Systems, methods, and sensor devices for sensing changes in the concentration of microorganisms

Abstract

A sensor device for sensing a change in the concentration of microorganisms, comprising a waveguide interferometer having a sensing arm and a reference arm, a microfluidic channel for a fluid containing microorganisms, and capture means in the microfluidic channel for physically capturing microorganisms as the fluid flows along the microfluidic channel so as to concentrate the microorganisms in a sensing region of the microfluidic channel. The sensing arm is configured to guide sensing light, the reference arm is configured to guide reference light, and the waveguide interferometer is configured to cause the sensing light to interfere with the reference light. The waveguide interferometer and the microfluidic channel are configured to allow the sensing light to interact with the fluid and microorganisms in the sensing region of the microfluidic channel. The sensor device can be used to sense a change in the concentration of microorganisms such as bacteria due to the growth of the microorganisms. The sensor device can be used to sense the sensitivity of the growth of the microorganisms to one or more microbial growth inhibitory substances such as one or more antibiotics. The present disclosure also relates to a reader device and an associated method for reading the sensor device.

Description

Technical Field

[0001] The present disclosure relates to systems, methods, and sensor devices for sensing a change in concentration of microorganisms such as bacteria (e.g., due to growth of the microorganisms) and, in particular but not exclusively, for sensing the sensitivity of growth of the microorganisms to one or more microbial growth inhibitory substances such as one or more antibiotics. The present disclosure also relates to a reader device for reading the sensor device. Background Art

[0002] It is well known that clinicians such as doctors send body fluid samples such as urine, blood, etc. to a central hospital laboratory where culture-based tests can determine the bacterial count, identify the bacterial species, and their sensitivity to antibiotics. However, these tests often take several days, and thus it is not uncommon for antibiotics to be prescribed before the test but later found to be wrong or unnecessary. This can lead to faster evolution of bacteria to develop resistance to antibiotics, which has a dire impact on the future of global healthcare. A recent review on antimicrobial resistance recommended that by 2020, all prescriptions should be supported by diagnostic tests. Summary of the Invention

[0003] It should be understood that any one or more features of any one of the following aspects of the present disclosure may be combined with any one or more features of any other of the following aspects of the present disclosure.

[0004] According to at least one aspect of the present disclosure, there is provided a sensor device for sensing a change in concentration of microorganisms, the sensor device comprising:

[0005] A waveguide interferometer having a sensing arm and a reference arm;

[0006] A microfluidic channel for containing a fluid of microorganisms; and

[0007] Capture means in the microfluidic channel for physically capturing microorganisms as the fluid flows along the microfluidic channel so as to concentrate the microorganisms in a sensing region of the microfluidic channel,

[0008] wherein the sensing arm is configured to direct sensing light, the reference arm is configured to direct reference light, and the waveguide interferometer is configured to interfere the sensing light with the reference light, and

[0009] wherein the waveguide interferometer and the microfluidic channel are configured to allow the sensing light to interact with the fluid and microorganisms in the sensing region of the microfluidic channel.

[0010] As the concentration of microorganisms in the fluid within the sensing region of the microfluidic channel changes, any change in the optical path length difference between the sensing arm and the reference arm will result in a change in the phase difference between the sensing light and the reference light, and thus result in a change in the intensity of the light at the output of the waveguide interferometer. Therefore, the evolution of the intensity of the light at the output of the waveguide interferometer over time can provide a measurement of the change in the concentration of microorganisms in the fluid within the sensing region of the microfluidic channel. Accordingly, the sensor device can be used to measure the change in the concentration of microorganisms in the fluid. Specifically, the sensor device can be used to measure the growth or reduction of microorganisms in the fluid. The sensor device can be used to measure the rate of change of the concentration of microorganisms in the fluid.

[0011] The microorganisms can include at least one of bacteria, fungi, and algae.

[0012] The fluid can be a body fluid, such as urine, blood, saliva, sputum, etc.

[0013] The fluid can be a non-body fluid.

[0014] The fluid can be water.

[0015] The sensing arm can be configured to direct the sensing light as a guided optical mode.

[0016] The sensing arm and the microfluidic channel can be configured to allow the evanescent field of the guided optical mode to interact with the bacteria in the sensing region.

[0017] The sensing arm can include an optical waveguide, such as a single-mode optical waveguide.

[0018] The reference arm can be configured to direct the reference light as a guided optical mode.

[0019] The reference arm can include an optical waveguide, such as a single-mode optical waveguide.

[0020] The guided optical mode in the optical waveguide of each of the sensing arm and the reference arm can include a guided transverse magnetic (TM) optical mode. Using the TM optical mode can provide higher measurement sensitivity than the transverse electric (TE) optical mode, because the TM optical mode is less restricted and thus interacts more with the microorganisms in the sensing region of the microfluidic channel. Moreover, using the TM optical mode is more tolerant of manufacturing defects in the width and sidewall roughness of the waveguides in the sensing arm and the reference arm.

[0021] The guided optical mode in the optical waveguide of each of the sensing arm and the reference arm can include a guided transverse electric (TE) optical mode.

[0022] The capture device can be defined by the sensing arm.

[0023] The capture device may include one or more breaks or gaps in the sensing arm. One or more breaks or gaps in the sensing arm may be configured to capture and / or contain microorganisms while allowing fluid to flow through the one or more breaks or gaps in the sensing arm.

[0024] One or more breaks or gaps in the sensing arm may be defined in the waveguide core of the sensing arm. The waveguide interferometer and the microfluidic channel may be configured such that one or more breaks or gaps in the sensing arm are located in the sensing region of the microfluidic channel to allow the sensing light to propagate through any microorganisms located in any of the breaks or gaps in the sensing arm.

[0025] The waveguide core of the sensing arm may be defined by a plurality of holes or posts. Such a waveguide core may act as a photonic crystal waveguide. The capture device may be defined by a plurality of holes or posts.

[0026] One or more breaks or gaps in the sensing arm may be defined in the waveguide cladding of the sensing arm. One or more breaks or gaps in the sensing arm may be defined in the upper waveguide cladding and / or the lower waveguide cladding of the sensing arm.

[0027] The capture device may be defined by the path of the sensing arm. For example, the sensing arm waveguide may follow a path that defines one or more regions or bays for capturing and / or containing microorganisms to one side of the sensing arm waveguide. For example, the sensing arm waveguide may follow a meandering, sinusoidal, or square wave path that defines one or more regions or bays for capturing and / or containing microorganisms to one side of the sensing arm waveguide. The sensing arm may define one or more gaps or breaks in the sensing arm to allow fluid to flow through the one or more breaks or gaps in the sensing arm.

[0028] The waveguide interferometer and the microfluidic channel may be configured to allow the reference light to interact with the fluid and microorganisms in the microfluidic channel. The waveguide interferometer and the microfluidic channel may be configured to expose the reference arm of the waveguide interferometer to the fluid and microorganisms. In use, the concentration of microorganisms near the reference arm may be much lower than the concentration of microorganisms in the sensing region near the sensing arm. Configuring the waveguide interferometer and the microfluidic channel to allow the reference light to interact with the fluid and microorganisms in the microfluidic channel or to expose the reference arm of the waveguide interferometer to the fluid and microorganisms results in a simpler sensor device and / or an easier-to-fabricate sensor device because there is no need to include additional overcoats or masks to prevent the reference arm from being exposed to the fluid and microorganisms in the microfluidic channel.

[0029] The waveguide interferometer and the microfluidic channel can be configured to prevent the reference light from interacting with the fluid and microorganisms in the microfluidic channel. The waveguide interferometer and the microfluidic channel can be configured to prevent the reference arm from being exposed to the fluid containing microorganisms. The sensor device can include a cover layer or mask located between the reference arm and the microfluidic channel, and the cover layer or mask prevents the reference light from interacting with the fluid and microorganisms in the microfluidic channel. The cover layer or mask can prevent the reference arm from being exposed to the fluid containing microorganisms. By preventing the reference light from interacting with the fluid and microorganisms in the microfluidic channel or preventing the reference arm from being exposed to the fluid containing microorganisms, the effective refractive index difference between the sensing arm and the reference arm and thus the phase difference between the sensed light and the reference light can be greater, such that the sensor device can provide a more sensitive measurement or a more accurate measurement of the change in the concentration of microorganisms.

[0030] The sensing arm and the reference arm can be symmetric, i.e., the sensing arm and the reference arm can have the same length. The sensing arm and the reference arm can be balanced, i.e., the sensing arm and the reference arm can have the same optical path length. For example, the sensing arm and the reference arm can be formed of the same material, can have the same cross-sectional geometry, and can have the same length. In terms of thermal stability, it is better to use balanced sensing and reference arms, i.e., using balanced sensing and reference arms can reduce any change in the intensity of the light at the output of the waveguide interferometer due to a change in temperature. Using balanced sensing and reference arms can also help cancel out any refractive index changes that are not caused by a change in the concentration of microorganisms in the sensing region. For example, when the waveguide interferometer and the microfluidic channel are configured to allow the reference light to interact with the fluid and microorganisms in the microfluidic channel, using balanced sensing and reference arms also helps cancel out any refractive index changes in the fluid that are not caused by a change in the concentration of microorganisms in the sensing region.

[0031] The sensing arm and the reference arm can be asymmetric, i.e., the sensing arm and the reference arm can have different lengths. The sensing arm and the reference arm can be unbalanced, i.e., the sensing arm and the reference arm can have different optical path lengths. Using unbalanced sensing and reference arms can be more sensitive to changes in the concentration of microorganisms in the sensing region, but may be less stable to temperature changes. Using unbalanced sensing and reference arms can allow the use of a spectral broadband light source and a spectrometer or the use of a tunable light source such as a tunable laser and a photodetector to measure the intensity of light at the output of the waveguide interferometer as a function of wavelength. The change in the concentration of microorganisms as a function of time can be determined from the change in the intensity of light at the output of the waveguide interferometer as a function of wavelength over time. For example, a change in the concentration of microorganisms can cause a change in the free spectral range or wavelength periodicity of the intensity of light at the output of the waveguide interferometer as a function of wavelength. Thus, using unbalanced sensing and reference arms can allow repeated measurements of the free spectral range of the intensity of light at the output of the waveguide interferometer at different times and allow determination of the change in the concentration of microorganisms over time based on the repeated measurements of the free spectral range.

