FR2783919A1 - Integrated optical biochemical sensor for detecting the different fluid components during fluid analysis uses wave guide and optical coupler on substrate having slotted fluid channel - Google Patents

Abstract

The sensor includes a channel (48) through which the fluid to be analyzed passes, an optical wave guide (52) arranged over a part or the whole of the length of the passage (48), a biochemical layer on the wall of waveguide in contact with fluid, sensitive to components to be detected, fluid transport system, with electrodes, light beam emitter and optical coupler. The channel (48), wave guide (52) and the optical coupler (68,78) are formed in a slot in a substrate (60). A cover (56) covering the upper face of the substrate (60) closes the slot to form the channel (48). The fluid transport system electrodes are formed on the cover (56) or the substrate (60). Voltage on the electrodes generates an electrical field which displaces the fluid.

Description

-1

INTEGRATED OPTICAL SENSOR

  TO DETECT THE COMPONENTS OF A FLUID

  The invention relates to biochemical sensors which are used to detect the components of a fluid and, more particularly, sensors of the optical type. In certain sensors of this type, for example, the phase speed of a light beam in an optical waveguide is modified by the variation of the refractive index of the wall of the guide due to the presence of a component. of the fluid to be analyzed, the fluid being in contact with the wall of the guide by means of a biochemical layer adapted to the component to be detected. Changes in phase velocity can then be accurately measured by an interferometric device such as

the Mach-Zehnder interferometer.

  In other sensors, the detection of the components of the fluid brought into contact with the waveguide implements other characteristics of these components such as their property of absorption of certain wavelengths or emission of

fluorescence.

  A structure of biochemical sensor according to the prior art of a certain type is represented in FIG. 1 and comprises a part or optical block 10 and a part or fluid block 12 for the passage of the liquid to be analyzed, these two parts 10 and 12 being assembled along their opposite faces 14 and 16 respectively. The optical unit 10 comprises a polymer substrate 18 on which an optical waveguide 20 is produced, a light source (light emitting diode or laser diode) 26 and a detector 30. On the substrate also exist two coupling networks 22 and 28 for, respectively, coupling the incident beam 24 to the waveguide and directing the

  output beam on detector 30.

  Part 12 is made so as to provide a passage 32 for the fluid to be analyzed, which fluid enters via an inlet duct 34 and exits via a duct

exit 36.

  The face of the waveguide 20 in contact with the liquid to be analyzed is covered over a certain length or surface with a detection substance 38

adapted to the component to be detected.

  In the structure of Figure 1, there is provided a cavity 40 above the coupling network 22 in which circulates a buffer solution, or fluid "neutral" vis-à-vis the propagation of waves. This buffer solution enters via a conduit 42 and exits via the conduit 36 without mixing with the fluid to be analyzed which leaves the passage 32. By this arrangement, it is avoided that the coupling network 22 is in contact with the fluid to be analyzed with the risk. that the latter modifies its optical properties. Of course, the same arrangement can be applied for the coupling network of

exit 28.

  Such a structure has the drawback of separating the two functions, optical on the one hand and fluidic on the other hand, which leads to manufacturing the two parts 10 and 12 separately and with very high precision with a view to their precise assembly. This therefore results in a high manufacturing cost, the higher the greater the number of measurement paths.

  in multi-analysis or multi-component sensors.

  An object of the present invention is to provide a new integrated optical sensor structure which is simple to manufacture and at a cost much lower than that of the structures of the prior art, which makes it easier to produce structures.

  multipath or multitrack for multi- sensors

analysis or multi-component.

  This object is achieved by making the optical part and the channel or conduit for passage of the fluid on the same side of a substrate, this side then being covered.

  a flat part forming a cover.

  The invention relates to an integrated optical sensor for detecting at least one component of a fluid to be analyzed comprising: - at least one channel or conduit for the passage of the fluid to be analyzed, - an optical waveguide disposed on all or part of the length of the channel, - a biochemical layer sensitive to at least said component to be detected disposed on the wall of the optical waveguide in contact with the fluid to be analyzed, - means for entering and leaving the fluid to be analyzed in the conduit, - means of transporting the fluid inside the conduit, - an emitter of a laser light beam, - means of optical coupling at the input and at the output of the optical waveguide for the entry and exit of the laser light beam, and - a detector of the laser light beam leaving the optical waveguide, characterized - in that the conduit, the optical waveguide and the optical coupling means are made in at least one engraved groove in a substrate, and - in that a cover covers the solid upper face of the substrate so as to close the

  groove and thus realize the conduit.

