Device and method for investigating analytes in liquid suspension or solution

Abstract

An optical detection device is provided for analyzing analytes in a liquid suspension or solution that can detect and process a large number of wavelengths of incident and fluorescent light simultaneously, which is small in size and can be easily adapted to different investigation requirements. The optical detection device may include a light supplying device, an analyte handling device, a light directing device, and a detector integrated on planar substrate devices, respectively. A plurality of optical waveguides are integrated in the substrate devices to direct light emitted by the light supplying device through the different sections of the optical detector to the detector. The analyte handling device may include an analyte channel for the liquid flow of the analyte suspension or solution and an analyte sorting device comprising several sorting channels.

1 ) Device for analysing analytes in a liquid suspension or solution comprising, an analyte handling means including an analyte input region, an analyte channel for carrying analytes in a liquid suspension or solution comprising a light receiving region for receiving light from a light supplying means to illuminate the analytes in an interrogation region of the analyte channel, an analyte output region, a light guiding means for directing light emerging from the analytes in the interrogation region to an optical detection means for detecting one or more properties of the analytes in the suspension or solution, characterised in that at least the analyte channel and a first optical waveguide for guiding light emerging from the analytes in the analyte channel are integrated on the same first planar substrate. 
     
     
         2 ) Device as claimed in  claim 1 , wherein a second optical waveguide guiding light emerging from the analytes in the analyte channel is integrated on the first planar substrate. 
     
     
         3 ) Device as claimed in  claim 1  or  claim 2 , wherein a third optical waveguide guiding light incident on the analytes in the analyte channel is integrated on the first planar substrate. 
     
     
         4 ) Device as claimed in any preceding claim, wherein the first optical waveguide is interfacing with the analyte channel, such that it collects light travelling in the analyte channel at an angle of between 30 and 60 degrees from the longitudinal axis of the analyte channel. 
     
     
         5 ) Device as claimed in any preceding claim, wherein the first optical waveguide is interfacing with the analyte channel, such that it collects light travelling in the analyte channel at an angle of substantially 45 degrees from the longitudinal axis of the analyte channel. 
     
     
         6 ) Device as claimed in any of  claims 2 - 5 , wherein the second optical waveguide is interfacing with the analyte channel, such that it collects light travelling in the analyte channel at an angle of between 60 to 120 degrees from the light collected by the first optical waveguide. 
     
     
         7 ) Device as claimed in any of  claims 2 - 6 , wherein the second optical waveguide is interfacing with the analyte channel, such that it collects light travelling in the analyte channel at an angle of substantially 90 degrees from the light collected by the first optical waveguide. 
     
     
         8 ) Device as claimed in any of  claims 3 - 7 , wherein the third waveguide divides into two waveguides for injecting light into two spatially separate interrogation regions in the analyte channel and at least one waveguide is provided for collecting light emerging from the analytes adjacent to each one of the separate interrogation regions. 
     
     
         9 ) Device as claimed in any preceding claim wherein doped absorbing regions are provided on the first substrate adjacent to the analyte channel and the waveguide(s) for reducing the amount of unguided light propagating in the first substrate. 
     
     
         10 ) Device as claimed in any preceding claim wherein the refractive index of any or all of the waveguides substantially matches the refractive index of the analyte suspension or solution. 
     
     
         11 ) Device as claimed in any preceding claim, wherein at least one waveguide is tapered at its interface with the analyte channel. 
     
     
         12 ) Device as claimed in any preceding claim, wherein a single or multiple dielectric coating is formed at the interface between at least one waveguide and the analyte channel. 
     
     
         13 ) Device as claimed in any preceding claim comprising a light supplying means for emitting light with a predetermined characteristic, which is changeable by interaction of the light with the analytes in the suspension or solution according to the properties of the analytes. 
     
     
         14 ) Device as claimed in any preceding claim, wherein the light supplying means is emitting light of one or more discrete wavelengths or wavelength bands λ, λ 1  . . . λ m . 
     
     
         15 ) Device as claimed in  claim 14 , wherein the wavelength or wavelength bands λ, λ 1  . . . λ m  is/are selected according to the properties of the analytes to be investigated. 
     
     
         16 ) Device as claimed in any of  claims 14  and  15  comprising a light detecting means, wherein the wavelength or wavelength bands λ, λ 1  . . . λ m  and wavelength or wavelength bands λ′ 1  . . . λ′ n  emitted by the analytes as a consequence of fluorescence can be discriminated by the light detecting means. 
     
