Centrifugal excitation fluid systems, devices and methods

Abstract

The fluid device (1) is configured to drive fluid movement under centrifugal force, comprising a central region about a central axis of rotation (X) of the device and a peripheral region extending radially outward from the central region. A fluid reservoir (4) located in the central region of the device receives a fluid sample and is in communication with at least one fluid system (6) extending radially outward from the fluid reservoir (4) to the peripheral region of the device. Each fluid system (6) includes a fluid analysis chamber (12) configured to retain a portion of the fluid sample for analysis. A fluid channel arrangement (26) is configured to allow fluid communication between the fluid reservoir (4) and the fluid analysis chamber (12), and the movement of the fluid sample through the fluid channel arrangement is driven by centrifugal force generated by the rotational motion of the device about the central axis of rotation (X). A valve mechanism (8) is arranged between the fluid reservoir (4) and the analysis chamber (12) and is configured to prevent fluid from flowing through that portion of the fluid channel arrangement (26) when the rotational speed of the device is less than a predetermined value. A cutout portion (24) of the device facilitates proper positioning of the fluid device (1) within the measuring apparatus. The invention also describes a device for driving the rotational motion of a fluid device and a method for moving a fluid sample within the fluid device.

Description

Technical Field

[0001] This disclosure relates to containers and apparatuses for fluid systems (jet systems) that incorporate centrifugal excitation, and particularly to the use of such containers and apparatuses for dispensing a portion of a fluid sample and subsequently analyzing the properties of the sample. Background Technology

[0002] A fluid system is a closed, interconnected network or structure containing channels, chambers, or reservoirs, and has dimensions ranging from millimeters to micrometers.

[0003] The flow of fluid through an interconnected network of channels and chambers in a fluid system can be driven or excited by centrifugal force / centripetal force, which is generated by the rotation of a platform or device formed within the fluid system.

[0004] This concept of centripetally exciting or driving fluid flow through a fluid system by rotation has been used in various devices and is applicable to a wide range of technical fields. Several different devices utilize concepts related to chemical and / or biological assays; in these cases, fluid property analysis is typically performed during or after such movement.

[0005] It is against this backdrop that this apparatus, system, and method were designed. Summary of the Invention

[0006] According to one aspect of this disclosure, a fluid device configured to drive fluid movement under centrifugal force is provided, the fluid device comprising: a central region about a central axis of rotation of the device and a peripheral region extending radially outward from the central region; a fluid reservoir disposed in the central region of the device for receiving a fluid sample, the fluid reservoir being in communication with at least one fluid system extending radially outward from the fluid reservoir to the peripheral region of the device; said or each fluid system comprising: a fluid analysis chamber configured to retain a portion of the fluid sample for analysis; a fluid channel arrangement configured to enable fluid communication between the fluid reservoir and the fluid analysis chamber, wherein movement of the fluid sample through the fluid channel arrangement is driven by centrifugal force generated by rotational motion of the device about a central axis of rotation; and a first valve mechanism configured to prevent fluid from flowing through a portion of the fluid channel arrangement when the rotational speed of the device is less than a first predetermined value, wherein the first valve mechanism is arranged between the fluid reservoir and the analysis chamber. In any aspect and embodiment, the valve mechanism may advantageously be a pneumatic gate or an "air spring".

[0007] Suitablely, in these aspects and embodiments, the fluid channel arrangement includes: a separation chamber configured to remove unwanted particles from a fluid sample before it enters an analysis chamber; and a first fluid channel extending radially outward from a fluid reservoir to the separation chamber. Preferably, the first fluid channel arrangement communicates with the separation chamber through a wall in a radially outer region of the separation chamber.

[0008] In some embodiments, the first fluid passage extends to the radially outermost portion of at least one fluid system. In other embodiments, the separation chamber is shaped to encompass the radially outermost point of the fluid system. In other particularly suitable embodiments, the fluid analysis chamber is radially arranged outside the separation chamber. Most preferably, the fluid analysis chamber is the radially outermost element of the fluid system. In embodiments, the fluid analysis chamber is cylindrical, having a generally circular cross-section in the axial plane of the device.

[0009] The separation chamber can be configured / shaped as a defined bag, "toe," or corner extending radially outward from the inlet of the first fluid channel. Advantageously, in this arrangement, the incoming unclarified fluid does not disturb any sediment stored / collected in the radially outermost portion of the separation chamber. In some embodiments, the separation chamber is wedge-shaped, wherein a relatively wider region of the separation chamber is located radially outside a relatively narrower region of the separation chamber. This may further facilitate sedimentation from the inlet of the first fluid channel.

[0010] In some embodiments, the depth (d) of the separation chamber defines the height between the bottom and top of the separation chamber, and a first fluid channel is arranged to communicate with the separation chamber at or near the bottom of the separation chamber, thereby allowing the separation chamber to load fluid samples from the bottom up.

[0011] Suitably, the fluid channel arrangement includes a second fluid channel configured for fluid communication between a separation chamber and a fluid analysis chamber, wherein a first valve mechanism is located in the flow path of the second fluid channel between the separation chamber and the analysis chamber. In these embodiments, the second fluid channel may suitably include a pair of channel arms configured to allow fluid to flow in substantially antiparallel directions (e.g., both the first and second channel arms may be arranged to extend in a generally radial direction), wherein the first valve mechanism is located in the flow path between the two channel arms. Thus, the second fluid channel may include a first channel arm for fluid communication between the separation chamber and the first valve mechanism, the first channel arm extending radially inward from the separation chamber to the first valve mechanism and communicating with the separation chamber through a wall in a radially inner region of the separation chamber. Therefore, it is advantageous that the first fluid channel communicates radially outward from the first channel arm of the second fluid channel with the separation chamber, so that unclarified fluid entering the separation chamber can be clarified before leaving the separation chamber in the direction of the valve mechanism.

[0012] Advantageously, the weir (or step) is located between the separation chamber and the inlet port of the second fluid channel, or at the junction of the separation chamber and the inlet port of the second fluid channel. The weir improves the separation / clarification function provided by the separation chamber by retaining the fluid sample in the separation chamber for a period of time during the clarification process. The weir also inhibits particles in the fluid from freely entering the second fluid channel. The height of the weir or step can be stepped, depending on preference and desired functionality.

[0013] Furthermore, in an embodiment, the second fluid channel includes a second channel arm for fluid communication between the first valve mechanism and the analysis chamber, the second channel arm extending radially outward from the first valve mechanism into the analysis chamber.

[0014] Advantageously, according to these aspects and embodiments, the first valve mechanism is located radially inside the separation chamber and / or the fluid analysis chamber.

[0015] In embodiments of this disclosure, a first valve mechanism defines a chamber for receiving a predetermined amount of gas, the chamber having dimensions along the x, y, and z axes, wherein the x-axis defines a radial direction, the y-axis defines a direction perpendicular to the x-axis in a radial plane, and the z-axis defines a direction parallel to the axis of rotation and perpendicular to both the x and y axes. In some preferred embodiments, the first valve mechanism has a maximum dimension along the z-axis (i.e., the maximum dimension of the chamber along the z-axis is greater than the maximum dimensions along the x and y axes). By configuring the maximum dimension of the valve mechanism along the axis of rotation, the radial dimension of the fluid device can be effectively reduced (e.g., by reducing the maximum x-axis dimension of the first valve mechanism); and / or the fluid device may preferably be able to include a greater number of fluid systems arranged circumferentially around the device (e.g., by reducing the maximum y-axis dimension of the first valve mechanism). Advantageously, the first valve mechanism is arranged radially outward circumferentially around the fluid reservoir and adjacent to the fluid reservoir. Typically, the first valve mechanism defines a chamber with a volume ranging from about 150 μl to 600 μl. In any such embodiment, the volume of the analytical chamber can range from about 30 μl to 150 μl. In some such embodiments, the volume of the precipitation chamber can range from about 60 μl to 300 μl. Therefore, according to aspects and embodiments of this disclosure, the volume of the precipitation chamber is suitably about twice the volume of the analytical chamber, and the volume of the air spring is suitably in the range of about two to four times the volume of the precipitation chamber. Advantageously, in conjunction with this embodiment, the volume of the air spring / valve mechanism can range from about 150 μl to 600 μl; and / or the volume of the analytical chamber can range from about 30 μl to 150 μl, and / or the volume of the precipitation chamber can range from about 60 μl to 300 μl.

[0016] Specifically used for determining the susceptibility of bacteria to one or more antibiotics, one or more fluid systems contain at least one antibiotic within their area, said antibiotic being in a form suitable for dissolving in a fluid sample. Advantageously, the antibiotic is in a dry form. In embodiments, the antibiotic is dry and reversibly adheres to the analytical chamber of the device. In some embodiments, a drug or other additive / chemical other than an antibiotic is contained in one or more fluid systems of the device according to this disclosure in a form suitable for dissolving in a fluid sample. Appropriately, one or more antibiotics, drugs, or chemicals may be selected based on the fluid sample, the nature of the expected infectious agent / pathogen, or the nature of the sample or pathogen to be evaluated.

[0017] In some embodiments, the fluid passage arrangement further includes a third fluid passage extending between the fluid analysis chamber and the second valve mechanism, wherein the second valve mechanism is located radially inward of the analysis chamber. Suitably, the first valve mechanism and / or the second valve mechanism each include a storage chamber for containing (compressed) gas. In some such embodiments, the second valve mechanism defines a chamber with a volume ranging from 10 μl to 50 μl. Therefore, typically, the volume of the second valve mechanism (if present) is smaller than the volume of the first valve mechanism (e.g., less than 3 to 15 times).

[0018] In use, the fluid within the device's fluid system is subjected to a combination of forces, including centrifugal force, gas pressure, and wicking / capillary force. This combination of forces may react against the centrifugal force and other forces. The wicking / capillary force arises from fluid movement through relatively narrow fluid channels, particularly in a very small (e.g., less than 100 μm) area at the junction of the fluid channel with the channel cover and bottom. To reduce any such undesirable fluid movement, one or more fluid channels in at least one fluid system may be configured with rounded inner corners to reduce capillary forces within the fluid system. In particular, the fluid channel between the fluid analysis chamber and the first valve mechanism (or the second channel arm of the second fluid channel) may at least have rounded inner corners. Similarly, the fluid channel between the first valve mechanism and the separation chamber (or the first channel arm of the second fluid channel) may have rounded corners. According to these aspects and embodiments of the present disclosure, the radius of curvature of the rounded inner corners may be from about 0.05 mm to 1 mm, for example, from 0.1 mm to 0.8 mm or from 0.2 mm to 0.6 mm (e.g., about 0.6 mm or less).

[0019] Suitably, at least one fluid system of the apparatus contains at least one drug for measuring a fluid sample, wherein the drug is disposed in a fluid analysis chamber; a first drug retention chamber located between a first valve mechanism and the fluid analysis chamber; or a second drug retention chamber located between a second valve mechanism and the fluid analysis chamber. The drug may be an antibiotic. Suitably, the drug is lyophilized and / or freeze-dried.

[0020] It should be understood that any one or more antibiotics may be included in the fluid device according to the invention. In various aspects and embodiments, those skilled in the art may select one or more antibiotics and one or more concentrations of one or more antibiotics for use in the system according to preference: for example, depending on the expected infectious agent, or based on a fluid sample used in conjunction with the fluid device. In certain embodiments, the drug / antibiotic may be selected from one or more of the group comprising / including: ciprofloxacin hydrochloride monohydrate (CIP); fosfomycin disodium salt (FOS); mecilinam hydrochloride (MEC HCl); nitrofurantoin sodium (NIT); trimethoprim lactate (TMP); and sulfamethoxazole sodium (SXT). In other embodiments, the drug / antibiotic is selected from one or more of the group comprising / including: amoxicillin; amoxicillin / clavulanic acid (2 / 1); cephalexin; ciprofloxacin; ertapenem; fosfomycin; levofloxacin; mecilinam; nitrofurantoin; trimethoprim; and trimethoprim / sulfamethoxazole (1 / 19). More specifically: at least one fluid system contains the antibiotic amoxicillin; at least one fluid system contains the antibiotic combination amoxicillin / clavulanic acid; at least one fluid system contains the antibiotic cephalexin; at least one fluid system contains the antibiotic ciprofloxacin; at least one fluid system contains the antibiotic ertapenem; at least one fluid system contains the antibiotic fosfomycin; at least one fluid system contains the antibiotic levofloxacin; at least one fluid system contains the antibiotic mecillin; at least one fluid system contains the antibiotic nitrofurantoin; at least one fluid system contains the antibiotic trimethoprim; and / or at least one fluid system contains the antibiotic combination trimethoprim / sulfamethoxazole; and optionally: at least one fluid system does not contain antibiotics and / or at least one fluid system contains an effective amount of bactericide. In some embodiments, the device comprises a variety of different antibiotics, such as those selected from those disclosed herein. In some embodiments, the device may comprise 2, 3, 4, 5, or 6 antibiotics or combinations thereof deposited in a plurality of different microfluidic systems. In some embodiments, the device comprises each of the antibiotics described above. Suitably, the antibiotic or other one or more drugs / chemicals are provided in a dry form or other form suitable to aid in the dissolution of the reagent in the sample solution.

[0021] According to aspects and embodiments of the invention, the apparatus of this disclosure comprises a plurality of fluid systems containing one of an antibiotic or a combination of antibiotics (or other agents), and each of the plurality of microsystems contains a different predetermined amount of antibiotic or combination of antibiotics, so that, in use, predetermined different concentrations of antibiotics (or other agents) are generated in the fluid sample in each analytical chamber of the plurality of fluid systems. Preferred apparatuses according to this disclosure comprise one or more antibiotics, the amounts of which are selected from the antibiotics and corresponding amounts in Tables 1 and / or 2. In particular, in embodiments of this disclosure, the amount of antibiotic contained in each fluid system is determined so that, in use, when dissolved in the amount of fluid sample passed through a first air spring / valve mechanism to fill the analytical chamber, the concentration of antibiotic in the fluid sample in the analytical chamber is approximately equal to a desired predetermined concentration. According to the CLSI standard, the concentration of the antibiotic (or combination of antibiotics) is suitably equal to the breakpoint of the corresponding bacteria. In other embodiments, according to the EUCAST standard, the concentration of the antibiotic (or combination of antibiotics) is equal to the breakpoint of the corresponding bacteria. In some embodiments, antibiotics may be present in different respective amounts in the plurality of separate fluid systems to achieve a desired range of different antibiotic concentrations in the final fluid sample from the plurality of separate fluid systems in use. For example, the desired / target antibiotic concentration may be a multiple of the CLSI and / or EUCAST concentration (e.g., multiples of 1x, 1.5x, 2x, 3x, 4x, 5x, 6x, 8x, 10x, or more). It should be understood that the potency of a particular antibiotic or other agent may be affected / altered by biological sample and / or growth medium conditions; therefore, the effective inhibitory or bactericidal concentration may differ from the concentration predicted by CLSI or EUCAST. Therefore, in all aspects and embodiments, any suitable antibiotic (or other agent) concentration or amount (or concentration range or amount range) may be included according to preference and desired results.

[0022] Advantageously, the fluid device includes a bacterial growth medium configured to promote the growth of bacteria that may be present in the fluid sample when mixed with it during use. In these embodiments, the growth medium is disposed in a fluid reservoir or in a growth medium compartment in fluid communication with the fluid reservoir. Advantageously, in any such embodiment, the growth medium is disposed in a growth medium compartment that is in fluid communication with the fluid reservoir via a filter element or membrane. The growth medium may be in concentrated liquid form, but is advantageously in solid or powder form. Solid form is generally preferred and may be easier to handle during device assembly. For example, the medium may be provided in the form of compressed granules or pills, or in powder form within a soluble capsule. Such capsule embodiments may be advantageous because the growth medium is protected from undesirable exposure to the atmosphere / environment before use; however, once released from the capsule, it may dissolve rapidly upon contact with a biological sample.

[0023] Therefore, membranes can be installed to filter the fluid sample before it enters the fluid system. Typically, it is advantageous to install a filter or other membrane after the fluid sample has been mixed with the growth medium. Filters or other membrane devices are beneficial in preventing undissolved fragments of the growth medium and / or other larger contaminants that may be present in the sample from entering the fluid system. Any suitable membrane / filter pore size can be used, for example, 100 μm, which can conveniently retain salts and other particulate matter (e.g., undissolved growth medium) of 100 μm and above. Convenient filters or membranes can be made of polymeric materials (e.g., polypropylene) or metallic materials (e.g., stainless steel). In some arrangements, metallic filter elements are preferred.

[0024] The fluid apparatus of any embodiment may include a sample receiving well for receiving fluid samples before they are transferred to a fluid reservoir and subsequently to at least one fluid system.

[0025] In some advantageous embodiments, the central region of the fluid apparatus includes a sample receiving well for receiving fluid samples. The sample receiving well communicates with a fluid reservoir, typically via a growth medium compartment that contains the growth medium, and filter elements can be axially arranged between the growth medium compartment and the fluid reservoir during use to filter the mixture of the fluid sample and the growth medium before it enters the fluid reservoir. Advantageously, the sample receiving well, the growth medium compartment, the filter elements, and the fluid reservoir are axially aligned in a straight line about the central axis of rotation of the apparatus.

[0026] In any embodiment of the device, a cap or lid may be provided to close the sample receiving well. Conveniently, the sample receiving well is formed within an upright neck portion in the central region of the device (which is also axially arranged about the central axis of rotation of the device). Suitably, the neck portion is provided with a retaining feature for engaging with a complementary retaining feature of the cap. In a particular embodiment, the retaining feature is a thread. For example, the outer wall of the neck portion may be provided with a male thread for engaging with a complementary female thread on the inner wall surface of the cap or lid.

[0027] Typically, the cover has a top wall / upper wall and an outer annular peripheral wall that extends downwards from the top wall. Conveniently, the inner surface of the outer peripheral wall may be threaded for complementary thread engagement with the neck portion of the fluid device.

[0028] Advantageously, in any embodiment of this disclosure, the cover may include a plug or plunger element configured to provide a sealing or frictional fit (e.g., via an annular skirt or flange) with the inner surface of the sample receiving well, such that when the cover engages with the neck of the fluid device, the plunger discharges a predetermined volume of fluid from the sample receiving well toward the central reservoir and fluid system, while the fluid substantially does not leak out of the fluid system across the plunger. Thus, the cover may include a cylindrical plunger element that stands upright from the top wall of the cover and is radially arranged within the outer annular peripheral wall. In these embodiments, the outer annular surface of the plunger element may be configured to mate with the inner annular surface of the sample receiving well so that a predetermined volume of fluid is discharged from the sample receiving well when the cover engages with the neck of the fluid device.

[0029] In alternative embodiments of this disclosure, there is no need to provide a plug or plunger element for the cap arranged to force the sample fluid downward toward the central reservoir. Instead, after the sample is mixed with the dissolved medium, it can pass through any filter / membrane arrangement arranged between the sample receiving well and the central reservoir under the influence of gravity (and centrifugal forces, pressure changes, or other forces acting on any liquid sample retained in the sample receiving well during use of the device). This simplifies the manufacture of the device without compromising performance.

[0030] To maintain the growth medium in a substantially clean or sterile environment, or to prevent the growth medium from being exposed to the environment before the device is used, a breakable sealing element can be conveniently provided. The sealing element is conveniently positioned between the sample receiving well and the growth medium compartment. Suitablely, the seal (which can be formed of any suitable material) is substantially impermeable to solid particles and / or liquids and / or gases. For example, the seal can be formed of foil material or plastic / polymer material. Alternatively, the seal may decompose / deteriorate or dissolve in the presence of water-based liquids (such as biological samples). The sealing element is secured in place using any suitable mechanism described herein (e.g., by adhesive). In alternative embodiments, for example, when the growth medium is otherwise protected relative to the environment, such as when the growth medium has a protective coating or is otherwise encapsulated in granular or powder form, such as in capsules or other similar pills, a seal may not be provided between the growth medium and the sample receiving well.

