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Title:
LAB-ON-PCB DEVICE AND METHOD FOR MANUFACTURING THEREOF
Document Type and Number:
WIPO Patent Application WO/2024/088766
Kind Code:
A1
Abstract:
The present invention relates to Lab-on-PCB device (1), comprising a base layer (400), a printed circuit board (200) comprising a substrate (204) with a conductor structure (203), a first electronic component (206) being mounted on said substrate (204), and a first measuring electrode (209) being arranged on said substrate (204) at a sample contact area (208) at a first side of said substrate (204) and being electrically connected to said first electronic component (206) via said conductor structure (203), wherein said printed circuit board (200) is attached to said base layer (400) by means of an adhesion layer (300), and a microfluidic device comprising a first sample reservoir (101), a first channel (102) and a first reaction chamber (103), wherein said first reaction chamber (103) is in fluidic communication with said first sample reservoir (101) via said first channel (102), and said first reaction chamber (103) is in fluidic communication with said first measuring electrode (209), wherein said microfluidic device is formed by a first cover layer (100) arranged on said printed circuit board (200), and said first cover layer (100) comprises a first cavity or recess (101, 102, 103) forming at least partly said first sample reservoir (101), said first channel (102) and said first reaction chamber (103), wherein said substrate (204) comprises one or more through-going recesses (210) which encircles in part said reaction contact area (208), wherein a part of said first cover layer (100) and/or said adhesion layer (300) engages in said one or more through-going recesses (210), particularly in a form-fitting and/or fluid-tight manner.

Inventors:
BIHLER ECKARDT (CH)
NEUBAUER BIRGIT (DE)
HAUER MARC ROBERT (CH)
SCHMIDT GREGOR (CH)
Application Number:
PCT/EP2023/078277
Publication Date:
May 02, 2024
Filing Date:
October 12, 2023
Export Citation:
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Assignee:
DYCONEX AG (CH)
International Classes:
B01L3/00; B29C43/18; B29C43/36; B29C65/18; B32B3/26; B32B15/08; B32B17/10; B29C43/52
Attorney, Agent or Firm:
BIOTRONIK CORPORATE SERVICES SE / ASSOCIATION NO. 1086 (DE)
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Claims:
Claims

1. Lab-on-PCB device (1) comprising

- a base layer (400),

- a printed circuit board (200) comprising a substrate (204) with a conductor structure (203), a first electronic component (206) being mounted on said substrate (204), and a first measuring electrode (209) being arranged on said substrate (204) at a sample contact area (208) at a first side of said substrate (204) and being electrically connected to said first electronic component (206) via said conductor structure (203), wherein said printed circuit board (200) is attached to said base layer (400) by means of an adhesion layer (300), and

- a microfluidic device comprising a first sample reservoir (101), a first channel (102) and a first reaction chamber (103), wherein said first reaction chamber (103) is in fluidic communication with said first sample reservoir (101) via said first channel (102), and said first reaction chamber (103) is in fluidic communication with said first measuring electrode (209), wherein said microfluidic device is formed by a first cover layer (100) arranged on said printed circuit board (200), and said first cover layer (100) comprises a first cavity or recess (101, 102, 103) forming at least partly said first sample reservoir (101), said first channel (102) and said first reaction chamber (103), characterized in that

- said substrate (204) comprises one or more through-going recesses (210) which encircles in part said reaction contact area (208), wherein a part of said first cover layer (100) and/or said adhesion layer (300) engages in said one or more through- going recesses (210), particularly in a form-fitting and/or fluid-tight manner.

2. Lab-on-PCB device according to claim 1, wherein said substrate (204) comprised a first reservoir area (214) being aligned to and optionally in fluidic communication with said first sample reservoir, and a first channel area (212) aligned to and optionally in fluidic communication with said first channel (102), wherein said first sample area (208) and optionally said channel area (212) and/or said first reservoir area (214) are encircled in part by said one or more through-going recesses (210), wherein a part of said first cover layer (100) and/or said adhesion layer (300) engages in said one or more through-going recesses, particularly in a form-fitting manner. Lab-on-PCB device according to claim 2, wherein said printed circuit board (200) comprises a pair of electrode (211) being arranged on said substrate (204) in or adjacent said channel area (212), wherein said pair of electrodes is configured to manipulate a liquid within said first channel (102). Lab-on-PCB device according to claim 2 or 3, wherein said base layer (400) is at least partially transparent, particularly within an area that is aligned with said first reservoir area (214), said first channel area (212) and/or said first reaction chamber (208), wherein optionally said adhesion layer (300) does not cover said printed circuit board at an opposite side of said first sample area (214), said first channel area (212) and/or said sample contact area (208). Lab-on-PCB device according to any one of the preceding claims, wherein

- said first cover layer (100) comprises a thermoplastic material, preferably a polyester, e.g. a polycarbonate, polyethylene terephthalate, or a liquid crystal polymer, wherein said first cover layer optionally has a melting temperature which is lower than the melting temperature of said substrate, and/or

