Method and apparatus

Abstract

An aspect of the disclosure provides an apparatus comprising: a droplet dispenser configured to deliver a droplet to a liquid system to generate a wave in the liquid system, light beam optics for illuminating an area of the liquid system with a light beam, and a light collector coupled to a detector and positioned for receiving a reflected light beam provided by reflection of the light beam by the liquid system, and the light collector being configured to sense: a first intensity of the reflected light beam corresponding to a first polarisation component of the reflected light beam; a second intensity of the reflected light beam corresponding to second polarisation component of the light beam after reflection; and, the apparatus further comprising a liquid motion sensor configured to sense further parameters of liquid motion associated with the delivery of the droplet to the liquid system.

Description

[0001] Method and Apparatus

[0002] Field of invention

[0003] The present disclosure relates to methods and apparatus for characterising an interaction between a stimulus and a liquid system, and more particularly to methods and apparatus for characterising such interactions based on properties of surface waves in the liquid system.

[0004] Background.

[0005] The surface of a material has a thermodynamic potential that is independent of its volume. The physical and chemical properties of a surface are derived from its thermodynamic potential. For example, the response of the surface to a mechanical perturbation is given by properties such as surface tension and lateral compressibility. Similarly, the response of the surface to an electromagnetic perturbation is given by properties such as surface dipole moment. As a result of these perturbation, different types surface waves may be generated on a surface e.g. a surface of a fluid (e.g. a liquid) forming an interface with another fluid (e.g. air) . Some example types of surface waves are: Rayleigh waves; Gravity waves; Capillary waves; Lucassen waves. The physics of these waves have been described in Nonlinear fractional waves at elastic interfaces Julian Kappler, Shamit Shrivastava, Matthias F. Schneider, and Roland R. Netz Phys. Rev. Fluids 2, 114804 - Published 20 November 2017. These waves may be hydrodynamically coupled.

[0006] Rayleigh waves are characterised by elliptical motion of a notional fluid particle in a plane which is perpendicular to the surface at equilibrium and parallel to the direction of propagation of the wave . Gravity waves are characterised by a displacement from equilibrium of a notional fluid particle at the surface wherein the displacement of the notional particle is characterised by having a restoring force of gravity or buoyancy.

[0007] Capillary waves are characterised by a displacement from equilibrium of a notional fluid particle wherein the displacement of the notional fluid particle is in a direction transverse to the surface at equilibrium and transverse to the direction of propagation of the wave and have a restoring force of surface tension .

[0008] Lucassen waves are characterised by a displacement from equilibrium of a notional fluid particle at a surface of a wave-medium by oscillation in a direction parallel to that surface at equilibrium and parallel to the direction of propagation of the wave. In Lucassen waves this notional particle is subject to a restoring force resulting from the surface elastic modulus of the surface of the wave-medium. Put another way Lucassen waves are compressionrarefaction waves which occur in the plane of a boundary (an interface) between a wave-medium and an adjacent medium such as air .

[0009] Lucassen waves have been observed in lipid monolayers and in other types of liquid systems.

[0010] Shamit Shrivastava , Matthias F. Schneider Opto-Mechanical Coupling in Interfaces under Static and Propagative Conditions and Its Biological Implications describes how a wave can be generated in a lipid monolayer mechanically with a dipper and how parameters of the generated wave, such as the intensity of fluorescent particles therein and the lateral pressure of the surface wave, can be measured, for example using a photo detector and a Wilhemly balance respectively . Shrivastava S, Schneider MF. 2014 Evidence for two-dimensional solitary sound waves in a lipid controlled interface and its implications for biological signalling. J. R. Soc. Interface 11: 20140098 describes a method in which Lucassen waves can be generated in a lipid monolayer and how parameters of said waves may be measured (e.g. fluorescence energy transfer (FRET) measurements; a piezo cantilever) . The document also describes how the state of a lipid monolayer may be characterised by a variety of thin film parameters (e.g. surface density of lipid molecules, temperature, pH, lipid-type, ion or protein adsorption, solvent incorporation, etc. ) and also how the state of the lipid monolayer can affect parameters of waves which propagate in the lipid monolayer .

[0011] Bernhard Fichtl, Shamit Shrivastava & Matthias F. Schneider, Protons at the speed of sound: Predicting specific biological signaling from physics Nature Scientific Reports describes how Lucassen waves can be generated in a lipid interface in response to a change in pH of the system and that the speed of these waves can be controlled by the compressibility of the interface. The document describes how parameters of these waves depend on the degree of change in pH. The document also describes how mechanical and electrical changes at the lipid interface can be measured (e.g. using a Kelvin probe) .

[0012] Lucassen waves may be described as interfacial compression waves and may be considered two-dimensional sound waves (sound waves confined to a surface which forms a boundary between two phases e.g. a fluid-air boundary) . In a manner analogous to sound waves, shock waves may exist in Lucassen wave systems (e.g. two- dimensional shock waves) . Lucassen shock waves may be characterised in the same way as Lucassen waves with the additional constraint that the waves are characterised by changes in the wave medium which are nonlinear and / or discontinuous. S . Shrivastava , Shock and detona tion waves a t an interface and the collision of action potentials , Progress in Biophysi cs and Molecular Biology, describes how Lucas sen shock waves may propagate through a lipid interface .

[0013] WO2019234437A1 describes how a lipid interface may be used to transmit and receive signal s . The document describes a signal proces sing device comprising : a first medium; a second medium; a lipid interface arranged between the first medium and the second medium, wherein the lipid interface compri ses a plurality of lipid molecules ; an input transducer arranged to apply an input signal to the lipid interface , wherein the input signal is arranged to generate a mechanical pul se in the lipid interface ; and an output transducer arranged to receive an output signal by detecting a mechanical response in the lipid interface from the mechanical pulse generated in the lipid interface by the input transducer ; wherein the lipid interface i s arranged to propagate the mechanical pulse from the input transducer via the lipid interface to the output transducer .

[0014] Summary

[0015] Aspects of the invention are set out in the independent claims and optional features are set out in the dependent claims . Aspects of the di sclosure may be provided in conj unction with each other and features of one aspect may be applied to other aspects .

[0016] The methods and apparatus of the present di sclosure may provide richer data for characteri sing surface wave modes in liquid systems .

[0017] Liquid systems in the present di sclosure may compri se a bulk liquid, which may carry a thin film at its surface or may otherwi se compri se an interface along which a wave may propagate . An aspect of the di sclosure provides an apparatus for characteri sing an interaction between a droplet and a liquid system, the apparatus comprising : a droplet di spenser configured to deliver a droplet to a liquid system to generate a wave in the liquid system, light beam optics for illuminating an area of the liquid system with a light beam, and a light collector coupled to a detector and positioned for receiving a reflected light beam provided by reflection of the light beam by the liquid system, and the light collector being configured to sense : a first intensity of the reflected light beam corresponding to a first polari sation component of the reflected light beam; a second intensity of the reflected light beam corresponding to second polari sation component of the light beam after reflection ; and, the apparatus further comprising a liquid motion sensor configured to sense further parameters of liquid motion as sociated with the delivery of the droplet to the liquid system .

