WO2023129103A2

WO2023129103A2 - A mini chip device system

Info

Publication number: WO2023129103A2
Application number: PCT/TR2022/051712
Authority: WO
Inventors: Caner DEMİR; Murat Öztürk
Original assignee: Genz Bi̇yo Teknoloji̇ Anoni̇m Şi̇rketi̇
Priority date: 2021-12-30
Filing date: 2022-12-30
Publication date: 2023-07-06
Also published as: WO2023129103A3

Abstract

Invention relates to a device system developed for production method of mini microfluidic chips to be used in medical device industry.

Description

A MINI CHIP DEVICE SYSTEM

Technical Field

The invention relates to a device system developed for production method of mini microfluidic chips to be used in medical device industry.

Prior Art

Today microfluidic chips are used in various fields such as chemistry, medicine, tissue engineering etc. and are also structures that can be used in medical field for the detection of antibodies, hormones, blood gases and proteins in blood, also for identification of cell types such as cancer cells and single cell living beings such as virus and bacteria.

Antibodies, proteins and other blood markers in blood are used for medical diagnosis and tracking purposes. They are essential markers to detect various antibody types such as IgG, IgM and IgA in blood, micro-organisms having potential to develop diseases in the body such as bacteria, viruses and response of the immune system developed against other potential pathogens and its level. In addition, as the vaccine stimulates immune system , it increases the level of antibodies in the blood, developed as response to vaccine. The levels of them are measured and thus effectiveness of the vaccine is determined.

Blood markers such as various proteins, enzymes, glycoprotein, hormones, and oxygen level of blood are used to find out health status and potential disease risks of a person. Levels of markers spreaded from tissues such as liver, heart, kidney, cancer vary subject to health status. For instance, troponin protein released into blood subject to cardiac muscle damage is an essential marker for measuring heart attack status or risk. Also, levels of hormones such as cortisol, testosterone give information about stress level and functionality of the immune system. Levels of blood gases give information to determine the way of attempt by medical staff during particularly operations and emergency interventions.

Foreign pathogens such as virus, bacteria and pathogen particles can be detected from body fluids such as blood, urine or saliva, tissue samples such as throat, nose swabs. One of the techniques used the most commonly for diagnoses of markers such as blood protein and hormones is ELISA (Enzyme Linked Immunosorbent Assay) technique. In ELISA method protein structures such as antibodies, short peptide chains, nucleic acid structure such as DNA and RNA or other special molecules such as synthetic polymers are used which can bind to the target marker. These structures are immobilized on a plastic surface, membrane or spherical structures and thus they are held on the surface where the relevant analysis will be made by binding them when encountered with targeted markers. The plastic materials used for coatings are structures comprising structures in the form of well and called microplate. Surfaces of these structures are modified generally chemically or physically to enhance coating efficiency and thus surface features required for the achievement of intended coating are obtained. Most ELISA systems are manufactured from materials such as polystyrene and polyvinyl consist of wells from 96 to 384. Having molecules such as glutaraldehyde, maleimide, hydrazine comprising active groups to provide covalent bonding on microplate surface enhances coating efficiency onto surface of desired structures such as protein, antibody, peptide. Molecules comprising the active group can be bonded to the surface as a result of various physical processes such as plasma applications, various chemical processes such as acid, base application, polymer bonding. Afterthese operations called activation, marker capturing structures such as protein, antibody or peptide can be coated onto the surface are immoblized by applying generally a temperature between +4 to 37’C for a time ranging from 24 to 1 hour/s in a relevant convenient solvent for each well. After this stage, flushing operations are conducted for each well to remove structures not bonded to the surface. In order to cover uncoated surfaces, bovine serum albumin (BSA), milk powder, casein, serum, detergents or polymers are used, and process called blocking is applied for each well. After blocking, depending on the process used, after certain washing or not washing, and after drying or cold storage, ready to use ELISA microplates are obtained. Liquid transfers in all of those processes, liquid dischargesand any solvent applications are made manually by micro pipettes or automatic pipetting instruments.

Principles of ELISA technique is also used in lateral flow tests based on imaging on membranes which have lower sensitivit. In these tests, the surface where coating is made is not plastic derivative but absorbing membrane form.

