A method for manufacturing microfluidic systems for medical diagnostics in thin-layered polyester materials and a microfluidic system for medical diagnostics manufactured by the method

Abstract

The object of the invention is a method for manufacturing microfluidic systems for a medical diagnostics of the Point-of-care type in thin-layered polyester materials, including designing of the geometry of layers in the microfluidic system, cutting out micropatterns, binding the layers and testing the tightness of the system, characterized in that as the polyester material are used the polyester films for medical applications, selected from a group containing of hydrophilic films and films coated on at least one side with an acrylic adhesive layer on which micropatterns are manufactured using laser microprocessing, further the foils are placed in alternated way to form layers, are aligned and are combined in a holder, wherein the micropatterns, after bonding of the film layers, form microfluidic microstructures with a resolution of at least 25 μm and maximum height of a partial-melting of the material of 20 μm, and a microfluidic system for medical diagnostics manufactured by this method.

Description

[0001] A method for manufacturing microfluidic systems for medical diagnostics in thinlayered polyester materials and a microfluidic system for medical diagnostics manufactured by the method

[0002] The object of the invention is a method for manufacturing microfluidic systems for medical diagnostics of Point-of-care (POC) type in thin-layered polyester materials, in particular for use in immunoassays with electrochemical and colorimetric detection and a microfluidic system for medical diagnostics manufactured by this method.

[0003] Lab-on-a-Chip devices have recently been attracting increasingly more interest. On one hand, global health care needs readily available and rapid tools for medical diagnostics to be able to detect new diseases. On the other hand, industry requires inexpensive tools that could be easily manufactured. Lab-on-a-Chip devices fulfill these requirements, and their attractiveness results first of all from the reduced volume of the sample needed to perform analysis, and this leads to advantages of reduced volumes of reagents necessary for the analysis and for biological reagents (enzymes, antibodies, etc.), the benefit from reduced volumes may be very significant. Another consequence resulting from the reduced volume of reagents and the microscopic dimensions of the reaction space is the improved transport of mass and energy which results in a shorter time of analysis, reduced energy demand of such microdevice and lower quantities of materials at the stage of production which is important in ultimate economic analysis.

[0004] The manufacturing technologies for Lab-on-a-Chip microdevices originate from electronic industry and they were initially derived from silicon processing technology based on photolithography, subsequently silicon was replaced with glass. Those materials could be used to manufacture highly precise microstructures, but the manufacturing step was very time and labor intensive. In addition, the prices of glass-based substrates were relatively high, and with respect to silicon this prevented mass production.

[0005] Therefore, poly(dimethyl siloxane) (PDMS) started gaining considerable popularity as the starting material for manufacturing Lab-on-a-Chip microdevices. This is a type of silicon elastomer whose cross-linking occurs in a block after the monomer and the cross-linking agent are blended. Owing to the material, it became possible to manufacture microsystems without a need for having complex and expensive infrastructure for photolithography. Manufacturing an appropriate mold was the key stage in the manufacturing of PDMS-based microdevices. Techniques based on photolithography, soft lithography based on capillary film, laser processing or mechanical means, such as milling or using a cutting plotter, could be used for this purpose. Another advantage of PDMS was its oxygen permeability, which was particularly important when manufacturing microdevices dedicated to biological applications. However, this was still a relatively expensive material, and relevant processing technologies were characterized by the low productivity, which practically disqualifies it as a universal material to be used in microdevices.

[0006] Plastic materials, mainly of the group of thermoplastic materials, are currently the most widely used materials. This results from the broad availability of thermoplastic materials and their extensive variety; therefore, materials having varied physical or chemical properties can be used depending on the requirements of the analytical procedure used in the microdevice.