[0018] The liquid motion sensor may compri se at least one of : a beam deflection sensor configured to sense deflection of the reflected light beam from a beam direction as sociated with specular reflection of the light beam from an undisturbed surface of the liquid system; and a droplet sensor , configured to sense delivery of the droplet to the liquid system.

[0019] An aspect of the di sclosure provides an apparatus for characteri sing an interaction between a stimulus and a liquid system, the apparatus comprising : a stimulator , configured to provide a stimulus to a liquid system to generate a wave , light beam optics for illuminating an area of the liquid system with a light beam, and a light collector coupled to a detector and positioned for receiving a reflected light beam provided by reflection of the light beam by the liquid system, and the light collector being configured to sense : a first intensity of the reflected light beam corresponding to a first polari sation component of the reflected light beam; a second intensity of the reflected light beam corresponding to second polari sation component of the light beam after reflection ; and, deflection of the reflected light beam from a beam direction as sociated with specular reflection of the light beam from an undi sturbed surface of the liquid system .

[0020] The stimulus may compri se a droplet compri sing an analyte .

[0021] The present di sclosure al so provides an apparatus compri sing : a droplet dispenser configured to deliver a series of droplets to a liquid system to generate a wave in the liquid system, wherein at least one of the liquid system and the droplet compri ses an analyte a droplet sensor configured to sense delivery of each droplet of the series of droplets to the liquid system to provide a corresponding plurality of sets of droplet data , a wave sensor configured to sense a surface wave in the liquid system for each droplet of the series of droplets corresponding plurality of sets of wave data ; and a controller configured to determine a property of the analyte based on the wave data and the droplet data . Each set of droplet data may compri se a time series indicating si ze of the corresponding droplet during an interval between formation of the droplet at the di spenser and coalescence of the droplet with the liquid system .

[0022] The analyte may compri se a biomolecule , such as a protein or a lipid, and the controller may be configured to determine a biophysical property of the analyte based on droplet data .

[0023] The present di sclosure al so provides an apparatus compri sing : a droplet dispenser configured to deliver a series of droplets to a liquid system to generate a wave in the liquid system, wherein at least one of the liquid system and the droplet compri ses an analyte a droplet sensor configured to sense delivery of each droplet of the series of droplets to the liquid system to provide a corresponding plurality of sets of droplet data , each set of droplet data compri sing a time series indicating si ze of the corresponding droplet during an interval between formation of the droplet at the di spenser and coalescence of the droplet with the liquid system; and a controller configured to determine a property of the analyte based on the droplet data .

[0024] The time interval may be a time between contact of the droplet with the liquid system and coalescence of the droplet with the liquid system . Coalescence in thi s contact may be total coalescence .

[0025] The droplet sensor may compri se a detector and a light beam illuminating the detector wherein the droplet i s formed in the path of the light beam to the detector and the optical data compri ses a time series of detected intensity of the light beam .

[0026] The apparatus may compri se a wave sensor . The wave sensor may compri se a light collector coupled to a detector and positioned for receiving a reflected light beam provided by reflection of the light beam by the liquid system, and the light collector being configured to sense : a first intensity of the reflected light beam corresponding to a first polari sation component of the reflected light beam; a second intensity of the reflected light beam corresponding to second polari sation component of the light beam after reflection .

[0027] The droplet data may comprise or consi st es sentially of data corresponding to a window interval between contact of the droplet with the liquid system and coalescence of the droplet with the liquid system .

[0028] The light collector may be configured to provide a signal indicating at least one of a magnitude and a direction of said deflection .

[0029] The light collector may compri se a divided detector comprising a plurality of light sensitive detector elements spatially arranged for sensing said deflection .

[0030] The divided detector may be segmented and the light sensitive elements are arranged in di fferent segments of the segmented detector . The light sensitive elements may be provided in an array, such as an image sensor but more simple segmented detectors may be used . The detector segments may compri se four segments which provide quadrants of a quadrant detector .

[0031] The light collector may comprise a beam splitter arranged to direct the first polarisation component of the reflected beam to the divided detector and to direct the second polari sation component to a second detector . The stimulus may compri se a droplet of liquid compri sing an analyte . The stimulator may compri se a droplet di spenser configured to provide a droplet to the liquid system to cause a wave in the liquid system .

[0032] The apparatus may further comprise a controller configured to characteri se the wave using wave data compri sing a time series of measurements of the first intensity, the second intensity, and the deflection .

[0033] The controller may be configured to determine a characteristic of the analyte based on the wave data .

[0034] The liquid motion sensor may compri se a droplet sensor .

[0035] The droplet sensor may be configured to provide droplet data indicating parameters of contact between the droplet and the liquid system . The parameters of contact may compri se a duration of the droplet at the surface of the liquid system. The duration of the droplet may correspond to a time for which the droplet persists at the surface of the liquid system during and / or after being di spensed from the di spenser . The duration may begin at contact between the droplet and the liquid system. The parameters of contact may compri se data indicating a spatial extent of contact between the droplet at the surface of the liquid system, such as a time series of data indicating said spatial extent . The droplet sensor may comprise an optical sensor configured to provide optical data obtained from the droplet at the surface of the liquid system . The optical sensor may compri se a camera and the optical data may compri se images . The optical sensor may compri se a photodetector and the optical data may compri se attenuation of a light beam, such as a laser beam . The light beam may be directed to the photodetector through the droplet at the point of contact .

[0036] The apparatus may further comprise a controller configured to characteri se the wave using wave data compri sing a time series of measurements of the first intensity, the second intensity, and the parameters of liquid motion .

[0037] The controller may be configured to determine a characteristic of the analyte based on the wave data .

[0038] An aspect of the di sclosure provides a method of characteri sing an interaction between a droplet of an analyte and a liquid system, the method compri sing : obtaining wave data compri sing

[0039] ( i ) parameters of liquid motion as sociated with the delivery of the droplet to the liquid system; and

[0040] ( ii ) a time series of measurements of a wave generated in a liquid system by the droplet , wherein the time series of measurements compri se a plurality of measurements of : a first intensity of a reflected light beam, reflected by the surface of the liquid system, wherein the first intensity corresponds to a first polari sation component of the reflected light beam; a second intensity of the reflected light beam corresponding to second polari sation component of the light beam after reflection ; and, the method further compri sing : characteri sing the analyte based on the time series of measurements of the first intensity, the second intensity, and the parameters of liquid motion .