- said adhesion layer (300) comprises a thermoplastic material, wherein said adhesion layer optionally has a melting temperature which is lower than the melting temperature of the substrate (204). Lab-on-PCB device according to any of the preceding claims, wherein said conductor structure the substrate (203) comprises a first conductor layer arranged on said first side of said substrate (204) and a second conductor layer arranged on a second side of said substrate (204), wherein said first conductor layer and said second conductor layer are in electrically conductive communication via at least one via (205) Lab-on- PCB device according to any of the preceding claims, wherein the base layer (400) comprises at least one material of the group comprising a metal, a glass and a plastic material, wherein the material of the base layer (400) has a melting temperature which is higher than the melting temperature of the connection layer (300) and/or the cover layer (100). Lab-on- PCB device according to any of the preceding claims, wherein the device (1) further comprises a second cover layer (500) which is bonded onto, for example laminated onto, the cover layer (100), and wherein said second cover layer (500) covers at least partially said first thermoplastic cover layer (100), wherein particularly said second cover layer comprises a thermoplastic material. Lab-on-PCB device according to any one of the preceding claims, wherein said substrate (204) is made form or comprises an epoxy resin, a polyimide, or a liquid crystal polymer. Lab-on-PCB device according to any of the preceding claims, wherein said first electronic component (206) is selected from a resistor, a capacitor, a coil, or an integrated circuit. Method for manufacturing a lab-on- PCB device (1), comprises the steps of:

- providing a a printed circuit board (200) comprising a substrate (204) with a conductor structure (203), a first electronic component (206) being mounted on said substrate (204), and a first measuring electrode (209) being arranged on said substrate (209) at a sample contact area (208) at a first side of said substrate (204) and being electrically connected to said first electronic component (206) by said conductor structure (203),

- proving a first cover layer (100) comprises a first cavity or recess (101, 102, 103), wherein said first cover (100) forms a micro fluidic device comprising a first sample reservoir, a first channel and a first reaction chamber formed by said first cavity or recess (101, 102, 103),

- arranging a base layer (400), an adhesion layer (300), said printed circuit board (200) and said first cover layer (200) in a layer-by-layer arrangement such that said adhesion layer is arranged between said base layer (400) and said printed circuit board (200), and said first reaction chamber of said first thermoplastic cover (200) is aligned and in fluid communication with said sample contact area (208) of said printed circuit board,

- joining said base layer (400), said adhesion layer (300), said printed circuit board (200), and said thermoplastic cover (100), preferably by means of heat and optionally pressure, wherein said substrate (204) comprises one or more through-going recesses (210) which encircles in part said sample contact area (208), wherein a part of said thermoplastic cover layer (100) and/or said adhesion layer (300) fills said one or more through-going recesses during said joining, particularly in a form-fitting and/or fluid- tight manner. Method according to claim 11, wherein a mold (700) is arranged on said first cover layer (100) before said joining, wherein said mold (700) comprises a protrusion that fills said first recess or cavity (101, 102, 103) of said first cover layer (100), particularly in an essentially form-fitting manner. The method according to any one of claims 11 to 12, wherein said mold comprises at least one opening, and the method further comprises discharging of excess melted material through said least one opening of said mold (700). Method according to claim 11 or, wherein the method comprises the additional step of bonding, for example laminating, the first cover layer (100) onto said printed circuit board (200) before said joining. Method according to any one of claims 11 to 13, wherein said method comprises a further step of bonding, for example laminating, a second cover layer (500) onto the first cover layer (100), wherein said second cover layer (500) is at least partially covering said first cover layer (100).

Description:
Lab-on-PCB device and method for manufacturing thereof

The invention is directed to a lab-on-PCB device comprising a layer-by-layer arrangement, wherein the LOC device is particularly suitable for the analysis of sample substances such as fluids. Further, the invention is directed to a method for manufacturing of the lab-on-PCB device.

Nowadays lab-on-chip (LOC) devices are used to implement one or more laboratory functions on a single integrated circuitry, particularly for biologic fluid materials. Even though LOC devices are often only a few centimetres in size, they have a wide range of applications. For example, LOC devices are used for electrochemical analysis applications, genomics applications, such as capillary electrophoresis and DNA microarrays, or for rapid screening etc.

In addition to the type of application, LOC devices can also be distinguished by whether they are disposable or reusable, as well as by the materials used for manufacturing and their design. One type of LOC device, for example, is based on silicon semiconductor technology which was not used for disposable devices up to now due to high costs. An affordable alternative is a device based on a glass substrate. However, the integration of electronics for measurement and evaluation of the sample material is very complex for those devices. A further type of LOC device uses plastic materials, wherein thermosetting plastics are glued together. In this type of LOC device, however, there are many interfaces, which cause diffusion when a fluid to be analysed is supplied to the LOC device. If diffusion occurs at the interfaces of such device and contact is made with electric circuitry or electronic components of the LOC device, this may lead to faulty measurement results or even failure of the LOC device. Consequently, there is a need for a lower-cost disposable LOC device which also allows easy integration of electronics for measurement and evaluation of the fluid material, while avoiding diffusion problems.

The above objective is solved by a lab-on-PCB device for analysis of a sample, for example a fluid sample, with the features of claim 1. In addition, the object is solved by a method for manufacturing of such a LOC device comprising the features of claim 11. Appropriate embodiments thereof are stated in the dependent claims and the following specification.

According to claim 1, a lab-on-PCB device is provided. The device comprises

- a base layer,

- a printed circuit board comprising a substrate with a conductor structure, a first electronic component being mounted on the substrate, and a first measuring electrode being arranged on the substrate at a sample contact area at a first side of said substrate and being electrically connected to the first electronic component via the conductor structure, wherein the printed circuit board is attached to the base layer by means of an adhesion layer, and

- a microfluidic device comprising a first sample reservoir, a first channel and a first reaction chamber, wherein the first reaction chamber is in fluidic communication with the first sample reservoir via the first channel, and the first reaction chamber is in fluidic communication with the first measuring electrode, wherein

- said microfluidic device is formed by a first cover layer arranged on the printed circuit board, and the first cover layer comprises a first cavity or recess forming the first sample reservoir, the first channel, and the first reaction chamber.