[0007] The technologies used for processing plastic materials are widely used in various branches of industry; these include for example injection molding and hot embossing. Mentioned technologies have high molding efficiency for respective parts, which, in combination with low prices of the raw materials, results in a low cost of a single part. As with the technology based on PDMS, designing an appropriate mold is a key aspect. Because the raw material is injected at high temperature and pressure conditions, steel molds are predominantly used but they are time-consuming and very expensive to manufacture. This technology is ideal in the conditions of a high throughput manufacturing when the final product is not modified in any way and, therefore, microdevices using the technology are not very universal. It is also to be noted that the stage of sealing microfluidic systems, known as bonding, that is, a process that involves combining two or more layers, is a limitation for all aforementioned technologies. Various approaches are used depending on the type of material. For silicon or glass, anodic bonding or direct thermal bonding is typically used. Furthermore, PDMS is bonded mainly after pre-activation of its surface with oxygen plasma. Thermoplastic materials, in turn, are typically bonded through direct thermal bonding or universal methods based on an adhesive may be used. However, most of the techniques are time-consuming, which result from the need for appropriately aligning the bonded elements with respect to one another and, on the other hand, from the need for using rather mild bonding conditions to avoid any deformation of microstructures. Therefore, automation of the process is rather complex and constant supervision is needed. Even if the mildest conditions possible are used, the methods frequently cannot be combined with analytical procedures based on biological reagents (such as antibodies) due to negative impact. Owing to the contactless type of laser processing, patterns of a very small geometry can be cut, which is difficult to achieve using traditional mechanical means. The presented manufacturing technology of the invention enables microstructures to be manufactured with a high degree of dimensional accuracy using the contactless feature of laser cutting which significantly reduces deviations from the predefined design during processing. The PET films from 3M company used in the object of the invention absorb electromagnetic energy with a wavelength of 9.3 pm much more effectively than other laser wavelengths (typically 10.6 pm) and, therefore, the area in which the laser beam interacts with the material is reduced, which presents a positive aspect of the technology in the context of differences presented in the art. For PET films, it is most preferred to use a laser system which emits electromagnetic radiation with a wavelength of 9.3 pm. However, reports on the use of systems which emit radiation with a wavelength of 10.6 pm are most commonly found in the scientific literature. Even though readily commercially available, laser plotters having such parameters have a lower quality of resulting structures, because the effect of photothermal interaction is seen in the greater number of defects in a form of e.g. a partialmelting of the material. This may for example result in the reduced lumen of the channel (for very narrow structures) or its heterogeneous profile and, therefore, uneven distribution of pressures in the diagnostic cassette, which may lead to a false result of analysis. The other common undesirable effect of laser microprocessing is the formation of a partial-melting of the material on the surface at the edges of the microstructures being cut. These height differences (between the highest point of the partial-melting and the baseline on the surface of a PET film layer) result in the lack of tightness between respective layers of an assembled diagnostic cassette which, therefore, also rules out its use in POC testing.

[0008] Reports known in the art present the use of CO2 laser processing as a technology for mechanical plastic processing, but they typically concern poly(methyl methacrylate) PMMA and the 10.6 pm configuration (e.g. Yingjie Liu et al., “DNA Amplification and Hybridization Assays in Integrated Plastic Monolithic Devices”, Anal. Chem., 2002, 1; 74(13):3063-70). In addition, the application of laser processing frequently concerns one of many layers in a hybrid device, while other layers are manufactured using a different technology, such as UV photoablation, and using other materials, such as polycarbonate. In addition, thermal bonding under pressure (139 deg., 2 tons) is used in known solutions, which cannot be applied when biosensitive and temperature sensitive materials are found inside the diagnostic cassette still before the layers are bonded as in the case when using immunoenzymatic assays based on antibodies in POC diagnostic cassettes. Information about the use of laser microprocessing technology for mechanically manufacturing patterns in microdevices can be found in the scientific literature. For example, in Hennig K. et al. “CO2-laser micromachining and back-end processing for rapid production of PMMA-based microfluidic systems”, Lab Chip, 2002, 2, 242-246, an immense potential of a CO2 laser system for the rapid production of microfluidic structures manufactured in polymer - PMMA, using a Synrad laser system is presented, without any specifics provided of the optical system in terms of the radiation source used (beam wavelength), what constitute a critical parameter for the electromagnetic radiation absorption process in materials.