ELISA technique can also be used on narrow channel structures named microfluidics, where reagents are used in less volumes in addition to standard ELISA microwells. Microfluidics can be made from various materials such as glass, PDMS (polydimethylsiloxane), PMMA (polymethyl methacrylate). Systems like microfluidic structures are similar to ELISA in respect to steps such as surface activation after microfluidic structure production, bonding of surface molecules and special structures, blocking etc. In addition to these steps, in the last step or at the beginning of the processes it should be sealed properly so as to enable leak-proof channel structure of microfluidic structure.

For fabrication of PDMS microfluidic chips, primarily, a main mould is developed by using photoresist polymers. Then PDMS is cast onto the forms and then cured by methods such as temperature etc. and original chips are produced. However, upper parts of the chips, channel structures facing the main form side are in open structure. For closing channels and providing leakage proof, glass, PDMS or other polymer films that can be bonded to the used PDMS are used.

Microfluidic chips can also be produced from PMMA and thermoplastic polymers such as polycarbonate, polystyrene. Desired channel structures can be provided on such materials by use of techniques such as injection moulding, laser, hot press, mechanical treatment. Regarding optic features, injection moulding and hot press application are preferred. Various methods can be used for bonding microfluidic chips produced with thermoplastic materials. Microfluidic components, the one including main channels and upper part can be bonded with hot press, or solvents such as ethyl alcohol or chloroform, depending on the type of the polymer (plastic). Ultrasonic welding method can be used. While the surfaces to be closed are compressed by means of convenient pressure, surfaces of polymeric material melted upon applying ultrasonic vibration are welded to one another. Besides these, various methods such as resin application, adhesive tapes or solvents can be used for leak proof sealing of the chips.

For activation of microfluidic channels and coating desired structures like protein onto surfaces, microfluidic chips are immersed into desired solutions before sealing or desired solutions are fed into channels after sealing the chips. Such methods are applied separately for each chip.

Standard ELISA microplates are produced for multiplex testing in a single run and the test process time period is in average about 45-60 minutes. For that reason, they are not suitable for single use, testing one sample at a time and cannot be used in rapid single use tests giving fast results. Reagent volume per well that is used for surface activation, coating and blocking stages in production are higher. Incubators or incubation rooms are required for the heating processes that might be necessary in activation and coating steps during production.. For homogenous process performance of solutions in wells, additional devices might be required such as microplate shakers for mixing solutions in the coating process.

Microfluidic chips can be designed for single use, differently from standard ELISA microplates. However, in general microfluidic chips need at least a surface containing channels and additionally a sealing proves as an additional process because of cover structure closing the surface. Factors such as temperature, pressure, solvent used in closing processes may damage physical and chemical structure of channels or immobilized proteins on the channel, or damage coated areas in channel surface. This case makes industrial reproducebility of the process more difficult.

Before microfluidic chips are sealed with a cover, microfluidic chips are to be immersed separately into chemical baths and washing baths required for surface activation. This constitutes additional process steps. If activation is made after chips are closed, feeding chemicals, waiting and flushing operations must be made separately for each chip. Performance of chemical application and washing operations separately for each chip has difficulties in terms of time period, effectiveness and industrial production. In production of the chips, after chip surfaces are closed, fluids such as other protein solvents that can be required to be applied must be applied separately for each chip. This makes continued production system development difficult. For preventing vaporization of solvents applied after microfludic chips are closed and preventing change of protein concentration to be covered in the solvent, channel inlet and outlet should be closed for each chip after giving solvent to channel or a closed system fluid flow cycle should be applied for each microfluidic chip. These conditions constitute additional difficulties in microfluidic chip processes and restrictions in mass production.

Taking all of those problems into consideration, in production of microfluidic chips that can be used for a single sample, development of a device system for a new production method wherein chips are treated collectively without need for putting different chemicals in flushing tanks and without need for separate devices for processes such as temperature application and shaking will eliminate said problems in microfluidic chip production.