According to the invention it is particularly envisioned that substrate comprises one or more through-going recesses which encircles in part the reaction contact area, wherein a part of the first cover layer and/or the adhesion layer engages in the one or more through-going recesses, particularly in a form-fitting and/or fluid-tight manner. Particularly, the lab-on-PCB device comprises a layer-by-layer arrangement which means that the device comprises layers having a large extension in two spatial directions and a small extension in a third spatial direction (vertical direction) perpendicular to the two spatial directions (layers) which may be distinguished on the basis of their materials and/or their functional properties, and wherein each layer is arranged one above the other into the third direction. Preferably, the base layer forms the bottom of the lab-on-PCB device, and the first cover layer to the top thereof. The printed circuit board is preferably arranged between the base layer and the first cover layer, wherein the printed circuit board may be bonded to or joined with the base layer by means of an adhesion layer being arranged between the printed circuit board and the base layer.

Typically, the base layer comprises a flat, for example square, oval or round, cross-section and main surfaces, which are at least mainly plain. When the lab-on-PCB device is used, it usually rests on one of these surfaces of the base layer, with the other surface being in contact with the adhesion layer, at least partially. In one embodiment, the adhesion layer may not cover an area of the printed circuit board where the one or more through-going recesses are provided in the substrate of the printed circuit is solely filled with material of the first cover layer. The base layer may provide the required stiffness to the LOC device.

The printed circuit board bonded to the base layer by the adhesion layer comprises the electric circuitry used for the application of the Lab-on-PCB device as well as at least one area, e.g. at least one reaction or sample contact area, of the Lab-on-PCB device that is intended to come into contact with a sample (e.g. a fluid sample) to be analysed. The printed circuit board comprises a substrate and the electric circuitry (electronics), wherein the substrate mechanically supports or integrates the electric circuitry. Electronic components of the electric circuitry are electrically connected by conductive tracks, pads and other features, for example having one or more sheet layers of conductive laminated material, such as copper, placed between or on sheet layers of a non-conductive laminated substrate material, e.g. such as a liquid crystal polymer. At a first surface opposite to the adhesion layer, the printed circuit board comprises a sample contact area with at least one electrode. A second surface of the printed circuit board opposite to the first surface contacts the adhesion layer. The electrode may be used for electrochemical- and/or impedance-based sensing, wherein said electrode is configured to be electrically connected to a measurement unit which may be external to the Lab-on-PCB device but electrically connected to the electrode, which may be formed as an electrically conductive pad located at the first surface. To electrically connect the electrode to a measurement unit the Lab-on-PCB device may comprise a card edge connector or a spring-loaded contact or other means for electrically connecting a measurement unit, for example located at a side surface of the printed circuit board.. The substrate of the printed circuit board may comprise at least one, for example, two or more layers of electrically conducting material (metal layer) forming a part of the electric circuitry, for example, in order to connect electrodes and other electronic components. In one embodiment, the substrate may be single-layered or multi-layered.

The sample contact area forms a preferably flat section of the first surface of the printed circuit board which is intended to contact the sample, for example a fluid sample, to be analysed by the Lab-on-PCB device. For example, the sample contact area may be formed as a circle, a triangle or a polygon or any combination of them. The at least one electrode is exposed at the sample contact area such that it directly contacts the respective sample when it is located at the sample contact area. In one embodiment, the at least one electrode is located in a central section of the sample contact area or of a section of it.

In order to prevent any diffusion and/or migration of sample material, in particular fluid material, located in the sample contact area to sections of the printed circuit board comprising the (sensitive) electric circuitry, the printed circuit board comprises at least one through going recess located in a section of the printed circuit board adjacent to one of the at least one sample contact area, wherein the at least one through going recess at least partly encircles the sample contact area. The through-going recess is filled with material of the adhesion layer and/or the first cover layer, thereby creating a sealing effect with regard to the sections of the printed circuit board outside the encircled area, in particular with regard to interfaces between the different layers in this area. In order to electrically connect the at least one electrode located at the sample contact area to the area outside the encircled area of the printed circuit board, a web or the like may span the one or more through going recesses at least one place. Thus, when viewed from above, the printed circuit board comprises at least one sample contact area each located within one adjacent through-going recess encircling the respective sample contact area and another area outside the at least one through-going recess channel. As already stated above, a part of the adhesion layer and/or the first cover layer extends into the through-going recess and forms a barrier to the sample material so that it cannot penetrate/migrate into the printed circuit board outside the one or more through-going recesses or sample contact area on the one hand. On the other hand, a contamination or moisture from the first and/or second surface of the printed circuit board or its volume is prevented by the barrier form by the part of the adhesion layer and/or first cover layer from entering the sample contact area from outside. As a result, a sample such as a cell culture may be cultivated at elevated temperature over longer time using the above-defined Lab-on- PCB device. Accordingly, the at least one through-going recess may have a complex form adapted to the circumference of the sample contact area. One through-going recess may fully or section-wise encircle the respective one of the at least one sample contact area. One sample contact area may be encircled by one through-going recess or by more than one though- going recesses separated along the circumference of the sample contact area. Altogether one sample contact area may be encircled by one through-going recess or several through-going recesses, for example, along more than 80% of its circumference or along more than 90% of its circumference or along more than 95% of its circumference.