[0009] It is known from Saied Assadollahi et al. “From Lateral Flow Devices to a Novel NanoColor Microfluidic Assay”, Sensors 2009, 9, 6084-6100, to use co-polyester hydrophobic PET films with a thickness of 0.6 mm as well as laser ablation with the following optimized parameters: resolution: 500 dpi, laser power: 70%, speed: 55 mm / s, offset (focus): 0.1 and 3 cycles of processing. Initially, the device constructed by the authors was made from a PET film sheet coated with a thin adhesive film. Therefore, the whole assembly did not have desired stability and strength required for handling. Ultimately, a double-adhesive film was used. Nevertheless, there is no information about the developed technology, that is, catalog numbers of the materials used, power and optical configuration of the laser system, thickness of the adhesive tape or dimensions of manufactured structures. Furthermore, for the traditional assay (LFA) developed by the authors, alignment of layers was not used either because this was not needed due to the simplicity of the device.

[0010] Information about products based on PET materials for biomedical applications can be found at manufacturers’ websites: https: / / www.strouse.com or https: / / www.3m.com, but only basic characteristics (mainly dimensional) of the materials are available and their processing technology is not disclosed.

[0011] From Zhuolun Meng et al. “A Smartphone-Based Disposable Hemoglobin Sensor Based on Colorimetric Analysis”, Sensors 2023, 23(1), 394, a diagnostic test is known which uses a microfluidic cassette for assaying hemoglobin based on colorimetry and a smartphone camera. The cassette presented in the publication is made from a film for medical use and filtration paper as well as a PDMS micropump, wherein a single channel with a chamber is manufactured in 3M 9962 and 9965 films using a Boss LS-1420 “hobby” laser cutter. Processing in the 3M 9965 adhesive tape was performed using the following parameters: MinPower (%)-l : 14, MaxPower (%)-l : 14, speed (mm / s): 9). The 3M 9962 film is used only as a sealing which does not undergo mechanical processing. The authors of the publication do not disclose any technical parameters of laser processing, such as laser power and wavelength of the electromagnetic radiation generated by the CO2 tube.

[0012] The object of the invention is to develop a novel method for manufacturing microfluidic devices, for a specific purpose of a microdevice to a medical diagnostic of the Point-of-care type that can be adopted to the mass production for the manufacturing of cheap, single use tests / diagnostic cartridges.

[0013] The object of the invention is a method for manufacturing microfluidic systems for a medical diagnostics of the Point-of-care type in thin-layered polyester materials, including designing of the geometry of layers in the microfluidic system, cutting out executive elements of the micropatterns, manufacturing the alignment system of the layers, bonding the layers and quality control involving testing the tightness of the system, characterized in as the polyester material are used the polyester films for medical applications, selected from a group containing of hydrophilic films and films coated on at least one side with an acrylic adhesive layer on which micropatterns are manufactured using laser microprocessing, further the foils are placed in alternated way to form layers, are aligned and are combined in a holder, wherein the micropatterns, after bonding of the film layers, form microfluidic microstructures with a resolution of at least 25 pm and maximum height of a partial-melting of the material of 20 pm.

[0014] Preferably, when a transparent film with hydrophilic coating on both sides whose total thickness is 90 pm is used in the method of the invention as the hydrophilic polyester film.

[0015] Preferably, when a film coated with an acrylic adhesive layer on both sides whose total thickness is 86 pm is used as the polyester film coated with an adhesive layer.

[0016] Preferably, when at least three layers of polyester films are alternately bonded with one another, preferably at least two layers of the film with hydrophilic coating on both sides are bonded with one film coated with an adhesive layer on both sides.

[0017] Preferably, when a laser system emitting radiation with a length of 9.3 pm, power of 30-35 W, cutting speed of 10% and the PPI parameter of 800 is used for laser microprocessing.

[0018] Preferably, when a compressed air flow with a pressure of 2 bar is used.

[0019] Preferably, when the micropatterns are cut out in the film coated with an adhesive layer which is bonded on both sides with films having hydrophilic coating on both sides.

[0020] Preferably, when confocal 3D surface topography imaging is used for testing system tightness in the method of the invention.

[0021] Preferably, when a holder in the form of a flat plate with 4 bars having 2.5 mm in height located in the corners, wherein the bar diameter at the top is 1.525 mm and that at the base is 1.575 mm, is used in the method of the invention for the alignment of layers before bonding.