As a result, due to above described disadvantages and inadequacy of existing solutions, it has been necessary to make development in the related art. Purpose of the Invention

The invention has been developed with inspiration from existing situations and aims to eliminate the above-mentioned disadvantages.

The device system of the invention enables the use of single-part chips containing one or more than one channels, suitable for mass production by use of injection molding technique, laser processing or machining process techniques and allows chemical modifications. Use of single part chip not requiring a lid structure eliminates all of the problems and difficulties encountered in sticking, welding etc. two-part chip used for obtaining leakage proof channel in former techniques.

The device system of the invention is designed as a closed loop system and achieves a leakage-proof line by aligning channel or channels and tightening of mini microfluidic chips, placed there and being parts of the device system, Thus, it is possible to apply processes such as not separately but collectively activation of surface on mini microfluid chips, protein coating, flushing or blocking. By help of a guide housing provided in the device system of the invention, establishment of a continuous line is provided by one or more than one channel located inside the chips placed in order side by side. Sealing provided by use of leakage proof materials such as gasket between chips enables various fluids or gases interactions by means of being on the same line of inner surface channels of multiple chips. Thus, processes such as chemical activation intended to be applied on mini microfluidic chip channels, protein bonding, drying, blocking can be applied to all chips forming the line and desired channel lines at the same time. In addition, by means of changing fluid lines to be bonded to device system, it becomes possible to apply desired chemicals to chips without need to carry to different process devices. This case provides an essential easiness in industrial production and eliminates need for immersing and washing baths.

Another advantage achieved with the invention is that it enables establishment of a closed-circuit system comprising all chips where applications will be conducted in terms of fluid and gas circulation. Thus, while chemicals and proteins are covered onto chip surface, vaporization subject to heat is prevented and long time periods provide interaction of channel surface and applied solvent. Application efficiency and advantage is also achieved for use of chemicals of costly or less needed which is needed for long term application. Since device system allows circulation of close circuit applied chemical in continued circulation, an additional mixing or shaking device is not needed. In addition, being a close circuit system, it facilitates use of chemicals that can be harmful for human health. On the other hand, as a bath tank system is not required, it is possible to process more chips with less amount of chemical. By help of heating and cooling plate provided in the device system, heat and moisture balance of liquids and gases passed through channel via mini microfluidic chips can be controlled easily. Therefore, it is not needed to place mini microfluidic chips into an extra heating oven.

In order to achieve above mentioned purposes, the invention relates to a device system for production method of mini microfluidic chips in medical device industry. Accordingly, the system comprises:

• Microfluidic chip of multiple number in single part prismatic form and sequenced side by side whereon chemical operations are applied,

• At least a channel located on microfluidic chip and providing conduct of desired coating on the surface,

• Chip surface functioning as mounting surface on microfluidic chip,

• Hole passing through microfluidic chip from top to end,

• Guide housing wherein microfluidic chips are sequenced in order,

• Main table having guide housing and supporting for alignment and tightening of microfluidic chips,

• Tightening cap applying compression from both sides onto microfluidic chip series sequenced in said guide housing and establishing sealing,

• Compression part located on said tightening cap and connected to microfluidic chips,

• Feeding holes located inside said tightening cap and providing fluid inlet and outlet,

• Compressing unit connected to main table and applying pressure onto tightening cap,

• Female bolt housing providing bolt connection between tightening cap and main table,

• Connection hoses providing fluid passing between different channel lines formed by microfluidic chips,

• Connection hole located in tightening cap wherein said tightening unit passes,

• Pump system located on microfluidic chip and providing conduct of desired coating onto the surface and capable to pump liquid into channels or sucking liquid, • Liquid chamber having desired liquid to be given to microfluidic channel system,

• Transmission connection hoses providing fluid flowing between said liquid chamber and the system,

• Channel inlet providing connection of feeding holes passing through said tightening cap and connection hoses,

• Discharge connections providing connection between tightening cap and connection hoses,

• Heating cooling table performing heating and cooling operation providing temperature balance of main table and surrounding the table,

• Jacket housing providing seating of heating cooling table onto main table from bottom and/or top.

• Inlet-outlet connections providing entering of fed liquids into and/or leaving heating cooling table,

• Fluid flow channels located inside heating cooling table.