On top of the printed circuit board, a first cover layer is provided covering the first surface of the printed circuit board, wherein the first cover layer is directly attached to the first surface of the printed circuit board. The first cover layer comprises at least one cavity or recess being aligned with the sample contact area so that the sample material may access the sample contact area. This means that the cavity or recess may be arranged directly above the sample contact area in the above-defined vertical direction of the Lab-on-PCB device. This definition includes the situation where the first cover layer comprises an cavity or recess having an outlet located directly above the sample contact area and an inlet opening offset from the outlet opening and the sample contact area. The first cover layer may cover the electronic components located at the top surface (first surface) of printed circuit board. In one embodiment, the first cover layer may have a form at its surface opposing the first surface of printed circuit board that is inverse to the form of the first surface of printed circuit board. The material of the first cover layer or the material of the adhesion layer may completely fill the one or more through-going recesses. Alternatively, each of the materials of the adhesion layer and the first cover layer may at least partially fill the one or more through-going recesses. In this embodiment, both materials together fill the one or more through-going recesses completely. Further, the printed circuit board, in particular its substrate, may comprise further at least one further through holes, through channels or recess which does not encircle the reaction sample contact area but may also be filled by material of the first cover layer and/or the adhesion layer. Other through holes of the printed circuit, in particular its substrate, may be filled by electrically conductive material thereby forming an electrical contact to an electronic component of the electrical circuitry of the printed circuit board.

In summary, the Lab-on-PCB device basically comprises at least four layers arranged on top of each other: the base layer, the adhesion layer, the printed circuit board and the first cover layer.

In one embodiment, said substrate comprised a first reservoir area being aligned to and optionally in fluidic communication with said first sample reservoir, and a first channel area aligned to and optionally in fluidic communication with the first channel, wherein the first sample area and optionally the channel area and/or the first reservoir area are encircled in part by the one or more through-going recesses, wherein a part of the first cover layer and/or the adhesion layer engages in the one or more through-going recesses, particularly in a formfitting manner.

In one embodiment, the printed circuit board comprises a pair of electrodes being arranged on said substrate in or adjacent the channel area, wherein the pair of electrodes is configured to manipulate a liquid within the first channel. Manipulation of the liquid may include altering the flow velocity and/or flow direction of the liquid. Particularly, electrically charged and/or magnetic particles within the liquid may be manipulated by an electrical field generated from or between the electrodes. In one embodiment, the base layer of the Lab-on-PCB device is at least partially transparent, particularly within an area that is aligned with the first reservoir area, the first channel area and/or the first sample area, wherein optionally the adhesion layer does not cover the printed circuit board at an opposite side of the first sample area, the first channel area and/or the sample contact area. Advantageously, the transparent areas of the base layer may be used as observation windows through which the sample or reactions within the sample may be inspected visually.

In one embodiment, the adhesion layer and/or the first cover layer comprise a material having a melting temperature which is lower than the melting temperature of the printed circuit board, i.e., the substrate of the printed circuit board. In one embodiment, the adhesion layer comprises a thermoplastic hot-melt adhesive. In another embodiment, the adhesion layer essentially consists of or comprises a thermoplastic material, particularly having a lower melting temperature than the substrate of the printed circuit board, wherein particularly the thermoplastic material may be, for example, a liquid crystal polymer. In one embodiment, the first cover layer essentially consists of or comprises a thermoplastic material having particularly a lower melting temperature than the substrate of the printed circuit board, wherein the thermoplastic material may be a liquid crystal polymer (LCP) , a polycarbonate, polyethylene terephthalate, polyester or the like, wherein the first cover layer may be manufactured by injection moulding.

In one embodiment at least one of adhesion layer and the first cover layer has a lower melting temperature than the substrate of the printed circuit board so that at least one of the materials flows into the at least one through-going recess when heated during manufacturing and thereby fills the respective through-going recess encircling the sample contact area. The materials of the first cover layer and the connection layer, however, may be configured such that they provide a permanent connection to the printed circuit board and, with regard to the adhesion layer, additionally to the base layer. In case one of the adhesion layer and the first cover layer has the same melting temperature or a higher melting temperature than the printed circuit board, the respective layer may also be bonded to the printed circuit board or the base layer in another way, for example using a (curable) adhesive. The first cover layer may be fixed to the printed circuit board by lamination or by using an adhesive, for example. The substrate of the printed circuit board may comprise a polymeric material, for example a polyimide, or a LCP, or a ceramic material, e.g. a LTCC or HTCC, or a glass fibre reinforced resin, e.g. FR4, and/or another material, which is electrically insulating. The conductor structure at or within the substrate may formed by a metal material, for example copper.

In a further embodiment, the printed circuit board comprises electronic components forming a part of the electric circuitry, for example a resistor, and/or a capacitor and/or a coil and/or an integrated circuit (IC). Typically, the electronic component is located in the area of the printed circuit board outside the at least one through channel, i.e. not in the direct vicinity of the sample contact area within the area encircled by the at least one through channel. For example, such electronic component is placed on the first surface of the printed circuit board and covered and thereby protected by the first cover layer. If in one embodiment the first cover layer melts during manufacturing, the first cover layer may wrap around the respective electronic component and seals it.