[0022] Preferably, when low-temperature lamination, which is preferable because temperaturesensitive biologically active components are located inside the microsystems, is used in the method of the invention for bonding layers.

[0023] Another object of the invention is the microfluidic system for the medical diagnostics of the Point-of-care type manufactured in thin-layered polyester materials using the method of the invention, which comprises at least three layers of polyester films bonded to one another in an alternate pattern in which microfluidic microstructures with a resolution of at least 25 pm and a maximum height of a partial-melting of the material of 20 pm are fitted, wherein aligning openings are placed in the layers of polyester films, moreover, the microsystem contains a top layer placed on the polyester layer being a hydrophilic film in which inlet and outlet openings are placed.

[0024] An advantage of the method of the invention is that polyester films having hydrophilic and adhesive properties are used as construction materials in order to manufacture the microscopic diagnostic devices as well as a laser plotter with a CO2 gas tube with a power of 30-35 W and a wavelength of the emitted beam of 9.3 pm is used for the microprocessing of the materials. The absorption of electromagnetic radiation by the processed material is the lowest in this wavelength range, what minimizes defects in microfluidic structures formed as a result of the thermal effect of the laser beam. The use of a laser system equipped with a special optical system consisting of a collimator and a set of lenses is the key and integral step of the method for manufacturing microstructures in polyester films of the invention, because laser power density in this arrangement is increased, and the laser beam is focused in a smaller spot, what results that the microfluidic parts are manufactured with high precision and resolution.

[0025] Advantage of the method of the invention is that it facilitates quality control of the structures being manufactured via 3D imaging using a laser confocal microscope and a method for the connection of thin-layered microsystems with an element that induces liquid flow (a syringe / peristaltic pump). In addition, the method of the invention allows highly effective, easy and rapid manufacturing of microsystems for medical diagnostics with practically any geometry having resolution determined by the resolution of the laser system. The easy design and manufacturing of the microsystems of the invention is a significant innovation in terms of the fast prototyping of the microdevices of the Point-of-care type. Compared to the commercially available tools, specialized laboratory facilities as needed for photolithography based technology or hot embossing technology are not required. In addition, the microsystems manufactured according to the invention have low unit manufacturing cost because widely available and inexpensive materials offered by various manufacturers are used. The films are available in many options in terms of thickness and surface properties and their processing methods can be easily adapted to large scale manufacturing. In addition, the available films have medical certificates so that the whole commercialization process of a medical product is much more streamlined.

[0026] The polyester films having hydrophilic properties of the invention ensure qualitatively better filling of the microstructures with aqueous solutions, more easy displacement of air and less susceptibility to the retention of air bubbles, in particular in dead volumes. Air bubbles presence is the factor that affects analytical conditions, such as by disrupting the mixing of two streams, and is the factor that prevents determination of an analyte when it is combined with electrochemical or optical detection methods.

[0027] The use of thin-layer PET films of the invention is extremely beneficial and economically justified in the manufacture of POC diagnostic tests / cassettes for which the technology has been developed. Commercially available products in this area typically use thermoplastic materials and an injection method which is costly and labor-intensive in manufacturing the base mold. As a result, the cassettes are rather sizeable, which results in the increased consumption of reagents and construction materials and the price of a single test is high.

[0028] The invention was illustrated with a help of the figures placed in the drawing, among which:

[0029] Fig. 1 shows a photograph of a microstructure manufactured in a 3M 9965 double-adhesive film using a VLS 2.30 laser system equipped with an HPDFO module and LTT Vi30.

[0030] Fig. 2 presents a scheme of the geometry of the microsystem of the invention, from left: 1 hydrophilic layer, 2 adhesive layer, 3 hydrophilic layer, wherein: 4 indicates aligning openings, 5 indicates a microfluidic structure, 6 indicates inlet openings of the microsystem, 7 indicates an outlet opening of the microsystem.

[0031] Fig. 3 shows an Olympus LEXT OLS4000 confocal microscope photograph which presents the topography of the 3M™ polyester film after laser processing: the cross section of a microchannel.

[0032] The invention is illustrated by the embodiments shown below which are not limiting in any way, and their purpose is only to illustrate the invention.

