Technical Field

The present disclosure relates to immersion probes and more particularly to immersion probes for monitoring crystallisation processes and related methods.

Background

Solid crystalline materials may typically be produced in controlled crystallisation processes where an undersaturated solution of a material is cooled in a controlled way to form crystals in the solution that can then be collected.

Crystallisation processes can be monitored using optical imaging to collect images of the crystals in the solution. Optical imaging means typically feature a transparent window through which images can be obtained with an imaging device. Optical imaging immersion probes can be used to image crystallisation processes in situ.

Summary

Aspects of the invention are as set out in the independent claims and optional features are set out in the dependent claims.

Crystallisation and associated fouling on immersion probes for monitoring crystallisation processes is a temperature dependent mechanism that depends on the level of solubility of a crystallisation component in a solution at a particular temperature. During a crystallisation process the temperature of a solution can be decreased to prompt the growth of crystals from the solution. When using an immersion probe to monitor such a mixture, fouling in the form of crystallisation on a transmissive element of the probe, through which energy is transmitted to and/or from the sample to monitor the sample, can disrupt measurements. For example fouling can obscure images obtained using an immersion probe and reduce image quality and reliability or can cause unreliable spectroscopic measurements.

Fouling may be addressed by physically removing crystals from the transmissive element manually or using an automatic device attached to the probe to mechanically wipe or brush the transmissive element. However, manual intervention to remove the probe from a sample medium will disrupt measurements and disrupt the carefully controlled crystallisation process. Manual intervention also requires action to be taken by an operator, which may lead to increased production cost, especially when the process is continuously operated. Automatic devices that can mechanically remove fouling from the transmissive element include small and complex mechanisms that can gather and trap crystals and provide additional nucleation sites.

Fouling may also be addressed by providing a coating on the transmissive element that chemically resists the deposition of crystals. However, chemically resistant coatings may be specific to certain compounds and may not be suitable for use in a variety of systems. In addition, a thin coating can be damaged and removed by abrasive crystals.

Fouling may also be addressed by increasing the temperature of the crystallisation system to dissolve the crystals. However, heating the solution also disrupts the optimum temperature profile and can dissolve crystals that the system is intended to produce, and so heating the solution can reduce the efficiency of the crystallisation process.

Fouling may also be addressed by washing the transmissive element to dissolve solid material on the window, and in a crystallisation process this may comprise washing the window with an undersaturated solution. However, this can affect the overall concentration of the system and therefore affect a controlled profile by which crystallisation is intended to proceed.

Aspects and examples of the present disclosure aim to address the above problems.

In an aspect, there is provided an immersion probe for monitoring crystallisation processes, the probe comprising:

a transmissive element through which energy can be provided to and/or from a sample to monitor the sample; and

a heater configured to heat the transmissive element.

An immersion probe as referred to herein may comprise, for example, a probe that is typically, in use, submerged in a sample medium to be analysed such that analytical information is gathered by a part of the probe that is at least partially submerged. Thus, the transmissive element of the immersion probe through which energy can be provided to and/or from the sample will suitably, in use, be at least partially submerged in a sample medium to be analysed. In a crystallisation process the sample medium in which an immersion probe may be used to provide analysis is typically a solution containing the material to be crystallised or a suspension of crystals in the solution. The probe may comprise an elongate probe body, where the window is disposed at a distal end of the probe body for immersion in the sample medium to be analysed.

The immersion probe may be configured to monitor the sample by providing energy through the transmissive element to the sample to be monitored and receiving energy from the sample through the transmissive element. The immersion probe may be arranged to only provide energy to the sample through the transmissive element, for example where the immersion probe provides energy to the sample and a second probe is used to receive energy from the sample. In some examples, the immersion probe may be arranged to only receive energy from the sample through the transmissive element, for example where energy, for example lighting, is provided to the sample separately and the immersion probe is used to receive energy from the sample.

The probe may comprise more than one transmissive element, where energy is provided to the sample through a first transmissive element, and energy is received from the sample through a second transmissive element. For example, the first and second transmissive elements may arranged in different angular positions relative to the sample to be monitored, for example the first transmissive element may be arranged to provide energy to the sample from one direction and the second transmissive element arranged to receive energy from the sample in the opposite direction relative to the sample, for example to provide backlighting to the sample. The first and second transmissive elements may be arranged to provide energy to the sample and to receive energy from the sample in substantially the same direction relative to the sample, for example the first and second transmissive elements may be substantially coplanar. The first and/or the second transmissive element may be heated by the heater, which may comprise a first and second heater arranged to heat the first and second transmissive elements.

Monitoring crystallisation processes may comprise obtaining images through the transmissive element, for example optical images or ultrasound images. Monitoring crystallisation processes may alternatively or additionally comprise obtaining information about the sample by spectroscopy, for example by irradiating the sample with radiation through the transmissive element and/or receiving radiation from the sample through the transmissive element. For example the radiation may be electromagnetic radiation, which may include electromagnetic radiation visible or non-visible frequencies such as radio wave, microwave, ultraviolet, infrared and/or X-rays. The transmissive element may comprise any suitable material capable of permitting the energy to be provided to and/or from the sample through the transmissive element to monitor the sample.

The immersion probe may be an immersion probe for optical imaging of crystallisation processes. The transmissive element through which energy can be provided to and/or from a sample may be a window through which optical images of a sample can be obtained, with a heater configured to heat the window.

The immersion probe may be suitable for optical imaging over a range of wavelengths such as ultraviolet (UV), visible light and/or infrared. In particular, the immersion probe may be suitable for, or configured for optical imaging in the visible light wavelength range (e.g. from about 380 nm to about 760 nm). The immersion probe may be suitable for spectroscopic analysis over a range of visible and non-visible wavelengths, for example ultraviolet-visible (UV-Vis) spectroscopy, infrared spectroscopy, or Raman spectroscopy.

The window through which optical images of a sample can be obtained may comprise any material that is suitable to permit optical images to be obtained through the window and may be chosen based on the desired physical durability and/or chemical resistance. The window may comprise a glass or a crystalline material, for example the window may comprise silica (for example fused silica), glasses (for example borosilicate glass), quartz, polymeric materials (for example polycarbonate), or sapphire. In particular, the window may comprise sapphire. Depending on the desired use, the window material may be selected to allow transmission of UV, visible and/or infrared light for obtaining optical images, and visible light in particular. The window material may be selected based on the predicted physical or chemical effect on the window of components of the sample medium to be monitored, for example to minimise or avoid abrasion by crystals or corrosion.