  In such a sensor, the means of transport, which must ensure the regular passage of the fluid to be analyzed in the channel, will advantageously make use of the technique of electrophoresis; the necessary electric field is then created by means of electrodes produced, at the level of the channel, either on the substrate or on the cover. Other techniques can also be implemented, such as those using micropumps or any other means to generate a pressure difference between the inlet and the outlet of the channel. The means for entering and leaving the fluid to be analyzed can be produced in the substrate or in

lid.

  Such a sensor structure according to the invention makes it possible to produce a multi-component sensor by producing a plurality of conduits in parallel on the same substrate, each conduit being adapted, via the sensitive biochemical layer, to

  detect one of the components of the fluid to be analyzed.

  The input optical coupling network is, for example, single while the optical output coupling network can be single or comprise a

  optical coupling network by component to be detected.

  The fluid inlet and outlet means can be provided for circulating a buffer solution at the level of the optical coupling networks, while the fluid to be analyzed circulates only in the conduits

  including sensitive biochemical layers.

  Other characteristics and advantages of the present invention will appear on reading the

  following description of specific examples of

  realization, said description being made in relation

  with the accompanying drawings in which: - Figure 1 is a structure of an integrated optical sensor according to the prior art, - Figure 2 is a perspective view of a structure according to the invention, - Figure 3 is a perspective view of a basic structure of a Mach-Zehnder interferometric sensor, - Figure 4 is a view, in simplified section, of a sensor in which the inlet and outlet conduits of the fluid to be analyzed cross the substrate, - Figure 5 is a simplified sectional view of a sensor in which the inlet and outlet conduits of the fluid to be analyzed pass through the cover, and - Figures 6, 7, 8 and 9 are diagrams

  showing multi-analysis or multi-component sensors.

  A variant of an integrated optical sensor of the MachZehnder interferometer type according to the invention comprises (FIGS. 2 and 3) a substrate 60 in which are made at least two grooves 62 and 64 separated by a wall 46, these two grooves having a common inlet 48 and a common outlet 50. The bottom of the grooves 62 and 64 is covered with a dielectric layer 52 which constitutes a waveguide for a light beam 24 (FIG. 1) not shown in FIGS. 2 and 3. Depending on the method of manufacturing which will be described below, a dielectric layer 54 can also cover the upper face of the substrate as well as the upper surface of the wall 46 separating the two grooves 62 and 64. The upper face of the substrate 60 receives a cover 56 whose face lower is fixed on the dielectric layer 54 in a sealed manner so that the grooves 62, 64 in combination with the inlet 48 and the outlet 50 provide channels or conduits for the p assage of a fluid to be analyzed. It should be noted that the dielectric layers 52 and 54 have the same thickness because they come from a

same deposit operation.

  The bottom of one of the channels 62 or 64 formed by the external surface of the waveguide comprises, over a certain length, a deposit (not shown) of a biochemical substance sensitive to the component to be detected in the fluid. Alternatively, different chemicals can be deposited in the

two channels.

  The manufacture of the structure described in relation to FIGS. 2 and 3 may include the following steps: - take a substrate, for example, made of quartz, - make, in the substrate, the grooves 62 and 64, the inlet 48 and the output 50, as well as the input and output coupling networks 22 and 28, by structuring techniques, such as those used for manufacturing integrated circuits and using photolithography and wet or dry etching , - depositing in a single operation the dielectric layers 52 and 54 over a thickness sufficient to obtain a waveguide on the bottom of the grooves, and covering the product obtained with the cover 56 by sealing the latter on the dielectric layer 54 for obtain the watertightness of the channels obtained from

  grooves covered by the cover.

  According to a particularly interesting variant of mass production of inexpensive components, the structured quartz substrate is used as a model for a production by replication of polymer-based components (for example, polycarbonate). For this, a mold is produced by electrodeposition of Nickel on the structured substrate, to reproduce the structures of the model, then this mold is used for the reproduction in quantity of components identical to the model in a polymer material, said reproduction being made by stamping or stamping. hot (called "hot-embossing" in Anglo-Saxon literature). Other replication techniques realizing the transfer of the structures of a model in a

  inexpensive substrate can also be used.

  Once obtained, the structured components (grooves and coupling structures), the steps of depositing the material constituting the waveguide, the material constituting the sensitive layer and fixing the

  cover are executed as shown above.

  The simplified diagrams of FIGS. 4 and 5 show two exemplary embodiments of the inlet and the outlet of the fluid to be analyzed, a first example (FIG. 4) in which the inlet 80 and outlet 82 conduits are produced in the substrate. 60 and a second example (FIG. 5) in which the inlet 84 and outlet 86 conduits are produced in the cover 56, their orifice towards the outside can end in

  a flare or funnel 68 and 70.

