EP2131965A2

EP2131965A2 - Thin film coating method

Info

Publication number: EP2131965A2
Application number: EP07870244A
Authority: EP
Inventors: Steve Martin; Pascal Faucherand; Lucie Jodin; Jérôme GAVILLET
Original assignee: Commissariat a lEnergie Atomique CEA
Current assignee: Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
Priority date: 2006-11-28
Filing date: 2007-11-06
Publication date: 2009-12-16
Also published as: FR2909013B1; WO2008068401A3; US20100028526A1; WO2008068401A2; FR2909013A1

Abstract

The invention relates to a thin film coating method using a thin film having minimal adhesion in relation to biological species, of the type comprising the deposition of a thin film with -COOH function. The invention is characterised in that the method includes a step involving the vapour phase chemical decomposition of a carbonaceous precursor containing neither a carboxyl group nor a carbonyl group, in the presence of water. The invention is particularly suitable for use in the field of thin films.

Description

THIN FILM COATING PROCESS

The invention relates to a thin film coating method with minimal adhesion to biological species.

Implants, catheters, intraocular lenses or more generally all bio-systems (bio-components) require non-adherent surfaces to the biological material (non-fouling) such as proteins, lipids or cells.

Indeed, the reactions to a solid-liquid interface, are generally complex, multiple and specific to the nature of the species in the presence. In all these cases, the reactions lead to a localized biological disturbance of the host medium characterized by the formation of an interfacial layer between the foreign object (the implant, the catheter, the intraocular lens) and the medium of the host. welcome (the body, the eye). Controlling the activity of this interface layer is necessary for the balance of compatible conditions between matter and living (bio compatibility).

The constituent materials of the various bio-systems are generally chosen for their mechanical, optical, or electrical properties but are mostly not or not very biocompatible.

To solve this problem, it has been proposed to deposit a thin layer of a biocompatible material, with a thickness of less than 1 .mu.m, on the bio-system.

The approach commonly adopted to date consists in attempting to incorporate a -COOH (carboxylic acid) functionality present in a starting precursor of the final material. Indeed, the minimal adhesion materials vis-à-vis biological species in general have a -COOH group.

Their deposition can be carried out, as described for example in the international patent application WO 03/090939, by plasma using a precursor comprising the -COOH group, which can be written in the form X-COOH.

WO 03/090939 also describes the use of a precursor comprising a carbonyl group, the -OH functionality being brought by a donor gas such as water. Thus, in the process described in this document, either the -COOH functionality is already present in the precursor, or the presence of a carbonyl group -C = O in the precursor used is essential because it is the group which will make it possible to forming the -COOH functionality, for example by injecting water or methanol into the plasma apparatus together with the carbonyl precursor.

The plasma technique makes it possible to break some bonds in the precursor X, which will allow the attachment of material on the desired support. But the essential bond between the precursor X and the group -COOH or -C = O is fragile: the plasma must not destroy it. We are therefore limited in plasma power.

As a result, the materials obtained are no longer crosslinked: they have poor mechanical and chemical resistance. It is also limited in this process on the choice of the precursor and therefore the final matrix, and therefore on the properties other than non-adhesion.

Thus, it has been proposed to produce polyethylene oxide / polyethylene glycol coatings which is the reference biocompatible material. It can be deposited in thin film by plasma or by grafting or by different chemical processes in the liquid phase.

The problem with these types of treatments is that they are not compatible with most microelectronics technologies and therefore are not suitable for the realization of integrated biocomponents because of a non-conforming deposit, and / or low adhesion and / or complexity of the process used.

It was then proposed to make a "PEO-like" coating by plasma polymerization. PEO-like is a polyethylene oxide having a composition slightly different from the polyethylene oxide obtained by liquid phase synthesis. But, again, the major problem encountered is the need to maintain the starting functionality (usually ethylene oxide EO (-CH2-CH2-O) _n ). This constraint requires, in this case also, to use very low power plasmas leading to the production of deposits, certainly biocompatible, but, again, not or very little crosslinked. Furthermore, there is known a process for etching organic materials in which the water is injected into a plasma (EJ Tonnis & al.

Vac. Sci. Technol. A18.2., Mar / Apr 2000). Indeed, the molecule H ₂ O leads to the formation of OH radicals ^" particularly effective for the etching of organic materials, which is to be avoided in a coating process.

To summarize, the biocompatible thin film deposition processes of the prior art lead to deposits with many disadvantages among which can be mentioned:

- low mechanical strength, - low stability over time (aging),

a low resistance to organic solvents,

- the handling and release of precursors harmful to the environment and dangerous for humans,

a nature of the matrix imposed by the precursor comprising the -COOH or -C = O functionality.