The probe may comprise an elongate probe body, where the transmissive element is disposed at a distal end of the probe body for immersion in a sample medium.

The probe may further comprise an energy sensor system for receiving energy from the sample through the transmissive element. The energy sensor system may comprise an imaging system. The energy sensor system may comprise a spectral sensor for receiving electromagnetic energy from the sample and providing spectroscopic information, for example the spectral sensor may comprise a spectral sensor for infrared or Raman spectroscopy. The energy sensor system may comprise an ultrasound receiver. The probe may comprise an energy transmitter configured to provide energy to the sample through the transmissive element to monitor the sample. In general, the energy transmitter and the energy sensor system may be selected based on the respective other of the energy transmitter and the energy sensor system, for example a sensor system configured to detect the energy generated by the energy transmitter.

The energy transmitter may comprise an ultrasound emitter, or a source of electromagnetic radiation. For example, the energy transmitter may comprise one or more lasers, LEDs, or fluorescent lights. The energy transmitter may produce monochromatic light, or may produce light of multiple wavelengths, for example a range of wavelengths or multiple specific wavelengths. The energy transmitter may for example produce light in the ultraviolet (e.g. UV/vis), visible and/or infrared (near, mid or far) regions.

The electromagnetic radiation may be generated remotely and transmitted to the transmissive element, for example by lenses or fibre optics, and/or electromagnetic radiation may be generated and transmitted directly from the source of the radiation through the transmissive element.

In an embodiment, the energy sensor system may comprise an imaging system for obtaining images through the window. The imaging system may comprise an optical sensor for collecting optical images. The optical sensor may be remote from the window, and the probe configured to transmit images using transmission optics from the window to the optical sensor. Transmission optics for transmitting the images may comprise lenses, optical fibres or other suitable reflective or refractive means. In some instances, the imaging system may be arranged to obtain images directly through the window, for example an optical sensor arranged to obtain images through the window without additional optics between the optical sensor and the window.

The optical sensor may comprise any suitable sensor and may, for example comprise a sensor for detecting visible light, UV light, infrared light and/or X-rays. The optical sensor may comprise a photodiode sensor or a photo integrated circuit. In embodiments, the optical sensor may comprise a CCD (charge coupled device) sensor, a CMOS (complementary metal-oxide semiconductor) sensor, a NMOS (n-type metal-oxide semiconductor) sensor, an X-ray sensor, a InGaAs sensor or a silicon photodiode array. In particular the imaging sensor may comprise a CCD sensor. The optical sensor may comprise a digital camera. The sensor may comprise a combination of sensors, for example sensors for both imaging and spectral analysis, for example the energy sensor system may comprise both an imaging system and a spectral sensor.

The optical sensor may be suitable for obtaining images at a rate of at least 30 frames per second, for example at least 60 frames per second or at least 90 frames per second. By using a higher frame rate, images of moving particles may be imaged so as to appear stationary. In addition, at higher frame rates, several similar images of a corresponding sample may be obtained and averaged to improve the image signal to noise ratio. An increased number of images captured may also allow more individual particles or crystals to be analysed.

In embodiments, the probe comprises a lens system through which optical images are obtained, wherein the distance of the focal point from the probe window can be adjusted. The lens system may be a unifocal lens system.

The imaging system may comprise a front light arranged to provide illumination to the sample that can be observed as backscattered light from the sample. The front light may comprise any suitable light source. The front light may comprise one or more light emitting diodes (LEDs), for example, the front light may comprise one or more LEDs that provide light in the visual light range of the electromagnetic spectrum. The front light may provide light to the sample with a luminous flux of at least 100 lumens, for example at least 200 lumens, for example from 100 to 400 lumens, for example from 200 to 300 lumens. In some implementations, the front light may comprise a laser.

The front light may comprise a remote light source that provides light to the sample by optics such as lenses or optical fibres. In embodiments, the front light may provide light to the sample through the same optics used for the collection of images. Alternatively, the front light may comprise a light source, for example an LED, arranged to provide direct illumination to a sample.

The probe comprises a heater configured to heat the transmissive element, which can allow the transmissive element to be heated independently from the temperature control of a bulk sample medium in which, in use, the probe is immersed. This can allow fouling on the transmissive element to be controlled by heating the transmissive element, without substantially affecting a controlled temperature profile of the bulk sample medium. When the probe is immersed in a sample medium, heating the transmissive element can form a layer of the sample medium around the transmissive element that is at a higher temperature than the bulk temperature of the sample medium, and prevent crystallisation around the transmissive element that can interfere with monitoring the sample, for example by obscuring images.

Reference to the temperature of the“bulk” sample medium can be considered to refer to an average temperature across the sample medium in which the probe is immersed.

The heater may be configured to heat the transmissive element of the probe and/or a section of the probe adjacent the transmissive element, more than other parts of the probe. For example, the heater may be arranged to only provide heat to a part of the probe comprising the transmissive element so that the heating is localised to that part of the probe.

In embodiments, the heater may be arranged to be adjacent the transmissive element, for example the heater may be arranged between the probe body and the transmissive element, for example, the heater may be disposed adjacent a surface of the transmissive element facing a wall of the probe body or the interior of the probe body. The heater may at least partially surround the transmissive element. The heater may surround the transmissive element, for example it may encompass the majority of the edge of the transmissive element, for example it may completely encircle the transmissive element. Whether or not the surrounding heater completely encloses the periphery of the transmissive element, it may be arranged to ensure that heat energy can be provided to the transmissive element from at least two sides. The heater may be arranged to heat the transmissive element whilst leaving the transmissive element unobscured, for example for the collection of images. The heater may surround a portion of the window through which energy is provided, for example through which images are collected. The heater may or may not be in direct contact with the transmissive element.

In embodiments, the probe comprises one or more temperature sensors for monitoring the temperature of the transmissive element. The one or more temperature sensors may be configured to monitor the temperature of the transmissive element directly and/or indirectly. For example, one or more temperature sensors may be configured to directly monitor the temperature of the transmissive element material itself, and/or one or more temperature sensors may be configured to monitor a part of the probe or the sample medium in which the probe is immersed that is in thermal contact with the transmissive element. The one or more temperature sensors may be affixed to the transmissive element or affixed to the probe body adjacent the transmissive element. The one or more temperature sensors may be connected to the transmissive element by a heat transfer medium that has higher thermal conductivity than the probe housing. The one or more temperature sensors may be disposed inside the probe body or may be disposed outside the probe body.

