Production process of a micro/nano-fluidic device having at least one channel with a section of micro/nano -metric size

The present invention refers to a production process of a micro/nano-fluidic device having at least one channel with a section of micro/nano -metric size.

Micro/nano -fluidics plays a role of rising importance in many fields, as carrying out chemical analysis and medical diagnosis, as well as performing chemical synthesis processes (quick tests and microreactors for the pharmaceutical industry).

More in detail, the employment of micro/nano-channels on Lab On a Chip devices allows for enhancing their efficiency and to reduce the quantity of necessary reagents and so the costs for performing large scale analysis tests.

In the genomic field, the interaction between DNA molecules and nano metric section channels allows for a new genetic code detection and sequencing system. The methodologies based on such interaction represent an evolution compared to the traditional ones, for example the ones based on the use of agarose gel.

By using the small channels section, experiments for the study of single molecules can be carried out, for example by stretching them in order to study one particular binding energy.

In the field of the biomedical life support devices for a patient, the micro/nano-channels can be used in filtering or in extracorporeal circulation systems. In detail, the availability of rounded section micro/nano-channels is of fundamental importance in oxygenators for the blood extracorporeal circulation. In such application, the presence of edges brings an increase in shear stresses acting on red blood cells and the formation of stagnation areas, which can cause hemolysis and possibly thrombi with serious damages for the patient health.

According to the above brief explanation, it is evident that the availability of suitable micro/nano-fluidics devices will be a key factor to develop in-depth the potentials of a series of technologies extremely promising at the moment.

An object of the present invention is providing an improved process in the production of such micro/nano-fluidics devices.

According to this invention, this object is reached thanks to a production process of a micro/nano-fluidic device having at least one channel with a section of micro/nano -metric size, including the following steps:

- making on a surface of a first substrate a draft excavation of said channel,

- constraining a second substrate to said surface of the first substrate, in order to close the draft excavation longitudinally, and

- inserting in said draft excavation a chemical etching solution able to etch at least the second substrate in order to remove the material in the area corresponding to the draft excavation, thus obtaining the desired transversal section channel.

The invention process includes a reduced number of steps and does not need expensive and slow growing and alignment techniques of the two substrates, but uses a low-cost chemical etching technique. On the whole, therefore, it is definitely more competitive than the conventional processes from the point of view of the costs.

The materials employed for the substrates can be of the biocompatible kind, so that the obtained device can be used without problems in the biomedical, biologic and medical fields. Particularly suitable materials, which can be employed for the first and second substrates are glasses, such as borosilicate glass, and silicon compounds, such as silicon oxide and silicon nitride. In principle, also metallic materials can be used, provided that their surface roughness features are compatible with the reduced dimensions of the section of the channels that have to be realized. The first and second substrates can be made of the same as well as different materials.

The draft excavation can be obtained for example by using a further chemical etching solution, or through a physical etching method, as for example "reactive ion etching" after masking the areas of the first substrate surface that should not be etched.

The constrain between the second and the first substrate can be realized for example through a "bonding" method such as "anodic bonding", "fusion bonding", "eutectic bonding" or other kind of "bonding" methods commonly used in the micro fabrication technology.

In order to obtain the desired shape of the channel transversal section, it is possible to choose a chemical etching solution that, inserted in the draft excavation, is able to etch, beyond the second substrate, the first one as well.

In order to improve the material etching uniformity through chemical etching solution inserted in the draft excavation, such solution can be under pressure and/or stirred by ultrasonic agitation.

By matching the first and second layer materials selection with the features of the etching solutions used to realize the draft excavation and subsequently for the insertion in the latter, the transversal section of the obtained channels can be shaped in the desired way. In detail, if isotropic profile etching solutions are used, the transversal section channels will be round-shaped, for example circular or ellipsoidal. As already said, such round-shaped sections are crucial in oxygenators for the blood extracorporeal circulation where the formation of stagnation areas and increasing shear stresses acting on red blood cells must be avoided.

