Apparatus, system and method for measuring properties of a sample

Abstract

An apparatus (1) comprising an optical device (2) for monitoring bacterial growth of a dosed liquid biological sample. The apparatus is provided with a sample container port for receiving, in use, a sample container (6) having at least one detection chamber (20) for containing a dosed sample. The optical device (2) comprises a light source (22) configured to emit light along an incident beam axis which, in use, intersects at least one detection chamber (20) of the sample container (6) and illuminates a dosed sample contained in the detection chamber (20). The optical device (20) comprises a first photodetector (26) configured to receive light scattered by bacteria in the sample. The optical device (2) comprises a light collection arrangement (24) configured to collect light exiting the detection chamber (20) that has been positively scattered by bacteria in the sample at a scattering angle range of between about + / - 4 and + / - 20 degrees relative to the incident beam axis and direct the collected scattered light to the first photodetector (26); and prevent non-scattered light travelling parallel to the incident beam axis and exiting the detection chamber (20) from reaching the first photodetector (26). The optical device (2) comprises at least one processor configured to: measure an intensity of the scattered light received by the first photodetector (26); determine a respective representative quantity or concentration of bacteria in the sample from the intensity of the scattered light; repeat the measuring and determining steps at a series of predetermined intervals to determine changes in the representative quantity or concentration of bacteria in the sample over time; and determine a respective susceptibility of the bacteria in the sample to a respective drug.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to devices, apparatuses, systems and methods for measuring properties of a sample, in particular for measuring optical properties of a biological sample containing microorganism particles, such as bacteria. BACKGROUND

[0002] Many techniques are known for measuring properties of a sample, in particular for measuring optical properties of a biological sample, such as the concentration of particles within the sample. For example, absorption spectrophotometers measure the relative absorbance of a sample; scattering spectrophotometers, flow cytometers and nephelometers measure the light scattered by particles in a sample.

[0003] The practical application of such measurement techniques is in the processing and analysis of clinical samples, such as urine, blood, etc., in which cases it is desirable to determine the number and / or type of bacteria present in a given sample, in order to determine the most appropriate treatment regime for the patient / subject (e.g. the type and dosage of antibiotic that should be administered). For example, the measurement of the time-dependent bacterial concentration of a clinical sample that has been administered a particular drug or antibiotic allows the determination of the sensitivity of the bacteria to that drug (and hence the efficacy of that drug relative to the particular bacterial strain present in the sample).

[0004] Various systems using such techniques are known for these practical applications. For example, WO 2016 / 128747 incorporates the use of an integrating sphere light collector in which a (dosed) clinical sample to be analysed is placed. When the sample is illuminated, the bacteria present in the sample scatter some of the light; this scattered light is reflected and diffused by the reflective inner surface of the integrating sphere. WO 2019 / 166799 describes a similar system comprising a pair of optically connected chambers that use an integrating light collector to detect light scattered by the sample. WO 2018 / 091922 describes a combined cartridge in which a clinical sample can be initially incubated to increase the concentration of bacteria present in the sample; subsequently a plurality of separate sample portions are combined with various different drugs / antibiotics, and the optical properties of each individual sample portion are measured to determine the sensitivity of the bacteria to each drug.

[0005] It is against this background technology that the present devices / apparatuses, systems and methods have been conceived. SUMMARY

[0006] According to one aspect of the present disclosure, there is provided an optical apparatus / device for monitoring bacterial growth and / or determining the number or concentration of bacteria in a dosed liquid biological sample, the apparatus / device comprising: a light source configured to emit light along an incident beam axis, in use, intersecting a detection chamber of a sample container housing the dosed sample and illuminating the dosed sample housed within the detection chamber; a first photodetector configured to receive light scattered by particles in the sample; a light collection arrangement configured to: collect light exiting the detection chamber that has been forward scattered by particles in the sample within a scattering angle range of between about + / - 4 and + / - 20 degrees relative to the incident beam axis and direct the collected scattered light to the first photodetector, and prevent non-scattered light travelling parallel to the incident beam axis and exiting the detection chamber from reaching the first photodetector; and at least one processor configured to: measure the intensity of the scattered light received by the first photodetector, determine a respective representative amount or concentration of particles present in the sample based on the intensity of the scattered light, repeat the measuring and determining steps at a series of predetermined intervals to determine changes in the representative amount or concentration of particles present in the sample over time, and determine respective changes in the amount or concentration of particles in the sample. Preferably, the particles in the sample are bacteria and the changes in the representative amount or concentration of particles in the sample over time are indicative of the sensitivity of the bacteria in the sample to a drug / antibiotic. In some embodiments, the forward scattered light can be measured within a scattering angle range of between about + / - 5 and + / - 20 degrees relative to the incident beam axis.

[0007] Advantageously, the apparatus of the present disclosure is able to capture a large proportion (e.g. about 95%) of the forward scattered light produced by the interaction of the incident beam with particles in the sample, as this light is scattered primarily over a relatively small scattering angle (such as those described above). Thus, the apparatus of the present disclosure maximises the amount of scattered light intensity that can be collected from a single sample, which in turn means that a statistically significant result can be obtained using a relatively small sample volume, particularly in respect of changes in scattered light intensity over time.

[0008] In embodiments of this aspect of the disclosure, the amount or concentration of particles / bacteria is determined quantitatively. In other embodiments, it is suitable to determine the amount or concentration of particles / bacteria qualitatively, i.e. such that the relative amount or concentration is determined as a function of time: such qualitative measurements are suitable and can be preferred for simplifying data processing, as changes in the amount or concentration of particles / bacteria can often be reliably assessed relative to other time points and assays. In any embodiment of this aspect of the disclosure, the optical device is configured to receive a sample container comprising at least one detection chamber for containing a biological sample. The biological sample can potentially contain pathogenic bacteria.

[0009] In some embodiments, the first photodetector can also be used in combination with a lock-in amplifier to isolate the received signal having a specific frequency. The frequency to be isolated can correspond to the modulation frequency of the light emitted from the light source. This advantageously allows to filter out noise signals from other frequencies, thereby improving the signal-to-noise ratio of the obtained signal.

[0010] Suitably, the light collection arrangement is configured such that only the forward scattered light within an angular range of about + / - 4 and + / - 20 degrees relative to the incident beam axis is collected and directed towards the first photodetector. More specifically, the range of scattering angles of the collected scattered light is between +4 and +16 degrees and between -4 and -16 degrees relative to the incident beam axis, even more specifically between +5 and +16 degrees and between -5 and -16 degrees relative to the incident beam axis. Advantageously, given that the majority (about 95%) of the light scattered by interaction with particles in the sample is scattered only at a small range of angles relative to the incident beam axis, the above configuration maximizes the proportion of scattered light that can be collected by the first photodetector, while minimizing the amount of non-scattered light that is also collected.

[0011] In some embodiments, the light collection arrangement comprises: (1) a concave elliptical reflector configured to collect and reflect light within an angular range of between about + / - 4 and + / - 20 degrees relative to the incident light beam axis only towards the first photodetector, so that the light is received by the first photodetector; or (2) a concave elliptical reflector configured to collect and reflect forward scattered light within an angular range of between about + / - 4 degrees and + / - 20 degrees relative to the incident light beam axis towards a condenser arranged to receive the light reflected by the concave elliptical reflector and focus the received light onto the first photodetector. Such a configuration advantageously allows the use of only one main component (or even two cooperating components) to collect light within the desired scattering angular range, thereby minimising the number of components (which therefore need to be precisely positioned and aligned with each other) that need to be included in the light collection arrangement. Furthermore, the use of a single (appropriately shaped and sized) reflector is beneficial as it reduces the space required to house the light collection arrangement, which in turn can allow the size of the entire device itself to be reduced. It is also noted that the use of a concentrating element or condenser further increases the amount and proportion of scattered light that can be collected by the photodetector, potentially increasing the sensitivity of the entire device to detect smaller changes in the intensity of the scattered signal.

[0012] In some embodiments, wherein the light collection arrangement comprises a concave elliptical reflector shaped to reflect forward scattered light from the sample to the first photodetector or a condenser, and wherein the concave elliptical reflector comprises an aperture aligned with the incident light beam axis and configured to allow non-scattered light from the detection chamber to pass through the concave elliptical reflector. Such a configuration advantageously prevents non-scattered light from being inadvertently collected along with the scattered light, and helps to ensure that a representative measurement of the actual scattering is obtained (and therefore a more accurate, representative determination of the amount of particles present in the sample is obtained). This arrangement, particularly in combination with the range of scattering angles described above, enables a balance to be struck between capturing as much scattered light as possible, such that the amount of non-scattered light that is also captured is minimised, whilst maintaining a sufficient width of the light source beam to adequately illuminate the sample and produce a significant amount of scattering. Furthermore, the ability to maintain a constant alignment of the light source beam with the aperture is advantageous for optimal light collection. The non-scattered light can be directed to a beam dump or to a separate exit port.

[0013] In some embodiments, the optical apparatus further comprises a second photodetector arranged to receive non-scattered light; optionally wherein the second photodetector is positioned on an opposite side of the light collection arrangement to the sample and aligned with the incident light beam axis to receive non-scattered light. Advantageously, the second photodetector enables non-scattered (“baseline level”) light to be collected and processed, which in turn allows characteristics of that light to be determined. If noise obtained in scattered and non-scattered light is common or correlated (e.g. due to vibrations arising from motor operation within the apparatus), then these characteristics can be utilised during processing of the scattered light collected by the first photodetector to implement noise reduction techniques. Additionally or alternatively, the non-scattered light can also be analysed to assess light source stability and determine variations in the intensity of the incident light that can affect the scattered light signal.

[0014] In some embodiments, the light collection arrangement comprises first and second condenser lenses and a mirror, wherein: the first condenser lens is configured to direct scattered light to the second condenser lens and to focus non-scattered light travelling along the incident light beam axis onto the mirror; and the second condenser lens is configured to receive scattered light from the first condenser lens and to focus that scattered light onto the first photodetector. The mirror can be arranged along the incident light beam axis between the first and second condenser lenses and can be configured to reflect non-scattered light away from the first photodetector. This arrangement provides an alternative configuration that enables scattered and non-scattered light to be separated for respective processing and analysis, and can provide benefits relative to the previously described light collection arrangement comprising an elliptical reflector. For example, although more components are used in the two condenser lens arrangement, these components can be easier to manufacture or sourced more simply (e.g. COTS or commercial off-the-shelf components can be more readily available).

[0015] In some embodiments, the mirror is arranged to reflect non-scattered light towards a second photodetector configured to receive non-scattered light from the mirror. As described in relation to the configuration comprising an elliptical reflector, the ability to collect and process non-scattered light provides advantages in terms of processing respective scattered light signals and in particular in relation to noise characterisation and reduction.

[0016] Suitably, the apparatus can further comprise a sample container carousel arranged within the sample container port for engaging a sample container and configured to align a detection chamber of the sample container containing at least a portion of a biological sample with the incident light beam axis of the light source of the optical apparatus. Advantageously, the apparatus can be configured to engage with individual sample containers containing samples to be irradiated by using a sample container carousel that provides interfacing and engagement functionality between the apparatus and the sample container. This increases the ease with which one or more samples can be aligned with the optical apparatus for measurement purposes.

[0017] In some embodiments, the apparatus further comprises a motor operably coupled to the sample container carousel and configured to rotate the carousel to periodically align and misalign the detection chamber containing at least a portion of the biological sample with the incident beam axis of the light source. Automating the alignment of a particular sample portion with the incident beam advantageously streamlines the measurement process and improves the efficiency with which a plurality of different measurements of scattered light intensity can be obtained, as well as the repeatability of such measurements.

[0018] Suitably, for example, the sample container carousel can be configured to interface with a sample container comprising a plurality of detection chambers, and the sample container carousel can be configured to rotate to sequentially align and misalign each of the plurality of detection chambers of the sample container with the incident beam axis of the light source. Advantageously, the above-described configuration provides improvements relating to the parallelisation of the sample processing and analysis procedure: the use of a rotatable sample container carousel in combination with a sample container comprising a plurality of detection chambers means that a plurality of individual sample portions can be illuminated and the intensity of scattered light obtained over the course of one measurement cycle / run. This increases the number of samples that can be analysed within a given time period, which is particularly advantageous when used in the context of determining the susceptibility of bacteria in a sample to one or more different drugs (and / or concentrations of drug). This in turn means that the appropriate drug for treating a particular patient / subject can be determined quickly and efficiently, which is particularly useful when implementing the apparatus for point-of-care use.

[0019] In some embodiments, the sample container carousel comprises one or more openings configured to, in use, align with one or more detection chambers of the sample container when the sample container is correctly interfaced with the sample container carousel. The sample container carousel provides support and movement functionality for the sample container as a whole, with the openings provided advantageously ensuring that only the appropriate / selected portions of the sample container (e.g. those corresponding to the one or more detection chambers) are positioned / placed in alignment with the incident beam and illuminated as required.

