Sample cartridge
The sample cartridge addresses the challenges of bacterial assessment by using a priming channel and gas spring arrangements to control fluid flow, ensuring simultaneous filling and accurate bacterial concentration and imaging in multiple chambers.
Patent Information
- Application Number
- PCT/EP2025/054199
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-02-16
- Filing Date
- 2025-02-17
- Publication Date
- 2025-08-21
AI Technical Summary
Existing cartridge-based fluid sample assessment systems face challenges in accurately and consistently assessing bacteria presence due to low bacterial concentrations, complex handling mechanisms, short shelf life, and limitations in imaging bacteria within fluid samples, often requiring laborious and complicated testing to find optimal growth and visual enhancement methods.
A sample cartridge with a priming channel and branch channels that utilize a sealable vent and gas spring arrangements to control fluid flow, ensuring simultaneous filling of multiple sample chambers without active components, and incorporating analyte chambers and absorptive elements to manage reagents and fluid distribution for accurate bacterial growth and imaging.
The cartridge enables efficient, simultaneous processing and imaging of bacteria in multiple sample chambers with controlled reagent distribution, reducing complexity and increasing reliability while ensuring accurate bacterial concentration and imaging.
Smart Images

Figure EP2025054199_21082025_PF_FP_ABST
Abstract
Description
[0001] Sample Cartridge
[0002] This application claims priority from EP24158221.2 filed 16 February 2024 and from EP24158226.1 filed 16 February 2024, and from EP24158224.6 filed 16 February 2024, the contents and elements of which are herein incorporated by reference for all purposes.
[0003] Field of the Invention
[0004] The present invention relates to sample cartridges and to sample chambers of said cartridges for processing a fluid sample and particularly, although not exclusively, to sample cartridges and sample chambers for processing a fluid sample containing bacteria.
[0005] Background
[0006] Fluid sample processing and assessment is a key component of many medical tests. For example, in diagnosing infections, a fluid sample may need to be investigated for the presence of bacteria.
[0007] Numerous challenges arise when it comes to accurately and consistently assessing a fluid sample for the presence of bacteria, particularly when the assessment involves the visual investigation of the fluid sample. For instance, the number of bacteria present in a given fluid sample may be relatively low and the bacteria itself may be difficult to image, meaning that some means of encouraging bacterial growth to increase the number of bacteria, i.e., increase the bacterial concentration, in a sample and / or visual enhancement may be required.
[0008] However, it is often necessary to test several different means of encouraging bacterial growth and / or visual enhancement depending on the fluid sample and bacteria in question. Performing multiple such tests in order to identify the optimal combination is often laborious and complicated.
[0009] A further challenge arises when it comes to imaging the bacteria suspended in the fluid suspension due to the shallow depth of field of most microscopic imaging systems.
[0010] There exist several examples of cartridge-based fluid sample assessment systems. However, the cartridges often have a short shelf life, require particularly complicated active mechanisms for handling the fluid sample and / or are only able to perform a single test at a given time.
[0011] The present invention has been devised in light of the above considerations.
[0012] Summary of the Invention
[0013] At its most general, the present invention provides a means of processing a fluid sample in order to assess the presence of bacteria within said fluid sample. The various aspects of the present invention improves over existing cartridge-based fluid sample assessment systems based on the considerations outlined above as well as others. According to a first aspect of the invention, there is provided a sample cartridge for processing a fluid sample, the sample cartridge comprising: an inlet for receiving the fluid sample; a priming channel having an upstream priming end and a downstream priming end opposite the upstream priming end, wherein the priming channel is in fluid communication with the inlet at the upstream priming end of the priming channel; and a plurality of sample chambers, each sample chamber in fluid communication with the priming channel by way of one of a plurality of branch channels, each branch channel having an upstream branch end and a downstream branch end, wherein an upstream branch end of each of the branch channels is fluidically connected to the priming channel, between the upstream priming end and the downstream priming end of the priming channel, and wherein the downstream branch end of each of the branch channels is fluidically connected to a respective one of the sample chambers, and wherein the priming channel comprises a sealable vent located at the downstream priming end of the priming channel.
[0014] There is provided a sample cartridge for processing a fluid sample, and in particular a fluid sample containing bacteria. The cartridge includes an inlet for receiving the fluid sample, which is then provided to a priming channel.
[0015] The priming channel is fluidically connected, at an upstream priming end, to the fluid inlet and fluidically connected, at a downstream priming end, to a sealable vent, which is open when the priming channel has not been filled. As the fluid sample is provided to the fluid inlet, the priming channel will begin to fill with the fluid sample. As the priming channel fills, the fluid sample will flow from the upstream priming end to the downstream priming end forcing air in the priming channel out through the sealable vent. The sealable vent may be sealed when the priming channel has filled with the fluid sample or as the priming channel is filling with fluid sample.
[0016] The cartridge includes a plurality of sample chambers, each of which are connected to the priming channel by way of a respective branch channel. Each of the branch channels are connected to the priming channel at different positions between the fluid inlet and the sealable vent. Due to static pressures within the sample chambers, once the priming channel has filled with fluid sample sufficiently to pass a given branch channel, the filling of said branch channel will be resisted by the building air pressure therein and the priming channel will fill ahead of any of the branch channels because of the pressure release of the sealable vent. Due to dynamic pressures in the flowing fluid sample, there will be slight filling of the branch channels as the priming channel continues to fill.
[0017] Once the sealable vent is sealed, the pressure release of the sealable vent is no longer available to the priming channel and the branch channels will begin to fill at substantially similar times. In this way, the fluid sample may be processed in each of the plurality sample chambers substantially simultaneously.
[0018] The sample cartridge may be a cartridge for receiving and holding, or containing or storing, the fluid sample therein. The sample cartridge may be adapted to be received at, in or on, an apparatus for imaging the contents of the plurality sample chambers containing the fluid sample. At least one surface of the sample cartridge may be optically transparent. All of the surfaces of the sample cartridge may be adapted to allow at least some light to pass through. All of the internal surfaces of the sample cartridge, i.e., those surfaces in contact with the fluid sample may be biologically inert so as not to affect the bacteria held in the fluid sample. The sample cartridge may be any suitable cassette, magazine, canister, container, capsule or case for receiving and storing a fluid sample.
[0019] The fluid sample may be any liquid containing bacteria. For example, the fluid sample may comprise one or more of: urine; blood; saliva; and any other human or animal secretion.
[0020] The sample cartridge comprises a channel network for routing the fluid sample from the fluid inlet to the plurality of sample chambers. The priming channel is the channel of the sample cartridge that first receives the fluid sample from the fluid inlet. The branch channels are the channels of the sample cartridge that fluidically connect the priming channel to the sample chambers, each sample chamber being connected to the priming channel by a single branch channel.
[0021] The fluid sample flows along the priming channel and to the sealable vent first, and then, when the sealable vent is sealed, to the branch channels and the sample chambers. Put another way, the fluid sample does not flow to the sample chambers until after the priming channel has been primed, i.e., filled with fluid sample.
[0022] In some examples, the sealable vent is a hydrophobic vent, and wherein the hydrophobic vent is gas permeable in a dry state, and wherein the hydrophobic vent is sealed in a wet state.
[0023] The hydrophobic vent is gas permeable when dry and is liquid impermeable up to a predetermined pressure threshold. The predetermined pressure threshold may be higher than pressures within the cartridge during use. The hydrophobic vent may be any suitable hydrophobic material, such as a hydrophobic paper or permeable membrane.
[0024] In this way, there is provided a cartridge for receiving a fluid sample and routing the fluid sample to a plurality of sample chambers in the same filling action, without requiring further input. Put another way, there is provided a sample cartridge adapted to automatically fill a plurality of sample chambers with a received fluid sample, without requiring any intervention other than providing the fluid sample to an inlet.
[0025] When the sample cartridge is dry, i.e., before any fluid sample has been introduced to the fluid inlet, the channel network is filled with air. As the fluid sample is introduced to the priming channel, via the fluid inlet, the air in the channel network is displaced. The hydrophobic vent is the only external outlet in the sample cartridge, meaning that the hydrophobic vent is the only point at which air in the sample cartridge may escape and thereby release pressure. As the fluid sample flows along the priming channel, the fluid sample is effectively sealing each of the branch channels and sample chambers with air still inside, creating a pressure differential between the sample chambers and the priming channel. This pressure differential will cause the priming channel to fill first, due to the continue pressure release of the hydrophobic vent, until the hydrophobic vent is sealed and the pressure in the priming channel begins to build, causing the fluid sample to begin flowing along the branch channels towards the sample chambers.
[0026] Alternatively, the sealable vent may be any other suitable sealable vent for sealing the priming channel, such as: a mechanical vent; a pneumatic vent; and the like. In some examples, each of the plurality of branch channels comprises a branch inlet section extending from the upstream branch end of the branch channel to a downstream branch inlet end, and wherein an angle between a priming flow vector, the priming flow vector being defined from the upstream priming end to the downstream priming end of the priming channel, and a branch flow vector, the branch flow vector being defined from the upstream branch end to the downstream branch inlet end, is an acute angle.
[0027] Put another way, the plurality of branch channels may each connect to the priming channel at an angle, and more specifically, at an angle that changes the direction of flow of the fluid sample. In other words, the transition between the priming channel and the branch channel may force a change in the direction of flow of the fluid sample in order to reduce the dynamic pressure effects that would cause the branch channels to fill before the priming channel has been filled.
[0028] In this way, the branch channel may be prevented from filling before the priming channel has been filled due to the additional pressure required to cause the fluid sample to change flow direction and fill the branch channels.
[0029] In some examples, each of the plurality of branch channels comprises at least one bend between the upstream branch end and the downstream branch end of the branch channel, and optionally wherein each of the plurality of branch channels is routed such that fluid sample flowing along a portion of each branch channel flows in a direction opposite to fluid sample flowing in the priming channel.
[0030] In this way, the pressure required to fill the branch channel may be further increased in order to ensure the sample chambers do not fill before the priming channel has been filled with the fluid sample. By providing a bend in the branch channels, even if some fluid sample enters the branch channels before the priming channel has been completely filled due to the dynamic pressure of the flowing fluid sample, the downstream branch end may be distanced from the upstream branch end of the branch channel to prevent fluid sample from entering the sample chamber itself.
[0031] Thus, the channel network of the sample cartridge may be arranged in order to control the flow of the fluid sample without requiring any active components. Put another way, the distribution of fluid sample from the fluid inlet to the sample chambers may be controlled passively based on pressure differentials alone, thereby reducing the complexity of the sample cartridge, and reducing the possible points of failure within the cartridge itself, thereby increasing the reliability of the sample cartridge.
[0032] In some examples, at least one of the plurality of branch channels further comprises an analyte chamber between the upstream branch end and the downstream branch end, wherein the analyte chamber comprises a reagent to be mixed with the fluid sample as the fluid sample flows through the analyte chamber.
[0033] In this way, reagents may be introduced to the fluid sample as it flows through the sample cartridge from the priming channel to the sample chambers via the branch channels. By providing the analyte chamber along the branch channels, as opposed to the priming channel, it is ensured that the sample proportion of analyte may be provided to the fluid sample received in each sample chamber. Thus, each portion of the fluid sample received in the respective sample chambers may be received at the same time and with a controlled amount of reagent mixed in, thereby providing multiple consistent testing environments within a single sample cartridge. The controlled amount of reagent may be the same across all, or some, of the analyte chambers. Alternatively, each reagent chamber may contain different amounts of the same reagents, different reagents or no reagent.
[0034] In some examples, reagents may be provided outside of the analyte chamber elsewhere within the sample cartridge for mixing with the fluid sample. For example, reagents may be provided in the branch channel, such as between the analyte chamber and the sample chamber.
[0035] In some examples, the analyte chamber is provided downstream of the at least one bend.
[0036] In this way, the distance between the point at which the branch channel is joined to the priming channel and the reagents may be controlled to ensure that the reagents in the analyte chamber are not introduced to the fluid sample until the fluid sample has begun distributed to all of the sample chambers, i.e. , after the priming channel has been filled. Accordingly, unintentional and premature mixing of the reagent with the fluid sample may be avoided.
[0037] In some examples, the analyte chamber comprises one or more mixing structures adapted to generate turbulence in a flow of fluid sample through the analyte chamber.
[0038] In this way, the reagent may be more evenly distributed and mixed within the fluid sample as it travels from the priming channel to the given sample chamber.
[0039] In some examples, the plurality of sample chambers comprises: a first row of sample chambers provided on a first side of the priming channel; and a second row of sample chambers provided on a second, opposing side of the priming channel to the first row. Put another way, the sample chambers may be arranged on either side of the priming channel.
[0040] In some examples, the upstream branch ends of the plurality of branch channels fluidically connecting the first row of sample chambers to the priming channel are aligned with the upstream branch ends of the plurality of branch channels fluidically connecting the second row of sample chambers to the priming channel.
[0041] In this way, the channel network, and in particular the sample chambers and the branch channels, may be symmetrical along the line of the priming channel. In this way, the manufacture of the sample cartridge may be simplified.
[0042] In some examples, the upstream branch ends of the plurality of branch channels fluidically connecting the first row of sample chambers to the priming channel are offset, along the length of the priming channel, from the upstream branch ends of the plurality of branch channels fluidically connecting the second row of sample chambers to the priming channel.
