EP2332652A1 - Fluid magnetic particle transport system - Google Patents

Abstract

The system has engageable and diengageable magnetic sources (3) operating in a fluid channel (1) and arranged in an axial fluid channel direction at two opposite sides outside of the fluid channel in an alternative sequence. The magnetic sources have main effective directions (6) aligned in inclination to the fluid channel and pointing in same axial direction to the fluid channel. The magnetic sources are formed by soft magnetic structures in area of influence of a magnet source e.g. permanent- or electromagnets.

Description

The invention relates to a fluidic magnetic particle transport system for suspended in a fluid magnetic particles in a fluid channel according to the first claim.

Fluidic magnetic particle transport systems of the type mentioned initially serve to transport magnetic particles in a fluid, preferably suspended in a liquid suspension. In contrast to pumps, the particles are not transported together with the fluid or the remaining constituents of the suspension, but selectively. The non-magnetic constituents of the fluid or suspension are thus not directly, i.e., through the fluidic magnetic particle transport system. possibly influenced by the magnetic particles.

Selective transport of certain suspension components is particularly useful in bioanalytics or biosynthesis, e.g. in the isolation of certain active substances of particular importance. In this case, certain molecules of a target substance are bound to the magnetic particles and forwarded via a fluidic channel or reaction system for subsequent synthesis or analysis. Alternatively, it is generally possible by means of a corresponding selective transport to carry out a separation or mixing of particles in a fluid.

In [1], a selective transport system for magnetic particles in a fluid is described by way of example. In this case, the suspension is oscillated back and forth in channels with fluid and particles in channels, wherein only in the partial movements in one direction, a magnetic field is turned on. Thus, in this partial movement, the magnetic particles are fixed to the channel walls, while they are driven in the opposite partial movement together with the fluid.

The aforementioned transport process thus requires an oscillating movement of the entire suspension in synchronism with the magnetic field switching, which considerably limits the field of use.

Further, [2] discloses a magnetic particle selective transport system in suspension through a channel. For this purpose, switchable electromagnetic sources, which act on the suspension in the channel, are arranged on both sides of the channel wall in an axially alternating side arrangement. For selectively conveying the magnetic particles in the channel, the sources are driven one after the other in the axial direction, with only a maximum of one magnetic source being active, similar to a running light circuit. The magnetic particles collect in each case on the channel wall at the respectively activated source in order to be attracted to the opposite channel wall during the next switching operation by the source which is now activated in the axial conveying direction. The transport process is carried out discontinuously. However, the transport system is characterized by a complex structure with a large number of electromagnets, which are not only individually controlled, but in total constitute a heat source.

A disadvantage of the aforementioned transport systems is also that the magnetic particles during transport systematically repeatedly the channel walls are fixed, which in particular the substances adhering to the magnetic particles are unintentionally transferred to the channel wall.

Based on this, the object of the invention is to propose a magnetic magnetic transport system for magnetic particles in a suspension in a channel with improved selectivity of the transport process and increased efficiency. In particular, a contact of the channel wall by the particles in the suspension during the transport process should be basically reducible.

The object is achieved by a fluidic magnetic particle transport system with the features of claim 1. The back to this dependent claims give advantageous embodiments of the uses again.

The invention relates to a fluidic magnetic particle transport system for suspended in a fluid magnetic particles in a fluid channel. Provided on the channel are a multiplicity of magnetic sources which can be switched on and off in the fluid channel and which are arranged in the axial fluid channel direction on at least two opposite sides outside the fluid channel in alternating sequence.

In operation, the magnetic particles are each from one of the active, i. energized magnetic source in the fluid attracted. In doing so, the active sources are deactivated again upon reaching the magnetic particles, i. switched off and at the same time activated by switching in each case the next following magnetic sources on a preferably different channel side. The magnetic particles are thus deflected by this switching before reaching a magnetic source by a magnetic field switching to the respective following source to this.

Preferably, in the context of a possible embodiment, the switching already takes place before reaching the magnetic particle of the wall, when the first magnetic particles cross the main direction of action of the following source, come to less than 10%, preferably 5% of the fluid channel diameter or the first magnetic particles or a maximum concentration of magnetic particles is in the region of the main direction of action of the following source. With otherwise transparent suspension, the concentrations can be detected optically, for example, by extinciton measurements by means of a laser beam through the crossing point between the main directions of action of two successive magnetic sources and, if empirical values can not be used, for the determination and / or controlling the switching or the switching frequency.