[0032] The sensing arm can be folded such that the sensing arm passes through the sensing region of the microfluidic channel multiple times. This can increase the overall phase change experienced by the sensing light in the sensing arm, thereby improving the sensitivity of the measurement of the change in the concentration of microorganisms.

[0033] The reference arm of each waveguide interferometer can be folded.

[0034] The sensor device can include:

[0035] A plurality of waveguide interferometers, each waveguide interferometer having a sensing arm and a reference arm;

[0036] A plurality of microfluidic channels for fluids and microorganisms; and

[0037] Capture means in each microfluidic channel for physically capturing microorganisms as the fluid flows along the corresponding microfluidic channel so as to concentrate the microorganisms in the corresponding sensing region.

[0038] Each sensing arm can be configured to direct sensing light, each reference arm can be configured to direct reference light, and each waveguide interferometer can be configured to interfere the corresponding sensing light with the corresponding reference light. The waveguide interferometer and the microfluidic channel can be configured to allow the sensing light in the sensing arm of each waveguide interferometer to interact with the fluid and microorganisms in the sensing region of the corresponding microfluidic channel.

[0039] One of the microfluidic channels can contain a first microorganism growth inhibitory substance. Such a sensor device can allow measurement of the sensitivity of microorganisms to the first microorganism growth inhibitory substance.

[0040] One of the microfluidic channels may include a first microbial growth inhibiting substance at a position upstream of a corresponding sensing region in the one of the microfluidic channels.

[0041] One or more of the other microfluidic channels may include a corresponding microbial growth inhibiting substance different from the first microbial growth inhibiting substance. Such a sensor device may allow for the sensitivity of the microorganism to different microbial growth inhibiting substances.

[0042] One or more of the other microfluidic channels may include a corresponding microbial growth inhibiting substance different from the first microbial growth inhibiting substance at a position upstream of the corresponding sensing region.

[0043] One or more of the other microfluidic channels may not include any microbial growth inhibiting substance. Any one of the microfluidic channels that does not include any microbial growth inhibiting substance may be used as a reference microfluidic channel. Specifically, the measurement of the intensity of light as a function of time at the output of a waveguide interferometer corresponding to a microfluidic channel that includes a microbial growth inhibiting substance may be compared with the measurement of the intensity of light as a function of time at the output of a waveguide interferometer corresponding to the reference microfluidic channel in order to provide a relative measurement of the sensitivity of the growth of the microorganism in the microfluidic channel that includes the microbial growth inhibiting substance. In the case where the reference microfluidic channel does not have any microbial growth inhibiting substance, the intensity of light at the output of the corresponding waveguide interferometer may depict a series of interference fringes as the microorganism grows, i.e., the intensity of light as a function of time at the output of the waveguide interferometer corresponding to the reference microfluidic channel is generally oscillatory. However, if the microbial growth inhibiting substance is effective in another microfluidic channel such that the growth of the microorganism in that another microfluidic channel is slowed down, then the interference fringes of that another microfluidic channel may be longer than the interference fringes of the reference microfluidic channel. If the microbial growth inhibiting substance is effective in another microfluidic channel such that the growth of the microorganism in that another microfluidic channel stops, then the interference fringes in that another microfluidic channel may effectively disappear.

[0044] Each microfluidic channel may include a different microbial growth inhibiting substance.

[0045] Only one microfluidic channel may not include any microbial growth inhibiting substance.

[0046] The microorganism may include bacteria and each microbial growth inhibiting substance may include an antibiotic.

[0047] Each microfluidic channel may include a well for receiving a microbial growth inhibiting substance, such as a through hole or a groove. The well may be located at a position upstream of the corresponding sensing region in the same microfluidic channel.

[0048] Each capture device can be located downstream of the sensing arm of the corresponding waveguide interferometer.

[0049] Each capture device can be located at the same position as the sensing arm of the corresponding waveguide interferometer along the corresponding microfluidic channel.

[0050] Each capture device can be located near the sensing arm of the corresponding waveguide interferometer. For example, each capture device can be located above, over, on top of, below, beneath, under, and / or beside the sensing arm of the corresponding waveguide interferometer.

[0051] The capture device in each microfluidic channel can define one or more gaps configured to allow fluid to flow through the capture device but prevent microorganisms from passing through the capture device.

[0052] Each waveguide interferometer can be defined on or near the surface of the photonic chip. The capture device can define one or more gaps between the capture device and the surface of the photonic chip, where each gap is configured to allow fluid to flow through the gap between the capture device and the surface of the photonic chip but prevent microorganisms from passing through the gap between the capture device and the surface of the photonic chip.

[0053] The capture device in each microfluidic channel can include a plurality of capture features, where the capture features are configured to physically capture microorganisms when fluid flows along the microfluidic channel.

[0054] The capture features can define one or more gaps configured to allow fluid to flow through the capture features but prevent microorganisms from passing through the capture features.

[0055] Each capture feature can define one or more gaps between the capture feature and the surface of the photonic chip, where each gap is configured to allow fluid to flow through the gap between the capture feature and the surface of the photonic chip but prevent microorganisms from passing through the gap between the capture feature and the surface of the photonic chip.

[0056] The capture device in each microfluidic channel can include a row of capture features.

[0057] The capture device in each microfluidic channel can include two or more rows of capture features.

[0058] Two or more rows of capture features can be staggered.

[0059] Each capture feature can include a capturer configured to physically capture microorganisms when fluid flows along the microfluidic channel.

[0060] Each capturer can include one or more features extending into the corresponding microfluidic channel to define a compartment in the corresponding microfluidic channel for accommodating one or more microorganisms.

[0061] The sensing arm of each waveguide interferometer can be folded such that the sensing arm passes through the corresponding sensing region of the corresponding microfluidic channel multiple times. This can increase the overall phase change experienced by the sensing light in the sensing arm, thereby improving the sensitivity of the measurement of the concentration change of the microorganism.

[0062] The reference arm of each waveguide interferometer can be folded.

[0063] The sensing arm and the reference arm of each waveguide interferometer can be symmetric, i.e., the sensing arm and the reference arm can have the same length. The sensing arm and the reference arm of each waveguide interferometer can be balanced, i.e., the sensing arm and the reference arm of each waveguide interferometer can have the same optical path length. For example, the sensing arm and the reference arm of each waveguide interferometer can be formed of the same material, can have the same cross-sectional geometry, and can have the same length. Using balanced sensing and reference arms can be better in terms of thermal stability, i.e., using balanced sensing and reference arms can reduce any change in the intensity of the light at the output of each waveguide interferometer due to a change in temperature. Using balanced sensing and reference arms can also help cancel out any refractive index change that is not caused by the concentration change of the microorganism in each sensing region. For example, when each waveguide interferometer and the corresponding microfluidic channel are configured to allow the reference light to interact with the fluid and the microorganism in the corresponding microfluidic channel, using balanced sensing and reference arms can also help cancel out any refractive index change of the fluid that is not caused by the concentration change of the microorganism in the sensing region of the corresponding microfluidic channel.

[0064] The sensing arm and the reference arm of each waveguide interferometer can be asymmetric, i.e., the sensing arm and the reference arm can have different lengths. The sensing arm and the reference arm of each waveguide interferometer can be unbalanced, i.e., the sensing arm and the reference arm of each waveguide interferometer can have different optical path lengths. Using unbalanced sensing arms and reference arms can be more sensitive to changes in the concentration of microorganisms in the sensing region of each microfluidic channel, but may be less stable to changes in temperature. Using unbalanced sensing arms and reference arms can allow the use of a spectral broadband light source and a spectrometer or the use of a tunable light source such as a tunable laser and a photodetector to measure the intensity of light at the output of each waveguide interferometer as a function of wavelength. The change in the concentration of microorganisms as a function of time can be determined based on the change in the intensity of light at the output of each waveguide interferometer as a function of wavelength over time. For example, a change in the concentration of microorganisms can cause a change in the free spectral range or wavelength periodicity of the intensity of light at the output of each waveguide interferometer as a function of wavelength. Therefore, using unbalanced sensing arms and reference arms can allow repeated measurements of the free spectral range of the intensity of light at the output of each waveguide interferometer at different times and allow the determination of the change in the concentration of microorganisms over time based on the repeated measurements of the free spectral range of each waveguide interferometer.

[0065] The sensor device can include filtration equipment at a position upstream of the corresponding sensing region in each microfluidic channel, wherein the filtration equipment is configured to capture debris or particles larger than the microorganisms, such as debris or particles having a minimum size larger than the maximum size of the microorganisms.

[0066] Each filtration equipment can include one or more protrusions, such as one or more cylindrical columns extending into the corresponding microfluidic channel, wherein the one or more protrusions define at least one gap larger than the maximum size of the microorganisms.

[0067] Each waveguide interferometer can be defined by a photon chip.

[0068] Each microfluidic channel can be defined by a microfluidic chip.

[0069] The microfluidic chip can include one or more fluid inlets for injecting fluid into one or more of the microfluidic channels.

[0070] The photon chip and the microfluidic chip can be aligned so as to align the sensing arm of each waveguide interferometer with the sensing region of the corresponding microfluidic channel.

[0071] The microfluidic chip can be configured such that each filtration equipment is located at the same distance from the fluid inlet. This means that when the fluid and the microorganisms are injected into the plurality of microfluidic channels via the fluid inlet, the fluid and the microorganisms should reach the filtration equipment in each microfluidic channel simultaneously.

[0072] The microfluidic chip can be configured such that each well for receiving antibiotics is located at the same distance from the fluid inlet. This means that when the fluid and the microorganisms are injected into the plurality of microfluidic channels via the fluid inlet, the fluid and the microorganisms should reach the wells in each microfluidic channel simultaneously.