  In these FIGS. 4 and 5, the broken lines 72 indicate the detection zone formed by the optical waveguide coated by the sensitive biochemical layer, the elements referenced 74 and 76 indicate electrodes which are connected to sources of positive potential or negative and the elements referenced 78 and 68 indicate the optical coupling networks of entry and exit of the light beam

in waveguide 52.

  In the diagrams of FIGS. 4 and 5, it is assumed that the substrate 60 is made of a transparent material allowing the passage of the incident beam from an external source to the input coupling network 78 and the passage of the output beam from the output coupling network 68 to an external detector. The realization of the light source and the detector in the same substrate of the sensor is also possible for a better compactness of the assembly, the material of the substrate in this case

be chosen accordingly.

  The electrodes 74 and 76 serve to move, by electrophoresis, the fluid to be analyzed in the passage conduits. As indicated above, other arrangements of these electrodes may be provided depending on the applications envisaged or the requirements

Manufacturing.

  Due to its simplicity of manufacture, the device according to the invention can be used to simultaneously detect several components regardless of the physical phenomenon used to detect the component: fluorescence,

  refractometry, interferometry, absorption, etc ...

  Thus, the device of FIG. 6 relates to refractometry, the devices of FIGS. 7 and 8 relate to the implementation of the interference phenomenon while the device of FIG. 9 relates to the implementation of the phenomenon of

fluorescence.

  The device of FIG. 6 allows the simultaneous detection of seven components in the same fluid using seven channels or channels 901 902, 903, 904, 905, 906 and 907, each channel comprising a specific biochemical sensitive layer 921, 922, 923, 924, 925, 926 and 927. The fluid to be analyzed enters through inlet 102 and is distributed in the seven channels or channels and exits through

exit 104.

  The light beam 106 enters the waveguide through the optical coupling network 108 and leaves it

by the coupling network 110.

  The means of transport (for example, electrodes) for moving the fluid have not been shown. Each biochemical layer is adapted to detect a component and this results in different exit angles of the exit light beams, depending on the

  component that is present in this fluid.

  According to an alternative embodiment, a coupling network can be provided in each measuring arm 901 to 907, each network delivering an output beam to a given detector. The input network being unique for all the measuring arms, it even becomes possible to calibrate the sensor to take into account

possible optical losses.

  The devices in FIGS. 7 and 8 make it possible to carry out several component detections simultaneously by implementing the interference phenomenon. Thus, in FIG. 7, the fluid to be analyzed penetrates through the inlet 102 and is then oriented towards three channels 120, 122 and 124, each channel then being divided into two equal parallel sub-channels (1201, 1202), (1221 , 1222) and (1241, 1242) which recombine

  then to allow the fluid to exit at 104.

  The light beam enters via the network 108 and leaves via the networks 126, 128 and 130 arranged after the recombination of the two sub-channels. In each channel, 122 and 124, a sub-channel 1201, 1221 and 1241 serves as a reference, represented by a hexagon, while the other sub-channel 1202, 1222 and 1242 serves as a measurement and incorporates a sensitive layer represented by a

rectangle.

  In this structure of FIG. 7, the optical coupling networks 108, 126, 128 and 130 are in contact with the liquid to be analyzed, which can alter the measurements and, to remedy this, the structure of FIG. 8 is proposed. in which the optical coupling networks are in contact with a buffer solution. This structure, which is identical to that of FIG. 7 from the optical point of view, is different from the point of view of the fluid paths. In fact, fluid paths are provided which only concern the optical coupling networks and fluid paths

  which only concern the measurement paths.

  The coupling networks 108, 126, 128 and 130 are arranged in channels separate from the measurement channels, 122 and 124. Thus, the fluid to be analyzed penetrates through the inlet 132e disposed downstream of the input coupling network 108 and exits via three outputs 132sl, 132s2 and 132s3 arranged upstream of the

output coupling 126, 128 and 130.

  The buffer solution enters via inlet 102e and leaves via outlet 102S for the coupling network 108 and it enters via inlet 104e and exits respectively through exits 104sl, 104s2 and 104s3

  for coupling networks 126, 128 and 130.

  In the structure of FIG. 9, implementing the fluorescence or absorption detection, the fluid to be analyzed enters through inlet 102 and exits through five outlets 1041, 1042, 1043, 1044 and 1045

  each corresponding to a passageway or conduit.

