A flow cell unit to be docked against a flat lid surface to form a closed flow cell arrangement, the flow cell unit comprising a top surface with protruding walls of elastic material defining three or more adjacent elongated flow channels, each flow channel comprises a first fluid port and a second fluid port, wherein the walls separating adjacent flow channels comprises a valve section of reduced height, thereby allowing selective opening and closing of a flow path transverse to the elongated flow channels by controlling the docking force between flow cell and the lid surface to an open docking state and a closed docking state respectively.

This application is a filing under 35 U.S.C. 371 of international application number PCT/SE2012/051036, filed Sep. 28, 2012, which claims priority to Sweden application number 1100724-2 filed Sep. 30, 2011, the entire disclosure of which is hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to a flow cell unit, and a fluidic system for biosensor system or the like, and more particularly to a flow cell unit, and a fluidic system for a biosensor system with increased capacity.

BACKGROUND OF THE INVENTION

Biosensor systems that can monitor interactions between molecules, such as biomolecules, in real time are maintaining increasing interest. A representative such biosensor system is the BIACORE® Surface Plasmon Resonance (SPR) instrumentation sold by GE Healthcare which uses surface plasmon resonance (SPR) for detecting interactions between molecules in a sample and molecular structures immobilized on a sensing surface. As sample is passed over the sensor surface, the progress of binding directly reflects the rate at which the interaction occurs. Injection of sample is followed by a buffer flow during which the detector response reflects the rate of dissociation of the complex on the surface. A typical output from the BIACORE® system is a graph or curve describing the progress of the molecular interaction with time, including an association phase part and a dissociation phase part. This binding curve, which is usually displayed on a computer screen, is often referred to as a “sensorgram”.

SUMMARY OF THE INVENTION

The object of the invention is to provide a new flow cell unit, and a fluidic system using the same, which flow cell unit, and fluidic system overcomes one or more drawbacks of the prior art flow cell units, and a fluidic systems. This is achieved by the flow cell unit, and a fluidic system as defined in the independent claims.

One advantage with the flow cell arrangement of the present invention is that it allows increased number of detector spots for interaction studies in a robust, simple, low-cost, and efficient way. Furthermore embodiments of the flow cell arrangement allow faster provision of two-dimensional detection spot arrays.

A more complete understanding of the present invention, as well as further features and advantages thereof, will be obtained by reference to the following detailed description and drawings.

DETAILED DESCRIPTION OF THE INVENTION

As mentioned above, the present invention relates to

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person skilled in the art related to this invention. Also, the singular forms “a”, “an”, and “the” are meant to include plural reference unless it is stated otherwise.

Before describing the present invention in more detail, however, the general context in which the invention is intended to be used will be described.

Chemical sensors or biosensors are typically based on label-free techniques, detecting a change in a property of a sensor surface, such as e.g. mass, refractive index, or thickness for the immobilised layer, but there are also sensors relying on some kind of labelling. Typical sensor detection techniques include, but are not limited to, mass detection methods, such as optical, thermo-optical and piezoelectric or acoustic wave methods (including e.g. surface acoustic wave (SAW) and quartz crystal microbalance (QCM) methods), and electrochemical methods, such as potentiometric, conductometric, amperometric and capacitance/impedance methods. With regard to optical detection methods, representative methods include those that detect mass surface concentration, such as reflection-optical methods, including both external and internal reflection methods, which are angle, wavelength, polarization, or phase resolved, for example evanescent wave ellipsometry and evanescent wave spectroscopy (EWS, or Internal Reflection Spectroscopy), both of which may include evanescent field enhancement via surface plasmon resonance (SPR), Brewster angle refractometry, critical angle refractometry, frustrated total reflection (FTR), scattered total internal reflection (STIR) (which may include scatter enhancing labels), optical wave guide sensors; external reflection imaging, evanescent wave-based imaging such as critical angle resolved imaging, Brewster angle resolved imaging, SPR-angle resolved imaging, and the like. Further, photometric and imaging/microscopy methods, “per se” or combined with reflection methods, based on for example surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS), evanescent wave fluorescence (TIRF) and phosphorescence may be mentioned, as well as waveguide interferometers, waveguide leaky mode spectroscopy, reflective interference spectroscopy (RIfS), transmission interferometry, holographic spectroscopy, and atomic force microscopy (AFR).