[0020] In some embodiments, the sample container carousel comprises one or more detectable calibration features for determining the position and / or orientation of the sample container carousel relative to the incident beam axis of the light source. The above-described configuration advantageously allows a determination to be made as to when or when a given detection chamber is / will be in alignment with the incident beam, thereby ensuring that the appropriate portion or“window” of the measurement signal strength corresponding to the signal obtained from that particular detection chamber can be extracted, processed and analysed. This advantageously reduces the impact of any drift or inconsistency in the rotational speed of the motor (which can occur over the course of a measurement cycle), thereby improving the signal-to-noise ratio of the signals obtained.

[0021] Suitably, the device can further comprise a calibration feature reader, in use in communication with the processor of the device for determining a time interval between detection of the calibration feature by the calibration feature reader and the associated detection chamber coming into alignment with the incident beam axis of the light source. The calibration reader can be configured to detect the presence of the calibration feature (e.g. passing through the calibration reader itself) and to associate detection of the calibration feature with the position of the associated detection chamber of the sample container.

[0022] In some embodiments, the processor of the optical apparatus: (1) is in communication with the first photodetector, to measure the intensity of scattered light received by the first photodetector during a predetermined time window corresponding to a time period in which the detection chamber of the sample container is aligned with the incident beam axis of the light source; (2) adjusts the length of said predetermined interval based on detection of the or each calibration feature. Advantageously, this provides an alternative or additional mechanism for ensuring good correlation between the presence of the detection chamber in the path of the incident beam and the extraction or processing of the appropriate portion of the signal obtained for analysis.

[0023] In some embodiments, the processor of the optical apparatus is programmed to repeat the measurement step of measuring the intensity of scattered light received by the first photodetector and the determination step of determining the respective representative quantity or concentration of bacteria present in the sample over time periodically over a time period of between about 20 minutes and about 2 hours, between about 20 minutes and about 1.5 hours, between about 20 minutes and about 1 hour, or between about 30 minutes and about 1 hour. This enables the scattered light intensity to be monitored and analysed over a long period of time, so that changes in the measured intensity over this time period can be detected and assessed. For example, such changes can be used to determine changes in the number of particles in the sample, which are indicative of a related change in bacterial growth within the sample, and can be indicative of an increase (or lack of) sensitivity of the bacteria to the particular drug being tested.

[0024] In some embodiments, the device can comprise a temperature control system for controlling the temperature of the air inside the device. Suitably, the device can further comprise at least one heating element and optionally at least one air flow regulator arranged, in use, to bring warm air into contact with a sample container received within the sample container port of the optical apparatus, to maintain the biological sample within the detection chamber at a desired temperature. For example, to maintain the temperature between 36°C and 37°C, which is a favourable temperature with respect to the growth of bacteria within the sample under analysis; maintaining such a temperature during the measurement cycle optimises the conditions for bacterial growth during the measurement cycle.

[0025] In some embodiments comprising a pair of heating elements, each heating element is operatively associated with a fan in use to push warm air towards the sample container port to heat the sample within the detection chamber of a sample container received within the device port. Such a configuration is particularly beneficial or useful to ensure a uniform flow of heated air through the device and across the sample container in situ to maintain a desired temperature profile on the sample container.

[0026] In some embodiments, when used for a sample comprising urine of a patient or subject, the light source of the optical device is a laser light source, for example at a wavelength between 620 nm and 780 nm, or in a range of wavelengths corresponding to visible red light. However, other wavelengths of light can also be used, particularly when the sample corresponds to other biological fluids such as blood. It is also noted that the use of a laser light source such as a laser diode enables the frequency and amplitude of the emitted light to be relatively easily controlled and modulated as required; the phase of the modulation signal can also be controlled.

[0027] In some embodiments, the predetermined interval at a rotational speed of 100 rpm corresponds to approximately 0.6 seconds. This corresponds to a suitable measurement frequency at a suitable motor speed, although it will be appreciated that the measurement frequency and / or motor speed can be varied as required (for example, a faster rotational speed of around 200 rpm can also be used, which will exert a greater force on the fluid sample under consideration); furthermore, the processing of the obtained signal can involve the averaging of a plurality of individual measurement values, which is beneficial for noise reduction.

[0028] In some embodiments, the processor of the optical device is configured to identify a plurality of periodically occurring peak features in the measured light intensity, and to perform the measurement and determination steps only between adjacent peak features. This configuration advantageously ensures that the desired portion of the signal corresponding to the scattered light resulting from the interaction with the sample in the detection chamber is extracted from the obtained signal. It can also minimise the level of noise in the extracted signal, for example by avoiding the inclusion of light scattered by other parts of the device (for example, the sample container carousel or parts of the sample container that do not contain any sample) in the extracted signal. This improves the signal-to-noise ratio of the signal being processed.

[0029] According to another aspect of the present disclosure, there is provided a system for monitoring bacterial growth of a dosed liquid biological sample, the system comprising: a device / apparatus as defined above; and a sample container comprising a plurality of detection chambers, each detection chamber configured to contain a dosed liquid biological sample; wherein the system further comprises: a sample positioning mechanism configured to sequentially align each of the plurality of detection chambers with the incident beam axis such that the light source illuminates the dosed liquid biological sample contained within the illuminated detection chamber. As described above in relation to the device / apparatus, the ability to simultaneously process multiple different samples over the course of one measurement cycle has benefits relating to the parallelisation of sample processing, corresponding to an increase in the speed and efficiency with which useful results can be obtained, as well as a reduction in associated costs.

[0030] Suitably, the sample positioning mechanism can comprise a rotating or carousel mechanism configured to rotate the sample container so as to sequentially align each of the plurality of detection chambers with the incident beam axis.

[0031] In some embodiments, the system can further comprise a support structure arranged to support the optical apparatus. Providing such a support structure can advantageously allow the optical components to be uncoupled or isolated from the remainder of the system components, which for example reduces the impact of vibrations resulting from operation of the sample positioning mechanism / motor on the optical components and their alignment with one another during measurement. The support structure can comprise an opening configured to receive a portion of the sample container comprising at least one of the plurality of detection chambers, such that when the portion of the sample container is located within the opening, the at least one of the plurality of detection chambers is positionable along the incident beam axis between the light source and the light collector. Such a configuration advantageously ensures good / proper alignment of the sample container (and each detection chamber provided therein) with the incident beam. Furthermore, providing a suitably configured opening in the support structure can have benefits in terms of guiding the user to correctly interface the sample container with the sample port when inserting the sample container into the device.

[0032] Suitably, the system can further comprise a temperature control system configured to maintain the temperature of the liquid biological sample at a temperature of between approximately 35° and 37.5°. In some embodiments, the temperature control system comprises a heating arrangement comprising a heating element arranged to generate heat, and an air circulation system configured to distribute the generated heat evenly across the plurality of detection chambers of the sample container. In some embodiments, the circulation system comprises at least one recirculation duct and an associated fan arranged to drive an airflow through the heating element. As described above in relation to the device, this arrangement maintains a suitably desired temperature within the device and around the sample container, which is suitable to promote the growth of bacteria within the sample. This increases the concentration of bacteria in the sample, thereby increasing the corresponding intensity of scattered light that can be obtained from a given sample volume.

[0033] According to another aspect of the disclosure, there is provided a method for determining the susceptibility of bacteria in a sample to a drug, the method comprising: containing a dosed liquid biological sample in a detection chamber of a sample container; illuminating the sample in the detection chamber with light emitted by a light source along an incident beam axis through the detection chamber; collecting, by a light collector, light scattered by interaction with bacteria in the sample, the light being scattered along a forward scatter within a scatter angle range of + / - 4 and + / - 20 degrees relative to the incident beam axis; focusing, by the light collector, the collected scattered light onto a first photodetector; determining, by a processor, the intensity of the scattered light collected by the first photodetector and a corresponding extent of bacterial growth in the sample; repeating, by the processor, the determining step at a series of predetermined intervals; determining, by the processor, a change in the extent of bacterial growth in the sample over time; and determining, by the processor, the susceptibility of the bacteria in the sample to the drug used to dose the sample based on the determined change in the extent of bacterial growth in the sample over time. In some embodiments of the disclosure and any other aspect of the disclosure, the scattered light is detected within a scatter angle range of + / - 5 and + / - 20 degrees relative to the incident beam axis.

[0034] It will be appreciated that various features described above in relation to the apparatus and / or system are equally applicable to the above-described method.

[0035] For example, in some embodiments, the sample container comprises a plurality of detection chambers, at least two of the plurality of detection chambers containing samples dosed with different drugs, and the method comprises: sequentially positioning each of the plurality of detection chambers containing dosed samples in the light emitted along the incident beam axis; performing each subsequent step of the method for each of the plurality of detection chambers; and determining the relative susceptibility of the bacteria in the sample to the respective drug used to dose the sample to identify the most effective drug for a treatment regime.

[0036] In some embodiments, the sample container comprises a plurality of detection chambers, at least two of the plurality of detection chambers containing samples dosed with the same drug at different drug concentrations, and the method comprises: sequentially positioning each of the plurality of detection chambers containing dosed samples in the light emitted along the incident beam axis; performing each subsequent step of the method for each of the plurality of detection chambers; and determining the relative susceptibility of the bacteria in the sample to the respective concentration of the drug used to dose the sample to identify the most effective drug concentration for a treatment regime.

[0037] Suitably, the method can further comprise: collecting, by a second photodetector, non-scattered light passing through the or each detection chamber parallel to the incident beam axis; and comparing the intensity of the non-scattered light collected by the second photodetector with the intensity of the scattered light collected by the first photodetector for the same detection chamber.

[0038] It is expressly intended that aspects, embodiments, examples and alternatives described in the preceding paragraphs, in the claims, and / or in the following description and drawings, and / or combinations of any of them, can be implemented independently of one another or in any combination. That is, any embodiment or feature can be used in any combination with any other embodiment or feature, unless the features are incompatible. The applicant reserves the right to change any originally filed claim, or a corresponding claim in an application designating this nonprovisional application, based on any subsequent claim, allowing the applicant to pursue the filing date of this nonprovisional application while pursuing claims directed to encompassing, and / or invented, subject matter as set forth in any originally filed claims or drawings, or to reserve the right of applicants to, support any amendments made during the prosecution of the application or claims designating this nonprovisional application, including a reservation of the right to continue pursue claims in a divisional application or continuation application filed after the filing date of this nonprovisional application. BRIEF DESCRIPTION OF DRAWINGS

[0039] The above and other aspects of the present disclosure will now be described, by way of example only, with reference to the attached drawings in which:

[0040] Figure 1A and Figure 1B show a front perspective view and a rear perspective view, respectively, of an apparatus for determining the susceptibility of bacteria in a clinical sample to various drugs according to an embodiment of the present disclosure;

[0041] Figure 2 shows a vertical cross-sectional view of the apparatus of Figure 1 ;

[0042] Figure 3A and Figure 3B are perspective views of parts of the apparatus of Figure 1, and Figure 3C illustrates Figure 3A and Figure 3B the internal airflow and temperature gradients of the parts of the apparatus shown;

[0043] Figure 4 is a schematic diagram of an optical arrangement used in the apparatus of Figure 1 according to an embodiment of the present disclosure;

[0044] Figure 5 is a schematic diagram of an alternative optical arrangement that can be used in the apparatus of Figure 1 according to another embodiment of the present disclosure;

[0045] Figure 6 is a schematic diagram of an alternative optical arrangement that can be used in the apparatus of Figure 1 according to another embodiment of the present disclosure;

[0046] Figure 7 is a flowchart illustrating the various steps of a method of determining the drug susceptibility of bacteria in a clinical sample using the apparatus of Figure 1.

[0047] Figure 8 shows different plots of detector intensity output over time in the apparatus of Figure 1, illustrating the effect of different drugs on bacteria in a clinical sample;

[0048] Figure 9A and Figure 9B is an elevational view of a sample container usable in the apparatus of Figure 1 to analyse a clinical sample; and Figure 9C shows an exploded view of another sample container usable in the apparatus of Figure 1 ;

[0049] Figure 10 is a plan view of the sample container of Figure 9, and Figures 10A to 10E illustrates Figure 11 different parts of the fluidic structure of the container of

[0050] Figure 11 shows a plot of measured detection intensity over time when the sample container of Figure 10 is used in the apparatus of Figure 1 ;

[0051] Figure 12A is a bottom perspective view of a sample carousel usable in the apparatus of Figure 1, interfacing with the sample container of Figure 9, and Figure 12B is a perspective view of a controller used in the sample carousel of Figure 12A ;

[0052] Figure 13 illustrates different plots of detector intensity output over time in the apparatus of Figure 1, showing the signal-to-noise ratio achievable in the apparatus of Figure 1 ; and

[0053] Figure 14 is a plan view of an alternative design of sample container, which can also be used in the apparatus of Figure 1 to analyse a clinical sample.

[0054] In the drawings, like features are denoted by like reference numerals. DETAILED DESCRIPTION

[0055] Specific examples and embodiments of the present disclosure will now be described, in which many features will be discussed in detail in order to provide a thorough understanding of the concepts defined in the claims. However, it will be apparent to those skilled in the art that the present disclosure can be implemented without all the specific details, and in some cases, in order to avoid unnecessarily obscuring the present disclosure, well-known methods, techniques and structures have not been described in detail.