     
         17 ) Device as claimed in any of  claims 14 - 16 , wherein none of the wavelength bands have and overlap with one another of more than −20 dB 
     
     
         18 ) Device as claimed in any of  claims 14 - 16 , wherein none of the wavelength bands λ 1  . . . λ m , λ′ 1  . . . λ′ n  have and overlap of more than −30 dB 
     
     
         19 ) Device as claimed in any preceding claim, wherein a first liquid guiding means is provided for introducing sheath fluid into the analyte channel and a second liquid guiding means is provided for introducing the analyte suspension into the analyte channel, wherein the two liquid guiding means are formed such that they allow for hydrodynamic focusing of the analyte suspension or solution into the centre of the analyte channel. 
     
     
         20 ) Device as claimed in any preceding claim wherein an analyte channel is machined or etched into the top surface of the first planar substrate and the analyte channel is open towards the said top surface, and wherein the analyte channel is sealed by attaching a fourth substrate to the first substrate that extends over the area of the analyte channel. 
     
     
         21 ) Device as claimed in  claim 20 , wherein apertures are provided in the fourth substrate, such that liquid guiding means can be connected to the device for injecting liquid into and receiving liquid from the analyte channel via analyte input and output ports. 
     
     
         22 ) Device as claimed in any of  claims 1 ,  2 ,  4 - 7 ,  9 - 21 , wherein the analyte channel extends along an edge of the first substrate such that light illuminating the analytes in an interrogation region in the analyte channel can be received from the edge of the substrate. 
     
     
         23 ) Device as claimed in any of  claims 1 ,  2 ,  4 - 7 ,  9 - 21 , wherein the waveguide and the analyte channel are formed by the same recess in the first substrate, such that incident light is introduced into the interrogation region by directing light along the analyte channel. 
     
     
         24 ) Device as claimed in any preceding claim, including at least one of an analyte sorting means according to any of  claims 30 - 32 , a light supplying means according to any of  claims 33 - 37 , a light directing means according to any of  claims 38 - 40 , and a light detecting means according any of  claims 41 - 47 . 
     
     
         25 ) Device as claimed in  claim 24 , wherein at least two of the analyte sorting means according to any of  claims 30 - 32 , the light supplying means according to any of  claims 33 - 37 , the light directing means according to any of  claims 38 - 40 , and the light detecting means according any of  claims 41 - 47  can be connected to one another by means of optical fibres. 
     
     
         26 ) Device as claimed in any of  claim 24  or  25 , wherein at least two of the analyte sorting means according to any of  claims 30 - 32 , the light supplying means according to any of  claims 33 - 37 , the light directing means according to any of  claims 38 - 40 , and the light detecting means according any of  claims 41 - 47  are integrated on the same planar substrate. 
     
     
         27 ) Device as claimed in any of  claims 1 - 26 , or light supplying means as claimed in any of  claims 33 - 37 , or light directing means as claimed in any of  claims 38 - 40 , wherein any of the first substrate, the second substrate, and the third substrate is made of silica. 
     
     
         28 ) Device as claimed in any of  claims 1 - 26 , or light supplying means as claimed in any of  claims 33 - 37 , or light directing means as claimed in any of  claims 38 - 40 , wherein any of the first substrate, the second substrate, and the third substrate is made of silica-on-silicon. 
     
     
         29 ) Device as claimed in any of  claims 1 - 26 , or light supplying means as claimed in any of  claims 33 - 37 , or light directing means as claimed in any of  claims 38 - 40 , wherein any of the first substrate, the second substrate, and the third substrate is made of silicon-on-insulator. 
     
     
         30 ) Analyte sorting means for sorting analytes in a liquid suspension or solution, comprising a plurality of sorting channels comprising at least one y-junction are integrated on the first substrate, wherein opposite polarity electrodes are formed in the first substrate on either side of the at least one y-junction. 
     
     
         31 ) Analyte sorting mans as claimed in  claim 28  wherein the plurality of sorting channels is formed as a cascade of y-junctions comprising at least two stages. 
     
     
         32 ) Analyte sorting means as claimed in  claim 29 , wherein a plurality of contact traces are formed on the first substrate to connect an external computer controlled power supply to the each of a plurality of pairs of opposite plurality electrodes formed in the first substrate. 
     
     
         33 ) Light supplying means for use with a device for analysing analytes in a liquid suspension or solution, wherein one or several components of the light supplying means are integrated on a second planar substrate. 
     
     
         34 ) Light supplying means as claimed in  claim 33 , wherein at least one or more light emitting diodes or laser diodes are attached to the second planar substrate. 
     
     
         35 ) Light supplying means as claimed in  claim 34  wherein at least one integrated optical waveguide for carrying light from the light emitting diode(s) or laserdiode(s) is leading from the light emitting diode(s) or laserdiode(s). 
     