Commercially available biosensors include the afore-mentioned BIACORE® system instruments, manufactured and marketed by GE Healthcare, which are based on surface plasmon resonance (SPR) and permit monitoring of surface binding interactions in real time between a bound ligand and an analyte of interest. In this context, “ligand” is a molecule that has a known or unknown affinity for a given analyte and includes any capturing or catching agent immobilized within the sensing volume (detection volume) at the surface, whereas “analyte” includes any specific binding partner thereto.

While in the detailed description and Examples that follow, the present invention is illustrated in the context of SPR spectroscopy, and more particularly the BIACORE® system, it is to be understood that the present invention is not limited to this detection method. Rather, any affinity-based detection method where an analyte binds to a ligand immobilised on a sensing surface may be employed, provided that a change at the sensing surface can be measured which is quantitatively indicative of binding of the analyte to the immobilised ligand thereon.

The phenomenon of SPR is well known, suffice it to say that SPR arises when light is reflected under certain conditions at the interface between two media of different refractive indices, and the interface is coated by a metal film, typically silver or gold. In the BIACORE® instruments, the media are the sample and the glass of a sensor chip which is contacted with the sample by a microfluidic flow system. The metal film is a thin layer of gold on the chip surface. SPR causes a reduction in the intensity of the reflected light at a specific angle range of reflection. The angle of minimum reflected light intensity, so-called SPR-angle, varies with the refractive index close to the metal surface on the side opposite from the reflected light, in the BIACORE® system the sample side.

A schematic illustration of the BIACORE® system is shown inFIG. 1. Sensor chip1has a gold film2supporting capturing molecules (ligands)3, e.g. antibodies, exposed to a sample flow with analytes4, e.g. an antigen, through a flow channel5. Mainly monochromatic p-polarised light6from an illumination unit7(e.g. LED) is coupled by a prism8to the glass/metal interface9where the light undergoes attenuated total reflection due to the SPR, forming the SPR-curve. The intensity of the reflected light beam10is detected by an optical detection unit11(e.g. a photodetector array).

When molecules in the sample bind to the capturing molecules on the sensor chip surface, the concentration, and therefore the refractive index at the surface changes and an SPR response, change in SPR-angle, intensity, or SPR-curve shape parameter, due to the shift in SPR-curve angular position, is detected. Plotting the response against time during the course of an interaction will provide a quantitative measure of the progress of the interaction. Such a plot, or kinetic or binding curve (binding isotherm), is usually called a sensorgram, also sometimes referred to in the art as “affinity trace” or “affinogram”. In the BIACORE® system, the SPR response values are expressed in resonance units (RU). One RU represents a change of 0.0001° in the angle of minimum reflected light intensity, or SPR-curve centroid angle, which for most proteins and other biomolecules correspond to a change in concentration of about 1 pg/mm2on the sensor surface. As sample containing an analyte contacts the sensor surface, the capturing molecule (ligand) bound to the sensor surface interacts with the analyte in a step referred to as “association.” This step is indicated on the sensorgram by an increase in RU as the sample is initially brought into contact with the sensor surface. Conversely, “dissociation” normally occurs when the sample flow is replaced by, for example, a buffer flow. This step is indicated on the sensorgram by a drop in RU over time as analyte dissociates from the surface-bound ligand.

A representative sensorgram (binding curve) for a reversible interaction at the sensor chip surface is presented inFIG. 2, the sensing surface having an immobilised capturing molecule, or ligand, for example an antibody, interacting with a binding partner therefor, or analyte, in a sample. The vertical axis (y-axis) indicates the response (here in resonance units, RU) and the horizontal axis (x-axis) indicates the time (here in seconds). Initially, buffer is passed over the sensing surface giving the baseline response A in the sensorgram. During sample injection, an increase in signal is observed due to binding of the analyte. This part B of the binding curve is usually referred to as the “association phase”. Eventually, a steady state condition is reached at or near the end of the association phase where the resonance signal plateaus at C (this state may, however, not always be achieved). It is to be noted that herein the term “steady state” is used synonymously with the term “equilibrium” (in other contexts the term “equilibrium” may be reserved to describe the ideal interaction model, since in practice binding could be constant over time even if a system is not in equilibrium). At the end of sample injection, the sample is replaced with a continuous flow of buffer and a decrease in signal reflects the dissociation, or release, of analyte from the surface. This part D of the binding curve is usually referred to as the “dissociation phase”. The analysis is ended by a regeneration step where a solution capable of removing bound analyte from the surface, while (ideally) maintaining the activity of the ligand, is injected over the sensor surface. This is indicated in part E of the sensorgram. Injection of buffer restores the baseline A and the surface is now ready for a new analysis.