[0056] Figure 1 shows front (see Figure 1A ) and rear perspective views (see Figure 1B), according to embodiments of the present disclosure, the device 1 can be used to provide a portable, standalone, and integrated module that can be used for point-of-care testing. In this case, the device can be used to test a clinical sample (e.g., urine, blood, etc.) from a patient or subject to determine the susceptibility of bacteria in the sample to different types and concentrations of drugs. As described below, the device 1 is capable of quickly (i.e., within about an hour) determining and implementing a particularly effective drug and treatment regimen, thereby providing a patient with an effective infection treatment regimen much more quickly than detection and diagnostic devices that rely on existing technologies.

[0057] Referring at least to FIG. 1 and Figure 2 The device detects and measures the amount or intensity of light scattered by particles (particularly bacteria) in a clinical sample over time, thereby enabling a corresponding determination of a representative amount or concentration of bacteria in the sample over time. The device 1 includes an optical apparatus or arrangement 2, as well as a sample positioning mechanism 4. These two components are configured to interact with a removable sample container 6 that houses a clinical sample being analyzed, so as to enable the aforementioned determination of a representative amount or concentration of bacteria.

[0058] In particular, the sample positioning mechanism 4 is configured to engage and support the sample container 6 in a manner such that at least a portion of the sample container 6 is optically coupled or connected with components of the optical apparatus 2. In more detail, the sample positioning mechanism 4 includes a sample turntable or sample carrier 8, as well as an operably coupled motor 10, such as a BLDC (brushless DC) motor or other similar drive mechanism, which controls movement of the sample turntable 8 (and thereby the engaged sample container 6). In use, when the sample container 6 and the optical apparatus 2 are optically coupled, the optical apparatus 2 is configured to illuminate a portion of the clinical sample housed within the sample container 6. The optical apparatus 2 is also configured to detect and measure light scattered by bacterial particles in the illuminated portion of the clinical sample. The detected scattered light intensity can then be analyzed to determine properties of the bacteria in the sample, particularly a relative amount or concentration of bacteria in the sample over time.

[0059] The device 1 includes a housing or casing 12 that houses the other components of the system 2. In the illustrated embodiment, the casing 12 includes a base 12a on which the other device components are mounted; a front body portion 12b and a rear body portion 12c that provide walls of the casing 12; and a moveable / detachable lid 12d. In the illustrated embodiment, the lid 12d is hingedly attached to the rear body portion 12c, although other attachment mechanisms could of course be used. The lid 12d, together with the body portions 12b, 12c and the base 12a, forms an enclosure that houses the various device components when the device 1 is in use. However, it will be appreciated that the various portions of the casing 12 could instead be provided as more or fewer portions than those illustrated herein. The device 1 also includes a closure / fastening mechanism 13 for retaining the lid 12d in a closed, locked position, for example after the sample container 6 has been inserted into the desired position within the device 1 and engaged with the sample carousel 8. The closure mechanism 13 includes an actuator 13a (shown in more detail in Figure 2 ) located within the device casing 12 that is programmably actuated in the event that the lid 12d is to be opened.

[0060] The device 1 also includes a temperature control module or arrangement 14 (highlighted in Figure 3A ) that is configured to maintain the temperature within the casing 12 (and in particular the region surrounding the sample container 6) within a preferred temperature range (e.g. about 36 to 38°, more particularly about 36 to 37°). This temperature range is particularly desirable to promote and maintain the growth of bacteria in a clinical sample under optimal growth conditions. In addition, the illustrated device also includes a user interface 15, such as an interactive touch screen display, through which a user of the device 1 can interact with and program various aspects of the device 1; view certain results; and / or monitor the progress of the analysis process. For example, patient or subject details can be input by the user; measurement parameters can be displayed and altered using the interface; software updates for the device 1 can also be downloaded via the user’s interaction with the user interface 15; measurement progress and various intermediate and final results can also be displayed to the user via the user interface 15. In addition, the user interface 15 can be used to provide instructions to the user to guide them through the various steps in the process of loading a sample into the sample container 6 and subsequently engaging the sample container 6 with the sample carousel 8 correctly.

[0061] Finally, the device 1 comprises one or more processors or processing units 16, which provide programmable control over various device components (e.g., the optical apparatus 2, the sample positioning mechanism 4, the lid closure mechanism 13, and / or the user interface 15). In some embodiments, it will be appreciated that control of specific functions and components of the device can be divided / distributed to specific one or more of these processing units 16. In these embodiments, control of certain functions that require real-time monitoring and have associated safety implications (e.g., related to the optical apparatus 2 and the temperature control arrangement 14) can be controlled by one processing unit 16; while control of certain functions related to user interaction and connectivity (e.g., the user interface 15) can be controlled by a separate processing unit 16. Moreover, in some cases, the device 1 can be provided with side vents / openings (not shown), which can increase airflow and facilitate cooling of the processing units 16, to prevent undesired temperature increases within the device 1.

[0062] As mentioned above, the sample container 6 corresponds to a separate component that can be inserted into the device 1 in order to enable performance of the required measurements and tests. Generally, the sample container 6 can be provided as and / or effectively serve as a disposable component (i.e., usable for testing one clinical sample). Accordingly, such components are also referred to in the art as “consumables”. Further details regarding suitable and advantageous configurations of this consumable sample container 6 will be provided later with reference to Figs. 9 to Figure 11 Further details regarding suitable and advantageous configurations of this consumable sample container 6 will be provided later with reference to Figs. 9 to

[0063] Reference will now be made to Figure 2 and Fig. 3 to provide further details regarding the configuration of various components of the device 1 and the interaction between these components.

[0064] In particular, as can be seen in these figures, the motor 10 is mounted to and supported by the base 12a of the housing 12; the motor 10 also effectively forms a support base on which many of the remaining components of the device 1 are mounted or attached. The sample carousel 8 is substantially circular in shape and is mounted above and connected to the motor 10 by a rotatable shaft 17, which extends along a vertical extension axis “X” that passes through the center of the sample carousel 8. Accordingly, rotational movement of the sample carousel 8 about the central axis “X” can be driven by the motor 10.

[0065] The sample carousel 8 comprises a plurality of openings 18 that are disposed in radial intervals around the sample carousel 8. According to the illustrated embodiment, the openings 18 are positioned radially around the outer periphery of the sample carousel 8 (these openings are not visible in Figs. 1 and 2, but are visible in Figs. 3 and 4). According to the illustrated embodiment, the openings 18 are arranged in a circular pattern around the sample carousel 8.Figure 12A is shown in more detail). The sample container 6 preferably comprises a respective plurality of detection chambers 20 (Fig. 9 and Figure 10 is shown in more detail), which are arranged at the same radial intervals around the sample container 6 and each of which is configured to contain a portion of a clinical sample to be analysed. The openings 18 in the sample carousel 8 are arranged such that, when the sample container 6 is correctly interfaced and / or engaged with the sample carousel 8, the position of each of the plurality of openings 18 aligns with and corresponds to the position of one of the plurality of detection chambers 20 provided within the sample container 6. The detection chambers 20 can thus be located at any suitable location of the sample container 6, for example in its outer region. As will be understood by the skilled person, the alignment between each opening 18 and the corresponding detection chamber 20 should be suitable to allow light from a light source (as described below) to pass through the opening 18 into the corresponding detection chamber 20. Reference is made to Figure 12A This interfacing between the sample container 6 and the sample carousel 8 is described in more detail.

[0066] The optical apparatus 2 comprises a light source 22 and collimating optics (not shown); a light collector or light collection arrangement 24; and at least one photodetector 26. The light source 22 emits light along an incident beam axis "Y" and illuminates one or more sample portions present in one or more detection chambers 20 of the sample container 6. The light collector 24 collects light forward scattered by bacterial particles within the sample. Advantageously, the light collector 24 collects light scattered at an angle of between about + / - 24 degrees, about + / - 20 degrees or about + / - 16 degrees from the incident beam axis Y, more particularly, collects light scattered between +3 degrees and +24 degrees and -3 degrees and -24 degrees; +4 degrees and +20 degrees and -4 degrees and -20 degrees; +5 degrees and +16 degrees and -5 degrees and -16 degrees on either side of the incident beam axis Y (e.g. in a ring around a particular radius of the beam). More particularly, the collected light can be scattered between +4 degrees and +16 degrees and -4 degrees and -16 degrees on either side of the incident beam axis Y. It will be appreciated that minor differences due to the curvature of the light collector 24 can mean that light is collected over slightly different angular ranges on either side of the incident beam axis Y (e.g. between about 3 degrees and 16 degrees on one side and between about 4 degrees and 16 degrees on the other side). The skilled person will of course appreciate that it is also possible to collect light scattered over smaller angles (i.e. less than + / - 3 or 4 degrees on either side of the incident beam axis); however, this will increase the proportion of non-scattered incident light collected by the light collector 24. The width of the incident beam can be reduced to allow for the collection of light scattered at smaller angles without including too large a proportion of non-scattered light; however, this in turn will result in less of the sample being illuminated, thereby reducing the amount of scattered light produced. A balance therefore needs to be struck in this regard, which will be discussed in more detail later. The collected scattered light is directed by the light collector 24 to the photodetector 26, where, for example, the intensity of the collected scattered light is analysed to determine the relative amount or concentration of bacteria in the sample in the detection chamber at a given point in time as a function of the amount of scattered light detected. The various components of the optical apparatus 2 are mounted to a support plate or structure 28 to form an optical "tower" which, in the illustrated embodiment, extends substantially vertically upwards from and is supported by the motor 10 or its housing 10a. However, it will be appreciated that the mounting of the optical "tower" 28 can be independent of and detachable from the motor 10 and its housing 10a so as to isolate the optical apparatus 2 from any vibrations that can be generated by the motor 10. In either case, the optical tower 28 structure is also therefore substantially perpendicular to the plane in which the sample turntable 8 and sample container 6 rest when in use. The incident beam axis "Y" of the light emitted from the light source 22 is therefore parallel to the rotational axis "X" of the sample turntable 8 but is laterally offset by a distance "d".

[0067] The lateral offset "d" between the rotational axis X and the incident beam axis Y corresponds substantially to the radial distance of (the centre of) the detection chamber 20 from the centre of the sample container 6, and also to the radial distance between the centre of the sample carousel 8 and the area of the opening 18 provided within the platform. A gap or cut-out 30 is provided in the support structure 28 for the optical apparatus 2, which is located (somewhere in the vertical plane) between the light source 22 and the light collection arrangement 24 and in the plane of the sample carousel 8; the cut-out 30 is sized and positioned to receive the radially outer portion of the sample carousel 8 within it. Thus, this received portion of the sample carousel 8 (and hence, the corresponding portion of the sample container 6 when the sample container 6 is engaged with the sample carousel 8) can extend into and through the support structure 28 and optical tower, so as to intersect the incident beam axis Y of the light emitted from the light source 22. In fact, the sample carousel 8, support structure 28, optical apparatus 2 and sample container 6 are designed and adapted so that, in use, the light emitted by the light source 22 passes through one of the openings 18 of the sample carousel 8, and subsequently into the corresponding detection chamber 20, so as to enable the portion of sample contained within that detection chamber 20 to be illuminated and analysed.

[0068] As a result, each detection chamber 20 of the sample container 6 can be positioned in turn on the incident beam axis "Y" by the light path from the light source 22 by rotation of the motor 10 of the sample container 6 when the sample container 6 is engaged with the sample carousel 8. Thus, the scattered light from the bacterial particles in the portion of sample contained in each detection chamber 20 can be collected and measured in turn by the optical apparatus 2. In some embodiments, the "measurement" is a quantitative assessment of the amount of light intensity scattered by the bacteria in the sample; whereas in other embodiments, a qualitative assessment of the relative amount of scattering caused by the sample in different sample chambers can be performed.

[0069] In the depicted embodiment, the optical apparatus support structure 28 comprises an upper (overhanging) cover portion 32 which covers some of the components of the optical apparatus 2 (e.g. the light collection arrangement 24 and photodetector 26) and can also provide some support functionality for these components. The upper cover 32 also provides the additional useful function of preventing unscattered light travelling along the substantially vertical incident beam axis "Y" from leaving the device 1, or accidentally reaching a user of the device 1 (e.g. in the case that the lid 12d of the housing 12 is removed while the light source 22 is emitting light). Reference will be made to the upper cover 32 later in this description. Figures 4 to 7 Further details are provided in relation to various configurations of the optical apparatus 2.

[0070] Turning now to the temperature control module 14, as Figure 2 , Figure 3A , Figure 3B and Figure 3CAs shown, this part of the apparatus 1 is also mounted over and supported by the motor 10 and its housing 10a, and includes at least one heating element 34 and a circulation arrangement 36. Each heating element 34, e.g. a heating coil or arrangement of heating coils, can be located within a respective compartment or chamber 38 located below the sample turntable 8. In the illustrated embodiment, a pair of heating elements 34 are provided (see Figure 3A ), located in a plane below the sample turntable 8 and above the motor 10: each of the pair of heating elements 34 is located on a respective side of the optical equipment support structure 28. The skilled person will appreciate that each heating element 34, in use, heats the air in its vicinity; this heated air rises towards the underside of the sample turntable 8 and its associated sample containers 6. The circulation arrangement 36 then causes the air to be more widely circulated through the apparatus housing 12, thereby maintaining a substantially constant flow of heated air past and around the sample containers 6; as a result, the temperature of the contents of the sample containers 6 is maintained within a desired (optimal) temperature range to facilitate rapid growth and proliferation of bacteria. In the illustrated embodiment, the circulation arrangement 36 comprises a pair of recirculation ducts 40 having air inlets 40a located above the sample containers 6 and air outlets 40b located below the sample turntable 8. In this way, the temperature of the air inside the apparatus can be quickly adjusted as required. The circulation arrangement 36 also comprises one or more associated fans 42 or other mechanisms to drive an airflow around the circulation arrangement 36. In particular, in the illustrated embodiment, each heating element 34 has an associated fan 42 to drive the air heated by that heating element to be circulated through the circulation arrangement 36.