[0041] An aspect of the di sclosure provides a method of characteri sing an interaction between a stimulus and a liquid system, the method compri sing : obtaining wave data comprising a time series of measurements of a wave generated in a liquid system by the stimulus , wherein the time series of measurements compri se a plurality of measurements of : a first intensity of a reflected light beam, reflected by the surface of the liquid system, wherein the first intensity corresponds to a first polari sation component of the reflected light beam; a second intensity of the reflected light beam corresponding to second polari sation component of the light beam after reflection ; and, deflection of the reflected light beam from a beam direction as sociated with specular reflection of the light beam from an undi sturbed surface of the liquid system, and the method further compri sing : characteri sing the interaction based on the time series of measurements of the first intensity, the second intensity, and the deflection .

[0042] The method may compri se identi fying, in the wave data based on the deflections , at least one of ( a ) first data subset substantially unaf fected by reflections of the wave in the liquid system and (b ) a second data subset as sociated with reflections of the wave in the liquid system . Identi fying the first data subset may comprise identi fying a time interval of the wave data substantially unaf fected by reflections of the wave in the liquid system.

[0043] Identi fying the second data subset may comprise identifying a time interval of the wave data as sociated with reflections of the wave in the liquid system.

[0044] Identi fying the first data subset may comprise identi fying components of variance in the wave data associated with reflections of the wave in the liquid system and removing those components of the variance from the wave data . The components of variance in the wave data as sociated with the reflections of the wave ma be identi fied based on the deflection measurements .

[0045] Identi fying the first data subset may comprise a deconvolution of the deflections from the first intensity measurements and the second intensity measurements .

[0046] The method may comprise applying a first analysis to the first data subset and a second analysi s to the second data subset .

[0047] The deflections may compri se a magnitude and a direction .

[0048] The method may compri se determining a direction of the deflections , and the first and second subsets may be identified based on said direction .

[0049] The stimulus may compri se an analyte , provided in a droplet to cause a wave in the liquid system .

[0050] The wave data may be obtained from a data store , such as a memory or non-volatile data storage . The wave data may be obtained over a network from a remote device . The method may further comprise performing measurements to acquire the wave data. For example, the method may further comprise dispensing the droplet to cause the wave, illuminating an area of the liquid system with a light beam, receiving a reflected light beam provided by reflection of the light beam by the liquid system, and sensing the first intensity the second intensity and the deflection of the reflected light beam.

[0051] In the presence of viscoelastic thin films on the surface of a liquid, multiple surface wave modes governed by different physics and timescales can co-exist and co-propagate. Embodiments of the disclosure may address the problem of how to resolve the information contained in such waves.

[0052] Some embodiments use the first intensity measurements, the second intensity measurements, and the deflections to provide an overdetermined system to allow wave modes which otherwise may be difficult or impossible to characterise to be completely specified. The use of multiple angles and / or multiple wavelengths may enable information existing in the dynamic surface modes to be obtained more rapidly (e.g. , in parallel from measurement of a single interaction point between liquid system and illumination) .

[0053] Embodiments of the present disclosure may enable more complete data defining the wave to be determined than systems which only use polarisation because the deflection measurements can also provide an indication of the surface disturbances of the liquid system at the illuminated location. This can allow such disturbances to be accounted for in analysis of the data, so as to control for effects associated with such disturbance. One way to do this is to segment the data in time domain - for example by identifying time intervals in the data with a high degree of such disturbance and removing those time intervals so as to provide a data subset which is free of the effects of the disturbance. Another way to do this is to include the deflection data in a model , such as a linear regres sion model , and then to provide a subset of the data which does not include the components which can be accounted for by effects of the deflection . Other approaches include deconvolution, and other approaches may al so be used .

[0054] It will be appreciated in the context of the present disclosure that the change in polarisation caused by reflection at an interface is related to the refractive index differences at the interface . Refractive index may be related to the surface characteristics of a liquid . Accordingly, the wave measurement module of embodiments described herein can provide measurements which comprise , in a time series of samples , such as the s-p ratio , information about variations in those characteristics as a function of time . This may enable complex wave modes with many degrees of freedom to be characterised . The liquid system' s surface may carry a thin film, and features of the wave data may be associated with variations in density and / or position of that thin film, as well as the orientation of molecules within the film. The analyte in the droplets described herein may comprise a biomolecule or a composition comprising such a biomolecule . As will be appreciated, following deposition of the biomolecule in a droplet , the biomolecule itself may populate a pre-existing thin film, or a thin film may be generated from the droplets , for example the thin film may be formed by the biomolecule itself .

[0055] Where a thin film is present typically, the thin film comprises a type of liquid which is different from that of the volume of liquid system. The liquid thin film and the volume of liquid may therefore have an interface between them such as a liquid-liquid interface . The thin film may have viscoelastic properties . These and other types of thin films may exhibit a variety of surface wave modes in response to stimulus . Examples of such wave modes comprise Rayleigh waves , gravity waves , capillary waves and Lucassen waves .

[0056] Examples of types of liquid which provide the thin film include proteins and lipids and other types of liquid . It will be appreciated in the context of the present disclosure that such materials may also be held ( e . g . , dispersed in suspension or otherwise ) in the volume of liquid and dynamic equilibrium may exist between the thin film and the material held in the volume of liquid .

[0057] It will also be appreciated in the context of the present disclosure that duration of a droplet may be defined as a time to partial coalescence or a time to total coalescence . For example , when the dispenser places a droplet on the surface of the liquid system, gravity draws the droplet downward until the interface between the droplet and the liquid system become sufficiently close that attractive Van der Waals forces initiate coalescence between the droplet and the liquid system . A "fluid neck" j oins the droplet to the liquid system and capillary waves may propagate away from the initial point of contact . Two outcomes may follow . Either total coalescence , in which the droplet merges entirely with the liquid system, or partial coalescence in which a fraction of the droplet merges with the liquid system and a daughter droplet is left behind . The daughter droplet left behind by partial coalescence may "bounce" or otherwise dwell on the surface of the liquid system before undergoing similar process ( es ) until total coalescence occurs . The droplet duration referred to herein may comprise duration data indicating the time to partial and / or total coalescence of the droplet .

[0058] One way to measure droplet duration and partial and / or total coalescence is using a high-speed camera, such as a 3000 frame per second camera . Another way of providing droplet data is to illuminate the droplet with a light beam, such as a laser , as it leaves the dispenser to contact the film and to measure the attenuation of the light beam, for example using a photodetector . Such measurements may provide a time series of measurements for each droplet . This time series may begin as the droplet is formed at the dispenser . This time series may end when the droplet has totally coalesced with the liquid system or when the subsequent droplet is formed at the dispenser . Other methods of observing and timing the process of droplet coalescence may also be used .