     
         36 ) Light supplying means as claimed in  claim 34  wherein several waveguides are leading from each one in an array of light emitting diodes or laserdiodes and a dispersive element is integrated on the second planar substrate for combining light of different wavelengths λ 1  . . . λ m  received from the waveguides into a single output waveguide. 
     
     
         37 ) Light supplying means as claimed in  claim 36  wherein the dispersive element is an arrayed waveguide grating or a transmission grating formed by an array of recesses etched into the second substrate. 
     
     
         38 ) Light directing means for use with a device for analysing analytes in a liquid suspension or solution, wherein at least one dispersive element, at least one optical waveguide for carrying light towards the dispersive element, and at least one plurality of output waveguides collecting light of wavelengths or wavelength bands λ 1  . . . λ m , λ′ 1  . . . λ′ n  to be separated by the at least one dispersive element are integrated on a third planar substrate. 
     
     
         39 ) Light directing means as claimed in  claim 38 , wherein the dispersive element is an arrayed waveguide grating or a transmission grating formed by an array of recesses etched into the second substrate. 
     
     
         40 ) Light directing means as claimed in any of  claims 38  and  39 , wherein one dispersive element, one optical waveguide for carrying light towards the dispersive element, and one plurality of output waveguides collecting light of wavelengths or wavelength bands λ 1  . . . λ m , λ′ 1  . . . λ′ n  to be separated are provided each for separating light received from a forward scatter path and for separating light from a side scatter path leading from an analyte interrogation region. 
     
     
         41 ) Light detecting means for use with a device for analysing analytes in a liquid suspension or solution, wherein at least one optical detector is integrated in or hybridised on a fifth planar substrate. 
     
     
         42 ) Light detecting means for use with a device as claimed in  claim 41 , wherein a plurality of optical detectors is provided with one detector each being provided for detecting a different one of the wavelengths λ 1  . . . λ m , λ′ 1  . . . λ′ n . 
     
     
         43 ) Light detecting means as claimed in any of  claims 41  and  42 , wherein any of the detectors are photodiodes. 
     
     
         44 ) Light detecting means as claimed in any of  claims 41 - 43 , wherein each detector is mounted on top of one of several v-grooves terminating in an inclined end face formed in the fifth substrate, the v-grooves extending to the edge of the substrate. 
     
     
         45 ) Light detecting means as claimed in any of  claims 41 - 44 , wherein the fifth substrate is butt-coupled to the third substrate and bonded by means of an appropriate glue or resin. 
     
     
         46 ) Light detecting means as claimed in any of  claims 41 - 45 , wherein each in the plurality of detectors receives light from a different waveguide in at least one of the pluralities of output waveguides integrated in the third planar substrate. 
     
     
         47 ) Light detecting means as claimed in any of  claims 41 - 46 , wherein an array of detectors is provided each for receiving light transmitted from a forward scatter path and light transmitted from a side scatter path leading from an analyte interrogation region. 
     
     
         48 ) Use of the optical detection device as claimed in any of  claims 1 - 29  for investigating the properties of one or more analytes in a liquid suspension or solution. 
     
     
         49 ) Use of the optical device as claimed in  claim 48 , wherein the optical properties of the one or more analytes in the suspension or solution are marked by markers with known optical properties and the one or more wavelength or wavelength band(s) λ 1 , . . . , λ m  of the light supplying means are selected according to emission and absorbtion maxima of the used markers. 
     
     
         50 ) Use of the optical device as claimed in any of  claims 48  and  49 , wherein the markers for the analytes are fluorescent. 
     
     
         51 ) Use of the optical detection device as claimed in  claims 48 - 50  for sorting the analytes of the suspension or solution according their different optical properties by guiding them into different sorting channels for different properties. 
     
     
         52 ) Method for investigating analytes in a liquid suspension or solution using an optical detection device as claimed in one of the  claims 1 - 29 . 
     
     
         53 ) Method for investigating analytes in a liquid suspension or solution using an optical detection device as claimed in  claim 52 , wherein at least two wavelengths or wavelength bands λ 1 , . . . , λ n , λ′ 1 , . . . , λ′ n  in the light emerging from the analytes are detected simultaneously. 
     
     
         54 ) Method using an optical device as claimed in any of  claims 52  and  53 , wherein the flow of the analyte suspension or solution through the analyte channel and the sorting channels is reversible. 
     
     
         55 ) Method using an optical device as claimed in any of  claims 52 - 54 , wherein the sheath fluid introduced by the first input channel confines the analyte suspension or solution introduced by the second input channel in the centre of the analyte channel. 
     
     
         56 ) Method using an optical device as claimed in  claim 52 - 55 , wherein the light illuminating the analytes in the interrogation region is introduced to interrogation region by directing it along the analyte channel.