DE102018210700A1 - Electrode arrangement for a microfluidic device, in particular for a microfluidic flow cell, and method - Google Patents

Abstract

The invention relates to an electrode arrangement (100) for a microfluidic device (1000), in particular for a microfluidic flow cell (1000), comprising a fluidic layer (110), a substrate layer (130) and one between the fluidic layer (110) and the substrate layer (130 ) arranged membrane (120), the substrate layer (130) having a first channel structure (150) connected to a first electrode (131) and a second channel structure (160) connected to a second electrode (132), the first channel structure (131 ) and the second channel structure (132) are fluidically and electrically separated from one another, the first channel structure (131) being at least partially delimited by a first membrane area (171) and the second channel structure (132) being at least partially delimited by a second membrane area (172) , wherein the first membrane region (171) and the second membrane region (172) have a cavity (180) of the fluidic layer adjacent to the membrane (120) limit t (110), so that depending on one in the first channel structure (150) or in the second channel structure (150) by a pressure generated by a liquid electrolyte (190), the first membrane area (171) or the second membrane area (172 ) to form a first electrolyte electrode (141) or a second electrolyte electrode (142) in the cavity (180). The invention further relates to a method (600) for operating such an electrode arrangement (100) and a flow cell (1000).

Description

State of the art

Flow cells are used in microfluidics to separate biological cells or DNA, for example by size, using dielectrophoresis.

For example, Salmanzadeh et al., "Isolation of rare cancer cells from blood cells using dielectrophoresis," 2012 Annual International Conference ofthe IEEE Engineering in Medicine and Biology Society, San Diego, CA, 2012, pp. 590-593, doi: 10.1109 / EMBC.2012.6346000 a type of dielectrophoresis is known, wherein channels filled with electrolyte, separated from the flow cell by a thin polymer layer and contacted elsewhere with needle-like electrodes are used to generate the electric field. The local deformation of the field strength of the field takes place through insulating posts in the flow cell.

Disclosure of the invention

Advantages of the invention

Against this background, the invention relates to an electrode arrangement for a microfluidic device, in particular for a microfluidic flow cell. The electrode arrangement comprises a fluidic layer, a substrate layer and a membrane arranged between the fluidic layer and the substrate layer. In other words, the electrode arrangement comprises a layer structure, a first layer, referred to as a fluidic layer, from a second layer, referred to as a substrate layer, being at least partially separated by a membrane.

The substrate layer has a first channel structure connected to a first electrode and a second channel structure connected to a second electrode, the first channel structure and the second channel structure being fluidically and electrically separated from one another. A channel structure is to be understood in particular as a channel or a plurality of channels connected to one another, wherein the channel or the channels can be formed in the form of recesses or cavities in the substrate layer. A fluidic separation of the channel structures is to be understood in particular to mean that no fluid can move or extend from the first channel structure into the second channel structure, in particular due to a barrier, for example comprising material of the substrate layer. Electrical separation of the channel structures is to be understood in particular to mean that the first channel structure and the second channel structure are electrically insulated from one another, in particular by an electrically non-conductive material of the substrate view.

The first channel structure is at least partially delimited by a first membrane area and the second channel structure is at least partially delimited by a second membrane area. The first membrane area and the second membrane area further delimit a cavity of the fluidic layer adjacent to the membrane, so that depending on a pressure generated in the first channel structure or in the second channel structure by a liquid electrolyte, the first membrane area and the second membrane area, respectively, form expands a first electrolyte electrode or a second electrolyte electrode into the cavity.

The electrode arrangement according to the invention has the advantage that electrodes can be formed dynamically in the fluidic layer. It is particularly advantageous that the formation of the electrodes can be controlled in a simple manner by controlling the pressure in the channel structures. By controlling the size and geometry of the electrodes via the pressure, the shape and the amount of the electrical field formed can advantageously also be controlled. It is also advantageous that metallic and permanently installed electrodes can be dispensed with and the electrodes are instead realized by parts of the membrane filled with electrolyte. In particular, microstructuring of electrodes can advantageously be omitted. This also facilitates the production of the layer structure of the electrode arrangement using the injection molding process. In addition, the number of electrodes can be increased in a simple manner by changing or expanding the channel structures, in particular by increasing the number of channels adjacent to the membrane, which are opposite the cavity. This means that the throughput of the flow cell can also be expanded without having to resort to higher electrical voltages.

In particular, the membrane at least partially forms a wall that at least partially delimits the channels of the channel structures. This has the advantage that a change in the pressure in the channel structures can act directly on the membrane for an expansion of the membrane into the cavity.

The first channel structure and / or the second channel structure preferably comprise two or more parallel channels for the formation of electrolyte electrodes arranged in parallel. As a result, a regular electric field can advantageously be generated in the cavity.