The structural and characteristics features of the invention and all advantages will be understood better in detailed descriptions with the figures given below and with reference to the figures, and therefore, the assessment should be made taking into account the said figures and detailed explanations.

Brief Description of the Figures

Figure 1 is a top view of microfluidic chip in the system of the invention.

Figure -2 is a side view of microfluidic chip in the system of the invention.

Figure -3 is a side perspective view of microfluidic chip in the system of the invention.

Figure -4 is a perspective view of microfluidic chip in the system of the invention.

Figure -5 is a view of gasket of the system of the invention.

Figure -6 is a view of tightening cap of the system of the invention.

Figure 7 is a view of demounted form of tightening caps.

Figure 8 is a side view of heating cooling table.

Figure 9 is a top cross-sectional view of heating cooling table. Figure 10 is a perspective view of microfluidic chip.

Figure 11 is a view of mounted form of tightening caps.

Figure 12 is a view of mounted system.

Figure 13 is another view of fully mounted system.

Description of Part References

1. microfluidic chip

2. Channel

3. Chip surface

4. Hole

5. Guide housing

6. Female bolt housing

7. Main table

8. Gasket

9. Tightening cap

10. Compression part

11. Feeding holes

12. Discharge connections

13. Connection hole

14. Compression unit

15. Channel inlet

16. Connection pipes

17. Pump systems 18. Transfer connection hoses

19. Liquid chamber

20. heating cooling table

21. Jacket housing

22. Flow paths

23. Inlet-outlet connections

Detailed Description of the Invention

In this detailed description, the preferred embodiments of the system being subject of the invention have been described only for purpose of better understanding of the matter.

Invention is a device system for mini microfluidic chips production method in medical device industry. Accordingly, the system comprises microfluidic chip (1 ) of multiple number in single part prismatic form and sequenced side by side whereon chemical operations are applied, at least a channel (2) located on microfluidic chip (1) and providing conduct of desired coating on the surface, chip surface (3) functioning as mounting surface on microfluidic chip (1), hole (4) passing through microfluidic chip (1 ) from top to end, guide housing (5) wherein microfluidic chips (1) are sequenced in order, main table (7) having guide housing (5) and supporting for alignment and tightening of microfluidic chips (1), tightening cap (9) applying compression from both sides onto microfluidic chip (1) series sequenced in said guide housing (5) and establishing sealing, compression part (10) located on said tightening cap (9) and connected to microfluidic chips (1), feeding holes (11) located inside said tightening cap (9) and providing fluid inlet and outlet, compressing unit (14) connected to main table (7) and applying pressure onto tightening cap (9), female bolt housing (6) providing bolt connection between tightening cap (9) and main table (7), connection hoses (16) providing fluid passing between different channel lines formed by microfluidic chips (1), connection hole (13) located in the said tightening cap (9) wherein said tightening unit (14) passes, pump system (17) located on microfluidic chip (1) and providing conduct of desired coating onto the surface and capable to pump liquid into channels (2) or sucking liquid, liquid chamber (19) having desired liquid to be given to microfluidic chip (1) channel system, transmission connection hoses (18) providing fluid flowing between said liquid chamber (19) and the system, channel inlet (15) providing connection of feeding holes (11) passing through said tightening cap (9) and connection hoses (23), discharge connections (12) providing connection between tightening cap (9) and connection hoses (18), heating cooling table (20) providing temperature balance of main table (7) and surrounding the table and thus performing heating and cooling operation Jacket housing (21 ) providing seating of heating cooling table (20) onto main table (7) from bottom and/or top, inlet-outlet connections (23) providing entering of fed liquids into and/or leaving heating cooling table (20), fluid flow channels (22) located inside heating cooling table

(20).

Device system of the invention whose perspective view of mounted form is given in Figure 12 basically comprises guide housing (5) main table (7), single part mini microfluidic chips (1 ) fitting guide housing (5), tightening caps (9) and heating cooling table (20). A preferred embodiment of the invention comprises gasket (8) of convenient geometry with holes (4) located on microfluidic chip (1) and providing sealing.