[0071] Figure 3C The movement of air achieved by the temperature control module 14 is explained in more detail. Each heating element-fan pair is located at the bottom of its respective recirculation duct 40. The fan 42 drives a constant flow of air through / over the associated heating element 34; this heated air is then driven from the respective outlet 40b of the recirculation duct 40 into the antechamber or intermediate compartment 43 below the sample turntable 8. The heated air then rises upwards through the apparatus, flowing over and around the sample containers 6, cooling in the process. The relatively cooler air then enters the air inlet 40a of the recirculation duct 40 to replace the air expelled by the fan 42 and flows back down to the heating element-fan pair. Since the recirculation ducts 40 are located on either side of the optical equipment 2, the material used to manufacture these ducts 40 is suitably moulded and configured to prevent the heated air from causing the optical equipment components to overheat. This helps to prevent any unwanted warping or malfunction of these components, or any erroneous measurements made as a result of overheating.

[0072] It will be appreciated that, although Figure 3A , Figure 3B and Figure 3CThe device shown in the middle has a pair of heating elements, each comprising a plurality of heating coils, although one or more heating elements can be suitable depending on preference and design. Moreover, although a plurality of heating coils can be advantageous in providing rapid heating of air within the chamber in this embodiment of the application, a single heating coil can also be used, and optionally many other forms and configurations of one or more heaters can be used by the skilled person and can be selected depending on preference. Similarly, although the device is described as having a pair of fans (one assigned to each heating element) to push the hot air around the inner cavity of the device, in embodiments the fans are not necessary, for example air flow caused by rotation of the sample container 6 and sample carousel 8 can be able to generate movement of the heated air towards and around the sample container 6.

[0073] It has been demonstrated that providing an effective mirror arrangement of pairs of heating elements 34 and fans 42 (each pair having its respective recirculation duct 40) on either side of the sample carousel 8 is particularly useful for maintaining good heating balance within the device 1. It also compensates for any heating asymmetry that can arise due to the sample containers 6 continuing to rotate in a particular direction. Moreover, heating the sample containers 6 in this "bottom-up" manner (i.e. air is heated and rapidly rises through the sample containers 6) enables the sample portions contained in their respective detection chambers to be heated more quickly and easily without wasting excessive amounts of heat (and heating time) on the material of the sample containers 6 themselves. Thus, where the sample containers 6 comprise a plurality of samples, each located in a different detection chamber 20 around the periphery of the sample container 6, heating of the samples within each detection chamber 20 is advantageously uniform. In some cases, a desired uniform temperature of the samples in the sample containers 6 can be maintained with the aid of a temperature measuring device (such as an infrared or infrared thermometer) located within the device 1 (for example above or adjacent to the sample containers 6).

[0074] Figure 4Details of an example arrangement of optical components in the optical apparatus 2 are shown. In this arrangement, the light source 22 corresponds to a laser module having a laser diode, which is used to generate light of a specific wavelength (e.g. visible red light in the wavelength range between 620 nm and 780 nm, more specifically, visible red light of about 635 nm) for illuminating a sample portion contained in the detection chamber 20. Note that the above-mentioned wavelengths have been envisaged for the analysis of urine samples; however, the wavelength of the light used can be different depending on the nature of the sample to be analysed. For example, near-infrared wavelengths (between about 650 nm and about 1350 nm) can be used for blood samples. The laser diode is connected to a signal generator (not shown), which is adapted to control the modulation frequency and amplitude of the laser output. The photodetector 26 corresponds to a photodiode connected to a lock-in amplifier (also not shown); the lock-in amplifier, in turn, is connected to the signal generator for the laser diode. This enables the photodiode to isolate and filter out specific received signals having a frequency corresponding to the modulation frequency generated by the signal generator for the laser diode. This allows noise signals of other frequencies (e.g. background noise, electrical noise) to be filtered out, thereby improving the signal-to-noise ratio obtained using the optical apparatus 2. These components can be controlled by one or more of the processors 16 of the system, which can for example take the form of one or more printed circuit boards (PCBs) or other types of microcontrollers.

[0075] In this example, the light collector 24 comprises a reflector or reflective surface, which in the illustrated embodiment is mounted to the support structure 28 so as to extend across the incident beam path. In particular, Figure 4 The light collector 24 in the illustrated embodiment corresponds to a curved, concave elliptical mirror 44 having an off-centre hole, aperture or opening 46 provided therein. The mirror 44 is mounted to the support structure 28 so that the hole 46 is aligned with the incident beam axis "Y", thereby allowing non-scattered light exiting the detection chamber 20 and travelling along the beam axis Y to pass directly through the mirror 44 substantially undeflected; this non-scattered light is thus prevented from reaching the photodetector 26. In addition, the mirror 44 is arranged at an angle and size such that light positively scattered by particles in the sample (in particular, light scattered within an angular range of about +4 and +16 degrees, and about -4 and -16 degrees, of the incident beam axis Y) is reflected by the mirror 44 and towards the photodetector 26. In some other embodiments, the light reflected by the mirror 44 towards the photodetector 26 can be within an angular range of about +5 and +16 degrees, and about -5 and -16 degrees, of the incident beam axis Y.

[0076] Those skilled in the art will appreciate that there is an interplay between the size of the light collector (mirror) aperture 46, the width of the light beam from the light source 22, and the width (diameter) of each detection chamber 20 of the sample container 6 through which the light beam passes when considering the sensitivity of scattered light detection. A balance needs to be struck between these values to optimise the sensitivity of scattered light detection. Increasing the width of the light beam from the light source 22 increases the number of (bacterial) particles in the sample that are illuminated by the light beam; thus, this increases the amount of scattered light produced in any given scattering event that can be detected. However, increasing the overall width of the light beam that illuminates the sample within the detection chamber 20 for the amount of time that the measurement of scattered light emanating from the detection chamber 20 is performed, provides a longer ‘clean’ measurement path / area of the light beam through the sample (away from the walls of the detection chamber 20 that can cause internal scattering that can reduce the accuracy of performing detection of scattered light from the sample). Thus, while increasing the width of the light beam increases the detection sensitivity, the width of the light beam should still be kept less than the width / diameter of the detection chamber 20 to balance these two factors. Furthermore, it will also be appreciated that configuring the system such that the diameter of the aperture 46 in the light collector (mirror) is as close as possible to the width of the light beam will enable as much scattered light as possible to be collected and directed towards the photodetector 26, whilst minimising the amount of non-scattered light that is collected. However, if the width of the light beam is too close to the diameter of the aperture 46, then slight deviations in the path that the light beam travels in during the measurement (e.g. due to vibration of the components or machining tolerances) can adversely affect the alignment of the light beam with the aperture 46; thus, this will have a corresponding negative impact on the detection sensitivity.

[0077] In one particular embodiment, it is envisaged that the detection chamber 20 has a diameter of approximately 4mm, in which case a light beam width of approximately 1mm to 3mm (in particular 1.5mm to 2.4mm) will provide a good balance between the number of illuminated bacterial particles and the length of the ‘clean’ measurement path within the detection chamber 20. In such an embodiment, a light beam width of approximately 1.5mm would be suitable to use, for example, in the case where the width of the aperture 46 is selected to be approximately 3mm, as this also leaves sufficient margin between the aperture width and the light beam width to account for machining tolerances and / or system vibration. However, in the case where the aperture 46 is increased (e.g. to a diameter of 4mm to match the diameter of the detection chamber 20), the light beam width used can also be increased accordingly (e.g. between 2mm and 2.4mm).

[0078] In the arrangement of the illustrated embodiment, a concave elliptical reflector 44 reflects the positively scattered light at a defined angle, away from the incident beam axis Y (and at approximately 90 degrees relative to the incident beam axis Y), to focus it onto the photodetector 26. One or more system processors 16 are associated with the photodetector 26 and process the detection signal generated by the photodetector 26 to calculate the intensity of the detected scattered light. A graph or plot of the detector output (which corresponds to the measured intensity of the scattered light over time) can be generated; an example of such a graph is shown below. Figure 8 As shown. The chart and / or the data used to generate the chart can be displayed to the user via user interface 15 at regular intervals, for example, as a basic real-time indication of progress; or as a final (summary) output once the analysis process for a given sample is completed.

[0079] like Figure 4 As shown, the system of this embodiment also includes a second photodetector 48 aligned with the incident beam axis "Y" but located on the side of the light collector 24 opposite to the sample, and arranged to detect and measure unscattered light passing through the aperture 46 in the mirror 44. This second photodetector 48 also corresponds to a photodiode, configured substantially the same as the first (main) photodetector 28, i.e., the second photodetector 48 is connected to the signal generator of the light source 22 via a lock-in amplifier to ensure that the second photodetector 48 (and / or one of the processors 16 associated with the photodetector 48) is also capable of filtering out the desired laser signal frequency (and phase) from any noise signals different from the laser's frequency. Providing this additional second photodetector 48 allows for baseline measurements of the unscattered laser. This baseline measurement can be compared with the scattered light intensity measured using the first (main) photodetector 26, which allows, for example, the detection of anomalies in the illumination; it also allows for the evaluation and consideration of laser stability during analysis. It should be understood that in any embodiment of this disclosure, the second photodetector 48 may be omitted. In some such embodiments, a beam collector or other device may be used to collect the unscattered light from the laser.

[0080] In some cases, the reflector 44 is manufactured using a custom molding process to ensure appropriate dimensions, shape, and reflective properties. In such a process, the reflective surface of the reflector 44 can be formed, for example, by coating the reflector surface with aluminum or reinforced aluminum (vapor phase). In some optional cases, the reflectivity of the reflector (around 650 nm) should be greater than 90% (e.g., at least 95% or 98%), and the surface roughness of the reflector should be less than [specified value]. (For example, less than) Less than or even smaller ).Although Figure 4The illustrated optical arrangement is particularly advantageous in reducing the number of components required to perform the present disclosure, but other optical arrangements are possible. For example, Figure 4 The custom concave elliptical mirror 44 in FIG. 4A can be replaced with a pair of reflective elements, e.g., a first mirror deflecting the forward scattered light onto a focusing lens or a second concave mirror focusing the reflected light from the first mirror onto the photodetector 26. Additionally or alternatively, one or more additional light focusing components can be incorporated into the optical apparatus arrangement 2 in relation to or associated with the photodetector 26. For example, one or more light focusing components (e.g., focusing lenses) can be arranged to form a "light focusing cone" around the photodetector 26 to maximize the amount of scattered light collected by the photodetector 26.

[0081] Figure 5 Another optical apparatus arrangement 2' is shown in FIG. 4B, in which an off-the-shelf concave mirror 44' can be used instead of a custom shaped mirror 44' (but the reflectivity and surface roughness properties should be comparable). In this case, the curvature of the mirror 44' can not necessarily be configured to focus all (or at least substantially most) of the forward scattered light from the sample interaction onto the photodetector 26. In this case, an additional light focusing component 50 (e.g., a Fresnel lens or other focusing lens) can be introduced in the optical arrangement in the optical path between the mirror 44' and the photodetector 26 to ensure as much of the forward scattered light reflected by the mirror 44' as possible is captured and focused onto the photodetector 26. This maximizes the total amount of scattered light that can be obtained using the optical apparatus 2', which in turn increases the sensitivity of the overall apparatus to detect smaller changes in the relative number or concentration of bacteria in the sample over time. In other embodiments, as mentioned above, the lens 50 can be replaced with a second mirror configured to reflect light onto the photodetector 26. In addition to (or as an alternative to) the light focusing component 50 described above, one or more additional light focusing components described above in relation to the optical apparatus arrangement 2 of FIG. 4A can also be incorporated into the optical apparatus 2'. Figure 4

[0082] Figure 6 ​A further alternative optical arrangement 2" is shown, which also collects scattered and non-scattered light separately - the beam paths of these two types of light are shown. In this alternative arrangement, the light collector 24 comprises a pair of condenser lenses 52a, 52b, which are separated by a distance "a" (which is greater than the focal length of the first lens 52a) and are oriented so that the convex surfaces of the lenses face each other along the incident beam axis Y. In this configuration, any diverging beam of light that is incident on the first condenser lens 52a will be collimated into a parallel beam, which is also parallel to the incident beam axis Y. Subsequently such a parallel beam, when incident on the second condenser lens 52b, will converge towards a point at a further distance along the incident beam axis Y. However, any parallel beam that passes through the centre of the first condenser lens 52a (or within a region corresponding to light scattered at a maximum predetermined angle of, for example, 5° from 0°) will instead be converged to a point at the focal length of that lens 52a. In the arrangement 2" shown, the light collector 24 also comprises a mirror 54, which is located at a position corresponding to the focal length of the first condenser lens 52a, and which is sized and oriented to reflect only light incident on the first lens at an angle of no more than the maximum predetermined angle described above. Thus, light that has passed through the sample substantially without scattering will impinge on the surface of the mirror before reaching the second condenser lens 52b, and will be deflected away from the second lens 52b. In the depicted embodiment, the mirror 54 is angled (substantially 45 degrees) relative to the incident beam axis Y (although other angles can at least be selected), so that any beam of light incident on the mirror 54 is reflected at approximately 90 degrees relative to the incident beam axis Y and directed out of the main incident beam path; thus, this beam does not reach the second condenser lens 52b.