[0059] The data indicating spatial extent of the droplet may indicate a spatial extent of interaction between the droplet and the liquid system and / or may comprise the size of the droplet . It will be appreciated in the context of the present disclosure that the size of a droplet may be characterised by its diameter .

[0060] An aspect of the di sclosure provides a method of characteri sing an analyte , the method compri sing : obtaining wave data comprising a time series of measurements of a wave caused in a liquid system by provi sion of a droplet of the analyte to the liquid system; obtaining timing data indicating timing of the measurements relative to the provi sion of the droplet ; and, selecting a window interval preceded by an earlier interval beginning with the provi sion of the droplet and followed by a later interval during which the wave persi sts ; determining a characteristic of the analyte based on the wave data in the window interval in preference to measurements of the wave outside the window interval .

[0061] Obtaining the wave data may compri se sensing di splacements of a surface of the liquid system at a measurement location on a surface of the liquid system.

[0062] The window interval may end at a time selected based on a di stance between the measurement location and a nearest edge of the surface .

[0063] The window interval may be selected based on a characteri stic of the liquid system .

[0064] The window interval begin at one of : ( a ) a time selected based on a kinetic energy imparted to the liquid system by the droplet ; and

[0065] (b ) a time selected based on an expected interaction strength between the analyte and a component of the liquid system .

[0066] The component may be provided in a thin film at the surface of the liquid system .

[0067] The wave data may be obtained from a measurement location on a surface of the liquid system.

[0068] The later interval may begin at one of :

[0069] ( a ) a time as sociated with arrival of reflections of the wave at the measurement location ;

[0070] (b ) a time as sociated with onset of dominance of bulk mechanical ef fects in the liquid system .

[0071] In an aspect there is provided an apparatus compri sing : a trough for holding liquid system; a droplet provider for providing a droplet to a liquid system held in the trough ; a wave measurement module , configured to sense di splacements of a surface of the liquid system at a measurement location on a surface of said liquid system; and, a controller configurable with data defining a window interval and being further configured to : obtain, from the wave measurement module , wave data compri sing a time series of measurements of a wave caused in the liquid system by provision of a droplet of the analyte to the liquid system; obtain timing data indicating timing of the measurements relative to the provision of the droplet ; and to , provide the wave data and the timing data for determining a characteristic of the analyte based on the wave data in the window interval in preference to measurements of the wave outside the window interval .

[0072] The controller may be preconfigured with a plurality of window interval s , and operable to select a window interval based on control data .

[0073] The controller may be configured to select a window interval based on at least one of : a distance between the measurement location and a nearest edge of a surface of the liquid system; a characteri stic of the liquid system; a kinetic energy imparted to the liquid system by the droplet ; an expected interaction strength between the analyte and a component of the liquid system, for example wherein the component i s provided in a thin film at the surface of the liquid system.

[0074] The controller may be configured to determine an end of the window interval based on arrival of reflections of the wave at the measurement location .

[0075] The controller may be configured to determine an end of the window interval based on dominance of mas s ef fects in the liquid system .

[0076] Embodiments of the di sclosure provide apparatus configured to perform any one or more of the methods described or claimed herein

[0077] Embodiments of the di sclosure provide a computer program product compri sing program instructions configured to program a proces sor to perform any one or more of the methods described or claimed herein . Any feature of any one of the examples di sclosed herein may be combined with any selected features of any of the other examples described herein . For example , features of methods may be implemented in suitably configured hardware , and the configuration of the speci fic hardware described herein may be employed in methods implemented using other hardware .

[0078] Brief description of the drawings

[0079] Embodiments of the di sclosure will now be described, by way of example only, with reference to the accompanying drawings , in which :

[0080] Figure 1 i s a functional block diagram of an apparatus according to the present di sclosure ;

[0081] Figure 2 i s a flowchart depicting a method of acquiring wave data by operation of an apparatus such as that shown in Figure 1 ;

[0082] Figure 3 i s a flowchart depicting a method of characterising an analyte using wave data such as that provided by a method according to Figure 2 ; and

[0083] Figure 4 provides a schematic illustration of data provided by methods of the present disclosure .

[0084] In the drawings like reference numeral s indicate like elements .

[0085] Specific description

[0086] Figure 1 shows an apparatus 1 for characteri sing an interaction between a droplet of liquid 33 and a liquid system 3 . The droplet may compri se an analyte and the apparatus may be configured to characteri se the analyte based on wave data obtained from a series of waves caused, in the liquid system, by a series of such droplets .

[0087] The wave data may be based on the polarisation of a light beam 7 reflected by the liquid system ( e . g . reflected from the surface of the liquid system in the presence of the wave ) . The wave data further compri ses , for each wave of the series , parameters of liquid motion as sociated with the delivery, to the liquid system, of the droplet which caused that wave .

[0088] The parameters of liquid motion may compri se deflection data as sociated with deflection of the reflected light beam 7 . The parameters of liquid motion may be associated with the droplet itsel f and may compri se parameters of contact , such as a duration of the droplet at the surface of the liquid system, and a spatial extent of that contact .

[0089] In particular , the apparatus may provide first intensity data (which may indicate one polarisation component ) and second intensity data (which may indicate another polari sation component ) . The two polari sation components may be orthogonal to each other and may be the s-polari sation and p-polari sation components respectively . The apparatus may al so provide a series of measurements of deflection of the reflected light beam from a direction as sociated with specular reflection from the undisturbed liquid system . It will be appreciated in the context of the present di sclosure that the undisturbed liquid system may generally have a flat hori zontal surface at a level which i s predetermined by the volume of liquid and the si ze of the trough in which it i s held . The deflection may be a measurement of the angular deflection of the reflected beam away from a direction of specular reflection as sociated with that undi sturbed surface .

[0090] A time series of these measurements can be used to characterise the interaction between a droplet and the liquid system . The data time series for each droplet may compri se time series of first intensity data and second intensity data in addition to the parameters of liquid motion . The apparatus 1 shown in Figure 1 comprises, a dispenser 9, light beam optics 11, a light collector 13, a detector 15, and a wave measurement module 17. As illustrated in Figure 1, the apparatus 1 also comprises a reservoir 23 holding a liquid system 3. The liquid system generally comprises a volume of liquid 21 which may have the liquid thin film at its surface. The reservoir 23 may be provided by a trough, such as a Langmuir trough.

[0091] Also shown in Figure 1 are mechanical fixtures 19 for holding the apparatus in position with respect to the reservoir 23, but it will be appreciated that these fixtures 19 are not essential and may be made and sold separately from the apparatus 1 itself. The wave measurement module 17 is connected to the dispenser 9 and to the detector 15 for the communication of control signals and data, it may also be connected to the light beam optics 11.