In one embodiment, the first cover layer of the device comprises at least one through channel connecting the first reservoir aligned with the sample contact area and a second reservoir aligned with a second sample contact area. Thus, this at least one through channel within the first cover layer forms a connection between at least two sample contact areas or regions of one sample contact area. Hence, the through channel may be used, for example, to analyse and/or manipulate a sample substance supplied to the Lab-on-PCB device using each of the first and second sample contact areas and, therefore, to allow application of different analysis and/or manipulation methods to one sample. Such through-channels forming microfluidic connections between different sample contact areas may be arranged as desired in the first cover layer and thus serve for transport, mixing, etc. of the sample, in particular of a fluid sample.

In one embodiment, the substrate is multi-layered and/or comprises at least one via. As described before, the printed circuit board comprises at least one partial layer of conductive laminated material located between or on at least one sheet layer of a non-conductive material, wherein the at least one layer of conductive material as partly forms the conductor structure. An exemplary configuration of the printed circuit board comprises a sheet layer of non-conductive material, to which conductive material, i.e. a conductive partial sheet layer, is provided on one side, e.g. on the first surface. Another exemplary embodiment comprises an additional conductive partial sheet layer on the second surface of the non-conductive material, wherein the different conductive layers may be interconnected by means of one or more vias. For example, electronic components may be deposited on the first surface of the non-conductive sheet layer and the predominant part of the connecting conductor paths may be deposited on the second surface of the non-conductive sheet layer. In another embodiment, the printed circuit board may comprise several electrically non-conductive and conductive sheet layers, wherein the electrically conductive sheet layer covers only a part of the respective conductive layer and the whole multi-layered structure is laminated.

In one embodiment, the base layer comprises at least one material of the group comprising a metal, a glass and a plastic material, wherein the material of the base layer has a melting temperature which is higher than the melting temperature of the adhesion layer and/or the cover layer. Using a base layer comprising a material with a melting temperature higher than the melting temperature of the adhesion layer and/or the first cover layer guarantees during manufacturing that the base layer stays stiff and supports the overlying layers when the adhesion layer and/or the first cover layer start melting. The melting of the adhesion layer and/or the first cover layer however during manufacturing causes filling the one or more through-going recesses going through the substrate of the printed circuit board.

In another embodiment, the first cover layer is laminated onto the printed circuit board. The lamination may be a cold or a hot lamination, wherein during said cold lamination an adhesive may be used which is activated by temperature and/or pressure. In addition, hot lamination may be used, wherein an adhesive is used in order to generate the permanent connection. The melting temperature of the first cover layer may be higher than the melting temperature of the printed circuit board. Prior establishing the permanent connection of first cover layer and printed circuit board, the first cover layer may be detachably pinned to the printed circuit board thereby forming an interim attachment. The first cover layer may be permanently connected to part of the first surface of the printed circuit board. This does not only apply to lamination of the first cover layer but also to the connection formed by an adhesive and to other types of attachment.

In one embodiment, the first cover layer comprises at least one recess at its surface directly adjacent to printed circuit board, wherein the at least on recess is at least partly aligned with the one or more through-going recesses of the substrate and is at least partly filled with material of the adhesion layer. In this embodiment, the melted material of the adhesion layer, which bonds the base layer to printed circuit board, at the same time fills the one or more through-going recesses in the substrate of the printed circuit board and the recess of the first cover layer and thus also fixes the first cover layer to the printed circuit board and enlarges the barrier into the opposite layer, the printed circuit board. This expands the sealing effect with regard to the sample contact area.

In one embodiment, the LOC device further comprises a second cover layer which is bonded onto, for example laminated onto, the first cover layer, and wherein the second cover layer covers at least partially the first cover layer. It may fully cover the first cover layer, in one embodiment. Using a second cover layer may be especially helpful when liquids, reagents and samples are pre-filled to the Lab-on-PCB in order to react or mix with a sample applied to the Lab-on-PCB later for analysis. In this case, the protection layer may prevent the prefilled substance from leaking out of the Lab-on-PCB device. The second cover layer may also protect the sample contact area or the electronic components of the electrical circuit. The second cover layer may also be used to print a brand logo, an expiry date, a sterilizing date or other useful information onto the Lab-on-PCB device. Depending on the purpose of the second cover layer, it may therefore be designed differently. For example, the second cover layer may be transparent, coloured or opaque, and/or it may have a film-like or platelike design.

Analogously, the above objection is solved by a method for manufacturing a lab-on-chip device according to the above explanation, wherein said method comprises the following steps:

• providing a a printed circuit board comprising a substrate with a conductor structure, a first electronic component being mounted on said substrate, and a first measuring electrode being arranged on the substrate at a sample contact area at a first side of the substrate and being electrically connected to the first electronic component via the conductor structure ,

• proving a first cover comprises a first cavity or recess, wherein the first cover(lOO) forms a micro fluidic device comprising a first sample reservoir, a first channel and a first reaction chamber formed by the first cavity or recess ,

• arranging a base layer, an adhesion layer, the printed circuit board and the cover (200) in a layer-by-layer arrangement such that the adhesion layer is arranged between the base layer and the printed circuit board, and said first reaction chamber of the first cover (200) is aligned and in fluid communication with said sample contact area of the printed circuit board,

• joining said base layer, the adhesion layer, the printed circuit board, and the thermoplastic cover.

According to the invention, it is particularly envisioned that the substrate comprises one or more through-going recesses which encircles in part the sample contact area (208), wherein a part of the thermoplastic cover layer and/or the adhesion layer fills the one or more through- going recesses during the joining, particularly in a form-fitting and/or fluid-tight manner.