[0073] The microfluidic chip can be configured such that each capture device is located at the same distance from the fluid inlet. This means that when the fluid and the microorganisms are injected into the plurality of microfluidic channels via the fluid inlet, the fluid and the microorganisms should reach the capture devices in each microfluidic channel simultaneously.

[0074] The photon chip can define one or more optical outputs, each optical output being connected to an output waveguide of a corresponding waveguide interferometer.

[0075] Each output waveguide can be a single-mode output waveguide.

[0076] The photon chip can define a single optical output.

[0077] The photon chip can define an input waveguide extending from a single optical input. The input waveguide can be a single-mode input waveguide.

[0078] The photon chip can define one or more waveguide couplers or waveguide splitters that connect the input waveguide of the photon chip to the input waveguides of each waveguide interferometer. Using a single optical input can ensure that the ratio of the optical power levels at the inputs of different waveguide interferometers remains stable or constant if the coupling of light from a light source to the single optical input of the photon chip changes or if the output optical power of the light source changes.

[0079] The photon chip can define a reference waveguide, to which one of the optical outputs of the photon chip is connected. The reference waveguide can be a single-mode reference waveguide.

[0080] A waveguide coupler or waveguide splitter can connect the single optical input of the photon chip to the reference waveguide. Such a reference waveguide can be used to monitor fluctuations in the coupling of light from a light source to the single optical input of the photon chip or fluctuations in the output optical power of the light source, and to normalize the light intensity at the outputs of different waveguide interferometers accordingly.

[0081] The single optical input can be located at a first edge of the photon chip and one or more optical outputs can be located at a second edge of the photon chip opposite the first edge.

[0082] The single optical input and one or more optical outputs can be located at the same edge of the photon chip.

[0083] The photon chip can define at least one bend in at least one of the input waveguide, the output waveguide, and the reference waveguide.

[0084] The photonic chip may comprise or be formed of a material that does not absorb at the wavelength of light propagating through each waveguide interferometer.

[0085] The photonic chip may comprise or be formed of at least one of silicon-on-insulator material, silicon dioxide or glass, polymer material, and silicon nitride.

[0086] The photonic chip may be disposable.

[0087] The microfluidic chip may comprise or be formed of at least one of polydimethylsiloxane (PDMS), silicon dioxide or glass, polymer material, silicon, and silicon nitride.

[0088] The microfluidic chip may be disposable.

[0089] According to at least one aspect of the present disclosure, there is provided a sensor device for sensing a change in the concentration of microorganisms, the sensor device comprising:

[0090] A plurality of waveguide interferometers, each waveguide interferometer having a sensing arm and a reference arm; and

[0091] A plurality of microfluidic channels, each channel being configured to accommodate a fluid containing microorganisms,

[0092] Wherein each sensing arm is configured to direct sensing light, each reference arm is configured to direct reference light, and each waveguide interferometer is configured to interfere the corresponding reference light with the corresponding sensing light, and

[0093] Wherein each waveguide interferometer and the corresponding microfluidic channel are configured such that the sensing light of each waveguide interferometer interacts with a greater concentration of microorganisms in the corresponding microfluidic channel than the corresponding reference light,

[0094] Wherein one of the microfluidic channels contains a first microbial growth inhibitory substance, and

[0095] Wherein one or more of the other microfluidic channels contain corresponding microbial growth inhibitory substances different from the first microbial growth inhibitory substance and / or one or more of the other microfluidic channels do not contain any microbial growth inhibitory substance.

[0096] Each microfluidic channel may contain a different microbial growth inhibitory substance.

[0097] Only one microfluidic channel may not contain any microbial growth inhibitory substance.

[0098] One of the microfluidic channels may contain the first microbial growth inhibitory substance at a position upstream of the microfluidic channel located at the corresponding sensing arm.

[0099] One or more of the other microfluidic channels may include a corresponding microbial growth inhibitory substance at a position upstream of the corresponding sensing arm, the corresponding microbial growth inhibitory substance being different from the first antibiotic.

[0100] The sensor device may include capture means in each microfluidic channel for physically capturing microorganisms as the fluid flows along the microfluidic channel so as to concentrate the microorganisms in the corresponding sensing region of the microfluidic channel.

[0101] Each waveguide interferometer and the corresponding microfluidic channel may be configured to allow the sensing light to interact with the fluid and microorganisms in the sensing region of the corresponding microfluidic channel.

[0102] According to at least one aspect of the present disclosure, there is provided a reader device for reading the sensor device as described above, the reader device comprising:

[0103] A light source for emitting light to be coupled into each waveguide interferometer;

[0104] One or more optical detectors for detecting the light output from each waveguide interferometer and generating corresponding electrical signals; and

[0105] A controller for determining a change or rate of change in the concentration of microorganisms in the sensing region of each microfluidic channel based on the evolution of the corresponding electrical signal over time.

[0106] As the concentration of microorganisms in the sensing region of the sensing arm of the waveguide interferometer corresponding to a particular microfluidic channel changes (e.g., due to growth or reduction of microorganisms in the sensing region), the optical path length difference and thus the phase difference between the sensing light and the reference light in the corresponding waveguide interferometer also change. Accordingly, the intensity of the light at the output of each waveguide interferometer may oscillate, and the corresponding electrical signal detected by the corresponding optical detector may oscillate as the concentration of microorganisms in the sensing region of the corresponding microfluidic channel changes (e.g., due to growth or reduction of microorganisms within the sensing region).

[0107] The controller may be configured to determine a change or rate of change in the concentration of microorganisms in the sensing region of the corresponding microfluidic channel based on the oscillation in the corresponding electrical signal.

[0108] The controller may be configured to determine a change or rate of change in the concentration of microorganisms in the sensing region of the corresponding microfluidic channel based on the frequency of the oscillation in the corresponding electrical signal.

[0109] The controller can be configured to determine the change or rate of change of the concentration of microorganisms in the sensing region of the microfluidic channel containing the first microbial growth inhibitory substance relative to the change or rate of change of the concentration of microorganisms in the sensing region of the microfluidic channel containing a different microbial growth inhibitory substance based on the oscillations in the electrical signals corresponding to a microfluidic channel containing the first microbial growth inhibitory substance and the oscillations in the electrical signals corresponding to a microfluidic channel containing a different microbial growth inhibitory substance.

[0110] The controller can be configured to determine the change or rate of change of the concentration of microorganisms in the sensing region of each microfluidic channel containing a microbial growth inhibitory substance relative to the change or rate of change of the concentration of microorganisms in the sensing region of the microfluidic channel containing no microbial growth inhibitory substance based on the oscillations in the electrical signals corresponding to each microfluidic channel containing a microbial growth inhibitory substance and the oscillations in the electrical signals corresponding to the microfluidic channel containing no microbial growth inhibitory substance.

[0111] The light source can include a coherent light source or a single-frequency light source, such as a laser or an optical parametric oscillator (OPO).

[0112] The light source can include a continuous wave (CW) light source.

[0113] The reader device can include a heater for heating the sensor device.

[0114] The reader device can include one or more alignment stages for aligning the light source and / or the optical fibre-pigtail of the light source relative to the sensor device.

[0115] The reader device can include one or more alignment stages for aligning one or more optical detectors relative to the sensor device.

[0116] The reader device can include one or more alignment stages for aligning the sensor device relative to at least one of the light source, the optical fibre-pigtail of the light source, and one or more optical detectors.

[0117] The reader device can include an injection pump for injecting a fluid containing microorganisms into each microfluidic channel. Once the fluid is injected into the microfluidic channel, the flow of the fluid stops. This can prevent any accumulation of microorganisms in any microfluidic channel that is associated with fluid flow and not related to microbial growth.

[0118] According to at least one aspect of the present disclosure, there is provided a sensing system for sensing a change in the concentration of microorganisms, the sensing system including the sensor device as described above and the reader device as described above.

[0119] According to at least one aspect of the present invention, a sensing method for sensing a change in the concentration of microorganisms is provided, the sensing method comprising:

[0120] Causing a fluid containing microorganisms to flow along a microfluidic channel;

[0121] Physically capturing the microorganisms while the fluid flows along the microfluidic channel so as to concentrate the microorganisms in a sensing region of the microfluidic channel;

[0122] Propagating sensing light along a sensing arm of a waveguide interferometer;

[0123] Propagating reference light along a reference arm of the waveguide interferometer; and

[0124] Causing the sensing light to interfere with the reference light,

[0125] wherein the waveguide interferometer and the microfluidic channel are configured such that the sensing light interacts with the microorganisms in the sensing region of the microfluidic channel.

[0126] According to at least one aspect of the present invention, a sensing method for sensing a change in the concentration of microorganisms is provided, the sensing method comprising:

[0127] Causing a fluid containing microorganisms to pass along a plurality of microfluidic channels;

[0128] Propagating sensing light along a sensing arm of each of a plurality of waveguide interferometers;

[0129] Propagating reference light along a reference arm of each of the plurality of waveguide interferometers;

[0130] Causing the sensing light to interfere with the corresponding reference light,

[0131] wherein each waveguide interferometer and the corresponding microfluidic channel are configured such that the sensing light of each waveguide interferometer interacts with a greater concentration of microorganisms in the corresponding microfluidic channel than the corresponding reference light,

[0132] wherein one of the microfluidic channels contains a first microorganism growth inhibitory substance, and

[0133] wherein one or more of the other microfluidic channels contain corresponding microorganism growth inhibitory substances different from the first microorganism growth inhibitory substance and / or one or more of the other microfluidic channels do not contain any microorganism growth inhibitory substance.