[0092] Where a thin film is present on the liquid system 3 the film may comprise a type of liquid which is different from that of the volume of liquid 21. The liquid thin film and the volume of liquid 21 may therefore have an interface between them such as a liquidliquid interface. The thin film may have viscoelastic properties. These and other types of thin films may exhibit a variety of surface wave modes in response to stimulus. Examples of such wave modes comprise Rayleigh waves, gravity waves, capillary waves and Lucassen waves. Examples of types of liquid which provide the thin film include proteins and lipids and other types of liquid. It will be appreciated in the context of the present disclosure that such materials may also be held (e.g. , dispersed in suspension or otherwise) in the volume of liquid and dynamic equilibrium may exist between the thin film and the material held in the volume of liquid 21. Examples of types of liquid which may provide the volume of liquid 21 comprise aqueous solutions. The light beam optics 11 comprise a source of polarised light arranged to illuminate an area of the liquid system 3 with a beam 7 having a selected angle of incidence a. The light beam 7 may also be coherent. Examples of suitable light sources include lasers and the light beam optics may comprise a polariser.

[0093] The light collector 13 comprises a detector 15 and is arranged to receive the beam of light 7 after reflection by the area of the liquid system and to provide the reflected beam of light to the detector. The light collector 13 is positioned so that the optical axis of the light collector 13 is directed to the area of the liquid system at the angle of specular reflection, a, of the light beam incident on the surface of the liquid system when it is undisturbed (e.g. flat and level at equilibrium) .

[0094] The detector 15 is configured to sense parameters of the light received from the light collector 13 and to provide signals to the wave measurement module 17 including those parameters. Typically, those parameters comprise the polarisation of the light beam 7. For example the parameters may comprise a measure of the intensity of one or more polarisation components of the received light, such as the intensity of (a) an first component of the second polarisation and / or (b) a second component of the second polarisation. The second component may be orthogonal to the first component. The first component may be the s-component and the second component may be the p-component.

[0095] As illustrated, the detector 15 may comprise two light sensors 15- 1, 15-2 and a beam splitter 15-3. The beam splitter 15-3 may provide a first polarisation component of the reflected beam to the first light sensor 15-1 and a second polarisation component to the second light sensor 15-2. The first light sensor 15-1 comprises a plurality of light sensitive detector elements. These elements are arranged at predefined positions relative to the expected beam direction ( the undeflected beam) . For example , the detector elements may be arranged as four quadrants of a circle centred on the expected beam direction . Because the detector i s divided in thi s way, it i s able to provide a signal indicating the position at which beam strikes the detector . For example , i f all quadrants detect equal intensity, the beam deflection may be zero . The extent of beam deflection may be determined based on di f ferences between the signal intensity detected in each quadrant . Such a detector may be capable of providing data indicating both the magnitude and the direction of deflection of the beam.

[0096] The di spenser 9 i s positioned with respect to the liquid system 3 so that it can apply a droplet 33 to the liquid system. For example , the dispenser 9 may compri se a source of a test substance and may be configured to contact the surface of the liquid system 3 with a droplet 33 of the test substance to stimulate a wave in the liquid system . The di spenser may be configured to dispense droplets onto the liquid system at a selected rate - e . g . a selected volume flow rate of the droplet liquid .

[0097] The apparatus may comprise a droplet sensor 35 . As illustrated in Figure 1 , the droplet sensor 35 generally compri se s an optical detector , such as a light beam arranged to illuminate a photodetector and positioned so that the droplets obstruct the light beam as they are di spensed onto the surface of the liquid system .

[0098] In thi s example , the data from the droplet sensor 35 may indicate the spatial extent of the droplet in amount of attenuation of the light beam caused by the droplet - a larger degree of attenuation being associated with a larger droplet . In thi s example , the data from the droplet sensor may al so indicate the duration of the droplet at the surface in the duration of attenuation caused by each droplet . Other types of droplet sensor may al so be used . For example , an imager such as a digital camera may be positioned to capture images of the droplet as it i s provided to the liquid system . Regardless of how the droplet sensor 35 is implemented, it may provide a time series of data for each droplet indicating the si ze ( e . g . spatial extent ) of the droplet over time . Thi s time series may span a window interval beginning with formation of the droplet at the di spenser or with contact between the droplet and the liquid system . Thi s window interval may end with coalescence of the droplet with the liquid system.

[0099] Each droplet may create a wave 5 in the liquid system 3 exhibiting some or all of the above wave modes .

[0100] The wave measurement module 17 i s configured to control the di spenser 9 to apply the droplet to the liquid system 3 , and to operate the detector 15 to collect a time series of samples of the light received at the detector 15 . These samples may comprise samples of the intensity of the one or more polarisation components and parameters of the liquid motion such as a measurement of the deflection and / or droplet parameters as mentioned above . A measure of deflection may be provided for each pair of polari sation measurements in a time series . The deflection measurements need not be of the same duration or the same timebase as the polarisation data . The wave measurement module may al so be configured to determine parameters of contact . These parameters may compri se droplet data , such as the time series explained above which can be obtained from the droplet sensor 35 for each droplet . The droplet data may compri se parameters of contact such as data indicating a spatial extent of the droplet at the surface of the liquid system, and / or duration of contact between the droplet and the liquid system . Accordingly, it can be seen that the apparatus may provide , for each droplet , wave data both defining the wave itsel f with sufficient degrees of freedom that the various wave modes may be derivable from the data but al so compri sing further parameters of the liquid motion associated with that droplet. These parameters of liquid motion may indicate the deflection (e.g. angular deflection) of the surface at the measurement location and / or may comprise the droplet data.

[0101] Typically, the sample rate for the wave data (e.g. polarisation measurements) is at least 1MHz, for example 10MHz. The wave measurement module may also be configured to apply a low pass filter to the time series before down-sampling the data to 20kHz or thereabouts. Typically, the sample rate of the down-sampled time series is selected based on the size of the illuminated area and the expected speed of the wave in the thin film. For example, the expected speed may be approximately 1 ms-1and the illuminated area may have a diameter of ~5mm, in which case the upper limit on the frequency of surface waves that can be meaningfully sampled will be 10kHz. The sample rate of the down-sampled time series may be selected to ensure that the measurement remains well within this available bandwidth.