[0033] Example 1

[0034] Films having hydrophilic / hydrophobic properties and adhesive properties are offered by various manufacturers and have different thickness options. Commercially available polyester films are offered by manufacturers, such as 3M™, Coveme, Adhesive Research. They have special certificates so that they can be easily implemented in health care products (such as diagnostic strip tests or medical devices). In the method of the invention, two types of thin-layered polyester films from 3M™ were preferably selected as the construction material of the microfluidic systems. A transparent polyester film with hydrophilic coating on both sides (3M™ 9962) and thickness of 90 pm and a polyester film coated with an acrylic adhesive layer on both sides (3M™ 9965) and thickness of 86 pm, which is additionally coated with additional protective layers. Both materials are intended for medical devices and they can be used for transporting liquids in strip tests or Lab-on-a-chip designs.

[0035] In the presented method of the invention, the polyester films are stored in a form of rolls protected from humidity and light (room temperature, relative humidity: 40% - 60%) before being processed. The expiry date of hydrophilic films is one year after the manufacturing date. After this period the manufacturer does not guarantee the preservation of properties particularly the wetting angle at the original level. Whereas, the storage period of adhesive films is longer (owing to the use of protective layers), up to two years.

[0036] The method for manufacturing microfluidic systems for medical diagnostics in thin-layered polyester materials of the invention consists of four main stages: i) designing the geometry of layers in the microfluidic system, ii) cutting out micropattems in polyester films using a laser plotter, iii) binding the layers with one another (bonding process), iv) testing the tightness of the microsystem manufactured using a laser plotter with a CO2 gas tube having a power of 30-35 W and a wavelength of the emitted beam of 9.3 pm, and a cutting speed of 10%, PPI parameter equal 800 and compressed air flow at a pressure of 2 bar.

[0037] The design of the geometry of the diagnostic microfluidic system may be created using any graphics design software for creating and editing vector graphics (such as CorelDRAW®, AutoCAD®, SolidWorks®), afterwards the design is exported directly from graphic software or indirectly via an appropriate format (such as pdf) to the software of the laser plotter. To achieve effective cutting of high-quality microstructures, necessarily processing parameters need to be optimized and adjusted to a specific material. The optimization includes cutting speed (movement of the lens carriage), laser power and PPI (number of laser pulses generated per a length of 1 inch). In order to obtain structures with the desired quality it is necessary to use of the axial air flow or inert gas on the zone of interaction of laser radiation with the material being processed. Owing to a stream of compressed air with a pressure of 2 bar, no smoke residue in the material due to thermal interactions between the material and the laser beam remains on the polyester film being processed, and further the air flow minimalizes the zone of thermal interaction of laser radiation.

[0038] After the microfluidic layers of the invention have been completed, precision of the realization should be inspected. In the process of optimization and selection of the parameters of the laser micromachining the microscopy methods are preferably used. The best effect is achieved using a laser confocal microscope, for example from the Olympus LEXT OLS 3000 (alternative - Keyence VHX7000 system) that provides 3D imaging with very high resolution. Owing to this quality control, it can be assured that the layers in polyester films manufactured using laser microprocessing have no defects (e.g. in the form of a partial-melting of the material due to thermal effects) and they may be tightly bonded with one another in the low-temperature lamination process, which is a highly effective bonding method, that involves bonding the layers by applying appropriate pressure. This can be achieved in this case owing to the multi-layered and alternated layer design of the diagnostic microfluidic system (hydrophilic layer / adhesive layer). In addition, low- temperature lamination (at room temperature) is extremely favorable and practically applicable for bonding structures, wherein one of the layers in a diagnostic cassette is a biosensitive layer with immobilized biologically active substances which would be destroyed at temperatures as high as 100°C. Temperatures above 40°C would already be dangerous in terms of protein denaturation and stability of other reagents. After the stage of layer bonding of the invention, tightness of the microfluidic system is tested by passing liquid, such as water, through the microstructures. For this purpose for example, syringe pumps (for example KD Scientific LEGATO® 100) or peristaltic pumps (for example Ismatec® REGLO ICC) are used. Tygon-type thermoplastic tubing and a special interface that enables contact between the tubing end and the microsystem inlet, in the form of, for example, a nanoport with a capillary on which the tubing is fitted, are used for connecting the pump with the microfluidic system. Another solution is a direct connection via an adapter in which stub tubes are fitted onto which the tubing is fitted, wherein the adapter with a thickness of several millimeters is manufactured from polymer, e.g. PMMA, PEEK, PVC in a micromilling process. The nanoports or adapters with stub tubes constitute the upper layer of the microsystem and an adhesive layer is needed to connect it with the actual microsystem. Both solutions differ, because tubing with various internal diameters can be used.