[0083] As with the optical arrangements 2, 2' shown in Figure 4 and Figure 5 , Figure 6 The laser diode light source 22 in the current arrangement 2" emits light along the incident beam axis Y, which illuminates a sample in the detection chamber 20 of the sample container 6; bacteria in the sample scatter the incident beam in the forward direction and over a relatively small angular range. Furthermore, as with the optical arrangements of Figure 4 and Figure 5 , in the optical arrangement 2" of Figure 6 two photodetectors are provided: a first "off-axis" photodetector 26' is positioned at an angular offset (of approximately 90 degrees) relative to the incident beam axis Y; a second "on-axis" photodetector 48' is positioned in alignment with the incident beam axis Y. However, in the arrangement 2" of Figure 6In the optical arrangement of the prior art, non-scattered light passing through and out of the detection chamber 20 with a parallel light beam is focused by a first condenser lens 52a onto a mirror 54 and then onto an off-axis photodetector 26' which is offset. Forward scattered light beams resulting from the interaction of the incident light with the bacteria in the sample are focused by a pair of collimating lenses 52a, 52b onto an on-axis photodetector 48'. This is in stark contrast to the arrangement of the prior art in which Figure 4 and Figure 5 In the arrangement of the prior art, the on-axis (main) photodetector 48 detects the non-scattered baseline laser light, while the off-axis photodetector 26 detects the scattered light. Figure 4 and Figure 5 In the arrangement of the prior art, the on-axis (main) photodetector 48 detects the non-scattered baseline laser light, while the off-axis photodetector 26 detects the scattered light.

[0084] By using one of the above optical apparatus arrangements 2, 2', 2", the device 1 is able to optimise / maximise the collection of light scatter which is useful in assessing the properties and / or quantity of bacteria in a sample. This is because the applicants have recognised that the majority (about 95%) of the light scattered due to such bacterial interaction is scattered at a relatively small range of angles either side of the incident light beam axis Y, for example between + / - 20 degrees from the incident light beam axis Y (more particularly between about 4 or 5 degrees to 16 degrees on either side of the incident light beam axis Y). Thus instead of needing an integrating sphere light collector or other form of light collector which makes use of multiple reflections and / or diffusion of the scattered light to increase the collection intensity (in some cases including backscattered light), a simplified light collection arrangement can be used which is configured to collect light scattered over those identified angular ranges which are most relevant to assessing / measuring particles in a sample and direct / concentrate the collected light onto a photodetector.

[0085] A method of using the above device 1 will now be described with reference to Figure 7

[0086] First, in step 105, the user places the clinical sample safely in the sample container 6 and then in step 110, the sample container 6 is inserted into place within the device 1. This includes correctly aligning the sample container 6 with the optical tower support structure 28 (e.g. aligning the indented or cut-out section or other surface feature 58 of the sample container 6 with the corresponding / complementary structure of the support structure 28 or device 1) and engaging the sample container 6 and sample turntable 8, for example by a snap-in and pull-out mechanism. In some embodiments, this process can be guided by the user interface 15 (e.g. via a series of diagrams and corresponding written / oral instructions). In some embodiments, the sample turntable 8 itself can also be removable for easy cleaning as required. The lid 12d of the device 1 is then closed and locked into place; and in step 120, the user interacts with the user interface 15 to initiate the pre-programmed sequence of actions to be taken by the various components of the device 1 to perform the desired sample analysis.

[0087] ​Before performing these pre-programmed actions, or indeed as part of these actions, the device 1 can be configured to identify the sample container 6 in step 115 and determine information relating to this particular sample container 6 based on data provided on the sample container 6 itself or its packaging. In some cases, this information can be contained in or obtainable by a unique identification code provided on the sample container 6, which can comprise a unique identifier associated with the sample container 6 itself, a unique identifier associated with the particular batch of which the sample container 6 forms a part, and a use-by date for the contents of the sample container 6. This identification code can be provided in the form of an RFID tag or a barcode (e.g. a 2D barcode), which can be scanned by the device 1 either prior to insertion of the sample container 6 (e.g. via a separate scanner associated with the device 1) or even after insertion of the sample container 6 (e.g. by a scanner integrated into the device 1). For example, an internal barcode scanner / reader 59 (in the device shown in Figure 2 FIG. 4) is shown mounted on an internal wall of the device housing 12. In this embodiment, the scanner 59 is mounted at a particular angle such that it is directed towards an identification RFID tag or barcode located on the sample container. For example, the barcode or other identification method can be located on an angled portion 58a of the sample container 6 (e.g. located near the cut-out section 58 of the sample container so as to be read by the scanner 59 as soon as the sample container 6 is inserted into the device 1, as shown in Figure 9A and 9B FIG. 4).

[0088] Additional information can also be provided as part of or in addition to the identification code, for example details of the particular drug provided within each detection chamber 20 of a given sample container 6, such that the analysis is performed with knowledge of the drug being tested. Furthermore, details regarding software updates that can need to be implemented can also be included as part of the information provided; this enables the device 1 to readily and efficiently obtain information from the sample container 6 itself regarding the appropriate software updates and changes that can need to be made.

[0089] Additionally or alternatively, the unique identification code can be provided on the packaging of the sample container 6 (e.g. on a box containing one or more sample containers 6 of a particular batch), or even provided with the packaging, for example in the form of a USB stick that is associated with the packaging and has been pre-loaded with the relevant identification information. Advantageously, utilising the packaging or a separate USB stick to provide this information increases the storage space available to contain the data, thereby enabling more data to be provided within the identification code. In this case, the device housing 12 can be provided with a port for receiving the USB stick and interfacing with the USB stick.

[0090] The device 1 can also be programmed to verify that the sample container 6 is one of an approved batch of containers for use with the device 1 (e.g., to identify any counterfeit or unauthorized sample containers and prevent their use with the device 1). In this regard, the sample container 6 can be provided with an identifying (anti-counterfeiting) feature that is detectable by the device 1; this can be provided as part of the unique identification code described above or in addition thereto. The device 1 can be programmed to reject or refuse to process any sample container 6 that does not include such a feature.

[0091] As will be described in more detail subsequently with reference to Figure 10 and Figure 11 The sample container 6 includes a central sample chamber 60 in which the clinical sample is initially retained, and a plurality of detection chambers 20 that represent the final destination of each individual sample portion, in which the sample portions are illuminated and analyzed. Accordingly, the first series of pre-programmed actions performed by the device 1 in step 125 are to operate the motor 10 to rotate at a particular rotational frequency, in certain predetermined directions, and for specific durations, in order to re-distribute portions of the clinical sample from the central sample chamber 60 to each of the plurality of detection chambers 20. This series of actions includes the following sequential steps: (a) mixing the clinical sample with a growth medium 62 provided within the sample container 6 to provide an environment conducive to bacterial growth; (b) distributing smaller sample portions into each of a plurality of radially extending fluidic structures 64 to separate unwanted particulates (e.g., sediment, etc.) from the sample; (c) mixing the smaller sample portions with a respective medicament (e.g., antibiotic) provided within each fluidic structure 64; and (d) retaining the final medicated sample within its respective detection chamber 20 for illumination and analysis over time. Of course, in certain applications, a control sample is not exposed to the antibiotic or other medicament.

[0092] Once the process has been executed and the various dosing sample portions have been re-assigned to their respective detection chambers 20, the next series of pre-programmed actions taken by the device 1 relate to the analysis of the sample within each detection chamber 20. The motor 10 is programmed to drive the sample turntable 8 and associated sample containers 6 to rotate at a constant rotational speed (e.g. 100 or 200 rpm) for an extended period of time (e.g. over a period of approximately 60 to 90 minutes) such that a given point on the sample container 6 (e.g. a particular detection chamber 20) performs a full rotation approximately every 0.6 seconds. Thus, in use, each detection chamber 20 will pass through the incident beam axis Y at a predetermined interval (e.g. approximately every 0.6 seconds for a rotational speed of 100 rpm). From this, each sample portion in its respective detection chamber 20 is illuminated in turn (every predetermined time interval) and the scattered light is collected by the photodetector 26 and can be processed / analysed at regular intervals throughout the course of the assay (e.g. bacterial growth / antibiotic susceptibility assay). At a given frequency of measurement, in some cases it is envisaged that a (weighted) rolling average of the sample measurement values can be used to process and combine the scattered light measurements obtained from each detection chamber 20. This will advantageously reduce the noise associated with each average sample measurement point (by taking the square root of the number of individual measurements to arrive at a weighted average). For example, in some cases it is envisaged that a rolling average can be applied to 100 measurements (i.e. over 60 seconds at an envisaged rotational speed of 100 rpm). In some embodiments, the rotational speed of the sample turntable 8 (and sample containers 6) is selected according to pre-programmed / factory settings; and can be determined according to the processing speed of the device 1 and / or the desired frequency of measurement. Thus, the rotational speed of the sample containers 6 during the assay can be faster or slower than 100 rpm (e.g. between 50 rpm and 300 rpm). Similarly, the length of the assay can also be based on pre-programmed / factory settings, or in some embodiments can be set according to user preference. For example, the length of the assay can be determined by the type of bacteria and / or the antibiotic to be tested against; and can be between approximately 20 minutes and 4 hours, for example between approximately 20 minutes and 2 hours, or between approximately 20 minutes and 1.5 hours. In some preferred embodiments, the length of the assay is between approximately 20 minutes and 1 hour, or between approximately 30 minutes and 1 hour.

[0093] As briefly mentioned earlier in this document, the signal strength generated by the primary "signal" photodiode 26 (in optical arrangements 2 and 2') and 48 (in optical arrangement 2") as a result of the measured scattered light intensity is related to the amount and / or concentration of (bacterial) particles in the sample under analysis / determination. In other words, a larger / stronger signal corresponds to a larger amount of light scattering, and thus, for a larger scattered light intensity, this in turn indicates a higher concentration of (bacterial) particles in the sample. Hence, a graphical representation of the detection signal (based on the scattered light intensity) over time can be used to visualize the time-varying changes in the number and / or concentration of bacteria in the sample, thereby showing and eventually determining the sensitivity of the bacteria in that sample to the type and concentration of the drug used for that particular sample.

[0094] Figure 8 An example of such a graphical representation is shown, in which the sensitivity of bacteria in a clinical sample to five different antibiotic drugs is tested. In this example, the sample container 6 is divided into 28 individual detection chambers 20 and the associated channels for separating the clinical sample into the 28 detection chambers 20, so that up to 28 separate determinations can be performed simultaneously. The 28 determinations are divided into four regions - labeled regions 1 to 4 (see Figure 8 ) - in each of which five antibiotic sensitivity tests are performed, as well as a negative control (in which the detection chamber is altered (e.g. made opaque) to prevent the passage of incident light) and a positive control (tracking un-inhibited bacterial growth without any antibiotic). In this case, five different antibiotics are provided in each of the five determination chambers of each region, respectively, so that the bacterial sensitivity test for each antibiotic can be repeated 4 times in each sample container 6, once in each of the four regions. In this way, the reproducibility of the determination around the sample container 6 can also be assessed. The sample container 6 is rotated at approximately 100 rpm and measurements of the scattered light intensity collected from each detection chamber 20 are made over a period of approximately 80 minutes.

[0095] From Figure 8The plots in FIG. 2 can clearly show that those detection chambers used as positive controls exhibit an exponential increase in detected scattered light intensity (and thus a corresponding exponential increase in bacterial number and / or concentration) over the course of the measurement. This reflects the degree of increase in bacterial number and / or concentration that would normally be expected (under the assay conditions) if no drug or other inhibitor were present and the bacteria were able to grow and replicate normally in the solution containing sufficient growth medium. At the same time, the detection chambers used as negative controls show minimal detected intensity throughout the measurement, as would be expected. Of the five detection chambers containing various antibiotics, four show a change in detected intensity, indicating a decrease in bacterial number and / or concentration (relative to the positive control) due to the effect of the antibiotic, i.e. the curves have a lower or negative gradient relative to the positive control curve, but still have values higher than the negative control line (at least initially). The sample that shows the greatest decrease in light scattering measurement intensity over time (relative to the positive control sample) in the various dosing samples (in theory) would correspond to the sample in which the particular type and / or concentration of antibiotic present in the dosing sample is most effective against the strain of bacteria present in the clinical sample. Thus, it can be determined relatively easily in a relatively short time period which antibiotic and which concentration is likely to be most effective in treating the patient from which the clinical sample was obtained.