Therefore, a further subject of the present invention is represented by a micro/nano-fluidic device obtainable by the above-captioned process and having at least one round-shaped channel with a transversal section of micro/nano -metric size, which is for example circular or ellipsoidal.

Further advantages and features of the present invention will be apparent from the detailed description hereafter reported, provided only by way of non-limiting example with reference to the enclosed drawings where: the figures going from Ia to Ig give a schematic description of the different subsequent steps of a process of the invention, and figure 2 is a schematic perspective view of a device, which is produced through the invention process.

A fabrication process of a micro/nano-fluidic device, which presents a plurality of channels with micro/nano -metric size section, provides for, first of all, submitting a wafer 10 of massive silicon to a treatment in aggressive solution and then a transit in fluoridic acid in order to remove the native oxide (fig. Ia).

Then the wafer 10 is oxidized in order to form a superficial layer 12 of oxide of thickness for example equal to 1 μm (fig. Ib). Alternatively, the superficial layer 12 could be obtained by means of a deposition technique, such as Chemical Vapour Deposition (CVD), Low Pressure Chemical Vapour Deposition (LPCVD), Physical Vapour Deposition (PVD).

Subsequently, the superficial layer 12 is coated with a film 14 of resist, for example PMMA, (fig Ic), on which it is patterned by means of electron beam lithography (fig. Id) the top plan view of the configuration of the draft channels that have to be realized. This technique allows for obtaining a resolution of the order of nanometer, thus allowing for obtaining a first substrate 16 having a surface 18 on which the top plan view of the desired configuration of the channels is made.

The surface 18 is then submitted to a chemical etching with a fluoridic acid solution, for example the solution "Buffered Oxide Etch", typically used for the oxide etching. In this way, it is realized a draft excavation 20 in all the areas where the film of resist has been removed by means of electron beam lithography (fig. Ie), while the remaining areas are masked by the film 14 and thus protected. The utilized solution has an isotropic etching profile, so that each excavation 20 has a transversal section which has substantially a

semicircular shape, and its employment must be interrupted before the entire thickness of the layer 12 of oxide is taken away by the solution.

At the surface 18 of the first substrate 16 it is constrained a borosilicate glass wafer acting as a second substrate 22 (fig. If) in order to seal longitudinally the draft excavations 20 leaving the ends thereof open. The constrain is obtained by a "bonding" technique, which could be "anodic bonding", "fusion bonding", "eutectic bonding" or other kinds of "bonding" usually employed in micro fabrication technologies.

Finally it is inserted in each draft excavation 20 a chemical etching solution able to etch both the substrates (fig. Ig). Also this solution has an isotropic etching profile, so that the etching result is the formation of channels 24, which have a transversal section that is round- shaped. If the channels length 24 is so high that it prevents the diffusive process of the etching solution active agent from performing a uniform etching action on their entire length, this uniformity could be obtained by means of ultrasonic agitation and/or by increasing the pressure, with which the etching solution is inserted in the draft excavations 20.

It is thus realized (fig. 2) a micro/nano-fluidic device 26 made by the first 16 and second 22 substrate joined together, on which interfacial surface 18 a plurality of channels 24 of micro/nano -metric size having a transversal round shaped section, in particular a circular one, was obtained.

Such a device can be employed in several field, for example:

- in medical and biomedical field, for the realization of devices in the life-support of the patient (such as for example extracorporeal oxygenators) and in analysis and therapy (such as for example filtration systems);

- in chemical field, for the realization of chemical analysis on miniaturized devices;

- in genetic field, for the realization of Lab On Chip devices for the analysis of the genetic code;

- in the field of the cellular mechanics, for the fabrication of devices for cellular tests.

Of course, within the principle of the invention, the particulars of the realization and the modes of actuation could widely differ respect to those described for exemplificative purpose, without for this reason being far away from the field of the invention as defined in the annexed claims.