IT202000004015A1 - TRAINING SYSTEM FOR FEEDING A FLUID IN A MICROCAMERA OF A MICROFLUID DEVICE - Google Patents

Description

DESCRIPTION

of the patent for industrial invention entitled:

? TRAINING SYSTEM FOR FEEDING A FLUID IN A MICROCAMERA OF A MICROFLUID DEVICE?

TECHNIQUE SECTOR

The present invention? relating to a training system for feeding a fluid into a micro-chamber of a microfluidic device.

ANTERIOR ART

Microfluidics? the science of systems that treat and manipulate small quantities? of fluids through channels of a few hundred micrometers, in which the phenomena of capillarity? dominate the dynamics of fluids. This characteristic has led to the development of devices capable of controlling the handling of fluids in a remarkably precise manner in many different contexts, for example in the semiconductor industry and in the field of micro-electromechanics. However, in addition to physics and engineering, microfluidics has recently embraced other disciplines, such as chemistry and biology. Indeed the same approach? has been successfully applied to address complex issues of biology and medicine in order to build in vitro models that are useful for understanding certain cellular and biological processes. Can microfluidic devices simulate units? functionalities of a tissue or organ on a small organ-on-achip surface or they can replace and complement many laboratory functions on a lab-on-a-chip. There? yes ? proved to be particularly advantageous both in basic research and in the field of diagnostics. Over the years, many microfluidic devices have been designed and brought to market for biomedical applications such as DNA sequencing, functional genomics and single cell studies. Examples of different specialized biomedical fields will be listed below: neural tissue engineering, cancer testing, bone metastases, drug discovery and screening, diagnostics.

The main advantages of a microfluidic device in in vitro modeling of diseases are:

? allow you to work on a single cell scale;

? they allow in vitro modeling and in vitro techniques that take into account the 3D architecture of the tissues and the chemical / physical composition of the microenvironment, which cannot be considered in a single-layer 2D cell culture;

? have a high level of standardization and reproducibility;

? they require low-budget production;

? they maximize the information that can be collected from small samples, thus reducing testing costs compared to conventional laboratory equipment.

The miniaturization and the reduction of costs for the operator working in the biomedical field also allow to increase the scalability. and the number of experiments that can be repeated in a single run. Finally, the microfluidic devices represent an opportunity? excellent for reducing the use of animal experiments, thus solving ethical issues. An important example? the use of microfluidics for preclinical screening during the drug discovery process.

However, despite the fact that for the past two decades these devices have been designed to be applied on a large scale, their use is not? still widespread in institutes and companies? of research. One of the reasons that can? justify this situation? the fact that getting close to microfluidic devices can be considered tiring. The acquisition of new technologies always requires a very specific training period and new learning curves. Indeed, the manipulation of microfluidic devices involves several technical obstacles that arise from the miniaturization of the wells. The fluid filling procedure is performed in extremely small ducts and channels. Delicacy, precision of movements and hand-eye coordination are essential for the correct use of these devices and the brain requires specific training to improve muscle memory and fine movements of the upper limbs and hands. However, microfluidic devices cost much more. of traditional in vitro plastic supports and, nowadays, there is no? a reference system for exercises aimed at developing skills? of movement with microfluidic devices. As a result, many end users may not intend to change their conventional methods and tools for an expensive and time-consuming workout, but it does not guarantee certainty.

The development of a device at a price within everyone's reach, which can? be used both to assess the level of ability? manuals of an operator that to improve the precision of gestures, could solve the problem.

DESCRIPTION OF THE INVENTION

Purpose of the present invention? to provide a training system for feeding a fluid into a micro-chamber of a microfluidic device, which training system is a low-cost, easy-to-read device for assessing and training skills. individual manipulation of operators (for example researchers, technicians and students) in the feeding of fluids in microfluidic chambers.

Therefore, according to the present invention, a training system is provided for feeding a fluid into a micro-chamber of a microfluidic device according to the attached claims.