[0134] The microorganisms may include bacteria and each microorganism growth inhibitory substance may include an antibiotic. Description of the Drawings

[0135] A system, method, and sensor device for sensing a change in concentration of a microorganism will now be described by way of non-limiting example only with reference to the following drawings, in which:

[0136] Figure 1A is a schematic diagram of a sensing system including a sensor device and a reader device;

[0137] Figure 1B is Figure 1A a schematic plan view of a photon chip of the sensor device of Figure 1A in which a plurality of photodetectors and lasers of the reader device of

[0138] Figure 2A is Figure 1A a schematic view of the underside of the lower layer of a microfluidic chip of the sensor device of

[0139] Figure 2B is Figure 2A a schematic sectional view BB of the lower layer of the microfluidic chip shown in

[0140] Figure 2C is Figure 2A a schematic sectional view AA of the lower layer of the microfluidic chip shown in

[0141] Figure 3A is Figure 1A a schematic view of the underside of the upper layer of a microfluidic chip of the sensor device of

[0142] Figure 3B is Figure 3A a schematic sectional view YY of the upper layer of the microfluidic chip shown in

[0143] Figure 4 is Figure 2A a plan schematic view of the lower layer of a microfluidic chip of Figure 1B and a photon chip of Figure 3A before the upper layer of the microfluidic chip of Figure 2A is positioned above the lower layer of the microfluidic chip of

[0144] Figure 5 is Figure 2A a schematic plan view of a filtration arrangement of the lower layer of a microfluidic chip of

[0145] Figure 6 is for Figure 2A a schematic plan view of an alternative filtration arrangement of the lower layer of a microfluidic chip of

[0146] Figure 7A is in Figure 1B a waveguide interferometer defined on the upper side of a photon chip ofFigure 2A Schematic plan view of corresponding microfluidic channels defined by the lower layer of a microfluidic chip;

[0147] Figure 7B is Figure 7A Detailed schematic plan view of the capture device and sensing area;

[0148] Figure 7C is Figure 7B Schematic XX cross-sectional view;

[0149] Figure 7D is Figure 7B Schematic YY cross-sectional view;

[0150] Figure 8 is for Figure 1A Schematic plan view of the first alternative capture device and sensing area for a sensing device;

[0151] Figure 9 is for Figure 1A Schematic plan view of the second alternative capture device and sensing area for a sensing device;

[0152] Figure 10 is for Figure 1A Schematic plan view of the third alternative capture device and sensing area for a sensing device;

[0153] Figure 11 is for Figure 1A Schematic plan view of the fourth alternative capture device and sensing area for a sensing device; and

[0154] Figure 12 is for Figure 1A Schematic plan view of the fifth alternative capture device and sensing area for a sensing device. Detailed implementation mode

[0155] Although many features of the system and method are described below in specific combinations, those of ordinary skill in the art will understand that many features provide the same effects or advantages described below when used in combinations different from the specific combinations described, and that many features provide the same effects or advantages described below when used separately from any other features described below.

[0156] First, referring to Figure 1A , a sensing system generally labeled 2 is shown in the figure, which is used to sense changes in the concentration of microorganisms in the form of bacteria in a fluid sample in the form of urine, specifically but not exclusively, to sense the sensitivity of bacteria to one or more antibiotics. The sensing system 2 includes a sensor device generally labeled 4 and a reader device generally labeled 6 for reading the sensor device 4.

[0157] The sensor device 4 includes a photonic chip in the form of a disposable silicon-on-insulator photonic chip 8 and a disposable microfluidic chip 10 including or formed of polydimethylsiloxane (PDMS). The microfluidic chip 10 includes a lower layer 10a and an upper layer 10b. The microfluidic chip 10 also includes some absorbent material 11 for absorbing fluid.

[0158] As will be described in more detail below, the features of the photonic chip 8 are aligned with the features of the microfluidic chip 10. Then the upper side 7 of the photonic chip 8 is attached (e.g., bonded) to the lower side 9 of the microfluidic chip 10 to avoid any subsequent misalignment of the features of the photonic chip 8 with the features of the microfluidic chip 10.

[0159] The reader device 6 includes a light source in the form of a single-frequency continuous-wave laser 12 configured to emit light at a wavelength of 1550 nm and a plurality of optical detectors in the form of a plurality of photodiodes 14a, 14b, 14c, 14d, and 14e, where each photodiode 14a, 14b, 14c, 14d, and 14e is configured to detect light at a wavelength of 1550 nm. The reader device 6 also includes one or more alignment stages 18 for aligning the laser 12 relative to the sensor device 4 and one or more alignment stages 19 for aligning the photodiodes 14a, 14b, 14c, 14d, and 14e relative to the sensor device 4. Although not explicitly shown in Figure 1A and Figure 1B it will be understood by those skilled in the art that the reader device 6 may include one or more lenses, such as one or more objective lenses, for coupling the light output from the laser 12 into the photonic chip 8. The reader device 6 also includes a heater 16 for heating the sensor device 4, an injection pump 20, and a section of tubing 22 connecting the injection pump 20 to the fluid inlet of the upper layer 10b of the microfluidic chip 10. The reader device 6 also includes a controller 26. As Figure 1A indicated by the dashed lines in

[0160] Figure 1B A plan view of the photonic chip 8 is shown after the laser 12 and the photodiodes 14a, 14b, 14c, 14d, and 14e are aligned with the sensor device 4. As Figure 1BAs shown in, the photonic chip 8 defines a single-mode input waveguide 29, a plurality of waveguide splitters or Y-junctions 36, a plurality of waveguide interferometers in the form of four identical Mach-Zehnder waveguide interferometers 30a, 30b, 30c, and 30d, a plurality of single-mode output waveguides 31a, 31b, 31c, and 31d, and a single-mode reference waveguide 31e. The photonic chip 8 defines a single optical input 32 at the input of the input waveguide 29 and a plurality of optical outputs 34a, 34b, 34c, 34d, and 34e at the outputs of the output waveguides 31a, 31b, 31c, 31d, and the reference waveguide 31e. The input waveguide 29 connects the single optical input 32 of the photonic chip 8 to the input of the first waveguide splitter or Y-junction 36. The waveguide splitter or Y-junction 36 connects the input waveguide 29 to the inputs of each of the waveguide interferometers 30a, 30b, 30c, and 30d and the input of the reference waveguide 31e. The output of each of the waveguide interferometers 30a, 30b, 30c, and 30d is connected to a corresponding one of the optical outputs 34a, 34b, 34c, and 34d via a corresponding one of the output waveguides 31a, 31b, 31c, and 31d.

[0161] As Figure 2A - Figure 2C shown in, the lower side 41 of the lower layer 10a of the microfluidic chip 10 defines a plurality of microfluidic channels in the form of four microfluidic channels 40a, 40b, 40c, and 40d. The lower layer 10a of the microfluidic chip 10 also defines a fluid inlet in the form of a through-hole 42 and a plurality of fluid outlets in the form of a plurality of through-holes 44a, 44b, 44c, and 44d. Each of the fluid inlet 42 and the fluid outlets 44a, 44b, 44c, and 44d extends from the lower side of the lower layer 10a to the upper side 43 of the lower layer 10a. The lower layer 10a of the microfluidic chip 10 also defines a fluid manifold 45 connected to the fluid inlet 42. Each of the microfluidic channels 40a, 40b, 40c, and 40d extends from the fluid manifold 45 to a corresponding one of the fluid outlets 44a, 44b, 44c, and 44d. The lower layer 10a of the microfluidic chip 10 also defines filtration means 46a, 46b, 46c, and 46d for capturing debris or particles larger than bacteria, wells in the form of grooves 47a, 47b, 47c, and 47d located downstream of the filtration means 46a, 46b, 46c, and 46d, and capture means 48a, 48b, 48c, and 48d for capturing bacteria located downstream of the grooves 47a, 47b, 47c, and 47d in each of the microfluidic channels 40a, 40b, 40c, and 40d. As Figure 2AAs indicated, the microfluidic channels 40b, 40c, and 40d contain different microbial growth inhibitory substances in the form of different antibiotics in the corresponding grooves 47b, 47c, and 47d. Specifically, each of the grooves 47b, 47c, 47d contains a corresponding different dried antibiotic formed by dispensing (e.g., pipetting) the relevant antibiotic in solution into the grooves 47b, 47c, 47d and allowing the solution to dry. The groove 47a of the microfluidic channel 40a does not contain any antibiotic.

[0162] As Figure 3A and Figure 3B shown in, the upper layer 10b of the microfluidic chip 10 defines a fluid inlet in the form of a through-hole 50 and another fluid outlet in the form of a through-hole 52. The lower side 51 of the upper layer 10b of the microfluidic chip 10 defines a groove 54 that can be used as a fluid collection container. The fluid outlet 52 extends from the groove 54 on the lower side 51 of the upper layer 10b to the upper side 53 of the upper layer 10b. When the upper layer 10b of the microfluidic chip 10 is aligned with the lower layer 10a of the microfluidic chip 10 and the lower side 51 of the upper layer 10b is deployed towards the upper side 43 of the lower layer 10a, the fluid inlets 50 and 42 of the upper layer 10b and the lower layer 10a are respectively aligned, and the groove 54 defined in the lower side 51 of the upper layer 10b is aligned with the fluid outlets 44a, 44b, 44c, and 44d at the upper side 43 of the lower layer 10a to allow the groove 54 to receive fluid from each of the fluid outlets 44a, 44b, 44c, and 44d. As will be described in more detail below, an injection pump 20 is used to inject a fluid containing bacteria into the fluid inlets 50 and 42, flow along the microfluidic channels 40a, 40b, 40c, and 40d and out through the fluid outlets 44a, 44b, 44c, and 44d, into the groove 54, and then from the groove 54 to the fluid outlet 52, whereby any excess fluid is absorbed by the absorbent material 11.

[0163] Now refer to Figure 4 , a plan view is shown of the alignment of the lower layer 10a of the microfluidic chip 10 with the photon chip 8 after injecting a fluid 60 containing bacteria 62 into each of the microfluidic channels 40a, 40b, 40c, and 40d via the fluid inlet 42. As Figure 4 shown in, the capture devices 48a, 48b, 48c, and 48d of each of the microfluidic channels 40a, 40b, 40c, and 40d are generally respectively aligned with the corresponding sensing arms of the corresponding ones of the waveguide interferometers 30a, 30b, 30c, and 30d.