[0031] In a particularly advantageous embodiment, the cap includes one or more protrusions radially arranged inside the cap and erected downwards from the cap. These protrusions are configured to pierce a sealing element (if present) between the sample receiving well and the growth medium compartment to allow fluid communication between the sample receiving well and the growth medium compartment. It is understood that piercing the sealing element allows the fluid sample held in the sample receiving well to mix with the growth medium held in the growth medium compartment. In a preferred embodiment, one or more protrusions are arranged erect downwards from the lower surface of a plunger element (if present). The one or more protrusions can take any effective form, such as any of the forms or configurations described herein. For example, they can take the form of fins or blades, capable of piercing the seal between the growth medium compartment and the sample receiving well and improving the mixing of the fluid sample with the growth medium to improve dissolution. Furthermore, in some embodiments, the fins or blades may be configured to scrape the inner wall of the growth medium compartment during use to facilitate the dissolution of growth medium adhering to the wall of the device.

[0032] The fluid device of any embodiment of this disclosure may include a collar element that engages between the neck and cap of the device and is configured to limit the engagement depth between the cap and the neck, such that the cap cannot be fully engaged with the neck of the device before the user intends to use it. For example, by preventing accidental full engagement between the cap and the neck / body of the device, the user will not accidentally lock the cap to the neck (a latching feature exists to control reuse or exposure to contaminated devices), and / or will not accidentally puncture a sealing element (if present), exposing the growth medium to the environment (for this purpose, one or more protrusions are provided on the underside of the cap). In some embodiments, the collar element is integrally formed with the cap. In other embodiments, the collar element is formed separately from the cap. In some such embodiments, the collar element may be integrally formed with the outer peripheral wall of the cap, and the connection between the collar and the cap is configured to be (manually) breakable, allowing the user to remove the collar from the cap without tools. If the collar is formed separately from the cap, this advantageously allows the collar to be formed of a different material than the cap, for example, a cheaper, easier-to-remove, or more recyclable material can be used. However, in some embodiments, the cap limiting feature may not be a ring, but any other suitable mechanism, such as a tab to prevent the cap from fully engaging with the neck of the device.

[0033] In one embodiment, the fluid device may include a funnel element configured to guide a fluid sample to the top of a sample receiving well.

[0034] In any embodiment, the neck portion may consist of an outer annular wall and an inner annular wall, the inner annular wall defining at least a portion of the sample receiving well, and the outer annular wall having a fixing feature for engaging with a complementary fixing feature of the cover. In some such embodiments, the space between the outer and inner annular walls of the neck portion defines an annular chamber, or may be divided into multiple radially segmented chambers by multiple radially spaced walls or ribs. Advantageously, the annular chamber or at least one radially segmented chamber is configured as an overflow chamber, which is in fluid communication with the sample receiving well through at least one overflow orifice. Advantageously, the overflow orifice is arranged such that a predetermined maximum volume of fluid sample can be received in the sample receiving well before the fluid sample in the sample receiving well reaches the height of at least one overflow orifice. Thus, the overflow feature limits the amount of fluid that can be poured into the sample receiving chamber while mitigating the possibility of fluid overflowing outside the device. In embodiments, the overflow orifice is disposed in the wall of the sample receiving well or in a funnel element configured to guide the fluid sample into the top of the sample receiving well. Thus, the overflow orifice can communicate with the upper region of the overflow chamber. As noted, during use, the overflow chambers help prevent or reduce the risk of external contamination of the fluid device by trapping excess fluid samples in one or more overflow chambers of the fluid device, which are sealed relative to the environment by engaging a cap on the neck of the device.

[0035] In some embodiments, at least one of the radially segmented chambers is configured as a gas release chamber, which is in fluid communication with a central fluid reservoir via at least one gas release orifice communicating with a lower region of the gas release chamber. The arrangement allows gas within the fluid reservoir to be discharged upwards into the at least one gas release chamber when the fluid reservoir is filled with fluid samples from the sample receiving well. This configuration advantageously allows air to be removed from the fluid reservoir so that it can be filled with fluid samples; it also prevents overpressure of the fluid samples within the fluid device; and in use, it prevents the formation of a vacuum behind the fluid samples when they are evacuated from the central fluid reservoir and dispersed into various fluid systems. In these embodiments, gas / fluid release orifices may also be provided on the top surface of the neck, funnel, and / or lid to equalize the pressure within the device. Any such gas release orifice may preferably be covered with a hydrophobic membrane to prevent leakage of liquid samples from the device.

[0036] Conveniently, in some embodiments, the bottom surface of the cap's plug or plunger may be provided with one or more gas release orifices, allowing gas to escape from the sample receiving well and / or the central fluid reservoir during use, as described above. Such orifices may preferably be covered by an impermeable liquid membrane or a hydrophobic membrane to prevent liquid sample leakage from the device. Suitably, in these embodiments, a plurality of second gas release orifices are provided through the top surface of the cap (communicating with the first set of gas release orifices) to allow gas escape and / or equalize the pressure within the device with atmospheric pressure.

[0037] In various aspects and embodiments, one or more orifices may be provided on the top of the cap to provide a "breather," thereby equalizing the pressure between the device interior and the atmosphere. Such orifices may be suitably covered by a filter or membrane (preferably a hydrophobic filter or membrane) to prevent fluid from escaping from the sample receiving well. This filter or membrane suitably has a perforation diameter chosen to equalize the pressure between the device and the atmosphere, thus preventing pressure buildup; for example, approximately 0.45 μm is small enough to prevent bacterial entry without unduly restricting airflow to achieve pressure equalization. This breather can be conveniently positioned at the center of the cap, communicating with the sample receiving well, thus eliminating the need for an additional or dedicated gas release chamber.

[0038] Typically, in embodiments of this disclosure, the fluid device includes a body and a base, wherein a fluid reservoir and at least one fluid system are defined within the body of the device and exposed on their underside. In these embodiments, the base may be connected to the body to seal the fluid system, thereby preventing fluid leakage. Thus, the base forms the lower surface or base of the central fluid reservoir and fluid system. Importantly, at least a portion of the base (which defines the lower surface of at least one fluid analysis chamber) is optically transparent to light of a desired wavelength. In some such embodiments, the base is a membrane configured to be secured to the body of the device by an adhesive, heat seal, or any other suitable mechanism. In some advantageous embodiments, an adhesive may be used; in other advantageous embodiments, a heat seal is used.

[0039] In embodiments, the fluid device may include an antibiotic susceptibility plate comprising a variety of antibiotics. Suitably, the amounts of the various antibiotics used may be selected from the amounts of one or more antibiotics disclosed in Table 1, Table 2, or Table 3. In a particular embodiment, the fluid device suitably includes an antibiotic susceptibility test plate with antibiotic concentrations according to the CLSI and / or EUCAST standards defined in Table 3. However, in other embodiments, the appropriate antibiotic concentration of one or more selected antibiotics may be determined independently of any standard system; for example, to optimize an assay system for a specific purpose, such as in detecting antibiotic susceptibility to urinary tract infection (UTI) pathogens.

[0040] In a second aspect, an apparatus is provided, comprising: a fluid device according to any aspect or embodiment of the present disclosure; a drive mechanism for driving rotational movement of the fluid device about a rotational axis of the fluid device; and a controller that executes machine-readable code to cause the drive mechanism to control the flow of fluid samples from a fluid reservoir to said or each analytical chamber.

[0041] In an embodiment of the second aspect, the device may include optical equipment comprising: a light source configured to emit an incident light beam and illuminate a fluid sample in the one or each fluid analysis chamber; and a photodetector configured to detect scattered light exiting the one or each fluid analysis chamber.

[0042] Embodiments of this aspect may also include a sample container turntable arranged to engage with the container and configured to periodically align and dealign the or each fluid analysis chamber with an incident beam from a light source of an optical device.

[0043] Conveniently, at least one processor is configured to analyze the detected scattered light to determine one or more properties of the fluid sample contained in the fluid analysis chamber. Suitably, the properties determined are selected from: the relative amount of bacteria; the relative concentration of bacteria; the change in the relative amount of bacteria over time; the change in the relative concentration of bacteria over time; the qualitative amount of bacteria; the qualitative concentration of bacteria; the actual amount of bacteria; the change in the relative amount of bacteria over time; or the change in the actual concentration of bacteria present in the fluid sample in the analysis chamber over time.

[0044] According to a third aspect, a method is provided for moving a fluid sample from a fluid reservoir through a fluid system formed in a fluid device, the fluid system including a fluid analysis chamber and a fluid channel arrangement configured to achieve fluid communication between the fluid reservoir and the fluid analysis chamber, the method comprising: rotating the fluid device about a rotation axis at a first rotational speed for a first duration by a drive mechanism to generate a first centrifugal force sufficient to drive the fluid sample from the fluid reservoir to a first portion of the fluid channel arrangement; preventing the fluid sample from flowing forward from the first portion of the fluid channel arrangement into a second portion of the fluid channel arrangement by a pressure applied by a valve mechanism opposite to the first centrifugal force; and rotating the fluid device about a rotation axis at a higher second rotational speed for a second duration by a drive mechanism to generate a second centrifugal force sufficient to overcome the pressure of the valve mechanism and drive the fluid sample into the second portion of the fluid channel arrangement and thus into the fluid analysis chamber.

[0045] In some embodiments, an initial “mixing” rotational phase may be present to allow the fluid sample to be adequately mixed with and dissolve any growth medium, after which the fluid sample (with the dissolved growth medium) is dispensed around the fluid system of the apparatus. The initial mixing rotation can last for any suitable duration and speed, but should be selected to ensure that the fluid sample is not dispensed into the channels of the fluid system before the growth medium is properly dissolved in the sample. For example, the mixing phase may include the fluid apparatus reciprocating or oscillating (clockwise and counterclockwise / forward and backward alternating) at a speed of about 250 rpm to about 750 rpm (e.g., between about 400 rpm and 600 rpm). In an advantageous embodiment, the oscillating mixing step is about 500 rpm. Suitablely, depending on the solubility of the medium, such initial mixing may be performed for a duration of about 30 seconds to 1 minute, with a maximum of about 10 minutes. For example, for a desired number of repetitions (e.g., 3 to 10 times, 4 to 8 times; or 5 or 6 times), inertial mixing may last for a period of 3 to 10 seconds (e.g., 4 to 8 seconds, such as 5 or 6 seconds) in each direction. In one advantageous embodiment, the initial media mixing phase can be performed in a cycle of 5 seconds 5 times in each direction at a speed of approximately 500 rpm.

[0046] In some embodiments of the method, the first rotational speed used to dispense and clarify the fluid sample may be between 1800 and 3000 rpm; such as between approximately 2000 and 2800 rpm or between approximately 2200 and 2600 rpm. In an advantageous embodiment, the first rotational speed is approximately 2600 rpm. The first rotational speed is applied for approximately 30 seconds; such as between approximately 10 and 20 seconds. In an advantageous embodiment, the first rotational speed is applied for approximately 15 seconds. However, in some embodiments, a longer first rotational time (e.g., approximately 1 minute or longer) may be selected, depending on the type of particles to be removed. Appropriately, the rotational speed and time are sufficient to fill a first portion of the fluid channel arrangement with a portion of the fluid sample and allow specific substances in the fluid sample to deposit to form a clarified sample. Preferably, particulate matter with a diameter of approximately 10 μm or larger is deposited in the first portion of the fluid channel arrangement.

[0047] In any embodiment, the second rotational speed for filling the analytical chamber is suitably higher than about 1900 rpm: for example, between about 2800 and 4500 rpm; such as between about 3000 and 4200 rpm, or between about 3200 and 4000 rpm. In an advantageous embodiment, the second rotational speed is about 4000 rpm. The second rotational speed is determined by a valve mechanism that provides reverse pressure for the movement of the fluid sample toward and through the valve mechanism. In embodiments, the second rotational speed is applied for about 10 to 30 seconds; for example, about 12 to 25 seconds, or about 14 to 20 seconds. In an advantageous embodiment, the second rotational speed is applied for about 15 seconds. The fluid device is rotated at the second rotational speed to fill the analytical chamber with the fluid sample.

[0048] Subsequently, embodiments of this aspect may include rotating the fluid device at a slower third rotational speed between approximately 1300 rpm and 1500 rpm. At this speed, the gas within the valve mechanism 8 can expand and again provide sufficient pressure to prevent fluid from flowing through the valve. This creates a physical gas barrier between the fluid in the first portion of the fluid passage arrangement and the fluid in the second portion of the fluid passage arrangement.

[0049] The method may also include providing a predetermined amount of one or more antibiotics in a portion of the fluid channel arrangement, the antibiotics being in a form that readily dissolves in the fluid sample upon contact with it to achieve a predetermined desired antibiotic concentration. Advantageously, the antibiotics are provided, for example, in a dry form on a surface of the analytical chamber. In some cases, the antibiotics may not immediately dissolve in the fluid sample; therefore, the method may also include performing inertial mixing to promote the dissolution of the antibiotic (or other agent) in the fluid sample.

[0050] Therefore, the method may further include performing a subsequent inertial mixing step after the analytical chamber is filled with the fluid sample, including reciprocating or oscillating rotation (alternating clockwise and counterclockwise rotation) of the fluid device at a speed of approximately 500 rpm to approximately 2000 rpm (e.g., between approximately 800 rpm and 1800 rpm or between approximately 1000 rpm and 1600 rpm). In an advantageous embodiment, the oscillating inertial mixing step is approximately 1500 rpm. This inertial mixing can be performed for any suitable duration: typically, depending on the solubility of the drug or other chemical, the duration is approximately 30 seconds to 1 minute, with a maximum of approximately 10 minutes. For example, for a desired number of repetitions (e.g., 3 to 10 repetitions, 4 to 8 repetitions; or 5 or 6 repetitions), the inertial mixing may last for 3 to 10 seconds in each direction (e.g., 4 to 8 seconds, such as 5 or 6 seconds). In an advantageous embodiment, the inertial mixing may be performed in cycles of 5 times for 6 seconds in each direction at a speed of approximately 1500 rpm.

[0051] The method may also include rotating the fluid device at a predetermined speed while performing measurements on the fluid within the analysis chamber. For example, the method may include analyzing a single (drug-administered) fluid sample in each analysis chamber by exposing it to a light source, thereby measuring or simply detecting the amount of light scattering caused by particulate matter (e.g., bacteria present in each sample) that changes over time. Changes in the amount of light scattering caused by a sample may indicate the amount (e.g., concentration) of particulate matter (especially bacteria) present in the fluid sample. Advantageously, the method involves detecting a decrease in the amount of light scattering to indicate the sensitivity of the relevant bacterial strain (multiple strains) present in the sample to a drug (used to administer the drug to the sample) or drug concentration. In some embodiments, the amount of light scattering may be proportional to the relative or even absolute concentration of bacteria in the sample; and may be determined by an appropriate algorithm based on the amount of light scattering.

[0052] This method may also include analyzing samples in each fluid analysis chamber. During the analysis, the fluid apparatus is adapted to rotate in the same direction at a constant rate (e.g., between approximately 50 and 300 rpm; for example, between 100 and 200 rpm; particularly between approximately 100 rpm or approximately 150 rpm). The duration of rotation at this rate depends on the length of the measurement and may last approximately 20 to 90 minutes; such as approximately 30 to 75 minutes, or approximately 30 to 60 minutes. The method suitably includes sequentially illuminating the fluid samples in each analysis chamber at predetermined time intervals determined by the rotation speed; and measuring the amount of light scattered by particles (e.g., bacteria) in the fluid samples using a photodetector. Conveniently, the amount of scattered light can be correlated with or proportional to the amount and / or concentration of particulate matter (e.g., bacteria) in the fluid samples. Thus, an increase in scattered light indicates an increase in the amount of particles (e.g., bacteria), and vice versa.

[0053] In some embodiments, the analysis is based on a (weighted) smoothed average of sample measurements. Advantageously, the smoothed average can be applied to 50 to 500 measurements, especially more than 100 measurements, which is equivalent to reading each analysis point for 60 seconds at a rotation speed of 100 rpm.

[0054] In one embodiment, the fluid device includes a plurality of detection chambers, at least two of which contain a fluid sample to which different amounts of the same drug / agent / antibiotic are added to provide two different concentrations of drug in their respective fluid samples. The method may then include: sequentially positioning each of the plurality of detection chambers containing the drug-dosing sample in light emitted along the axis of an incident beam; performing each subsequent step of the method for each of the plurality of detection chambers; and determining the relative sensitivity of bacteria in the sample to a respective concentration of drug used to administer the fluid sample, thereby determining the most effective drug concentration to be used in the treatment regimen. In the same or alternative embodiment, the fluid device includes a plurality of detection chambers, at least two of which contain a fluid sample to which different drugs / agents / antibiotics are added to provide two different active agents against the same bacteria. The method may then include: sequentially positioning each of the plurality of detection chambers containing the drug-dosing sample in light emitted along the axis of an incident beam; performing each subsequent step of the method for each of the plurality of detection chambers; and determining the relative sensitivity of bacteria in the sample to a corresponding drug / agent / antibiotic used to administer the fluid sample, thereby determining the most effective drug to be used in the treatment regimen.

[0055] Suitable, the method may further include: collecting non-scattered light parallel to the incident beam axis through the one or each detection chamber via a second photodetector; and comparing the intensity of the non-scattered light collected by the second photodetector with the intensity of scattered light collected by the first photodetector in the same detection chamber.

[0056] Within the scope of this application, it is expressly intended that the various aspects, embodiments, examples, and alternatives described in the preceding paragraphs, claims, and / or the following description and drawings, in particular their individual features, may be presented independently or in any combination. That is, all embodiments and / or features of any embodiment may be combined in any manner and / or combination unless such features are incompatible. The applicant reserves the right to amend any originally filed claim or accordingly file any new claim, including the right to modify any originally filed claim to subordinate to and / or incorporate any feature of any other claim, even if not initially filed in this manner. Attached Figure Description

[0057] The above and other aspects of this disclosure will now be described by way of example only, with reference to the accompanying drawings, in which:

[0058] Figure 1 This is a side view of a sample container body comprising a plurality of fluid systems capable of centrifugally agitating sample fluid, according to an embodiment of the present disclosure.

[0059] Figure 2A Showing Figure 1 A plan view of the sample container body; Figure 2B Showing Figure 2A A diagram showing the unfolded fluid system set up in a sample container; Figure 2C A plan view of the sample container body according to an alternative embodiment is shown; Figure 2D Showing Figure 2C An expanded diagram of some fluid systems set up in the sample container;

[0060] Figure 3 yes Figure 1 The vertical cross-sectional view of the assembled sample container body 2 shows the various flow paths of the clinical sample fluid in the central part of the container;

[0061] Figure 4 It includes Figure 3 A vertical cross-sectional view of the assembled fluid device 1 of the sample container body, which also includes a lid for holding the clinical sample fluid inside the sample container;

[0062] Figure 5A An exploded view of a fluid device 1, which can be used to implement a method for clinical sample analysis according to another embodiment of the present disclosure, is shown; Figure 5B A cross-sectional view of the fluid device 1 according to this embodiment is shown; Figure 5C An exploded view of a fluid apparatus 1 according to another embodiment of the present disclosure is shown; Figure 5D An exploded view of a fluid apparatus 1 according to yet another embodiment of the present disclosure is shown;

[0063] Figure 6A yes Figure 5A and Figure 5B A three-dimensional view of the bottom of the container lid shown; Figure 6B yes Figure 4 A side view of the container lid;

[0064] Figure 7A yes Figure 5C and Figure 5D An exploded perspective view of the top of the container lid shown. Figure 7B yes Figure 5C and Figure 5D Bottom view of the container lid;

[0065] Figure 8 This is a flowchart illustrating the various steps of a method for manufacturing a complete sample container and lid according to an embodiment of the present disclosure;

[0066] Figures 9A to 9E A schematic snapshot of a sample container is shown, according to an embodiment of the present disclosure, during the process of redistributing sample fluid from a central reservoir of the container to a single fluid system;

[0067] Figure 10 This explains the redistribution and Figures 9A to 9E The flowcharts for each step of the sample fluid method are shown.