In embodiments, the probe comprises one or more temperature sensors arranged to monitor the temperature of a portion of the sample medium surrounding the transmissive element that is heated by the heater. The probe may additionally or alternatively comprise one or more temperature sensors arranged to monitor the temperature of a portion of the sample medium that is not substantially heated by the heater, i.e. the bulk sample medium in which the probe is immersed.

In embodiments, the probe may comprise a controller configured to control the heater to heat the transmissive element to a temperature that is higher than the temperature of a bulk sample medium in which a portion of the probe that comprises the transmissive element is immersed.

The controller may be configured to monitor the temperature of the bulk sample medium, for example connected to receive signals from one or more temperature sensors, and to control the heating to heat the transmissive element to a temperature that is higher than the monitored temperature. The controller may receive an indication of the monitored temperature from external temperature sensors, for example sensors are not integrated as part of the probe, for example a temperature sensor affixed to a container that contains the bulk sample medium. The controller may alternatively or additionally receive an indication of the monitored temperature from temperature sensors integrated with the probe, for example sensors affixed to the probe but arranged to monitor a portion of the sample medium which is substantially not heated by operation of the heater. The monitoring may be performed at defined time intervals or may be substantially continuous.

The controller may be configured to control the heating to heat the transmissive element to a temperature that is higher than a set temperature profile of the bulk sample medium. For example, the temperature of the bulk sample medium may not be monitored by the controller, but the controller may store a temperature profile, where the sample medium is controlled to maintain that temperature profile, and heat the transmissive element to a temperature higher than that temperature profile.

The controller may be configured to control the heating based on an input from a user, for example by receiving an input signal to adjust the heating, for example to turn the heating on or off. The controller may be configured to control the heating based on the detection of fouling on the transmissive element, for example by determining that collected images show fouling and activating the heating in response to the determination.

It will be appreciated that above a certain temperature, for a crystallisation system at a particular concentration, crystals will not generally form. Accordingly, heating of the transmissive element may not be required at such times. Thus, in embodiments, the controller is configured to control the heating to heat the transmissive element only when the sample medium has a temperature lower than a threshold temperature. The threshold may be a static threshold or may be dynamic threshold. For example, the threshold may be adjusted dynamically based on system properties (e.g. concentration).

The heater may comprise any suitable means for heating the transmissive element. In embodiments, the heater comprises a heating element, such as an electric heating element, arranged on or in the transmissive element and/or the body of the probe to heat the transmissive element. For example, the heater may comprise a trace heater.

In embodiments, the probe comprises a probe body configured so that a gas can flow through the interior of the probe body, wherein the heater comprises a heater configured to heat the gas that flows through the probe body to heat the transmissive element. The heater configured to heat the gas may comprise a heat exchanger or may comprise any other suitable means for heating the gas. The heater configured to heat the gas supplied to the probe may be disposed on or inside the probe body or may be separate from the probe body.

In some instances, a heater configured to heat the gas supplied to the probe may not necessarily be present, but the probe body is still configured so that a gas can flow through the interior of the probe body so that the flow of gas can serve to reduce condensation inside the probe.

The gas supplied to the probe may be provided through a gas filter, which may be arranged in the gas flow path prior to the heater configured to heat the gas.

In a further aspect, there is provided a method for reducing or preventing fouling on an immersion probe in a crystallisation process, comprising:

heating a transmissive element of the probe through which energy can be provided to and/or from a sample to monitor the sample; and controlling said heating to heat the transmissive element to a temperature that is higher than the temperature of a sample medium in which a portion of the probe that comprises the transmissive element is immersed.

The method may comprise monitoring the temperature of the sample medium and controlling the heating to heat the window to a temperature that is higher than the monitored temperature, and/or may comprise controlling the heating to heat the window to a temperature that is higher than a known temperature profile of the sample medium. In some instances, the heating may only be performed when the sample medium has a temperature lower than a threshold temperature, which may be set based on the temperature at which crystals typically form in a particular crystallisation system, or may be a set temperature based on when fouling was observed previously in the system. The threshold may be a static threshold or may be dynamic threshold. For example, the threshold may be adjusted dynamically based on system properties (e.g. concentration).

The method may comprise reducing or preventing fouling on an optical imaging immersion probe during a crystallisation process. The crystallisation process may be a batch process where a quantity of crystals are produced for a period of time then obtained from a sample medium. Alternatively, the process may be a continuous process where crystals and undersaturated solution are continuously removed and replaced by saturated solution for crystallisation.

The method may comprise controlling the heating by receiving an input signal to adjust the heating, for example to turn the heating on or off. The method may comprise controlling the heating based on the detection of fouling on the transmissive element, for example by determining that collected images show fouling and activating the heating in response to the determination.

The method may comprise heating a window of the probe through which optical images can be obtained, and controlling said heating to heat the window to a temperature that is higher than the temperature of a sample medium in which a portion of the probe that comprises the window is immersed.

In a further aspect, there is provided a method for retrofitting an immersion probe system, for example an optical imaging immersion probe system, configured so that a gas can flow through the interior of the probe body, wherein the method comprises introducing to the system a heater that is arranged to heat the gas that flows through the interior of the probe body.

In a further aspect, there is provided an immersion probe for optical imaging of crystallisation processes, the probe comprising:

a window through which optical images of a sample can be obtained;

a front light for providing illumination to the sample; and

a backlight arranged to provide illumination towards the window through the sample.

Features of the probe may be substantially as described previously herein. In addition, the probe comprising a front light and a backlight may additionally comprise a heater as described previously.

The front light and backlight may comprise any suitable light source, for example a light source as described previously. In embodiments, the front light and/or the backlight comprise one or more light emitting diodes (LEDs). The front light and/or the backlight may also comprise a laser.

The front light and/or backlight may comprise a remote light source that provides light to the sample by optics such as lenses or optical fibres. In embodiments, the front light may provide light to the sample through the same optics used for the collection of images. Alternatively, the front light and/or backlight may comprise a light source, for example an LED, arranged to provide direct illumination to a sample.

In embodiments, the backlight is arranged at a distal end of the probe and is separated from the window by a spacing to enable the sample to be interposed between the backlight and the window, for example the spacing between the window and the backlight may define a volume that is open to the space around the probe so that when the probe is immersed in a sample medium, the sample medium can freely enter the volume. The backlight and the window may be separated along a longitudinal axis of the probe or perpendicular to the longitudinal axis. For example, the backlight and the window may be separated along a longitudinal axis of the probe, with the backlight arranged to direct light proximally from a distal end of the probe.