[0043] In this way, the branch channels may be offset along the length of the priming channel. For example, the upstream branch ends of the branch channels connecting the first row of branch channels to the priming channel may be interleaved with the upstream branch ends of the branch channels connecting the second row of branch channels to the priming channel. Alternatively, the upstream branch ends of the branch channels may be offset at either side of the priming channels at another regular, or irregular, interval. In this way, the number of sample chambers that can be provided within the sample chamber may be tuned or maximised.
[0044] In some examples, the sample cartridge further comprises a plurality of gas spring arrangements, wherein each gas spring arrangement is fluidically connected to a respective one of the plurality of sample chambers downstream of said respective sample chamber.
[0045] A gas spring arrangement, or a gas spring, may be a chamber having only a single inlet / outlet and containing only gas, or air. As air is a compressible fluid, when a chamber or channel fluidically connected to the gas spring is filled, for example with a fluid sample, the air within the gas spring arrangement will be compressed and the pressure within the gas spring arrangement will increase.
[0046] When the priming channel is filled with the fluid sample, and the sealable vent is sealed, the sample cartridge becomes a pressure sealed unit. At this point, the gas spring arrangements connected to each of the sample chambers will cause the pressure acting against the fluid sample across all of the branch channels to equalise before all of the branch channels begin to fill equally. Therefore, the provision of the gas spring arrangements balance the filling of the sample chambers such that each sample chamber is filled at substantially the same time, or simultaneously.
[0047] The volume of the gas spring arrangements, and in particular the volume of the gas spring arrangements relative to the air being displaced when the fluid sample is introduced to the sample cartridge, governs the pressure along each respective branch channel. For example, a gas spring arrangement having a larger volume will generate a lower pressure compared to a gas spring arrangement with a smaller volume in branch channels having equivalent dimensions. Having lower pressures within the sample cartridge may reduce the risk of the sample cartridge leaking during or after testing of the fluid sample.
[0048] In some examples, each of the gas spring arrangements may have the same volume. In other examples, each of the gas spring arrangements may have different volumes. In some cases, the gas spring arrangements may be divided into one or more subsets of gas spring arrangements, wherein each subset of gas spring arrangements has a different volume, but each gas spring arrangement within a given subset of gas spring arrangements has the same volume. The volume of each gas spring arrangement may be adjusted in order to control the filling rate of, and / or the volume of fluid sample received at, the respective sample chamber as desired.
[0049] By way of an example, the different gas spring arrangement volumes may be used to control the reagent concentration in the fluid sample as it reaches the sample chamber, by controlling the volume of fluid sample that is mixed in analyte chambers having the same amount of reagent present. In another example, where a fluid sample is expected to have different concentrations of pathogens present, the different gas spring arrangement volumes may be used to distribute the fluid sample to sample chambers at a volume appropriate for the different concentrations of pathogens, for example a lower volume of fluid sample may be provided to a sample chamber for a high concentration of a pathogen and a higher volume of fluid sample may be provided to a sample chamber for a low concentration of another pathogen. The gas spring arrangements may cause the fluid sample to oscillate slightly between the downstream end of the branch channel and the sample chamber. In the case where reagents are provided in the branch channel between the sample chamber and the analyte chamber, i.e., towards the upstream end of the branch channel, the oscillation, or backflow, in the fluid sample may be leveraged to cause the reagent to be mixed with the fluid sample.
[0050] In some examples, each sample chamber comprises a partition dividing each sample chamber into an upstream sub-chamber and a downstream sub-chamber, wherein the upstream sub-chamber is fluidically connected to the downstream branch end of the branch channel, and wherein the downstream subchamber is fluidically connected to the upstream sub-chamber via the partition.
[0051] The partition may be a membrane. In some examples, the partition may be a fluid-permeable membrane. The fluid-permeable membrane may have a fluid entry pressure threshold that the fluid sample in the upstream sub-chamber must exceed before the fluid sample moves from the upstream sub-chamber to the downstream sub-chamber. For example, the partition may be a fluid permeable filter.
[0052] The fluid-permeable membrane may be a hydrophilic, polytetrafluoroethylene (PTFE) membrane. The polytetrafluoroethylene (PTFE) membrane may have a thickness of between about 80pm to 90pm, for example 85pm. The polytetrafluoroethylene (PTFE) membrane may have a pore size of between about 0.1 pm to 1 .5pm, for example 0.22pm. The fluid-permeable membrane may be an Omnipore™ membrane.
[0053] In this way, each sample chamber may be filled in stages with the upstream sub-chamber filling before the downstream sub-chamber. By sub-dividing each of the sample chambers with a partition in this manner, an additional pressure threshold is introduced in order for the fluid sample to reach the downstream sub-chamber of each sample chamber, meaning that the upstream sub-chamber of each of the sample chamber may be filled prior to the filling of the downstream sub-chamber. Accordingly, the filling of the sample chambers may be controlled with greater accuracy without requiring any additional active components to be added to the sample cartridge.
[0054] In some examples, each gas spring arrangement comprises: a priming gas spring fluidically connected to the upstream sub-chamber; and a balancing gas spring fluidically connected to the downstream subchamber.
[0055] Put another way, the gas spring arrangement may be a two-stage gas spring adapted to control the filling of each sub-chamber the given sample chamber. In particular, the priming gas spring may regulate the pressure within the branch channel and the upstream sub-chamber as the upstream sub-chamber fills with the fluid sample, which may result in a reduction in the amount, or number, of bubbles that form or get trapped between the fluid sample and the partition. In other words, the priming gas spring may provide somewhere for any air trapped in the fluid sample to go before the fluid sample enters the downstream sub-chamber.
[0056] Once the upstream sub-chamber has been filled sufficiently, and the pressure in the priming gas spring has reached a predetermined threshold, the fluid sample may be forced into the downstream subchamber through the partition. For example, where the partition is a fluid-permeable membrane as outlined above, the fluid sample may be forced into the downstream sub-chamber through the fluid- permeable membrane when the pressure in the priming gas spring causes the pressure in the fluid sample in the upstream sub-chamber to exceed the fluid entry pressure of the fluid-permeable membrane. The nature and function of the partition is discussed in further detail below.
[0057] The balancing gas springs may control the rate of filling of the downstream sub-chambers across all of the sample chambers by balancing the pressure difference between the upstream sub-chamber and the downstream sub-chamber in each sample chamber.
[0058] It should be noted that whilst the priming gas spring and the balancing gas spring are separate, both will act on the fluid sample as it travels along the priming channel the branch channels and begins to fill the upstream sub-chamber. Put another way, at the initial stages of filling the sample cartridge, the priming gas spring and the balancing gas spring may act as a single gas spring. It is not until the priming gas spring reaches a state of maximum compression that the balancing gas springs will become the sole gas spring controlling the filling of all of the sample chambers to completion.
[0059] In some examples, the balancing gas spring is fluidly connected to the downstream sub-chamber by a plurality of ducts, and wherein the balancing gas spring comprises a plurality of gas spring chambers fluidically connected to each other, and wherein each of the plurality of ducts is fluidically connected to a respective one of the plurality of gas spring chambers.
[0060] By providing multiple ducts connecting the balancing gas spring and the downstream sub-chamber, the fluidic connections between the balancing gas spring and the sample chamber may be provided with redundancy in order to reduce the likelihood of the fluidic connection between the balancing gas spring and the sample chamber becoming blocked and disabling the balancing gas spring.
[0061] According to a second aspect of the invention, there is provided a method for filling a sample chamber of a sample cartridge with a fluid sample, the method comprising: providing a fluid sample to an inlet of the sample cartridge, thereby filling a priming channel of the sample cartridge, the priming channel having an upstream priming end and a downstream priming end opposite the upstream priming end, wherein the priming channel is fluidically connected to the inlet at the upstream priming end of the priming channel; sealing a sealable vent at the downstream priming end of the priming channel when the priming channel is filled with the fluid sample; continuing to provide the fluid sample to the inlet of the sample cartridge, thereby causing the fluid sample to flow through a plurality of branch channels, which fluidically connect to the priming channel at an upstream branch end of each branch channel and to a sample chamber at a downstream branch end of each branch channel, thereby filling a plurality of sample chambers.
[0062] In some examples, the sample cartridge further comprises a plurality of gas spring arrangements fluidically connected to one of the plurality of sample chambers downstream of said sample chamber, and wherein the method further comprises: dynamically balancing the fluid flow along the plurality of branch channels and into the plurality of sample chambers by compressing air within the plurality of gas spring arrangements as the fluid sample flows along the plurality of branch channels and towards the plurality of sample chambers, and optionally wherein the method further comprises filling the plurality of sample chambers substantially simultaneously by dynamically balancing the fluid flow along the plurality of branch channels and into the plurality of branch chambers.
[0063] According to a third aspect of the invention, there is provided a sample cartridge for processing a fluid sample, the sample cartridge comprising: an inlet for receiving the fluid sample; a main channel having an inlet end fluidically connected to the inlet; a plurality of sample chambers, each sample chamber fluidically connected to the main channel by way of one of a plurality of branch channels; and a plurality of gas spring arrangements, each gas spring arrangement being fluidically connected to one of the plurality of sample chambers, wherein each gas spring arrangement comprises: an upstream gas spring fluidically connected to the sample chamber at a first position; and a downstream gas spring fluidically connected to the sample chamber at a second position different to the first position.
[0064] There is provided a sample cartridge for processing a fluid sample, and in particular a fluid sample containing bacteria. The cartridge includes an inlet for receiving the fluid sample, which is then provided to a main channel.
[0065] The main channel is fluidically connected, at an upstream end, to the fluid inlet and fluidically connected to a plurality of sample chambers, each of which are connected to the main channel by way of a respective branch channel. In other words, there is provided a cartridge for receiving a fluid sample and routing the fluid sample to a plurality of sample chambers in the same filling action, without requiring further input.
[0066] Put another way, there is provided a sample cartridge adapted to automatically fill a plurality of sample chambers with a received fluid sample, without requiring any intervention other than providing the fluid sample to an inlet.
[0067] As outlined above, a gas spring arrangement, or a gas spring, may be a chamber having only a single inlet / outlet and containing only gas, or air. As air is a compressible fluid, when a chamber or channel fluidically connected to the gas spring is filled, the air within the gas spring arrangement will be compressed and the pressure within the gas spring arrangement will increase.
[0068] When the main channel is filled with the fluid sample and the fluid sample begins to flow along a branch channel, the given branch channel and connected sample chamber and gas spring arrangement becomes a pressure sealed unit. At this point, the gas held in the given gas spring arrangement will cause the pressure acting against the fluid sample in the branch channel to increase and the fluid sample will preferentially flow along the main channel until all of the branch channel pressures have equalised, at which point the branch channels begin to fill equally. Therefore, the provision of the gas spring arrangements balance the filling of the sample chambers such that each sample chamber is filled at substantially the same time, or simultaneously.
[0069] The gas spring arrangement is a two-stage gas spring adapted to control the filling of each sample chamber in stages. In particular, when the upstream gas spring reaches a state of maximum compression, the downstream gas spring will continue to control the filling of all of the sample chambers to completion. In this way, the control of the filling of the sample chambers may be made more accurate whilst only using passive elements. The upstream gas spring may be equivalent to the priming gas spring described above and the downstream gas spring may be equivalent to the balancing gas spring described above.
[0070] In some examples, the gas spring arrangement may comprise a volume adjustment element for adjusting a volume of the gas spring arrangement. The volume adjustment element may be provided in the upstream gas spring or the downstream gas spring. The upstream gas spring or the downstream gas spring may each comprise a respective volume adjustment element.
[0071] In some examples, the sample cartridge may be formed by injection moulding. In such examples, the portion of the injection mould for forming the volume adjustment element may be machine, or may comprise an adjustable pin, for adjusting the volume of the volume adjustment element. For example, by machining the portion of the injection mould for forming the volume adjustment element to remove material, the volume of the volume adjustment element may be increased, thereby decreasing the volume of the gas spring arrangement and, for example, decreasing the volume of the upstream gas spring and / or the downstream gas spring.
[0072] In the example where the sample cartridge comprises a plurality of sample chambers, each coupled to a respective gas spring arrangement, the volume adjustment element of each respective gas spring arrangement may be adjusted by machining the respective portions of the injection mould for forming the volume adjustment elements to ensure that the volume of each gas spring arrangement, for example the volume of each downstream gas spring, is uniform across the sample cartridge, such that the fluid sample is distributed uniformly between the sample chambers. In this way, any inconsistencies in the manufacture of the sample cartridge, such as moulding errors, may be accounted for and mitigated.
[0073] According to a fourth aspect of the invention, there is provided a sample cartridge for processing a fluid sample, the sample cartridge comprising: a fluid pathway having an upstream end and a downstream end, wherein the fluid pathway is adapted to receive the fluid sample at the upstream end and route the fluid sample to the downstream end; a sample chamber fluidically connected to the downstream end of the fluid pathway, the sample chamber comprising: a partition dividing the sample chamber into an upstream sub-chamber and a downstream sub-chamber, wherein the upstream sub-chamber is fluidically connected to the downstream end of the fluid pathway, and wherein the downstream sub-chamber is fluidically connected to the upstream sub-chamber via the partition; and an absorptive element adapted to absorb at least part of the fluid sample, wherein the absorptive element is provided in the downstream sub-chamber.