From the profiles of the association and dissociation phases B and D, respectively, information regarding the binding and dissociation kinetics is obtained, and the height of the resonance signal at C represents affinity (the response resulting from an interaction being related to the change in mass concentration on the surface). This will now be explained in more detail below.

A detailed discussion of the technical aspects and the basic optical principles of BIACORE® instruments and the phenomenon of SPR may be found in U.S. Pat. No. 5,313,264.

FIGS. 3aand 3bschematically illustrate the optical system in such a prior art BIACORE® system, whereFIG. 3bis a top view andFIG. 3ais a cross-sectional side view of the plane P inFIG. 3b. Such systems comprises an illumination unit7comprising a light source24and wedge forming optics26, arranged to direct a wedge shaped beam of light6at a line shaped detection area9on the SPR sensor surface2transverse to the direction of propagation of light. For illustrative purposes, all refractive elements in the light path have been omitted (e.g. optics for coupling the beam to the sensor surface like a prism as is shown inFIG. 1) or replaced by general “optics” units (e.g.20and26). The wedge shaped beam of light6is essentially uniform in the transverse direction as illustrated inFIG. 3b, and strikes the illustrated line shaped detection area9at angles of incidence relevant for SPR detection such as from 62 to 78 degrees. Rays with all the intermediate (e.g. between 62° and 78 degree) angles of incidence are present in the beam. The system further comprises a detection unit11with special, anamorphic detection optics20for directing light reflected from the SPR sensor surface1onto a two-dimensional optical detector unit22such that the angle of reflection is imaged along one dimension (column) and the width of the detection area along the other (row). For illustration purposes, consider only one incident plane, light incident e.g. at 62° is reflected on the sensitized surface9and is imaged by the detection optics20on only one single detection element28A of the two-dimensional optical detector unit22. Similarly, light incident with an angle of 78° will be imaged on one single single detection element28H. Light having incident angle values intermediate between 62 and 78 degrees will similarly strike those single detection elements which are situated between elements28A and28H in the same detector column; inFIGS. 3aand 3bthis is illustrated as being a vertical column.

The light source24, e.g. a light emitting diode, emits a type of light that is substantially monochromatic in character (bandwidth ˜50 nm), and furthermore is incoherent and has a center wavelength of an order of magnitude of about 650 to about 850 nm. Alternatively, the light source24is a laser, e.g. a semiconductor laser, a dye laser or a gas laser, emitting substantially monochromatic and coherent light. The light source24may also take the form of a low coherent edge emitting diode like either a superluminescent or superradiant diode (SLD), or an ELED.

Light rays having a different plane of incidence parallel to the plane of incidence P will in a similar way be imaged on individual detection elements belonging to other columns of the two-dimensional optical detector unit22. Every detection element of a row thus corresponds to one specific angle of incidence. Thus to each column of the two-dimensional optical detector unit22corresponds a respective part of the sensing surface as seen in the transverse direction of the conduit portion. Depending on the width of the sample flow channel, the magnification of the detection optics, the surface dimensions of the individual detection elements, and the spaces between them, a particular number of detection element columns may be required for imaging the total width of the flow channel portion in question.

In the embodiment ofFIGS. 3aand 3b, nine detection spots13a-13ifor interaction analysis are illustrated allowing registration of up to nine independent interactions simultaneously. As is well established in the art, a ligand is immobilized on each detection spot (one or more spots may intentionally be left without ligand to serve as a reference channel for mitigating non-specific contributions to the SPR response) and the same or different analytes are brought into contact with the sensor spots. According to one embodiment, as is shown in U.S. Pat. No. 5,313,264, each detection spot13is associated with a flow channel for passing the analyte over the spot, but alternatively two or more detection spots13may be arranged in one single flow cell e.g. capable of hydrodynamic addressing of individual detection spots13(as is disclosed in U.S. Pat. No. 7,811,515).

In the prior art systems of the type shown inFIGS. 3aand 3b, the max theoretical number of detection spots is limited by the number, of pixel rows on the two-dimensional optical detector unit22, while the practical number depends on the size of the detection spots13and associated fluidic system. However, in many situations there is a need for higher throughput and thus more detection spots are desired on the sensor surface.