The backlight and the window may be spaced apart by at least 3 mm, for example at least 4 mm and/or may be spaced apart by no more than 10 mm. For example, the backlight and the window may be spaced apart by from 3 mm to 10 mm, for example from 4 mm to 8 mm, for example about 5 m to 7 mm. Reduced spacing may allow the size of the probe tip, and consequently the size of the probe as a whole, to be minimised. Reduced spacing may also improve illumination of the sample and the quality of images obtained. Increased spacing may reduce the possibility of solids, such as crystals, becoming trapped in the spacing and blocking it. Increased spacing may also aid cleaning of the probe.

The front light and/or the backlight may be arranged to provide focussed light to the sample, for example light focussed on the field of view of an imaging system. For example, the front light and/or the backlight may comprise focussing optics such as lenses. Providing focussed light from the front light and/or the backlight may allow reflection of light that may affect images to be reduced. Where the front light is provided by optics that are shared with an imaging system, the front light may be focussed on the field of view of the imaging system. The backlight may be overfocussed on the field of view of the imaging system so as to encompass the area of the field of view, for example the backlight may be focussed so as to illuminate an area that is larger than the field of view of the imaging system. In some embodiments, the backlight may provide dispersed light, or may provide collimated light.

Light provided by the front light and/or the backlight may be homogenised, for example the front light and/or the backlight may comprise a beam homogeniser.

In some examples, the front light may be optional and the immersion probe may comprise a window through which optical images of a sample can be obtained and a backlight arranged to provide illumination towards the window through the sample.

The probe may comprise an elongate probe body, with the window and the backlight disposed at a distal end of the probe body for immersion in a sample medium. For example, the probe may be arranged with the window at a distal end of the elongate probe body, and a neck extending distally from the probe body attached to a head comprising the backlight.

The probe may be configured so that one or more operating parameters of the front light and/or the backlight can be controlled differently from the backlight or the front light respectively. For example, the probe may be configured so that one or more operating parameters of the front light or backlight can be changed relative to each other. The probe may be arranged to transmit light and/or power for the front light and the backlight separately through the body of the probe. For example, the probe may be configured so that one or more operating parameters of the front light and/or the backlight can be independently varied. Operating parameters of the front light and/or backlight may comprise intensity of the illumination. Operating parameters may additionally or alternatively comprise continuity of the illumination. For example, the front light and/or the back light may be operated continuously, may be operated in a stroboscopic mode, or may be triggered when an image is obtained.

In embodiments, the probe comprises a controller. The controller may be configured to obtain an image taken through the window and, based on the obtained image, adjust one or more operating parameters of the front light and/or the backlight.

One or more operating parameters of the front light and/or backlight may be adjusted based on the image quality. For example, the intensity of the illumination from the front light and/or the backlight may be adjusted when the image quality is found to be unsatisfactory.

Illumination from the front light of the probe can provide backscattered light from particles such as crystals in the medium being analysed, which may aid analysis of the physical properties of the surface, or analysis of their morphology. Illumination from the backlight can lead to an image having sharper edges for the objects in the image, which may aid the collection of quantitative information about particles such as size and shape distribution of the particle population.

The controller may be configured to analyse an image to determine a level of sharpness of edges of objects in the image, and where the level of sharpness is below a threshold value, to increase the backlight intensity, and/or decrease the front light intensity. By way of example, determining a level of sharpness may comprise using image gradients and/or image derivatives to evaluate the sharpness of objects in an image, for example using a Gaussian derivative focus measurement to analyse object edges in the image. The controller may be configured to determine a level of sharpness for multiple images obtained under different lighting conditions and adjust intensity of the backlight and/or the front light to increase sharpness based on the determined sharpness of the images.

The controller may be configured to time adjustments in the illumination from the front light and the backlight with the collection of images so as to provide different illumination conditions in different images. For example, an image may be obtained with the backlight illumination optimised to provide sharp edges for objects in the image for analysing quantitative information, and a separate image may be obtained with the front light illumination optimised for surface or morphology analysis. For instance, one of the front light or backlight may be increased in intensity, and additionally or alternatively, at the same time the illumination from the respective other of the front light or backlight may be decreased in intensity. Where images of the sample are collected quickly (for example at a rate of at least 30 frames per second), images of substantially the same sample may be obtained under different illumination conditions. For example the front light and the backlight may be operated in a stroboscopic mode to give alternating illumination. Alternatively, the illumination from the front light and the backlight may be balanced to optimise for sharp edges in the image and surface/morphology analysis in the same image.

The illumination from the front-light and/or backlight may be triggered based on when an image is being obtained. For example, when an image is to be obtained, the illumination from the front light and/or the backlight may be activated, and may be subsequently deactivated after the image has been obtained. The triggered activation of the front light and/or the backlight may also comprise controlling the relative intensity of the front light and/or backlight based on the desired image properties.

In a further aspect, there is provided a method for obtaining images using an optical imaging immersion probe, wherein the probe comprises a window through which optical images of a sample can be obtained, a front light for providing illumination to a sample and a backlight for providing illumination towards the window through the sample, the method comprising: obtaining an image through the window; and

based on the obtained image, adjusting one or more operating parameters of the front light and/or the backlight.

In a further aspect, there is provided a computer-implemented method of processing images of a sample from an optical imaging immersion probe, the method comprising:

obtaining one or more images taken by an optical imaging immersion probe;

analysing the one or more images; and

based on the analysis, outputting an alert signal and/or a control signal to adjust an operating parameter of the optical imaging immersion probe.

The method may comprise adjusting one or more of the images to improve the image quality, for example adjusting contrast of the image. Analysing the one or more images may comprise detecting one or more particles captured in the image and determining size and/or shape and/or degree of agglomeration information about the particles.

In some instances, analysing the one or more images may comprise determining whether fouling is present on a window of the probe through which images are taken and optionally outputting an alert signal and/or a control signal to reduce fouling when fouling is detected. For example, a heater could be controlled by the control signal to heat the window of the optical imaging probe to reduce fouling.

By way of example, determining whether fouling is present may comprise comparing one or more images to one or more previously obtained images, and determining the presence of a persistent object or region in the compared images. For example, where one or more objects are detected in an image, and one or more similar objects (e.g. in terms of position, shape and/or size) are detected in one or more subsequent images, fouling may be indicated.