Mini microfluidic chips (1) constituting a component of device system of the invention is produced by means of injection forming, laser treatment or machining treatment techniques and preferably of transparent structure. Thermoplastic polymers, PDMS or glass can be used in microfluidic chip (1) production. As seen from top in Figure 1 and from perspective in Figure 10, mini microfluidic chips (1) constituting a component of device system of the invention is of structure comprising one or more than one channel (2). As seen in Figure 1 the channels (2) are in form of holes (4) passing from one end to the other along x plane of the chip. As seen in Figure 2, the holes (4), when viewed from y-z plane, can be fully cylindrical, rectangular, ellipsoid or bottom and top parts can be flat and side parts can be of circle spiral.

Thanks to bottom and top part of channel (2) being parallel to one another in Y-Z axis and parallel to Y axis, a geometric structure minimizing refracting optically in Z axis. Surfaces of microfluidic chips (1) on Y-Z axis are flat and facilitates placement of gasket (8) between mini microfluidic chips (1) to provide sealing. xLength of microfluidic chip (1 ) in Y axis can be between 10 mm and 100 mm subject to number of channels (2) desired to be therein. Height of microfluidic chip (1) in Z axis can range from 2 mm to 10 mm to have high optical permeability. Length of microfluidic chip (1 ) on X axis is of the same size as the channel (2) it is in and may range from 2 mm to 20 mm. Height of channel (2) inside microfluidic chip (1) parallel to Z axis on Y--Z plane may range from 0,1 mm to 5 mm. Width of channel (2) parallel to Y axis in Y-Z plane may range from 0,1 mm to 10 mm.

In the device system of the invention, microfluidic chips (1) are sequenced into a guide housing (5) in the device main table (7) shown in Figure 4 and cross-section view shown in Figure 3 in a manner they follow each in multiple numbers and have gasket (8) between them for sealing. Forthat reason, microfluidic chip (1 ) geometry is of compatible form and size with channel (2). Outer geometry of microfluidic chip (1) is preferably in rectangular prism to facilitate side by side order of microfluidic chips (1 ) and continued line formation of channels located therein. Gaskets (8) shown in Figure 5 having holes in the shape of parts in the Y-Z plane of mini microfluidic chips (1) and having alignment housing are placed between the mini microfluidic chips (1) located into guide housing (5) in the device main table. The gaskets (8) can be made from any flexible material such as silicone, rubber, nytril, nytryl-rubbery, synthetic rubbery, polyurethane and derivatives, PTFE (polytetrapholorethylen), polyoxymethylene which provides sealing when compressed and of resistance does not get affected by chip process chemically shaped by laser cut technique, blade cut or injection forming technique. As shown in figure 7, microfluidic chips (1 ) of demounted form and gaskets (8) are put into guide housing (5) in order to complete mounting works in the housing. In another application, gaskets (8) sequenced in guide housing after inserted into pins that can be provided on microfluidic chips (1). Main table (7) can be of sizes enabling placement of microfluidic chip (1 ) in 10 to 200 pieces. Sizes of the guide housing (5) in the main table (7) can be adjustable to needed microfluidic chip (1) sizes.

Mini microfluidic chips (1) and gaskets (8) located into guide housing (5) are tightened by means of tightening caps (9) shown in demounted and mounted forms in figure 7 and fixed in full mounted status into housing as shown in figure 11 . microfluidic chips (1 ) have two tightening compression caps (9) tightening them for each main table (7). As shown in figure 6 tightening caps (9) have a compressing part (10) entering guide housing (5) in main table (7). Tightening caps (9) aligned into guide housing (5) are tightened by means of compression units (14) as shown in figure 7 characterized preferably by bolt and through connection hole (13) as shown in Figure 6 and from both sides by female bolt housing (6) shown in figure 3 towards device main table (7). Clips that can be manually tightened can also be used instead of bolt. Purpose of tightening is to obtain leakage proof along microfluidic chip (1) channels (2) and provide transfer of liquids to be applied externally to lines without loss. As shown in figure 6 tightening caps (9) have feeding holes (11) located therein in a mannerto be aligned to channels (2) of microfluidic chips (1). While one side of feeding holes (11 ) is connected to microfluidic chip (1) channel (2) lines by means of gasket (8) shown in figure 7, other side has discharge connections (12) where liquid feeding or discharge pipes can be fitted as shown in figure 6. As feeding and outlet channels of each channel line on chip are separate, connection pipes (16) shown in figure 7 provide connection of channels (2) one another and thus allows various connection probabilities such as not using designated channels (2). Device main table (7) and tightening caps (9) can be produced from metal materials eligible for machining such as aluminium, steel, copper or polymer materials that can be processed such as poly oxy methilene, cestamide, polypropylene, polyamide, PTFE.