[0102] The wave measurement module 17 may be configured to control the timing of these samples based on the operation of the dispenser 9, for example so that the surface wave 5 in the area of the thin film illuminated by the beam 7 can be sampled at a selected time after the droplet and for a selected duration. The time and / or duration typically are selected based on the distance from the part of the liquid system 3 to which the droplet is applied to the illuminated area. The wave measurement module may be further configured to provide a particular sampling scheme for a particular measurement type. The wave measurement module may be configured to implement a first sampling scheme to perform a first measurement type and to implement a second, different, sampling scheme to perform a second, different, measurement type. For example, to measure viscosity or hydrophobicity in a lipid thin film, or to measure binding in a protein thin film, the wave measurement module may use a long sampling duration ( total time for which samples are collected) . Recording of a single droplet typically has a time resolution of microsecond and duration of seconds . Thi s can be suf ficient for measurement of properties of molecule that interact strongly with the film and / or are fast , for example electrostatic interaction or hydrogen bonding . In some embodiments multiple such stimulations with a repetition rate of few seconds observed over a course of minutes to hours could provide improved measurement of properties of molecules that interact weakly and / or slowly with the film, for example binding or reaction kinetics . In other modes , the wave measurement module may be configured to sample data in a selected time interval following the application of a droplet to the thin film, and to repeat the same sampling in that same time interval after subsequent stimuli to provide repeated measurements . Such measurements may be of relatively short duration .

[0103] One example of acquisition and analysi s of data according to the present di sclosure will now be described with reference to Figure 2 and Figure 3 and Figure 4 .

[0104] Figure 2 illustrates a method of operating the above apparatus to acquire wave data for an analyte .

[0105] As illustrated, the wave measurement module 17 operates the di spenser 9 to di spense 102 a droplet 33 to the liquid system 3 . A droplet 33 is formed at a noz zle of the di spenser 9 , adj acent to the surface of the liquid system 3 .

[0106] The droplet sensor 35 provides a signal 410 to the controller indicating the size of that droplet , which i s encoded by the wave measurement module 17 in a time series of samples to provide droplet data 412 . Thi s time series of samples reflects the growth of the droplet at the di spenser until its contact with the liquid system 3 . Contact of the droplet 33 with the liquid 3 may trigger a surface wave 5 in the liquid system 3 . The droplet sensor 35 continues to sense 104 the si ze of the droplet 33 to provide droplet data 412 as the droplet goes through the proces s of coalescence with the liquid system 3 .

[0107] It can therefore be seen that , during admini stration of the droplet , the droplet data 412 may provide parameters of the contact between the droplet 33 and the liquid system 3 , such as the time taken for the droplet 33 to merge with the liquid system and / or the spatial extent of that droplet during its lifetime at the surface . Thi s duration may correspond to the time between contact between the droplet and the surface of the liquid system and total coalescence of the droplet with the liquid system . Thi s provides a set of droplet data 412 for each droplet during an interval between formation of the droplet at the di spenser and coalescence of the droplet with the liquid system .

[0108] The wave measurement module 17 may be configured to identi fy contact of the droplet 33 with the liquid system based on a maximum in the droplet data 412 ( e . g . the signal 410 from the droplet sensor 35 indicating that the droplet 33 has reached a maximum si ze ) . The wave measurement module 17 may be configured to select the droplet data 412 which corresponds to the window interval 400 between contact and coalescence with the liquid system and to use that part of the droplet data to characterise the analyte . Coalescence in thi s context may be total coalescence or partial coalescence . The wave measurement module 17 may be configured to determine coalescence based the droplet si ze dropping below a minimum si ze ( e . g . based on a threshold applied to the droplet data ) . It can therefore be seen ( as illustrated in Figure 4 ) that the time series of droplet data 412 may be divided between a window interval that precedes contact with the liquid system and a window interval 400 which follows contact between the liquid system and the droplet .

[0109] The wave evoked by contact of the droplet 33 with the liquid system 3 the droplet travels outwardly, acros s the liquid system from the location at which the droplet i s applied .

[0110] The light beam optics 11 illuminate 105 an area of the surface of the liquid at a measurement location spaced from the location at which the droplet i s applied . The wave which propagates from the droplet to the measurement location reaches the measurement location a short time after the contact time .

[0111] The wave measurement module 17 operates the detector 15 to take a series of samples 106 of the light beam 7 reflected by the illuminated area of the liquid and provided by the light collector 13 to the detector 15 . Accordingly, the disturbance of the liquid system 3 at the measurement location as a function of time can be recorded in a series of samples of wave data 414 ( a time series ) corresponding to the measured polari sation intensity 408 at the surface of the liquid system . Each sample in that time series may compri se polari sation data , which may be in the form of the intensity of the s-polari sation component and the intensity of the p-polari sation component of the reflected light . The segmented detector may al so provide 109 a time series of beam deflections as sociated with the time series of polari sation measurements .

[0112] The wave measurement module 17 may be configured to determine 108 an indication of the polari sation angle of the reflected beam 7 , such as a ratio of the intensity of the s-component to the intensity of the p-component for each sample . The wave measurement module may derive features of the wave 5 in the liquid system from thi s time series . Examples of features of the respective wave modes include its amplitude , frequency content , phase velocity, group velocity, phase and so forth . The wave may comprise a Lucas sen wave mode and other wave modes. The wave measurement module 17 may then use these features, such as features of the Lucassen wave, to provide information about the droplet. It will be appreciated in the context of the present disclosure that the change in polarisation caused by reflection by a thin film is related to the refractive index of that film. The wave measurement module 17 may also use the signal from the segmented detector to determine 109 a magnitude and / or a direction of a deflection of the reflected beam and associate such deflection measurements with the polarisation measurements .

[0113] It can be seen in Figure 4 that the wave data may comprise a series of window intervals 402, 404, 406 during which the wave 5 measured at the measurement location exhibits differing characteristics.

[0114] The wave measurement module 17 may therefore be configured to identify, in the wave data, a set of window intervals including:

[0115] • an initial interval 402, beginning with the provision of the droplet 33 to the liquid system, which may comprise transient effects associated with the kinetic effects on the liquid system 3 of the droplet.

[0116] • an intermediate window interval 404 during which the kinetic effects dominate to a lesser degree and effects associated with the properties of the analyte in the droplet and its interactions with the liquid system contribute more to the wave characteristics;

[0117] • a later interval 406 during which wave motion persists but which may be characterised by less predictable wave behaviour. This later interval may be associated with the arrival, at the measurement location, of one or more reflections of the initial wave 5. Such reflections may be associated with a wave that has already passed the measurement location the initial wave being reflected back on itsel f . Thi s later interval may al so be as sociated with onset of dominance of bulk mechanical ef fects in the liquid system.

[0118] The apparatus may be configured to repeat 110 the foregoing steps ( 102 to 109 as illustrated in Figure 2 ) for a series of droplets . This may provide a set of time series of measurements , each time series corresponding to a wave , and each wave being generated by contact between the liquid and a droplet . This may generate wave data comprising a plurality of individual waveforms , each corresponding to the physical measurement of one wave , generated in the liquid by contact with the droplet of sample . Typically, the wave data 414 associated with each droplet comprises a waveform of pairs of polarisation intensity values and may also comprise corresponding deflection values . For example , a waveform provided by a time series of three-element tuples ( first polarisation intensity, second polarisation intensity, and deflection) . A series of droplets therefore provides a set of waveforms , each of which may provide a measurement of the physical wave in the liquid system having sufficient degrees of freedom to encode the relevant wave modes which make up that physical wave . The characterisation provided by the polarisation data may be further enriched by the measurement of deflection, because this may enable mechanical and other effects , such as effects caused reflection of the wave in the liquid back onto itself , to be accounted for in the data ( e . g . by deconvolution or modelling or otherwise ) . Where other parameters of liquid motion are collected for the droplet then these may also be provided with the wave data for that droplet . For example , the droplet sensor 35 may provide a time series of droplet data 410 for each time series of the wave data , so that both the formation and coalescence of the droplet with the liquid system and the propagation of the wave itself are represented by the wave data and the droplet data together .