In some instances, analysing the one or more images may comprise determining a level of sharpness of objects in the image, and where the level of sharpness is below a threshold value, to send an alert signal or a control signal to increase backlighting of the sample, and/or to decrease front lighting of the sample relative to the backlighting.

The images may be stored in a local memory or may be distributed to a remote computer via a network. The images and/or information may also be displayed to a user.

In further aspects, there are provided a computer program product comprising program instructions configured to program a computer system to perform the methods described herein, and a control system for an immersion probe, comprising a processor and computer memory comprising the program instructions.

In a further aspect, there is provided a system comprising an immersion probe and a control system as described herein.

Aspects of the invention may be provided in conjunction with each other and features of one aspect may be applied to other aspects.

Brief Description of Drawings Embodiments of the disclosure will now be described, by way of example only, with reference to the accompanying drawings, in which:

Figure 1 illustrates a solubility curve for a crystallisation process;

Figures 2A and 2B show a side view of an example immersion probe and a schematic view of the distal end of the probe;

Figures 3A and 3B show a side view of an example immersion probe and a schematic view of the distal end of the probe;

Figures 4A and 4B show a side view of an example immersion probe and a schematic view of the distal end of the probe.

Figure 5 shows examples of different temperature profiles to control fouling in crystallisation processes.

Specific Description

Described herein with reference to the Figures are immersion probes and methods for optical imaging of crystallisation processes. In particular, described herein are optical imaging immersion probes comprising a heater that is configured to heat the window of the optical immersion probe through which images are obtained. Providing an immersion probe having a heater configured to heat the window allows heating of the window to be independent from the temperature control of the bulk sample medium in which the window of the immersion probe is immersed. In this way, the window can be heated to prevent or reduce fouling due to the formation of crystals on the window without substantially altering the temperature profile of the bulk sample medium. Also described herein is an immersion probe for optical imaging, comprising a front light and a backlight arranged to provide illumination towards the probe window through a sample. Providing both front lighting and backlighting on the immersion probe can allow the immersion probe to capture higher quality images in situ without requiring a sample to be removed from a crystallisation vessel and analysed externally.

Figure 1 illustrates how a solubility curve may vary with temperature, and how dissolution and crystallisation are favoured by increasing or decreasing temperature, respectively. There is a temperature dependent solubility curve for crystallization processes where the system is in thermodynamic equilibrium. When the system is saturated, there is no driving force for formation of crystals or fouling. When the system is undersaturated, i.e. when the concentration level of the solution is less than the saturation concentration at the specific temperature, material transfers from the solid phase to the liquid phase in order to drive the system to a balanced equilibrium state, i.e. material is dissolved. When system is supersaturated, the solution concentration is higher than the thermodynamic equilibrium concentration, and so material transfers from solution to the solid phase in order to drive the system to a balanced equilibrium state, which is when crystallization occurs.

Figure 2A shows an example immersion probe 100 and two insets (a) and (b) showing more detailed views of the distal end of the probe 100 (inset (b)) and the connection between the probe 100 and a container 103 (inset (a)). The probe body comprises a housing 101 and an elongate stem 108 extending from the housing 101. The probe head comprises a heater 104 arranged at a distal end of the stem 108 to heat a window 102 through which optical images can be obtained. The heater may be connected to a controller 110 or a power supply by a connection 109. The connection 109 may be provided through the inside of the stem 108.

The probe shown in Figure 2A also comprises a neck 318 and a head 314 comprising a backlight 312, and these features are described in more detail with reference to Figures 4A and 4B.

As illustrated in inset (a) of Figure 2A, in use, the stem 108 may be inserted into a container 103 such that the window at the head of the probe at a distal end of the stem is immersed in a sample medium 105 to be analysed. As shown, in use the stem may project into a closed container 103 through an aperture 113 in the container 103. The aperture 113 may form a seal with the probe stem 108 to substantially prevent the sample medium 105 from escaping through the aperture 113. The aperture 113 may comprise a seal selected based on the size of the probe stem 108, which may for example have a diameter of from 10 mm to 40 mm, for example from 15 mm to 30 mm, for example about 20 mm to 25 mm. The aperture 113 may comprise a seal configured to meet the needs of the particular system, for example in terms of the chemical nature of the sample medium 105 or conditions of temperature and/or pressure in the container 103. The probe 100 and the aperture 113 may interact so that the probe 100 can be manually removed from the aperture, for example to perform maintenance on the probe 100 or the container 103. For example the stem 108 may slidably interact with the aperture 113 to allow insertion or removal of the probe. The stem 108 may lock in place in the aperture 113 such that the lock must be released before the probe 100 can be removed. It will be appreciated that the probe may also be used to analyse a sample medium in different environments such as open containers for example.

Inset (b) of Figure 2A shows a view of the distal end of the probe 100. The probe comprises a window 102 on a distal end surface of the probe stem 108, where the window 102 provides a transparent section of the probe body through which optical images can be obtained. The probe 100 comprises a heater 104 disposed adjacent to and surrounding a portion of the window 102 through which images are collected. The heater 104 is arranged to heat the window 102. In use, when the window 102 is heated, a layer 115 of sample medium adjacent the window may be formed that is of higher temperature than the bulk sample medium 105. The heater may be connected to a power supply and/or controller for controlling the heating by a connection 109. The level of heating may be controlled by changing the intensity of the heating, for example by varying the voltage or the current to an electric heating element. Alternatively or additionally, the level of heating may be varied by controlling the frequency and/or duration of time that the heater 104 is on, for example by providing a modulated signal to the heater 104. For example, the duty cycle of a signal to the heater 104 may be adjusted to alter the level of heating.

Figure 2B shows an example schematic view of the stem 108 of a probe 100. A window 102 is disposed at a distal end of the stem 108. The window 102 may be made from any suitable transparent material that allows optical images to be obtained through it. While the window 102 is shown as disposed as being disposed on a distal end of the stem, the window may suitably be arranged on a different surface of the probe 100, for example on a lateral surface of the stem 108. The shape of the window 102 may be selected to conform to the cross- sectional shape of the stem 108. For example, the window 102 may define a circular path through which optical images may be obtained.

The probe 100 comprises a heater 104 arranged at the distal end of the stem 108 and arranged to heat the window 102. The heater 104 may be any heater suitable for transferring heat to the window 102. In examples the heater 104 may be an electric heating element such as a trace heater.