[0164] Now refer to Figure 5 , a plan view is shown of the region of the microfluidic channel 40a near the corresponding filtering device 46a. As Figure 4As shown, the filtration device 46a includes a plurality of pillars 70 extending into the microfluidic channel 40a and defining a plurality of gaps, where the size of each gap is larger than the bacteria 62 contained in the fluid 60. Specifically, each gap is larger than the maximum size of the bacteria 62. Those of ordinary skill in the art will understand that the other filtration devices 46b, 46c, and 46d in the other microfluidic channels 40b, 40c, and 40d are the same as the filtration device 46a.

[0165] Now referring to Figure 7A , a detailed view of the corresponding regions of the waveguide interferometer 30a and the microfluidic channel 40a is shown. As Figure 7A shown, the waveguide interferometer 30a includes a single-mode waveguide sensing arm 80a and a single-mode waveguide reference arm 82a. A section of the sensing arm 80a is folded to define three parallel waveguide portions to increase the interaction length between the light in the sensing arm 80a and the bacteria 62 in the fluid 60 in the microfluidic channel 40a. Similarly, a section of the reference arm 82a is folded to define three parallel waveguide portions. Although not explicitly shown in Figure 7A , those skilled in the art will understand that the sensing arm 80a and the reference arm 82a are unbalanced (i.e., the sensing arm 80a and the reference arm 82a have different optical lengths) to improve the measurement sensitivity.

[0166] The capture device 48a includes two rows of staggered capturers 84a, which are located near and downstream of the folded section of the sensing arm 80a in the flow of the fluid 60. Each capturer 84a is configured to physically capture the bacteria 62 when the fluid 60 flows along the microfluidic channel 40a. Specifically, as Figure 7C and Figure 7D shown, each capturer 84a includes one or more features extending into the microfluidic channel 40a to define a compartment 86a in the microfluidic channel 40a for accommodating one or more bacteria 62. Each capturer 84a also defines a gap 87a between the capturer 84a and the upper surface 7 of the photon chip 8, and the gap 87a is configured to allow the fluid 60 in the microfluidic channel 40a to flow under the capturer 84a but prevent the bacteria 62 from passing under the capturer 84a. Without wishing to be bound by theory, it may be the case that the fluid flowing through the bacteria 62 captured in the capturer 84a and passing through the gap 87a between the capturer 84a and the upper surface 7 of the photon chip 8 will cause the fluid 60 to exert a downward force on the bacteria 62 captured in the capturer 84a, and this downward force can be used to fix the bacteria 62 captured in the capturer 84a on the upper surface 7 of the photon chip 8. As can be seen from Figure 7B , Figure 7C and Figure 7DIt will be appreciated that, in use, the capture device 48a is used to concentrate the bacteria 62 in the sensing region 88a of the microfluidic channel 40a, which sensing region 88a is located above the folded section of the sensing arm 80a.

[0167] Those of ordinary skill in the art will understand that the waveguide interferometers 30b, 30c, and 30d are the same as the waveguide interferometer 30a described in the reference Figure 7A Specifically, each of the waveguide interferometers 30b, 30c, and 30d includes a sensing arm 80b, 80c, and 80d and a reference arm 82b, 82c, and 82d, respectively. Each of the sensing arms 80b, 80c, and 80d has a corresponding folded section. Similarly, each of the reference arms 82b, 82c, and 82d has a corresponding folded section. Each of the other microfluidic channels 40b, 40c, and 40d defines a corresponding capture device 48b, 48c, and 48d, respectively. Each of the capture devices 48b, 48c, and 48d is the same as the capture device 48a described in the reference Figure 7B , Figure 7C and Figure 7D and is used to concentrate the bacteria 62 in the corresponding sensing regions 88b, 88c, and 88d located above the folded sections of the corresponding sensing arms 80b, 80c, and 80d, respectively.

[0168] In use, a urine sample (required <1 ml) is mixed with a biological growth medium powder (here Mueller Hinton Broth, at a concentration of 21 mg / ml, but other media can also be used) in a test tube and inverted several times. The medium powder is used to promote the growth of bacteria in the urine and buffer the chemical and pH differences between urine samples. Then the urine / media solution 60, 62 is aspirated into a syringe and connected to the microfluidic chip 10 via a flat syringe needle and a flexible tube 22, and the flexible tube 22 is connected to the fluid inlet 50 of the upper layer 10b of the microfluidic chip 10. Before stopping the flow, the injection pump 20 pumps the urine / media solution 60, 62 into the microfluidic channels 40a, 40b, 40c, and 40d of the microfluidic chip 10.

[0169] As urine / culture medium solutions 60, 62 enter the microfluidic channels 40a, 40b, 40c, and 40d, the filtration devices 46a, 46b, 46c, and 46d capture any debris larger than the bacteria 62 within the urine / culture medium solutions 60, 62, the dried antibiotics 49b, 49c, and 49d reconstitute in the urine / culture medium solutions 60, 62 within the microfluidic channels 40b, 40c, and 40d, and any bacteria 62 present in the urine / culture medium solutions 60, 62 are physically captured via the capture devices 48a, 48b, 48c, and 48d within the sensing regions 88a, 88b, 88c, and 88d respectively located above the sensing arms 80a, 80b, 80c, and 80d of the corresponding waveguide interferometers 30a, 30b, 30c, and 30d. Any non-bacterial material entering the capture devices 48a, 48b, 48c, and 48d can cause an initial change in the intensity of light at the output of the waveguide interferometers 30a, 30b, 30c, and 30d during fluid flow, but does not contribute to the dynamic change in the intensity of light at the output of the waveguide interferometers 30a, 30b, 30c, and 30d due to the growth of bacteria over time.

[0170] In use, those of ordinary skill in the art will understand that the sensor device 4 can have a standard form factor and the reader device 6 can include one or more reference features relative to which the sensor device 4 can be aligned to achieve an initial rough alignment between the sensor device 4 and the reader device 6. The controller 26 of the reader device 6 then controls the alignment stages 18, 19 to actively align the laser 12 to the sensor device 4 and to actively align the plurality of photodiodes 14a, 14b, 14c, 14d, and 14e to the sensor device 4. Specifically, in the case where the laser 12 emits single-frequency continuous-wave (CW) light at 1550 nm, the controller 26 controls the alignment stages 18, 19 to maximize the value of the electrical signal generated by the photodiode 14e corresponding to the reference waveguide 31.

[0171] The heater 16 maintains the temperature of the sensor device 4 at the optimal growth temperature of 37 °C, and the bacteria captured in the sensing regions 88a, 88b, 88c, and 88d grow in the urine / culture medium powder mixture. The growth of the bacteria respectively changes the effective refractive index of the sensing arms 80a, 80b, 80c, and 80d of each of the waveguide interferometers 30a, 30b, 30c, and 30d, thus respectively causing an optical phase change relative to the corresponding reference arms 82a, 82b, 82c, and 82d. The light from the laser 12 passes through each of the waveguide interferometers 30a, 30b, 30c, and 30d and is respectively measured by the corresponding photodetectors 14a, 14b, 14c, and 14d.

[0172] The laser 12 emits light with transverse magnetic (TM) polarization because it has been found that this polarization provides maximum measurement sensitivity and better manufacturing tolerances. When the optical phase on the sensing arms 80a, 80b, 80c, 80d changes due to bacterial growth, this causes an intensity change at the waveguide output of each waveguide interferometer 30a, 30b, 30c, and 30d respectively due to the interference between the light propagating in each sensing arm 80a, 80b, 80c, 80d and the light propagating in the corresponding reference arms 82a, 82b, 82c, 82d.

[0173] Although the reference arms 82a, 82b, 82c, and 82d of each waveguide interferometer 30a, 30b, 30c, and 30d are exposed to the fluid 60 and the bacteria 62 such that the light propagating along the reference arms 82a, 82b, 82c, and 82d can interact with the fluid 60 and the bacteria 62 in the corresponding microfluidic channels 40a, 40b, 40c, and 40d, the bacterial concentration near the reference arms 82a, 82b, 82c, and 82d is much lower than the bacterial concentration near the sensing regions of the corresponding sensing arms 80a, 80b, 80c, and 80d because there is no capture device in the reference arms 82a, 82b, 82c, and 82d. Exposing the sensing arms 80a, 80b, 80c, and 80d and the reference arms 82a, 82b, 82c, and 82d of each waveguide interferometer 30a, 30b, 30c, and 30d to the fluid 60 and the bacteria 62 in this way helps to improve the measurement immunity to any changes in the bulk refractive index of the fluid and the bacteria that are not caused by bacterial growth.

[0174] If the bacteria 62 grow in any of the sensing regions 88a, 88b, 88c, and 88d, then the phase and thus the intensity at the output of the corresponding waveguide interferometers 30a, 30b, 30c, and 30d change over time. The intensity measured by the photodiodes 14a, 14b, 14c, and 14d traces a series of fringes or oscillations corresponding to the optical interference pattern as the bacteria grow. The frequency of these fringes depends on the number and growth rate of the bacteria. If the bacteria are sensitive to the antibiotics 49b, 49c, 49d reconstituted in the corresponding microfluidic channels 40b, 40c, 40d, then the bacteria in the relevant microfluidic channels 40b, 40c, 40d stop growing and the rate of intensity change associated with the relevant microfluidic channels 40b, 40c, 40d decreases relative to the rate of intensity change associated with the reference microfluidic channel 40a that does not contain any antibiotics. In fact, as the phase shift in the sensing arms 80b, 80c, 80d corresponding to the relevant microfluidic channels 40b, 40c, 40d of the waveguide interferometers 30b, 30c, 30d slows down or stops, this results in a decrease in the frequency and / or flattening of the intensity fringes or oscillations.