The claims describe preferred embodiments of the present invention and are an integral part of the description.

BRIEF DESCRIPTION OF THE DRAWINGS

Will the invention come? now described with reference to the attached drawings which show a non-limiting embodiment thereof, in detail:

figure 1? a plan view of a training system for feeding a fluid into a micro chamber of a microfluidic device in a closed configuration and made according to the present invention;

figure 2? a perspective view of the training system of figure 1 in the closed configuration;

figure 3? a plan view of the training system of Figure 1 in an open configuration;

figure 4? a schematic sectional view of a portion of the training system of figure 1;

figure 5? a plan view of a unit? test of the training system of figure 1;

figure 6? a plan view of the unit? test of figure 5 after a correct feeding;

figures 7-10 are plan views of the unit? of test of figure 5 after wrong feeding.

PREFERRED EMBODIMENTS OF THE INVENTION

In figure 1 the number 1 indicates, in its entirety, a training system for the feeding (filling) of a fluid in a micro-chamber of a microfluidic device.

The training system 1 comprises a support plate 2 (table) which has a rectangular shape and supports a plurality of elements. of unit? 3 of tests (cells) arranged in rows and columns in such a way as to form a chessboard. The training system 1 also includes? a cover plate 4 (table) which? arranged above the support plate 2 and comprises a plurality of of through openings 5, each arranged in correspondence with a relative unit? 3 test; according to a preferred embodiment shown in the annexed drawings, each through opening 5 has a square shape.

The cover plate 4? hinged to the support plate 2 to rotate about an axis 6 of rotation between a working position (shown in Figures 1 and 2), in which the cover plate 4? arranged above the support plate 2, and a cleaning (washing) position (shown in Figure 3), in which the cover plate 4? separated from the support plate 2. According to a preferred embodiment shown in the annexed drawings, the support plate 2 and the cover plate 4 have the same rectangular shape and are hinged to each other at an angle; in other words, the axis 6 of rotation? arranged at a corner of the support plate 2 and of the cover plate 4.

The cover plate 4? arranged at a certain distance (for example a few or a few millimeters), greater than zero, from the support plate 2 to keep the support plate 2 separate from the cover plate 4, thus avoiding the smearing of fluids by capillarity? from the support plate 2 to the cover plate 4, what can? happen during the procedures for feeding test fluids into the units? 3 of test. According to a preferred embodiment shown in Figure 4, a spacer element 7? arranged between the cover plate 4 and the support plate 2; in the illustrated embodiment, the spacer element 7 has a thickness of 3 mm. In particular, as shown in Figure 4, the cover plate 4? hinged to the support plate 2 using a self-locking screw 8 coupled to a nut 9 (washers can also be supplied).

As shown in figure 5, each unit? Test 3 comprises a main channel 10 engraved in the support plate 2 and adapted to be loaded with a test fluid.

According to a possible (but not limiting) embodiment, the test fluid can? be Betadine? or similar, that is? an antiseptic that is used to disinfect the skin before and after surgery, has a red color (therefore it is clearly visible) and? available all the way at low price; Betadine? has a low surface tension and properties? intense dyes and, moreover,? totally safe to handle.

Each main channel 10 extends from one end to the other. 11 initial, in which the test fluid must be loaded, at one end? 12 final opposite to the end? 11 initial, which is reached by the test fluid by capillarity? (starting from the initial 11 end); in other words, in use, the test fluid is loaded into the main channel 10 only at the end? 11 initial and flows along the main channel 10 by capillarity? towards the extremity 12 final.

Each main channel 10 has a spiral shape starting from the end. 11 initial placed in the center of the spiral and ending with the extremity? Final 12 placed on the outer edge of the spiral; in particular, each main channel 10 has a shape a? G? in which the extremity? 11 initial? arranged in the center of the? G ?.