In use, the heater 104 is operable to heat the window 102. By heating the window 102, deposition of solid material from the sample medium on the window may be reduced or avoided. Heating the window 102 may form a layer 115 of sample medium around the window 102 that is heated to a higher temperature than the bulk sample medium 105. The thickness of the layer 115 may vary based on the temperatures of the window 102 and the bulk sample medium 105, flow rate of the sample medium past the window 102, and the physical properties of the sample medium such as viscosity and thermal conductivity. The higher temperature of the layer 115 of sample medium around the window 102 shifts the saturation curve so that dissolution of solid material is favoured over crystallisation. Even for relatively small laboratory crystallization systems the volume of the container 103 comprising the sample medium 105 is typically large compared to the size of the window 102 such that the effect of heating the window 102 is negligible on the temperature of the bulk sample medium 105. For example, the volume of a container 103 in which the probe is immersed may be at least 100 mL, and industrial systems may be over 1000 L. Laboratory containers may have a volume of from about 100 mL to 500 L, for example from about 1 L, 5 L or 20 L to about 50 L or 300 L.

The heater 104 can be connected to a controller 110 by connection 109. Connection 109 may be configured to transmit power and/or control signals to the heater 104. The controller 110 may be configured to control the heater 104 to heat the window 102 to a temperature higher than the sample medium 105 in which the window is immersed. For example, the heater 104 may heat the window 102 to be at least about 2 °C to 10 °C higher than the temperature of the bulk sample medium 105, such as at least about 5 °C higher. The heater 104 may heat the window 102 to be no more than 20 °C higher than the temperature of the bulk sample medium 105, or may heat the window to be no more than 10 °C higher than the temperature of the bulk sample medium 105. The temperature of the window 102 may be varied within a temperature range above the temperature of the bulk sample medium 105, for example in response to the presence of fouling. Alternatively, the temperature of the window 102 may be maintained at a substantially constant temperature above the temperature of the bulk sample medium 105 to prevent fouling.

The controller 110 may monitor the temperature of the bulk sample medium 105 and/or the window 102 in real time and control the heater 104 based on the monitored temperature. For example the controller 110 may monitor the temperature of the window 102 and compare it to a set temperature profile of the bulk sample medium 105. For example, in a crystallisation process, the temperature of the bulk sample medium can be controlled to give an optimised temperature profile for producing the desired crystalline product. The controller 110 may store information relating to a set temperature profile and use that information to adjust the temperature of the window 102 to be above the profile temperature. The controller 110 may additionally or alternatively monitor the temperature of the bulk sample medium 105 and compare that temperature to the temperature of the window 102. The controller 110 may control the heating based on manual input signals to turn on or turn off the heating. The controller 110 may control the heating based on the detection of fouling on the window 102, for example by determining that collected images show fouling and activating the heating in response to the determination.

Above a certain temperature threshold, the bulk sample medium 105 may be at a high enough temperature that deposition of solid material on the window 102 is negligible. Under such conditions, it may be beneficial to avoid operating the heater 104 to save power and/or to avoid wear to components of the probe 100. Therefore, the controller 110 may only control the heater 104 to heat the window when the sample medium has a temperature lower than a threshold temperature, which may be a static temperature threshold or a dynamically adjusted threshold temperature.

The controller 110 may monitor the temperature of the window 102 and/or the bulk sample medium 105 by receiving information from temperature sensors arranged to monitor the temperature of the window 102 and/or bulk sample medium 105. The temperature sensors may be integrated as part of the probe 100, or may be external sensors that provide temperature information to the controller 110.

The probe 100 comprises an imaging system 106 for obtaining optical images of the sample through the window 102. The imaging system 106 may comprise an optical sensor 106a for recording images such as a camera, which may be arranged to take images directly through the window 102. Alternatively, the optical sensor 106a may be remote from the window and the imaging system 106 may comprise optics for transmitting images through the window 102 to the optical sensor 106a. For example, the imaging system 106 may comprise lenses, optical fibres or other suitable reflective or refractive means for transmitting optical images to the optical sensor 106a. Although in Figure 2B the imaging system 106 is shown schematically as being disposed in the stem 108 of the probe 100, it will be appreciated that the imaging system may extend throughout the probe body, for example images may be transmitted from the window 102 through the probe body to an optical sensor 106a disposed in the housing 101.

The imaging system 106 may comprise a front light 106b arranged to provide illumination to the sample and providing backscattered light from the sample. The front light 106b may comprise any suitable light source, for example LEDs or lasers. It will be appreciated that the specific light source used may be varied to optimise for the sample being imaged and the properties of the sample that the image is intended to display. The front light 106b may comprise a remote light source that provides light to the sample by optics such as lenses or optical fibres. The front light 106b may provide light to the sample through at least some of the same optics of the imaging system 106 that are used for the collection of images to an optical sensor 106a. Alternatively, the front light 106b may comprise a light source arranged to provide direct illumination to a sample. Whether the front light 106b shares optics that are used for imaging or not, the front light 106b may provide illumination of the sample through the window 102. It will be appreciated that while the optical images are collected through the window 102, illumination from a front light 106b may in some instances be provided separately and not through the window.

The imaging system 106 can be connected to the controller 110, whereby the controller may store and/or distribute the images collected by the imaging system 106. The controller may be configured to control the imaging system 106 to alter properties of the collected images. For example the controller 110 may control the imaging system to adjust the focus of images or may control the intensity of illumination from the front light 106b. In addition, the controller 110 may be configured to analyse images collected by the imaging system 106 to detect fouling on the window 102. Detecting fouling on the window 102 may comprise comparing image properties to properties of images where fouling on a window was known to have occurred. The comparison may for example be against image properties for images collected by the same probe 100 or stored image properties from other probes. The controller 110 may be configured to detect fouling on the window 102 in real time and, in the event that fouling is present, issue an alert signal to a user and/or control the heater 104 to heat the window 102 to reduce fouling. Imaging system 106 may be connected to the controller 110 by a connection 107, which may be configured to transmit control signals to the imaging system and/or to transmit image data to the controller from the imaging system. Connection 107 may also be used to provide power and/or control signals to a front light 106b of the imaging system 106.

Although a specific arrangement is shown in Figures 2A and 2B, it will be appreciated that other arrangements of the probe 100 are possible.