[0175] The sensor device 4 is designed such that in addition to the reference microfluidic channel 40a without antibiotics, multiple antibiotics 49b, 49c, 49d can be tested simultaneously. The controller 26 of the reader device 6 can then determine the most effective or most suitable antibiotic based on the electrical signals generated by the photodetectors 14a, 14b, 14c, and 14d. Specifically, the controller 26 compares the frequency, magnitude, and / or shape of the stripes or oscillations in the electrical signals corresponding to the microfluidic channels 40b, 40c, and 40d with the frequency, magnitude, and / or shape of the stripes or oscillations in the electrical signal corresponding to the reference microfluidic channel 40a without antibiotics. The controller 26 identifies the most effective or most suitable antibiotic as the antibiotic corresponding to the electrical signal with the lowest oscillation frequency in the microfluidic channel. Those of ordinary skill in the art will understand that measuring the relative growth or decline of bacteria in the presence of one or more different antibiotics as described above using such a sensor device 4 with waveguide interferometers 30a, 30b, 30c, and 30d does not require the reader device 6 to have a spectrometer or a tunable light source, thus allowing the use of a relatively simple disposable sensor device 4 and a relatively simple reading device 6 to perform rapid measurements of different bacterial efficacies.

[0176] Reference Figure 6 , shows an alternative filtering arrangement 146a used in the microfluidic channel 40a, which replaces the reference Figure 5 described filtering arrangement 46a. As Figure 6 shown, the alternative filtering arrangement 146a includes multiple rows of staggered posts 70 that extend into the microfluidic channel 40a defining multiple gaps, where the size of each gap is greater than the bacteria 62 contained in the fluid 60. Specifically, each gap is greater than the maximum size of the bacteria 62. Those of ordinary skill in the art will understand that the other microfluidic channels 40b, 40c, and 40d can have the same alternative filtering arrangement as the alternative filtering arrangement 146a.

[0177] Reference Figure 8 , shows a first alternative capture arrangement 148a used in the microfluidic channel 40a, which replaces the reference Figure 7B , Figure 7C and Figure 7D described capture arrangement 48a. As Figure 8As shown, the first alternative capture device 148a defines a plurality of capturers 184a that are located near and downstream of the folded section of the sensing arm 80a in the flow of the fluid 60. Each capturer 184a is configured to physically capture bacteria 62 as the fluid 60 flows along the microfluidic channel 40a. Each capturer 184a includes one or more features extending into the microfluidic channel 40a to define a corresponding compartment in the microfluidic channel 40a to accommodate one or more bacteria 62. Each capturer 184a also defines a gap between the capturer 84a and the upper surface 7 of the photon chip 8, and this gap is configured to allow the fluid 60 in the microfluidic channel 40a to flow through the gap below the capturer 184a but prevent the bacteria 62 from passing through the gap below the capturer 184a. In use, the capture device 148a is used to concentrate the bacteria 62 in the sensing region 88a of the microfluidic channel 40a, and this sensing region 88a is located above the folded section of the sensing arm 80a. Corresponding capture devices identical to the capture device 148a can be provided in other microfluidic channels 40b, 40c, and 40d to concentrate the bacteria 62 in the corresponding sensing regions 88b, 88c, and 88d of the other microfluidic channels 40b, 40c, and 40d.

[0178] Reference Figure 9 , a second alternative capture device 248a used in the microfluidic channel 40a is shown, which replaces the capture device 48a described in reference Figure 7B , Figure 7C and Figure 7D described. As Figure 9As shown, the second alternative capture device 248a defines three rows of staggered capturers 284a that are aligned with the folded section of the sensing arm 80a. Specifically, each row of capturers 284a is generally aligned with one of the waveguide sections in the folded section of the sensing arm 80a. Each capturer 284a is configured to physically capture bacteria 62 as the fluid 60 flows along the microfluidic channel 40a. Each capturer 284a includes one or more features extending into the microfluidic channel 40a to define a corresponding compartment in the microfluidic channel 40a to accommodate one or more bacteria 62. Each capturer 284a also defines a gap between the capturer 284a and the upper surface 7 of the photon chip 8, which is configured to allow the fluid 60 in the microfluidic channel 40a to flow through the gap below the capturer 284a but prevent the bacteria 62 from passing through the gap below the capturer 284a. In use, the capture device 248a is used to concentrate the bacteria 62 in the sensing region 88a of the microfluidic channel 40a, which is located above the folded section of the sensing arm 80a. Corresponding capture devices identical to the capture device 248a can be provided in other microfluidic channels 40b, 40c, and 40d to concentrate the bacteria 62 in the corresponding sensing regions 88b, 88c, and 88d of the other microfluidic channels 40b, 40c, and 40d.

[0179] Reference Figure 10 , a third alternative capture device 348a used in the microfluidic channel 40a is shown, which replaces the reference Figure 7B , Figure 7C and Figure 7D described capture device 48a. As Figure 10As shown, the third alternative capture device 348a defines a single-row catcher 384a aligned with the folded section of the sensing arm 80a. Specifically, each catcher 384a extends through all three waveguide sections in the folded section of the sensing arm 80a in the direction of fluid flow. Each catcher 384a is configured to physically capture bacteria 62 when the fluid 60 flows along the microfluidic channel 40a. Each catcher 384a includes one or more features extending into the microfluidic channel 40a to define a corresponding compartment in the microfluidic channel 40a to accommodate one or more bacteria 62. Each catcher 384a also defines a gap between the catcher 384a and the upper surface 7 of the photon chip 8, which is configured to allow the fluid 60 in the microfluidic channel 40a to flow through the gap below the catcher 384a but prevent the bacteria 62 from passing through the gap below the catcher 384a. In use, the capture device 348a is used to concentrate the bacteria 62 in the sensing region 88a of the microfluidic channel 40a, which is located above the folded section of the sensing arm 80a. Corresponding capture devices identical to the capture device 348a can be provided in other microfluidic channels 40b, 40c, and 40d to concentrate the bacteria 62 in the corresponding sensing regions 88b, 88c, and 88d of the other microfluidic channels 40b, 40c, and 40d.

[0180] Reference Figure 11 , a fourth alternative capture device 448a used in the microfluidic channel 40a is shown, which replaces the reference Figure 7B , Figure 7C and Figure 7D described capture device 48a. As Figure 11 shown, the fourth alternative capture device 448a defines a row of capture features 484a, which are located near and downstream of the folded section of the sensing arm 80a in the flow of the fluid 60. The adjacent capture features 484a define a gap therebetween, which is configured to allow the fluid 60 in the microfluidic channel 40a to flow through the gap but prevent the bacteria 62 from passing through the gap. Each capture feature 484a also defines a gap between the capture feature 484a and the upper surface 7 of the photon chip 8, which is configured to allow the fluid 60 in the microfluidic channel 40a to flow through the gap below the capture feature 484a but prevent the bacteria 62 from passing through the gap below the capture feature 484a. In use, the capture device 448a is used to concentrate the bacteria 62 in the sensing region 88a of the microfluidic channel 40a, which is located above the folded section of the sensing arm 80a. Corresponding capture devices identical to the capture device 448a can be provided in other microfluidic channels 40b, 40c, and 40d to concentrate the bacteria 62 in the corresponding sensing regions 88b, 88c, and 88d of the other microfluidic channels 40b, 40c, and 40d.

[0181] ReferenceFigure 12 , shows a fifth alternative capture device 548a for use in microfluidic channel 40a, which replaces reference Figure 7B , Figure 7C and Figure 7D The capture device 48a described. Figure 12 As shown in , the fifth alternative capture equipment 548a defines a continuous capture feature 584a, which is located near and downstream of the folded section of the sensing arm 80a in the flow of the fluid 60. The capture feature 584a defines a gap between the capture feature 584a and the upper surface 7 of the photonic chip 8, which is configured to allow the fluid 60 in the microfluidic channel 40a to flow through the gap below the capture feature 584a but prevent bacteria 62 from passing through the gap below the capture feature 584a. In use, the capture equipment 548a is used to concentrate the bacteria 62 in the sensing area 88a of the microfluidic channel 40a, which is located above the folded section of the sensing arm 80a. The corresponding capture equipment identical to the capture equipment 548a can be provided in the other microfluidic channels 40b, 40c and 40d so as to concentrate the bacteria 62 in the corresponding sensing areas 88b, 88c and 88d of the other microfluidic channels 40b, 40c and 40d.

[0182] It will be appreciated by those skilled in the art that various modifications to the above described systems and methods are possible. For example, rather than using a pipette to dispense antibiotics 49b, 49c, and 49d in solution into corresponding wells or recesses 47b, 47c, and 47d in corresponding microfluidic channels 40b, 40c, and 40d, one or more of antibiotics 49b, 49c, and 49d may be dispensed by inkjet printing and allowed to dry.

[0183] Although the reference arms 82a, 82b, 82c, and 82d of each waveguide interferometer 30a, 30b, 30c, and 30d are exposed to the fluid 60 and bacteria 62 such that light propagating along the reference arms 82a, 82b, 82c, and 82d can interact with the fluid 60 and bacteria 62 in the corresponding microfluidic channels 40a, 40b, 40c, and 40d, the sensing device 4 can be configured to prevent the reference arms 82a, 82b, 82c, and 82d of each waveguide interferometer 30a, 30b, 30c, and 30d from being exposed to the fluid 60 and bacteria 62 to prevent light propagating along the reference arms 82a, 82b, 82c, and 82d from interacting with the fluid 60 and bacteria 62 in the corresponding microfluidic channels 40a, 40b, 40c, and 40d. For example, the sensor device 4 can include a cover layer or mask that prevents the reference arms 82a, 82b, 82c, and 82d from being exposed to the fluid 60 and bacteria 62 so as to prevent light propagating along the reference arms 82a, 82b, 82c, and 82d from interacting with the fluid 60 and bacteria 62 in the corresponding microfluidic channels 40a, 40b, 40c, and 40d while still exposing the sensing arms 80a, 80b, 80c, and 80d to the fluid 60 containing bacteria 62 to allow light propagating along the sensing arms 80a, 80b, 80c, and 80d to interact with the fluid 60 and bacteria 62 in the corresponding microfluidic channels 40a, 40b, 40c, and 40d. Preventing the reference arms 82a, 82b, 82c, and 82d of each waveguide interferometer 30a, 30b, 30c, and 30d from being exposed to the fluid 60 and bacteria 62 in this way can improve measurement sensitivity but reduce the measurement immunity to any changes in the bulk refractive index of the fluid and bacteria that are not caused by bacterial growth.