[0039] Various laser systems were tested during the development of the method of the invention: LTT Vi30 (9.3 and 10.6 pm), GCC Spirit LS (9.3 and 10.6 pm) and Universal Laser System (9.3 pm) in terms of their usefulness for manufacturing diagnostic cassettes. In spite of an improved construction quality of microfluidic structures using a light source emitting a laser beam of a length of 9.3 pm for the GCC laser system, the dimensions of defects formed still significantly exceeded the defined experimentally acceptable 25 pm. Therefore, it was decided to test a laser system based on an optical system ensuring an extremely focused laser beam, thereby enabling very precise cutting of materials. The laser system used, manufactured by Universal Laser Systems, is equipped with an HPDFO (High Power Density Focusing Optics) system consisting of a collimator and a specially designed set of lenses. The collimator widens and straightens the beam that leaves the laser and subsequently focuses the laser beam using the HPDFO unit in a spot much smaller compared to standard optical systems with increased laser power density. Owing to a lower diameter of the laser beam (of 30 pm), higher resolution for manufacturing microstructures in the 3M 9965 film was obtained, which, in combination with the use of the axial air flow, resulted in no formation of “partial-melting” or “singe” of the adhesive film material on the edges compared to the LTT Vi30 laser system (Fig. 1). Therefore, acceptable dimensions of the microstructure were obtained, which translated into its effective bonding with hydrophilic layers.

[0040] The relationship between the width of the channels in terms of beam power and number of beam passes in the same channel was evaluated during process optimization of laser processing. Laser beam power was changed in the experiments in a range of between 3 and 4.5 W for the VLS 2.30 laser system (30 W, 9.3 pm) and between 4.5 and 10.5 W for the ULTRA X6000 laser system (30 W, 9.3 pm), and passes changed between 1 and 5 times. A typical channel had a width of about 55 pm (VLS 2.30), while the narrowest channel formed had a width of about 30 pm (ULTRA x6000), which means that the developed method can provide dimensionally much smaller structures than the solutions presented in the scientific literature (Table 1).

[0041] Table 1. List of the effect of laser processing parameters on the width of microchannels.

[0042] Example 2

[0043] The topography shown in Fig. 2 presents a four-layer structure of an example microfludic system obtained according to the invention which consists of a polyester film layer with hydrophilic coating on both sides (manufacturer: 3M™, catalog no.: 9962) and total thickness of 90 pm which serves as the underlying surface of a microreactor. Biological reagents, such as antibodies, the primary ingredient of enzyme-linked immunoassays, based on which diagnostic tests are performed in microdevices can be adsorbed on the microreactor surface after appropriate local modification before bonding. The intermediate layer of the microsystem is a polyester film coated with a thin acrylic adhesive layer on both sides (manufacturer: 3M™, catalog no.: 9965) and total thickness of 86 pm in which pass-through openings and a network of microchannels 5 to facilitate liquid transport with the reaction zone (microreactor) are made. The top layer of the microsystem is again the hydrophilic 3M™ 9962 film which has a sealing role in which openings serving as an inlet 6 and an outlet 7 of the microfluidic system are made only. Aligning openings 3 were also included in all layers at the design process stage to ensure precise binding of layers in the low- temperature lamination process which involved aligning and binding respective layers in the holder and subsequently applying pressure using a silicon roller to bond the layers, wherein the holder was made in the PEEK material using precise micromilling using a DATRON neo series2 milling machine in the form of a flat plate with 4 bars having 2.5 mm in height located in the comers, wherein the bar diameter at the top was 1.525 mm and that at the base was 1.575 mm.