[0096] Of course, it is possible (indeed likely) that a plurality of different antibiotics are identified as possible to which the bacteria in the sample are susceptible. Various different approaches have therefore been considered for determining the most appropriate antibiotic for treatment. For example, the susceptibility results can be presented to the user in real time, and the analysis can be terminated at any point after at least one antibiotic has been identified as effective. However, this is not necessarily the most appropriate antibiotic to administer; for example, if the reaction of the bacterial culture changes over a slightly longer time period, or if one antibiotic needs to take effect for a longer time initially. Alternatively, another approach can be to limit the time for which the test is performed (e.g. to 30 minutes, 45 minutes or 1 hour), and to present the results to the user after this time: this can mean that a plurality of antibiotics (or even none) and / or a plurality of dosage levels can be considered for administration to the patient. Another option is to only display the results after a certain number of antibiotics have been identified as effective. This of course means that the timescale required for the test will vary. Of course, a combination of these approaches can be employed.

[0097] It will be appreciated that the drugs or antibiotics used in each assay and the concentration of each drug or antibiotic can be selected based on a number of determining factors, such as the field of use of the device and / or the suspected medical indication and the bacterial infection likely to be screened for. For example, when the biological sample comprises urine for the determination of antibiotic susceptibility for urinary tract infections (UTIs), the antibiotics used can be selected from one or more of the following: amoxicillin; amoxicillin / clavulanic acid (2 / 1); cefadroxil; ciprofloxacin; ertapenem; fosfomycin; levofloxacin; mezlocillin; nitrofurantoin; trimethoprim; trimethoprim / sulfamethoxazole (1 / 19). However, the antibiotics selected and their concentration or concentration range can take the form of any antibiotic(s) (concentration) to provide the desired results during screening.

[0098] It is also apparent from a comparison of the graphs for the different regions that an increase in signal noise level is detected during rotation - the signal measurements obtained for region 4 (corresponding to the detection chamber 20 towards the end of each full rotation) show a greater scatter in noise than the signal measurements obtained for region 1. This will be described in more detail later with reference to Figure 11 The cause of the increase in noise and techniques for processing this increased noise are described in more detail with reference to Figure 13 The results of this technique are shown in Figure 12, from which it can be seen that the variation in signal to noise ratio for the different detection chambers 20 in different regions of the sample container 6 is much smaller and more consistent with each other. This will be described in more detail later with reference to Figure 13 This is described in more detail below.

[0099] However, it will be appreciated by the skilled person that the disclosed embodiments of the present disclosure provide benefits relating to the parallelisation of sample analysis. In particular, the design of the sample container 6 means that multiple tests for different drugs (at a plurality of different concentrations) can be performed on a sample from the same subject in one measurement period, with the results directly compared with each other, thereby minimising the equipment and time required to perform the assessment. This parallel analysis of multiple different drugs and concentrations also helps to eliminate the impact of the environment on the results of the sample tests for a single subject.

[0100] To assist in understanding the function of the device, reference will now be made to Figures 9 and Figure 10 The consumable sample container 6 will now be described briefly.

[0101] As previously mentioned, the sample container 6 is substantially circular in vertical cross-section and comprises a common (central) sample well or reservoir 60 which is in fluid communication with a plurality of detection chambers 20 which are spaced around the radially outer portion of the container 6. Each detection chamber 20 is fluidically connected to the common sample reservoir 60 via a respective fluidic structure or system 64 (comprising a plurality of fluidic channels 66, 68). However, the detection chambers 20 are otherwise fluidically isolated from one another. The fluidic structure 64, sample reservoir 60 and detection chambers 20 are provided at the base of the sample container 6. The fluidic structure 64 utilises centrifugal force generated by the rotation of the sample container 6 by the motor 10 to cause sample to flow from the sample reservoir 60 through the respective fluidic channels 66, 68 and ultimately to the respective associated detection chamber 20. The radial distance of each detection chamber 20 from the central rotational axis X of the sample container 6 corresponds to “d” - the distance between the rotational axis X of the sample container 6 and the incident light beam axis Y - to ensure that, in use, when the sample container 6 is rotated within the device 1, the light beam from the light source 22 will in turn pass through the detection chambers 20 to allow individual measurements of scattered intensity to be obtained from each sample portion in the sample container 6.

[0102] It will be appreciated that, since the detection chambers 20 are provided as being integrated within the illustrated sample container 6, the sample container 6 (or at least the portion of the sample container 6 containing the detection chambers 20) is made from a material which is transparent to light (or at least substantially transparent to light at the wavelength of the light source 22) so as to allow light from the light source 22 to enter and exit the detection chambers 20. In particular, in the illustrated configuration, incident light from the light source 22 passes through the base or underside of the sample container 6 at a location aligned with the illuminated detection chamber 20 and exits the top surface of the sample container 6 towards the light collector 24. However, it will be appreciated that other configurations / relationships between the light source 22, detection chambers 20 and light collector 24 are possible and fall within the scope of the present disclosure.

[0103] Figure 10 The illustrated sample container comprises 19 detection chambers 20 and their associated fluidic structures 64; and has a “cut-out” section 58 which is approximately the size of four or five detection chambers 20 and their associated fluidic structures 64. However, it will be appreciated that different numbers of detection chambers and / or different sizes or shapes of cut-out section 58 (or even no cut-out section, as is the case for sample containers used to generate data for Figure 8 Practicality and efficiency reasons for maximising the number of fluidic structures 64, for example, the cut-out 58 can subtend an angle of between about 20° to 60° (suitably between about 30° to 50°).

[0104] In a convenient mode of manufacture, the fluidics system 64 is formed as channels, reservoirs and grooves in the lower surface of the sample container 6. Thus, to form a closed system, a bottom cover 6c is attached to the bottom of the sample container 6, covering the surface area corresponding to the bottom of the sample container 6, to close the assembly and cover the fluidics system 64 and the sample reservoir 60 formed in the lower surface of the sample container 6 (see Figure 9C ). Suitably, the bottom cover 6c is a film. Without the bottom cover 6c, the fluidics system 6 would be open to the environment and would not contain liquids when the fluidics device 1 is in use. This bottom cover 6c is optically transparent at least in the area(s) axially below the detection chambers 20 to allow for subsequent analysis of the bacteria (or other particulate matter to be assessed for light scattering ability) in the respective detection chambers 20. In some embodiments, the bottom cover 6c can be opaque to light in specifically defined areas (e.g. below the detection chambers 20 providing a negative optical control in use).

[0105] The bottom cover 6c can be attached to the bottom side of the sample container 6 by any one or more of several well-known suitable sealing techniques, such as heat sealing, ultrasonic welding, liquid adhesive sealing, or the bottom cover 6c can comprise a single / double-sided adhesive film. Regardless of the sealing technique employed, it is important to ensure that a high level of optical clarity is maintained and that the reflection of incident light from the bottom cover 6c or any adhesive used is minimal (especially in the area covering the detection chambers 20) to avoid adversely affecting the subsequent analysis process. Furthermore, the sealing process should be compatible with (and should avoid interfering with) any components of the sample container 6 (e.g. any medicaments stored within the container). In particular, to avoid possible contamination of the liquid sample in use, it is desirable that the upper surface of the bottom cover 6c within the fluidics system 64 is free / minimally exposed to adhesive or other chemicals. An additional layer 6d can be attached to the bottom side of the sample container 6 (see Figure 9C ), and can comprise the barcode or other identification means described previously, configured to be located on the sloped portion 58a of the sample container 6.

[0106] Conveniently, the sample container 6 comprises a sample receiving well 69, in which an appropriate volume of sample is loaded, and which is contained with growth medium or culture medium 62 axially below the receiving well 69 Figure 9A , 9B), which promotes the growth of bacteria in the sample fluid and is configured to mix with the sample after the sample has been loaded into the receiving well 69 of the sample container 6 but before the sample enters the common sample reservoir 60, axially below the growth medium 62 (itself located in) the growth medium 62. Conveniently, as in the depicted embodiment, the growth medium is dried (e.g. freeze-dried or lyophilised). However, a liquid, concentrated growth medium can also be used. In alternative embodiments, a powdered dry growth medium can also be used, and can help the medium to dissolve quickly in the fluid sample. In some embodiments, it is envisaged that the growth medium can be contained in a dissolvable capsule / pill.

[0107] In one embodiment, the sample container 6 is provided with a lid or cap 6a, which is securable to the container 6 for use. In the depicted embodiment, the cap 6a comprises an integral plunger or plug 6b, and one or more protrusions 65 on the underside of the container plug 6b. When the cap 6a is engaged with the sample container 6, e.g. by a threaded engagement, the or each protrusion 65 pierces a foil / film 67 covering the growth medium 62, thereby bringing the sample into contact with the growth medium 62. As the cap 6a is screwed further into position to seal the sample within the sample container 6, the plug 69 fills at least part of the receiving well 69 and forces the sample and growth medium 62 into the common sample reservoir 60. It will be appreciated that the volume of the receiving well 69 and the extent to which the plug 6b can extend into the receiving well 69 can be used to regulate the volume of sample and growth medium that is pushed into the common sample reservoir 60. Furthermore, the amount / concentration of growth medium contained in the sample container 6 (prior to mixing with the sample) can be determined to provide the desired concentration of growth medium in the volume of sample / growth medium that is pushed into the common sample reservoir 60. Note that if the growth medium is contained in a dissolvable capsule or pill, it can not be necessary to use a foil / film 67 to cover the growth medium; therefore, the protrusions 65 for piercing this foil / film 67 can also be omitted in this case, if desired.

[0108] Once the sample and growth medium 62 have been brought into contact with each other and the cap 6a has been secured, the sample container 6 can be inserted into place in the device 1. As previously mentioned, it is preferable to design the sample container 6 to be inserted into the device 1 in a particular orientation. Advantageously, in the described embodiment, the asymmetry in the sample container 6, in particular the cut-out section 58 of the sample container 6, can be used to initially align the sample container 6 with the main optical support structure 28. Thus, in this orientation, the sample container 6 does not substantially extend through the cut-out 30 of the optical support structure 28 when the sample container 6 is initially inserted into the device 1. In other words, the relative alignment of the cut-out section 58 with the optical support structure 28 guides the insertion of the sample container 6 into the device 1 and avoids the possibility of damage to the device 1 and / or the sample container 6 due to incorrect alignment during insertion.

[0109] After sample container 6 is inserted into device 1, a set of programmed operations begins. Now refer to... Figure 10 Describe the effects of these operations on the fluid sample within sample container 6.

[0110] like Figure 10A As shown, each flow control structure 64 and its associated detection chamber 20 constitute a essentially self-contained system within the sample container 6. Figure 10 (The circle "A" in the diagram indicates this). Although a common sample reservoir 60 exists, fluid flow between adjacent flow control structures 64 is impossible due to the centripetal / centrifugal forces during use, thus avoiding potential cross-contamination between various drug-administered sample portions that will be analyzed individually in their respective detection chambers 20. Each flow control structure 64 includes a radially extending first "inlet" microchannel 66 (…). Figure 10A (Highlighted in the image), the microchannel, in its outermost radial extent, connects with the clarification (precipitation) chamber or well 70 (highlighted in the image). Figure 10C (Highlighted in the middle) Fluid communication. The clarification chamber 70, in its innermost radial range, is connected by a weir (dam) 70a (…). Figure 10B It is in fluid communication with a second microchannel 68, which is typically U-shaped, in... Figure 10D Highlighted in the image. The second microchannel 68 has a pair of radially extending first channel arms 68a and second channel arms 68b, configured to allow fluid to flow in a generally antiparallel direction. The first channel arm 68a extends between the clarification chamber 70 and the "air spring" or pneumatic (bypass) valve 72 (sometimes referred to in the art as a "pneumatic spring" or "air ballast chamber"), as shown in the image. Figure 10B As shown in the figure; while the second channel arm 68b extends between the air spring 72 and the detection chamber 20. Figure 10E The detection chamber 20 is highlighted in the image. Appropriately, in any embodiment of this disclosure, each of the fluid channels 66, 68a, and 68b is arranged generally radially.

[0111] In this case, the term "air spring" is used to refer to a pocket of gas that is compressed and under increasing pressure as fluid (liquid) moves through the fluidic structure 64 fluidic channels, and thus can be configured to resist the flow of fluid between the two channel arms 68a, 68b unless sufficient fluidic force is applied to the gas. In other words, the air spring provides a fluidic sealing and access control function between different regions of the fluidic structure 64, such as between the two channel arms 68a, 68b. Considered in another way, movement of sample fluid relative to the air spring 72 can be controlled by a balance / difference between pressures: that is, the centrifugal pressure differential caused by the rotating disk of the sample container 6 must overcome the increasing pressure (overpressure) caused by the reduced gas volume before liquid moves through the air spring valve mechanism 72. It will be appreciated, however, that alternative valve or sealing mechanisms can alternatively be used to provide the corresponding functionality without departing from the scope of the present disclosure.