According to a particularly advantageous development of the invention, at least some of the Channels of the first channel structure are interlocked with at least some of the channels of the second channel structure. By such an at least partial interlocking of the first channel structure with the second channel structure, electrodes arranged in a row can advantageously be realized with alternating polarity. This further development also facilitates parallelization of dielectrophoresis units in the flow cell.

In a particularly preferred development of the invention, the cavity has structures for locally changing an electrical field generated by the electrolyte electrodes. In particular, the structures are electrically non-conductive structures, that is to say insulators. In combination with the electrolyte electrodes, this can cause a local deformation of the field strength of the electrical field in the cavity.

The structures are preferably designed in the form of projections, in particular as posts. The change in the field strength can be set in a well-defined manner by choosing the shape and size, in particular the thickness, of the projections.

According to a particularly advantageous development of the invention, the structures are arranged on a wall delimiting the cavity, the wall being arranged opposite the membrane delimiting the cavity. On the one hand, this advantageously allows the space available in the cavity to be optimally utilized and, on the other hand, a hindrance to the expansion of the membrane into the cavity by the structures is reduced or completely prevented.

In a further embodiment of the invention, the electrode arrangement according to the invention can have one or more further channel structures for forming further electrolyte electrodes, the channel structures being fluidly and electrically separated from one another. The invention is thus advantageously easily scalable in accordance with the requirements for the flow cell.

The invention also relates to a flow cell comprising an electrode arrangement according to the invention.

The invention further relates to a method for operating the electrode arrangement according to the invention, the liquid electrolyte exerting pressure on the first membrane area or on the second membrane area to form the first electrolyte electrode or the second electrolyte electrode in the cavity by expanding the membrane into the cavity becomes.

Regarding the advantages of the method according to the invention, reference is made to the corresponding advantages of the device according to the invention explained above.

list of figures

Exemplary embodiments of the invention are shown schematically in the drawings and are explained in more detail in the description below. The same reference numerals are used for the elements shown in the various figures and acting in a similar manner, and the elements are not repeated.

• 1 ein Ausführungsbeispiel der erfindungsgemäßen Elektrodenanordnung als Teil eines Ausführungsbeispiels der erfindungsgemäßen Flusszelle,
• 2 ein Flussdiagramm eines Ausführungsbeispiels des erfindungsgemäßen Verfahrens.

Show it

• 1 an embodiment of the electrode arrangement according to the invention as part of an embodiment of the flow cell according to the invention,
• 2 a flowchart of an embodiment of the method according to the invention.

Embodiments of the invention

1a and 1b show an embodiment of the electrode assembly according to the invention 100 , for example as part of a microfluidic flow cell 1000 , As especially in the exploded view of the 1a shown includes the electrode assembly 100 three layers, namely a fluidic layer 110 which by a deformable membrane 120 from a substrate layer 130 is separated. For example, the layers 110 . 120 . 130 can be fluidly connected to one another by a laser welding process. The fluidic layer 110 and the substrate layer 130 can each have a stable polymer such as polycarbonate, for example with a layer thickness of 500 to 2000 micrometers. The membrane 120 can comprise, for example, a deformable, connectable polymer such as thermoplastic polyurethane, for example with a thickness between 50 and 400 micrometers, so that the deformability of the membrane 120 is guaranteed.

The fluidic layer 110 includes a cavity 180 which is particularly important for the core functionality of the flow cell 1000 is provided, in particular for the separation of biological cells as described above. The substrate layer 130 comprises a first channel structure 150 with first channels 155 and a second channel structure that is fluidically and electrically separated therefrom 160 with second channels 165 , each with an electrode 131 . 132 can be contacted and thus can be switched in opposite polarity via a voltage source. Contacting the channels 155 . 165 the electrodes are used in particular through the use of a liquid electrolyte 190 in the channels 155 . 165 , As in 1a shown, can in particular parallel channels 155 the first channel structure 150 with channels 165 the second channel structure 160 be toothed, what is arranged in a row of electrodes 140 results, as explained below. On the membrane 120 are in 1a membrane regions 170 shown which channels 155 . 165 the first and the second channel structure 150 . 160 limit. As in the sectional view in 2 B shown, it enables the electrode arrangement according to the invention 100 that in the substrate layer 130 with electrolyte 190 filled channels 155 . 165 be pressurized such that this membrane area 170 in the cavity 180 the fluidic layer 110 bulge in and thus in the cavity 180 opposite pole electrodes 140 form. The membrane areas 170 thus represent the limitation of electrolyte-filled electrolyte electrodes 140 in this 1a becomes a first membrane area as an example 171 and a second membrane area 172 shown, which is also the first electrolyte electrode 141 or the second electrolyte electrode 142 form. As an electrolyte 190 For example, an electrically conductive liquid can be used, for example a buffer such as phosphate buffered saline, for example with a conductivity between 10 and 20 millisiemens per centimeter.

