graphene liquid cell 100 has a periphery 103 formed by local contact of the upper graphene film 102 with the lower graphene film 101. The upper graphene film 102 and the lower graphene film 101 collectively form a boundary of the graphene liquid cell 100. Thus, the upper graphene film 102 and the lower graphene film 101 collectively define an interior space 104 of the graphene liquid cell 100. The interior space 104 is filled with a liquid 105 containing samples of interest. These samples of interest may include, for example, nanoparticles, biomolecules, macromolecular assemblies, or any combination thereof.

[0021] A plurality of spherical nanoparticles 106 are contained between the upper graphene film 102 and the lower graphene film 101. The spherical nanoparticles 106 are thus present in the internal space 104 of the graphene liquid cell 100. The spherical nanoparticles 106 are arranged in a single layer. Thus, the spherical nanoparticles 106 functionally constitute a spacer between the graphene films 101, 102 described above.

[0022] The spherical nanoparticles 106 play a major role in defining the thickness, especially the maximum thickness, of the graphene liquid cell 100. Thus, the thickness of the graphene liquid cell 100 can be adapted to the sample of interest by using spherical nanoparticles 106 with an appropriate diameter. Depending on the sample of interest, the spherical nanoparticles 106 can have a diameter ranging between 1 nanometer and 10 micrometers. More specifically, the spherical nanoparticles 106 can have a diameter less than 3 micrometers, or even less than 1 micrometer. Even more specifically, the spherical nanoparticles 106 can have a diameter less than 100 nm. In that case, it is consistent with the International Organization for Standardization (ISO) definition of a nanoparticle as a discrete nano object with all three orthogonal dimensions less than 100 nm. However, spherical nanoparticles with a thickness of about 800 nm have provided satisfactory results in obtaining graphene liquid cells such as the graphene liquid cell 100 shown in FIG. 1. Thus, the term nanoparticles can be broadly interpreted in the context of this application.

[0023] The spherical nanoparticles 106 may also serve to define the lateral dimensions, including the length and width, of the graphene liquid cell 100. When the spherical nanoparticles 106 are relatively dense, the upper graphene film 102 may be spread across a number of the spherical nanoparticles 106, as shown in Figure 1. Thus, at least a portion of the interior space 104 of the graphene liquid cell 100 may be occupied by the spherical nanoparticles 106 at 50% to 90%.

[0024] Thus, the graphene liquid cell 100 shown in FIG. 1 may have significantly larger lateral dimensions than conventional graphene liquid cells formed without spherical nanoparticles therein. Such larger lateral dimensions may leave space for movement, distortion, and aggregation of the sample within the graphene liquid cell 100. This allows for imaging of such dynamic processes by transmission electron microscopy and other imaging techniques. The lateral dimensions of the graphene liquid cell 100 may range between 10 nanometers and 50 micrometers.

[0025] Thus, the spherical nanoparticles 106 functionally constituting the spacers in the graphene liquid cell 100 shown in FIG. 1 provide several advantages. First, the spherical nanoparticles 106 control the thickness of the graphene liquid cell 100. Furthermore, the spherical nanoparticles 106 allow the graphene liquid cell 100 to have larger lateral dimensions compared to conventional graphene liquid cells. Finally, it has been found that the spherical nanoparticles 106 may also contribute to a higher yield of suitable graphene liquid cells during the graphene liquid cell manufacturing process. Overall, the spherical nanoparticles 106 allow control over the graphene liquid cell 100, so that the cell can be better tailored with respect to the sample contained therein.

[0026] For example, assume that the sample of interest includes individual proteins of nanometer size, typically less than 1 nm. For such samples, a suitable size for the graphene liquid cell 100 is on the order of 100 nm x 100 nm x 10 nm, with 100 x 100 nm in lateral dimensions and 10 nm in thickness. As another example, the sample of interest may include vesicles or viruses, with the size of these samples being on the order of tens of nanometers, e.g., between 50 nm and 100 nm. For such samples, a suitable size for the graphene liquid cell 100 is on the order of 300 nm x 300 nm x 100 nm, with 300 nm x 300 nm in lateral dimensions and 100 nm in thickness. As yet another example, the sample of interest may include a whole biological cell or a complex sample with different parts. For such samples, a suitable size for the graphene liquid cell 100 is on the order of 1000 nm x 1000 nm x 500 nm, with 1000 nm x 1000 nm in lateral dimensions and 500 nm in thickness.

[0027] Figure 2 illustrates the preparation of a graphene liquid cell 200. Figure 2 provides a top-view photograph of a portion of the preparation of the graphene liquid cell 200. The portion consists of a number of relatively large graphene liquid cells. The graphene liquid cells may have a structure corresponding to the graphene liquid cell 100 shown generally in Figure 1 and described previously herein.