Based on the above-mentioned procedure, magnetic particles in the fluid channel can pass on to each subsequent switching of one to each subsequent, arranged on an opposite fluid channel side magnetic source and thus selectively transported through the fluid channel, without resulting in a contact of the channel walls. For the switching of the magnetic sources means are provided for switching at least from one to another magnetic source.

An essential feature combination of the invention is the grouping of sources per page around the fluid channel, combined with synchronous group-wise driving of the magnetic sources and the feature that the magnetic sources have a main magnetic direction of action oriented obliquely to the fluid channel, not only the main directions of action of all sources a pointing in the fluid channel radial magnetic field component, but preferably also have an axially directed to the fluid channel magnetic field component. The axially oriented field component allows for better axial transport efficiency of the particles in the fluid channel.

The means for switching preferably comprise means for a switching circuit for the magnetic sources, wherein the magnetic sources of a group in each case together and against the sources of at least one other group wer-switched.

Preferably, the axially aligned field components of all sources in one and the same direction. Further preferably, the main directions of action of all magnetic sources per group, more preferably also all sources in total each have a uniform, ie equal angle to the fluid channel, which in turn benefits the preferred uniform delivery in the axial direction.

The target molecules to be transported with the magnetic, preferably magnetic particles in the suspension are preferably reversibly immobilized on the particle surfaces. In the influence of a magnetic field of the aforementioned magnetic sources takes place a selective movement and thus a transport of the particles in the fluid. In this case, the transport directions of the particles in otherwise flow-free suspension of the vectorially determinable sum of the respective attacking individual magnetic forces follow.

In the context of the invention, the magnetic particles pass from the magnetic field of one source to that of the next source of another group on another side of the channel, forming a zig-zag-like transport path. Preferably, the magnetic sources to each other on a groupwise offset and opposite arrangement, wherein the sources in the axial direction are further preferably positioned at the same distance from each other.

Preferably, the channel is rectilinear and has a constant flow area.

Preferably, all magnetic sources per group are identical or identical and arranged to the fluid channel. Further, they are arranged in a row with a preferably constant distance from each other. More preferably, said distances and training are identical in all, especially in opposite groups.

• Fig.1 eine prinzipielle Aufsicht des fluidischen Magnetpartikeltransportsystems mit geradlinig verlaufenden Fluidkanal sowie
• Fig.2 eine prinzipielle Aufsicht des fluidischen Magnetpartikeltransportsystems mit schlangenförmig verlaufenden Fluidkanal.

The invention will be explained in more detail below with reference to exemplary embodiments with the following figures. Show it

• Fig.1 a basic plan view of the fluidic magnetic particle transport system with rectilinear fluid passage and
• Fig.2 a basic plan view of the fluidic magnetic particle transport system with serpentine running fluid channel.

Both figures show exemplary embodiments with a fluid channel 1 having a multiplicity of magnetic sources 3 acting in the fluid channel and arranged directly on the fluid channel walls 2 , which in turn are divided into two groups 4 and 5 on both sides of the fluid channel. The main directions of action 6 of the sources 3 point through the fluid channel walls into the interior of the fluid channel filled with the suspension 1. The main directions of action 6 of the sources 3 preferably per group 4 or 5 preferably span with the channel walls 2 a respective uniform angle α or β . They penetrate the channel wall 2 at respective penetration areas 7 , wherein the magnetic sources 3 are preferably arranged directly on the outer surfaces of the channel wall 2 . In the exemplary embodiments, the angles α and β equal, wherein the main directions of action on the respective opposite Durchdringungsbereichen 7 adjacent upstream source is preferably directed at the Fluidkanalwandung 2. 3 Furthermore, in the figures, the axial transport direction 9 of the magnetic particles is reproduced.

While Fig.1 shows a first embodiment with a straight fluid channel 1 , the course of the fluid channel of the second embodiment according to. Fig.2 The main direction of action 6 of the magnetic sources 3. By the latter design is advantageously avoided larger Magnetfeldinhomogenitäten and thus also areas with low magnetic field strength (dead volumes) in the fluid channel. This will not only reduces reagent consumption, but also supports more efficient and faster transport of magnetic particles in the suspension.

The channel walls are made to avoid remanent magnetization effects such as permanent magnetic attachment of individual particles of a non-magnetizable material, preferably plastic or glass. To avoid an influence of residual magnetisms on the channel inner wall, the channel wall has a minimum wall thickness of 10%, preferably 15% of the channel width. They are like in for example Fig.1 represented over the axial extent of the magnetic sources 3 constant or wise, as Fig.2 exemplified, a varying wall thickness. Preferably, the wall thickness - as well as in Fig.2 shown - in the projection areas 7, preferably all magnetic sources 3 equal.