[0074] There is provided a sample cartridge for processing a fluid sample, and in particular a fluid sample containing bacteria. The cartridge includes a fluid pathway for receiving the fluid sample and routing to a sample chamber. The sample cartridge may include one or more, or all, of the aspects described above. For example, the fluid pathway may include the priming channel, or main channel, and the branch channels described above and the sample chamber may include one or more of the sample chambers described above.
[0075] The sample cartridge may be a cartridge for receiving and holding, or containing or storing, the fluid sample therein. The sample cartridge may be adapted to be receiving at, in or on, an apparatus for imaging the contents of the plurality sample chambers containing the fluid sample. At least one surface of the sample cartridge may be optically transparent. All of the surfaces of the sample cartridge may be adapted to allow at least some light to pass through. All of the internal surfaces of the sample cartridge, i.e., those surfaces in contact with the fluid sample may be non-reactive so as not to affect the bacteria held in the fluid sample. The sample cartridge may be any suitable cassette, magazine, canister, container, capsule or case for receiving and storing a fluid sample.
[0076] The fluid sample may be any liquid containing bacteria. For example, the fluid sample may comprise one or more of: urine; blood; saliva; and any other human or animal secretion.
[0077] The sample chamber is divided, or partitioned, into an upstream sub-chamber, which is directly fluidically connected to the fluid pathway, and a downstream sub-chamber, which is fluidically connected to the upstream sub-chamber via, or through, the partition.
[0078] In this way, the sample chamber may be filled in stages with the upstream sub-chamber filling before the downstream sub-chamber. By sub-dividing the sample chamber with a partition in this manner, an additional pressure threshold is introduced in order for the fluid sample to reach the downstream subchamber, meaning that the upstream sub-chamber of each of the sample chamber may be filled prior to the filling of the downstream sub-chamber. Accordingly, the filling of the sample chambers may be controlled with greater accuracy without requiring any additional active components to be added to the sample cartridge.
[0079] The absorptive element is provided in the downstream sub-chamber of the sample chamber. The absorptive element may comprise a hydrogel. The absorptive element does not begin to absorb the fluid sample until the fluid sample begins to pass through the partition and into the downstream sub-chamber, meaning that the upstream sub-chamber has the opportunity to fill before the absorption of the fluid sample begins.
[0080] In some examples, the absorptive element may comprise a superabsorbent polymer. For example, the superabsorbent polymer may be sodium polyacrylate.
[0081] By positioning the absorptive element in the downstream sub-chamber of the sample chamber, separated from the upstream sub-chamber by way of a partition, the amount of fluid sample held in the sample chamber may be accurately controlled.
[0082] In other words, there is provided a cartridge for receiving a fluid sample and maintaining an accurate amount of fluid sample in the sample chamber in the same filling action, without requiring further input.
[0083] Put another way, there is provided a sample cartridge adapted to automatically fill a sample chamber with a desired amount of fluid sample, without requiring any intervention other than providing the fluid sample to an inlet of the fluid pathway.
[0084] In some examples, the absorptive element is three-dimensional, i.e., not planar. Put another way, the absorptive element may be provided in a format that is not sheet-like. For example, the absorptive element may be spherical, or substantially spherical or rounded. In an example, the absorptive element may be provided in the form of a ball of hydrogel. In some examples, the absorptive element comprises a dissolvable coating to adjust an absorption rate of the fluid sample by the absorptive element.
[0085] For example, the dissolvable coating may retard the absorption of the fluid sample by the absorptive element. In this way, the downstream sub-chamber may at least partially fill with the fluid sample before the absorptive element begins to absorb the fluid sample. Accordingly, the delay in the absorbing of the fluid sample may prevent the fluid sample from being absorbed prematurely, for example, before the upstream sub-chamber has filled fully, or to a desired point or for a desired length of time.
[0086] In another example, the dissolvable coating may accelerate the absorption of the fluid sample by the absorptive element. In this way, the absorption of the fluid sample, and any associated changes in volume of the absorptive element and any results of this change in volume (examples of which are described further below), may be accelerated.
[0087] In some examples: in the absence of the fluid sample in the downstream sub-chamber, the absorptive element is in a dehydrated state; and in the presence of the fluid sample in the downstream sub-chamber, the absorptive element is adapted to absorb at least part of the fluid sample to change from the dehydrated state to a hydrated state, and wherein, a volume of the absorptive element in the hydrated state is larger than a volume of the absorptive element in the dehydrated state.
[0088] Put another way, the absorptive element may swell on the absorption of the fluid sample in order to change in size. In other words, a greater proportion of the downstream-sub chamber may be occupied by the absorptive element in its hydrated state compared to the absorptive element in its dehydrated state.
[0089] In this way, the pressure within the sample chamber and the fluid pathway may be controlled, and in particular prevented from falling, as the fluid sample in the downstream sub-chamber is absorbed.
[0090] In some examples, the absorptive element is movably received in the downstream sub-chamber when the absorptive element is in the dehydrated state. Put another way, the absorptive element may not be fixed, or held, at a particular position in the downstream sub-chamber. In this way, the absorptive element is free to move as it absorbs the fluid sample passing through the partition and may be free to move and expand as it changes from the dehydrated state to the hydrated state. Accordingly, the absorptive element may be prevented from ceasing to absorb the fluid sample due to, for example, becoming trapped or stuck in a position that does not allow for more expansion to occur.
[0091] In some examples, a volume of the downstream sub-chamber is lower than the volume of the absorptive element in the hydrated state, such that the absorptive element in the hydrated state exerts a force on the partition.
[0092] Put another way, in the hydrated state, the absorptive element may be larger than the downstream subchamber. In this way, the downstream sub-chamber may be filled with the absorptive element after a sufficient quantity of the fluid sample has been absorbed. Accordingly, the amount of fluid sample held in the sample chamber may be accurately controlled.
[0093] In some examples, the partition is flexible such that the partition deforms under the force exerted by the absorptive element in the hydrated state. In this way, the shape of the partition may be altered by the absorptive element, and in particular by the expansion of the absorptive element. For example, the expanding absorptive element may push the partition into the upstream sub-chamber. Accordingly, the amount of fluid sample held in the sample chamber may be controlled in a further manner by the absorptive element and the deformation of the partition.
[0094] In some examples, the partition is adapted to become transparent on contact with the fluid sample.
[0095] In this way, bacterial growth may be imaged through the partition without impacting the image quality obtained, thereby providing more degrees of freedom for orienting the sample chamber in an imaging system.
[0096] In addition, if the partition were not transparent until rehydration, there would be provided an additional visual indication of whether the sample chamber contained, or has recently, contained fluid. In this way, it can be assessed whether a sample chamber has not filled properly or if a sample chamber has already been used.
[0097] In some examples, the upstream sub-chamber comprises a bacterial growth platform. Aspects of the bacterial growth platform are discussed in further detail below; however, the bacterial growth platform may be any platform or material suitable for encouraging the growth of bacteria. By providing a bacterial growth platform within the sample chamber, bacteria present in the fluid sample may be encouraged to grow in number on the bacterial growth platform. Bacterial growth may then be measured, and in some cases compared to a control sample chamber (which may be a sample chamber of the sample cartridge absent of any reagent and / or bacterial growth platform) over time in order to derive clinical information.
[0098] In some examples, the partition comprises a fluid permeable filter adapted to prevent the passage of bacteria through the filter, the bacteria being present in the fluid sample. Put another way, as the fluid sample flows through the partition from the upstream sub-chamber to the downstream sub-chamber, the bacteria present in the fluid sample may be captured on the partition. In this way, bacteria present in the fluid sample may be concentrated to a given position within the sample chamber.
[0099] When imaging a sample chamber to investigate the presence of bacteria within the fluid sample, the imaging systems used typically have a very shallow depth of field. This means that imaging bacteria suspended freely within a fluid is extremely difficult to perform with any accuracy.
[0100] By concentrating the bacteria at a known location within the sample chamber, such as the partition, the bacteria may be more readily and accurately imaged.
[0101] In some examples, a volume of the sample chamber is lower than the volume of the absorptive element in the hydrated state, such that the partition is deformed to contact the bacterial growth platform.
[0102] In this way, the bacteria captured at the partition may be forced into contact with the bacterial growth platform, thereby ensuring that any bacteria present in the fluid sample will be cultured within the sample chamber and so improving the accuracy of testing the fluid sample with the sample cartridge.
[0103] In some examples, the partition is deformed to be substantially flattened against the bacterial growth platform. In this way, the bacteria present in the fluid sample is concentrated in one place, i.e., the partition, of the sample chamber, which is then forced into contact with the bacterial growth platform in order to encourage said concentrated bacteria to grow and flattened in order to keep the bacteria in a single plane for accurate imaging. Further, when the partition is flattened against the bacterial growth platform, the partition clamps the bacteria in place, preventing any lateral movement, i.e., movement in the plane perpendicular to the movement of the partition towards the bacterial growth platform, from occurring, thereby further improving the imaging accuracy that can be achieved using the sample cartridge.
[0104] In some examples, the fluid pathway widens along a downstream direction as it approaches the sample cartridge from an upstream direction.
[0105] In this way, the number of bubbles present in the upstream sub-chamber may be reduced as the upstream sub-chamber may fill more completely before the partition is wetted by the fluid sample, which may cause pockets of air to become trapped in the upstream sub-chamber.
[0106] As outlined above, the absorptive element may comprise a superabsorbent polymer such as sodium polyacrylate, which may be provided in the form of a hydrogel.
[0107] In some examples, the absorptive element may be provided as a hydrogel ball or sphere. In some examples, the absorptive element may be provided as a flattened sphere, such that the absorptive element may be provided as a hydrogel disc, which may also be referred to as a short cylinder or puck.
[0108] The downstream sub-chamber may be shaped to according to the shape of the absorptive element in order to accommodate the absorptive element.
[0109] In some examples, the downstream sub-chamber may have a substantially oval cross-section. In some examples, the perimeter of the downstream sub-chamber may be described by a first arced side wall and a second arced side wall, the first arced side wall being connected to the second arced side wall by a pair of converging straight side walls. A radius of the first arced side wall may be larger than a radius arc of the second arced side wall such that the pair of straight side walls converge towards the second arced side wall from the first arced side wall.
[0110] In the example where the absorptive element comprises a hydrogel disk, the hydrogel disk may be provided within the arc of the first arced side wall. The radius of the hydrogel disk may be between the radius of the first arced side wall and the radius of the second arced side wall. The radius of the hydrogel disc may be within 0.1 mm ofthe radius of the radius of the first arced side wall.
[0111] As outlined above, a characteristic of hydrogels, and superabsorbent polymers in general, is the ability to absorb a significant amount of liquid, which leads to a large expansion of the absorptive element when the absorptive element comes into contact with the fluid sample. For example, sodium polyacrylate is able to absorb between 100 and 1000 times its mass in water.
[0112] By providing the hydrogel disk with a snug fit within the arc of the first arced side wall, the expansion of the hydrogel disk may be limited, or confined, by the first arced side wall, meaning that the expansion of the hydrogel must occur across the area bounded by the converging straight walls towards the arc of the second arced side wall. The partition between the upstream sub-chamber and the downstream sub-chamber may be provided within the arc of the second arced side wall. The partition may comprise a circular aperture covered by a fluid-permeable membrane as described above.
[0113] As a hydrogel disk absorbs fluid sample, the fluid sample is absorbed by the outer layers of the superabsorbent polymer forming the hydrogel disk first. In some cases, this may mean that the outer portions of the hydrogel disk in the downstream sub-chamber may contain a greater proportion of fluid sample than inner portions of the hydrogel disk, which may in turn mean that the outer portions of the hydrogel disk have a refractive index closer to the fluid sample than the inner portions.
[0114] By providing the hydrogel disc in a position offset from the partition, for example by providing the hydrogel disc within the arc of the first arced side wall and the partition within the arc of the second arced side wall, the partition may be contacted by an outer portion of the hydrogel disk as the hydrogel disk expands on contact with the fluid sample.
[0115] Therefore, the refractive index of the portion of the hydrogel disk in contact with the partition may have a refractive index similar to that of the fluid sample, meaning that the bacteria may be imaged through the hydrogel disk without negatively impacting the quality of the image significantly.
[0116] Further, by positioning the hydrogel disc as outlined above such that the hydrogel disk is consistently provided with the fluid sample in a targeted region of the hydrogel disk, the portion of the hydrogel disk that forms an area with a refractive index similar to that of the fluid sample is formed more rapidly compared to an absorptive element that is allowed to freely absorb fluid sample from any direction.
[0117] In some examples, the downstream sub-chamber may comprise a substantially circular outer perimeter. In some examples, the downstream sub-chamber may comprise a plurality of retaining members projecting from a side wall of the downstream sub-chamber towards the absorptive element for retaining the absorptive element in a predetermined position. For example, the downstream may comprise three retaining members. The three retaining members may be uniformly spaced about the side wall of the downstream sub-chamber.
[0118] The plurality of retaining members may each comprise a rounded distal tip, the rounded distal tip being located at a distal end of each retaining member opposite the side wall of the downstream sub-chamber and proximate the absorptive element. The rounded distal tip may be provided on the retaining members to prevent the absorptive element from rupturing when expanding against the retaining members. The retaining members may be integrally formed with the side wall of the downstream sub-chamber.