[0068] Figure 11 A vertical cross-sectional view of an optical analysis device that can be used in conjunction with the sample container shown in the above figures to determine the susceptibility of bacteria in clinical samples to various drugs is shown.

[0069] Figure 12 yes Figure 11 A perspective view of a portion of the device shown;

[0070] Figure 13 yes Figure 11 A perspective view of the bottom of the sample turntable at the junction with the fluid apparatus described and shown herein;

[0071] Figure 14 In an example implementation Figure 11 A schematic diagram of the optical arrangement used in the device shown;

[0072] Figure 15 It shows the use of Figure 11 A flowchart illustrating the steps of the method for determining the drug susceptibility of bacteria in clinical samples using the apparatus shown and the sample container described herein.

[0073] Figure 16 Showing Figure 11 The different curves of detector intensity output over time in the device shown illustrate the effects of different antibiotics on bacteria in clinical samples; and

[0074] Figure 17 An alternative arrangement of the fluid system used according to an embodiment of this disclosure is shown.

[0075] In the accompanying drawings, similar features are indicated by similar reference numerals. Detailed Implementation

[0076] Specific examples and embodiments of this disclosure will now be described, in which many features will be discussed in detail to provide a thorough understanding of the concepts defined in the claims. However, it will be apparent to those skilled in the art that this disclosure may be practiced without all specific details, and in some cases, well-known methods, techniques, and structures have not been described in detail to avoid unnecessarily obscuring this disclosure.

[0077] Figure 1 A portion of the fluid device 1 is shown, which is configured to centrifugally stimulate the dispensing / movement of fluid samples via multiple fluid systems; the sample portion is retained in a separate detection / analysis chamber for subsequent analysis.

[0078] In the most general sense, fluid device 1 (see also Figures 2 to 1) Figure 5D The device comprises a body 2 having a centrally located main fluid reservoir 4 in which a fluid sample is initially introduced and retained. Multiple fluid systems 6 are spaced apart around the main fluid reservoir 4, extending radially outward and in fluid communication with it. In use, the rotational motion of the fluid device 1 about a central axis of rotation “X” is configured to apply centrifugal force to the fluid sample retained in the main fluid reservoir 4, thereby driving a smaller portion of the initial fluid sample into each individual fluid system 6.

[0079] The fluid sample is controlled by a combination of one or more different centrifugal forces applied through the subsequent flow of a single fluid system 6 (e.g., by applying different rotational speeds at predetermined time intervals). Additional control of the fluid flow is achieved by using one or more valve mechanisms / pneumatic springs located at key points within each fluid system. Specifically, in each fluid system 6, a valve mechanism 8 is located at the midpoint of the flow path between the inlet point 10 of the fluid system and the fluid analysis chamber 12. The valve mechanism 8 is configured to apply a pressure opposite to the flow force of the fluid sample when the container 1 rotates at a speed below a predetermined threshold, thereby preventing fluid flow into the fluid analysis chamber 12. In this case, the centrifugal force applied to the fluid sample by the rotation of the container 1 will be insufficient to overcome the reaction force of the compressed gas in the valve mechanism 8 until the fluid device 1 rotates at a sufficiently high speed.

[0080] Typically, in aspects and embodiments of this disclosure, Figure 1The sample container body 2 is formed and molded from an optically transparent substrate material (e.g., a plastic material such as polycarbonate). The vertical cross-section of the container body 2 is generally circular and divided into two main parts: (i) a radially inner wall portion 14 having a main fluid reservoir 4 formed therein and having an upwardly extending wall to form a cylindrical container neck 16; and (ii) a radially outer portion 18 having a plurality of fluid systems 6 formed therein. The container neck 16 is configured to receive a cap or lid 20, which can be secured to the container body 2 in use to ensure that the fluid sample is securely retained within the assembled container 1. In this regard, the container neck 16 in the illustrated embodiment includes a plurality of external protrusions / threads 22a configured to engage with corresponding internal protrusions / threads 20a provided on the cap 20 (shown in more detail in Figures 5 and 6) to achieve a secure engagement between the cap 20 and the container body 2. Of course, it is understood that any other suitable mechanism can also be used to secure the cap to the container body, such as a snap-fit ​​or friction mechanism or a clip / latch / bolt. For clarity and for the sake of disclosure, it should be understood that the various embodiments of this disclosure are not intended to be limited to including every feature described in relation to the drawings, especially where the features particularly described are clearly not required or optional.

[0081] exist Figure 1 In the illustrated embodiment, the outer portion 18 of the container body 2 includes a cutout segment 24 configured to facilitate a specific orientational interface and engagement between the fluid device 1 and a device containing an optical analysis apparatus used in subsequent analysis of fluid samples within the container assembly 1. Thus, the “generally circular” container body 2 may include radial cutouts. The cutout segment 24 also includes an angled wall 25 located on the radially inner surface of the cutout segment 24, on which identification codes (e.g., in the form of RFID tags or barcodes) or other information may be placed for storing detailed information about the fluid device 1 and its contents. As will be described in more detail later, the size and configuration of the cutout segment 24 can interface with a portion of the optical analysis apparatus during subsequent analysis of fluid samples, and therefore can be any suitable size and shape. For practical and efficiency reasons, in order to maximize the number of fluid systems 6, the cut may, for example, be subtend at an angle of approximately 20° to 60°, and appropriately between approximately 30° and 50°; however, any suitable angle that helps to properly align the device in the analytical apparatus is advantageous.

[0082] Figure 2A Showing Figure 1 The plan view of the container body 2 is shown to highlight further details of the main fluid reservoir 4 and the fluid system 6 disposed therein. Figure 2BAn enlarged view of a fluid system 6 is shown. As previously described, each fluid system 6 includes a fluid analysis chamber 12, which represents the final destination of a portion of the fluid sample within that particular fluid system 6. Furthermore, each fluid system 6 includes a fluid channel arrangement 26 that provides a fluid flow path connecting the main fluid reservoir 4 at the center of the container body 2 and the corresponding fluid analysis chamber 12 in the radially outer portion of the container body 2.

[0083] More specifically, the fluid channel arrangement 26 includes a first inlet fluid channel 28 having an inlet port 28a located at its radially innermost extent (relative to the rotation axis X of container 1), which communicates with the main fluid reservoir 4; and an outlet port 28b located at its radially outermost extent, which communicates with the intermediate separation chamber or clarification chamber 30. In the illustrated embodiment, the outlet port 28b is positioned toward the radially outermost limit of the fluid system 6. In other embodiments, for example, as... Figure 2C and Figure 2D As shown, the separation chamber 30 is not located at a radially external position of the fluid system 6.

[0084] Special Reference Figure 2BThe separation chamber 30 is formed in a well shape within the base of the radially outer portion 18 of the container body 2 and is configured to separate unwanted particles / impurities from the remainder of the fluid sample. The exit port 28b of the first fluid channel 28 communicates with the separation chamber 30 toward its radially outermost wall / edge, thereby achieving a so-called "bottom feed" function for introducing sample fluid into the separation chamber 30 (i.e., the fluid sample enters the separation chamber 30 at its radially outermost extent). Therefore, in any embodiment, the fluid channel 28 advantageously communicates with the separation chamber 30 at its radially outermost edge. However, in some embodiments, the separation chamber 30 is advantageously shaped such that its radially outermost wall is angled away from the axis of rotation X and the exit port 28b of the fluid channel 28 (e.g., forming a sedimentation zone spaced apart from port 28b). In this way, particles in the fluid entering the settling chamber 30 settle and aggregate at a distance from port 28b, for example, in the "toe" or "bag" 30a of the separation chamber 30, so that the settling is not disturbed by the inflowing fluid (which would be detrimental to the process of forming a clear fluid sample). Once within the separation chamber 30, the fluid in the radial interior of the settling chamber 30 is clarified. The clarified fluid is pushed from the settling chamber 30 to the valve mechanism 8 and the analysis chamber 12 (described below) when needed via a "bottom feed" of the incoming fluid sample (i.e., the inflowing fluid enters the settling chamber 30 towards the radial outer limit of the chamber). In contrast, if port 28b is positioned towards the radial inner edge of the settling chamber 30, the fluid flowing in from the main fluid reservoir 4 (through fluid channel 28) will mix with the clarified fluid in the radial interior of the settling chamber 30, potentially pushing the unclarified fluid towards the analysis chamber 12. Furthermore, the bottom feed arrangement allows the fluid system to advance fluid from the main fluid reservoir 4 to the analysis chamber 12 using only a single pneumatic gate / air spring. The complexity of manufacturing and subsequent fluid sample movement control is reduced by controlling the rotational speed rather than operating hard / mechanical valves.

[0085] The fluid channel arrangement 26 also includes a second fluid channel 32 having an inlet port 32a communicating with the separation chamber 30 and an outlet port 32b communicating with the fluid analysis chamber 12. A weir (or step) 30a is located between the separation chamber 30 and the inlet port 32a of the second fluid channel 32, which may help improve the separation / clarification function provided by the separation chamber 30. Given the weir 30a, the volume of clarified fluid sample within the separation chamber 30 must be large enough to overflow the weir and enter the second fluid channel 32, while unwanted impurities can remain inside the separation chamber 30 (in fact, these impurities will precipitate on the radial outer wall of the separation chamber). In practice, the centrifugal force acting on the liquid sample pushes heavier particles / unwanted impurities outward toward the outermost radial wall of the separation chamber 30, keeping them at the furthest point from the weir 30a, as shown in the figure. The weir is typically located at the radial inner edge of the separation chamber 30. This, along with other advantageous features such as the radial orientation of port 28b toward the outermost radial wall of the separation chamber 30, reduces the likelihood of unwanted particulate matter being pushed into / inhaled into the second fluid channel system 32.

[0086] Usefully, as may be used in any aspect and embodiment of this disclosure, the presence of the weir 30a increases the height of the bottom plate / bottom of the fluid channel 32 relative to the bottom plate of the separation chamber 30 and helps to minimize the volume of fluid that must pass through the fluid channel 32. By minimizing the volume of liquid discharged towards the valve mechanism 8 by centrifugal force, the volume of gas discharged into the valve mechanism 8 is also reduced / minimized, thereby reducing the pressure increase within the valve mechanism 8 and reducing the rotational speed required to push the liquid sample through the valve mechanism 8 (as described below). In embodiments, in use, the rotational speed of the container 1 is selected to capture / sediment particles with a diameter greater than 10 μm, thereby keeping the relevant bacteria in suspension.

[0087] The second fluid channel 32 is substantially U-shaped and includes first and second channel arms 32c, 32d, which are arranged to provide fluid flow paths in generally antiparallel directions. Specifically, the first channel arm 32c extends substantially (anti)parallel to the first fluid channel 28, allowing a fluid sample to flow radially inward (towards the axis of rotation X of the fluid device 1) out of the separation chamber 30 and along the first channel arm 32c; the second channel arm 32d extends substantially (anti)parallel to the first channel arm 32c and allows the fluid sample to reverse its flow direction (relative to the flow in the first channel arm 32c), allowing the fluid sample to move radially outward toward the fluid analysis chamber 12. Suitably, in any embodiment of this disclosure, each fluid channel 28, 32a, and 32b is arranged substantially radially.

[0088] The two channel arms 32c, 32d are fluidly connected to each other at their innermost radial extent via a valve mechanism 8 (in the illustrated embodiment) which takes the form of a gas-filled (e.g., air) reservoir. As fluid (liquid) moves toward the valve mechanism 8 through the fluid passages of the fluid system 6, the gas is compressed and subjected to increased pressure. Therefore, the compressed gas can be configured to impede / prevent fluid flow between the two channel arms 32c, 32d by applying gas pressure opposite to the centrifugal force applied to the fluid sample by the rotation of the fluid device 1. Such a valve mechanism is sometimes referred to in the art as a "pneumatic (bypass) valve," "pneumatic spring," "air ballast chamber," or "air spring."

[0089] Now refer to Figure 2C and Figure 2D An improved embodiment of the fluid device 1 is described. In this embodiment, as before, the separation chamber 30 communicates with the main / central fluid reservoir 4 via the fluid channel 28 and an inlet in the radially outer portion / edge of the separation chamber 30. The separation chamber 30 is advantageously shaped as a wedge, having a wider end / portion radially located outside the relatively narrow radially inner end / portion. In this way, sediment can be conveniently collected in region 30a of the sedimentation chamber 30, away from the communication point (28b) between the fluid channel 28 and the separation chamber 30, to reduce interference of the inflowing fluid with any sediment in the separation chamber 30 that has been separated from the clarified fluid, and the wedge shape of the sedimentation chamber 30 also helps to optimize the use of the available area of ​​the circular / disc shape of the fluid device at different radial distances from the central reservoir 4.

[0090] In this embodiment, the first channel arm 32c connecting the separation chamber 30 and the valve mechanism 8 is relatively short, while the second channel arm 32b connecting the valve mechanism 8 and the fluid analysis chamber 12 is longer because the separation chamber 30 is located radially between the valve mechanism 8 and the fluid analysis chamber 12. In this way, the combination of greater centrifugal force and pressure from the valve mechanism 8 helps to retain the fluid sample within the analysis chamber 12 during the incubation and measurement phases of the disclosed method, which will be further described below.

[0091] Optionally, in any other aspect and embodiment described herein, the inner corners 32d' and 32d" of the channel arm 32d may be rounded (with increased curvature) to reduce any wicking / capillary forces that could adversely affect the movement or retention of the fluid sample in the analysis chamber 12. Similarly, the inner corners 32c' and 32c" of the channel arm 32c may also be rounded to avoid sharp angles approaching 90°. Of course, it may also be necessary to form the inner corners of the fluid channel 28 with a slight curvature to avoid wicking / capillary forces in that channel. For example, in a fluid channel with a width of approximately 1.5 mm and a depth of approximately 0.75 mm, the inner corners may have a radius of curvature between approximately 0.05 and 1 mm. In some examples, the radius of curvature is approximately 0.6 mm; in other examples, the radius of curvature is approximately 0.1 mm, approximately 0.2 mm, or approximately 0.3 mm.

[0092] The mechanism for dispensing fluid samples into container body 2 will be described in more detail later; however, a brief overview of the flow path of the fluid sample through fluid system 6 between one of the main fluid reservoir 4 and fluid analysis chamber 12 will be provided now to set the elements of the fluid system in the background.

[0093] The sample fluid is initially located in the main fluid reservoir 4; the fluid device 1 rotates at a first speed to generate centrifugal force sufficient to drive a small portion of the sample fluid into each fluid system 6: specifically, the fluid sample portion enters each fluid system 6 through a corresponding one of a plurality of first fluid channels 28 and into the corresponding separation chamber 30. The first rotational speed is maintained for a first period of time sufficient to drive enough fluid into each fluid system 6 to fill each fluid channel 28, and then begins filling the separation chamber 30, allowing time for particulate matter to precipitate from the solution in the separation chamber 30. In use, the rotational speed can be selected to allow time for filling the separation chamber 30 with the fluid sample and to prevent the fluid sample from being driven forward toward the air spring / valve mechanism before the desired outcome. A weir 30a (or dam / local wall) at the radially inner edge of the sedimentation chamber 30 is used to retain the fluid within the sedimentation chamber 30 until clarification / desired forward movement of the fluid toward the analysis chamber 12. Once sedimentation is sufficiently complete, the level of the fluid sample portion in each system 6 can be increased by increasing the rotational speed. When the clarified solution in each fluid system 6 reaches the top of its respective weir 30a, the clarified solution overflows and enters the associated first channel arm 32c. However, this first velocity is chosen too low to apply sufficient centrifugal force to the fluid sample to allow the sample to overcome the reverse pressure generated by the gas compression within the valve mechanism 8, thus preventing the fluid from passing through valve 8 into the second channel arm 32d. In other words, the movement of the sample fluid relative to valve mechanism 8 is controlled by a balance / difference between pressures: that is, the centrifugal pressure difference caused by the rotating disk must overcome the pressure increase (overpressure) caused by the reduced gas volume before the liquid can move through valve mechanism 8.

[0094] To further push the liquid sample toward the analysis chamber 12, the fluid device 1 rotates at a higher second speed, generating sufficient centrifugal force to overcome the gas pressure of the valve mechanism 8—thus overcoming the "seal" (pressure blockage) provided by the valve mechanism 8—and allowing the fluid sample to flow into the second channel arm 32d. Continued rotation at this second speed drives additional fluid through the second channel arm 32d, thereby allowing the fluid sample to enter and fill the fluid analysis chamber 12. Typically, the analysis chamber 12 takes the form of a cylindrical well disposed within the base of the container body 2. Advantageously, in any embodiment of the invention, the second channel arm 32d communicates with the bottom of the analysis chamber 12. In this way, the movement of the clarified fluid sample toward and into the analysis chamber 12 causes the gas previously located in the second channel arm 32d and the analysis chamber 12 to be removed from the analysis chamber 12 and moved radially inward toward the valve mechanism 8. This avoids pressure blockage and / or air bubbles being trapped within the analysis chamber 12, which could reduce the accuracy / sensitivity of the analysis performed on the fluid sample. Once sufficient fluid has passed through valve mechanism 8, the rotational speed of container 1 can be reduced to retain the fluid sample within fluid analysis chamber 12 and the second channel arm 32d, but to prevent (due to the air pressure of valve mechanism 8) backflow of the fluid sample into the first channel arm 32c. This is explained by reducing the rotational speed, allowing the air in chamber 8 to expand freely again due to the lower pressure. When this occurs, the fluid in chamber 30 is pushed back into channel 28 and into the central chamber 4. This creates an air barrier between the fluid in analysis chamber 12 and the fluids in separation chamber 30 and the central reservoir 4, thus preventing cross-contamination. Furthermore, backflow of fluid from analysis chamber 12 can be prevented because once the air in analysis chamber 12 is purged, there is no force pushing the liquid sample radially inward toward valve mechanism 8.

[0095] It is worth noting that the gating level of valve mechanism 8 determines the internal pressure changes within fluid system 6, which is necessary for fluid to move through channels 28, 32 and chamber 30 toward the corresponding analysis chamber 12. Therefore, in embodiments where the valve mechanism is a pneumatic bypass valve or an "air spring," it should be appreciated that the volume of valve mechanism 8 can be selected to provide appropriate resistance / gating to prevent fluid movement, taking into account: (i) the volume of fluid that must be pushed through fluid system 6 to fill analysis chamber 12; and (ii) the desired rotational speed of fluid device 1 during analysis. For example, a larger volume air spring would reduce the rotational speed required to move a specified volume of fluid sample through the valve because the additional gas compressed into the air spring (by the movement of the specified volume of liquid sample) would result in a relatively small increase in gas pressure within valve mechanism 8, which must be overcome by centrifugal force.

[0096] Therefore, in embodiments of this disclosure, the volume of the air spring can be suitably related to the volume of the detection chamber, which in turn can be suitably related to the volume of the sedimentation chamber 30, which must clarify sufficient fluid to fill the analysis chamber 12. Thus, the volume of the sedimentation chamber 30 is suitably about twice the volume of the analysis chamber 12, and the volume of the air spring 8 is suitably in the range of about two to four times the volume of the sedimentation chamber 30. For example, the volume of the air spring 8 can be in the range of about 150 μl to 600 μl. In contrast, the volume of the analysis chamber 12 can be in the range of about 30 μl to 150 μl, and the volume of the sedimentation chamber 30 can be in the range of about 60 μl to 300 μl. In a specific embodiment of this disclosure, the volume of the air spring 8 is about 400 μl; the volume of the analysis chamber 12 is about 50 μl; and the volume of the sedimentation chamber 30 is about 100 μl. In other specific embodiments of this disclosure, the volume of the air spring 8 is approximately 400 μl; the volume of the analysis chamber 12 is approximately 125 μl; and the volume of the precipitation chamber 30 is approximately 200 μl.