Inset (b) of Figure 3A shows an example immersion probe 200 comprising a heater 104’ configured to heat a gas flow 212, provided from a gas supply 217, to produce a heated gas flow 212’. As described in relation to Figure 2, the probe has a probe body comprising a housing 101 and a stem 108 extending from the housing having a window 102 for obtaining optical images at a distal end of the stem 108. The heated gas flow 212’ may be fed to the probe 200 via a connector 219 at a proximal end of the stem 108. The probe 200 is arranged so that the heated gas supplied through connector 219 flows through the stem 108 to heat the window 102.

Inset (a) of Figure 3A shows an example immersion probe with a gas flow 212 supplied to the probe 200 through the connection 219, where the gas from the gas supply 217 is not heated prior to feeding the gas into the probe 200. For example, the supply of gas to flow through the probe, even where no heater is present, may prevent or reduce the formation of condensation inside the probe 200 when the probe 200 is used in a low temperature sample medium.

The probe 200 as shown in Figure 3A (a) or (b) may additionally comprise a heater at the distal end of the stem and/or a controller as described in relation to Figure 2.

Figure 3B shows an example schematic view of the stem 108 of a probe 200. As described in relation to Figure 2, a window 102 is disposed at a distal end of the stem 108 and an imaging system 106 is arranged to obtain optical images through the window 102 and is connected to a controller 110 by a connection 107.

A gas flow 212 is heated in heater 104’ to produce a heated gas flow 212’. The heater 104’ may comprise any suitable means for heating the gas and may, for example, comprise an electric heating element arranged to heat the gas flow 212, or may comprise a heat exchanger arranged to heat the gas flow 212 by direct or indirect contact with a heated fluid. The probe 200 is configured so that the heated gas 212’ flows through the stem 108 so as to heat the window 102. It will be appreciated that, in addition to heating the window 102, the heated gas flow 212’ may heat the probe body and any components inside the probe body, for example the imaging system 106 and connection 107, as the gas 212’ passes through the probe. The probe 200 may be arranged so that the flow of gas 212’ is at least partially insulated from the stem 108 and components inside the stem 108, but is permitted to heat the window 102. For example, the heated gas flow 212’ may be directed through the probe 200 from a connector 219 inside a conduit, which may be insulated, and provided to the window 102. Alternatively, the flow of heated gas 212’ may be permitted to flow throughout the probe 200, which may allow the flow of gas 212’ to prevent or reduce condensation inside the probe 200 when it is used in a low temperature sample medium.

The flow of heated gas 212’ may be exhausted from the probe as an exhaust flow 214 through an exhaust outlet. The interior of the probe 200 may define a flow path for the heated gas flow 212’ from a connector 219, through the probe 200, past the window 102, and to an exhaust port.

The heater 104’ may be disposed outside the probe body between a gas source 217 and a connector 219 as shown in inset (b) of Figure 3A. Alternatively, the heater 104’ may be integrated into the probe body to heat a gas flow that is directed to the window 102.

A controller 110 may be coupled to the heater 104’ by a connection 109 and configured to control the heating of the window 102 as described in relation to Figure 2. Instead of monitoring the temperature of the window 102, the heater 104’ may monitor the temperature of the gas heated by the heater 104’ so as to indirectly monitor the temperature that the window 102 is heated to. Where the heater 104’ is separate from the probe, control of the heating may be provided separately or integrated with control of the imaging system, and heating control may be integrated into the heater 104’.

Where a probe 200 is arranged to provide a gas flow 212 through the probe without a heater for the gas flow, for example as shown in inset (a) of Figure 3A, such a probe may be retrofitted to include a heater 104’ arranged to heat the gas flow 212. In this way, a probe that may not comprise means for heating the window 102 may be modified to provide a heated gas flow 212’ that can heat the window 102 to prevent or reduce fouling on the window 102.

Although a specific arrangement is shown in Figures 3A and 3B, it will be appreciated that other arrangements of the probe 200 are possible. For example the probe 200 may comprise a neck 318 and a head 314 comprising a backlight 312, as described in relation to Figures 4A and 4B.

Although Figures 2 and 3 have been described with reference to an optical imaging immersion probe comprising a window, this is merely one illustrative example and the probe may be an immersion probe for monitoring crystallisation processes comprising a transmissive element through which energy can be provided to and/or from the sample to monitor the sample.

Figure 4A shows a view of an example immersion probe 300. As described in relation to Figures 2 and 3, probe 300 has a probe body comprising a housing 101 and a stem 108, a window 102 and an imaging system 106. The imaging system 106 comprises an optical sensor 106a for producing optical images of the sample. The optical sensor may comprise a camera such as a digital camera, and may, for example, comprise CCD (charge coupled device) sensor or a CMOS (complementary metal-oxide semiconductor) sensor. The optical sensor may be operable to obtain images at a rate of at least 30 frames per second.

The optical sensor 106a is disposed in the housing 101 , and transmission optics 106c are arranged to transmit images from the window 102 to the optical sensor 106a. The transmission optics 106c may comprise an optical lens system configured to project images of the sample obtained through the window to the optical sensor 106a.

The imaging system 106 may comprise a front light 106b arranged to provide illumination to the sample. The front light 106b may be disposed in the housing 101 and project light through the transmission optics 106c to a sample to be imaged. As illustrated in the inset of Figure 4A, light from the front light 106b may be focussed by the transmission optics through the window 102 onto a field of view 319. The distal end of the stem 108 comprises a neck 318 connecting a head 314 to the stem 108 as described in more detail in relation to Figure 4B. The head comprises a backlight 312 for providing light towards the window 102 through the sample in the field of view 319.

Figure 4B shows an example schematic view of the stem 108 of a probe 300. The probe comprises a neck 318 that extends distally from the end of the stem 108 and supports a head 314. The head 314 is arranged to oppose the window and the distal surface of the stem 108 from which the neck 318 extends, for example the probe is arranged such that the neck 318 and head 314 form an extension of the stem 108, having a spacing 316 between the head 314 and the window 102 through which a sample can flow. The field of view 319 is disposed in the volume defined by the spacing 316. The head 314 comprises a backlight 312. The backlight is arranged to provide illumination towards the window 102 through the sample in the spacing 316 and through the field of view 319. The spacing 316 between the window 102 and the backlight 312 may be selected such that sufficient light from the backlight 312 can pass through the sample in the spacing 316 and be collected by the imaging system 106. It will be appreciated that the illumination intensity of the backlight 312 may be varied to account for the size of the spacing 316 and/or for how optically absorbent the sample medium interspersed between the backlight 312 and the window 102 is. The spacing between the window 102 and the backlight 312 may for example be in the range of about 3 mm to 10 mm, for example about 4 mm to 8 mm, for example about 6 mm.