[0119] The downstream sub-chamber may comprise a plurality of expansion areas, each expansion area being provided between adjacent retention members. The side wall of the downstream sub-chamber may be curved between the expansion areas and the retaining members, and in particular between the portion of the side wall of the downstream sub-chamber defining a given expansion area and the adjacent pair of retaining members extending from said portion of the side wall. In the example where the downstream sub-chamber comprises three retention members, the downstream sub-chamber may comprise three expansion areas. The cross-section of the downstream sub-chamber may therefore comprise a rounded trefoil shape.
[0120] The partition between the upstream sub-chamber and the downstream sub-chamber may be provided within a perimeter bounded by the distal ends of the retaining members. The partition may comprise a circular aperture covered by a fluid-permeable membrane as described above. The partition may therefore be substantially concentric with a hydrogel disk retained by the retaining members.
[0121] By providing the hydrogel disk with a snug fit within the retaining members, the expansion of the hydrogel disk may be limited, or confined, by the retaining members, meaning that the expansion of the hydrogel must occur into the expansion areas bounded by the retaining members.
[0122] As a hydrogel disk absorbs fluid sample, the fluid sample is absorbed by the layers of the superabsorbent polymer forming the hydrogel disk that come into contact with the fluid first. By providing the hydrogel disc in a position concentric with the partition, for example by providing the hydrogel disc between the retaining members, the centre of the hydrogel disk may be contacted by the fluid sample first and the outer portions of the hydrogel disk, which may not come into contact with the fluid sample, are forced into the expansion zones by the expansion of the centre of the hydrogel disk. The retaining members maintain the contact between the central portion of the hydrogel disk and the partition as the hydrogel disk expands meaning that the central portion of the hydrogel disk is consistently provided with fluid sample to absorb.
[0123] Therefore, the refractive index of the portion of the hydrogel disk in contact with the partition may have a refractive index similar to that of the fluid sample, meaning that the bacteria may be imaged through the hydrogel disk without negatively impacting the quality of the image significantly.
[0124] Further, by positioning the hydrogel disc as outlined above such that the hydrogel disk is consistently provided with the fluid sample in a targeted region of the hydrogel disk, the portion of the hydrogel disk that forms an area with a refractive index similar to that of the fluid sample is formed more rapidly compared to an absorptive element that is allowed to freely absorb fluid sample from any direction.
[0125] According to a fifth aspect of the invention, there is provided a method for filling a sample chamber of a sample cartridge with a fluid sample, the sample chamber comprising a partition dividing the sample chamber into an upstream sub-chamber and a downstream sub-chamber, and wherein the sample chamber comprises an absorptive element provided in the downstream sub-chamber adapted to absorb at least part of the fluid sample, the method comprising: providing a fluid sample to a fluid pathway of the sample cartridge, thereby filling an upstream sub-chamber of the sample chamber that is fluidically connected to a downstream end of the fluid pathway; and continuing to provide the fluid sample to the fluid pathway of the sample cartridge, thereby causing the fluid sample to flow through the partition from the upstream sub-chamber to the downstream sub-chamber.
[0126] In some examples, the partition is flexible and the upstream sub-chamber comprises a bacterial growth platform, and wherein the method further comprises: deforming the partition to contact the bacterial growth platform, wherein deforming the partition comprises: continuing to provide the fluid sample to the fluid pathway of the sample cartridge, thereby causing the fluid sample to be absorbed by the absorptive element, such that the absorptive element changes from a dehydrated state to a hydrated state, wherein a volume of the absorptive element in the hydrated state is larger than a volume of the sample chamber such that the absorptive element in the hydrated state exerts a force on the partition, thereby deforming the partition to contact the bacterial growth platform.
[0127] In some examples, the method further comprises continuing to supply fluid sample to the fluid pathway of the sample cartridge, thereby providing a flow of fluid sample to the absorptive element as the fluid sample in the sample chamber is absorbed. In this way, the absorptive element is prevented from drying out the other components of the sample chamber, such as the partition or the bacterial growth platform.
[0128] According to a sixth aspect of the invention, there is provided a sample chamber for receiving a fluid sample, wherein the sample chamber comprises: a dehydrated bacterial growth platform adapted to rehydrate on contact with the fluid sample to encourage bacterial growth in the sample chamber, the bacteria being present in the fluid sample.
[0129] There is provided a sample chamber for receiving a fluid sample and culturing bacteria present in the fluid sample. The sample chamber may be provided on any of the sample cartridges described above. The sample chamber may include any of the features described above with reference to the sample chambers of the sample cartridges described.
[0130] As discussed below, a bacterial growth platform may be any material suitable for bacterial survival. The bacterial growth platform may comprise a combination of a bacterial growth medium and a gelling agent.
[0131] Typically, bacterial growth platforms are hydrated due to the fact that bacterial growth requires the presence of water or moisture. Nutrients may be added to a fluid sample in order to encourage bacterial growth therein; however, this is often not suitable in imaging applications where imaging bacteria in fluid suspension is difficult to perform with any accuracy, due to the movement of bacteria and the small working distance of the microscope objective lens at higher magnification levels. In laboratory settings, bacterial growth platforms are prepared fresh as needed or can be stored with a relatively short shelf life. If such a bacterial growth platform were to dehydrate and degrade, or dry out sufficiently, it would ordinarily be disposed of.
[0132] However, the present inventors have discovered that a dehydrated bacterial growth platform can be used to encourage bacterial growth from bacteria present in a fluid sample due to the rehydration of the bacterial growth platform by said fluid sample.
[0133] In addition, the use of a dehydrated bacterial growth platform may elongate the shelf life of the sample cartridge due to the fact that any nutrients for encouraging bacterial growth in the dehydrated bacterial growth platform are essentially preserved.
[0134] In some examples, the dehydrated bacterial growth platform comprises a dehydrated gel medium, such as dehydrated agar or agarose.
[0135] Agar and agarose are commonly used in laboratory settings as a gelling reagent to provide a semi-solid surface for bacteria to grow on, often combined with liquid media that contain nutrients for encouraging bacterial growth, and is often made fresh when needed. However, typically, agar and agarose are only utilised in a hydrated state and is disposed of if it becomes dehydrated for any reason. By providing dehydrated agar or agarose as the dehydrated gel medium that forms part of the dehydrated bacterial growth platform of the present invention, the sample chamber may utilize a reliable bacterial growth platform in a manner that drastically extends the shelf life of the sample chamber.
[0136] In some examples, the dehydrated bacterial growth platform is provided as a film on an internal surface of the sample chamber.
[0137] The bacterial growth platform is where bacteria suspended in the fluid sample will begin to grow within the sample chamber. This is particularly true when the sample chamber includes an absorptive element adapted to expand and press a flexible filter, adapted to prevent bacteria from passing therethrough, against the bacterial growth platform.
[0138] As outlined above, imaging systems for capturing images of bacteria typically have very shallow depths of field, meaning that only shallow planes can be captured in focus by the system. By providing the bacterial growth platform as a film on a surface of the sample chamber, the bacterial growth is encouraged to occur on said film, meaning that the bacterial growth will occur on a thin, flat surface that can be readily imaged by a system having a shallow depth of field.
[0139] In some examples, the film has a thickness between 0.1 pm and 100 pm, for example a thickness between 0.5 pm and 75 pm, for example a thickness of 50 pm. As bacterial growth only occurs on the surface of a bacterial growth platform, a thin film of bacterial growth platform may be sufficient to encourage bacterial growth in the sample chamber whilst still maintaining a small form factor for the sample chamber itself.
[0140] In some examples, the film has a thickness of 100 pm on rehydration. For example, the dehydrated bacterial growth platform may have a thickness of 50 pm, and may then swell to a thickness of 100 pm on rehydration.
[0141] In some examples, the bacterial growth platform comprises a bacterial growth medium.
[0142] In this way, the bacterial growth platform may be provided with a bacterial growth medium including nutrients for encouraging bacterial growth on the bacterial growth platform.
[0143] In some examples, the sample chamber further comprises a partition dividing the sample chamber into an upstream sub-chamber and a downstream sub-chamber, wherein the downstream sub-chamber is fluidically connected to the upstream sub-chamber via the partition, and wherein the dehydrated bacterial growth platform is provided in the upstream sub-chamber.
[0144] For example, when the downstream sub-chamber contains an absorptive element as described above, the expansion of the absorptive element forces the partition into contact with the bacterial growth platform and clamps it flat in place in order to encourage bacterial growth in a given plane. Accordingly, the bacteria is located in the optimal place, for both encouraging bacterial growth and imaging the bacteria, in a manner that is automated entirely by the introduction of a fluid sample to the sample chamber and without requiring any active, or powered, components or any user input. In some examples, the dehydrated bacterial growth platform is provided on an internal surface of the upstream sub-chamber opposite the partition. The bacterial growth platform may maintain a separation with the partition on rehydration in the absence of another force bringing them together, for example the expansion of the absorptive element. In some examples, the dehydrated bacterial growth platform is arranged parallel to the partition.
[0145] In this way, the contact between the partition and the bacterial growth platform may be controlled by the swelling of an absorptive element as described above. This may provide a means of achieving equal contact time between the bacteria captured by the partition and the bacterial growth platform across multiple sample chambers connected, for example, by a channel network as described above.
[0146] In some examples, the sample chamber further comprises a fluid inlet fluidically connected to the upstream sub-chamber, and wherein the fluid inlet is located adjacent the dehydrated bacterial growth platform. In this way, the fluid sample is introduced to the dehydrated bacterial growth platform immediately upon entry into the sample chamber. Accordingly, the process of rehydrating the bacterial growth platform may begin as the sample chamber starts filling and may be completed before bacterial growth may need to begin.
[0147] In some examples, the sample chamber further comprises an absorptive element adapted to absorb at least part of the fluid sample, wherein the absorptive element is provided in the downstream sub-chamber and adapted to reduce a humidity of the sample chamber to prevent rehydration of the dehydrated bacterial growth platform prior to contact with the fluid sample.
[0148] Put another way, in addition to the functions described above, the provision of an absorptive element within the sample chamber may prevent the premature rehydration of the dehydrated bacterial growth platform, i.e. , prior to the introduction of the fluid sample into the sample chamber. Further, the absorptive element may maintain the dehydrated state of any other components, such as reagents, prior to the introduction of the fluid sample to the sample cartridge. In this way, the shelf life of the dehydrated bacterial growth platform, the sample chamber and the sample cartridge comprising said sample chamber may be extended.
[0149] According to a seventh aspect of the invention, there is provided a sample cartridge for processing a fluid sample, the sample cartridge comprising: a fluid pathway having an upstream end and a downstream end, wherein the fluid pathway is adapted to receive the fluid sample at the upstream end and route the fluid sample to the downstream end; and a sample chamber as discussed above, wherein the sample chamber is fluidically connected to the downstream end of the fluid pathway.
[0150] According to an eighth aspect of the invention, there is provided a method for encouraging bacterial growth from a fluid sample, the method comprising: providing the fluid sample to a dehydrated bacterial growth platform, thereby rehydrating the dehydrated bacterial growth platform to encourage bacterial growth.
[0151] According to a ninth aspect of the invention, there is provided a method for processing a fluid sample using a sample cartridge, the method comprising: providing the fluid sample to a fluid pathway of the sample cartridge at an upstream end of the fluid pathway; providing the fluid sample to a sample chamber fluidically connected to a downstream end of the fluid pathway by continuing to provide the fluid sample to the fluid pathway, wherein the sample chamber comprises a dehydrated bacterial growth platform and providing the fluid sample to the sample chamber comprises: providing the fluid sample to the dehydrated bacterial growth platform, thereby rehydrating the dehydrated bacterial growth platform to encourage bacterial growth.
[0152] According to a tenth aspect of the invention, there is provided a sample cartridge for processing a fluid sample, the sample cartridge comprising: a fluid pathway having an upstream end and a downstream end, wherein the fluid pathway is adapted to receive the fluid sample at the upstream end and route the fluid sample to the downstream end; and a sample chamber fluidically connected to the downstream end of the fluid pathway, the sample chamber comprising: a chamber wall at least partially defining an internal cavity of the sample chamber, the internal cavity being adapted to receive the fluid sample from the fluid pathway, wherein the chamber wall comprises a recess; and a dehydrated bacterial growth platform for encouraging bacterial growth of bacteria present in the fluid sample, wherein the dehydrated bacterial growth platform is provided in the recess of the chamber wall.
[0153] The fluid pathway may be the same as, or similar to, the fluid pathways described above.
[0154] The recess in the chamber wall may be a shallow recess. In other words, a width of the recess may be greater than a depth of the recess. The recess may be a cylindrical recess. Accordingly, a diameter of the cylindrical recess may be greater than a height of the cylindrical recess.
[0155] In some examples, the recess may have a depth of between 0.1 pm and 100 pm, for example a depth between 0.5 pm and 75 pm, for example a depth of 50 pm.
[0156] As discussed above, a bacterial growth platform may be any material suitable for bacterial survival and / or proliferation. The bacterial growth platform may comprise a combination of a bacterial growth medium and a gelling agent. The present inventors have discovered that a dehydrated bacterial growth platform can be used to encourage bacterial growth of the bacterial cells present in a fluid sample due to the rehydration of the bacterial growth platform by said fluid sample.