[0097] Considering the overall outline of the sample container body 2, which is typically disc-shaped with a raised inner core to accommodate the filter 42, the medium 36, and the sample receiving well / reservoir 48 (see... Figure 1 , Figure 3 and Figure 4 Therefore, the necessary volume of the valve mechanism (e.g., air spring 8) can encompass a relatively large proportion of the outer region 18 of the sample container body 2—particularly according to the preferred embodiments of this disclosure, when the valve mechanism 8 is located in the relatively smallest radially innermost volume of the outer region of the sample container body 2. Thus, when the maximum dimension of the valve mechanism 8 (“air spring”) is generally arranged in the plane of the fluid system, i.e., in the axial plane of the container body 2, the surface area enclosed by the valve mechanism 8 is larger, and the container body 2 must be larger in the radial direction to accommodate the required number of fluid systems 6, or fewer fluid systems 6 can be accommodated in the device. In some embodiments of this disclosure, it may be desirable to form a generally flat device 1, for example, to improve the stacking of the devices 1. However, increasing the size of the container body may be undesirable for many reasons, such as environmental reasons (an increase in the amount of material to be used and disposed of, e.g., plastics); and economic reasons (e.g., transportation, storage, and the need for a larger diagnostic / measurement device simply for compatibility with the container body 2). Therefore, ideally, the device 1 and the body 2 can be made as small as possible, especially in radial dimensions, while maintaining the maximum ideal number of fluid systems 6. Based on these objectives, it is advantageous to oriented the valve mechanism 8 such that the main dimensions of the valve 8 / gas chamber are perpendicular to the radial axis of the container body; that is, the main dimensions of the valve 8 are arranged substantially parallel to the X-axis passing through the central region of the container body 2 and the main fluid reservoir 4. Therefore, as... Figure 3 and Figure 4As best shown, the valve mechanism 8 of each fluid system 6 can be provided by a corresponding air chamber 8 arranged around the outer edge of the main fluid reservoir 4 and the sample receiving well 48. In an embodiment, the air chambers of the plurality of valve mechanisms 8 can be axially located below the outer wall 16a of the neck 16, particularly circumferentially arranged around the main fluid reservoir 4 and the filter element 42, and are generally axially oriented to reduce the depth of the valve mechanism 8 in the radial dimension. In this way, the size (especially the radial dimension) of the container body 2 can be reduced while maintaining the same or improved functionality.

[0098] In specific embodiments, the fluid device 1 described above may be part of a larger overall system or apparatus for processing and analyzing the properties of clinical fluid samples (such as urine or blood). Furthermore, this analysis may involve the assessment / analysis of light scattering caused by the concentration of particulate matter (e.g., bacteria) in the clinical sample. Thus, the fluid device 1 can be used, in particular, to determine the drug susceptibility of bacteria in order to determine appropriate treatment for the infected person providing the sample. In some embodiments, the device may be used in methods for assessing the relative concentration of light-scattering particles in a fluid sample, or for estimating the amount or concentration of light-scattering particles in a fluid sample. In particular embodiments, a “concentration gradient” of light-scattering particles (such as bacteria) may be determined.

[0099] Now will provide information about Figure 3 The description up to Figure 7 illustrates various aspects and embodiments of the fluid device 1 in the specific context of clinical sample analysis for determining bacterial drug susceptibility. However, it is worth noting that these fluid devices 1 may also have other uses (as described above), and some features described subsequently may be modified to suit these uses.

[0100] Special Reference Figure 3 and Figure 4 These figures show Figure 1 Vertical cross-sectional perspective view of container body 2 ( Figure 3 () and a vertical cross-sectional perspective view of the microfluidic device 1 including the container body 2. Figure 4According to various embodiments of this disclosure, these devices have been configured for clinical sample analysis. In addition to the body 2 of the sample container described above, the fluid device 1 also includes a growth medium or culture medium 36 (typically provided in solid form in such embodiments) that promotes bacterial growth in the clinical sample fluid for analysis of growth characteristics. Conveniently, as in the depicted embodiments, the growth medium is dried (e.g., lyophilized or freeze-dried) and is in solid form. However, powdered dried growth medium can also be used, which can help the medium dissolve rapidly in the fluid sample. In particular, the powdered growth medium can be contained in a soluble / degradable capsule, for example, which releases the powder when opened. In alternative embodiments, a concentrated liquid growth medium can be used instead. The growth medium 36 is initially isolated in the inner wall portion 14 of the container body 2 (see...). Figure 1 In the illustrated embodiment, the compartment 38 is located substantially vertically (along the central rotation axis X of the fluid device 1) within the main fluid reservoir 4. Figure 3 Above.

[0101] In the depicted embodiment, the top and bottom of the growth medium compartment 38 are sealed by foil covers 40a, 40b to isolate the growth medium 36 from the external environment, particularly ensuring separation from the fluid sample when the sample is first introduced into the fluid device 1. The foil covers 40a, 40b can be attached to their desired locations (e.g., around the periphery of their respective housings) using any suitable heat-sealing technique (or adhesive or welding) to seal the compartment containing the growth medium 36. A filter element 42 is also located below the growth medium compartment 38 and above the main fluid reservoir 4, and is secured (e.g., by heat sealing, adhesive, or welding) to extend substantially through the inner diameter of the inner wall portion 14 of the container body 2. The filter element 42 provides a mechanism for filtering out impurities exceeding a predetermined size (determined by the filter's properties) from the sample before it enters the main reservoir 4; and can take the form of a porous membrane with a pore size of approximately 100 μm. As those skilled in the art will understand, the filter pore size is selected to allow bacteria in the sample (at most a few micrometers in size) and dissolved growth media to pass through the filter and into the main fluid reservoir 4. However, the filter is selected to prevent salts and other relatively large particles in the sample from passing through; for example, fragments of perforated foil, clumps of undissolved growth media, and larger human tissue cells and fibers from the sample. (See below for more information.) Figure 5A The description, in the embodiments, includes foil caps 40a, 40b and a compartment 38 for receiving growth medium 36, as well as a filter element 42, which can be conveniently disposed in a separate capsule component 43 or 430 (see [link to description]). Figure 5C and Figure 5DThis capsule component is manufactured separately from the other components of the main container body 2 and is inserted during the assembly of the sample container. This will be described in more detail later. It will be understood that in some embodiments, the foil caps 40a, 40b can be replaced with other methods of sealing the medium compartment 38. For example, the seal can be made of paper material or a material dissolved in a fluid such as a liquid sample. In some embodiments, the lower seal 40b can be optional, and alternatively, the drying medium can be held directly in the medium compartment by the filter element 42. In some embodiments, the upper seal 40a is also optional and can be omitted. In some embodiments, the medium can be provided in (concentrated) liquid form.

[0102] In a convenient manufacturing mode, the fluid system 6 is formed as channels and grooves in the lower surface of the container body 2. Therefore, to form a closed system, a bottom cover 44 having a surface area covering area corresponding to the base of the container body 2 is attached to the bottom of the fluid device 1 to enclose the components and cover the fluid system 6 and fluid reservoir 4 formed in the lower surface of the body of the container body 2. In some embodiments, the container body 2 may be provided with short walls or lips 222 extending downward from the outer periphery of the container body, and the bottom cover 44 may extend through the base of the container body 2 between the outer peripheral lips. In other embodiments, the container body may include downwardly projecting plugs or posts spaced around the outer periphery of the radially outer portion 18 of the container body 2, instead of the outer peripheral walls 222. Suitablely, the bottom cover 44 is a membrane. As will be described in more detail later, the presence of the bottom cover 44 is important because the fluid system 6 can be conveniently molded to the base forming the substrate of the container body 2. Without the bottom cover 44, the fluid system 6 would be open to the environment and unable to contain liquid when using the fluid device 1. The bottom cover 44 is optically transparent, at least in the area axially below (some of) the analysis chambers 12, to allow subsequent analysis of bacteria (or other particulate matter to be evaluated for light scattering) in the respective fluid analysis chambers 12. In some embodiments, the bottom cover is opaque to light in a specific restricted area (e.g., below the analysis chamber 12 which may be used to provide an optical negative control). The bottom cover 44 can be attached to the underside of the sample container body 2 using any one or more of a number of well-known suitable sealing techniques, such as heat sealing, ultrasonic welding, liquid adhesive sealing, or the bottom cover 44 may comprise a single-sided / double-sided adhesive film.

[0103] Regardless of the sealing technology employed, it is crucial to ensure a high level of optical clarity and minimize the reflection of incident light from the bottom cover 44 or the adhesive used (especially in the area covering the fluid analysis chamber 12) to avoid adverse effects on subsequent analytical processes. Furthermore, the sealing process should be compatible with (and should avoid interference with) any components of the fluid device 1 (e.g., any drugs deposited within the container). In particular, to prevent potential contamination of liquid samples in use, it is best to have little or no exposure to adhesives or other chemicals on the upper surface of the bottom cover 44 within the fluid system channels and reservoir. It should also be recognized that the connection between the container body 2 and the bottom cover 44 must be as strong and consistent as possible to completely seal all channels and chambers and mitigate the effects of undulations or other undesirable surfaces on the cover 44 (which could interfere with the consistency of light transmission through the analysis chamber 12). Therefore, the surface of the container body 2 connected to the cover 44 should be as flat as possible, with minimal surface features or irregularities. For example, a flatness of less than about 70 μm (peak deviation from a flat surface), less than about 50 μm, or between about 40 μm and 20 μm or lower is desirable.

[0104] It is also conceivable that any other component of the container body 2 and the fluid device 1 can be formed by a suitable additive manufacturing process, so that in some such processes, the bottom cover 44 can be integrally formed with the body of the container body 2, thereby avoiding the need for a separate bottom cover 44.

[0105] In the depicted embodiment, a packing insert or funnel 46 is provided to facilitate the introduction of fluid samples into the fluid device 1, which is located within and engages with the upper part of the container neck 16. Figure 3 and Figure 4 As shown, the container neck 16 includes a cylindrical outer wall 16a, radially spaced from a cylindrical inner wall 16b. As illustrated, the inner wall 16b surrounds and forms a cylindrical sample reservoir or receiving well 48 into which the fluid sample is initially introduced; therefore, the receiving well 48 is located at the center of the cylindrical container neck 16. In the depicted embodiment, a plurality of radially spaced walls 50 (e.g., Figure 5A (As best shown) Radially spaced within the container neck 16, extending between the inner wall 16b and the outer wall 16a to form generally wedge-shaped spaces 52a, 52b between adjacent spacer walls 50. In embodiments of this disclosure, spaces 52a, 52b may alternate around the container neck 16.

[0106] The funnel 46 includes an annular edge 54 and a downwardly projecting annular skirt 58 that extends radially inward along the edge 54, guiding the fluid sample into a cylindrical sample receiving well 48 as it is poured into the fluid device 1 through the funnel 46. In the depicted embodiment, the annular skirt 48 is provided with a plurality of holes or slots 60 as overflow features to reduce the likelihood of liquid sample overflowing due to overfilling of the sample reservoir or receiving well 48. In the depicted embodiment, three slots 60 are formed in the funnel skirt 58, but more or fewer slots may be provided (e.g., one, two, or four). Multiple protrusions (e.g., walls) 56 (such as...) Figure 5A (As best shown) Protruding downwards from the underside of the funnel 46 along each slot 60, these protrusions are positioned to define open channels 56a. The size and shape of the protrusions 56 are adapted to complement and be received by the space 52a in the container neck 16, so that each open channel 56a can guide overflowing fluid into the closed receiving space 52a.

[0107] The protrusion 56 also facilitates fixing the funnel 46 in the desired orientation within the neck 16. Furthermore, as... Figure 5A As shown in the embodiments, the lower surface of the funnel 46 may also be provided with a plurality of downwardly projecting positioning fins or pins 57, which may be configured to contact the radially inner surface of the outer wall 16a of the neck 16. Such pins 57 may also be used to position and fix the funnel 46 in the desired orientation within the neck 16.

[0108] In an embodiment, such as Figure 3 and Figure 4 As shown, the lower / bottom surface of the edge 54 and / or the annular skirt 58 may be located on the top surface of the spacer wall 50; and the radially inner portion of the annular skirt 58 may be configured to rest against and intersect with the upper surface of the inner wall 16b of the container neck in order to properly position the funnel 46 in the neck 16. In some embodiments (such as...) Figure 3 and Figure 4 As shown, the funnel 46 may also include a second set of annularly spaced holes or slots 74b, which, when the funnel is properly positioned within the neck 16, are vertically aligned with the space 52b and together form part of the “breathing” mechanism described below. In an alternative embodiment, instead of a dedicated breathing channel, a breathing hole may be provided at the top 20c of the cover 20 to equalize the gas pressure within the device with atmospheric pressure.

[0109] Figure 3 The flow of a fluid sample within a fluid device 1 is illustrated according to an embodiment of the present disclosure.

[0110] In use, the user initially pours the sample fluid into the cylindrical receiving well 48, and the fluid sample is contained within the receiving well 48 and prevented from reaching the growth medium 36 by the upper foil cover 40a. Subsequently, after the upper foil cover 40a (and the lower foil cover 40b, if present) are perforated or removed, the fluid sample can flow sequentially through the compartment 38 containing the growth medium 36, through the filter element 42, and into the main fluid reservoir 4 located at the bottom of the container body 2.

[0111] If the sample level in sample reservoir 48 reaches the overflow level, the excess fluid will flow through slot 60 into the internal outflow chamber space 52a, which is a dead-end volume, and remain there (see...). Figure 3 (The wide gray arrow in the image). However, other convenient overflow mechanisms can also be used. For example, in another embodiment, the funnel skirt 58 may extend radially inward toward the inner wall 16b and be arranged such that its lower surface is axially spaced above the upper edge of the inner wall 16b to create one or more circumferential channels / openings communicating with at least one space 52a, so that if the sample loaded into the reservoir 48 exceeds the volume defined by the inner wall 16b of the container neck 16 and the bottom of the reservoir 48, the excess sample fluid will flow through the upper edge of the inner wall 16b into the space 52a.

[0112] To reduce the possibility of inaccurate importation of clinical samples during use, overflow collection features can be provided. Therefore, in Figure 1 , Figure 3 and Figure 4 In the illustrated embodiment, an annular channel or groove 63 is provided to collect fluid that may overflow along the outer surface of the neck 16 and guide it into an overflow chamber 62 disposed around the outer periphery of the outer wall 16a, which is radially disposed between the outer wall 16a and the upright annular wall 62a. It should be appreciated that the overflow chamber 62 may not, and does not need to, completely surround the outer wall 16a; instead, a groove 63 that can completely surround the outer wall 16a can drain the overflowing fluid into the overflow chamber 62, which only surrounds a portion of the outer wall 16a. Figure 3 and Figure 4 As shown, an annular groove 63 is conveniently created by providing a short, upright portion of an annular wall 62a, which is concentric with and surrounds the lower portion of the container neck 16. Therefore, in these embodiments, the annular wall 62a extends above the upper surface of the chamber 62 to form a partially enclosed channel. In alternative embodiments, as... Figure 5A and Figure 5B In the illustrated embodiment, the annular wall 62a does not include an upright circumferential protrusion, thus eliminating the need for an annular groove 63, which can be omitted or provided by an alternative fluid capture volume / overflow chamber 62b radially outward from the outer wall 16a of the neck 16. For example, in various embodiments of this disclosure, such as Figure 5BAs shown, the overflow chamber 62b can be located in the space between the outer wall 16a of the neck 16 and the inclined wall 25 on the radially inner surface of the cut section 24. An opening (not depicted) can be provided on the top wall of the overflow chamber 62b to allow overflow fluid to enter the overflow chamber 62b.

[0113] Figure 5A and Figure 5B The images show an exploded perspective view of a fluid device 1 according to another embodiment of the present disclosure, and an exploded perspective view of a container body 2 when the lid 20 is attached to the neck 16 of the container body 2 (although not fully engaged). Figure 5A A vertical cross-sectional view of the fluid device 1 in the figure, wherein similar features are formed by... Figure 3 and Figure 4 The same reference numerals are used in the embodiments associated with them. Figure 5C and Figure 5D Exploded perspective views of the fluid apparatus 1 according to two other embodiments of the present disclosure are shown, wherein the same reference numerals are used to describe similar features.

[0114] Figure 6A Showing Figure 5A and Figure 5B Detailed exploded view of the middle cover 20, and Figure 6B according to Figure 4 The embodiments provide further details about the cover 20. Figure 7A Showing Figure 5C and Figure 5D Detailed exploded view of the lid 200 in the middle, and Figure 7B Additional details of the lid 200 as viewed from below are provided.

[0115] As previously described, the caps 20, 200 are sized and shaped to fit the container neck 16, having an upper surface 20c configured to cover the internal volume of the neck 16, and downwardly projecting annular walls 20b, 200b whose inner surfaces define a plurality of female (inwardly projecting) threads 20a, 200a, configured to complement and engage with external (male) threads 22a on the radially outer surface of the outer wall 16a of the container neck. Therefore, the engagement between threads 22a, 20a, 200a allows the cap 20 to be screwed onto and secured to the container neck 16. To avoid the reuse of consumables and / or to minimize the risk of potentially contaminated samples escaping from the fluid device 1 during or after use, a locking mechanism can be provided as a complementary pair of features, one of which is provided on the caps 20, 200, and the other on the container body 2. In the illustrated embodiment, the locking mechanism includes a pair of complementary latching configurations 64a, 64b – one (64a, as shown) Figure 6A and 7B (As best shown) is located on the lower inner surface of the cover 20, and correspondingly another 64b (feature 64b, such as) Figure 5A ,5C (As shown in 5D best) is located on the lower portion of the outer surface of the outer wall 16a. Complementary latching features are appropriately configured such that once the covers 20, 200 are tightened to their predetermined final position, the latching structures 64a, 64b engage with each other, securely locking the covers 20, 200 in place on the container neck 16.

[0116] It is worth noting that the volume of the liquid sample used for measurement and thus its loading into container body 2 may be important. For example, it may be necessary to mix a predefined volume / amount of clinical sample with a predetermined amount of growth medium so that any bacteria can grow optimally within the fluid device 1 for analysis / assay. With this in mind, in Figure 4 , Figure 5B and Figure 6A In one embodiment, for measuring the volume of a clinical sample mixed with the medium and loaded into the main fluid reservoir 4, the cap 20 includes an inner cylindrical extension, plunger, or plug 66, the size and shape of which can form a substantially sealing fit within a cylindrical receiving well 48 disposed in the container neck 16. Figure 5B and Figure 6A In the illustrated embodiment, the plug 66 includes a resilient, outwardly projecting flange or skirt 66a that forms a sealing contact with the inner surface of the receiving well 48. Furthermore, considering the cross-sectional area of ​​the plug 66 (or receiving reservoir 48), the depth of the plug 66 can be conveniently configured such that when the cap 20 is fully screwed into the container body 2, the plug 66 moves downward a distance into the receiving reservoir 48, allowing a predetermined desired volume of liquid sample flowing from the receiving reservoir 48 to flow into the main fluid reservoir 4. In other embodiments, the plug 66 and skirt 66a may be used to facilitate the flow of sample fluid from the receiving well 48 to the fluid reservoir 4, but may not have a defined "metering" function. Alternatively, as... Figure 7A and Figure 7B As shown in the embodiment of the cover 200, the lower side of the cover 200 does not have a plug 66. In these embodiments, during use, the liquid sample can flow from the receiving well 48 into the main fluid reservoir 4 through the filter 42 under the action of gravity, capillary force, and centrifugal force. In these embodiments, the amount of fluid entering the main fluid reservoir 4 can be successfully controlled by the volume of the main fluid reservoir 4.