An advantageous embodiment of the electrode arrangement according to the invention 100 includes in the cavity 180 insulating structures 181 , especially protrusions 181 such as posts or columns, which are used to deform the electrolyte electrodes 140 serve generated electric field, which in turn the resulting dielectrophoretic force on particles in the flow cell 1000 affected. As shown in Figures la and 1b, these structures 181 advantageously on one of the membranes 120 opposite side or wall 182 of the cavity 180 be arranged, in this example on the inner top 182 of the cavity 180 ,

A voltage source with 12 volt direct voltage, 200 to 500 volt alternating voltage at a frequency between 50 and 200 kilohertz can be used, for example, preferably with a tunable frequency. For example, this results in an average strength of the electric field in the flow cell 1000 from 10,000 to 500,000 volts (V) per meter (m), using the insulating structures 181 For example, a field strength gradient between 10 ^ 10 and 10 ^ 16 V ^ 2 / m ^ 3 can cause, depending in particular on geometries, arrangements, material or shapes of the structures 181 ,

2 shows a flow chart for an embodiment of the method according to the invention 600 , the procedure 600 for example with the embodiment of the electrode arrangement according to the invention described above 100 can be carried out. In a first step 601 becomes the electrode assembly 100 provided. In a second step 602 become the electrolyte electrodes 140 dynamically trained by the liquid electrolyte 190 a pressure on the first membrane area 171 or on the second membrane area 172 to form the first electrolyte electrode 141 or the second electrolyte electrode 142 in the cavity 180 about an expansion of the membrane 120 in the cavity 180 is exercised. Then in a third step 603 the flow cell 1000 are operated as intended, for example for separating biological cells of different sizes as described above, the electrolyte electrodes 140 can be adjusted in size and thus strength via the pressure setting as required.

Claims (9)

Electrode arrangement (100) for a microfluidic device (1000), in particular for a microfluidic flow cell (1000), comprising a fluidic layer (110), a substrate layer (130) and a membrane (130) arranged between the fluidic layer (110) and the substrate layer (130) 120), characterized in that the substrate layer (130) has a first channel structure (150) connected to a first electrode (131) and a second channel structure (160) connected to a second electrode (132), the first channel structure (131) and the second channel structure (132) are fluidically and electrically separated from one another, the first channel structure (131) being at least partially delimited by a first membrane area (171) and the second channel structure (132) being at least partially delimited by a second membrane area (172), wherein the first membrane region (171) and the second membrane region (172) have a cavity (180) of the fluidic layer (1 10), so that depending on one in the first channel structure (150) or in the second channel structure (150) by a pressure generated by a liquid electrolyte (190), the first membrane area (171) or the second membrane area (172) Forming a first electrolyte electrode (141) or a second electrolyte electrode (142) in the cavity (180). Electrode arrangement (100) after Claim 1 The first channel structure (150) and / or the second channel structure (160) comprise two or more parallel channels (155, 165) for the formation of electrolyte electrodes (140, 141, 142) arranged in parallel. Electrode arrangement (100) according to one of the preceding claims, wherein at least some of the channels (155) of the first channel structure (150) are arranged in mesh with at least some of the channels (165) of the second channel structure (165). Electrode arrangement (100) according to one of the preceding claims, wherein the cavity (180) has structures (181) for locally changing an electric field generated by the electrolyte electrodes (140, 141, 142). Electrode arrangement (100) after Claim 4 , the structures (181) being in the form of projections (180), in particular posts or columns. Electrode arrangement (100) after Claim 4 or 5 , wherein the structures (181) are arranged on a wall (182) delimiting the cavity (180), the wall (182) being arranged opposite the membrane (120) delimiting the cavity (180). Electrode arrangement (100) according to one of the preceding claims, wherein one or more further channel structures (150, 160) for forming further electrolyte electrodes (140), the channel structures being fluidly and electrically separated from one another. Microfluidic flow cell (1000) comprising an electrode arrangement (100) according to one of the preceding claims. Method (600) for operating an electrode arrangement (100) for a microfluidic device (1000), in particular for a microfluidic flow cell (1000), the electrode arrangement (100) having a fluidic layer (110), a substrate layer (130) and one between the fluidic layer (110) and the substrate layer (130), the substrate layer (130) having a first channel structure (150) connected to a first electrode (131) and a second channel structure (160) connected to a second electrode (132), wherein the first channel structure (150) and the second channel structure (160) are fluidically and electrically separated from one another, the first channel structure (150) being at least partially delimited by a first membrane region (171) and the second channel structure (160) at least partially by a second Membrane area (172) is limited, the first membrane area (171) and the second membrane area (172) adjoining the membrane (120) delimit the cavity (180) of the fluidic layer (110) and, in the first channel structure (150) and / or in the second channel structure (160), a pressure on the first membrane area (171) or on the second one by means of a liquid electrolyte (190) Membrane area (172) for forming a first electrolyte electrode (141) or a second electrolyte electrode (141) in the cavity (180) by extending the membrane (120) into the cavity (180).

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