[0184] Although the photon chip 8 is defined using a silicon-on-insulator material system, the photon chip 8 can include or be formed from a photonics material system that includes, but is not limited to, silica or glass, polymers, silicon nitride, and the like.

[0185] Although the photon chip 8 was described above as defining a waveguide splitter or Y-junction for connecting a single optical input 32 to the input of each of the waveguide interferometers 30a, 30b, 30c, and 30d, the photon chip 8 can alternatively define a directional coupler for connecting a single optical input 32 to the input of each of the waveguide interferometers 30a, 30b, 30c, and 30d. Alternatively, the photon chip 8 can define a multimode interference (MMI) splitter for connecting a single optical input 32 to the input of each of the waveguide interferometers 30a, 30b, 30c, and 30d. The MMI splitter can be more compact than using a splitter, Y-junction, or directional coupler.

[0186] The photon chip 8 may define a mode converter or a spot size converter for converting the optical field of light incident on the photon chip 8 into an optical field having a mode distribution that more closely matches the mode distribution associated with the waveguide splitter and the waveguide interferometer.

[0187] The photon chip 8 may define a grating input coupler for coupling light from a laser into the photon chip 8. The photon chip 8 may define one or more grating output couplers for coupling light from the photon chip 8 into the photodiodes 14a, 14b, 14c, 14d, and 14e.

[0188] Although the photon chip 8 has been described above as having a single optical input 32 located at a first edge of the photon chip 8 and a plurality of optical outputs 34a, 34b, 34c, 34d, and 34e located at a second edge of the photon chip 8 opposite the first edge, the optical input 32 and the plurality of optical outputs 34a, 34b, 34c, 34d, and 34e may be located at the same edge of the photon chip 8 and the photon chip 8 may accordingly define at least one of an input waveguide 29, output waveguides 31a, 31b, 31c, 31d, and a reference waveguide 31e. For example, the photon chip 8 may define at least one bend in at least one of the input waveguide 29, output waveguides 31a, 31b, 31c, 31d, and the reference waveguide 31e such that the optical input 32 and the plurality of optical outputs 34a, 34b, 34c, 34d, and 34e are located at the same edge of the photon chip 8. Such a chip arrangement may allow the laser 12 and the photodiodes 14a, 14b, 14c, 14d, and 14e to be mounted on the same set of alignment stages. This may reduce the number of alignment stages required and / or simplify the alignment between the reader device 6 and the photon chip 8. In an alternative variant, the photon chip 8 may be mounted on a set of alignment stages and the photon chip 8 may be moved relative to the laser 12 and the photodiodes 14a, 14b, 14c, 14d, and 14e.

[0189] Although the sensing arms 80a, 80b, 80c, 80d and corresponding reference arms 82a, 82b, 82c, 82d of each waveguide interferometer 30a, 30b, 30c and 30d are described above as being unbalanced (i.e., having different optical lengths) to improve measurement sensitivity, those skilled in the art will understand that the sensing arms 80a, 80b, 80c, 80d and corresponding reference arms 82a, 82b, 82c, 82d of each waveguide interferometer 30a, 30b, 30c and 30d can be balanced (i.e., having the same optical length). In terms of thermal stability, it is better to use such balanced sensing arms and reference arms, that is, using balanced sensing arms and reference arms can reduce any change in the intensity of light at the output of the waveguide interferometer due to temperature changes. Using balanced sensing arms and reference arms also helps to cancel out any refractive index changes that are not caused by changes in the concentration of bacteria in the sensing region. For example, when the waveguide interferometer and the microfluidic channel are configured to allow the reference light to interact with the fluid and bacteria in the microfluidic channel, using balanced sensing arms and reference arms can also help to cancel out any refractive index changes of the fluid that are not caused by changes in the concentration of bacteria in the sensing region.

[0190] The laser 12 may include one or more lenses for collimating the light output from the laser 12.

[0191] The reader device 6 may include one or more lenses, such as one or more objective lenses, for coupling the light output from the laser 12 to a single optical input 32 of the photon chip 8.

[0192] The laser 12 may include a housing or body and an output fiber pigtail extending from the housing or body. One or more alignment stages may be configured to move the output fiber pigtail relative to the photon chip without moving the housing or body of the laser.

[0193] The fiber pigtail may include or be formed of polarization-maintaining (PM) fiber. The use of PM fiber may allow control of the polarization of the light coupled into the photon chip 8.

[0194] The reader device 6 may include a fiber collimator arrangement for collimating the light output from the fiber pigtail and a lens (such as an objective lens) for focusing the light output from the fiber collimator arrangement into the input waveguide of the photon chip 8.

[0195] The reader device 6 may include a polarizer located between the fiber collimator arrangement and the lens for polarizing or further polarizing the light output from the fiber collimator arrangement.

[0196] Although the laser 12 emits single-frequency continuous-wave light with a wavelength of 1550 nm, the single-frequency continuous-wave light can have any other suitable wavelength.

[0197] Although the laser 12 is used to emit single-frequency continuous-wave light, any light source capable of emitting coherent CW light can be used. For example, an optical parametric oscillator (OPO) can be used.

[0198] Although the microfluidic chip 10 is defined using PDMS, the microfluidic chip 10 can include or be formed of silica or glass, polymers, silicon, silicon nitride, etc.

[0199] Rather than the lower layer 10a of the microfluidic chip 10 defining wells in the form of grooves 47a, 47b, 47c, 47d between the filtration devices 46a, 46b, 46c, 46d and the capture devices 48a, 48b, 48c, 48d in each of the microfluidic channels 40a, 40b, 40c, 40d as shown in Figure 2A , 2B and 2C, the lower layer 10a of the microfluidic chip 10 can define wells in the form of through-holes for loading antibiotics, where the through-holes extend through the lower layer 10a of the microfluidic chip 10 at positions between the filtration devices 46a, 46b, 46c, 46d and the capture devices 48a, 48b, 48c, 48d in each of the microfluidic channels 40a, 40b, 40c, 40d. Once the lower layer 10a of the microfluidic chip 10 is bonded to the photon chip 8, the antibiotics 49b, 49c, 49d can be loaded into one or more of the microfluidic channels 40b, 40c, 40d via such through-holes, and the through-holes can be sealed when the upper layer 10b of the microfluidic chip 10 is subsequently placed on top of the lower layer 10a of the microfluidic chip 10. Using such through-holes for loading antibiotics avoids any requirement to load any antibiotics into the grooves 47b, 47c, 47d in the lower layer 10a of the microfluidic chip 10 before the lower layer 10a of the microfluidic chip 10 is bonded to the photon chip 8. This can be advantageous as it can avoid any alteration, damage, and / or contamination of the antibiotics 49b, 49c, 49d that would otherwise occur if the antibiotics 49b, 49c, 49d were loaded into the grooves 47b, 47c, 47d in the lower layer 10a before the lower layer 10a of the microfluidic chip 10 is bonded to the photon chip 8.

[0200] Antibiotics 49b, 49c, and 49d can be introduced as fluids into each well. Antibiotics 49b, 49c, and 49d can be introduced before and / or during measurement of bacterial growth. The microfluidic chip 10 can be configured such that each well can receive a corresponding one of antibiotics 49b, 49c, and 49d from a respective container, tube, or reservoir of antibiotics 49b, 49c, and 49d. For example, the microfluidic chip 10 can define separate fluid inlets for each of the antibiotics 49b, 49c, and 49d to allow each of the antibiotics 49b, 49c, and 49d to be injected or dispensed as a fluid separately into corresponding microfluidic channels 40b, 40c, and 40d.

[0201] Rather than using the upper layer 10b of the microfluidic chip 10 that defines the through-hole 50 and aligning the upper layer 10b of the microfluidic chip 10 with the lower layer 10a of the microfluidic chip 10 such that the through-hole 50 is aligned with the fluid inlet 42 defined by the lower layer 10a of the microfluidic chip 10, the upper layer 10b of the microfluidic chip 10 can have a different size and / or shape from the lower layer 10a of the microfluidic chip 10 such that when the upper layer 10b of the microfluidic chip 10 is aligned with the lower layer 10a of the microfluidic chip 10, the upper layer 10b of the microfluidic chip 10 does not extend through the fluid inlet 42 defined by the lower layer 10a of the microfluidic chip 10.

[0202] The fluid reservoir 54 can be large enough to accommodate a limited excess volume of the fluid 60 when the fluid 60 and the bacteria 62 are injected into the microfluidic channels 40a, 40b, 40c, and 40d of the microfluidic chip 10. This can obviate any requirement for using absorbent material 11.

[0203] The lower layer 10a of the microfluidic chip 10 can be configured such that each of the filtration devices 46a, 46b, 46c, and 46d is located at the same distance from the fluid inlet 42. This means that when the fluid 60 and the bacteria 62 are injected into the microfluidic channels 40a, 40b, 40c, and 40d via the fluid inlet 42, the fluid 60 and the bacteria 62 should reach the filtration devices 46a, 46b, 46c, and 46d in each of the microfluidic channels 40a, 40b, 40c, and 40d simultaneously.

[0204] The lower layer 10a of the microfluidic chip 10 can be configured such that each of the grooves or wells 47a, 47b, 47c, and 47d is located at the same distance from the fluid inlet 42. This means that when the fluid 60 and the bacteria 62 are injected into the microfluidic channels 40a, 40b, 40c, and 40d via the fluid inlet 42, the fluid 60 and the bacteria 62 should reach the grooves or wells 47a, 47b, 47c, and 47d in each of the microfluidic channels 40a, 40b, 40c, and 40d simultaneously.

[0205] The lower layer 10a of the microfluidic chip 10 can be configured such that each capture device 48a, 48b, 48c, 48d is located at the same distance from the fluid inlet 42. This means that when the fluid 60 and bacteria 62 are injected via the fluid inlet 42 into the microfluidic channels 40a, 40b, 40c, 40d, the fluid 60 and bacteria 62 should reach the capture devices 48a, 48b, 48c, 48d in each of the microfluidic channels 40a, 40b, 40c, 40d simultaneously.