[0117] To control the mixing time between clinical samples and growth media, for example, Figure 4 and Figure 5A As shown in the embodiment, a plurality of angled / pointed fins or protrusions 68 are formed and extend from the underside of the cylindrical plug 66. Alternatively, as... Figure 5C , Figure 5D , Figure 7A and Figure 7BAs shown in different embodiments, multiple angled / pointed fins or protrusions 68 may be formed from the underside of the cap 200. Once the liquid sample is loaded into the receiving reservoir 48, the caps 20, 200 are screwed onto the container neck 16, and the protrusions 68 advance vertically downward through the liquid receiving reservoir 48 and the sample, eventually piercing the top foil cap 40a, thereby allowing the sample fluid in the cylindrical receiving well 48 to enter the lower compartment 38 and mix with the growth medium 36. Further rotation and downward movement of the caps 20, 200 will cause the protrusions 68 to subsequently pierce the bottom foil cap 40b, thereby allowing the mixture of fluid sample and growth medium 36 to exit the compartment 38, pass through the filter element 42, and enter the main fluid reservoir 4 at the bottom of the container body 2. Advantageously, during the process of rotating the caps 20, 200 to further screw them into the container neck 16, the protrusion 58 also provides the additional function of agitating and / or stirring the sample fluid and growth medium mixture (before piercing the bottom foil cap 40b) to help break down the growth medium 36 into increasingly smaller particles and improve its miscibility and solubility with the sample fluid. For this purpose, the protrusion 68 can be shaped like blades or fins to improve the mixing of the sample fluid and the medium. Advantageously, the protrusion 68 is configured to scrape the sides of the growth medium compartment 38 to further aid in the mixing of the growth medium 36 with the sample fluid by removing any medium that may adhere to the walls of the chamber 38.

[0118] As the caps 20 and 200 advance downwards through the neck 16, the increasing liquid sample is pushed past the filter element 42 and into the main fluid reservoir 4. To ensure the main fluid reservoir 4 is completely filled with the liquid sample and to avoid trapped air bubbles, it is beneficial to provide air / fluid release mechanisms 52b and 74b in fluid communication with the main fluid reservoir 4. Figure 4 and Figure 5B The lid 20 is tightened further downwards, and the liquid sample continues to fill the main fluid reservoir 4 by expelling air. Air can escape from the container body 2 by passing upwards through the filter element 42 and the release chamber 52b, then through the opening 74b and the edge 54 of the funnel 46. To ensure all air is expelled, it is preferable to push more liquid sample than needed to fill the reservoir 4 into the main fluid reservoir 4. Excess liquid sample can also escape from the main fluid reservoir 4 like air (as described above) through the same release mechanisms 52b, 74b. For this purpose, the bottom surface of chamber 52b (unlike chamber 52a) is not sealed. Furthermore, this release mechanism allows gas (air) to return to the reservoir 4 as the sample fluid moves radially outwards from the reservoir 4 to fill the fluid system 6, thus preventing the formation of a vacuum in the reservoir 4 that would be detrimental to the operation of the fluid system 6. Therefore, the release mechanism allows the air pressure in the reservoir 4 to be equal to atmospheric pressure.

[0119] In alternative embodiments, such as Figure 5BAs shown in Figure 6, instead of a slot 74b in the funnel 46, a gas release mechanism is provided through a series of holes / orifices 74” on the lower surface of the plug through the cap 20. These holes / orifices can be conveniently covered by a breathable membrane 75 (see Figure 6) to prevent liquid leakage. Alternatively, in any such embodiment, the end of the plug 66 may be formed wholly or partially by a gas-permeable but fluid-impermeable membrane to avoid the need to provide multiple separate orifices / breathing holes 74”. In such and similar embodiments, more orifices 74a may be provided in the top surface 20c of the cap 20 (as depicted in Figure 7, another embodiment of the cap 20) to allow for equal pressure with atmospheric pressure. These orifices may also be covered by a breathable membrane 21.

[0120] In other alternative embodiments of the lid 200 and the container body 2, such as Figure 5C , Figure 5D , Figure 7A and Figure 7B As shown, for example, a dedicated release chamber 52b with an associated opening 74b may not be provided. Instead, a simpler air escaping and pressure equalization mechanism is provided, comprising one or more orifices (or openings) 74a that pass through the top of the cover 200 and communicate with the sample receiving well 48 and the main reservoir 4, allowing air or other gases to escape directly from the receiving well 48. One or more orifices 74a are conveniently covered by a hydrophobic filter / breathable membrane 75 in a similar manner to those described above. Another pressure relief membrane 21 may also be provided on the hydrophobic membrane 75. However, in other embodiments, only one of membranes 75 and 21 may be present, which is sufficient to prevent unwanted fluid movement. For example, in some embodiments, feature 21 may be a label.

[0121] Advantageously, in embodiments of this disclosure, the dimensions of the optional plug 66 and protrusion 68 of the caps 20, 200 should ensure that when the caps 20, 200 are fully engaged with and secured to the container body 2, the protrusion 68 does not touch / contact the filter 42; for example, the tip of the protrusion 68 is held in the axial space between the bottom foil cap 40b and the filter 42 to avoid undesirably puncturing or breaking the filter element 42.

[0122] To prevent accidental puncture of the membrane or foil cover 40a (if present) by the user before planned use and exposure of the medium to the environment (with the indirect risk of contamination), a safety (anti-fouling) measure 70 can be advantageously provided, as illustrated in the following embodiments: According to one embodiment Figure 4 and Figure 6B According to another embodiment Figure 5A and Figure 5B ; and according to yet another embodiment Figure 5C Safety measures should be appropriately implemented in the form of annular spacers or collars 70, which (in...) Figure 4and 6B In the illustrated embodiment, the collar 70 is integrally formed with the lower outer peripheral wall 20b of the lids 20 and 200 and configured to fit around the container neck 16. Therefore, when the lids 20 and 200 are engaged with the container neck 16, the collar 70 is vertically positioned below the lids 20 and 200. Figure 4 As shown, the width of the collar 70 is designed such that, when the cap 20 is tightened onto the container neck 16, with the collar 70 in place, the collar 70 prevents the caps 20, 200 from being tightened downwards to a degree sufficient to allow the protrusion 68 projecting from the underside of the plug 66 to pierce the top foil cap 40a (or alternatively, another cap element). Therefore, this mechanism ensures that the growth medium 36 is not accidentally exposed to the atmosphere and potential sources of contamination before use, and maintains the separation of the sample fluid and the growth medium 36 until the intended assay is performed, where the cap is securely attached to the container body 2. Suitably, the assay device in which the fluid device 1 is mounted during use can be configured, for example, not to be accepted and / or operated with the fluid device 1 until the cap 20 is fully engaged with the container body 2, thereby ensuring that the caps 20, 200 are completely sealed and locked onto the container body 2 to properly accommodate any clinical sample.

[0123] Therefore, in order to fully engage the caps 20 and 200 and the container body 2 to begin the measurement, for example, in Figure 4 and Figure 6B In some embodiments, the collar 70 must be removed by pulling / tearing the collar from the wall 20b of the cover 20, 200. For this purpose, the collar may be provided with a pull tab 70a for easy gripping / use. Advantageously, the connection between the collar 70 and the side wall 20b of the cover is perforated or otherwise weakened to allow the collar to be removed without much force. For example, it is generally preferred that the user manually removes the collar from the cover 20, 200. Alternatively, as... Figure 5A , Figure 5B and Figure 5C As shown in the embodiments, the collar 70 can be provided separately from the caps 20, 200. This advantageously means that the collar 70 can be formed of a different material than the caps 20, 200 (if desired); for example, the collar 70 can be formed of a recyclable material (such as cardboard). Furthermore, providing the collar 70 separately from the caps 20, 200 increases the ease with which the user can remove the collar 70. Once the collar 70 is removed from the caps 20, 200, the caps 20, 200 can be securely attached to the container body 2 for normal use. Furthermore, it should be noted that... Figure 5A and Figure 5B In this embodiment, the upper wall 62a of the groove (and the groove 62) are absent, which allows the collar 70 to be removed without first (partially) loosening the cap 20.

[0124] However, it should be understood that any other suitable mechanism conceived by those skilled in the art may also be used to prevent the caps 20, 200 from undesirably and prematurely becoming fully engaged with the container body 2. Advantageously, such an alternative mechanism allows the caps 20, 200 to remain on the container body 2 (if desired), while the protrusion / blade 68 does not penetrate the sample receiving well / reservoir 48 sufficiently to pierce the cap 40a (or other cap that may be used) until the device is required to be used.

[0125] like Figure 6A , Figure 6B , Figure 7A and Figure 7B As shown, the outer circumferential wall 20b of the lids 20, 200 includes a plurality of radially spaced tabs or ridges 72, improving the user's ability to hold the lids 20, 200 when rotating them to secure them to the container neck 16. In particular, in the described embodiment, the top surface 20c of the lids 20, 200 includes a series of through-holes / orifices 74a serving as pressure vents, covered by a pressure-reducing membrane 21. While... Figure 7A and 7B In some embodiments, the orifice 74a is further covered with a hydrophobic film 75. According to embodiments of this disclosure, when the caps 20, 200 are screwed down to secure them in place on the container neck 16, the opening 74a allows gas contained in the neck 16, chamber 52b, and / or central reservoir 4 to escape from the device 1 via different paths. As previously described, according to Figure 3 and Figure 4 In one embodiment, the gas released from the reservoir 4 advances through the chamber 52b and the vent 74b provided in the edge 54 of the funnel 46. Alternatively, according to Figure 5A , Figure 5B As in the embodiment of Figure 6, the gas released from the reservoir 4 and well 48 advances through a vent / opening 74” and an orifice 74a in the bottom surface of the plug or plunger 66, the orifice 74a being positioned to communicate with the radial volume inside the plug 66 (rather than the radial volume outside the plug 66), such as Figure 3 and Figure 4 As shown in the embodiments. In another alternative, according to Figure 7A and Figure 7B In one embodiment, the gas released from the reservoir 4 and well 48 proceeds directly through the orifice 74a through the top of the cover 200. Therefore, these openings 74a in the covers 20, 200 and / or funnel 46 or plug 66 together help regulate / release pressure that may arise within the assembled device 1 during and after the covers 20, 200 are secured.

[0126] Figure 8A flowchart is shown illustrating the various steps of a method 300 for manufacturing a fluid device 1, which includes a container body 2 and caps 20, 200. Notably, a preferred method involves manufacturing the caps 20, 200 and various components of the container body 2 separately. Typically, all these individual components are supplied together as an assembled fluid device 1 to the end user. However, it is envisioned that certain components can be supplied separately or in a discrete form; for example, media and / or filter components could be supplied as separate units 43, 430 to allow for the use of different clinical samples and the performance of different assays.

[0127] In a suitable embodiment (e.g.) Figure 5A As shown, the collar 70 is initially created and molded as an element separate from the rest of the cap 20. In some embodiments, alternatively, the collar 70 may be manufactured integrally with the rest of the cap as a removable (peelable) strip (e.g., by molding) to create the finished cap 20 in step 305. The container body 2 may also be molded using a specially designed mold in step 310. This step also includes molding a single fluid system 6 into the underside of the base portion forming the radially outer portion 18 of the container body 2.

[0128] Capsules 43 and 430 and funnels 46 and 460 were also manufactured separately by molding at this stage.

[0129] Subsequently, in step 315, the growth medium 36 is placed and sealed within capsules 43, 430. Conveniently, the bottom foil cap 40b is first sealed or welded to the appropriate position within capsules 43, 430; then, the growth medium 36 is deposited on top of the foil cap 40b; finally, the top foil cap 40a is sealed or welded in place to complete compartment 38 and isolate the growth medium 36 from the external environment. Then, in step 320, the filter element 42 can be sealed or welded below the bottom foil cap 40b. Alternatively, in some embodiments, the individual elements contained in capsules 43, 430 may be incorporated directly into the main container body 2 without creating separate capsules 43, 430 to contain the growth medium 6. In these embodiments, the bottom foil cap 40b is sealed or welded in place within the container neck 16; the growth medium 36 is deposited on top of the foil cap 40b; then the top foil cap 40a is sealed or welded in place to complete compartment 38 and isolate the growth medium 36 from the external environment. In step 320, the filter element 42 is resealed or welded to the bottom foil cap 40b. As previously described, in some embodiments, the growth medium 6 may be provided as a powder or concentrated liquid instead of dried granules or capsules. As those skilled in the art will understand, capsules 43, 430 may be assembled in a different order than described above, and any alternative manufacturing order is intended to fall within the scope of this aspect and embodiments. For example, as Figure 5AAs shown, capsule 43 can be positioned to communicate with sample receiving well 18 from below; and as Figure 5C and Figure 5D As shown, capsule 430 can be positioned from above in sample receiving well 18. It is desirable that capsules 43 and 430 be manufactured under "clean" conditions. In some embodiments, it may be preferred that capsule 43 be manufactured under "sterile" conditions.

[0130] It is understood that the lids 20, 200, the container body 2, the fluid system 6, the funnels 46, 460, and the capsules 43, 430 can alternatively be manufactured in any suitable manner, for example, by 3D printing / additive manufacturing, or by a convenient combination thereof.

[0131] Then, in step 325, the drug / antibiotic to be tested is appropriately deposited at the corresponding location within each fluid system 6 (e.g., within the fluid analysis chamber 12). Conveniently, in the final product, at least the drug / antibiotic is in dry form, for example, because it is initially deposited at the bottom of the fluid analysis chamber and dried thereon. This helps ensure that the drug will remain effective even if the sample container is not used for a long period of time (e.g., up to 2 years, up to 12 months, up to 6 months, or about 1 to 3 months). However, as those skilled in the art will appreciate, other forms / drug doses / antibiotics may be used depending on preference or suitability—for example, the drug may be deposited on paper (e.g., filter paper) placed in a region of the fluid system 6 to dissolve into the liquid sample, or the drug may be present in liquid form. In step 335, in Figure 5C and Figure 5DIn this embodiment, once all these individual components—funnels 46, 460 and (if suitable) growth medium capsules 430—have been created, the finished fluid device is assembled by inserting funnels 46, 460 into the neck of the container body 2 and inserting capsules 43, 430 into the receiving areas on the underside or top side of the container body 2. In step 335, after all the individual components have been incorporated into the sample container body 2, the bottom cap 44 is sealed or welded to the bottom of the sample container body 2. However, it is understood that funnels 46, 460 may actually be inserted at different stages of the process (e.g., after the bottom cap 44 is attached). Advantageously, the bottom cap 44 is a membrane / sheet that can be sealed to the underside of the container body 2 by any convenient means, such that a fluid seal is formed around the edges of all channels and chambers of the fluid system 6 to prevent fluid leakage from the fluid system 6 during use. The proper seal between the cap 44 and the container body 2 can be tested by any known procedure (e.g., pressure testing). Then, in step 340, the final fluid device 1 can be assembled by combining the container body 2 with the plug having the corresponding caps 20, 200 and collar 70, and packaged (possibly as part of a larger batch of containers) for distribution.

[0132] Optionally, in some cases, additional components may be included in the packaging; these components may contain information relating to the corresponding batch of fluid device 1 and / or details of the analyses and processes to be performed subsequently. This additional information may be stored in the form of a memory stick, chip, or RFID tag, as needed.

[0133] Once the fluid device 1 is provided to the end user, the sample fluid is transferred to and contained within the fluid device 1 through the following steps: removing caps 20 and 200 and separating the collar 70 from caps 20 and 200 (or removing the collar 70 from the neck 16 of the container body 2 if caps 20 and 200 are formed separately, or removing it from cap 20 if it is integrally formed with cap 20); pouring the sample fluid into the container body 2 (i.e., into the receiving well 48) until the desired (or indicated) level is reached; and securing caps 20 and 200 above the neck 16 of the container body 2—then the sample-containing fluid device 1 is placed into the assay (diagnostic / testing) device and driven by a series of rotational motion stages to ensure that a well-mixed portion of the sample (containing an appropriate concentration of growth medium 36 to promote bacterial growth) is dispensed into each fluid system 6, and a portion is ultimately retained in the corresponding fluid analysis chamber 12 for subsequent analysis. Such rotational motion is typically driven by a motor or other programmable drive mechanism to which the fluid device 1 is operatively coupled, for example, as part of a large programmable analytical apparatus / device.

[0134] Now refer to Figures 9A to 9EA schematic snapshot plan view of the sample container body 2 shown. Figure 10 The flowchart shown in method 500 describes the various stages of the sample (re)allocation process for clinical sample analysis.

[0135] The process begins at step 505 (see...). Figure 10 In this process, by fixing the caps 20 and 200 to the container body 2, the fluid sample and the growth medium mixture are located within the main fluid reservoir 4; this stage is as follows: Figure 9A As shown. Then, in step 510, an initial rotating "mixing" phase is performed, in which the fluid device 1 undergoes reciprocating or oscillating rotation—the sample container is driven at a first speed (e.g., about 250 rpm to about 1500 rpm; e.g., about 500 rpm) and a first duration (typically about 30 seconds to 1 minute, up to about 10 minutes), rotating alternately clockwise and counterclockwise to promote thorough inertial mixing and dissolution of the growth medium 36 in the fluid sample; this process is as follows Figure 9B As shown. For example, five reciprocating cycles can be performed in each direction, lasting five seconds, and repeated five times.

[0136] Once the growth medium 36 is sufficiently mixed and dissolved in the fluid sample, a second stage of dispensing and clarifying rotation is performed in step 515, wherein the fluid device 1 rotates at a higher second rotational speed (up to about 1800 rpm to 3000 rpm) in one direction (clockwise in the illustrated embodiment) for a second duration (e.g., from about 10 to 30 seconds). In an embodiment, the clarifying rotation may last for about 15 seconds at a speed of about 2600 rpm. This rotational motion generates and applies centrifugal force to the fluid sample in the main fluid reservoir 4, forcing the fluid sample to flow radially outward along its respective first fluid channel 28 and into the associated separation chamber 30 of each fluid system 6. The prolonged rotation during this stage in step 520 will allow the fluid sample present in each separation chamber 30 to clarify as larger particulate matter deposits at its radially outer edges. The rotational speed at this stage is selected to balance the force on the fluid pushing it further inward from the separation chamber 30 and the pressure applied by the compressed gas within the valve mechanism (air spring) 8. This prevents the fluid sample from overflowing the associated weir 30a and entering the corresponding first channel arm 32c of the second fluid channel 32; as Figure 9CAs shown. Next, in step 525, the sample container rotates for a third duration (approximately 10 to 30 seconds) at a higher speed (above 1900 rpm, for example, between approximately 2800 rpm and 4500 rpm) in the third stage. In an embodiment, the analysis chamber filling rotation may be at approximately 4000 rpm for approximately 15 seconds. However, it is understood that the selected rotation speed can be adjusted according to the specific valve mechanism 8 (e.g., the volume of the air spring), which determines the force required to push the clarified fluid sample through the valve mechanism 8. The centrifugal force generated by this higher rotational motion drives substantially all the remaining fluid sample present in the main fluid reservoir 4 into the individual fluid system 6; which in turn further (radially inward) discharges the clarified fluid already present in the separation chamber 30 into the first channel arm 32c of the second fluid channel 32. Thus, the fluid filling the first channel arm 32c applies pressure to the valve mechanism 8, a pressure high enough to overcome the opposing pressure applied by the compressed gas contained in the valve mechanism reservoir; the fluid sample can then enter the second channel arm 32d, and subsequently into each fluid analysis chamber 12. This is shown in Figure 9D middle.