FIGS. 4ato 5bshows a schematic embodiment of a new Surface Plasmon Resonance (SPR) biosensor system concept, wherein the number of detection spots13is doubled without the need to significantly redesign the optics of the system. This system concept is disclosed in great detail in the co-pending patent application SE1150890-0

By providing a second light source24bspaced apart from the first light source24aby a suitable distance in the plane P, and suitably controlling the emission of light from the light sources, the illumination unit is arranged to selectively direct the wedge shaped beam of light6at two spaced apart line shaped detection areas9aand9b, respectively, on the SPR sensor surface1transverse to the direction of propagation of light. In general, all elements of the prior art SPR system ofFIGS. 3aand 3bmay be left unchanged, but as will be appreciated by a person skilled in the art there may be optimizations available. It shall be noted that the displacement of the second light source24band the associated beam paths is exaggerated for illustrative purposes, and the real displacement in a working optical design may be very small to achieve a suitable distance between the detection areas9aand9bon the sensor surface. The real displacement may further be restricted by the optical properties (e.g. aperture/imaging area) of all other optical components along the path.

According to one embodiment containing two light sources24aand24babout 0.3 mm apart, two light beams could be generated at the same time giving two detection areas9aand9babout 1 mm apart on the sensor surface1.

Since the two detection areas9aand9bfor each detection spot13pair (spots arranged in the same plane parallel to the plane P) will be imaged onto the same pixel column on the two-dimensional optical detector unit22the two interaction responses measured as one SPR-curve (one dip in the reflectance curve) at the time, cannot be registered completely simultaneous. Therefore, in order to register interaction data independently from detection spots13along the two detection areas9aand9b, the two light sources24aand24bare alternately switched on and off at a suitable frequency, in synchronization with the readout from the two-dimensional optical detector unit22. By this, two nearly simultaneous sets of sensorgrams can be generated, one for each of the two detection spot-rows.

As previously mentioned, the design does not need to be limited to two detection areas9aand9b, andFIGS. 6aand 6bdiscloses an embodiment with 5 parallel detection areas9ato9e, hence providing45detection spots13.

Further, another way to increase the number of detection spots significantly is to use a true two-dimensional SPR detection system where the whole sensor surface is imaged onto a two-dimensional optical detector unit22while scanning the incident angle of the light, one embodiment of such a system is schematically disclosed inFIGS. 6aand 6bwherein the number of detection spots13is the same as in the embodiment ofFIGS. 6aand 6b. Further details of a 2D SPR system can e.g. be found in US2009-0213382.

However, in order to fully gain the benefits of increased optical detection capacity, there is a need for flow cell arrangements capable of providing liquid handling to provide the corresponding number of individual detection spots in an efficient way.

FIGS. 8aand 8bschematically disclose a flow cell arrangement30comprising a flow cell unit32to be docked against the sensor surface1by applying a docking force to form separate elongated flow channels34a-itransverse to the two detection areas9aand9b. Each flow channel34a-icomprises a first fluid port36and a second fluid port38to enable a fluid flow in the flow channel34. As will be evident below, both first and second fluid ports36,38may be used as inlet and/or outlet ports in order to provide the desired flow patterns in the flow cell arrangement30.

In the disclosed embodiments, the flow cell unit32is shown docked to a sensor surface of a SPR biosensor element, but in a general fluidic system, the flow cell unit32may e.g. be docked against any suitable flat lid surface capable of forming a closed flow cell arrangement together with the flow cell unit32.

The fluid flow through the flow cell arrangement is controlled by a fluid control system42connected to the first and second fluid ports36,38of the flow cell unit30by fluid conduits40. In the disclosed embodiment, the fluid conduits40are only shown connected to the ports36,38of one single fluid channel34, but it should be understood that all ports36,38of all fluid channels34a-iare connected to the fluid control system42by corresponding conduits40. Moreover, the conduits40are shown e.g. as tubes or capillaries, but according to an alternative embodiment, the conduits may be formed in an integral fluid block. The fluid control system42may be any suitable system capable of controlling the flow in the flow cell arrangement in accordance with the specific requirements of the fluidic system wherein the flow cell arrangement is used. According to one embodiment, the fluid control system42comprises one dedicated pump (not shown) for each fluid channel34and associated valves (not shown) in order to independently control the fluid flow in each fluid channel34. Alternatively, the fluid control system42comprises a multi-channel pump to control the fluid flow simultaneously in two or more of the flow channels, e.g. a multi-channel peristaltic pump or the like.