[0119] The wave measurement module 17 may assemble the sets of wave data and droplet data from these droplets into an array 420 , 422 . Each row or column of that array corresponding to the waveform ( s ) of polarisation and deflection data obtained by measuring the physical wave caused in the liquid by a corresponding one of the droplets . The droplet data 422 may also be included in this array 420 or it may be treated separately . It will be appreciated in the context of the present disclosure that the arrangement of the data in an array is merely optional and other formatting and arrangement of the data may be used .

[0120] Figure 3 illustrates a method of characterising an analyte using such data .

[0121] In this method, polarisation intensity values , such as those of the wave data described above are obtained 202 for a plurality of droplets . Parameters of the liquid motion, such as droplet data 412 , 422 , corresponding to that wave data are also obtained 204 and may be included in the array .

[0122] To characterise 206 the analyte , the wave measurement module 17 may then operate on that array 420 , 422 to identify separable contributions to the variance in that data . This may be done by a dimensionality reduction technique , for example , the processor may be configured to apply a principal components analysis ( PCA) to the array . It will be appreciated in the context of the present disclosure that such analysis generates a number of coefficients and a number of vectors . For example , the coefficients , p, may be the eigenvalues and the vectors , P, the eigenvectors of the covariance matrix of the wave data . Other dimensionality reduction techniques may be used to identify one or more separable contributions .

[0123] These analyses may be performed by any appropriate method so as to identi fy features of the data . The wave measurement module 17 may be configured to provide a feature vector . Such vectors may permit comparisons to be performed between analytes according to a "distance" in the vector space . Thi s di stance may be a Euclidean di stance and clustering metrics may be used to as ses s similarities between analytes . A variety of different techniques may be applied - for example the parameters of the liquid motion may provide a model to control for effects of surface deflection and / or droplet size and / or droplet energy effects.

[0124] One way to do this is to use the deflection data to identify when reflections of the wave in the liquid system cause the wave to interfere with itself at the measurement location. The controller may use the deflection data to identify a first subset of the measurements substantially unaffected by reflections of the wave in the liquid system. It may also use the deflection data to identify a second subset of the measurements associated with reflections of the wave in the liquid system. The two subsets may be analysed separately to characterise the analyte.

[0125] It will be appreciated by the skilled addressee in the context of the present disclosure that the methods and apparatus explained herein may be implemented in a variety of different ways.

[0126] Variations in density in the thin film at the area illuminated by the light beam can be detected by the wave measurement module as variations in the polarisation angle of the reflected beam, which can be observed in the (optionally filtered and down-sampled) time series of samples obtained from the illuminated area. This data may provide an indication of time varying disturbances in the density of the surface of the liquid system, thereby enabling Lucassen waves to be observed. This can enable parameters of the Lucassen waves such as their phase, amplitude, frequency content, phase velocity, group velocity and so forth. Embodiments permit measurement of how the polarization vector has changed upon reflection, e.g. , how the direction of polarization has changed and also how the distribution of polarization has changed for example the extent to which a highly polarised beam becomes less polarised after interaction. Further embodiments are envisaged .

[0127] For example , in some embodiments of the method according to Figure 4 , the droplet data may be used alone to characteri se the analyte . For example , the droplet data may be used to determine a property of the analyte . An array 422 may be assembled compri sing the droplet data for a plurality of droplets and a feature vector may be provided based on that droplet data 422 . The droplet data for the analyte may be compared against that which has been provided for other analytes so as to determine a property of that analyte .

[0128] The array of droplet data may al so be used with the wave data in the analysis described above .

[0129] It i s to be understood that any feature described in relation to any one embodiment may be used alone , or in combination with other features described, and may al so be used in combination with one or more features of any other of the embodiments , or any combination of any other of the embodiments . Furthermore , equivalents and modi fications not described above may al so be employed without departing from the scope of the disclosure .

[0130] For example , the measure of the change in polari sation angle may be determined without the need to measure both components by measuring the change in one of the components caused by reflection and providing some adj ustment to account for attenuation of the beam . The signal may be filtered and down sampled before determining the polarisation angle of the reflected beam, of the polari sation angle may be determined first . In some embodiments the two polari sation signal s may be combined in the analogue domain prior to digitisation .

[0131] The liquid systems described herein may comprise thin films carried at their surfaces . Examples of thin film materials include lipids and proteins . Embodiments of the present di sclosure do not need a thin film . Instead embodiments may have a simple liquid provided in a reservoir and a stimulus can be applied on the surface of a simple liquid . The liquid systems may compri se components selected according to the properties or expected properties of the analyte . For example , where the analyte i s a protein, such as an antibody, material in the liquid system may be selected according to an interaction property of the antibody .

[0132] Wave measurement modules described herein may be coupled to the light collector and / or the detector which i s coupled to the light collector , thereby to provide surface wave data to characteri se a Lucassen wave in the liquid thin film based on the second polari sation .

[0133] Where ranges are recited herein these are to be understood as di sclosures of the limits of said range and any intermediate values between the two limits .

[0134] With reference to the drawings in general , it will be appreciated that schematic functional block diagrams are used to indicate functionality of systems and apparatus described herein . It will be appreciated however that the functionality need not be divided in thi s way, and should not be taken to imply any particular structure of hardware other than that described and claimed below . The function of one or more of the elements shown in the drawings may be further subdivided, and / or di stributed throughout apparatus of the di sclosure . In some embodiments the function of one or more elements shown in the drawings may be integrated into a single functional unit .

[0135] In some examples the functionality of the wave measurement module 17 and other controllers and proces sing means described herein may be provided by any appropriate electronic logic such as digital logic and mixed analogue and / or digital proces sing and / or control functionality . Thi s functionality may al so be provided in a single integrated processing unit or it may be di stributed between one or more devices . For example , the functions as sociated with the control of the apparatus illustrated in Figure 1 in actually acquiring the measurement data may be performed by the wave measurement module and the data analysi s to characteri se the analyte based on that measurement data may be performed by a separate data processor . Such controllers may compri se a general purpose proces sor , which may be configured to perform a method according to any one of those described herein . In some examples the controller may comprise digital logic , such as field programmable gate arrays , FPGA, application speci fic integrated circuits , AS IC , a digital signal processor , DSP, or by any other appropriate hardware . In some examples , one or more memory elements can store data and / or program instructions used to implement the operations described herein . Embodiments of the di sclosure provide computer program products such as tangible , non-transitory storage media compri sing program instructions operable to program a proces sor to perform any one or more of the methods described and / or claimed herein and / or to provide data processing apparatus as described and / or claimed herein . Such a controller may compri se an analogue control circuit which provides at least a part of thi s control functionality . An embodiment provides an analogue control circuit configured to perform any one or more of the methods described herein .