Raw material to be used for manufacture of microfluidic chips (1) and chemical treatments and chemical solvents to be applied onto chips can be of different types depending on purpose of use of chips. For such treatments, bases such as sodium hydroxide, polymers such as polyethylinimine, cross-binding molecules such as glutaraldehyde malemiyde, vairous solvent types such as proteins can be used. Different temperature requirements may be needed during application of different solvents. For instance, while increase in temperature enhances surface activation in sodium hydroxide solvents used to for active surface in PMMA materials, it decreases activation period. On the other hand, a special temperature such as 37‘C or +4 ‘C may be needed for protein coating onto microfluidic chip (1 ) surfaces (3). In order to respond to such process parameters, device system of the invention has a heating cooling table (20) of which cross-section view is given in figure 9. Heating cooling table (20) comprises winter paths (22) wherein water, oil and similar liquids can flow, and inlet-outlet connections (23) as shown in figure 9. The liquid heated or cooled at an external circulation bath is supplied into heating cooling table (20) via a convenient connection apparatus and located under device main table (7). As shown in figure 8 heating cooling table (20) from side part having connection part, it comprises a jacket housing (21 ) matching outer geometry of device main table (7) and provides fully seating of main table (7) onto surface. Main table (7) can be located on both surfaces of heating cooling block. Main table (7) remaining between heating cooling blocks are surrounded by these blocks. With this feature, both homogenous heat distribution in microfluidic chips (1) located along guide housing (5) is provided and also with help of more than one main table (7) located on one another, number of microfluidic chips (1) processed in unit volume is increased and advantage in industrial production is achieved. In addition, extra heating oven or chamber is not needed. microfluidic chips (1) are placed in device system and after tightening caps (9) are tightened, liquid connections intended to be used inside microfluidic chips (1) can be connected to channel inlets (15) required to be provided on tightening cap (9) as shown in figure 7. For supply of liquid into channel line or circulation of the liquids, various pump systems (17) such as peristaltic pump, piezoelectric pump, injection pump can be used in transfer connection hoses (18) between liquid chamber (19) and tightening cap (9). The liquids supplied to desired chip (1) channel (2) lines are collected from outlet connections and given to same liquid chamber (19) again and thus circulation can be provided. The purpose herein is to provide continuous flowing of applied liquid. Thus thermodynamically occurrence of low energy areas that can occur around surfaces close to micro level of microfluidic chips (1) is prevented, temperature distribution is balanced and probability of encountering of chip surface (3) with chemicals is increased. This provides application of mini microfluidic chips to chemical treatments by use of more effective and repeatable processes. The continued flow inside microfluidic chip (1) channels (2) do not need additional shaking or mixing as it generates continued mixing effect. Device system of invention not requiring additional oven, incubation chamber, shaking device provides achievement of a compact structure.

To enable application of chemicals different from one another, each chemical chamber my use a separate pump or transmission can be provided by use of a single pump by means of opening -closing a valve system for chambers organized as required. In addition, connection pipes (16) feeding the same pump are immersed into liquid chambers (19) containing different chemicals and thus passing of different chemicals through the system can also be provided. Pump systems (17) providing positive pumping can be used in the system as well as pump systems (19) performing collection of liquid into chamber (19) on outlet side of channels can be used. When chemicals or proteins not required to make circulation in the system are used, liquid is injected in the desired line of tightening cap and thereafter both ends of the line are closed by a plug or valve and thus vaporization is prevented.