According to a preferred embodiment, each main channel 10 comprises a succession of parallel or perpendicular linear segments 13-18. In particular, each main channel 10 includes:

? a linear segment 13 that begins with the extremity? 11 initial;

? a linear segment 14 connected to the linear segment 13, perpendicular to the linear segment 13 and having pi? or less the same length as the linear segment 13;

? a linear segment 15 connected to the linear segment 14, perpendicular to the linear segment 14, parallel to the linear segment 13 and having a length greater than the linear segments 13 and 14 (the length of the linear segment 15 should be more or less twice the length of the linear segment 13);

? a linear segment 16 connected to the linear segment 15, perpendicular to the linear segment 15, parallel to the linear segment 14 and having pi? or less the same length as the linear segment 15;

? a linear segment 17 connected to the linear segment 16, perpendicular to the linear segment 16, parallel to the linear segment 15 and having pi? or less the same length as the linear segments 15 and 16; And

? a linear segment 18 connected to the linear segment 17, perpendicular to the linear segment 17, parallel to the linear segment 16, ending with the extremity? 12 final and having a shorter length than linear segment 13.

According to a preferred embodiment, the linear segments 14-18 are arranged along the perimeter of a square.

Each unit? 3 test includes a control channel 19 that surrounds the end? 11 of the main channel 10 into which the test fluid is to be loaded. According to a preferred embodiment, each control channel has a? C? Shape. and the end? 11 initial of main channel 10? placed inside the control channel; in other words, each control channel 19 shaped like a? C? ? arranged inside the main channel 10 in the shape of a? G ?.

According to a preferred embodiment, each control channel 19 comprises a succession of parallel or perpendicular linear segments 20-24. In particular, each control channel 19 comprises:

? a linear segment 20;

? a linear segment 21 connected to the linear segment 20, perpendicular to the linear segment 20 and having a shorter length than the linear segment 20;

? a linear segment 22 connected to the linear segment 21, perpendicular to the linear segment 21, parallel to the linear segment 20 and having the same length as the linear segment 20;

? a linear segment 23 connected to the linear segment 20 at the end? opposite to the linear segment 21, perpendicular to the linear segment 20 and having a much shorter length than the linear segment 20.

? a linear segment 24 connected to the linear segment 22 at the end? opposite to the linear segment 21, perpendicular to the linear segment 22, aligned with the linear segment 23 and having the same length as the linear segment 23.

According to a preferred embodiment, each main channel 10? engraved in the support plate 2, has a width of 0.4 mm and has a depth? 0.2 mm; in the same way, each control channel 19? engraved in the support plate 2, has a width of 0.4 mm and has a depth? 0.2 mm. This miniaturized volume allows fluids to flow into channels 10 and 19 by capillarity.

According to a possible embodiment, the plates 2 and 4 are made starting from methacrylate sheets (3 mm high), which are then cut / laser engraved (the channels 10 and 19 are engraved, the through openings 5 are cut) . Instead of methacrylate sheets? You can use polycarbonate sheets or PVC sheets.

The dimensions of plates 2 and 4 are generally chosen using a standard SBS (Society for Biomolecular Screening) plate (127.76 x 85.48 x 14.8 mm) as a reference.

To use the training system 1, a user uses a micropipette which is initially filled with the test fluid (eg Betadine? Or similar, as mentioned above); the dosing outlet of the micropipette is placed (usually with the help of a microscope) above (and very close) to the extremity. 11 initial of the main channel 10 of a unit? 3 test and then the micropipette is operated to load a given quantity? calibrated test fluid (plus or minus 1.3? l) in main channel 10.

If the test fluid is loaded in the right place (the starting end 11 of the main channel 10), in the quantity? right (about 1.3? l) and with the right flow (i.e. not too fast), the final result should be as shown in figure 6: the test fluid loaded in the main channel 10 completely fills the main channel 10 (and main channel 10 only) without overflow from main channel 10.