[0112] First, the motor 10 rotates the sample container 6 alternately clockwise and counter-clockwise (i.e., performs a reciprocating / oscillating motion) at an initially relatively low speed (e.g., about 500 rpm or less), and for a predetermined period of time (about 30 seconds to about a few minutes) to ensure that the sample is thoroughly mixed with the growth medium 62 within the sample reservoir 60.

[0113] Subsequently, the sample container 6 is rotated in one direction at an increased rotational speed; the speed used varies depending on various factors (such as the geometry of the sample container 6), and thus, in some cases, a speed of up to about 1600 to 1900 rpm can be used, while in other cases, a speed of up to 2600 rpm can be used where greater centrifugal force is required. This results in sufficient centrifugal force to cause the mixed sample to flow outwardly from the central sample reservoir 60 along each radially extending first fluidic channel 66 and into the respective clarification chamber 70. This rotational speed is maintained for a predetermined time (e.g., about 30 seconds) to allow the sample to substantially fill the individual clarification chambers 70, and to exert sufficient centrifugal force to cause large particles (e.g., on the order of 10 pm or greater) to be deposited around the outer edges of the clarification chambers 70. At the end of this rotational cycle, sufficient sample fluid has entered the clarification chambers 70 to raise the liquid level in these chambers above the level of the weirs 70a; the overflow fluid displaces into the first channel arm 68a of the second fluidic channel 68. Any precipitates present in the sample fluid are deposited and retained in the clarification chambers 70, such that the fluid sample entering the fluidic channel 68 contains substantially only particles below about a few microns (such as bacterial cells). In practice, in use, the centrifugal force acting on the liquid sample pushes the heavier particles / undesirable impurities outwardly to the most radially outer walls of the clarification chambers 70, such that these impurities are held in the furthest position from the weirs 70a.

[0114] Once most of the fluid sample has been re-distributed from the central sample reservoir 60 into the individual fluidic structures 64, the rotational speed of the sample container 6 is increased (the speed used varies depending on various factors (including the geometry of the sample container 6), so in some cases the speed is, for example, above 1900 rpm or above 2600 rpm and up to about 3000 rpm, 3600 rpm or 4000 rpm). This provides sufficient centrifugal force to the sample fluid flow to overcome the pressure exerted by the air spring 72 and into the second fluidic channel arm 68b of the second fluidic channel 68. Once the air spring 72“seal” (pressure block) is overcome in this way, the sample fluid is able to flow through the second microchannel arm 68b and into the detection chamber 20. This process of directing sample fluid from the clarification chamber 70 to the detection chamber 20 can take, for example, on the order of about 20 seconds or so to ensure sufficient sample fluid enters each detection chamber 20 while avoiding the possibility of antibiotic contamination of the main fluid reservoir 60 (explained in more detail below).

[0115] In the illustrated embodiment, there is a particular type and concentration of drug (antibiotic) in each detection chamber 20. Conveniently, the drug / antibiotic is in dry form, for example, as a result of being initially deposited on the base of the detection chamber 20 and dried thereon during manufacture of the sample container 6. However, those skilled in the art will appreciate that other forms of drug / antibiotic can be used depending on preference or suitability - for example, the drug can be deposited on paper (e.g. filter paper) which is placed in the region of the fluidic structure 64 to dissolve into the liquid sample, or the drug can be present in liquid form. Suitably, as the sample fluid flows into and fills the detection chamber 20, it thereby mixes with the deposited drug to the desired concentration. Once sufficient sample fluid has entered the detection chamber 20, the rotational speed of the sample container 6 is preferably reduced (e.g. from about 4000 rpm, 3600 rpm or 3000 rpm to about 1500 rpm) to retain the fluid sample within the detection chamber 20. By way of illustration, by reducing the rotational speed, the air in the air spring 72 is again free to expand as the pressure on it is less. When this occurs, the fluid in the clarification chamber 70 is pushed back into the first fluidic channel 66, into the central sample reservoir 60. This creates an air barrier between the fluids in the detection chamber 20, so cross-contamination does not occur. Furthermore, backflow of fluid from the detection chamber 20 is prevented as there is no force to push the liquid sample radially inwards towards the air spring 72 once the detection chamber 20 is emptied of air. Inertial mixing of the sample fluid is then carried out by the sample container 6 at a relatively low speed (e.g. between about 1300 rpm and 1800 rpm) for a predetermined period of time (about a few minutes, for example, 3 minutes) to solvate its respective drug.

[0116] The initial sample dispensing phase is now complete and the irradiation, measurement and analysis of the samples in their respective detection chambers 20 can begin. During this process, the motor 10 is configured to rotate the sample container 6 at a relatively low speed, for example, of the order of only 100 rpm or 200 rpm. As this process has been described in detail previously, it will not be repeated here.

[0117] Reference will now be made to Figure 11 Some additional detail is provided regarding the processing aspects for extracting the desired signal, namely the measured signal portion corresponding to light scattered by bacterial particles in the sample. The figure shows three graphs of the detected signal intensity as a function of time, illustrating the well-windowing technique used to extract the appropriate portion of the signal for analysis.

[0118] The inventors have noted that periodic peak features appear within the detected signal intensity measured by the photodetector, which are found to occur at points where light from the light source is incident on the walls / edges of the detection chamber 20 and are determined to be due to the inner walls of the detection chamber 20 rather than particles within the sample increasing the scattering of the incident light. Accordingly, Figure 11 The use of these peak features in the signal / data processing process is shown to more accurately determine the measured intensity signal segment corresponding to light passing through the detection chamber 20 and being scattered by the sample in the detection chamber. Figure 11 A (upper graph panel) depicts the measured scattered light intensity at the photodetector 26 as the sample container 6 is rotated relative to the light source. The depicted scattered light trace spans three detection chambers 20, namely three of the openings 18 in the sample turntable 8 and the solid regions either side thereof. The detected light intensity between the detection chambers 20 / openings 18 is removed, leaving only the detected scattered light intensity trace for the region spanned by the three detection chambers 20, as shown in the middle graph panel Figure 11 B). The processor can be configured to identify such periodically occurring peak features in the measured light intensity (as shown in Figure 11 A and Figure 11 B), which are not due to particles in the sample, to extract the measured intensity segment between adjacent peak features (as shown in Figure 11 C, lower graph panel), so that the scattered light intensity can be measured and determined relative to only the extracted segment (corresponding to light scattering by the sample and not the edges of the detection chamber 20) to determine bacterial growth. This can advantageously avoid performing processing on signal portions containing large noise spikes, and can allow the signal to be appropriately amplified.

[0119] In contrast to the (relatively more straightforward) approach of simply using a pre-defined "time window" to extract the "wanted" signal obtained from the measurements, i.e. extracting the data for each sample at a given time offset from the start of each new rotation of the sample container 6 within a pre-defined time period or "window", this technique provides an improvement in noise reduction. This is because small variations in the motor speed can cause the pre-defined "time window" to become misaligned with the actual signal corresponding to light scattered from bacteria in the sample, i.e. the pre-defined "time window" will "drift" over time relative to the actual required signal. This in turn means that the "time window" used for data extraction will overlap with the peak features (as described above, resulting from scattering by the edge of the detection chamber 20), and the extracted signal will include a greater amount of this increased scattering from the edge of the detection chamber 20, and thus exhibit a greater noise level. This "drift" or misalignment between the extraction "time window" and the actual time period in which the required signal lies is more pronounced in those samples measured towards the end of the rotation, as shown by the increased noise in the graph for region 4 (as shown in Figure 8 It will be noted that the well window technique described above can be more easily implemented in the context of post-processing of sample measurements, rather than as a mechanism for real-time extraction of specific signal sections for processing. Further or alternative mechanisms for reducing noise in the extracted signal have also been developed, which are able to more accurately identify the "window" in which the required signal from each detection chamber 20 lies; this mechanism will now be described in more detail in relation to Figure 12A and 12B .

[0120] Figure 12A A bottom perspective view of the sample turntable 8 is provided, and further details of the calibration aspects of the intensity measurement process will now be described with reference to this figure. Figure 12B A close-up view of the controller used in conjunction with the sample turntable 8 during calibration is provided.

[0121] In the embodiment shown in Figure 12A , the sample turntable 8 comprises an additional calibration ring or gear 80 located on its underside and comprising a plurality of calibration features or teeth 82. In the embodiment shown, the calibration features 82 correspond to a plurality of radially extending spokes projecting at intervals from the calibration ring 80, and are arranged such that each calibration feature 82 is associated with a respective one of the plurality of openings 18.

[0122] In use, when a sample container 6 is engaged with the sample carousel 8, each calibration feature 82 will therefore also be associated with a respective one of the plurality of detection chambers 20 in the sample container 6. The apparatus 1 further comprises a calibration reader or optical encoder 84 arranged within the apparatus 1 so as to be positioned adjacent the underside of the sample carousel 8 and configured to, in use, interface with each calibration feature 82 in turn as the sample carousel 8 is rotated by the drive shaft 17. In particular, the calibration reader 84 comprises an optical arrangement configured to detect each calibration feature 82 passing therethrough, for example by detecting a reduction or loss of an optical signal caused by the calibration feature 82 passing through and temporarily interrupting an optical beam path within the calibration reader 84 (as Figure 12B is shown in more detail).

[0123] As the calibration features 82 are each associated with one of the detection chambers 20, the calibration reader 84 can be used to detect each calibration feature 82 associated with each opening 18 of the sample carousel 8 and send a signal to the controller / processor of the apparatus 1 to initiate the measurement of scattered light intensity a predetermined time period after the detection of the calibration feature 82 and for a predetermined time period sufficient to encompass the time period in which the detection chamber 20 intercepts light from the light source 22 from impinging on the walls of the detection chamber 20 (i.e. sufficient to obtain the time period of the reading exemplified in C). Advantageously, in this way, the light scattering measurement window is reset multiple times per rotation of the sample container 6 to ensure that the photodetector reading is properly in phase with the detection chamber 20. It will be appreciated that the number of calibration features can be selected according to preference: for example, there can be one calibration feature associated with each opening 18 in the sample carousel 8 or there can be one calibration feature associated with a predetermined group of openings 18 (e.g. one calibration feature 82 for every 2, 3, 4, 5 or 6 etc. openings 18). Figure 11

[0124] Alternatively, the calibration features 82’ can take a different form. For example, as shown in the embodiment shown in Figure 2 , Figure 3A and Figure 3B the calibration features 82’ take the form of ribs, fins or flags which are arranged at intervals around the circumference of the sample carousel 8 and which (as shown in these figures) extend substantially downwardly from the bottom of the sample carousel 8. Thus, these ribs 82’ can be moulded and form an integral part of the sample carousel 8. In this case, the calibration reader 84 can instead be mounted and oriented so that the vertically extending ribs 82’ pass through the optical arrangement of the calibration reader 84. In Figure 3A and 3B ​In the illustrated embodiment, one calibration feature 82' is associated with each opening 18 of the sample carousel 8, such that each calibration feature 82 passes through the optical arrangement of the calibration reader 84 can form a trigger for reading or measuring the scattered light obtained from each respective detection chamber 20. Advantageously, this helps to prevent drift occurring in the "window" due to motor speed variations, as a particular indicator is associated with each opening 18, and hence each detection chamber 20.

[0125] Figure 13 The detector intensity output in the apparatus of Figure 1 is shown over time, illustrating the signal-to-noise ratio obtainable using the calibration features 82, 82' and calibration reader 84. As Figure 8 illustrated, the apparatus 1 is divided into four regions or quadrants, and each of the four plots represents the detector intensity measurements obtained from the detection chambers 20 located within the respective region. Note that when the detector intensity output plots were generated, no antibiotic or other drug was provided in the apparatus, and hence (as expected) these plots do not show any significant reduction in the detector intensity output, which would be expected if the bacteria present in the sample were susceptible to the antibiotic (as in the case Figure 13 illustrated). However, it is clear from the plots of Figure 8 that the variance in the signal-to-noise ratio observed in all cases is significantly reduced: the detector intensity plotted is relatively consistent across all four regions, with no one region showing higher noise than any other (as in the case of region 4 in Figure 13 . Figure 8

[0126] In some cases, it is envisaged that the calibration reader 84 (or the processor associated with the photodetector 26) can be configured to calculate the time interval between adjacent calibration features 82 passing through the reader 84, and compare these calculated intervals with a predetermined interval at which the intensity of the scattered light is measured. If there is a discrepancy between the measured "calibration" time interval and the predetermined measurement time interval, and the discrepancy exceeds a predetermined time interval, then the processor can be configured to change the measurement time interval so that it aligns with the "calibration" time interval. This ensures that the intensity measurement is taken when the detection chamber 20 is precisely aligned with the incident beam axis, i.e. when the light from the light source is incident substantially through the centre of the detection chamber 20.

[0127] Many modifications can be made to the above-described examples without departing from the scope of the disclosure as defined in the appended claims.

[0128] ​For example, the drug need not be disposed within the detection chamber 20, but can be located at a different part of the flowic structure 64, for example within the second channel arm 68b of the second microchannel 68. Additionally or alternatively, a second pneumatic valve or air spring can be disposed at a location in the flow path after the detection chamber to implement a different mechanism for effective mixing of the sample with the drug (through a back-and-forth "shaking" motion between the air springs).