While it is now possible to accommodate the first four disadvantages, there remains a hard point that can not be circumvented, which is the nature of the matrix and therefore the general physical properties of the deposit.

The present invention solves this problem by allowing the functionalization in situ, that is to say during the production of the coating, of any type of matrix. It thus becomes possible to choose a material for its properties, for example optical, and to add a non-fouling feature.

Thus, the invention relates to a process for functionalizing a thin film being grown by -COOH functions for, in particular, the production of non-adherent surface or minimal adhesion to the biological material, (non-fouling).

The invention is based on the principle of the chemical vapor phase decomposition of a carbon precursor, having no -COOH functionality or -C = O functionality, in the presence of water vapor.

Thus, the invention provides a thin-film coating method with minimal adhesion to biological species of the type comprising the deposition of a thin film with -COOH function, comprising a step of chemical vapor phase decomposition. a carbon precursor comprising neither carbonyl group nor carboxyl group, in the presence of water.

Said step of chemical vapor phase decomposition may be activated by plasma, and / or by heat input, and / or by addition of waves and / or radiation, preferably by plasma.

The chemical decomposition is preferably activated by plasma as an energy carrier. This plasma can for example be of the radiofrequency, low frequency, ECR (Electron Cyclic Resonance), ICP (Inductively Coupled Plasma), DBD (Dielectric Barrier Discharge) type. However, the use of heat, and / or of waves and / or radiation, and / or of several of these energy sources, possibly in combination with the plasma, is also part of the invention.

In a first preferred embodiment, the carbon precursor is a precursor of a hydrophobic material such as a fluorocarbon or organosilicon or mixtures thereof.

Preferably, the precursor of the hydrophobic material is C ₄ F ₈ or C ₂ F ₄ or hexamethyldisiloxane or mixtures thereof.

In a second preferred embodiment, the carbon precursor is a precursor of hydrophilic material such as a hydrocarbon. Preferably, the precursor of hydrophilic material is C ₂ H ₂ or C ₉ H ₁₀ or mixtures thereof

The invention will be better understood and other features and advantages thereof will appear more clearly in the light of the description which follows and which is made with reference to examples of implementations of the methods of the invention and the figures in which: FIG. 1 schematically represents an example of a device for implementing the method of the invention, FIG. 2 represents the infrared spectrum of a polytetrafluoroethylene-like (PTFE-like) film obtained from C ₄ F ₈ without functionalization, FIG. 3 represents the infrared spectrum of a PTFE-like film obtained from C ₄ F ₈ according to the method of the invention, FIG. 4 represents the infrared spectrum of an amorphous carbon film (α-CH), that is to say hydrophilic, without functionalization, obtained from C ₉ H ₀ , FIG. 5 represents the infrared spectrum of an α-CH film obtained from C ₉ H ₁₀ according to the process of the invention, FIG. 6 represents the infrared spectrum of a polymethyldisiloxane-like (PDMS-like) film obtained from hexamethyldisiloxane, without functionalization FIG. 7 represents the infrared spectrum of a PDMS-like film obtained from hexamethyldisiloxane according to the method of the invention, FIG. 8 is a schematic representation of a passive microfluidic valve according to one embodiment. of the invention.

Thus, in the process of the invention, a gaseous mixture, composed of at least one carbon precursor gas comprising at least one carbon atom but no -COOH functionality or -C = O functionality and water vapor, is used.

Of course, several such carbon precursors can be used simultaneously. Preferably, the gaseous mixture is entrained by a suitable carrier gas such as, for example, helium, argon or hydrogen or mixtures thereof.

The method of the invention makes it possible to obtain a film made of a material chosen for its properties, for example mechanical, optical or electrical properties, and to add thereto -COOH functionalities, while the film is being grown.

The method of the invention is to start forming a thin film with a precursor having no -COOH functionality or -C = O functionality, and to create the bond between the formed material and the -COOH functionality in situ.

It is sufficient that the precursor contains carbon and that water is introduced into the enclosure. Unexpectedly, it has been discovered that it is possible to manufacture resistant and, of course, non-adherent or minimally adherent deposits with biological species by the method of the invention allows to work at higher powers, plasma, when the plasma is used as a source of energy.

The precursor is any precursor containing carbon. It can be chosen to create a hydrophilic or hydrophobic coating film. By choosing a precursor of a hydrophilic material, a hydrophilic coating film will be obtained. Among the precursors of hydrophilic material, mention may be made of hydrocarbons.