In order to provide the desired two dimensional structure of detection spots, the flow cell arrangement according to the present invention is arranged to allow an alternative flow pattern transverse to the elongated fluid channels34a-I, as is disclosed in more detail with reference toFIGS. 9a-15d. According to one embodiment, the whole sensor surface1may be addressable to define detection spots13and the detection spots are defined by a fluidic process in alignment with the optical detection system or the like whereby the resulting detection spots in general are defined by intersections between fluid channels and the transverse flow pattern. Alternatively the sensor surface1comprises discrete sensor surfaces arranged in an array that is aligned with and which may be addressable by the flow cell arrangement.

FIGS. 9aand 9bshow, in two perspective views, one embodiment of a flow cell unit32according to the present invention with 8 adjacent elongated flow channels34a-hdefined by walls of elastic material44protruding a top surface46of the flow cell unit32. The walls44bseparating adjacent flow channels34comprises a valve section48of reduced height, thereby allowing selective opening and closing of a flow path transverse to the elongated flow channels34by controlling the docking force between flow cell unit32and the SPR sensor surface1to an open docking state and a closed docking state respectively (which is schematically shown inFIGS. 10b-d). In order to achieve the selective open and closed docking states, the walls44should be made of a suitable elastic material that can be deformed in order to encompass the valve functionality, while having suitable chemical stability with respect to the fluids to be used in the system. According to one embodiment the walls are made of an elastomer such as silicone rubber (PDMA, PDMS) or the like. The whole flow cell unit32may e.g. be molded in a suitable elastic material, but alternatively, sections of the flow cell unit32may be formed in another material, such as a rigid material providing increased support during docking, and whereby the elastic walls44attached to the top surface46of the flow cell unit32by suitable means, such as co-molding or the like. As is shown inFIGS. 9aand 9b, the valve sections48are formed with a flat valve face48aand inclined segments48bextending from the valve face to the top face of the walls44in order to achieve a smooth transition between the top face and the valve face to ensure sealing contact between the walls and the sensor surface in the closed docking state.

In order to achieve well defined force ranges for the open docking state and the closed docking state respectively, the flow cell unit32may comprise one or more force control elements50aand50bof elastic material, arranged to stepwise rise the docking force required to further compress the walls44, at one or both docking states.

FIG. 10ais a top view of a flow cell unit32with 9 adjacent elongated flow channels34a-idefined by walls44. AndFIGS. 10b-dshows the flow cell unit32ofFIG. 10ain cross section along in three different docking force states. According to one embodiment schematically disclosed inFIG. 10d, the walls44protrudes slightly further from the top surface46than the force control elements50a. Thereby the walls44are compressed slightly before the force control elements50aabuts the sensor surface1, as is illustrated inFIG. 10c, whereby the force needed to compress the walls44of the flow cell unit32increases in a stepwise manner creating a well-defined and sufficiently broad force range for the open docking state. Similarly, after applying further force, compressing both the walls44and the force control elements50afurther until force control elements50bis reached and the force needed to compress the walls44further increases a second time in a stepwise manner, thus creating a well-defined and sufficiently broad force range for the closed docking state. It should be noted that one of or both of the force control elements50aand50bmay be omitted in case the docking force may be controlled in a sufficiently precise manner. The dimensions of the walls44, flow channels34, valve sections48, force control elements50aand50betc. need to be adapted to the specific flow cell dimensions and requirements, which will be apparent to the skilled person.

FIGS. 11aand 11bshows one schematic example of a docking unit52arranged to control docking force between flow cell and the sensor surface1to an open docking state and a closed docking state respectively. The disclosed docking unit52is a mechanical arrangement based on a cam type actuator54with predefined docking force positions54aand54bfor the open and closed state respectively. In order to provide predefined docking force in the two docking states, the docking unit52comprises a force control arrangement, e.g. comprised of two parallel spring elements56aand56bof different length. In this way only one spring element56ais engaged in the open docking state shown inFIG. 11bwhereby the applied force is controlled by the characteristic of spring element56a. Whereas in the closed docking state, both spring elements56aand56bare engaged and the applied force is controlled by the combined characteristics of the two spring elements56aand56b.

According to an alternative embodiment, there is provided a docking force sensor and the docking unit is arranged to apply a predefined force based on feedback from the force sensor. In a SPR biosensor system the docking force sensor may be replaced by SPR based sensing of the docking force states, as it will be possible to register a change in the SPR response when the valve face48abuts the sensor surface1.