In one embodiment, the first cover layer and/or the adhesion layer essentially consists of or comprises a thermoplastic material, wherein joining is particularly performed by means of heat and pressure. Particularly, the base layer, the adhesion layer, the printed circuit board and the first cover layer are arranged layer-by-layer one above the other inside a tool, wherein said tool may comprise two heatable plates.

In one embodiment, a mold is arranged on the first cover layer before joining, wherein the mold comprises a protrusion that fills the first recess or cavity of said first cover layer, particularly in an essentially form-fitting manner. The mold may comprise silicone, polytetrafluoroethylene or a similar temperature stable material. Particularly, the mold encompasses at least the cover layer and optionally the printed circuit board so that the mold may overlap these layers on their side surfaces. Further, the mold may have a form that is the inverse one of the profile of the first surface of the first cover layer (opposite to the mold), thus completely enclosing it. For example, at least one projection of the mold projects into the first cavity or recess of the first cover layer. This is especially helpful if material of the first cover layer is (e.g. partially) melted during manufacturing in order to keep the profile of the first cover layer, in particular of its fist cavity or recess.

Particularly, a temperature-pressure-time profile applied may be generated by the heatable plates which may be moveable or, for example, by generating pressure inside the tool, and by supplying the heat by hot air or by heating the plates or the like. Regardless of how the temperature-pressure-time profile is applied, the tool preferably ensures melting of the first cover layer and/or the adhesion layer as well as filling and thereby sealing the one or more through-going recesses of the substrate of the printed circuit board encircling the respective sample contact area. The temperature-pressure-time profile causes that the layers are permanently fixed to each other and the at least one through hole is filled with the material as described above. Additionally, the cover layer and/or the adhesion layer may be provided with an greater thickness compared with the thickness of the respective layer in the completed Lab-on-PCB device so that part of the material of the respective layer is available for filling the one or more through-going recesses of the printed circuit board. After application of the temperature-pressure-time profile, the mold is removed from the Lab-on-PCB device and the Lab-on-PCB device is removed from the tool. In general, each single step of the manufacturing process of the Lab-on-PCB device may be executed manually, partially automated or fully automated.

The temperature-pressure-time profile may, for example, realize a pressure between 0.1 bar and 30 bar and/or a temperature between 50 centigrade Celsius and 325 centigrade Celsuis during between 1 and 30 minutes.

In one embodiment, the method comprises the additional step of bonding, for example laminating, the first cover layer onto the printed circuit board before arranging the first cover layer and the printed circuit board inside the tool. Laminating the first cover layer onto the printed circuit board, i.e. onto the first surface, prior arranging the base layer, the connection layer, the printed circuit board and the first cover layer inside the tool, may improve accuracy of arrangement of the layers thereby simplifying manufacturing of the LOC device and may already protect the sensitive electronic of the printed circuit board during insertion into the tool and during the application of the temperature-pressure-time profile. Additionally, gas cavities can be avoided.

In a further embodiment, the method comprises discharging of excess melted material through at least one opening of the mold, for example, provided in a side wall of the mold in order to deal with excess melted material of the cover layer and/or connection layer and avoid contamination of Lab-on-PCB device elements by this material. The excess melted material is discharged during application of the temperature-pressure-time profile.

In one embodiment, the method comprises a further step of bonding, for example laminating, a second cover layer onto the first cover layer, wherein the second cover layer is at least partially covering the fist cover layer. The benefit of the provision of a second cover layer has already been described above.

In one embodiment, the method comprises the additional step of sterilizing the completed lab-on-chip device, for example by using heat, e.g. provided by steam, or UV radiation. Sterilisation of the completed Lab-on-PCB device may remove any contamination at the Lab-on-PCB device and makes it ready to be used for sample analysis and/or manipulation.

The above automatable method produces cost-efficient disposable Lab-on-PCB devices which allow integration of electronic components for analysis and/or manipulation within the device and minimizes sample or contamination diffusion within the Lab-on-PCB device, in particular close to the sample contact area. Surprisingly, the simple steps of provision of one or more through-going recesses encircling the sample contact area within the printed circuit board and filling it afterwards with the material of at least one adjacent layer lead to above mentioned advantages of the above method without additional effort in the manufacturing process. The present invention will now be described in further detail with reference to the accompanying schematic drawings, wherein

Fig. 1 shows a first embodiment of a lab-on-chip device according to the invention in an exploded cross-sectional view;

Fig. 2 depicts the printed circuit board of the embodiment of Fig. 1 without the electronic component in a top view;

Fig. 3 shows the printed circuit board and a cover layer of the embodiment of Fig. 1 in an exploded cross-sectional view;

Fig. 4 shows a tool, a mold and the embodiment of Fig. 1 in an exploded cross- sectional view;

Fig. 5 shows the cover layer and the printed circuit board (as observed through the first cover layer) of the embodiment of Fig. 1 in a top view;

Fig. 6 shows a cross-sectional view of the arrangement of Fig. 5 sectioned along the axis A-A of Fig. 5 prior application of the temperature-pressure-time profile;

Fig. 7 shows a cross-sectional view of the arrangement of Fig. 5 sectioned along the axis B-B of Fig. 5 prior application of the temperature-pressure-time profile;

Fig. 8 shows the cross-sectional view of Fig. 6 after application of the temperature- pressure-time profile;

Fig. 9 shows the cross-sectional view of Fig. 7 after application of the temperature- pressure-time profile; and