[0028] FIG. 3 shows a small portion of the graphene liquid cell 200 preparation in more detail. FIG. 3 provides a top-view photograph of this small portion taken at high magnification. A similar small portion is shown in FIG. 2 by the white rectangle. The close-up photograph in FIG. 3 shows the relatively light round areas. These correspond to the spherical nanoparticles. The dark areas correspond to the liquid present between the spherical nanoparticles.

[0029] The preparation of the graphene liquid cell 200 as shown in Figures 2 and 3 can be obtained as follows. It is assumed that a liquid containing the sample of interest has already been prepared, hereafter referred to as the sample-containing liquid. Furthermore, it is assumed that the TEM support is first covered with a porous support thin film, and then provided with a lower graphene membrane.

[0030] The spherical nanoparticles, which may be dry, can be added to the sample-containing liquid and mixed. Thus, a dispersion of spherical nanoparticles in the sample-containing liquid is obtained, hereafter referred to as sample-nanoparticle dispersion. As explained above, the spherical nanoparticles have a diameter that depends on the desired thickness of the graphene liquid cell to be formed. The desired thickness is usually related to the sample of interest. The spherical nanoparticles are added to the sample-containing liquid such that the spherical nanoparticles in the sample-nanoparticle dispersion have a suitable density. As explained above, the suitable density depends on the desired lateral dimensions of the graphene liquid cell to be formed. The desired lateral dimensions are also usually related to the sample of interest.

[0031] In another embodiment, a dispersion of spherical nanoparticles in a liquid may be prepared separately first. This dispersion may then be added to the sample-containing liquid and mixed together. The appropriate density of the spherical nanoparticles can be determined by considering the following factors: The first factor relates to the concentration of the spherical nanoparticles in the dispersion first prepared; The second factor relates to the volume ratio of this dispersion to the sample-containing liquid to be mixed together; This determines to what extent the concentration of the spherical nanoparticles is diluted in the sample-nanoparticle dispersion.

[0032] The sample-nanoparticle dispersion is deposited on the bottom graphene membrane present on the TEM support. For that purpose, the technique described in WO 2021 / 123458 can be used. According to this technique, a droplet of the sample-nanoparticle dispersion carries an upper graphene membrane. Thus, when the droplet is deposited on the lower graphene membrane present on the TEM grid, at least a part of the droplet is sandwiched between the upper and lower graphene membranes. The excess amount of the sample-nanoparticle dispersion can then be removed, for example by an absorbent sheet. The upper and lower graphene membranes are brought into contact. Nanoscale pockets of the sample-nanoparticle dispersion are formed, such that a nanoscale volume of the sample-nanoparticle dispersion is tightly enclosed between the two aforementioned graphene membranes. These pockets constitute graphene liquid cells, while the spherical nanoparticles functionally constitute the spacers between the upper and lower graphene membranes, as shown in FIG. 1 and described herein above.

[0033] The spherical nanoparticles described herein above may be spherical nanoparticles developed for entirely different purposes, such as, for example, filtration or purification of substances. Spherical nanoparticles have a relatively high surface area to volume ratio. That is, spherical nanoparticles have a relatively large surface area relative to their volume. In fact, as the diameter of a sphere is reduced, its surface area increases exponentially with respect to its volume. For example, a quantity of spherical nanoparticles with a diameter of 10 nm that fills a 6 ml teaspoon has a larger surface area than a dozen double-sized tennis courts. The relatively high surface area to volume ratio makes spherical nanoparticles particularly suitable for filtration or purification of substances, and also as active pharmaceutical ingredients. The relatively large surface area of ​​spherical nanoparticles allows for extensive interactions with surrounding substances, which is important for filtration or purification, and also allows for high dissolution rates, which are desirable for active pharmaceutical ingredients.

[0034] The spherical nanoparticles may have a body of an inorganic material. The inorganic material may include at least one selected from a polymer, a metal, a metal oxide, a silicate, and a ceramic. The polymer may be, for example, polystyrene, polyethylene, or a combination thereof. The metal may be, for example, gold, platinum, or an alloy.

[0035] The spherical nanoparticles may include a coating on the body. The coating may include an organic material. The organic material has an affinity for at least a portion of the samples contained within the graphene liquid cell. This affinity may provide an immobilizing effect for the samples, rather than allowing them to float freely in the liquid within the graphene liquid cell. This immobilizing effect may prevent the samples from interacting with the liquid cell walls, e.g., from adhering to the graphene. Antibodies or proteins are examples of organic materials that provide such an immobilizing effect and may be included in the coating on the body of the spherical nanoparticles.