If the test fluid is loaded in the wrong place (outside the starting end 11 of the main channel 10), the final result? that shown in figure 7: the test fluid fills the control channel 19 instead of the main channel 10.

If the test fluid is loaded in the right place (at the beginning 11 of the main channel 10) but in the quantity? wrong (much less than 1.3? l), the final result? that shown in Figure 8: the test fluid loaded into the main channel 10 fills the main channel 10 only partially.

If the test fluid is loaded in the right place (at the beginning 11 of the main channel 10) but in the quantity? wrong (much more than 1.3? l), the final result? that shown in figure 9: the test fluid loaded in the main channel 10 completely fills the main channel 10 and overflows from the main channel 10 at the extremity? 12 final (or near the final 12 end).

If the test fluid is loaded in the right place (at the beginning 11 of the main channel 10) but with the wrong flow (ie too fast), the final result? the one shown in figure 10: the test fluid loaded in the main channel 10 overflows from the main channel 10 at the end? 11 initial.

According to a different embodiment not shown, the cover plate 4 is not? present (i.e. the support plate 2 is not covered by the cover plate 4).

According to a different embodiment not shown, in each unit? 3 test the control channel 19 does not? present (ie each test unit 3 includes only main channel 10).

According to a different embodiment not shown, in each unit? 3 test, the shape / size of the main channel 10 and / or the shape / size of the control channel 19 are different from the preferred (but not limiting) embodiment shown in the annexed drawings.

The embodiments described in the present disclosure can be combined with each other without thereby departing from the scope of protection of the invention.

The training system 1 described above has numerous advantages.

Firstly, the training system 1 described above reproduces the real difficulties? techniques of a microfluidic device; in other words, the difficulties? manipulation techniques of the training system 1 are similar to those of a microfluidic plate currently on the market for in vitro cell culture. Therefore the level of experience in the manipulation of microfluidic supports that can? be achieved with the training system 1 described above? significantly correlated to that obtained with a microfluidic plate currently on the market for in vitro cell culture.

The training system 1 described above has proved to be a valid tool for predicting the error rate in the loading of microfluidic plates currently on the market for in vitro cell culture; the training system 1 described above can? therefore, it can be used to evaluate the loading performance of commercially available microfluidic plates and to measure learning progress. Conceived starting from the difficulties? of users who find themselves using microfluidic devices for the first time, the development of the training system 1 described above can? be the trigger that triggers the creation of a series of preparatory tools or exercises to reduce the error rate of operators using microfluidics for the first time (ie technicians, researchers or students who have never used microfluidic devices). The training device 1 described above finds application in all those circumstances in which? it is necessary to prepare or keep up to date a large number of operators, without large financial resources that can be allocated to education on the purchase of microfluidic plates on the market.

Thanks to the inclusion in the design of the unit? 10 of tests of different indicators that are useful for obtaining feedback on different elements in order to check the performance in real time, the training system 1 described above lends itself to a self-learning and self-correcting process, to coordinate hand and head. For example, in addition to the training path consisting of the main channel 10,? there is an overflow indicator constituted by the control channel 19.

Another advantage of the training system 1 described above? that ? it is possible to see easily and quickly if the load of a unit? 10 test? performed correctly, even without using a microscope.

The presence of a cover plate 4 with through openings 5 increases the difficulty? technique in loading the units? 10 of test. In fact, the tip of the micropipette must be inserted inside a? Small? through opening 5; in other words, the presence of the openings 5 passing above the unit? 10 test reduces freedom? of movement (angle) of the micropipette and also reduces visibility.

The training system 1 described above can? be easily cleaned (washed) and, therefore, the operator who performs the training can? use it several times; in particular, to avoid limescale deposits in the channels 10 and 19, the support plate 2 can? be washed using demineralized (distilled) water.

Finally, the training system 1 described above has a very low production cost, why? ? made of? small pieces of plastic ?.