The backlight 312 may comprise any suitable light source, and may for example comprise a laser or one or more LEDs. As shown in the inset of Figure 4A, the backlight 312 may provide dispersed light towards the window 102 through the sample, while the front light may provide focused light onto the sample in the field of view 319. Where the backlight 312 light source does not generate dispersed light, dispersion of the backlighting may be achieved by use of dispersion optics. While the backlighting is shown in Figure 4A as being dispersed, the backlight 312 may be focussed on the field of view 319. In particular, the backlight 312 may be overfocussed on the field of view 319 so as to provide focussed backlighting that encompasses the field of view 319. By providing backlighting, images captured by the imaging system 106 may increase the sharpness of objects in an image, which may aid the collection of quantitative information about particles such as size and shape distribution of the particle population. In addition, by providing illumination from the front light 106b that is focused onto the field of view 319, backscattered light from crystals in the sample medium can be collected by the imaging system 106, which may aid analysis of the physical properties of the surface of crystals, or analysis of their morphology.

Although not explicitly shown in Figure 4, Light provided by the front light 106b and/or the backlight 312 may be homogenised, for example the front light 106b (and/or the transmission optics 106c) and/or the backlight 312 may comprise a beam homogeniser.

The front light 106b and the backlight 312 may each be controllable to adjust the intensity of the illumination. The front light 106b and/or the backlight 312 may be controllable to adjust the continuity of the illumination, for example to either provide light continuously or to provide light intermittently, for example in a stroboscopic pattern or when triggered by a controller 110

The probe 300 comprises a controller 110’ that is connected to the imaging system by a connection 107 and to the backlight 312 by a connection 311. The controller 110’ may be configured to control the transmission optics 106c to adjust the focus of images projected to the optical sensor 106a. For example, the controller 110’ may be configured to adjust the position and/or size of the field of view 319. The controller 110’ may also be configured to control the front light 106b and/or the backlight 312 to adjust the intensity of the illumination provided by the front light 106b or the backlight 312. The front light 106b and the backlight 312 are connected to the controller such that the illumination intensity from each light can be separately adjusted to improve image quality. The controller 100’ may also control the front light 106b and/or the backlight 312 to adjust the continuity of illumination. For example, the controller may be configured to control the front light 106b and/or the backlight 312 in at least one of a first mode where the illumination is continuous during use of the probe; and a second mode where the illumination is intermittent, for example in a stroboscopic pattern. The controller 110’ may be configured to time the illumination with the capturing of images by the optical sensor 106a. Variation in the intensity of the illumination from the front light 106b and/or the backlight 312 may be timed with the capturing of images so as to obtain several different images of a sample under different illumination conditions.

Although a specific arrangement is shown in Figures 4A and 4B, it will be appreciated that other arrangements of the probe 300 are possible. For example the probe 400 may comprise a heater and/or a gas flow system as described in relation to Figures 2 and 3.

Figure 5 illustrates an example implementation of heating control of anti-fouling systems such as are described herein in a crystallisation process.

Inset 400 shows an anti-fouling system where an optical imaging immersion probe comprises a heater configured to heat the window through which optical images of a sample can be obtained. Inset 450 shows a different anti-fouling system, where a heater is instead configured to heat the bulk sample medium.

Inset 400a shows graphically the variation in the temperature of the window (AFL), the optimal temperature profile (OTP) for the crystallisation process, and the temperature of the bulk sample medium (TS) in a continuous crystallisation process using the system 400. When the anti-fouling system is activated in response to the presence of fouling, i.e. when the heater is activated to heat the window, the temperature of the window is increased in order to remove and/or prevent fouling on the window. The temperature of the window is controlled to remain above the temperature of the bulk sample medium to remove and/or prevent fouling on the window, while the temperature of the bulk sample medium remains substantially constant and in line with the optimal temperature profile.

Inset 450a shows graphically the variation in temperature of the bulk sample medium (S1 , S2) and the optimal temperature profile (OTP) in a continuous crystallisation process corresponding to that shown in inset 400a, using the system 450. To prevent fouling, the temperature of the bulk sample medium is periodically increased from S1 to S2, moving the temperature of the bulk sample medium away from the constant optimal temperature profile, which corresponds to the temperature S1.

Inset 400b shows graphically the variation in the temperature of the window (AFL), the optimal temperature profile (OTP) for the crystallisation process, and the temperature of the bulk sample medium (TS) in a batch crystallisation process using the system 400. The optimal temperature profile decreases with time to control the growth of crystals in the bulk sample medium. When the heating of the window is activated in response to the presence of fouling and/or once the temperature of the bulk sample medium passes below a certain threshold temperature, the temperature of the window is increased above the bulk sample medium temperature in order to remove and/or prevent fouling on the window. As can be seen, the temperature of the bulk sample medium remains substantially in line with the optimal temperature profile throughout the crystallisation process.

Inset 450b shows graphically the variation in temperature of the bulk sample medium (TS) and the optimal temperature profile in a batch crystallisation process corresponding to that shown in inset 400b, using the system 450. When the heating is switched on to prevent fouling, the temperature of the bulk sample medium is periodically increased above the optimal temperature profile of the process.

In certain examples a controller described herein may be configured to perform any of the methods, or particular steps of said methods. A controller described herein may refer to a single controller and/or processor or control may be distributed between multiple controllers and/or processors. The activities and apparatus outlined herein may be implemented using controllers and/or processors which may be provided by fixed logic such as assemblies of logic gates or programmable logic such as software and/or computer program instructions executed by a processor. Other kinds of programmable logic include programmable processors, programmable digital logic (e.g., a field programmable gate array (FPGA), an erasable programmable read only memory (EPROM), an electrically erasable programmable read only memory (EEPROM)), an application specific integrated circuit, ASIC, or any other kind of digital logic, software, code, electronic instructions, flash memory, optical disks, CD- ROMs, DVD ROMs, magnetic or optical cards, other types of machine-readable mediums suitable for storing electronic instructions, or any suitable combination thereof.

The above embodiments are to be understood as illustrative examples. Further embodiments are envisaged. It is 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 modifications not described above may also be employed without departing from the scope of the invention, which is defined in the accompanying claims.

Other variations and modifications of the apparatus will be apparent to persons of skill in the art in the context of the present disclosure.