Claims

1. A device system for mini microfluidic chips production method in medical device industry characterized by comprising;

• microfluidic chip (1) of multiple number in single part prismatic form and sequenced side by side whereon chemical operations are applied,

• at least a channel (2) located on microfluidic chip (1 ) and providing conduct of desired coating on the surface,

• chip surface (3) functioning as mounting surface on microfluidic chip (1),

• hole (4) passing through microfluidic chip (1 ) from top to end,

• guide housing (5) wherein microfluidic chips (1 ) are sequenced in order,

• main table (7) having guide housing (5) and supporting for alignment and tightening of microfluidic chips (1),

• tightening cap (9) applying compression from both sides onto microfluidic chip (1) series sequenced in said guide housing (5) and establishing sealing,

• compression part (10) located on said tightening cap (9) and connected to microfluidic chips (1),

• feeding holes (11) located inside said tightening cap (9) and providing fluid inlet and outlet,

• compressing unit (14) connected to main table (7) and applying pressure onto tightening cap (9),

• female bolt housing (6) providing bolt connection between tightening cap (9) and main table (7),

• connection hoses (16) providing fluid passing between different channel lines formed by microfluidic chips (1 ),

• connection hole (13) located in tightening cap (9) wherein said tightening unit (14) passes,

• pump system (17) located on microfluidic chip (1 ) and providing conduct of desired coating onto the surface and capable to pump liquid into channels (2) or sucking liquid,

• liquid chamber (19) having desired liquid to be given to microfluidic chip (1 ) channel system,

• transmission connection hoses (18) providing fluid flowing between said liquid chamber (19) and the system, • channel inlet (15) providing connection of feeding holes (11) passing through said tightening cap (9) and connection hoses (23),

• discharge connections (12) providing connection between tightening cap (9) and connection hoses (18),

• heating cooling table (20) performing heating and cooling operation providing temperature balance of main table (7) and surrounding the table,

• jacket housing (21) providing seating of heating cooling table (20) onto main table (7) from bottom and/or top.

• inlet-outlet connections (23) providing entering of fed liquids into and/or leaving heating cooling table (20),

• fluid flow channels (22) located inside heating cooling table (20).

2. The system according to claim 1 characterized in that said microfluidic chips (1) being made from thermoplastic polymers, PDMS or glass material.

3. The system according to claim 1 characterized in that said holes (4) being fully cylindrical, rectangular, ellipsoid when viewed from Y-Z plane or flat and side sections of bottom and top parts being in arc shape.

4. The system according to claim 1 characterized in that length of microfluidic chip (1) in Y axis being between 10 mm and 100 mm subject to number of channels (2) desired to be therein.

5. The system according to claim 1 characterized in that height of said microfluidic chip (1 ) in Z axis being in range of 2 mm and 10 mm in order to have high optical permeability.

6. The system according to claim 1 characterized in that length of microfluidic chip (1) in X axis being of same size as the channel (2) where located and being between 2 mm and 20 mm.

7. The system according to claim 1 characterized in that height of channel (2) inside said microfluidic chip (1 ) parallel to Z axis on Y-Z plane being in range of 0,1 mm to 5 mm.

8. The system according to claim 1 characterized in that width of said channel (2) parallel to Y axis on Y-Z plane being in range of 0,1 mm to 10 mm.

9. The system according to claim 1 characterized by comprising gasket (8) of convenient geometry with holes (4) located on microfluidic chip (1) and providing sealing.

10. The system according to claim 1 characterized in that said gaskets (8) being made from any flexible material such as silicone, rubber, nytril, nytryl-rubbery, synthetic rubbery, polyurethane and derivatives, PTFE (polytetrapholorethylen), polyoxymethylene which provides sealing when compressed and of resistance does not get affected by chip process chemically shaped by laser cut technique, blade cut or injection forming technique.

11. The system according to claim 1 characterized in that said main table (7) and tightening caps (9) being produced from metal materials eligible for machining such as aluminum, steel, copper or polymer materials that can be processed such as poly oxy methylene, cestamide, polypropylene, polyamide, PTFE.

12. The system according to claim 1 characterized in that said compression unit (14) being bolt/clip/press.

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