Uniform magnetic sources 3 with a uniform angle α and β at a uniform wall thickness in the projection regions 7 are prerequisites for uniform magnetic field development in the suspension in the fluid channel around the main directions of action 6. Preferably, the penetration areas lie in the axial direction at a uniform distance D from each other (FIG. Fig.1 ). A uniform magnetic field development is very advantageous for a uniform transport dynamics of the magnetic particles in the suspension (fluid) and thus for a particle flow that is as constant as possible and also to avoid congestion and other local concentration peaks.

In both embodiments, the magnetic sources each comprise a passive soft magnetic structure, preferably the illustrated fluid channel directed plates 8 (preferred) or other slender structures such as needles of the rods in the influence of one or more magnetic fields of one or more magnetic sources, not shown. The illustrated In each case, plates 8 magnetize their own magnetic field and concentrate it in particular in front of and behind the plate ends. The main directions of action 6 of this magnetic field form a straight line with the plates or the slender structures.

Lean structures can be significantly magnetized only in the longitudinal direction, i. only with the vectorial portions, oriented parallel to the length, of the magnetic field lines of the magnetic fields used for the magnetization. At the tips of the structures around the main direction of action magenta field lines are concentrated.

In one embodiment, the magnetic sources used to magnetize the plates comprise two, ie for each group, 4 or 5 separately controllable electromagnets of different orientation. For economic and / or space reasons, the electromagnets use one and the same soft-magnetic core per magnetization direction in one possible embodiment. The orientation of the individual electromagnets is based on the respective orientation of one of the groups. Preferably, they are oriented parallel to the slender structures to produce advantageous parallel to the length oriented vectorial portions of the magnetic field lines. In principle, this also includes equipping each of the slender structures with their own magnetic field coil, the structure assuming the function of the soft magnetic core. The means for discontinuous or gradual switching preferably comprise an electrical switching between the two electromagnets. This embodiment advantageously has no moving parts.

Alternatively, the magnetic sources used to magnetize the plates comprise one or more oscillating permanent magnets or electromagnets, preferably rotating parallel to their orientation. One possible embodiment comprises one oriented parallel to the extent of the sources and around them Orthogonal rotating magnetic source, wherein the respective vectorially resulting portions of the magnetic field lines parallel to the slender structures in their amount sinusoidal, ie oscillating behave. Although this embodiment has moving parts, it is easy for the switching means to do. controllable via the speed in their AC switching frequency.

In both aforementioned embodiments are in a in Fig.1 and 2 illustrated planar arrangement of two groups 4 and 5 to a fluid channel 1, preferably one of two of the aforementioned magnetic sources above or below the planar arrangement provided.

In Fig.1 and 2 the plates of a group are arranged in a staircase, wherein the structures per group are aligned parallel to each other and are perpendicular to the structures of the other group. In this way, it is advantageously ensured that the magnetization of the structures of the sources of one group is maximum only if it is minimal in the structures of the other group. In a magnetic field of a rotating magnetic source mentioned above, the magnetization of the sources follows a sinusoidal course, wherein in groups arranged at right angles the magnetization curves of the two groups are opposite to each other. To ensure advantageous mutually identical or similar geometric relationships in the action of the magnetic sources in the fluid channel, the angles α and β are each 45 °.

The said plates, needles or rods or other slender structures have a ratio of length to width less than 5, preferably less than 10 and more preferably less than 20 .

Furthermore, the plates, needles or rods or other slender structures are limited in their length. Preferably takes place orthogonal view of in Fig.1 or 2 As a result, the slender structures shown do not overlap with the adjacent structures of the same group, so that the magnetic field lines emanating from the magnetic sources ideally only impinge upon a thin structure and only magnetize it; a split into two structures does not take place.