[0036] FIG. 4 illustrates a schematic of a graphene liquid cell 401 supported by a microfabricated base 402. FIG. 4 provides a schematic cross-sectional view of the graphene liquid cell 401 supported by the microfabricated base 402. The microfabricated base 402 may be in the form of a silicon-based chip microfabricated by at least one of the following techniques: electron beam lithography, photolithography, and focused ion beam milling. The microfabricated base 402 may form part of, for example, a TEM imaging platform, a lab-on-a-chip device, a microelectromechanical system (MEMS), and other types of nano- and micro-devices.

[0037] In this embodiment, the top graphene membrane 403 is supported by the microfabricated base 402 at its edge. Similarly, the bottom graphene membrane 404 is supported by the microfabricated base 402 at its edge. The two graphene membranes 403, 404 form the top and bottom seals, respectively, of the graphene liquid cell 401, which may be further bounded by the side edges 405 of the microfabricated base 402. The aforementioned entities define an interior space 406 of the graphene liquid cell 401. Similar to the graphene liquid cell 100 illustrated in FIG. 1, the interior space 406 may be filled with a liquid 407 containing the sample of interest. The side edges 405 may provide at least one orifice that allows fluid to enter and / or exit the interior space 406.

[0038] In this embodiment, a plurality of spherical nanoparticles 408 are also included between the upper graphene film 403 and the lower graphene film 404. The spherical nanoparticles 408 functionally constitute a spacer between the aforementioned graphene films 403, 404. The spherical nanoparticles 408 can also play a major role in defining the thickness of the graphene liquid cell 401 shown in FIG. 4. The spherical nanoparticles 408 can further play a major role in defining the shape of the graphene liquid cell 401. Thus, the spherical nanoparticles 408 can provide control over the thickness of the graphene liquid cell 401 supported by the microfabricated base 402 as well as control over the morphology of the graphene liquid cell 401.

[0039] (Note) The embodiments described above with reference to the drawings have been presented for the purpose of illustration. The invention can be implemented in many different ways. To illustrate this, a few options will be briefly presented.

[0040] The present invention can be applied to many types of products or methods related to thin film-based assemblies. In the presented embodiment, the thin film-based assembly is in the form of a graphene liquid cell, where the thin film is made of graphene. In other embodiments, the thin film may comprise another material, for example other so-called two-dimensional materials, for example hexagonal boron nitride, a stack of multiple layers of two-dimensional materials, or other thin (up to 10 nm) materials, such as silicon nitride membranes or amorphous carbon membranes. The thickness of the thin film is less than 10 nm, more specifically less than 5 nm, even more specifically less than 2 nm, even more specifically less than 1 nm. The thin film may be non-porous.

[0041] The thin film-based assemblies according to the invention can be useful for many different purposes, including but not limited to sample analysis, more specifically by transmission electron microscopy. For example, the thin film-based assemblies according to the invention can be used to define a space between two thin film surfaces through which a fluid, which may be a gas or a liquid, flows. In embodiments in which the thin film-based assemblies include cells, these may be other than the graphene liquid cells that have been described for illustrative purposes.

[0042] In a thin film-based assembly, at least one nanoparticle functionally constitutes a spacer, but this does not exclude embodiments in which the sample functionally constitutes a spacer in conjunction with one or more nanoparticles. This applies in particular to embodiments in which the sample is relatively large, such as a whole biological cell or a complex sample with different parts, for example as described herein above. For example, a biological cell with lateral dimensions of about 5 micrometers and a height of about 1 micrometer can be surrounded by several nanoparticles with a thickness of about 1 micrometer. These can jointly constitute a spacer in a graphene liquid cell or another form of thin film-based assembly.

[0043] There are many different ways to implement a thin film-based assembly according to the invention. In the embodiment presented herein, the thin film-based assembly includes a liquid enclosed by the thin film and a support base that can include an additional thin film. In other embodiments, the thin film-based assembly does not need to include a liquid, for example, because spherical nanoparticles are employed to facilitate the spreading of the thin film on the support base. In such an embodiment, for example, the conductivity of the thin film can be measured without the need for a substrate in contact with the thin film that could affect the measurement. Since the thin film is not in contact with the support base, but with the spherical nanoparticles that functionally constitute the spacers, a more true measurement can be made. That is, the spherical nanoparticles can affect the electrical properties of the thin film, as well as other properties, to a much lesser extent than if the support base were in contact. This example also shows that in a thin film-based assembly, the support base does not need to include an additional thin film.

[0044] There are many different ways to form thin film-based assemblies according to the present invention. As mentioned above, a dispersion of spherical nanoparticles in a liquid may be added to the support base. As another example, the spherical nanoparticles may be sprayed onto the support base. These spherical nanoparticles may be dry. Patterning the surface characteristics of the support base may be useful to obtain a specific distribution of spherical nanoparticles on the support base.