[0137] At the end of the third duration, sufficient fluid passes through the corresponding valve mechanism 8 to fill the corresponding fluid analysis chamber 12 (the gas previously present in the analysis chamber 12 is expelled and returned to the valve mechanism / air spring 8). At this stage, in any aspect and embodiment described in this disclosure, the rotational motion in step 530 may be reduced to a fourth speed (e.g., between approximately 3000 rpm and approximately 1300 rpm to 1500 rpm). At this speed, the gas within the valve mechanism 8 is able to expand and again provide sufficient pressure to overcome the radially inward movement of the fluid from the separation chamber 30, thereby forming a physical gas barrier between the fluid on the first (separation chamber 30) side of the valve 8 and the fluid on the second (analytical chamber 12) side of the valve 8, such as... Figure 9E As shown. At this stage, depending on the solubility of the drug to be tested in the fluid sample, the sample in analysis chamber 12 can be prepared for testing. Alternatively, an intermediate (fourth) rotation process can be implemented to promote thorough mixing and dissolution of the drug / antibiotic (stored within analysis chamber 12) in the fluid sample. As an example, the fluid device 1 can again rotate clockwise and counterclockwise alternately at a fourth speed for a fourth duration (e.g., approximately several minutes). This periodic reversal of the rotation direction correspondingly changes the direction of fluid movement, thereby promoting inertial mixing of the fluid sample with the corresponding drug (in this embodiment) already deposited within the fluid analysis chamber 12. Figure 9EOf course, in some applications, control samples are not exposed to antibiotics or other drugs in the analysis chamber 12. In any of the embodiments described herein, it has been found that inertial mixing can be improved by approximately matching the width to the depth of the analysis chamber (e.g., configuring the analysis chamber to have a width of about 4 mm and a depth of about 4 mm); especially in combination with cylindrical wells. Typically, the width and depth of the analysis chamber may be between 3 mm and 8 mm, depending on the desired volume to be tested and the required dimensions of device 1. It is advantageous for the width and depth to be approximately the same length.

[0138] After the fluid samples are properly mixed with their respective drugs, an analytical phase can be performed in step 535, where analysis is conducted by exposing individual (administered) sample portions in each fluid system 6 to a light source and measuring or simply detecting the amount of light scattering over time caused by particulate matter (e.g., bacteria present in each sample). Changes in the amount of light scattered by the sample, particularly a decrease in light scattering over time, may indicate the amount (e.g., concentration) of particulate matter (especially bacteria) present in the fluid sample. Therefore, it is advantageous that detecting a decrease in light scattering can indicate the sensitivity of the relevant bacterial strains present in the sample to the drug used to administer the sample, or to the drug concentration. By using the fluid device 1 and method 300 described above, the relative sensitivity of bacteria in a given sample to different types and concentrations of drugs can be determined, wherein each type and / or concentration of the analyte is provided in a different fluid system 6. In some embodiments, the amount of light scattering may be proportional to the relative or even absolute concentration of bacteria in the sample; and can be determined by an appropriate algorithm based on the amount of light scattering.

[0139] In one embodiment, for example, using Figures 1 to 5DThe fluid apparatus 1 and container body 2 shown may include 19 separate fluid systems 6. This will allow for the execution of any number of different tests up to 19. In some embodiments, a particular drug may be tested multiple times against the same fluid sample, for example, in separate analytical chambers 12 at different concentration ranges. In other embodiments, multiple different drugs may be tested against the same fluid sample, each drug being tested at one or more test concentrations. Negative and positive test comparisons may also be provided. For example, providing up to 19 test wells allows for the execution of tests for: (a) 5 or 6 different drugs (or drug mixtures), each at concentrations not exceeding 3; (b) 7 or 8 different drugs (or drug mixtures), each at concentrations not exceeding 2; or (c) various drugs (or drug mixtures) at various different concentrations. In each of these three cases, at least one control system may be retained, preferably at least two control systems (e.g., a fluid system without any drug—typically a positive control without drug, and a negative optical control whose chamber is optically opaque) for comparison. In other embodiments, a biological negative control may be included instead of an optical negative control, or a biological negative control may be included in addition to an optical negative control, for example by depositing a bactericidal chemical (e.g., triclosan) into one of the fluid systems. In summary, the effect of up to 18 different drugs / dose doses on a clinical sample can be tested using each fluid device 1. It is understood that the specific drug to be tested and the specific drug concentration to be tested may depend on the country / region where the device is used and / or on the bacterial infection and suspected medical indication that may be screened.

[0140] In another embodiment, for example using Figures 9A to 9E The fluid device 1 shown may include 24 individual fluid systems (e.g., in this embodiment, the base of the container body forms a complete circle without any segments or cuts). In this configuration, up to 7 different drugs at 3 different concentrations can be tested, while maintaining up to 3 control systems for comparison. In other words, each fluid device 1 can be used to test the effects of up to 23 different drug doses (or even more, if fewer control systems are used) on a single clinical sample.

[0141] Alternatively, the size of the sample container can be further reduced; the container body 2 could include as few as 16 or even 8 separate fluid systems 6. Such a container would occupy less physical space, but of course, it means that a smaller range of drug dosages (i.e., fewer drug types and / or concentrations) can be tested. This device facilitates more targeted testing and analysis while reducing the use and disposal of materials such as plastics.

[0142] It is understood that those skilled in the art can select the drug and drug concentration based on the intended end use of the device. Particularly in the case of using the fluid device 1 to test clinical samples containing urine from a patient or subject, and specifically in the case of using the fluid device 1 to determine the most suitable drug for treating urinary tract infections (UTIs), the drug / antibiotic deposited in the fluid device 1 may be selected from one or more of the following groups: ciprofloxacin hydrochloride monohydrate (CIP); fosfomycin disodium salt (FOS); mechilinam hydrochloride (MEC HCl); nitrofurantoin sodium (NIT); trimethoprim lactate (TMP); and sulfamethoxazole sodium (SXT). Appropriately, antibiotics may be selected from one or more of the groups consisting of the above-mentioned antibiotics.

[0143] In a preferred embodiment, the drug / antibiotic deposited in the fluid device 1 for assessing the drug susceptibility of bacteria present in the suspected UTI may be selected from one or more of the following groups: amoxicillin; amoxicillin / clavulanic acid (2 / 1); cephalexin; ciprofloxacin; ertapenem; fosfomycin; levofloxacin; mesialin; nitrofurantoin; trimethoprim; trimethoprim / sulfamethoxazole (1 / 19). Suitablely, antibiotics may be selected from one or more of the groups consisting of the above-mentioned antibiotics.

[0144] Bacteria that may be associated with and be measurable by UTI include: *Escherichia coli*; *Pseudomonas aeruginosa*; *Staphylococcus aureus*; *β-streptococcus*; *Staphylococcus* and *Pseudomonas aeruginosa*. Since more than one such bacterium may be present in a sample, and different bacteria may have different antibiotic susceptibility, it is advantageous to include a range of relevant antibiotics in a series of relevant quantities so that the concentration of the relevant antibiotic in the fluid sample to be measured in the analytical chamber 12 of apparatus 1 is within an appropriate range.

[0145] Advantageously, the fluid apparatus 1 and method of this disclosure use a variety of antibiotics: for example, between 2 and 18, between 2 and 15, or between 3 and 12, such as 4, 5, 6, 7, 8, 9, 10, or 11 different antibiotics and / or combinations thereof. Advantageously, each of one or more antibiotics is provided in multiple predetermined different amounts in each fluid system 6, so that once dissolved in the liquid sample, the antibiotic concentration in each analytical chamber 12 reaches the desired range for testing. Typically, each individual fluid system 6 contains only one preselected amount of antibiotic, so each test sample contains only one known concentration of antibiotic. However, it is conceivable that in some assays, it may be necessary to provide two or more preselected amounts of antibiotics (to produce the desired concentration in the same test sample), for example, to test the efficacy of multiple drugs against certain bacteria—for example, for an indication that can be used to treat a specific infection.

[0146] The effectiveness of antibiotics can be assessed based on the measurement of the minimum inhibitory concentration (MIC), which is the lowest concentration of antibiotic required to inhibit the growth of an organism. Those skilled in the art can readily obtain the MIC of a specific antibiotic for a specific bacterium. For example, in a simple method, bacteria are added to culture dishes containing different concentrations of antibiotic. The concentration of antibiotic is doubled in each successive culture dish, and the MIC is determined by the first culture dish after which no visible colonies are observed. In a preferred embodiment, when used, the aforementioned antibiotic can be deposited in the necessary amount to provide a predetermined concentration of drug dissolved in the fluid sample within each analytical chamber 12, ranging from approximately 1x to 5x MIC, approximately 1x to 3x MIC, or approximately 1x to 2x MIC. However, different concentrations may also be used, taking into account the assay conditions (including sample type and fluid / assay system).

[0147] Alternatively, the amount of antibiotic deposited in each fluid system 6 can be selected to provide a concentration of dissolved antibiotic in the fluid sample in each analytical chamber that is equal to or determined as a multiple of the bacterial "breakpoint" for the selected drug. The breakpoint is a selected concentration (mg / L) of antibiotic that defines whether a bacterium is sensitive, intermediate, or resistant to the antibiotic. If the MIC is less than or equal to the sensitivity breakpoint, the bacteria are considered sensitive to the antibiotic. If the MIC is greater than this value, the bacteria are considered intermediate or resistant to the antibiotic. Therefore, while the breakpoint can be considered as the differential concentration of antimicrobial agent used in the interpretation of susceptibility test results, the value of the breakpoint can be set based on clinical, pharmacological, microbiological, and / or pharmacodynamic considerations, which factors need to be frequently evaluated, and may vary over time or in the relevant region. For example, the European breakpoint is set by the European Committee for Antimicrobial Susceptibility Testing (EUCAST), while the US breakpoint is set by the Clinical Laboratory Standards Institute (CLSI). EUCAST and CLSI breakpoints differ for certain antibiotics and certain bacterial species; therefore, embodiments of this disclosure are intended to provide a fluid device 1 for use in the United States (and other regions) according to CLSI standards; other embodiments of this disclosure are intended to provide a fluid device 1 for use in Europe (and other regions) according to EUCAST standards. Some embodiments of this disclosure relate to a fluid device 1 that is usable in both Europe and the United States, conforming to the different standards of each system by providing an appropriate amount of antibiotic. It is important to recognize that the MIC and breakpoint concentration are standardized by CLSI and EUCAST for a single organism and are based on the antibiotic in the synthetic medium to test bacteria isolated from cultures in clinical samples. However, the devices and methods of this disclosure are not typically used under such “ideal” conditions. Therefore, in other embodiments, the amount of antibiotic (and synthetic concentration) to be introduced into the fluid device of this disclosure is selected based on the assay results (which are within the capabilities of those skilled in the art) to determine the active concentration or amount of each relevant antibiotic (or other drug) under the expected conditions of the test. For example, to determine the appropriate concentration of the antibiotic of interest, tests and error tests can be performed in clinical urine culture media or in the microfluidic system according to this disclosure. In this way, the amount of antibiotic (or other drug) deposited into the fluid device of this disclosure can be suitably the amount exhibiting the activity of most interest in the expected sample type. Therefore, a range of antibiotic amounts / concentrations can be determined, which may differ from predicted values ​​based on EUCAST or CLSI breakpoints, and these antibiotic amounts / concentrations are expected to identify and differentiate the activity of interest in the biological sample of interest. Furthermore, similar combinations and tests can be performed on combinations of antibiotics or other drugs to identify effective combinations and concentrations.

[0148] Therefore, embodiments of this disclosure are directed to a fluid device 1 according to any aspect and embodiment described herein, which contains an amount of antibiotic selected from amoxicillin, amoxicillin / clavulanic acid (2 / 1), cephalexin, ciprofloxacin, ertapenem, fosfomycin, levofloxacin, mecillin, nitrofurantoin, trimethoprim, and trimethoprim / sulfamethoxazole (1 / 19) in an amount sufficient to achieve a desired antibiotic concentration, for example, between 1x and 5x of the bacterial breakpoint in a fluid sample dissolved in the analysis chamber 12. In some embodiments, the amount of antibiotic is sufficient to achieve a desired antibiotic concentration between 1x and 3x, between 1x and 2x, and suitably 1x of the bacterial breakpoint in a fluid sample dissolved in the analysis chamber 12. Preferably, the fluid device 1 comprises at least 3, at least 5, at least 7, at least 9, or at least 11 different antibiotics (or combinations thereof) selected from the antibiotics listed above, wherein each fluid system 6 of the device 1 contains at most one antibiotic or combination thereof listed above. The amounts of the antibiotics described above can be determined according to EUCAST and / or CLSI standards. Tables 1 and 2 below show exemplary target concentrations to be achieved for each antibiotic used in the fluid apparatus according to this disclosure.

[0149]

[0150]

[0151] Table 1: Target concentrations of each antibiotic achieved in fluid samples within the analysis chamber 12 of the apparatus 1 according to this disclosure are applicable to countries using CLSI. The apparatus 1 according to this disclosure may contain one or more antibiotics listed in the left column (Column 1), and / or may contain one or more amounts of each antibiotic required to produce the dissolved antibiotic concentrations listed in any of columns 4 to 7.

[0152]

[0153]

[0154] Table 2: Target concentrations of each antibiotic achieved in fluid samples within the analysis chamber 12 of the apparatus 1 according to this disclosure are applicable to countries using EUCAST. The apparatus 1 according to this disclosure may contain one or more antibiotics listed in the left column (Column 1), and / or may contain one or more amounts of each antibiotic required to produce the dissolved antibiotic concentrations listed in any of columns 4 to 7.

[0155] Referring to Tables 1 and 2 above, those skilled in the art will understand that device 1 may contain one or more antibiotics in amounts intended to provide two or more concentrations listed in columns 4 through 7 for each particular antibiotic. In other embodiments, device 1 may contain multiple antibiotics (or combinations of antibiotics) listed in column 1, one or more of which are intended to provide one or more concentrations listed in columns 4 through 7 for each antibiotic.

[0156] In some embodiments, the fluid device 1 according to the present disclosure includes 16 test microsystems 6, each test microsystem containing an antibiotic (or multiple antibiotics) listed in column 1 of Table 3 (below), in an amount suitable for providing an antibiotic concentration in each corresponding analytical chamber 12 equal to the CLSI concentration listed in column 3 of Table 3 or the EUCAST concentration listed in column 4 of Table 3.

[0157]

[0158]

[0159] Table 3: Examples of antibiotics to be achieved in fluid samples within the corresponding analysis chamber 12 of apparatus 1 according to this disclosure and the target concentrations of each antibiotic applicable to countries using CLSI (column 3) or countries using EUCAST (column 4).

[0160] The fluid apparatus 1 according to embodiments of this disclosure (e.g., as shown in Table 3) may preferably include an additional fluid system 6 providing one or more positive controls and / or one or more negative controls for determining background levels of bacterial growth or light scattering. For example, the positive control fluid system 6 may not contain antibiotics to illustrate the rate of bacterial growth in the fluid sample under inhibition / optimal growth conditions. The negative control fluid system 6 may include an opaque surface on the analysis chamber to block light from passing through the analysis chamber 12 and may be collected as scattered light; and / or may contain a bactericidal (or bacteriostatic) agent (e.g., triclosan) within the microfluidic chamber to inhibit bacterial proliferation.

[0161] While Tables 1 to 3 above list some exemplary embodiments of the present disclosure and the concentrations of antibiotics that can be used, it is understood, as stated above, that other known antibiotics and / or concentrations of any such antibiotics may be used in accordance with the present disclosure: for example, those that have been determined to show desirable or beneficial results in the system / under the conditions of interest.

[0162] An embodiment will now be described in which the fluid device 1 is used in a device containing optical analysis equipment to process clinical samples and determine the drug sensitivity of bacteria in these samples by measuring changes in light scattering within the samples, which, according to the invention, indicates corresponding changes in the number or concentration of bacteria over time.

[0163] Figures 11 to 15 Details of an exemplary optical analysis apparatus that can be used for this purpose are shown. A general description of the apparatus is provided here; further details of the apparatus can also be found in the applicant’s co-pending application entitled “Apparatus, System and Method for Measuring Properties of a Sample” (see, for example, GB2001397.5).

[0164] Figure 11 A vertical cross-sectional view of a device or apparatus 1101 including an optical arrangement 1102 and a sample positioning mechanism 1104 is shown. These two components are configured to interact with a fluid device 1 that contains a clinical sample to be analyzed, thereby enabling the aforementioned bacterial concentration determination to be performed.

[0165] The sample positioning mechanism 1104 is configured to engage and support the fluid device 1, and to optically couple or connect at least a portion of the fluid device 1 to components of the optical device 1102. More specifically, the sample positioning mechanism 1104 includes a sample turntable or sample carrier 1108 and an operating coupling motor 1110, such as a BLDC (brushless direct current) motor or other similar drive mechanism, which controls the rotation of the sample turntable 1108 (and thus controls the rotation of the engaged fluid device 1). In use, when the fluid device 1 and the optical device 1102 are optically coupled, the optical device 1102 is configured to irradiate the portion of the clinical sample contained within the fluid analysis chamber 12 of the fluid device 1. The optical device 1102 is also configured to detect and measure the light scattered by bacterial particles in the irradiated portion of the clinical sample. The intensity of the detected scattered light can then be analyzed to determine the nature of the bacteria in the sample, particularly the bacterial concentration (relative concentration of cell division / growth rate) in the sample over time.

[0166] Device 1101 includes a housing or casing 1112 in which other components are housed. In the illustrated embodiment, casing 1112 includes: a base 1112a on which other device components are mounted; a front body portion 1112b and a rear body portion 1112c providing walls for casing 1112; and a movable / removable cover 1112d. In the illustrated embodiment, cover 1112d is hinged to the rear body portion 1112c; other attachment mechanisms and locations may also be used. Cover 1112d, together with body portions 1112b, 1112c and base 1112a, forms a casing that houses various device components when device 1101 is in use. However, it will be understood that the various portions of casing 1112 may be more or fewer than shown herein. The device 1101 also includes a closure / locking mechanism 1113 for retaining the cover 1112d in a closed, locked position, for example, after the fluid device 1 has been inserted into a predetermined position within the device 1101 and engaged with the sample turntable 1108. In various embodiments, the closure mechanism 1113 includes an actuator 1113a located within the device housing 1112, which is programmably actuated when the cover 1112d is open.

[0167] Device 1101 also includes a temperature control module or arrangement 1114 configured to maintain the temperature within housing 1112, particularly in the area surrounding fluid device 1, within a preferred temperature range (e.g., about 36 to 38°C, preferably about 36 to 37°C, for example about 37°C). This temperature range is particularly suitable for promoting and maintaining the growth of bacteria in clinical samples under optimal growth conditions. Furthermore, the illustrated device includes a user interface 1115, such as an interactive touchscreen display, through which a user of device 1101 can interact with and program various aspects of device 1101; view certain results; and / or monitor the progress of the analysis process. For example, a user can enter detailed information that allows identification of a patient or subject; can use the interface to display and change measurement parameters; can also download software updates for device 1101 through user interaction with user interface 1115; measurement progress and various intermediate and final results can also be displayed to the user through user interface 1115. Furthermore, the user interface 1115 can be used to provide instructions to the user, guiding them through the various steps of loading the sample into the fluid device 1 and subsequently properly engaging the fluid device 1 with the sample turntable 1108. For example, the user interface 1115 can instruct the user to perform the following steps: (i) remove the cap 20; (ii) remove the collar 70; (iii) pour the sample into the receiving well 48; and (iv) screw the cap 20 on. Finally, the device 1101 includes one or more processors or processing units 1116 that provide programmable control over various device components, such as the optical device 1102, the sample positioning mechanism 1104, the cap closing mechanism 1113, and / or the user interface 1115.

[0168] Now refer to Figure 12 and Figure 13 Provides more detailed information on the configuration of the various components of device 1101 and the interactions between these components.