• Herstellung mit Röntgentiefenlithographische Strukturierungsverfahren (z.B. LIGA-Verfahren): Der Fluidkanal und die weichmagnetischen schlanken Strukturen werden in einem Bauteil aus einem Resist (z.B. POM, PMMA etc.) strukturiert. In einem ersten Belichtungsschritt werden an der Position der weichmagnetischen Strukturen lithographisch Kavitäten geschaffen und galvanisch mit einem weichmagnetischen Material, vorzugsweise auf Eisen-Nickel-Basis wieder aufgefüllt. Alternativ lassen sich auch fertige Strukturen in die Kavitäten einsetzen. Erst anschließend erfolgt die lithographische Herauslösung und Abdeckung des Fluidkanals sowie die Bestückung mit den genannten Magnetquellen.
• Spangebende Einarbeitung von Vertiefungen für Kanal und magnetischen Quellen in ein Bauteil und bevorzugt Einsetzen der magnetischen Quellen in die dafür vorgesehenen Vertiefungen. Der Fluidkanal selbst wird durch eine rillenförmige und abgedeckte Vertiefung geschaffen.

A production of a preferred microfluidic magnetic particle transport system gem. Fig.1 or 2 For example, for analyzes or syntheses Favor on a laboratory scale (research and development) of a solid material is carried out as follows:

• Production with X-ray Depth Lithographic Patterning Methods (eg LIGA Method): The fluid channel and the soft magnetic slender structures are structured in a component made of a resist (eg POM, PMMA, etc.). In a first exposure step, lithographically cavities are created at the position of the soft-magnetic structures and are replenished galvanically with a soft-magnetic material, preferably based on iron-nickel base. Alternatively, finished structures can be inserted into the cavities. Only then does the lithographic separation and covering of the fluid channel and the assembly with the mentioned magnetic sources take place.
• Spinning incorporation of wells for channel and magnetic sources in a component and preferably insertion of the magnetic sources in the recesses provided for this purpose. The fluid channel itself is created by a groove-shaped and covered recess.

Alternatively, the fluid channel is formed by a hose (preferably of plastic or an elastomer) which is inserted and exchangeable separately in the depression or cavity. Through both said manufacturing process, a microstructured passive component is created, which can be used as a disposable part after, for example, an analysis or synthesis inexpensively disposable.

Literature:

1. [1] DE 10 2004 062 535 A1
2. [2] Joung J., Shen J., Grodzinski P .: Micropump Based on Alternation High-Gradient Magnetic Fields; IEEE Trans. Magn., Vol.36 (2000) No.4, 2012-2014

LIST OF REFERENCE NUMBERS

1

fluid channel

2

Fluidkanalwandung

3

magnetic source

4

first group

5

second group

6

Main direction of action

7

penetration

8th

soft magnetic plate

9

transport direction

Claims (10)

Fluidic magnetic particle transport system for suspended in a fluid magnetic particles in a fluid channel (1), comprising a) a multiplicity of magnetic sources (3) which can be switched on and off in the fluid channel and are arranged in the axial fluid channel direction on at least two opposite sides outside the fluid channel in alternating sequence,
characterized in that b) the sources of each page each form a group (4, 5) , c) means are provided for group-wise individual switching on and off of the sources as well as d) the magnetic sources have a main magnetic direction of action (6) oriented obliquely to the fluid channel, the main directions of action of all sources pointing in one and the same axial direction to the fluid channel. A fluidic magnetic particle transport system according to claim 1, wherein said means comprises a magnetic source switching circuit (3) , wherein the magnetic sources of one group (4) are respectively switched in common and against the sources of at least one other group (5) . Fluid magnetic particle transport system according to claim 1 or 2, wherein the magnetic sources (3) are formed by soft magnetic structures in the influence of a magnetic source. Fluid magnetic particle transport system according to claim 3, wherein the soft magnetic structures are formed by at an angle α and / or β to the fluid channel tapered rod or plate-shaped elements. Fluidic magnetic particle transport system according to claim 4, wherein the structures per group aligned parallel to each other and at an angle α = β = 45 ° impinge on the fluid channel (1) . Fluidic magnetic particle transport system according to claim 5, wherein the structures (3) in each case without overlapping to the respective adjacent structures (3) of the same group (4, 5) are designed and thereby arranged step-step. Fluid magnetic particle transport system according to one of claims 3 to 6, wherein the magnetic source comprises two separately controllable electromagnets of different orientation. A magnetic particle transport fluid system according to any one of claims 3 to 6, wherein the magnetic source comprises an oscillating permanent or electromagnet. Fluidic magnetic particle transport system according to one of the preceding claims, wherein only two groups (4, 5) of magnetic sources (3) are provided, which are arranged on both sides of the fluid channel (1) . Fluidic magnetic particle transport system according to one of the preceding claims, wherein said fluid channel serpentine interconnects the magnetic sources on the channel wall.

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