LIST OF NUMERICAL REFERENCES OF THE FIGURES

1 training system

2 support plate

3 units of test

4 cover plate

5 through openings

6 axis of rotation

7 spacer element

8 lives

9 nut

10 main channel

11 extremities initial

12 ends the final

13 segment

14 segment

15 segment

16 segment

17 segment

18 segment

19 control channel 20 segment

21 segment

22 segment

23 segment

24 segment

Claims (17)

CLAIMS 1) Training system (1) for feeding a fluid into a micro-chamber of a microfluidic device; the training system (1) comprises a support plate (2) which supports a plurality of of unit? Test (3), each comprising a main channel (10) engraved in the support plate (2) and adapted to be loaded with a test fluid. 2) Training system (1) according to claim 1, wherein each main channel (10) extends from one end (11) initial, in which the test fluid must be loaded, at one end? (12) final opposite to the end? (11) initial, which is reached by the test fluid by capillarity. 3) Training system (1) according to claim 2, in which each main channel (10) has a spiral shape starting from the end. (11) initial placed in the center of the spiral and ending with the extremity? (12) final placed on the outer edge of the spiral. 4) Training system (1) according to claim 2 or 3, wherein each main channel (10) has a? G? Shape in which the extremity? (11) initial? arranged in the center of the? G ?. 5) Training system (1) according to claim 2, 3 or 4, wherein each main channel (10) comprises a succession of parallel or perpendicular linear segments (13-18). 6) Training system (1) according to claim 5, wherein each main channel (10) comprises: a first linear segment (13) that begins with the extremity? (11) initial; a second linear segment (14) connected to the first linear segment (13) and perpendicular to the first linear segment (13); a third linear segment (15) connected to the second linear segment (14) and perpendicular to the second linear segment (14); a fourth linear segment (16) connected to the third linear segment (15) and perpendicular to the third linear segment (15); a fifth linear segment (17) connected to the fourth linear segment (16) and perpendicular to the fourth linear segment (16); And a sixth linear segment (18) connected to the fifth linear segment (17), perpendicular to the fifth linear segment (17) and ending with the extremit? (12) final. 7) Training system (1) according to one of claims 1 to 6, in which each unit? (3) test includes a control channel (19) surrounding the end? (11) of the main channel (10) into which the test fluid is to be loaded. 8) Training system (1) according to claim 7, wherein each control channel has a shape a? C? and the end? (11) initial of the main (10) channel? placed inside the control channel. 9) Training system (1) according to claim 7, wherein each main channel (10) has a? G? Shape and the? C? shaped control channel (19) ? arranged inside the main channel (10). 10) Training system (1) according to one of claims 1 to 9 and comprising a cover plate (4) which? arranged above the support plate (2) and comprises a plurality of of through openings (5), each arranged in correspondence with a relative unit? (3) test. 11) Training system (1) according to claim 10, wherein each through opening (5) has a square shape. 12) Training system (1) according to claim 10 or 11, wherein the cover plate (4)? arranged at a certain distance, greater than zero, from the support plate (2). 13) Training system (1) according to claim 10, 11 or 12 and comprising a spacer element (7) arranged between the cover plate (4) and the support plate (2). 14) Training system (1) according to one of claims 10 to 13, wherein the cover plate (4)? hinged to the support plate (2) to rotate between a working position, in which the cover plate (4)? arranged above the support plate (2), and a cleaning position, in which the cover plate (4)? separated from the support plate (2). Training system (1) according to claim 14, wherein the support plate (2) and the cover plate (4) have the same rectangular shape and are hinged to each other at an angle. Training system (1) according to one of claims 1 to 15, wherein: the support plate (2) has a rectangular shape; And the units (3) of tests are arranged in rows and columns in such a way as to form a chessboard. 17) Training system (1) according to one of claims 1 to 16, wherein each main channel (10)? engraved in the support plate (2), has a width of 0.4 mm and has a depth? 0.2 mm.