[0169] Specifically, as shown in the figure, motor 1110 is mounted on and supported by the base 1112a of housing 1112; motor 1110 also effectively forms a support base on which the remaining components of device 1101 are mounted or attached. Sample turntable 1108 is generally circular and is mounted above and connected to motor 1110 via a rotatable shaft 1117 extending along a vertically extending axis “X” passing through the center of sample turntable 1108. Therefore, rotational movement of sample turntable 1108 about the central axis “X” can be driven by motor 1110.

[0170] The sample turntable 1108 includes a plurality of openings 1118 arranged radially spaced around the sample turntable 1108. According to the depicted embodiment, the openings 1118 are radially positioned around the outer portion of the sample turntable 1108 such that, when the fluid device 1 is correctly oriented and engages with the sample turntable 1108, the position of each of the plurality of openings 1118 is aligned and corresponds to the position of one of a plurality of fluid analysis chambers 12 disposed within the fluid device 1. Therefore, the fluid analysis chamber 12 can be located at any suitable location on the fluid device 1, for example, in its outer region. As those skilled in the art will understand, the alignment between each opening 1118 and the corresponding fluid analysis chamber 12 should be adapted to allow light from a light source (described below) to pass through the opening 1118 and enter the corresponding fluid analysis chamber 12.

[0171] Optical device 1102 includes: a light source 1122 and collimating optics (not shown), such as a laser diode; a light collector or light-collecting arrangement 1124; and at least one photodetector 1126. The light source 1122 emits light along the incident beam axis “Y” and illuminates one or more sample portions in one or more fluid analysis chambers 12 of the fluid apparatus 1. The light collector 1124 collects light positively scattered by bacteria (particles) within the sample, particularly light scattered at angles of approximately + / -3 degrees to + / -24 degrees with respect to the incident beam axis Y, and at angles of approximately + / -4 degrees to + / -20 degrees with respect to the incident beam axis Y; in some embodiments, the light is scattered between +4 degrees and +16 degrees and between -4 degrees and -16 degrees on both sides of the incident beam axis Y (e.g., in a specific radius loop of the beam). In some embodiments, the collected light may be scattered between +5 degrees and +16 degrees and between -5 degrees and -16 degrees on both sides of the incident beam axis Y. Of course, those skilled in the art will recognize that light scattered at smaller angles (i.e., less than + / -3 degrees or + / -4 degrees to either side of the incident beam axis) can also be collected; however, this may undesirably increase the proportion of unscattered incident light collected by the collector 1124. The width of the incident beam can be reduced to allow the collection of light scattered at smaller angles without including too large a proportion of unscattered light; however, this, in turn, will result in a smaller amount of sample irradiated, which will reduce the amount of scattered light generated. Therefore, a balance needs to be struck in this regard.

[0172] The collected scattered light is guided by the light collector 1124 to the photodetector 1126, where the intensity of the collected scattered light can be analyzed, for example, to determine the relative number or concentration of bacteria in the test chamber sample at a given time point as the amount of scattered light detected varies.

[0173] Various components of the optical device 1102 are mounted on a support plate or structure 1128 to form an optical "tower," which, in the illustrated embodiment, extends substantially vertically upward from and is supported by the motor 1110 or its housing 1110a. However, it should be recognized that the mounting of the optical "tower" 1128 can be separated from or detached from the motor 1110 and its housing 1110a to isolate the optical device 1102 from any vibrations that may be generated by the motor 1110. Therefore, in either case, the optical tower 1128 structure is also substantially perpendicular to the plane in which the sample turntable 1108 and the fluid device 1 are located during use. Consequently, the incident beam axis "Y" of the light emitted by the light source 1122 is parallel to the rotation axis "X" of the sample turntable 1108, but laterally offset by a distance "d".

[0174] The lateral offset “d” between the rotation axis X and the incident beam axis Y substantially corresponds to the radial distance between the center of the fluid analysis chamber 12 and the center of the fluid device 1. Conveniently, the distance “d” can also be the same as or substantially the same as the radial distance between the center of the sample turntable 1108 and the opening 1118 disposed within the platform. The support structure 1128 of the optical device 1102 has a gap or cutout 1130 located between the light source 1122 and the light-collecting arrangement 1124 (somewhere in the vertical plane) and on the plane of the sample turntable 1108; the cutout 1130 is sized and positioned such that it is configured to receive a radially outer portion of the sample turntable 1108 therein. Thus, this received portion of the sample turntable 1108 (and the corresponding portion of the fluid device 1 engaged in use) can extend into the support structure 1128 and the optical tower, thereby intersecting with the incident beam axis Y of the light emitted from the light source 1122. In fact, the sample turntable 1108, support structure 1128, optical device 1102 and fluid device 1 are designed and adjusted so that, in use, the light emitted by the light source 1122 passes through one of the openings 1118 of the sample turntable 1108 and then enters the corresponding fluid analysis chamber 12 aligned with the corresponding opening 1118, thereby illuminating and analyzing the sample portion contained in the fluid analysis chamber 12.

[0175] Therefore, when the fluid device 1 is engaged with the sample turntable 1108, the light beam path emitted by the light source 1122 is rotated via the motor 1110 of the fluid device 1, and each fluid analysis chamber 12 of the fluid device 1 can be sequentially located in the incident beam axis "Y". Thus, the scattered light from bacterial particles in the sample portion contained in each fluid analysis chamber 12 can be sequentially collected and measured by the optical device 1102. In some embodiments, "measurement" refers to a quantitative assessment of the amount / intensity of light scattered by bacteria in the sample; while in other embodiments, a qualitative assessment of the relative amount of scattering caused by samples in different sample chambers can be performed.

[0176] In the depicted embodiment, the optical device support structure 1128 includes an upper (suspended) cover portion 1132 that supports some components of the optical device 1102, such as the light-collecting arrangement 1124 and the photodetector 1126. The cover 1132 also provides an additional useful function: preventing non-scattered light traveling along the substantially vertical incident beam axis "Y" from leaving the device 1101 or accidentally reaching the user of the device 1101 (e.g., in the case where the cover 1112d of the housing 1112 is removed and the light source 1122 emits light). Furthermore, the optical housing 1112 protects the optical components from sample marks that the user may leave on the outer surface of the device 1 before insertion into the device 1101.

[0177] like Figure 13 As shown, in an embodiment of this disclosure, the sample turntable 1108 includes an additional calibration ring or gear 1180 located below it and including a plurality of calibration features or teeth 1182. In the illustrated embodiment, the calibration features 1182 correspond to a plurality of radially extending spokes extending from the calibration ring 1180 at intervals, and are arranged such that each calibration feature 1182 is associated with a corresponding one of a plurality of openings 1118.

[0178] In use, when the fluid device 1 engages with the sample turntable 1108, each calibration feature 1182 will also be associated with a corresponding one of the plurality of fluid analysis chambers 12 in the sample container body 2. The device 1101 also includes a calibration reader 1184 located near the underside of the sample turntable 1108 and configured to sequentially intersect with each calibration feature 1182 as the sample turntable 1108 is rotated by the drive shaft 1117 during use. Specifically, the calibration reader 1184 may include an optical arrangement configured to, for example, detect each calibration feature 1182 passing through or via it by detecting a reduction or loss of light signal due to the calibration feature 1182 passing through and temporarily blocking the beam path within the calibration reader 1184.

[0179] Since each calibration feature 1182 is associated with a fluid analysis chamber 12, the calibration reader 1184 can be used to detect each calibration feature 1182 associated with each opening 1118 of the sample turntable 1108 and send a signal to the controller / processor of the device 1 to begin measuring the intensity of scattered light for a predetermined period of time after detecting the calibration feature 1182, and for a sustained predetermined period of time, sufficient to include the time during which the analysis chamber 12 intercepts light from the light source 1122 without impacting the walls of the analysis chamber 12 (i.e., sufficient to obtain the light or reading scattered by the fluid within each analysis chamber 12). Advantageously, in this way, the light scattering measurement window is reset multiple times per rotation of the fluid device 1 to ensure proper synchronization of the photodetector reading with the analysis chamber 12. It is understood that the number of calibration features can be selected according to preference: for example, there may be a calibration feature associated with each opening 1118 in the sample turntable 1108, or there may be a calibration feature associated with a predetermined group of openings 1118 (e.g., a calibration feature 1182 for every 2, 3, 4, 5 or 6 openings 1118, etc.).

[0180] Alternatively, the calibration feature 1182' can take a different form. For example, the calibration feature can take the form of ribs, fins, or flags arranged at circumferential intervals around the sample turntable 1108. In this case, the mounting and orientation of the calibration reader 1184 allows the calibration feature to pass through the optical arrangement of the calibration reader 1184. Appropriately, a calibration feature is associated with each opening 1118 of the sample turntable 1108 such that each calibration feature, through the channel of the optical arrangement of the calibration reader 1184, can form a trigger for reading or measuring the scattered light obtained from each corresponding analysis chamber 12. Advantageously, this helps prevent the "window" from drifting due to changes in motor speed, since a specific indicator is associated with each opening 1118, and therefore with each analysis chamber 12.

[0181] In some cases, it is conceivable that the calibration reader 1184 (or the processor associated with the photodetector 1126) can be configured to calculate time intervals between adjacent calibration features 1182 passing through the reader 1184 and compare these calculated intervals with predetermined intervals at which the intensity of the collected scattered light is measured. If there is a difference between the measured “calibration” time interval and the predetermined measurement time interval, and this difference exceeds the predetermined time interval, the processor can be configured to change the measurement time interval to align it with the “calibration” time interval. This ensures that intensity measurements are performed when the fluid analysis chamber 12 is precisely aligned with the incident beam axis, i.e., when the light from the light source substantially passes through the center of the fluid analysis chamber 12. Processing power and time are also saved by analyzing only the light scattering measurements within the appropriate time window.

[0182] Figure 14 Details of an example arrangement of the optical components in optical device 1102 are shown. In this arrangement, light source 1122 corresponds to a laser module having a laser diode for generating light of a specific wavelength (e.g., red light in the range of 620 nm to 750 nm, more specifically around 635 nm) to illuminate a portion of the sample contained in fluid analysis chamber 12. It is worth noting that the aforementioned wavelengths are envisioned for urine sample analysis; however, the wavelength of light used may vary depending on the nature of the sample to be analyzed. For example, near-infrared wavelengths (between approximately 650 nm and approximately 1350 nm) may be used in relation to blood samples. The laser diode is connected to a signal generator (not shown) suitable for controlling the modulation frequency and phase of the laser output. Photodetector 1126 corresponds to a photodiode connected to a lock-in amplifier (also not shown); the lock-in amplifier is in turn connected to the signal generator for the laser diode. This allows the photodiode to isolate and filter out specific received signals having a frequency and phase corresponding to the modulation frequency generated by the signal generator for the laser diode. This allows noise (optical) signals of other frequencies (such as background noise, electrical noise) to be filtered out, thereby improving the signal-to-noise ratio obtained using optical device 1102. These components can be controlled by one or more processors 1116 of the system, for example, processor 1116 can be in the form of one or more programmable circuit boards (PCBs).

[0183] The light collector 1124 in this example includes a reflector or reflective surface, which, in the illustrated embodiment, is mounted to the support structure 1128 to extend through the incident beam path. Specifically, Figure 14The light collector 1124 corresponds to a curved concave elliptical mirror 1144 having an eccentric opening, aperture, or aperture 1146 therein. The mirror 1144 is mounted to the support structure 1128 such that the aperture 1146 is aligned with the incident beam axis "Y," allowing unscattered light exiting the fluid analysis chamber 12 and traveling along the beam axis Y to pass cleanly through the mirror 1144 with substantially no deflection; thus, preventing this unscattered light from reaching the photodetector 1126. Furthermore, the mirror 1144 is arranged at such an angle, and its dimensions are such that light scattered in the forward direction by particles in the sample (particularly light scattered in the angular range of approximately +4 degrees to +16 degrees and approximately -4 degrees to -16 degrees along the incident beam axis Y) is reflected by the mirror 1144 and towards the photodetector 1126. In some other embodiments, the light reflected by mirror 1144 toward photodetector 1126 can be between approximately +3 and +24 degrees and approximately -3 and -24 degrees along the incident beam axis Y; between approximately +3 and +20 degrees and approximately -3 and -20 degrees; between approximately +5 and +20 degrees and approximately -5 and -20 degrees; or within an angular range between approximately +5 and +16 degrees and -5 and -16 degrees. In the arrangement of the illustrated embodiment, concave elliptical mirror 1144 reflects positively scattered light away from the incident beam axis Y within a defined angle (especially in the illustrated non-limiting embodiment, approximately 90 degrees relative to the incident beam axis Y) and focuses it onto photodetector 1126. One or more system processors 1116 are associated with photodetector 1126 and process the detection signal generated by photodetector 1126 to calculate the intensity of the detected scattered light. It can generate graphs or curves of the detector output (corresponding to the measured intensity of scattered light over time); examples of such graphs include... Figure 16 As shown. In some embodiments, the graph and / or the data used to generate it may be displayed to the user via the user interface 1115, for example, periodically as a basic real-time indication of the process, or as a final (summary) output after the analysis process for a given sample is completed.

[0184] like Figure 14As shown, the system of this embodiment also includes a second photodetector 1148, aligned with the incident beam axis "Y" but located on the opposite side of the collector 1124 from the sample, arranged to detect and measure unscattered light passing through the aperture 1146 in the mirror 1144. This second photodetector 1148 also corresponds to a photodiode, configured substantially the same as the first (main) photodetector 1128, i.e., the second photodetector 1148 is connected to the signal generator of the light source 1122 via a lock-in amplifier to ensure that the second photodetector 1148 (and / or a processor 1116 associated with the photodetector 1148) is also capable of filtering out the desired laser signal frequency and phase from any noise signals. Providing this additional second photodetector 1148 allows for baseline measurements of the unscattered laser, which can be compared with the scattered light intensity measured using the first (main) photodetector 1126. This allows, for example, the detection of anomalies in the irradiation; it also allows for the evaluation and consideration of laser stability during analysis. It should be understood that the second photodetector 1148 may be omitted in any embodiment of this disclosure. In some such embodiments, a beam collector or other device may be used to collect unscattered light from the laser.

[0185] Although Figure 14 The optical arrangement shown is particularly advantageous in reducing the number of components required to perform / implement this disclosure, but other optical arrangements are also possible. For example, Figure 14 The custom concave elliptical reflector 1144 can be replaced by a pair of reflective elements, such as a first reflector that deflects forward-scattered light onto a focusing lens or a second concave reflector that focuses reflected light from the first reflector onto a photodetector 1126.

[0186] Now refer to Figure 15 The method 700 for using the above-described device 1101 is described.

[0187] First, in step 705, the user securely places the clinical sample in the fluid device 1, and then in step 710, inserts the fluid device 1 into the appropriate position within the device 1101. This includes correctly aligning the fluid device 1 with the optical tower support structure 1128 (e.g., aligning the notch or cut section or other surface feature 24 of the fluid device 1 with the support structure 1128, wherein the shape and size of the cut section 24 is typically a mirror image of the outline of the optical tower support structure 1128, or a corresponding / supplementary structure of the device 1101), and engaging the fluid device 1 with the sample turntable 1108. In some embodiments, this process may be guided by a user interface 1115 (e.g., through a series of diagrams and corresponding written / verbal instructions). The housing cover 1112d of the device 1101 is then closed, and in step 720, the user interacts with the user interface 1115 to initiate a pre-programmed sequence of actions to be taken by the various components of the device to perform the desired sample analysis.

[0188] Before performing these pre-programmed actions, or actually as part of these actions, device 1101 may be configured to identify fluid device 1 in step 715 and determine information associated with that particular fluid device 1 based on data provided on the fluid device 1 itself or its packaging. In some cases, this information may be contained in or obtainable through a unique identification code provided on the fluid device 1, which may include a unique identifier associated with the fluid device 1 itself, a unique identifier associated with a specific batch of the fluid device 1 that forms part of it, and the date of use of the contents of the fluid device 1. This identification code may be provided in the form of an RFID tag or barcode (e.g., a 2D barcode), which may be scanned by device 1101 before insertion of the fluid device 1 (e.g., via a separate scanner associated with device 1101) or even after insertion of the fluid device 1 (scanned by device 1101, for example, by a scanner integrated into device 1101). For example, an internal barcode scanner / reader 1159 (in Figure 11 The device shown is mounted to the inner wall of the device housing 1112. In this embodiment, the scanner 1159 is mounted at a specific angle such that it is pointed at an identification RFID tag or barcode located on the sample container. For example, the barcode or other identification method may be located on the angled portion 25 of the fluid device 1 (e.g., near the cut section 24 of the fluid device 1 so that it can be read by the scanner 1159 once the fluid device 1 is inserted into the device 1101).

[0189] Additional information can also be provided as part of or supplementing the identification code, such as details of a specific drug provided in each fluid analysis chamber 12 of a given fluid device 1, enabling analysis to be performed knowing the drug being tested. Furthermore, details regarding potential software updates can also be included as part of the provided information; this allows device 1101 to easily and efficiently obtain information from the fluid device 1 itself regarding appropriate software updates and changes that may be necessary.

[0190] Alternatively or additionally, the unique identification code may be provided on the packaging of the fluid device 1 (e.g., on a box containing one or more fluid devices 1 from a specific batch), or even provided with the packaging, for example, in the form of a USB flash drive associated with the packaging and pre-loaded with the relevant identification information. Advantageously, using the packaging or a separate USB flash drive to provide this information increases the storage space available to hold the data, thereby enabling more data to be provided within the identification code. In this case, the device housing 1112 may be provided with a port for receiving and intersecting with the USB flash drive.

[0191] Device 1101 can also be programmed to verify that fluid device 1 is one of the containers in an approved batch that can be used with device 1101 (e.g., to identify any counterfeit or unauthorized sample containers and prevent them from being used with device 1101). In this regard, fluid device 1 may be provided with identification (anti-counterfeiting) features that can be detected by device 1101; this may be provided as part of or additional to the aforementioned unique identification code. Device 1101 may be programmed to object to or refuse to process any fluid device 1 that does not include such features, in order to avoid detecting unreliable or misleading results and reporting them to the user.

[0192] Therefore, the first series of pre-programmed actions performed by device 1101 in step 725 are used to operate motor 1110 to rotate at a specific rotational frequency, along a specific predetermined direction, and for a specific duration, in order to redistribute a portion of the clinical sample from the main fluid reservoir 4 of fluid device 1 to each of the plurality of fluid analysis chambers 12, that is, to perform Figure 10 Steps 510 to 530 of method 500 shown.

[0193] Once the process has been completed and the various drug-doped sample portions have been redistributed into their respective fluid analysis chambers 12, the next series of pre-programmed actions taken by the device 1101 involves analyzing the sample within each fluid analysis chamber 12, i.e., as will now be described. Figure 10Details of step 535 in method 500. Motor 1110 is programmed to drive sample turntable 1108 and associated fluid device 1 at a constant rotational rate (e.g., 100 rpm) over an extended period (e.g., over approximately 30 to 90 minutes), such that a given point on fluid device 1, such as a specific fluid analysis chamber 12, performs a complete rotation approximately every 0.6 seconds. Therefore, at a rotational speed of 100 rpm, each detection chamber 20 will pass through the incident beam axis Y at predetermined intervals (e.g., approximately every 0.6 seconds). Thus, each sample portion in its respective fluid analysis chamber 12 is sequentially irradiated (each predetermined time interval), and the scattered light is collected by photodetector 1126 and can be processed / analyzed at regular intervals during assays (e.g., bacterial growth / antibiotic susceptibility assays). Given the frequency of measurements, in some cases, it is conceivable that a (weighted) rolling average (moving average, sequential average) of the sample measurements can be used to process and combine the scattered light measurements obtained from each detection chamber 12. This will advantageously reduce the noise associated with each average sample measurement point (by combining the square root of the individual measurements to obtain a weighted average). For example, in some cases, it is conceivable that a smoothed average can be applied to 50 to 500 measurements (e.g., more than 100 measurements, equivalent to 60 seconds at a conceived rotation speed of 100 rpm). In some embodiments, the rotation speed of the sample turntable 1108 (and the fluid device 1) is selected based on pre-programmed / factory settings; and can be determined based on the processing speed of the device 1101 and / or the desired measurement frequency. Thus, the rotation speed of the fluid device 1 during the measurement can be faster or slower than 100 rpm (e.g., between 50 rpm and 300 rpm). Similarly, the duration of the measurement can also be based on pre-programmed / factory settings, or in some embodiments can be set according to user preferences. For example, the duration of the measurement can be determined by the type of bacteria and / or the antibiotic to be tested against; and can be between about 20 minutes and 4 hours, for example between about 20 minutes and 2 hours, or between about 20 minutes and 1.5 hours. In some preferred embodiments, the duration of the measurement is between about 20 minutes and 1 hour, or between about 30 minutes and 1 hour.