[0157] In some examples, the recess may be sized and shaped to accommodate the dehydrated bacterial growth platform. In some examples, the dehydrated growth platform may be sized and shaped to be received within the recess. As explained in further detail below, the dehydrated bacterial growth platform may be formed within the recess of the chamber wall during the manufacture of the sample cartridge.
[0158] In some examples, an upper surface of the dehydrated bacterial growth platform may be aligned with a cavity facing surface of the chamber wall.
[0159] In other words, the dehydrated bacterial growth platform may be substantially level, for flush, with the cavity facing surface of the chamber wall. The cavity facing surface of the chamber wall may be the surface of the chamber wall that faces the internal cavity of the sample chamber. The upper surface of the dehydrated bacterial growth platform may be the surface of the dehydrated bacterial growth platform that faces the internal cavity of the sample chamber. The cavity facing surface of the chamber wall and the upper surface of the dehydrated bacterial growth platform may be substantially parallel. The dehydrated bacterial growth platform may swell slightly on rehydration by the fluid sample as outlined above. In the case where the upper surface of the dehydrated bacterial growth platform is aligned with the cavity facing surface of the chamber wall when the dehydrated bacterial growth platform is in a dehydrated state, the dehydrated bacterial growth platform may protrude from the recess when the dehydrated bacterial growth platform is in a rehydrated state.
[0160] In some examples, the sample chamber may comprise at least one side wall at least partially defining the internal cavity of the sample chamber. The at least one side wall may comprise a fluid inlet fluidically connecting the internal cavity of the sample chamber to the downstream end of the fluid pathway.
[0161] The chamber wall may be a base wall or a top wall of the sample chamber. The chamber wall may be substantially perpendicular to the at least one side wall. In the example where the recess in the chamber wall is a shallow recess, the width of the recess may be perpendicular to the at least one side wall.
[0162] In some examples, a boundary surface of the fluid inlet may be aligned with the cavity facing surface of the chamber wall. In the example where the upper surface of the dehydrated bacterial growth platform is aligned with the cavity facing surface of the chamber wall, the upper surface of the dehydrated bacterial growth platform may be aligned with the boundary surface of the fluid inlet and the recess may be recessed with respect the boundary surface of the fluid inlet. The boundary surface may be a portion of the surface defining the perimeter of the fluid inlet in the at least one side wall of the sample chamber.
[0163] In this way, the fluid sample is introduced to the dehydrated bacterial growth platform immediately upon entry into the sample chamber. Accordingly, the process of rehydrating the bacterial growth platform may begin as the sample chamber starts filling and may be completed before bacterial growth may need to begin. By providing the dehydrated bacterial growth platform in the recess such that the upper surface of the dehydrated bacterial growth platform is aligned with the boundary surface of the fluid inlet, the upper surface of the dehydrated bacterial growth platform may be flooded with fluid sample immediately on the fluid sample entering the sample chamber, thereby ensuring full coverage of the dehydrated bacterial growth platform in fluid sample.
[0164] In some examples, the sample chamber may comprise an upstream sub-chamber and a downstream sub-chamber. The upstream sub-chamber may be fluidically connected to the downstream end of the fluid pathway. The downstream sub-chamber may be fluidically connected to the upstream sub-chamber. The chamber wall may at least partially define the upstream sub-chamber such that the recess may be provided in the upstream sub-chamber of the sample chamber. The upstream sub-chamber and the downstream sub-chamber may be configured as outlined above.
[0165] The downstream sub-chamber may comprise an absorptive element as described above. The absorptive element may function as described above with respect to the other aspects of the invention.
[0166] In some examples, the upstream sub-chamber may be separated from the downstream sub-chamber by a fluid permeable membrane, i.e., a partition as described above. The recess in the chamber wall and the fluid permeable membrane may be provided on opposing sides of the upstream sub-chamber. By providing the dehydrated bacterial growth platform within the recess in the chamber wall opposite the fluid permeable membrane, the dehydrated bacterial growth platform may maintain a separation with the fluid permeable membrane on rehydration in the absence of another force bringing them together, for example, the expansion of the absorptive element as described above. In some examples, the dehydrated bacterial growth platform is arranged parallel to the fluid permeable membrane.
[0167] In this way, the contact between the fluid permeable membrane and the bacterial growth platform may be controlled by the swelling of an absorptive element as described above. This may provide a means of achieving equal contact time between the bacteria captured by the fluid permeable membrane and the bacterial growth platform across multiple sample chambers connected, for example, by a fluid network as described above.
[0168] In some examples, the dehydrated bacterial growth platform may comprise a dehydrated gel medium, for example dehydrated agar or agarose.
[0169] Agar and agarose are commonly used in laboratory settings as a gelling reagent to provide a semi-solid surface for bacteria to grow on, often combined with liquid media that contain nutrients for encouraging bacterial growth, and are often made fresh when needed. However, typically, agar and agarose are only utilised in a hydrated state and are disposed of if they become dehydrated for any reason. By providing dehydrated agar or agarose as the dehydrated gel medium that forms part of the dehydrated bacterial growth platform of the present invention, the sample chamber may utilize a reliable bacterial growth platform in a manner that drastically extends the shelf life of the sample chamber.
[0170] In some examples, the bacterial growth platform comprises a bacterial growth medium. In this way, the bacterial growth platform may be provided with a bacterial growth medium including nutrients for encouraging bacterial growth on the bacterial growth platform.
[0171] In some examples, the sample cartridge may comprise a cartridge frame. The chamber wall may be coupled to the cartridge frame to form the internal cavity of the sample chamber. In some examples, the sample cartridge may comprise a plurality of sample chambers as outlined above.
[0172] In some examples, the sample cartridge may comprise a capping component. The capping component may comprise a respective chamber wall for forming a respective internal cavity of each of the plurality of sample chambers when the capping component is coupled to the cartridge frame. In some examples, the fluid pathway may be formed between the cartridge frame and the capping component when the capping component is coupled to the cartridge frame.
[0173] Put another way, the sample cartridge may comprise a layered construction with the cartridge frame forming a first layer and the caping component forming the second layer, and with the sample chambers and fluid pathways being defined in the space therebetween. The first layer and / or the second layer may be formed of rigid, transparent plastic. In some examples, both the first layer, i.e., the cartridge frame, and the second layer, i.e., the capping component may be formed from rigid, transparent plastic.
[0174] The cartridge frame and the capping component may be coupled together by way of an adhesive. For example, an adhesive layer may be sandwiched between the cartridge frame and the capping component in order to securely couple the cartridge frame to the capping component. In some examples, the cartridge frame and / or the capping component may comprise a rivet extending from one of the cartridge frames and the capping component to contact the other of the cartridge frame and the capping component. In the example where the capping component and the cartridge frame are formed of rigid plastic, the rivet may also be formed of rigid plastic and may be used to form a thermal weld between the capping component and the cartridge frame in order to reinforce the coupling.
[0175] According to an eleventh aspect of the invention, there is provided a method of manufacturing the sample cartridge described above, the method comprising: dispensing a liquid platform precursor into the recess of the chamber wall; and drying the liquid platform precursor to form the dehydrated bacterial growth platform in the recess.
[0176] As outlined above, the dehydrated bacterial growth platform may comprise a dehydrated gel medium, such as dehydrated agar or dehydrated agarose. In such examples, the liquid platform precursor may comprises a hydrated gel medium, such as agar or agarose, which is dispensed in liquid, or gel or aqueous, form into the recess of the chamber wall. The drying of the liquid platform precursor may be passive, i.e., by allowing the liquid platform precursor to dry through evaporation, or active, for example by heating or dehydrating the liquid flatform precursor.
[0177] As described above, the chamber wall may form part of a capping component that is part of the two-part construction of the sample cartridge. In this way, the dispensing of the liquid platform precursor can be simplified, because the liquid platform precursor can be directly dispensed into the recess before the capping component is coupled to the cartridge frame.
[0178] By providing the recess in the chamber wall for receiving the liquid platform precursor, as opposed to a flat surface, the manufacture and formation of the dehydrated growth platform may be greatly simplified.
[0179] For example, the liquid platform precursor may be dispensed anywhere within the recess in order to properly locate the dehydrated bacterial growth platform within the sample chamber. Accordingly, the accuracy of the placement of the dehydrated bacterial growth platform within the sample chamber is no longer dependent on the dispensing apparatus and the consistency of the manufacture of the sample cartridges may be improved.
[0180] Further, as the liquid platform precursor is immobilized within the recess of the chamber wall once dispensed, the drying time for the liquid platform precursor to form the dehydrated bacterial growth platform when compared to liquid platform precursor dispensed on a flat surface. In addition, the recess provides an improved containment of the liquid platform precursor, thereby preventing the liquid platform precursor from contacting other parts of the sample chamber or migrating from the desired position of the dehydrated growth platform.
[0181] In some examples, dispensing the liquid platform precursor into the recess of the chamber wall may comprise dispensing the liquid platform precursor until a target surface of the recess is covered by the liquid platform precursor. The target surface may be a bottom surface of the recess. In some examples, a dispensed volume of the liquid growth platform precursor may be greater than or equal to about 90% of the volume of the recess. In other words, the liquid platform precursor may be dispensed into the recess until the liquid platform precursor reaches a sidewall of the recess. In this way, contact angle between the liquid platform precursor may be altered, from being formed between the surface of the liquid platform precursor and the target surface to being formed between the surface of the liquid platform precursor and the side wall of the recess, thereby smoothing, or reducing, the meniscus formed by the surface tension in the liquid platform precursor. In some examples, the meniscus may change from a convex meniscus when the liquid platform precursor is only in contact with the target surface to a concave meniscus when the liquid platform precursor is in contact with the side wall of the recess.
[0182] By smoothing, for flattening, the meniscus of the liquid platform precursor, the distribution of the liquid platform precursor throughout the recess may be made more uniform. As a result, the dehydrated bacterial growth platform may be produced with a more even surface and a more even distribution of growth nutrients distributed therethrough. The more consistent thickness of the liquid platform precursor may reduce the drying period required to form the dehydrated growth platform. The dehydrated bacterial growth platform may also swell more evenly on rehydration as a result.
[0183] In some examples, after the step of drying the liquid platform precursor to form the dehydrated bacterial growth platform in the recess, the method may further comprise coupling the chamber wall to the cartridge frame to form the internal cavity of the sample chamber, for example as described above.
[0184] Whilst the various aspects of the invention have been laid out separately above, it should be noted that any aspect of the invention outlined above may be combined with any other aspect of the invention outlined above. Put another way, there is provided a sample cartridge for processing a fluid sample according to any aspect, or combination of aspects, described above.
[0185] The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.
[0186] Summary of the Figures
[0187] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:
[0188] Figures 1a to 1c show schematic representations of sample cartridges according to various aspects of the invention.
[0189] Figures 2 to 7 illustrate the filling of the sample cartridge of Figure 1 c with a fluid sample.
[0190] Figure 8 shows a schematic representation of an analyte chamber of a sample cartridge according to an aspect of the invention.
[0191] Figures 9 and 10 illustrate the passage of a fluid sample through the analyte chamber of Figure 8.
[0192] Figure 11 shows a schematic representation of a sample chamber according to an aspect of the invention. Figures 12 to 17 illustrate the filling of the sample chamber of Figure 11 with a fluid sample.
[0193] Figures 18a to 18d show a schematic representation of a sample chamber according to an aspect of the invention.
[0194] Figures 19a to 19b illustrate the dispensing of a liquid platform precursor into a recess of a chamber wall.
[0195] Figure 20 shows a schematic representation of a sample cartridge construction.
[0196] Detailed Description of the Invention
[0197] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference.
[0198] Figure 1a shows a schematic representation of a sample cartridge 100 for processing a fluid sample according to an aspect of the invention.
[0199] In the example shown in Figure 1 a, the sample cartridge 100 includes an inlet 110 for receiving the fluid sample and a priming channel 120 having an upstream priming end 122 and a downstream priming end 124 opposite the upstream priming end 122. The priming channel includes a sealable vent in the form of a hydrophobic vent 130 provided at its downstream priming end 124 and the priming channel 120 is in fluid communication with the fluid inlet 110 at its upstream priming end 122. The hydrophobic vent 130 is gas permeable in a dry state. A fluid sample provided to the sample cartridge 100 at the fluid inlet 110 will flow along the priming channel 120 from the upstream priming end 122 towards the downstream priming end 124 and the hydrophobic vent 130 as described further below with reference to Figures 2 to 7.
[0200] The sample cartridge 100 includes a plurality of sample chambers 140, each of which is fluidically connected to the priming channel 120 by way of a branch channel 150. The branch channels 150 are each connected to the priming channel 120 at an upstream branch end 152 and are each connected to a respective one of the plurality of sample chambers 140 at a downstream branch end 154.
[0201] The upstream branch ends 152 of all of the branch channels 150 connecting the sample chambers 140 to the priming channel 120 are fluidically connected to the priming channel 120 between the upstream priming end 122 and the downstream priming end 124 of the priming channel 120.
[0202] In the example shown in Figure 1a, the plurality of sample chambers 140 are arranged into a first row 142 of sample chambers and a second row 144 of sample chambers. The first 142 and second 144 rows of sample chambers 140 are arranged on opposite sides of the priming channel 120.