Fig. 10 depicts the printed circuit board, the first cover layer of the embodiment of Fig. 1 and an additional protection layer in a cross-sectional view. Fig. 1 depicts a layer-by-layer arrangement of a Lab-on-PCB device 1 in an exploded view with a first cover layer 100, a printed circuit board 200, an adhesion layer 300 and a base layer 400. During manufacturing a temperature-time-profile is preferably applied to said layered arrangement such that the first cover layer 100 and/or the adhesion layer 300 is at least partially melted so that the first cover layer 100, the printed circuit board 200, the adhesion layer 300 and the base layer are permanently fixed to each other in the shown arrangement. In the shown embodiment, the connection layer 300 is directly firmly bonded to the base layer 400 and the printed circuit board 200. Additionally, the first cover layer 100 is directly firmly boded to the printed circuit board 200. Accordingly, the materials of the layers are preferably selected so that the adhesion layer 300 and the first cover layer 100 have a lower melting temperature than the printed circuit board 200 and the base layer 400, respectively. Alternatively, an adhesive may be used at at least one of the interfaces between the layers in order to realize a permanent connection between the respective layers.

The printed circuit board 200 comprises a substrate 204, wherein the printed circuit board has a first surface 201 and a second surface 202. As depicted in Fig 1, each of the surfaces 201 and 202 of the printed circuit board 200 comprises a conductor structure 203, arranged on or integrated in the substrate 204, wherein a part of the conductor structure 203 may be arranged on the first surface 20 landmay be electrically connected to a part of the conductor structure 208 located on the second surface 202 by at least one via 205. The conductor structure of the printed circuit board 200 may comprises elements such as conductive tracks 203 or conductive pads. On the conductor structure, at least one electronic component 206 such as a resistor, capacitor, coil, integrated circuit (IC) or the like may be mounted, e.g. by means of SMT technologies. For the analysis of a sample, the Lab-on-PCB device 1 is additionally provided with at least one sample contact area 208 (see Fig. 2) comprising at least one electrode 209. The electrode 209 is typically electrically connected to the remaining electronic components 206 by the conductor structure, e.g. a conductive track 203, and may be electrically connected to a measurement unit by a connector provided at the side surface of the Lab-on-PCB device 1 (not shown). The sample contact area 208 is provided on the first surface 201 of the printed circuit board 200 of the Lab-on-PCB device 1. Typically, the material of the sheet-like, flat and stiff base layer 400 is chosen from a metal, a glass or a stiff plastic material. The material of the printed circuit board 200 preferably has a higher melting temperature than the first cover layer 100 and/or the adhesion layer 300. The substrate 204 may, for example, comprise a polyimide, a LCP, or a reinforced epoxy resin (e.g. FR4) glass or another material which is characterized, for example, by chemical inertness, low water absorption and easy adaptability to any three-dimensional shape. The substrate 204 may be single-layered or multi-layered. The adhesion layer 300 and the first cover layer 100 are preferably made form a thermoplastic material, preferably a LCP having a melting temperature of, for example, 265 centigrade Celsius. The material of the first cover layer 100 may comprise polycarbonate, polyethylene terephthalate, polyester or the like.

The sample contact area 208 is encircled by a through-going recess 210 located in the substrate 204 and being adjacent to the sample contact area 208. During manufacturing of the Lab-on-PCB device 1, this through-going recess 210 is filled with material of the adhesion layer 300 and/or with material of the first cover layer 100 as shown in Fig. 8 and 9, thereby sealing the sample contact area 208 in respect to the remaining area of the printed circuit board 200 outside the through-going recess 210 thereby reducing diffusion. Hence, sensitive components of the Lab-on-PBC, for example electronic component 206, that are located outside the sample contact area 208 and the through-going recess 210 are protected against sample material from the sample contact area 208 and/or the sample located within the sample contact area is protected from contamination from outside. The substrate 204 of the printed circuit board 200 is further provided with additional through holes 213, which may be filled with the respective melted material of the first cover layer and/or the adhesion layer as well. Such filled through holes 213 in the first cover layer 100, into which the molten material may flow, may further improve the sealing and bonding effect. Alternatively or additionally, the substrate 204 may comprise at least one groove (not through-going) that may be filled with said melted material, as well. The at least one through-going recess 210 and the through holes 213, as well as any other component into which the molten material may flow, may either be fully filled with only one melted material, i.e. the material of the first cover layer 100 or the adhesion layer 300, but may, however, also be partially filled with both materials depending on the melting temperature of the materials. The printed circuit board 200 shown in Fig. 2 comprises one sample contact area 208 accessible via two openings 101 (see Fig. 3) of the first cover layer 100. Each of the circular sections of the sample contact area 208 accessible via said openings 101 is fluidically connected to the other one via a channel area 212. The circular section of the sample contact area 208 located in Fig. 2 on the right hand side comprises an electrode 209. The channel area 212 of the sample contact area 208 can comprise an electrode structure 211 for sample analysis and/or manipulation. For example, if a substance is supplied to the left circular section of the sample contact area 208 via the left opening 101 in the cover layer 100, the sample may be transferred to the right-hand section of the sample contact area 208 via the channel section 212 using a microfluidic through channel 102 of the first cover layer 100 (see Fig. 6 and 8) connecting the left circular section and the right circular section of the sample contact area 208, wherein the microfluidic channel 102 distributes the sample material. Within the microfluidic channel 102 the sample material may be analysed by the electrode structure 211 and then, in the right hand section by the electrode 209. Of course, alternatively, the sample may be added to the right hand section of the sample contact area 208 first, so that the sample transport takes place in the reverse direction. As mentioned above, the bridging section 212 is delimited by the first cover layer 100, thereby forming the microfluidic through channel 102.