[0045] The term "spherical" used as an adjective for nanoparticles should be interpreted broadly. The term encompasses any shape that allows the nanoparticles to roll, so to speak, on a support base before a thin-film-based assembly is definitively formed. For example, the photograph shown in FIG. 3 shows that spherical nanoparticles do not have to be perfectly spherical, or even nearly perfectly spherical.

[0046] What has been said in this specification indicates that the embodiments described with reference to the drawings are illustrative of the invention, rather than limiting it. The invention can be implemented in many alternative ways, within the scope of the appended claims. All changes that come within the meaning and range of equivalence of the claims are embraced within their scope. Any reference signs in the claims should not be construed as limiting the scope of the claims. The verb "comprise" in the claims does not exclude the presence of other elements or steps than those recited in the claims. The same applies to similar verbs such as "include" and "contain". The recitation of an element in the singular in a product claim does not exclude the possibility that the product includes a plurality of said elements. Similarly, the recitation of a step in the singular in a method claim does not exclude the possibility that the method includes a plurality of such steps. The mere fact that each dependent claim defines a respective additional feature does not exclude combinations of the additional features other than those reflected in the claims.

Claims

1. A thin-film based assembly (100; 401, 402) comprising: a support base (101; 404); and a thin film (102; 403) having a thickness of less than 10 nm disposed on the support base, wherein the thin-film based assembly further comprises: at least one spherical nanoparticle (106; 408) included between the thin film and the support base, the at least one spherical nanoparticle having a shape that allows it to roll on the support base before the thin-film based assembly is definitively formed and functionally constituting a spacer between the thin film and the support base.

2. The thin-film based assembly according to claim 1, wherein the at least one spherical nanoparticle (106; 408) has a diameter in the range between 1 nanometer and 1 micrometer.

3. The thin-film based assembly according to claim 1 or 2, wherein a plurality of spherical nanoparticles (106; 408) occupy 50% to 90% in at least a part of the space (104; 406) between the thin film (102; 403) and the support base (101; 404).

4. The thin-film based assembly according to claim 1, comprising a cell having a peripheral portion (103) formed by the thin film (102) in local contact with the support base (101), wherein the at least one spherical nanoparticle (106) defines the thickness of the cell.

5. The thin-film based assembly according to claim 4, wherein the cell has a lateral dimension in the range from 10 nanometers to 50 micrometers.

6. The thin-film based assembly according to claim 4 or 5, wherein the cell contains a liquid (105).

7. The thin-film based assembly according to claim 4, wherein the cell contains a sample to be analyzed.

8. The thin-film based assembly according to claim 1, wherein the support base (101; 404) further comprises an additional thin film, and the at least one spherical nanoparticle (106; 408) functionally constitutes a spacer between the thin film (102; 403) and the additional thin film.

9. The thin-film based assembly according to claim 1, wherein the at least one spherical nanoparticle (106; 408) has a body of inorganic material.

10. The thin-film based assembly according to claim 9, wherein the inorganic material includes at least one of a polymer, a metal, a metal oxide, a silicate, and a ceramic.

11. The thin-film based assembly according to claim 9 or 10, wherein the at least one spherical nanoparticle (106; 408) includes a coating on the body.

12. The thin-film based assembly according to claim 11, wherein the coating includes an organic material.

13. The organic material has an affinity for a sample contained in a cell formed by the thin film (102) in local contact with the support base (101), and the affinity has a fixing effect on the sample in the cell. The thin-film based assembly according to claim 12.

14. The thin-film based assembly according to claim 13, wherein the organic material includes at least one of an antibody and a protein.

15. The thin-film based assembly according to any one of claims 1, 2, 4, 8, 9, wherein the thin film (102; 403) includes graphene.

16. Use of the thin-film based assembly according to claim 7 for analyzing the sample contained in the cell.

17. Placing spherical nanoparticles (106; 408) having a shape capable of rolling on a support base on the support base (101, 404); Placing a thin film (102; 403) on the support base, the thin film having a thickness of less than 10 nm, and the thin film being placed on the support base such that at least one spherical nanoparticle is included between the thin film and the support base, thereby functionally configuring the at least one spherical nanoparticle as a spacer between the thin film and the support base. A method for forming a thin-film based assembly, including the step of placing a thin film on the support base.

18. A method for forming a thin-film based assembly according to claim 17, wherein a cell is formed by locally contacting the thin film (102) with the support base (101), and at least one spherical nanoparticle (106) defines the thickness of the cell.

19. The method for forming a thin film-based assembly according to claim 17 or 18, wherein the at least one spherical nanoparticle (106; 408) is disposed on the support base (101, 404) together with a sample to be analyzed, whereby the at least one spherical nanoparticle and the sample are included in one medium (105, 407).