Preferably, in the case where it is desired to obtain a hydrophilic coating, C ₂ H ₂ or C ₉ H ₁₀ OR a mixture thereof. When it is desired to obtain a hydrophobic coating, a precursor of hydrophobic material, such as a fluorocarbon, preferably C ₄ F ₈ or C ₂ F _{4, is used} .

To form a hydrophobic film, it is also possible to use an organosilicon such as, for example, hexamethyldisiloxane (HMDSO) as a precursor material.

In other words, the invention allows the deposition of a film having the desired mechanical, electrical and / or optical characteristics, and a minimal adhesion to biological species, in particular, on all types of implanted biological systems, d. on the one hand, and on all types of fluid systems for biological applications, on the other hand.

Non-exhaustive examples include the treatment of intraocular implants, catheters, the treatment of channels of microfluidic systems (s) such as lab-on-chips or MEMS (Micro Electro Mechanical System), In fact, the reduction of scales gives the surfaces an increasing importance and it is therefore necessary to control their biological activities as well as possible.

In addition, thanks to the method of the invention, it is possible, for example, to render the inside of a channel non-adherent to the biological material. Indeed, depending on the choice of the functionalized starting material and thus the precursor used, the channel may be selected as hydrophilic or hydrophobic. This advantage is particularly interesting in the context of the realization of passive valves as will be explained in the examples. In order to better understand the invention, we will now give several examples of implementation and realization.

The examples of implementation and embodiment of the invention which are given below are given for illustrative purposes and should in no way be considered as limiting the invention.

The principle of the functionalization process of thin films being grown by COOH functions for the production of non-adherent surfaces to biological material as well as the thin-film coating method with minimal adhesion towards biological species of the invention will be described with reference to FIG.

The invention consists in injecting, in a closed enclosure, denoted 7 in FIG. 1, kept under vacuum thanks to the vacuum pump (not shown) connected to the pipe denoted 6 in FIG. 1, on the one hand the precursor (s) of the end materials of the coating, in gaseous form, through the pipe marked 2 in Figure 1, and, on the other hand, water vapor, through the pipe denoted 1 in Figure 1.

The pipes 1 and 2 are connected to a perforated pipe 3 denoted in FIG. 1 which allows the transport of the precursor (s) and the water vapor inside the enclosure 7. The sample to be coated, denoted by 8 FIG. 1 is placed on the sample holder marked 5 in FIG. 1, and the precursor (s) and the water are decomposed by plasma at the level of the chemical reaction zone, denoted 9 in FIG. 1, and the reaction products are deposited. on the sample 8.

This process allows in situ formation during growth of the carboxylic acid film and its incorporation into the growing layer.

As already mentioned, the injection of water vapor into the plasmas is generally reserved for etching. Indeed, the decomposition of the molecule H ₂ O leads to the formation of OH radicals ^" particularly effective for the etching of organic materials, which is to be avoided in a thin film coating process.

However, thanks to the processes of the invention in which the COOH-coating bond is carried out in situ, it is possible to use water not as an etching agent but as a functionalising vector. carboxylic acid functions (-COOH) of the growing layers, as will be shown in the examples which follow, since the methods of the invention make it possible to use higher plasma powers. Example 1

In this example, a PTFE-like layer functionalized by the method of the invention is deposited on a silicon substrate. The operating conditions for the deposition and growth of the layer are as follows: Precursor: C ₄ F ₈

- Power of the plasma: 300 W

Flow rate of the precursor C ₄ F ₈ : 80 cm ³ / min

- Flow rate of H ₂ O: 10 cm ³ / min

- Time: 1 mn - Pressure: 1 mb.

For comparison, a silicon substrate was coated with a layer obtained from the same precursor C ₄ F ₈ , without addition of water, under the same conditions.

The infrared spectrum of the deposit obtained without the addition of H ₂ O, that is to say non-functionalized, is represented in FIG.

As can be seen in FIG. 2, the coating obtained is not functionalized with COOH groups, this spectrum showing only the absorption peaks of the fluorocarbon matrix.

In contrast, the infrared spectrum of the deposit obtained with the process of the invention, that is to say using as precursor C ₄ F ₈ and water, very clearly shows the presence of COOH groups ( C = O about 1700 cm ^-1 , about 3500 cm ^-1 ).