[0129] Further, it should be noted that the design of the sample container 6 can be varied to vary the optical path length of the light passing through the detection chamber 20 by varying the depth of the detection chamber well. Increasing the optical path length will increase the signal: light will pass through more sample and interact with more bacterial particles in the process. Example path lengths that can be considered are between 4mm and 10mm (e.g. a well depth of 4mm, 6mm, 8mm or 10mm); varying the optical path length will also involve varying the dimensions of other features in the flowic system 64 (e.g. the clear well 70 and air spring 72).

[0130] Other mechanisms for improving the signal-to-noise ratio include "shielding" the edges of the detection chamber 20, for example by fixing a thin film or plastic sheet or other thin material to the bottom of the sample container 6 to prevent light from entering the sample container 6 or interacting with other parts of the sample container - for example, the diameter of the opening 18 in the sample carousel 8 can be smaller than the diameter of the detection chamber 20.

[0131] Further, the detection sensitivity can be increased by making some slight (optional) changes to the optical arrangement 2 to increase the signal-to-noise ratio of the detected scattered light. For example, the second photodetector 48 that collects non-scattered light can be tilted or angled with respect to the path of the non-scattered light beam to reduce unwanted reflections of this non-scattered light back into the optical system (where it can interact with other beams). In some cases, the first photodetector 26 can be shielded to reduce unwanted detection of stray light within the optical system.

[0132] As will be appreciated, when assembling the optical assembly, minimising the number of (separate) machined components of the optical assembly can improve the precision of the beam of light output from the light source 22 and the alignment of this beam with the detection chamber 20 and the aperture 46 in the light collector 24. Further, in certain cases, particularly where the light source takes the form of a laser (diode), the laser can be contained in a machined / easily replicated laser block to increase the consistency of the position of the laser beam when performing a measurement (and hence the ease with which good alignment is maintained within the optical system).

[0133] In relation to maintaining consistent alignment of the optical beam through the optical system, additional sensors (e.g. accelerometers) can be incorporated into the device 1 to measure vibrations occurring within the device 1 (e.g. due to the motor 10 rotating the sample container 6 and / or the fan 42 in the temperature control module 14). This helps to ensure that any vibrations are kept within / under an acceptable range, thereby avoiding adversely affecting the alignment of the components in the optical arrangement 2.

[0134] Finally, alternative designs of the sample container 6’ are also envisaged, as shown in Figure 14 From this figure, it can be seen that the relative positions of the clarification chamber 70’ and the detection chamber 20’ in this alternative sample container 6’ are different to the relative positions of the clarification chamber 70 and the detection chamber 20 in the sample container 6 shown in Figure 10 Specifically, in the sample container 6 shown in Figure 10 the radially outermost extent of the clarification chamber 70 lies at a greater distance from the central rotational axis of the sample container 6 than the radially outermost extent of the detection chamber 20. However, in the alternative sample container 6’, the opposite configuration is used: the radially outermost extent of the detection chamber 20 lies at a greater distance from the central rotational axis of the sample container 6’ than the radially outermost extent of the clarification chamber 70’. Figure 14 The latter arrangement shown in is advantageous in increasing the ease with which the fluid sample is held within the detection chamber 20’ for irradiation and measurement, as the centrifugal force acting on the fluid tends to move the fluid towards the radially outermost extent of the fluidic system 64. It will be appreciated that this adjustment in the relative position of the detection chamber 20 can require some corresponding changes to the relative positions of the components of the optical arrangement 2, to maintain the alignment of the light source 22, the detection chamber 20, the light collector aperture 46 and the light detectors 26, 48.

Claims

1. An apparatus comprising an optical device for monitoring bacterial growth of a dosed liquid biological sample, the apparatus comprising: a sample container port, in use, for receiving a sample container, the sample container having at least one detection chamber for containing a dosed sample; and the optical device comprising: a light source configured to emit light along an incident beam axis, in use, the incident beam axis intersecting at least one detection chamber of the sample container and illuminating a dosed sample contained within the detection chamber; a first photodetector configured to receive light scattered by bacteria in the sample; a light collection arrangement configured to: collect light exiting the detection chamber that has been forward scattered by bacteria in the sample within a scattering angle range of between about + / - 4 degrees and + / - 20 degrees relative to the incident beam axis and direct the collected scattered light to the first photodetector; and block non-scattered light travelling parallel to the incident beam axis and exiting the detection chamber from reaching the first photodetector; and at least one processor configured to: measure an intensity of the scattered light received by the first photodetector; determine a respective representative quantity or concentration of bacteria present in the sample based on the intensity of the scattered light; repeat the measuring and determining steps at a series of predetermined intervals to determine a representative quantity or concentration of bacteria present in the sample over time; and determine a respective susceptibility of the bacteria in the sample to the respective drug; wherein the light collection arrangement comprises: (1) a concave elliptical reflector configured to collect and reflect only light within an angular range of between about + / - 4 degrees and + / - 20 degrees relative to the incident beam axis towards the first photodetector for it to be received by the first photodetector; or (2) a concave elliptical reflector configured to collect and reflect only forward scattered light within an angular range of between about + / - 4 degrees and + / - 20 degrees relative to the incident beam axis towards a condenser, the condenser arranged to receive light reflected by the concave elliptical reflector and focus the received light onto the first photodetector.

2. The apparatus of claim 1, wherein, the range of scattering angles of the collected scattered light is between +4 and +16 degrees and between -4 and -16 degrees relative to the incident beam axis.

3. The apparatus of claim 1 or 2, wherein, the light collection arrangement comprises a concave elliptical reflector shaped to reflect forward scattered light from the sample to the first photodetector or condenser, and wherein the concave elliptical reflector comprises an aperture aligned with the incident beam axis and configured to allow non-scattered light from the detection chamber to pass through the concave elliptical reflector.

4. The apparatus of claim 1 or 2, wherein, the optical device further comprises a second photodetector arranged to receive non-scattered light.

5. The apparatus of claim 4, wherein the second photodetector is positioned on an opposite side of the light collection arrangement to the sample and aligned with the incident beam axis to receive the non-scattered light.

6. The apparatus of claim 1, comprising a sample container carousel disposed within the sample container port for engaging a sample container and configured to align a detection chamber of the sample container containing at least a portion of the biological sample with an incident beam axis of the light source of the optical device.

7. The apparatus of claim 6, comprising a motor operably coupled to the sample container carousel and configured to rotate the carousel to periodically align and misalign the detection chamber containing at least a portion of the biological sample with the incident beam axis of the light source.

8. The apparatus of claim 6 or 7, wherein, the sample container carousel is configured to engage a sample container comprising a plurality of detection chambers and the sample container carousel is configured to rotate to sequentially align and misalign each of the plurality of detection chambers of the sample container with the incident beam axis of the light source.

9. The apparatus of claim 6 or 7, wherein, the sample container carousel comprises one or more openings configured to align with one or more detection chambers of the sample container when the sample container is properly engaged with the sample container carousel in use.

10. The apparatus of claim 6 or 7, wherein, the sample container carousel comprises one or more detectable calibration features for determining a position and / or orientation of the sample container carousel relative to the incident beam axis of the light source.

11. The apparatus of claim 10, comprising a calibration feature reader in communication with the processor of the apparatus in use for determining a time interval between detection of a calibration feature by the calibration feature reader and alignment of the associated detection chamber with the incident beam axis of the light source.

12. The apparatus of claim 11, wherein, the processor of the optical device: (1) is in communication with the first photodetector to measure an intensity of the scattered light received by the first photodetector during a predetermined time window corresponding to a period of time in which a detection chamber of the sample container is aligned with the incident beam axis of the light source; or (2) adjusts a length of the predetermined interval based on detection of each calibration feature.

13. The apparatus of claim 1, wherein, the processor of the optical device is programmed to periodically repeat the measuring step of measuring an intensity of the scattered light received by the first photodetector and the determining step of determining a respective representative quantity or concentration of bacteria present in the sample over time for a period of time of between about 20 minutes and about 2 hours, between about 20 minutes and about 1.5 hours, between about 20 minutes and about 1 hour, or between about 30 minutes and about 1 hour.

14. The apparatus of claim 1, further comprising a temperature control system for controlling an air temperature within the apparatus.

15. The apparatus of claim 14, comprising at least one heating element and at least one air flow regulator arranged to contact, in use, warm air with a sample container received within the sample container port of the apparatus in order to maintain a biological sample within a detection chamber at a desired temperature.

16. The apparatus of claim 14 or 15, comprising a pair of heating elements, each operatively associated with a fan to push warm air towards the sample container port, in use, to heat a sample within a detection chamber of a sample container received within the sample container port of the apparatus.

17. The apparatus of claim 1, wherein, The light source of the optical apparatus is a laser light source.

18. The apparatus of claim 17, wherein, The laser light source has a wavelength between 620 nm and 780 nm.

19. The apparatus of claim 1 or 2, wherein, The predetermined interval corresponds to approximately 0.6 seconds at a rotational speed of 100 rpm.

20. The apparatus of claim 1 or 2, wherein, The processor of the optical apparatus is configured to identify a plurality of periodically occurring peak features in the measured light intensity and to perform the measuring step and the determining step only between adjacent peak features.

21. A system for monitoring bacterial growth of an administered liquid biological sample, the system comprising: an apparatus as defined in claim 1 or 2; and a sample container comprising a plurality of detection chambers, each detection chamber being configured to house an administered liquid biological sample; wherein the system further comprises: a sample positioning mechanism configured to align each of the plurality of detection chambers in turn with the incident beam axis such that the light source illuminates an administered liquid biological sample housed within the illuminated detection chamber.

22. The system of claim 21, wherein, The sample positioning mechanism comprises a rotating or carousel mechanism configured to rotate the sample container to sequentially align each of the plurality of detection chambers with the incident beam axis.

23. The system of claim 21, further comprising a support structure arranged to support the optical device, wherein, The support structure comprises an opening configured to receive a portion of the sample container comprising at least one of the plurality of detection chambers such that, when the portion of the sample container is located within the opening, the at least one of the plurality of detection chambers is positionable between the light source and the light collection arrangement along the incident beam axis.

24. The system of claim 21, further comprising a temperature control system configured to maintain a temperature of the liquid biological sample at a temperature between 35° and 37°.

25. The system of claim 24, wherein, The temperature control system comprises a heating arrangement comprising a heating element arranged to generate heat and an air circulation system configured to distribute the generated heat evenly across the plurality of detection chambers of the sample container.

26. The system of claim 25, wherein, The air circulation system comprises at least one recirculation duct and an associated fan arranged to drive an airflow through the heating element.

27. A method of determining susceptibility of bacteria in a sample to a drug, the method comprising: housing an administered liquid biological sample in a detection chamber of a sample container; illuminating the sample within the detection chamber with light emitted by a light source along an incident beam axis through the detection chamber; collecting, by a light collector, light scattered by interaction with bacteria in the sample, the light being forward scattered over a range of scattering angles of + / - 4 degrees to + / - 20 degrees relative to the incident beam axis, wherein the light collection arrangement comprises: (1) a concave elliptical reflector configured to collect and reflect only light within an angular range of between about + / - 4 degrees and + / - 20 degrees relative to the incident beam axis towards a first photodetector for it to be received by the first photodetector; or (2) a concave elliptical reflector configured to collect and reflect only forward scattered light within an angular range of between about + / - 4 degrees and + / - 20 degrees relative to the incident beam axis towards a condenser arranged to receive the light reflected by the concave elliptical reflector and focus the received light onto the first photodetector; focusing, by the light collector, the collected scattered light onto a first photodetector; determining, by a processor, an intensity of the scattered light collected by the first photodetector, and a corresponding representative quantity or concentration of bacterial particles present in the sample; repeating, by the processor, the determining step at a series of predetermined intervals; determining, by the processor, a change in the representative quantity or concentration of bacteria in the sample over time; and determining, by the processor, a susceptibility of the bacteria in the sample to a drug for administration to the sample based on the determined change in the representative quantity or concentration of bacteria in the sample over time.

28. The method of claim 27, wherein, the sample container comprises a plurality of detection chambers, at least two of the plurality of detection chambers containing samples administered with different drugs, and the method comprises: sequentially positioning each of the plurality of detection chambers containing the administered samples in the light emitted along the incident beam axis; performing each of the subsequent steps of the method for each of the plurality of detection chambers; and determining a relative susceptibility of the bacteria in the sample to the respective drug for administration to the sample to identify the most effective drug for a treatment regime.

29. The method of claim 27, wherein, the sample container comprises a plurality of detection chambers, at least two of the plurality of detection chambers containing samples administered with the same drug at different drug concentrations, and the method comprises: sequentially positioning each of the plurality of detection chambers containing the administered samples in the light emitted along the incident beam axis; performing each of the subsequent steps of the method for each of the plurality of detection chambers; and determining a relative susceptibility of the bacteria in the sample to the respective concentration of the drug for administration to the sample to identify the most effective drug concentration for a treatment regime.

30. The method of any of claims 27 to 29, comprising: collecting, by a second photodetector, non-scattered light passing through each detection chamber parallel to the incident beam axis; and comparing an intensity of the non-scattered light collected by the second photodetector to an intensity of the scattered light collected by the first photodetector for the same detection chamber.

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