  The light beam 106 enters through the coupling network 108 and exits through five optical coupling networks 1401, 1402, 1403, 1404 and 1405, each optical coupling network being associated with a sensitive biochemical layer corresponding to a component to be detected. As indicated above, each structure described in relation to Figures 6, 7, 8 or 9 implements a single physical phenomenon: refraction, interference, absorption or fluorescence. However, the invention makes it possible to produce structures which simultaneously implement several physical phenomena for the detection of the components. Thus, in a structure similar to that of FIG. 6, the channels 903 and 905, assumed to be of the same length, can implement the interference phenomenon according to a Mach-Zehnder cell on condition of providing an optical coupling network to the exit from the two channels 903 and 905. Other channels, for example the channels 901 and 902 can be of the fluorescence type according to the diagram of FIG. 9 with a

  output coupling network per channel.

  The advantages of the sensors according to the invention are, among others: - the structures are easy to produce and inexpensive, - these structures allow a large number of channels to be produced on the same substrate, each channel, or group of channels, making it possible to detect a particular component, - these structures can simultaneously implement several physical detection phenomena, - all the critical elements of the sensor can be produced on a single and same substrate, so that the cover can be a simple plate

  requiring no precise positioning.

  Although reference has been made, in the description

  above, to coupling networks produced on the waveguide for, respectively, coupling the incident light beam into the latter or extracting the output beam therefrom, it will be understood that other means can be used without limiting the scope of the present invention. Mention will be made, by way of example, of direct coupling consisting in injecting, by suitable optics, the incident light into a transverse wall of the waveguide and in

  extract the output beam in the same way.

  Regarding the light source, its choice will depend on the intended application. Thus, a laser source will be required when a precise wavelength and a defined propagation mode are necessary, while a light-emitting diode may be used in

  sensors using multi-mode waveguides.

  Finally, the detectors must be provided to detect the output information, whether this consists of an intensity, a wavelength, an interference fringe or an angular position. Among the detectors that can be used, one can mention charge coupled devices (CCD) and networks

of photodiodes.

Claims (9)

R E V E N D I C A T IONS   1. Integrated optical sensor for detecting at least one component of a fluid to be analyzed comprising: - at least one channel or conduit (48) for the passage of the fluid to be analyzed, - an optical waveguide (52) disposed on all or part of the length of the conduit, - a biochemical layer (72) sensitive to at least said component to be detected disposed on the wall of the optical waveguide in contact with the fluid to be analyzed, - input and output means (80, 82, 84, 86) of the fluid to be analyzed in the channel, - means of transport (74, 76) of the fluid inside the duct, - an emitter (26) of a beam (24) of light, - optical coupling means (68, 78) at the entry and exit of the optical waveguide for the entry and exit of the light beam, and - a detector (30) of the beam of light leaving the optical waveguide (52), characterized - in that the conduit (48), the optical waveguide (52) and the optical coupling means are re formed in at least one groove made in a substrate (60), and - in that a cover (56) covers the solid upper face of the substrate (60) so as to close   the groove and thereby making the conduit (48).   2. Sensor according to claim 1, characterized in that the means for transporting the fluid to be analyzed comprise electrodes (74, 76) produced on the cover (56) or on the substrate, said electrodes receiving voltages capable of generating a field   electric causing the displacement of said fluid.   3. Sensor according to claim 1 or 2, characterized in that the means for entering and leaving the fluid to be analyzed comprise conduits (80, 82) made in the substrate (60).   4. Sensor according to claim 1 or 2, characterized in that the means for entering and leaving the fluid to be analyzed comprise conduits (84, 86,   68, 70) made in the cover (56).   5. Sensor according to any one of   previous claims 1 to 4, characterized:   - in that the substrate (60) comprises a plurality of conduits (90, 120, 122, 124) arranged in parallel with respect to the means of input and output of the fluid to be analyzed, - in that each conduit is adapted, by means of the biochemical layer sensitive to detect one of the components of the fluid to be analyzed, and - in that the optical coupling means to   the input comprises a single coupling network (108).   6. Sensor according to claim 5, characterized in that the optical coupling means at the output   comprise a single coupling network (110).   7. Sensor according to claim 5, characterized in that the optical coupling means at the output comprise an optical coupling network (126, 128,, 1401 to 1405) per component to be detected in the fluid to analyze.   8. Sensor according to any one of   previous claims 5 to 7, characterized:   - in that the input means of the fluid to be analyzed are arranged downstream of the optical input coupling network, and - in that the output means of the fluid to be analyzed are arranged upstream of the coupling network output optics.   9. Sensor according to any one of   previous claims 5 to 7, characterized:   - in that the inlet means of the fluid to be analyzed are arranged in front of the optical coupling network, - in that the outlet means of the fluid to be analyzed are arranged downstream of the optical coupling network, and - in that the input and output optical coupling networks are each in a conduit in which a neutral fluid flows with respect to the   wave propagation in the optical waveguide.