The minimal adhesion property with respect to the biological species of these two layers was analyzed by protein labeling with Cy3 and Cy5 fluorophores of antigen, cell lysate, serum and biopsy. The results of this study clearly show that the layer functionalized by the process of the invention has a minimal adhesion towards the biological species while the non-functionalized layer has a high adhesion. At the same time, contact angle measurements were made on both surfaces. The contact angle for the non-functionalized surface is 110 ° and for the functionalized surface is 105 °. These results show that the functionalized layer has retained the low surface energy properties of the starting matrix.

This example shows that it is possible to achieve a hydrophobic surface with minimal adhesion to biological species.

Example 2

The coating of a silicon substrate by an amorphous carbon layer by the process of the invention was carried out under the following conditions:

- Precursor C9H10

- Power of the plasma: 100 W

Flow rate of the precursor C ₉ F ₁₀ : 500 cm ³ / min - Flow H ₂ O: 20 cm ³ / min

- Time: 2 minutes

- Pressure: 1 mb.

Another coating was made under the same operating conditions, but in the absence of water. The infrared spectrum of the deposit obtained without the addition of water is represented in FIG. 4. As can be seen in FIG. 4, the layer obtained is not functionalized with -COOH groups whereas, as seen in FIG. which represents the layer obtained with the method of the invention, the latter is functionalized. The contact angle measurements made on these two surfaces give, for the surface obtained according to the method of the invention a contact angle of 32 ° and, for the non-functionalized surface, a contact angle of 28 °. These results show that the layer obtained according to the process of the invention has retained the properties of high surface energy of the starting matrix. It is thus possible to produce a hydrophilic surface with minimal adhesion to biological species. Example 3

A PDMS-like layer was deposited on a silicon substrate by the method of the invention. The precursor used is hexamethyldisiloxane (HMDSO): - Plasma power: 100 W

Flow rate of the precursor HMDSO: 60 cm ³ / min - Flow of H ₂ O: 10 cm ³ / min Time: 2 mn Pressure: 1 mb. A layer was deposited in the same way on a silicon substrate. However, in this case, water was not injected into the plasma enclosure.

The infrared spectrum of the layer obtained by the method without injection of water is shown in FIG. 6. It clearly shows that the layer has not been functionalized by the -COOH groups.

On the other hand, the infrared spectrum represented in FIG. 7, obtained on the layer obtained by the process according to the invention, reveals the presence of these COOH groups.

Thus, all kinds of materials can be functionalized with carboxylic acid groups having non-adhesion or low adhesion properties with respect to the biological material. Example 4

The invention allows the deposition of a film with minimal adherence to biological species on all types of implanted biological systems on the one hand, and fluid systems for biological applications on the other hand.

For example, and as shown in FIG. 8, the microfluidic system channels (s) such as lab-on-chips or MEMS may be coated with a layer of material that is not adherent to the biological material, but also this layer may be rendered hydrophilic or hydrophobic.

FIG. 8 represents a passive micro-fluidic valve, which comprises a first channel denoted 9 and a second channel denoted 10 in FIG. 8. The wall, denoted 12 in FIG. 8, of the channel 9 is coated with a hydrophilic deposit with -COOH functionality, while the wall, denoted 11 in Figure 8, the channel 10, is coated with a material -COOH hydrophobic functionality.

The coating with a hydrophobic material of the wall 11 of the channel 10 makes it possible to prevent the rise of the fluid, flowing in the channel 9 in the direction of the arrow denoted F1 in FIG. 8, towards the channel 10, in which the fluid circulates in the the direction of the arrow marked F2 in Figure 8.

Claims

A thin-film coating method with minimal adherence to biological species of the type comprising the deposition of a thin film with -COOH functions, characterized in that it comprises a step of chemical vapor phase decomposition a carbon precursor comprising neither a carbonyl group nor a carboxyl group, in the presence of water.

2. Method according to claim 1, characterized in that said step of chemical vapor phase decomposition is activated by plasma, and / or by heat input, and / or by contribution of waves and / or radiation, preferably by plasma.

3. Method according to claim 1 or 2, characterized in that the carbon precursor is a precursor of a hydrophobic material such as a fluorocarbon or organosilicon or mixtures thereof.

4. Method according to claim 3, characterized in that the precursor of the hydrophobic material is C ₄ F ₈ or C ₂ F ₄ or hexamethyldisiloxane or mixtures thereof.

5. Method according to claim 1 or 2, characterized in that the carbon precursor is a precursor of hydrophilic material such as a hydrocarbon.

6. A method according to claim 5, characterized in that the hydrophilic material precursor is C2H2 or C ₉ Hi ₀ or mixtures thereof.