As can be appreciated by a skilled person, the desired docking force level for the different open and closed states respectively, may be achieved by precise and repeatable positioning of the docking unit52without any registration or specific control of the docking force.

FIG. 12ashows the flow cell unit32ofFIG. 10ain the closed docking force state, whereby 9 separate flow channels34a-iare formed, and 9 different sample solutions may e.g. be introduced in parallel. Similarly,FIG. 12bshows the flow cell unit32in the open docking force state whereby there is provided a flow path transverse to the elongated flow channels. As is shown in the disclosed example, two different sample fluids may be introduced through ports36iand38iat one end in the transverse direction and extracted at ports36aand38athe other end, thereby creating a transverse laminar flow with a well-defined interface60. In this way two different transverse sections58aand58bof the sensor surface can be addressed independently by suitable reagents to create two different detection surface states, e.g. during immobilization and/or detection steps in a biosensor system.

FIGS. 13a-fshows one possible series of process steps wherein the flow cell arrangement according to the present invention is utilized to immobilize ligands for detection using a two-line SPR biosensor, comprising the following steps:1. Activation of a first section58aby flowing activation fluid from port36ito port36a, while flowing a protecting fluid e.g. buffer from port38ito port38a. (FIG. 13a)2. Flowing ligand solutions along flow channels34a-iwhereby ligands get immobilized in the intersecting region of each channel and the first section58aforming detection spots along the SPR detection line9b. (FIG. 13b)3. Deactivation of the first section58aby flowing deactivation fluid from port36ito port36a, while flowing a protecting fluid e.g. buffer from port38ito port38a. (FIG. 13c)4. Optionally repeating steps a to c for the second section58bto correspondingly immobilize ligands at intersecting regions of said section forming detection spots along the SPR detection line9a. (FIGS. 13a-c), Alternatively, the detection spots in the second section58bare left blank as reference spots.5. Flowing analyte solutions along flow channels34a-iwhile registering interaction responses for the detection spots13along the SPR detection lines9aand9b(FIG. 13d)6. Regenerating the immobilized ligands at all detection spots13simultaneously by flowing regeneration fluid from ports36iand38ito ports36aand38a. (FIG. 13e)

FIGS. 14aand 14bshow one embodiment, where the interface position60of the transverse flowpath is shifted by controlling the relative flow rates of the two fluids, e.g. to provide hydrodynamic addressing of one or more additional transverse detection lines9c. Various methods of achieving hydrodynamic positioning of such an interface are e.g. disclosed in U.S. Pat. No. 7,811,515, U.S. Pat. No. 7,219,528, U.S. Pat. No. 7,015,043 and WO2003102580, which all are incorporated by reference.

FIGS. 15ato 15dshows an alternative embodiment comprising 5 transversely arranged inlet-outlet pairs62-64a-earranged to provide dedicated transverse laminar flow channels66a-ealong the transverse flow path during the open docking force state, thus avoiding the need for hydrodynamic positioning of the interface60to address additional detection areas on the sensor surface1. In the disclosed embodiment, the ports of the inlet-outlet pairs62-64a-eare arranged in the outer flow channels34aand34irespectively and said outer flow channels are shown to be used as ordinary flow channels during e.g. immobilization and/or detection, but in an alternative embodiment (not shown), the inlet-outlet pairs62-64a-emay be arranged in separate outer compartments not used as flow channels and which are opened and closed by a corresponding valve section48. As is disclosed inFIG. 15c, the inlet-outlet pairs62-64a-eare arranged to provide laminar flow channels66a-e, and in order to avoid distortion at the outer laminar flow channels66aand66erespectively, a laminar flow may also be established between the outermost first and second fluid ports36,38respectively. By this arrangement a large number of detection spots may be provided in an array where the fluid channels34a-icrosses the laminar flow channels66a-e. i.e. 45 independent detection spots.

FIGS. 16aand 16bshows an alternative use of the flow cell arrangement as disclosed inFIGS. 12ato 14b, wherein the outermost channels34aand34iand the associated ports36a,36i,38aand38iare dedicated for transverse flow only. By this restriction, liquid handling of reagents in the form of activation, deactivation and regeneration fluids is separated from the liquid handling of ligand and analyte sample solutions. By this separation time consuming washing steps etc can be eliminated for many types of interaction experiments. In an alternative embodiment, the ports36a,36i,38aand38idedicated for transverse flow only are arranged in positions optimized for laminar transverse flow in the flow cell in a similar way as the inlet outlet pairs62a-64ainFIG. 15a.