The substance may be supplied to at least one circular section of the sample contact area 208 via one opening 101 or both in the cover layer 100. As depicted in Fig. 3 and 5 each opening 101 is located directly above the respective circular section of the sample contact area 208.

For manufacturing of the Lab-on-PCB device 1, a tool 600 may be used to apply a tempera- ture-pressure-time profile to the layered arrangement. Fig. 4 shows an example of such tool 600 comprising two heating plates 601, which additionally are configured to exert pressure on the layer-by-layer arrangement by means of vertical displacement. Prior application of the temperature-pressure-time profile the base layer 400, the adhesion layer 300, the printed circuit board 200 comprising the electronic component 206, the first cover layer 100 and a mold 700 are accommodated one above the other in this order and in a pre-defined arrangement within the tool 600 between the two heating plates 601. The pre-defined arrangement defines the relative position of the layers perpendicular to the vertical direction, as well, wherein, in one embodiment, the tool 600 comprises a frame to realize correct spatial arrangement of each layer. To prevent the Lab-on-PCB device 1 from being damaged during manufacturing, the mold 700 is used. In addition, the mold 700 ensures that the openings 101 remain open or are created in the first cover layer 100. For that, the mold 700 comprises projections 701, which protrude into the openings 101 of the first cover layer 100. Further, the mold 700 comprises side walls 702 which encompass the first cover layer 100 and the printed circuit board 200. Relative slipping of the layers is prevented by the side walls 702 and the projections 701 of the mold 700. Further, in one embodiment, to withdraw excess melted material from the mold 700, at least one through going opening in the mold 700, for example within the side walls 702 of said mold 700 as described above may be provided. Furthermore, the mold 700 may comprise silicone, Teflon® or a similar temperature stable material.

The layers are fixed to the respective adjacent one by application of the pre-defined temperature-pressure-time profile. The pressure and elevated temperature are provided by the heating plates 601 which are moved against each other as represented by arrows 605. For example, the temperature-pressure-time profile is as follows heating up to a temperature of 300 centigrade Celsius at a pressure of 3 bar within 5 minutes.

Due to the elevated temperature, the material of the adhesion layer 300 and of the first cover layer 100 are melted, at least in a region at and near the interface to the base layer 400 and the printed circuit board 200 respectively. Thereby, the layers are attached to the respective adjacent layer and the melted material of the first cover layer 100 and/or the adhesion layer penetrate into and fill the at least one through-going recess 210 as indicated in Fig. 6, 7 and 8, 9, respectively. Fig. 6 and 7 show the through-going recess 210 prior application of the temperature-pressure-time profil, i.e. the unfilled through channel 210, whereas Fig. 8 and 9 show the though-going recess 210 during and/or after filling with material of the cover layer 100.

As an alternative to attaching the cover layer 100 to the printed circuit board 200 by melting, the first cover layer 100 may also be laminated or otherwise attached to the first surface 201 of the printed circuit board 200 in advance, i.e. before the layer arrangement is arranged in said tool 600. In this embodiment, the first cover layer 100 is pre-attached to the first surface 201 of the printed circuit board 200 and the first cover layer 100 is not melted during preattachment. In this embodiment, the at least one through-going recess 210 is filled with material of the adhesion layer 300 thereby creating the barrier for sample material and/or contamination as explained above.

After a temperature-pressure-time profile was applied to the layer arrangement by tool 600, the mold 700 is removed from said tool 600 and the Lab-on-PCB device 1 is taken out of the tool 600. Depending on the later application of the Lab-on-PCB device 1 and/or to protect the Lab-on-PCB device 1, for example during transport, a second cover layer 500 may be attached to the first cover layer 100. The second cover layer 500 may be laminated or otherwise attached to the first cover layer 100. Before attaching the second cover layer 500 to the first cover layer, the Lab-on-PCB device 1, e.g. the sample contact area 208, may be prefilled with a substance such as a fluid, reagent or sample needed for the later application, wherein when the Lab-on-PCB device 1 is used, for example, the second cover layer 500 is first removed from the first cover layer 100, and then a substance to be analysed may be supplied to the Lab-on-PCB device 1. The second cover layer 500 may completely or partly cover the first cover layer 100. For example, both openings 101 or only one of the openings 101 may be covered.

A fully manufactured Lab-on-PCB device 1 may have outer dimensions smaller than 100 mm. For example, the one side length of a LOC device 1 is between 10 mm and 100 mm.

In one embodiment, the Lab-on-PCB device 1 may be connected to a measurement unit, for example a computer, via electrical contacts provided at a side surface of the Lab-on-PCB device 1 (not shown). Electrical contacts may also be provided for the connection of other external devices. List of reference numerals

1 lab-on-PCB device

100 first cover layer

101 opening

102 through channel

200 printed circuit board

201 first surface

202 second surface

203 electrically conductive track

204 substrate

205 via

206 electronic component

207 pad

208 sample contact area

209 electrode

210 through-going recess

211 electrode structure

212 channel area

213 through hole

300 adhesion layer

400 base layer

500 second cover layer

600 tool

601 heatable plate

605 arrow

700 mold

701 projection

702 side wall