[0203] Figure 1a shows the upstream branch ends 152 of the plurality of branch channels 150 fluidically connecting the first row 142 of sample chambers 140 to the priming channel 120 being aligned with the upstream branch ends 152 of the plurality of branch channels 150 fluidically connecting the second row 144 of sample chambers 140 to the priming channel 120. In particular, the upstream branch ends 152 are aligned in pairs along the length ofthe priming channel 120 of such that an upstream branch end 152 of a branch channel 150 connected to a sample chamber 140 in the first row of sample chambers 142 is arranged on the opposite side of the priming channel 120 to an upstream branch end 152 of a branch channel 150 connected to a sample chamber 140 in the second row of sample chambers 144.
[0204] Figure 1 b shows a schematic representation of a sample cartridge 200 for processing a fluid sample according to an aspect of the invention. Features in common with those present in Figure 1 a share the same reference numerals.
[0205] In the example shown in Figure 1 b, the sample cartridge 200 comprises a plurality of gas spring arrangements 160, each of which is fluidically connected to a respective one of the plurality of sample chambers 140. The gas spring arrangements 160 are connected downstream of the sample chambers 140 along the fluid pathway, the fluid pathway including the branch channel 150 connecting the sample chamber 140 to the priming channel 120 and the portion of the priming channel 120 connecting the branch channel 150 to the fluid inlet 110. The priming channel 120 may also be referred to as a main channel in the absence of the hydrophobic vent shown in Figure 1 a.
[0206] Each gas spring arrangement 160 includes an upstream gas spring 162 fluidically connected to the sample chamber 140 at a first position and a downstream gas spring 164 fluidically connected to the sample chamber 140 at a second position different to the first position.
[0207] Exemplary gas spring arrangements 160, and in particular the two-stage gas spring arrangements 160 shown in Figure 1 b, are described in further detail below with respect to Figures 11 to 17.
[0208] In the example shown in Figure 1 b, the upstream branch ends 152 of the plurality of branch channels 150 fluidically connecting the first row 142 of sample chambers 140 to the priming channel 120 are offset, along the length of the priming channel 120, from the upstream branch ends 152 of the plurality of branch channels 150 fluidically connecting the second row 140 of sample chambers 140 to the priming channel 120. In the particular example shown in Figure 1 b, the upstream branch ends 152 connecting the first row 142 of sample chambers 140 to the priming channel 120 are interleaved with the upstream branch ends 152 connecting the second row 144 of sample chambers 140 to the priming channel 120.
[0209] Figure 1 c shows a schematic representation of a sample cartridge 300 for processing a fluid sample according to an aspect of the invention. Features in common with those present in Figures 1 a and 1 b share the same reference numerals.
[0210] The sample cartridge 300 shown in Figure 1 c shares a combination of the features of the sample cartridges described above with reference to Figures 1 a and 1 b. In particular, the sample cartridge 300 of Figure 1 c includes the hydrophobic vent 130 of Figure 1 a and the gas spring arrangements of Figure 1 b. Further, the downstream branch ends 152 of the branch channels 150 connecting the first 142 and second 144 rows of sample chambers 140 to the priming channel 120 of the sample cartridge 300 of Figure 1 c are aligned as shown in Figure 1 a.
[0211] In addition, each of the branch channels 150 of the sample cartridge 300 shown in Figure 1 c comprises an analyte chamber 170 between the upstream branch end 152 and the downstream branch end 154. The analyte chambers 170 comprise a reagent to be mixed with the fluid sample as the fluid sample flows through the analyte chamber 170 from the priming channel 120 to the sample chamber 140.
[0212] The contents of the analyte chamber 170 are discussed in further detail below with reference to Figures 8 to 10.
[0213] Figures 2 to 7 illustrate the filling of the sample cartridge 300 of Figure 1c with a fluid sample 180 intended for processing by the sample cartridge 300.
[0214] Figure 2 shows the sample cartridge 300 as the fluid sample 180 begins to enter the priming channel 120 from the fluid inlet 110. As the fluid sample 180 is introduced to the fluid inlet 110, the fluid sample 180 begins flowing from the upstream priming end 122 towards the downstream priming end 124 of the priming channel, as indicated by arrow A.
[0215] As the fluid sample 180 is introduced to the priming channel 120, via the fluid inlet 110, the air in the channel network is displaced and exits the sample cartridge 300 via the hydrophobic vent 130, as indicated by arrow B. The hydrophobic vent 130 will be dry at this stage and so will be gas permeable.
[0216] Figures 3 and 4 show the sample cartridge 300 as the fluid sample 180 continues along the priming channel 120 in direction A and past the downstream branch ends 152 of the branch channels 150 connecting the first 142 and second 144 rows of sample chambers 140 to the priming channel 120.
[0217] As the fluid sample 180 passes the downstream branch ends 152 of the branch channels 140, the branch channels 140, the sample chambers 150 and the gas spring arrangements 160 effectively become sealed as the only external air outlet in the sample cartridge 300 is the hydrophobic vent 130. Therefore, if a portion 181 of the fluid sample 180 flows along the branch channels 150, the air downstream of the portion 181 of the fluid sample 180 will be compressed and the pressure within the upstream gas spring 162 and the downstream gas spring 164 will increase. The increase in air pressure in the upstream gas spring 162 and the downstream gas spring 164 will exert a force 190, 191 against the portion 181 of the fluid sample 180 in the branch channel 150 and will prevent the fluid sample from continuing to flow along the branch channels 150 whilst the hydrophobic vent 130 remains dry and open to act as a pressure release.
[0218] In order to further guard against the fluid sample 180 progressing along the branch channels 150 too far, for example as far as the analyte chamber 170, each of the plurality of branch channels 150 comprises a branch inlet section 155 extending from the upstream branch end 152 of the branch channel to a downstream branch inlet end 156. The angle 157 between a priming flow vector, the priming flow vector being defined from the upstream priming end 122 to the downstream priming end 124 of the priming channel 120, and a branch flow vector, the branch flow vector being defined from the upstream branch end 152 to the downstream branch inlet end 156, is an acute angle.
[0219] Further, to prevent the analyte chamber 170 from being reached by the fluid sample 180 prematurely, the branch channels 150 may comprise at least one bend 158 between the upstream branch end 152 and the downstream branch end 154 of the branch channel 150. The branch channel 150 is routed to cause the fluid sample 180 in at least part of the branch channel 150 to flow in the opposite direction to the fluid sample 180 in the priming channel 120. As shown in Figures 1 c to 7, the analyte chamber 170 is provided downstream of the bend 158.
[0220] Figure 5 shows the sample cartridge 300 as the fluid sample 180 fills the priming channel 120 and wets the hydrophobic vent 130, thereby closing, or sealing, the hydrophobic vent 130.
[0221] Once the hydrophobic vent 130 has been wetted, and is no longer gas permeable, the sample cartridge 300 is essentially sealed. Therefore, any further fluid sample 180 introduced to the fluid inlet 110 will cause the fluid sample 180 to flow along the branch channels 150. As the filling of the branch channels has been arrested as the priming channel 120 fills by the pressure difference between the priming channel 120 and branch channels 150, due to the action of the gas spring arrangements 160 and the hydrophobic vent 130, all of the branch channels 150 will begin to fill simultaneously.
[0222] Further, as the gas spring arrangements, i.e., the upstream 162 and downstream 164 gas springs, connected to each sample chamber 140 are identical, the pressures in the gas spring arrangements 160 will tend towards equilibrium as the branch channels 150 continue to fill. This interaction between the gas spring arrangements 160 will force the branch channels 150 and the sample chambers 140 to fill with fluid sample 180 at the same rate.
[0223] As shown in Figures 6 and 7, the features of the sample cartridge 300 described above, and in particular the interaction between the hydrophobic vent 130 and the gas spring arrangements 160, means that the fluid sample 180 in each branch channel 150 will reach each analyte chamber 170 and then each sample chamber 140 at substantially the same time. Thus, the sample cartridge 300 provides a means of achieving simultaneous filling of a plurality of sample chambers 140 controlled using only passive pressure controls throughout the sample cartridge 300 activated by the fluid sample itself.
[0224] Figures 8 to 10 illustrate the filling of the analyte chamber 170 of the sample cartridge 300 with the fluid sample 180. For example, Figures 8 to 10 illustrate the state of the analyte chamber 170 between the states of the sample cartridge 300 shown in Figures 5 to 7.
[0225] The analyte chamber 170 includes a reagent 172 to be mixed with the fluid sample 180 as the fluid sample flows through the analyte chamber. The analyte chamber 170 further comprises mixing structures 173, 174 adapted to generate turbulence 175 in a flow of fluid sample through the analyte chamber in order to improve the mixing of the reagent with the fluid sample 180.
[0226] As shown in Figures 8 to 10, as the fluid sample 180 flows into and through the analyte chamber 170, the mixing structures 173, 174 disrupt the flow of the fluid sample 180 in order to generate turbulence 175. The turbulent flow of the fluid sample 180 encourages the mixing of the reagent 172 with the fluid sample. The fluid sample 180 with the reagent 172 suspended therein continues to flow through the reagent chamber 170 and out towards the sample chamber 140.
[0227] Figure 11 shows a sample chamber 140 according to an aspect of the invention. The sample chamber 140 shown in Figure 11 may represent each of the plurality of sample chambers 140 shown in Figures 1 to 7. The sample chamber 140 comprises an upstream sub-chamber 148 and a downstream sub-chamber 149 separated from each other, but fluidically connected via, a partition 143. The partition 143 is fluid permeable under a given pressure, meaning that below said given pressure the upstream 148 and downstream 149 sub-chambers are fluidically isolated from each other and above said given pressure upstream 148 and downstream 149 sub-chambers are fluidically connected to each other. The upstream sub-chamber 148 is fluidically connected to the downstream branch end 154 of the branch channel connecting the sample chamber 140 to the priming channel 120.
[0228] The upstream sub-chamber 148 is fluidically connected to a priming gas spring 262, which may be the upstream gas spring 162 described above with respect to Figures 1 to 7. The downstream sub-chamber 149 is fluidically connected to a balancing gas spring 264, which may be the downstream gas spring 164 described above with respect to Figures 1 to 7. The balancing gas spring 264 is fluidly connected to the downstream sub-chamber by a plurality of ducts 265, 266. The balancing gas spring comprises a plurality of gas spring chambers 267, 268, 269 fluidically connected to each other. Two of the gas spring chambers 267, 269 are directly fluidically connected to the downstream sub-chamber 144 via the ducts 265, 266 and one of the gas spring chambers 268 is only fluidically connected to the other gas spring chambers 267, 269.
[0229] In the example shown in Figure 11 , the sample chamber includes a dehydrated bacterial growth platform 145, in the form of a combination of dehydrated agarose, adapted to rehydrate on contact with the fluid sample, and a dehydrated growth medium containing nutrients to encourage bacterial growth in the sample chamber.
[0230] Figure 11 shows the dehydrated bacterial growth platform 145 provided as a film on an internal surface of the sample chamber 140, and in particular an internal surface of the upstream sub-chamber 148 parallel to the partition 143. The dehydrated bacterial growth platform 154 has a thickness between 0.1 pm and 100 pm, for example a thickness between 0.5 pm and 75 pm, for example a thickness of 50 pm. The dehydrated bacterial growth platform 145 is arranged adjacent the fluid inlet of the upstream sub-chamber 148, i.e., the downstream branch end 154 of the branch channel.
[0231] In the example shown in Figure 11 , the sample chamber 140 further comprises an absorptive element 146 adapted to absorb at least part of the fluid sample and adapted to reduce the humidity of the sample chamber 140 to prevent rehydration of the dehydrated bacterial growth platform 145 prior to contact with the fluid sample. In the particular example shown in Figure 11 , the absorptive element 146 is a spherical ball of hydrogel movably received in the downstream sub-chamber 144 of the sample chamber 140. The absorptive element 146 comprises a dissolvable coating 147 to retard the absorption of the fluid sample by the absorptive element once it is introduced to the downstream sub-chamber 149.
[0232] Figures 12 to 17 illustrate the filling of the sample chamber 140 shown in Figure 11 . As discussed above, the filling procedure illustrated in Figures 12 to 17 may occur in all of the sample chambers 140 of the sample cartridges shown in Figures 1a to 7 simultaneously.
[0233] The fluid sample 180 enters the upstream sub-chamber 148, at which point the entire branch channel 150 leading to the sample chamber will have been filled, for example as shown in Figure 6. The air pressure in the priming gas spring 262 and the balancing gas spring 264 will have been building as the branch channel 150 was filling with the fluid sample and forces 291 and 292 will be acting against the movement of the fluid sample into the sample chamber.
[0234] The fluid sample 180 fills the upstream sub-chamber 148 as shown in Figure 13 until the pressure in the priming gas spring 262 reaches the threshold pressure to cause the fluid sample to pass through the partition and into the downstream sub-chamber as shown in Figure 14.
[0235] As the fluid sample 180 comes into contact with the dehydrated bacterial growth platform 145, it rehydrates to form a bacterial growth platform suitable for encouraging the growth of bacteria thereon. The bacterial growth platform may swell on rehydration, for example to a thickness of 100 pm from a dehydrated thickness of 50 pm. Despite the swelling, the bacterial growth platform maintains a separation from the partition 143 in order to permit the free flow of fluid sample through the partition 143 without blocking the fluid pathway.