[0136] The above embodiments are to be understood as illustrative examples . Further embodiments are envi saged . It i s to be understood that any feature described in relation to any one embodiment may be used alone , or in combination with other features described, and may also be used in combination with one or more features of any other of the embodiments , or any combination of any other of the embodiments . Furthermore , equivalents and modi fications not described above may also be employed without departing from the scope of the invention, which is defined in the accompanying claims . These claims are to be interpreted with due regard for equivalents .

Claims

Claims :1 . An apparatus compri sing : a droplet di spenser configured to deliver a droplet to a liquid system to generate a wave in the liquid system, light beam optics for illuminating an area of the liquid system with a light beam, and a light collector coupled to a detector and positioned for receiving a reflected light beam provided by reflection of the light beam by the liquid system, and the light collector being configured to sense : a first intensity of the reflected light beam corresponding to a first polari sation component of the reflected light beam; a second intensity of the reflected light beam corresponding to second polari sation component of the light beam after reflection ; and, the apparatus further comprising a liquid motion sensor configured to sense further parameters of liquid motion as sociated with the delivery of the droplet to the liquid system .2 . The apparatus of claim 1 wherein the liquid motion sensor compri ses at least one of : a beam deflection sensor configured to sense deflection of the reflected light beam from a beam direction as sociated with specular reflection of the light beam from an undisturbed surface of the liquid system; and a droplet sensor , configured to sense delivery of the droplet to the liquid system .3 . The apparatus of claim 2 wherein the liquid motion sensor compri ses the beam deflection sensor , for example wherein the beam deflection sensor i s integrated into the light collector .4 . The apparatus of any preceding claim wherein the beam deflection sensor is configured to provide a signal indicating at least one of a magnitude and a direction of said deflection .5 . The apparatus of claim 3 or 4 wherein the light collector compri ses a divided detector comprising a plurality of light sensitive detector elements spatially arranged for sensing said deflection .6 . The apparatus of claim 3 , 4 or 5 wherein the divided detector i s segmented and the light sensitive elements are arranged in di f ferent segments of the segmented detector .7 . The apparatus of claim 6 wherein the detector segments compri ses four segments which provide quadrants of a quadrant detector .8 . The apparatus of claim 5 , 6 or 7 wherein the light collector compri ses a beam splitter arranged to direct the first polari sation component of the reflected beam to the divided detector and to direct the second polarisation component to a second detector , for example wherein the second intensity corresponds to the total intensity sensed by the divided detector .9 . The apparatus of any preceding claim wherein the liquid motion sensor comprises the droplet sensor .10 . The apparatus of claim 9 wherein the droplet sensor i s configured to provide droplet data indicating parameters of contact between the droplet and the liquid system.11 . The apparatus of claim 10 wherein the parameters of contact compri se a time series indicating si ze of the droplet .

12. The apparatus of claim 11, wherein the apparatus is configured to provide one such time series for each droplet, wherein the time series corresponds to an interval between formation of the droplet and coalescence of the droplet with the liquid system, such as an interval between contact of the droplet with the liquid system and coalescence of the droplet.

13. The apparatus of claim 11 or 12 wherein the droplet sensor comprises an optical sensor configured to provide optical data obtained from the droplet at the surface of the liquid system.

14. The apparatus of claim 13 wherein the optical sensor is provided by one of: (a) a camera, wherein the optical data is based on images of the droplet; and (b) a detector and a light beam illuminating the detector wherein the droplet is formed in the path of the light beam to the detector and the optical data comprises a time series of detected intensity of the light beam.

15. The apparatus of any preceding claim further comprising a controller configured to characterise the analyte based on wave data comprising a time series of measurements of the first intensity, the second intensity, and the parameters of liquid motion .

16. The apparatus of claim 15 wherein the controller is configured to determine a characteristic of the analyte based on the wave data .

17. A method of characterising an interaction between a droplet of an analyte and a liquid system, the method comprising: obtaining wave data comprising(iii) parameters of liquid motion associated with the delivery of the droplet to the liquid system; and( iv) a time series of measurements of a wave generated in a liquid system by the droplet , wherein the time series of measurements compri se a plurality of measurements of : a first intensity of a reflected light beam, reflected by the surface of the liquid system, wherein the first intensity corresponds to a first polari sation component of the reflected light beam; a second intensity of the reflected light beam corresponding to second polari sation component of the light beam after reflection ; and, the method further compri sing : characteri sing the analyte based on the time series of measurements of the first intensity, the second intensity, and the parameters of liquid motion .18 . The method of claim 17 wherein the parameters of liquid motion compri se at least one of :( a ) deflections of the reflected light beam from a beam direction as sociated with specular reflection of the light beam from an undi sturbed surface of the liquid system; and(b ) parameters of contact between the droplet and the liquid system .19 . The method of claim 18 wherein the parameters of contact compri se a time series indicating si ze of the droplet .20 . The method of claim 19 , comprising obtaining wave data for a plurality of droplets and providing, for each droplet , a time series of droplet data indicating si ze of the droplet , wherein the time series corresponds to an interval between formation of the droplet and coalescence of the droplet with the liquid system .21 . The method of any of claims 17 to 20 , wherein the parameters of liquid motion compri se deflections and the method compri ses identi fying, based on the deflections , a first subset of the measurements substantially unaf fected by reflections of the wave in the liquid system and a second subset of the measurements as sociated with reflections of the wave in the liquid system.22 . The method of claim 21 compri sing applying a first analysi s to the first subset and a second analysi s to the second subset .23 . The method of claim 21 or 22 wherein the deflections compri se a magnitude and a direction and the first and second subsets are identi fied based on said direction .24 . The method of any of claims 19 to 23 further compri sing determining a feature vector based on the time series of measurements of the first intensity, the second intensity, and the parameters of liquid motion, and using the feature vector to determine a property of the analyte .25 . The method of any of claims 19 to 24 further compri sing di spensing the droplet to cause the wave , illuminating an area of the liquid system with a light beam, receiving a reflected light beam provided by reflection of the light beam by the liquid system, and sensing the first intensity the second intensity and the parameters of liquid motion .26 . A computer program product configured to program a proces sor to perform the method of any of claims 19 to 24 .

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