[0044] Respective microstructures were manufactured using an ULTRA X6000 (Universal Laser Systems) laser system assisted by compressed air of a pressure 2 bar with the following parameters for the 3M™ 9962 film:

[0045] • Power: 30%

[0046] • Speed: 10%

[0047] • PPI: 800 and for the 3M™ 9965 film:

[0048] • Power: 35%

[0049] • Speed: 10%

[0050] • PPI: 800.

[0051] Subsequently, precision of the result was inspected to ensure that no defects that would prevent subsequent sealing of the layers were present. The quality control was performed using an Olympus LEXT OLS4000 3D confocal microscope system. Confocal laser microscopy is used for contactless 3D observations and measurements of surface features in high resolution. The technology was used to obtain microscopic images of the film surface after laser microprocessing. Height differences between the flat film surface and the microchannel edge were observed (height of a partial-melting of the material formed because of thermal interactions between the laser beam and the polyester film). Fig. 3 shows example photographs presenting the topography of section surfaces of the materials after laser processing, and it was found that the maximum height of a partial-melting of the material (difference between the highest point at the microchannel edge and the flat film surface as the baseline) on the edges of the cut-out parts was 20 pm. The data were obtained from calculations based on the resulting cross-sectional profiles of film surfaces.

Claims

Claims1. A method for manufacturing microfluidic systems for a medical diagnostics of the Point- of-care type in thin-layered polyester materials, including designing of the geometry of layers in the microfluidic systems, cutting out micropatterns, binding the layers and testing the tightness of the system, characterized in that as the polyester material are used the polyester films for medical applications, selected from a group containing of hydrophilic films and films coated on at least one side with an acrylic adhesive layer on which micropatterns are manufactured using laser microprocessing, further the foils are placed in alternated way to form layers, are aligned and are combined in a holder, wherein the micropatterns, after solidification of the film layers, form microfluidic microstructures with a resolution of at least 25 pm and maximum height of a partial-melting of the material of 20 pm.

2. A method of claim 1, characterized in that a transparent film with hydrophilic coating on both sides whose total thickness is 90 pm is used as the polyester hydrophilic film.

3. A method of claim 1, characterized in that a film coated with an acrylic adhesive layer on both sides, whose total thickness is 86 μm, is used as the polyester film coated with an adhesive layer.

4. A method of claim 1 or 2 or 3, characterized in that at least three layers of polyester films are alternately bonded with one another, preferably at least two layers of a film with hydrophilic coating on both sides are bonded with one film coated with an adhesive layer on both sides.

5. A method of any of claims 1 to 4, characterized in that a laser system emitting radiation with a length of 9.3 μm, power of 30-35 W, cutting speed of 10% and the PPI parameter of 800 is used for laser microprocessing.

6. The method of claim 5, characterized in that compressed air flow with a pressure of 2 bar is used.

7. The method of claim 5, characterized in that the micropatterns are manufactured in the film coated with an adhesive layer which is bonded on both sides with films having hydrophilic coating on both sides.

8. The method of any of claims of 1 to 7, characterized that confocal 3D surface topography imaging is used for testing system tightness.

9. The method of any of claims 1 to 8, characterized in that a holder in the form of a flat plate with 4 bars having 2.5 mm in height located in the corners, wherein the bar diameter at the top is 1.525 mm and that at the base is 1.575 mm, is used for the alignment of layers before bonding.

10. The method of any of claims 1 to 9, characterized in that low-temperature lamination is used for bonding layers.

11. A microfluidic system for the medical diagnostics of the Point-of-care type manufactured in thin-layered polyester materials using the method of any of claims 1 to 10, characterized in that it comprises at least three layers of polyester films (1, 2, 3) bonded to one another in an alternate pattern in which microfluidic microstructures (5) with a resolution of at least 25 μm and maximum height of a partial-melting of the material of 20 pm are fitted, wherein aligning openings (4) are placed in the layers of polyester films (1, 2, 3) moreover the microsystem contains a top layer placed on the polyester layer being a hydrophilic film in which inlet (6) and outlet (7) openings are placed.

Images