[0236] The partition 143 shown in Figures 11 to 17, comprises a fluid permeable filter adapted to prevent the passage of bacteria through the filter. Therefore, as the fluid sample 180 passed through the partition from the upstream sub-chamber 148 to the downstream sub-chamber 149, bacteria contained within the fluid sample will be left on the partition.
[0237] Further, as the fluid sample 180 enters the downstream sub-chamber 149, the fluid sample 180 contacts the absorptive element 146 and begins to dissolve the dissolvable coating 147 as the sample chamber 140 continues to fill with the fluid sample.
[0238] As shown in Figure 15, once the dissolvable coating 147 of the absorptive element 146 has been dissolved, the absorptive element 146 begins to absorb the fluid sample 180. In the absence of the fluid sample 180 in the downstream sub-chamber 144, the absorptive element 146 is in a dehydrated state (as shown in Figure 12), and when the absorptive element 146 absorbs at least part of the fluid sample 180 it changes from the dehydrated state to a hydrated state. The volume of the absorptive element 146 in the hydrated state (as shown in Figures 15 to 17) is larger than a volume of the absorptive element 146 in the dehydrated state (as shown in Figures 12 to 14).
[0239] As shown in Figures 16 and 17, the volume of the downstream sub-chamber 149 is lower than the volume of the absorptive element 146 in the hydrated state and as the absorptive element 146 continues to swell, the absorptive element 146 exerts a force on the partition 143. The partition 143 being a flexible bacterial filter, the partition deforms under the force exerted by the expanding absorptive element 146 until the partition is flattened against the bacterial growth platform 145.
[0240] As the lower surface of the partition 143 is covered in bacteria captured from the fluid sample flowing through the partition 143 from the upstream sub-chamber 148 to the downstream sub-chamber 149, the bacteria will be brought into contact with the bacterial growth platform 145. Further, as the partition 143 is flattened against the bacterial growth platform 145, the bacteria growing on the bacterial growth platform will all be constrained to the same plane, which enables accurate imaging and analysis of the bacteria within the sample chamber. Figure 18a shows a schematic plan view of a downstream sub-chamber 300 of a sample chamber according to an aspect of the invention.
[0241] In the example shown in Figure 18a, the perimeter of the downstream sub-chamber 300 is described by a first arced side wall 301 and a second arced side wall 302. The first arced side wall 301 are connected to the second arced side wall 302 by a pair of converging straight side walls 303a, 303b. The radius of the first arced side wall 301 is larger than the radius arc of the second arced side wall 302 such that the pair of straight side walls 303a, 303b converge towards the second arced side wall 302 from the first arced side wall 301 .
[0242] Figure 18a shows an absorptive element in the form a hydrogel disk 304 provided within the arc of the first arced side wall 301 with a snug fit. By providing the hydrogel disk 304 with a snug fit within the arc of the first arced side wall 301 , the expansion of the hydrogel disk 304 must occur across the area bounded by the converging straight side walls 303a, 303b towards the second arced side wall 302.
[0243] The partition 305 between the upstream sub-chamber 306, which contains the dehydrated growth platform, and the downstream sub-chamber 300 is provided within the arc of the second arced side wall 302. The partition 306 shown in Figure 18a comprises a circular aperture covered by a fluid-permeable membrane.
[0244] Figure 18b shows a schematic plan view of a downstream sub-chamber 310 of a sample chamber according to an aspect of the invention.
[0245] In the example shown in Figure 18b, the downstream sub-chamber comprises three retaining members 311 projecting from a side wall 312 of the downstream sub-chamber towards the absorptive element, which is provided in the form of a hydrogel disk 304, for retaining the absorptive element in a predetermined position.
[0246] The retaining members 311 each comprise a rounded distal tip 313, the rounded distal tip being located at a distal end of each retaining member 311 opposite the side wall 312 of the downstream sub-chamber 301 and proximate the hydrogel disk 304. The retaining members 311 are integrally formed with the side wall 312 of the downstream sub-chamber.
[0247] In the example shown in Figure 18b, the downstream sub-chamber 310 comprises three expansion areas 314, each expansion area being provided between adjacent retention members 311 . The side wall 312 of the downstream sub-chamber 310 is curved between the expansion areas 314 and the retaining members 311 .
[0248] The partition 305 between the upstream sub-chamber 306 and the downstream sub-chamber 310 is provided within a perimeter bounded by the distal ends of the retaining members 311 . The partition 305 comprises a circular aperture covered by a fluid-permeable membrane. The partition 305 is substantially concentric with the hydrogel disk 304 retained by the retaining members 311 . By providing the hydrogel disk 304 with a snug fit within the retaining members 311 , the expansion of the hydrogel disk 304 must occur into the expansion areas 314 bounded by the retaining members 311 . The downstream sub-chamber 310 may comprise an air outlet 315 provided within each of the expansion areas 314, the air outlets 315 providing an air pathway between the downstream sub-chamber and the downstream air spring. The air outlets 315 being sized small enough to prevent the hydrogel disk 304 from expanding into the air pathway.
[0249] Figure 18c shows a schematic cross-section of a sample chamber 320 comprising the downstream subchamber 300 of Figure 18a. Figure 18d shows a schematic cross-section of the sample chamber 320 of Figure 18c after the sample chamber has been filled with fluid sample. The sample chamber 320 shown in Figure 18c may represent each of the plurality of sample chambers 140 shown in Figures 1 to 7.
[0250] The sample chamber 320 shown in Figures 18c and 18d may have a similar layout to the sample chamber 140 described above with respect to Figure 11 . The sample chamber 320 comprises an upstream sub-chamber 330 and a downstream sub-chamber 300 separated from each other, but fluidically connected via, a partition 305, which may comprise a fluid permeable membrane as outlined above. The upstream sub-chamber 330 is fluidically connected to the downstream branch end 154 of the branch channel connecting the sample chamber 320 to the priming channel 120 by way of a fluid inlet 322 formed in a side wall of the sample chamber.
[0251] The upstream sub-chamber 330 is fluidically connected to a priming gas spring 331 , which may be the upstream gas spring 162 described above with respect to Figures 1 to 7. The downstream sub-chamber 300 is fluidically connected to a balancing gas spring 321 , which may be the downstream gas spring 164 described above with respect to Figures 1 to 7. The balancing gas spring 321 is fluidly connected to the downstream sub-chamber by a ducts sized to prevent the hydrogel disk 304 from expanding into the air pathway connecting the balancing gas spring to the downstream sub-chamber 300.
[0252] In the example shown in Figures 18c and 18d, the sample chamber includes a dehydrated bacterial growth platform 332, in the form of a combination of dehydrated agarose, adapted to rehydrate on contact with the fluid sample, and a dehydrated growth medium containing nutrients to encourage bacterial growth in the sample chamber 320.
[0253] The sample chamber 320 comprises a chamber wall 333 at least partially defining an internal cavity 334 of the sample chamber 320, and in particular, the upstream sub-chamber 330. The internal cavity 334 receives the fluid sample 180 from the fluid pathway.
[0254] As shown in Figures 18c and 18d, the chamber wall comprises a recess 335. The dehydrated bacterial growth platform 332 is provided within the recess 335. The recess 335 in the chamber wall 333 is a shallow cylindrical recess with a width, or diameter, of the recess being greater than a depth of the recess.
[0255] As explained in further detail below with reference to Figures 19a to 19c, the dehydrated bacterial growth platform 332 may be formed within the recess 335 of the chamber wall 333 during the manufacture of the sample cartridge.
[0256] In the example shown in Figures 18c and 18d, an upper surface 332a of the dehydrated bacterial growth platform 332 is aligned with a cavity facing surface 336 of the chamber wall 336. The cavity facing surface 336 is also aligned with a boundary surface 323 of the fluid inlet 322. The upper surface 332a of the dehydrated bacterial growth platform 332 is therefore also aligned with the boundary surface 323 of the fluid inlet 322 and the recess 335 is recessed with respect the boundary surface 323 of the fluid inlet 322.
[0257] Figure 18d shows the sample chamber 320 of Figure 18c after the sample chamber 320 has been filled with fluid sample 180. The various components of the sample chamber 320 function in a similar manner to those outlined above with respect to Figures 12 to 17.
[0258] Figures 19a to 19c illustrate the dispensing of a liquid platform precursor 340 into a recess 335 of a chamber wall 333.
[0259] As outlined above, the dehydrated bacterial growth platform may comprise a dehydrated gel medium, such as dehydrated agar or dehydrated agarose. In such examples, the liquid platform precursor may comprises a hydrated gel medium, such as agar or agarose, which is dispensed in liquid, or gel or aqueous, form into the recess of the chamber wall.
[0260] Figure 19a shows an initial stage of dispensing of the liquid platform precursor 340 into the recess 335 of the chamber wall 333.
[0261] The liquid platform precursor 340 is dispensed onto the base surface 341 of the recess 335 as a target surface. At the initial stage shown in Figure 19a, the liquid platform precursor 340 behaves as though it had been dispensed onto a flat surface and forms a convex meniscus.
[0262] Figure 19b shows a progressed stage of dispensing of the liquid platform precursor 340 into the recess 335 of the chamber wall 333.
[0263] The liquid platform precursor 340 spreads across the base surface 341 of the recess 335 until the liquid platform precursor reaches a side wall 342 of the recess 335. The dispensing may continue until base surface 341 is covered by the liquid platform precursor 340.
[0264] Figure 19c shows a final stage of dispensing of the liquid platform precursor 340 into the recess 335 of the chamber wall 333.
[0265] After liquid platform precursor 340 has spread across the base surface 341 of the recess 335 and contacts the side wall 342 of the recess 335, the contact angle between the liquid platform precursor 340 and the recess 335 may be altered. In the example shown in Figures 19a to 19c, the meniscus formed by the liquid platform precursor changes from a convex meniscus, as shown in Figure 19a, to a concave meniscus, as shown in Figure 19c.
[0266] The liquid platform precursor 340 is then dried, either actively or passively, in order to form the dehydrated bacterial growth platform 332 shown above in Figures 18c and 18d.
[0267] Figure 20 shows a schematic representation of a sample cartridge construction. In particular, Figure 20 shows a view of the sample chamber 320 to illustrate the construction of the larger sample cartridge.
[0268] In the example shown in Figure 20, the sample cartridge comprises a cartridge frame 350. The chamber wall 333 is coupled to the cartridge frame to form the internal cavity of the sample chamber 320. The sample cartridge may comprise a plurality of sample chambers 320 as described above. The chamber wall 333 may form part of a capping component 360 that is part of a two-part construction of the sample cartridge. The capping component 360 may comprise a respective chamber wall 333 for forming a respective internal cavity of each of the plurality of sample chambers 320 when the capping component is coupled to the cartridge frame 350. The fluid pathway may also be formed between the cartridge frame 350 and the capping component 360 when the capping component 360 is coupled to the cartridge frame 350.
[0269] The cartridge frame 350 and the capping component 360 may be coupled together by way of an adhesive. In the example shown in Figure 20, the capping component 360 comprises a rivet 351 extending from the capping component 360 to contact the cartridge frame 350. In the example where the capping component 360 and the cartridge frame 350 are formed of rigid plastic, the rivet 351 is also formed of rigid plastic and may be used to form a thermal weld between the capping component 360 and the cartridge frame 350 in order to reinforce the coupling.
[0270] By providing a two-part sample cartridge construction, the dispensing of the liquid platform precursor 340 can be simplified, because the liquid platform precursor 340 can be directly dispensed into the recess 335 and dried to form the dehydrated bacterial growth platform 332 before the capping component 360 is coupled to the cartridge frame 350.
[0271] The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.
[0272] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.
[0273] For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations.
[0274] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.
[0275] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.
[0276] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example + / - 10%.
Claims
Claims:1 . A sample cartridge for processing a fluid sample, the sample cartridge comprising: a fluid pathway having an upstream end and a downstream end, wherein the fluid pathway is adapted to receive the fluid sample at the upstream end and route the fluid sample to the downstream end; and a sample chamber fluidically connected to the downstream end of the fluid pathway, the sample chamber comprising: a chamber wall at least partially defining an internal cavity of the sample chamber, the internal cavity being adapted to receive the fluid sample from the fluid pathway, wherein the chamber wall comprises a recess; and a dehydrated bacterial growth platform for encouraging bacterial growth of bacteria present in the fluid sample, wherein the dehydrated bacterial growth platform is provided in the recess of the chamber wall.
2. The sample cartridge according to claim 1 , wherein an upper surface of the dehydrated bacterial growth platform is aligned with a cavity facing surface of the chamber wall.
3. The sample cartridge according to any preceding claim, wherein the sample chamber comprises at least one side wall at least partially defining the internal cavity of the sample chamber, wherein the at least one side wall comprises a fluid inlet fluidically connecting the internal cavity of the sample chamber to the downstream end of the fluid pathway.
4. The sample cartridge according to claim 3, when dependent directly or indirectly on claim 2, wherein a boundary surface of the fluid inlet is aligned with the cavity facing surface of the chamber wall.