[0206] The lower layer 10a of the photon chip 8 and the microfluidic chip 10 can be configured such that the sensing arms 80a, 80b, 80c, 80d of each waveguide interferometer 30a, 30b, 30c, 30d are aligned relative to the corresponding capture devices 48a, 48b, 48c, 48d, such that the sensing light in the sensing arms 80a, 80b, 80c, 80d can interact with the fluid 60 and bacteria 62 in the corresponding sensing regions 88a, 88b, 88c, 88d of the microfluidic channels 40a, 40b, 40c, 40d, respectively.

[0207] Rather than mixing the fluid sample with the biological growth medium powder before injecting them into the microfluidic chip 10, the medium powder can be dried or formed on the microfluidic chip 10 in the same manner as the antibiotics, e.g., together with the antibiotics 49b, 49c, 49d at the corresponding grooves or wells 47b, 47c, 47d or at the fluid inlet 42.

[0208] Biological growth medium powders other than the Mueller-Hinton medium can be used to promote bacterial growth. For example, the L-broth biological growth medium powder can be used.

[0209] Although the sensing system, method, and sensor device have been described above in the context of measuring the sensitivity of bacteria in a urine sample to different antibiotics, the sensing system, method, and sensor device can be used to measure the sensitivity of bacteria in any body fluid to different antibiotics. For example, the sensing system, method, and sensor device can be used to measure the sensitivity of bacteria in blood, saliva, sputum, etc. to different antibiotics.

[0210] Although the sensing system, method, and sensor device have been described above in the context of measuring the sensitivity of bacteria in a urine sample to different antibiotics, the sensing system, method, and sensor device can be used to measure the sensitivity of any microorganism in any fluid to different microbial growth inhibitory substances. For example, the sensing system, method, and sensor device can be used to measure the sensitivity of fungi or algae in any fluid to different microbial growth inhibitory substances.

Claims

1. A sensor device for sensing a change in the concentration of microorganisms, the sensor device comprising: A waveguide interferometer having a sensing arm and a reference arm; A microfluidic channel for a fluid containing microorganisms; And Capture means in the microfluidic channel for physically capturing the microorganisms as the fluid flows along the microfluidic channel so as to concentrate the microorganisms in a sensing region of the microfluidic channel, wherein the capture means in each microfluidic channel defines one or more gaps configured to allow fluid to flow through the capture means but prevent the microorganisms from passing through the capture means, Wherein the sensing arm is configured to guide sensing light, the reference arm is configured to guide reference light, and the waveguide interferometer is configured to interfere the sensing light with the reference light, and Wherein the waveguide interferometer and the microfluidic channel are configured to allow the sensing light to interact with the fluid and the microorganisms in the sensing region of the microfluidic channel.

2. The sensor device according to claim 1, wherein the sensing arm comprises an optical waveguide, the reference arm comprises an optical waveguide, and the sensing light and the reference light each comprise a guided optical mode.

3. The sensor device according to claim 1 or 2, wherein the waveguide interferometer and the microfluidic channel are configured to allow the reference light to interact with the fluid and the microorganisms in the microfluidic channel, and / or wherein the waveguide interferometer and the microfluidic channel are configured to expose the reference arm of the waveguide interferometer to the fluid and the microorganisms.

4. The sensor device according to claim 1 or 2, wherein the waveguide interferometer and the microfluidic channel are configured to prevent the reference light from interacting with the fluid and the microorganisms in the microfluidic channel, and / or wherein the waveguide interferometer and the microfluidic channel are configured to prevent the reference arm from being exposed to the fluid and the microorganisms.

5. The sensor device according to claim 4, comprising a covering layer or mask located between the reference arm and the microfluidic channel, the covering layer or the mask preventing the reference light from interacting with the fluid and the microorganisms in the microfluidic channel, and / or preventing the reference arm from being exposed to the fluid and the microorganisms.

6. The sensor device according to any one of the preceding claims, comprising: A plurality of waveguide interferometers, each waveguide interferometer having a sensing arm and a reference arm; A plurality of microfluidic channels for the fluid and the microorganisms, and Capture means in each microfluidic channel for physically capturing the microorganisms as the fluid flows along the corresponding microfluidic channel so as to concentrate the microorganisms in the corresponding sensing region, Wherein each sensing arm is configured to guide sensing light, each reference arm is configured to guide reference light, and each waveguide interferometer is configured to interfere the corresponding reference light with the corresponding sensing light, and The waveguide interferometer and the microfluidic channel are configured to allow the sensing light in the sensing arm of each waveguide interferometer to interact with the fluid and the microorganisms in the sensing region of the corresponding microfluidic channel.

7. The sensor device according to claim 6, wherein one of the microfluidic channels contains a first microbial growth inhibitor.

8. The sensor device according to any one of the preceding claims, wherein each microfluidic channel includes a well for receiving a microbial growth inhibitor at a position upstream of the corresponding sensing region in the same microfluidic channel.

9. The sensor device according to any one of the preceding claims, wherein each capture means is located downstream of the sensing arm of the corresponding waveguide interferometer, or wherein each capture means is located at the same position as the sensing arm of the corresponding waveguide interferometer along the corresponding microfluidic channel.

10. The sensor device according to any one of the preceding claims, wherein the capture means in each microfluidic channel includes a plurality of capture features, wherein the capture features are configured to physically capture the microorganisms when the fluid flows along the microfluidic channel, and wherein the capture features define one or more gaps configured to allow the fluid to flow through the capture features but prevent the microorganisms from passing through the capture features.

11. The sensor device according to any one of the preceding claims, wherein the capture means in each microfluidic channel includes one or more rows of capture features.

12. The sensor device according to claim 10 or 11, wherein each capture feature includes a capturer configured to physically capture the microorganisms when the fluid flows along the microfluidic channel, and wherein each capturer includes one or more features extending into the corresponding microfluidic channel so as to define a compartment in the corresponding microfluidic channel for accommodating one or more microorganisms.

13. The sensor device according to any one of the preceding claims, wherein the sensing arm of each waveguide interferometer is folded such that the sensing arm passes through the corresponding sensing region of the corresponding microfluidic channel multiple times, and / or wherein the reference arm of each waveguide interferometer is folded.

14. The sensor device according to any one of the preceding claims, including filtering means at a position upstream of the corresponding sensing region in each microfluidic channel, wherein the filtering means is configured to capture debris or particles larger in size than the microorganisms.

15. A sensing method for sensing a change in the concentration of microorganisms, the sensing method comprising: Passing a fluid containing microorganisms along a microfluidic channel; Physically capturing the microorganisms by capture means when the fluid flows along the microfluidic channel so as to concentrate the microorganisms in the sensing region of the microfluidic channel, the capture means defining one or more gaps configured to allow the fluid to flow through the capture means but prevent the microorganisms from passing through the capture means; Propagating sensing light along the sensing arm of a waveguide interferometer; Propagating reference light along the reference arm of the waveguide interferometer; and Interfering the sensing light with the reference light. The waveguide interferometer and the microfluidic channel are configured such that the sensed light interacts with the microorganisms in the sensing region of the microfluidic channel.

16. The sensor device according to any one of claims 1 to 14 or the sensing method according to claim 15, wherein the fluid comprises a body fluid.

17. The sensor device according to any one of claims 1 to 14 or the sensing method according to claim 15, wherein the microorganisms comprise at least one of bacteria, fungi, and algae.

18. The sensor device according to claim 7 or 8, wherein the microorganisms comprise bacteria and each microorganism growth inhibitory substance comprises an antibiotic.

19. The sensor device according to claim 2 or any claim dependent on claim 2, wherein the sensing arm comprises a single-mode optical waveguide and / or the reference arm comprises a single-mode optical waveguide.

20. The sensor device according to claim 2 or any claim dependent on claim 2, wherein the guided optical mode comprises a guided transverse magnetic optical mode.

21. The sensor device according to claim 2 or any claim dependent on claim 2, wherein the waveguide interferometer and the microfluidic channel are configured to allow the evanescent field of the guided optical mode to interact with the microorganisms in the sensing region.

22. The sensor device according to claim 7 or any claim dependent on claim 7, wherein: one or more of the other microfluidic channels contain corresponding microorganism growth inhibitory substances different from the first microorganism growth inhibitory substance, and / or one or more of the other microfluidic channels do not contain any microorganism growth inhibitory substance.

23. The sensor device according to claim 9 or any claim dependent on claim 9, wherein each capture device is located near the sensing arm of the corresponding waveguide interferometer.

24. The sensor device according to any one of claims 1 to 14, wherein each waveguide interferometer is defined on or near the surface of a photon chip that defines one or more waveguide interferometers, and the capture device defines one or more gaps between the capture device and the surface of the photon chip, wherein each gap is configured to allow fluid to flow through the gap between the capture device and the surface of the photon chip, but prevent microorganisms from passing through the gap between the capture device and the surface of the photon chip.

25. The sensor device according to claim 11 or any claim dependent on claim 11, wherein the capture device in each microfluidic channel comprises two or more rows of staggered capture features.

26. The sensor device according to claim 10 or 11, wherein each waveguide interferometer is defined on or near the surface of a photonic chip that defines the one or more waveguide interferometers, and each capture feature defines one or more gaps between the capture feature and the surface of the photonic chip, wherein each gap is configured to allow fluid to flow through the gap between the capture feature and the surface of the photonic chip, but prevent microorganisms from passing through the gap between the capture feature and the surface of the photonic chip.

27. The sensor device according to claim 14 or any claim dependent on claim 14, wherein the filtering means is configured to capture debris or particles having a minimum size greater than the maximum size of the microorganisms.

28. The sensor device according to claim 14 or any claim dependent on claim 14, wherein each filtering means includes one or more protrusions extending into a corresponding microfluidic channel, wherein the one or more protrusions define at least one gap that exceeds the maximum size of the microorganisms.

29. The sensor device or sensing method according to claim 16, wherein, The body fluid includes urine, blood, saliva or sputum.

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