5. The sample cartridge according to any preceding claim, wherein the sample chamber comprises an upstream sub-chamber and a downstream sub-chamber, wherein the upstream sub-chamber is fluidically connected to the downstream end of the fluid pathway, and wherein the downstream subchamber is fluidically connected to the upstream sub-chamber, and wherein the chamber wall at least partially defines the upstream sub-chamber such that the recess is provided in the upstream subchamber of the sample chamber.
6. The sample cartridge according to claim 5, wherein the upstream sub-chamber is separated from the downstream sub-chamber by a fluid permeable membrane, and wherein the recess in the chamber wall and the fluid permeable membrane are provided on opposing sides of the upstream subchamber.
7. The sample cartridge according to any preceding claim, wherein the recess is a cylindrical recess.
8. The sample carriage according to any preceding claim, wherein the recess has a depth of between0.1 pm and 100 pm, for example a depth between 0.5 pm and 75 pm, for example a depth of 50 pm9. The sample cartridge according to any preceding claim, wherein the dehydrated bacterial growth platform comprises a dehydrated gel medium, for example dehydrated agar or agarose.
10. The sample cartridge according to any preceding claim, wherein the sample cartridge comprises a cartridge frame, and wherein the chamber wall is coupled to the cartridge frame to form the internal cavity of the sample chamber.
11. The sample cartridge according to any preceding claim, wherein the sample cartridge comprises a plurality of sample chambers.
12. The sample cartridge according to claims 10 and 11 , wherein the sample cartridge comprises a capping component, the capping component comprising a respective chamber wall for forming a respective internal cavity of each of the plurality of sample chambers when the capping component is coupled to the cartridge frame.
13. The sample cartridge according to claim 12, wherein the fluid pathway is formed between the cartridge frame and the capping component when the capping component is coupled to the cartridge frame.
14. A method of manufacturing the sample cartridge according to any of claims 1 to 13, the method comprising: dispensing a liquid platform precursor into the recess of the chamber wall; and drying the liquid platform precursor to form the dehydrated bacterial growth platform in the recess.
15. The method according to claim 14, wherein dispensing the liquid platform precursor into the recess of the chamber wall comprises dispensing the liquid platform precursor until a target surface of the recess is covered by the liquid platform precursor.
16. The method according to any of claims 14 to 15, wherein a dispensed volume of the liquid growth platform precursor is greater than or equal to about 90% of the volume of the recess.
17. The method according to any of claims 14 to 16 for manufacturing the sample cartridge according to any of claims 10 to 13, wherein, after the step of drying the liquid platform precursor to form the dehydrated bacterial growth platform in the recess, the method further comprises coupling the chamber wall to the cartridge frame to form the internal cavity of the sample chamber.
18. A sample cartridge for processing a fluid sample, the sample cartridge comprising: an inlet for receiving the fluid sample;a priming channel having an upstream priming end and a downstream priming end opposite the upstream priming end, wherein the priming channel is in fluid communication with the inlet at the upstream priming end of the priming channel; and a plurality of sample chambers, each sample chamber in fluid communication with the priming channel by way of one of a plurality of branch channels, each branch channel having an upstream branch end and a downstream branch end, wherein an upstream branch end of each of the branch channels is fluidically connected to the priming channel, between the upstream priming end and the downstream priming end of the priming channel, and wherein the downstream branch end of each of the branch channels is fluidically connected to a respective one of the sample chambers, and wherein the priming channel comprises a sealable vent located at the downstream priming end of the priming channel, and wherein the sealable vent is a hydrophobic vent, and wherein the hydrophobic vent is gas permeable in a dry state, and wherein the hydrophobic vent is sealed in a wet state.
19. The sample cartridge of claim 18, wherein the hydrophobic vent comprises filter paper.
20. The sample cartridge of any of claims 18 to 19, wherein each of the plurality of branch channels comprises a branch inlet section extending from the upstream branch end of the branch channel to a downstream branch inlet end, and wherein an angle between a priming flow vector, the priming flow vector being defined from the upstream priming end to the downstream priming end of the priming channel, and a branch flow vector, the branch flow vector being defined from the upstream branch end to the downstream branch inlet end, is an acute angle.
21. The sample cartridge of any of claims 18 to 20, wherein each of the plurality of branch channels comprises at least one bend between the upstream branch end and the downstream branch end of the branch channel, and optionally wherein each of the plurality of branch channels is routed such that fluid sample flowing along a portion of each branch channel flows in a direction opposite to fluid sample flowing in the priming channel.
22. The sample cartridge of any of claims 18 to 21 , wherein at least one of the plurality of branch channels further comprises an analyte chamber between the upstream branch end and the downstream branch end, wherein the analyte chamber comprises a reagent to be mixed with the fluid sample as the fluid sample flows through the analyte chamber.
23. The sample cartridge of claim 22, when dependent on claim 21 , wherein the analyte chamber is provided downstream of the at least one bend.
24. The sample cartridge of any of claims 22 to 23, wherein the analyte chamber comprises one or more mixing structures adapted to generate turbulence in a flow of fluid sample through the analytechamber.
25. The sample cartridge claimed in any of claims 18 to 24, wherein the plurality of sample chambers comprises: a first row of sample chambers provided on a first side of the priming channel; and a second row of sample chambers provided on a second, opposing side of the priming channel to the first row.
26. The sample cartridge claimed in claim 25, wherein: the upstream branch ends of the plurality of branch channels fluidically connecting the first row of sample chambers to the priming channel are aligned with the upstream branch ends of the plurality of branch channels fluidically connecting the second row of sample chambers to the priming channel; or the upstream branch ends of the plurality of branch channels fluidically connecting the first row of sample chambers to the priming channel are offset, along the length of the priming channel, from the upstream branch ends of the plurality of branch channels fluidically connecting the second row of sample chambers to the priming channel.
27. The sample cartridge claimed in any of claims 18 to 26, wherein the sample cartridge further comprises a plurality of gas spring arrangements, wherein each gas spring arrangement is fluidically connected to a respective one of the plurality of sample chambers downstream of said respective sample chamber.
28. The sample cartridge claimed in claim 27, wherein each sample chamber comprises a partition dividing each sample chamber into an upstream sub-chamber and a downstream sub-chamber, wherein the upstream sub-chamber is fluidically connected to the downstream branch end of the branch channel, and wherein the downstream sub-chamber is fluidically connected to the upstream sub-chamber via the partition.
29. The sample cartridge claimed in claim 28, wherein each gas spring arrangement comprises: a priming gas spring fluidically connected to the upstream sub-chamber; and a balancing gas spring fluidically connected to the downstream sub-chamber.
30. The sample cartridge claimed in claim 29, wherein the balancing gas spring is fluidly connected to the downstream sub-chamber by a plurality of ducts, and wherein the balancing gas spring comprises a plurality of gas spring chambers fluidically connected to each other, and wherein each of the plurality of ducts is fluidically connected to a respective one of the plurality of gas spring chambers.31 . A method for filling a sample chamber of a sample cartridge with a fluid sample, the method comprising: providing a fluid sample to an inlet of the sample cartridge, thereby filling a priming channel of the sample cartridge, the priming channel having an upstream priming end and a downstream priming end opposite the upstream priming end, wherein the priming channel is fluidically connected to theinlet at the upstream priming end of the priming channel; sealing a sealable vent at the downstream priming end of the priming channel when the priming channel is filled with the fluid sample, wherein the sealable vent is a hydrophobic vent, and wherein the hydrophobic vent is gas permeable in a dry state, and wherein the hydrophobic vent is sealed in a wet state, and wherein sealing the sealable vent comprises wetting the hydrophobic vent with the fluid sample; and continuing to provide the fluid sample to the inlet of the sample cartridge, thereby causing the fluid sample to flow through a plurality of branch channels, which fluidically connect to the priming channel at an upstream branch end of each branch channel and to a sample chamber at a downstream branch end of each branch channel, thereby filling a plurality of sample chambers.
32. The method claimed in claim 31 , wherein the sample cartridge further comprises a plurality of gas spring arrangements fluidically connected to one of the plurality of sample chambers downstream of said sample chamber, and wherein the method further comprises: dynamically balancing the fluid flow along the plurality of branch channels and into the plurality of sample chambers by compressing air within the plurality of gas spring arrangements as the fluid sample flows along the plurality of branch channels and towards the plurality of sample chambers, and optionally wherein the method further comprises filling the plurality of sample chambers substantially simultaneously by dynamically balancing the fluid flow along the plurality of branch channels and into the plurality of branch chambers.
33. A sample cartridge for processing a fluid sample, the sample cartridge comprising: a fluid pathway having an upstream end and a downstream end, wherein the fluid pathway is adapted to receive the fluid sample at the upstream end and route the fluid sample to the downstream end; a sample chamber fluidically connected to the downstream end of the fluid pathway, the sample chamber comprising: a fluid permeable partition dividing the sample chamber into an upstream sub-chamber and a downstream sub-chamber, wherein the upstream sub-chamber is fluidically connected to the downstream end of the fluid pathway, and wherein the downstream sub-chamber is fluidically connected to the upstream sub-chamber via the partition; and an absorptive element adapted to absorb at least part of the fluid sample, wherein the absorptive element is provided in the downstream sub-chamber.
34. The sample cartridge claimed in claim 33, wherein: in the absence of the fluid sample in the downstream sub-chamber, the absorptive element is in a dehydrated state; and in the presence of the fluid sample in the downstream sub-chamber, the absorptive element is adapted to absorb at least part of the fluid sample to change from the dehydrated state to a hydrated state, and wherein, a volume of the absorptive element in the hydrated state is larger than a volume of theabsorptive element in the dehydrated state.
35. The sample cartridge claimed in claim 34, wherein a volume of the downstream sub-chamber is lower than the volume of the absorptive element in the hydrated state, such that the absorptive element in exerts a force on the partition as the absorptive element swells from the dehydrated state to the hydrated state, and optionally wherein the partition is flexible such that the partition deforms under the force exerted by the absorptive element in the hydrated state.
36. The sample cartridge as claimed in any of claims 33 to 35, wherein the partition comprises a polytetrafluoroethylene membrane having a thickness between about 80pm to 90pm and a pore size of between about 0.1 pm to 1 .5pm..
37. The sample cartridge claimed in any of claims 33 to 36, wherein the upstream sub-chamber comprises a bacterial growth platform.
38. The sample cartridge claimed in claim 37, when dependent on claim 36, wherein a volume of the sample chamber is lower than the volume of the absorptive element in the hydrated state, such that the partition is deformed to contact the bacterial growth platform.
39. The sample cartridge claimed in claim 38, wherein the partition is deformed to be substantially flattened against the growth medium.
40. The sample cartridge claimed in any of claims 33 to 39, wherein the absorptive element is three- dimensional, and optionally wherein the absorptive element is spherical.41 . The sample cartridge claimed in any of claims 33 to 40, wherein the absorptive element comprises a hydrogel.
42. The sample cartridge claimed in any of claims 33 to 41 , wherein the partition comprises a fluid permeable filter adapted to prevent the passage of bacteria through the filter, the bacteria being present in the fluid sample.
43. The sample cartridge claimed in any of claims 33 to 42, wherein the fluid pathway widens along a downstream direction as it approaches the sample cartridge from an upstream direction.
44. The sample cartridge claimed in any of claims 33 to 43, wherein the downstream sub-chamber comprises: a first arced side wall; a second arced side wall; and a pair of straight side walls connecting the first arced side wall to the second arced side wall, wherein a radius of the first arced side wall is greater than a radius of the second arced side wall such that the pair of straight side walls converge towards the second arced side wall from the firstarced side wall.
45. The sample cartridge claimed in any of claims 33 to 43, wherein the downstream sub-chamber comprises a plurality of retaining members projecting from a side wall of the downstream subchamber towards the absorptive element for retaining the absorptive element in a predetermined position.
46. A method for filling a sample chamber of a sample cartridge with a fluid sample, the sample chamber comprising a partition dividing the sample chamber into an upstream sub-chamber and a downstream sub-chamber, and wherein the sample chamber comprises an absorptive element provided in the downstream sub-chamber adapted to absorb at least part of the fluid sample, the method comprising: providing a fluid sample to a fluid pathway of the sample cartridge, thereby filling an upstream sub-chamber of the sample chamber that is fluidically connected to a downstream end of the fluid pathway; and continuing to provide the fluid sample to the fluid pathway of the sample cartridge, thereby causing the fluid sample to flow through the partition from the upstream sub-chamber to the downstream sub-chamber.
47. The method of claim 46, wherein the partition is flexible and the upstream sub-chamber comprises a bacterial growth platform, and wherein the method further comprises: deforming the partition to contact the bacterial growth platform, wherein deforming the partition comprises: continuing to provide the fluid sample to the fluid pathway of the sample cartridge, thereby causing the fluid sample to be absorbed by the absorptive element, such that the absorptive element changes from a dehydrated state to a hydrated state, wherein a volume of the absorptive element in the hydrated state is larger than a volume of the sample chamber such that the absorptive element in the hydrated state exerts a force on the partition, thereby deforming the partition to contact the bacterial growth platform.
Citation Information
Patent Citations
Sample cartridge
EP4603186A1
Sample cartridge
EP4603571A1
Sample cartridge
EP4603572A1
Multi-flux microfluidic chip used for nucleic acid detection
CN110295107A
Disposable device for use in chemical, immunochemical and microorganism analysis
EP0282840B1