[0194] As briefly mentioned earlier in this document, the signal intensity generated by the main “signal” photodiode 1126, as a result of the measured scattered light intensity, is correlated with the amount and / or concentration of (bacterial) particles in the analyzed / measured sample. In other words, a larger / stronger signal corresponds to a greater amount of light scattering, and therefore, a greater scattered light intensity, in turn, indicates a higher concentration of bacterial particles in the sample. Therefore, a graphical representation of the detection signal (based on scattered light intensity) over time can be used to visualize and / or calculate the time-varying changes in the amount and / or concentration of bacteria in the sample, thereby demonstrating and ultimately determining the sensitivity of the bacteria in that sample to the type and concentration of the drug used on that particular sample.

[0195] Figure 16 An example of such a graphical representation is shown, in which the sensitivity of bacteria in a clinical sample to five different types of antibiotics was tested. In this example, the fluid device 1 is divided into 28 individual fluid analysis chambers 12 and associated channels for separating the clinical sample into the 28 fluid analysis chambers 12, allowing up to 28 individual assays to be performed simultaneously. The 28 assays are divided into four regions—labeled regions 1 to 4—and in each region, five antibiotic sensitivity tests are performed, along with a negative control (in which the fluid analysis chamber is altered (e.g., made opaque) to prevent incident light from passing through) and a positive control (tracking uninhibited bacterial growth in the absence of any antibiotics).

[0196] In this configuration, five different antibiotics are provided in each of the five assay chambers in each region, allowing for four repetitions of the bacterial susceptibility test for each antibiotic in each fluid device 1, with one test performed in each of the four regions. In this manner, the reproducibility of the assays around fluid device 1 can also be assessed. Fluid device 1 rotates at approximately 100 rpm, and the intensity of scattered light collected from each fluid analysis chamber 12 is measured over a period of approximately 80 minutes.

[0197] from Figure 16The graphs clearly show that, during the measurement period, the fluid analyzers used as positive controls exhibited an exponential increase in the intensity of detected scattered light (and thus a corresponding exponential increase in bacterial quantity and / or concentration). This reflects the extent of the increase in bacterial quantity and / or concentration (under the assay conditions) that would typically be expected if the absence of drugs or other inhibitors and the bacteria were able to grow and replicate normally in a solution containing an appropriate concentration of growth medium. Meanwhile, the fluid analyzers used as negative controls showed the lowest detection intensity throughout the measurement period, which was also expected. Of the five fluid analyzers in each quadrant containing various antibiotics, four showed changes in detection intensity indicating a decrease in bacterial quantity and / or concentration (relative to the positive control) due to the action of the antibiotics; i.e., the curves had a lower or negative gradient relative to the positive control curves, but still (at least initially) had values ​​higher than the negative control line. Among the various administered samples, the sample showing the largest decrease in light scattering measurement intensity over time compared to the positive control sample (theoretically) would correspond to the sample with the specific type and / or concentration of antibiotics most susceptible to the bacterial strains present in the administered sample. Therefore, it is relatively easy to determine in a short period of time which antibiotic and which concentration may be most effective in treating patients who have obtained this clinical sample.

[0198] Of course, it is possible (in fact, very likely) that multiple different antibiotics may be identified as those to which the bacteria in a sample may be sensitive. Therefore, various different methods have been considered for determining the most suitable antibiotic for treatment. For example, sensitivity results can be presented to the user in real time, and the analysis can be terminated at any point after at least one antibiotic has been determined to be effective. However, this is not necessarily the most suitable antibiotic to administer; for example, if the response of the bacterial culture changes over a slightly longer period, or if an antibiotic initially requires a longer incubation time to become effective. Alternatively, another approach could be to limit the time for performing the test (e.g., to 30 minutes, 45 minutes, or 1 hour) and present the results to the user after that time: this could mean that multiple antibiotics (or even none) and / or multiple dose levels could be considered for administering to the subject. Another option is to display results only after a certain number of antibiotics have been deemed effective. This, of course, means that the timescale required for the test will vary. Of course, combinations of these methods can be employed in embodiments of this disclosure.

[0199] Numerous modifications may be made to the above examples without departing from the scope of this disclosure as defined in the appended claims.

[0200] For example, the drug does not need to be provided in the fluid analysis chamber 12, but can be located in a different part of the fluid system 6, for example, in the second channel arm 32d of the second fluid channel 32.

[0201] Furthermore, or alternatively, a second valve mechanism containing a chamber for compressed storage gas may be positioned in the flow path of each fluid system 6, after the fluid analysis chamber 12, to allow for more efficient mixing of the sample and drug (through a back-and-forth "shaking" motion between the two valves during reciprocating rotation), where a particular drug may not dissolve rapidly in the fluid sample, such as... Figure 17 As shown.

[0202] Figure 17 An alternative arrangement of the fluid system 6' used according to an embodiment of this disclosure is shown. The fluid system 6' is generally arranged in accordance with FIG. 2, Figure 2A The intermediate fluid system 6 is arranged in the same manner in the area between the main fluid reservoir 4 and the analysis chamber 12. Therefore, the fluid system 6' includes a fluid channel arrangement 26 comprising a first inlet fluid channel 28 having an inlet port 28a located at its radially innermost extent and an outlet port 28b located at its radially outermost extent. The inlet port communicates with the main fluid reservoir 4, and the outlet port communicates with the separation chamber or clarification chamber 30. In the illustrated embodiment, the outlet port 28b is positioned towards the radially outermost extent of the fluid system 6; however, as Figure 2C and Figure 2DIn various embodiments, the fluid analysis chamber 12 may be the outermost radial fluid chamber. As previously described, the separation chamber 30 forms a well shape in the base of the radially outer portion 18 of the container body 2 and is configured to separate unwanted particles / impurities from the remainder of the fluid sample. The exit port 28b of the first fluid channel 28 preferably connects toward the outermost wall portion of the separation chamber well 30 (i.e., near the radial "base"). The fluid channel arrangement 26 also includes a second fluid channel 32 having an inlet port 32a communicating with the separation chamber 30 and an exit port 32b communicating with the fluid analysis chamber 12. A weir (or step) 30a is located between the separation chamber 30 and the inlet port 32a of the second fluid channel 32, which improves the separation / clarification function provided by the separation chamber 30. The second fluid channel 32 is substantially U-shaped and includes first and second channel arms 32c, 32d, which are arranged to provide generally antiparallel fluid flow paths on either side of the first valve mechanism / air spring 8. Therefore, the first channel arm 32c extends substantially (opposite) parallel to the first fluid channel 28, allowing the fluid sample to flow out of the separation chamber 30 and radially inward along the first channel arm 32c. The second channel arm 32d extends substantially (opposite) parallel to the first channel arm 32c, allowing the fluid sample to reverse its flow direction and move radially outward toward the fluid analysis chamber 12. These two channel arms 32c and 32d are in fluid communication with each other at their innermost radial extent via a first air spring 8. Therefore, the compressed gas can be configured to provide reverse pressure to counteract the centrifugal force applied to the fluid sample by the rotation of the fluid device 1, thereby preventing fluid from flowing between the two channel arms 32c and 32d. According to this embodiment, a third fluid channel 35 is provided to communicate with the analysis chamber 12, and the analysis chamber 12 is connected to the second valve mechanism or air spring 8'. The third fluid channel 35 has an inlet port 35a communicating with the analysis chamber 12 and an outlet port 35b communicating with the second valve mechanism 8'. The third fluid channel 35 is arranged generally (opposite to) parallel to the second channel arm 32d of the second fluid channel 32, such that the second valve mechanism 8' is radially arranged inside the analysis chamber 12. In some embodiments, an enlarged region 35c of the third fluid channel 35 may be provided, in which drugs / antibiotics may be placed instead of within the analysis chamber 12.

[0203] Conveniently, according to embodiments of this aspect of the disclosure, in use, once the sample fluid has filled the analysis chamber 12, the rotational speed of the fluid device 1 can be increased to force the liquid sample along the fluid channel 35 toward the second valve mechanism 8'. Once the liquid sample reaches region 35c of the fluid channel (in some embodiments, this region may not be an extended region of the fluid channel, but may simply correspond to the region of drug deposition), the sample can begin to dissolve the drug / antibiotic. By reducing the rotational speed of the fluid device 1, the pressure in the second valve mechanism 8' overcomes the centrifugal force of the liquid sample, and the sample is pushed back into the analysis chamber 12. Thus, by alternately increasing and decreasing the rotational speed, the liquid sample can be made to flow back and forth (shake) along the fluid channel 35 through region 35c, thereby efficiently dissolving antibiotics. These embodiments may be particularly advantageous for use with drugs that may not be readily soluble in the liquid sample, as the mixing between the sample and the drug may be improved. Embodiments of the fluid system 6' can generally be used according to the rotational speed patterns of the fluid system 6 (described above).

[0204] Furthermore, it is worth noting that the design of the fluid device 1 can be altered by changing the depth of the chamber well, thereby changing the optical path length of light passing through the fluid analysis chamber 12. Increasing the optical path length will increase the signal: the light will pass through more of the sample and interact with more bacterial particles in the process. Examples of conceivable path lengths are 3 mm to 10 mm or 4 mm to 8 mm (e.g., well depths of 4 mm, 5 mm, 6 mm, or 7 mm); changing the optical path length will also involve changing the dimensions of other features in the fluid system 6 (e.g., the clarification chamber 30 and the air spring 8 or springs 8, 8'). As described in previous embodiments, the volume of the second air spring / valve mechanism 8' can be selected according to preference (e.g., based on the volume of the analysis chamber 12 and / or the desired rotational speed of the device). In a particular embodiment, the volume of the second air spring 8' can be between approximately 10 μl and 50 μl.

[0205] Other mechanisms for improving the signal-to-noise ratio involve “masks” around the edges of the fluid analysis chamber 12, for example, by attaching a thin film or plastic sheet or other thin material to the bottom of the fluid device 1 to prevent light from entering the fluid device 1 or interacting with other parts of the fluid device. For example, the diameter of the opening 1118 in the sample turntable 1108 may be smaller than the diameter of the fluid analysis chamber 12.

Claims

1. A fluid device configured to drive fluid movement under centrifugal force, the fluid device comprising: A central region about the central axis of rotation of the device and a peripheral region extending radially outward from the central region; A fluid reservoir, disposed in the central region of the device for receiving fluid samples, the fluid reservoir being in communication with at least one fluid system extending radially outward from the fluid reservoir to the peripheral region of the device; Each fluid system includes: A fluid analysis chamber, configured to retain a portion of the fluid sample for analysis; A fluid channel arrangement configured to allow fluid communication between the fluid reservoir and the fluid analysis chamber, wherein the movement of the fluid sample through the fluid channel arrangement is driven by centrifugal force generated by the rotational motion of the device about the central axis of rotation; and A first valve mechanism is configured to prevent fluid from flowing through a portion of the fluid channel arrangement when the rotational speed of the device about the central axis of rotation is less than a first predetermined value, wherein the first valve mechanism is disposed between the fluid reservoir and the fluid analysis chamber, and the fluid channel arrangement includes: A separation chamber configured to remove unwanted particles from the fluid sample before it enters the fluid analysis chamber; A first fluid passage extends radially outward from the fluid reservoir to the separation chamber and communicates with the separation chamber through a wall in the radially outer region of the separation chamber; and A second fluid channel configured for fluid communication between the separation chamber and the fluid analysis chamber, the second fluid channel including a pair of channel arms configured to allow fluid to flow in an antiparallel direction, wherein the first valve mechanism is located in the flow path between the pair of channel arms of the second fluid channel.

2. The fluid apparatus of claim 1, wherein the separation chamber has a depth (d) defining a height between the bottom and the top of the separation chamber, and the first fluid passage is arranged to communicate with the separation chamber at or near the bottom of the separation chamber.

3. The fluid device according to claim 1 or 2, wherein the second fluid passage includes a first channel arm for fluid communication between the separation chamber and the first valve mechanism, the first channel arm extending radially inward from the separation chamber to the first valve mechanism and communicating with the separation chamber through a wall in a radially inner region of the separation chamber.

4. The fluid device according to claim 1 or 2, wherein the second fluid passage includes a second channel arm for fluid communication between the first valve mechanism and the fluid analysis chamber, the second channel arm extending radially outward from the first valve mechanism to the fluid analysis chamber.

5. The fluid device according to claim 1 or 2, wherein the inner corner of the channel arm is rounded to reduce wicking of fluid along the channel in the direction opposite to the centrifugal force acting on the fluid during use.

6. The fluid apparatus according to claim 1 or 2, wherein the first valve mechanism is located radially inside the separation chamber and / or the fluid analysis chamber.

7. The fluid apparatus of claim 1 or 2, wherein the first valve mechanism defines a chamber for receiving a predetermined amount of gas, the chamber having a maximum size on the x-axis, y-axis and z-axis, wherein the x-axis defines a radial direction, the y-axis defines a direction perpendicular to the x-axis in a radial plane, the z-axis defines a direction parallel to the axis of rotation and perpendicular to both the x-axis and the y-axis, and wherein the first valve mechanism has a maximum size on the z-axis.

8. The fluid device according to claim 1 or 2, wherein the first valve mechanism is arranged circumferentially around and adjacent to the fluid reservoir.

9. The fluid apparatus according to claim 1 or 2, wherein the fluid analysis chamber is arranged radially outside the separation chamber.

10. The fluid apparatus of claim 9, wherein the fluid analysis chamber is the outermost radial element of the fluid system.

11. The fluid apparatus according to claim 1 or 2, wherein the fluid analysis chamber is cylindrical and has a circular cross-section in the axial plane of the apparatus.

12. The fluid device according to claim 1 or 2, wherein one or more fluid systems contain at least one drug in a region thereof, the drug being in a form suitable for dissolution in the fluid sample.

13. The fluid apparatus of claim 1 or 2, wherein the fluid passage arrangement further comprises a third fluid passage arranged to extend between the fluid analysis chamber and the second valve mechanism, and wherein the second valve mechanism is located radially inside the fluid analysis chamber.

14. The fluid apparatus according to claim 1 or 2, wherein the at least one fluid system contains at least one drug for measuring the fluid sample, wherein the drug is disposed in the fluid analysis chamber, in a first drug retention chamber located between the first valve mechanism and the fluid analysis chamber, or in a second drug retention chamber located between the second valve mechanism and the fluid analysis chamber.

15. The fluid device of claim 12, comprising at least one fluid system containing an antibiotic or a combination of antibiotics; The antibiotics or combinations thereof are selected from the group consisting of: amoxicillin, amoxicillin / clavulanic acid, cephalexin, ciprofloxacin, ertapenem, fosfomycin, levofloxacin, mecillin, nitrofurantoin, trimethoprim, and trimethoprim / sulfamethoxazole.

16. The fluid apparatus of claim 15, comprising a plurality of fluid systems containing antibiotics or combinations of antibiotics, wherein each of the plurality of fluid systems contains a different predetermined amount of antibiotics or combinations of antibiotics, such that, in use, predetermined different concentrations of antibiotics or combinations of antibiotics are generated in fluid samples in each fluid analysis chamber of the plurality of fluid systems.

17. The fluid apparatus of claim 1 or 2 further comprises a bacterial growth medium configured to promote the growth of bacteria that may be present in the fluid sample when mixed with the fluid sample; the growth medium is disposed in the fluid reservoir or in a growth medium compartment in fluid communication with the fluid reservoir.

18. The fluid apparatus of claim 17, wherein the growth medium is disposed in a growth medium compartment, the growth medium compartment being in fluid communication with the fluid reservoir via a filter element or membrane.

19. The fluid apparatus of claim 17, further comprising a sample receiving well for receiving fluid samples to be transferred to the fluid reservoir and the at least one fluid system.

20. The fluid apparatus according to claim 1 or 2, wherein the central region of the fluid apparatus includes a sample receiving well for receiving fluid samples, and wherein, The sample receiving well is connected to the fluid reservoir via a growth medium compartment containing the growth medium and a filter element, the filter element being arranged to filter the mixture of fluid sample and growth medium before it enters the fluid reservoir during use.

21. The fluid device of claim 19, further comprising a cover for closing the sample receiving well, wherein the sample receiving well is formed within an upright neck portion in a central region of the device, the neck portion being provided with a fixing feature for engaging with a complementary fixing feature of the cover.

22. The fluid device of claim 21, wherein the cover has a top wall and an annular outer peripheral wall extending downward from the top wall, wherein the inner surface of the annular outer peripheral wall has threads for engaging with a complementary threaded portion of the neck of the fluid device.

23. The fluid device of claim 22, wherein the cover further comprises a cylindrical plunger element, the cylindrical plunger element standing upright from the top wall of the cover and arranged radially inside the annular outer peripheral wall; wherein the outer annular surface of the plunger element is configured to mate with the inner annular surface of the sample receiving well so as to discharge a predetermined volume of fluid from the sample receiving well when the cover is engaged with the neck of the fluid device.

24. The fluid apparatus of claim 20, wherein a ruptureable sealing element is provided between the sample receiving well and the growth medium compartment.

25. The fluid apparatus of claim 24, further comprising a cap for sealing the sample receiving well, wherein the sample receiving well is formed within an upright neck portion in a central region of the apparatus, the neck portion being provided with a fixing feature for engaging a complementary fixing feature of the cap, and further comprising one or more protrusions disposed radially inward of the cap and upright downward from the cap, and configured to: (i) pierce the sealing element between the sample receiving well and the growth medium compartment to allow fluid communication between the sample receiving well and the growth medium compartment; and / or (ii) agitate and / or mix the fluid sample with the growth medium in use to improve the solubility of the growth medium and the fluid sample.

26. The fluid device of claim 25, further comprising a collar element capable of engaging between the neck of the device and the cap, the collar element being configured to limit the engagement depth between the cap and the neck such that the one or more protrusions cannot puncture the sealing element when the collar element is in place.

27. The fluid apparatus of claim 19, further comprising a funnel element configured to guide the fluid sample to the top of the sample receiving well.

28. The fluid device of claim 21, wherein the neck portion is formed by an outer annular wall and an inner annular wall, the inner annular wall defining at least a portion of the sample receiving well, and the outer annular wall being provided with a fixing feature for engaging with a complementary fixing feature of the cap.

29. The fluid device of claim 28, wherein the space between the outer annular wall and the inner annular wall of the neck portion defines an annular chamber, or is divided into a plurality of radially segmented chambers by a plurality of radially spaced walls or ribs.

30. The fluid apparatus of claim 29, wherein the annular chamber or at least one radially segmented chamber is an overflow chamber, the overflow chamber being in fluid communication with the sample receiving well via at least one overflow orifice, the overflow orifice being arranged such that a predetermined maximum volume of fluid sample can be received in the sample receiving well before the fluid sample in the sample receiving well reaches the at least one overflow orifice.

31. The fluid apparatus of claim 29, wherein at least one of the radially segmented chambers is a gas release chamber, the gas release chamber being in fluid communication with the fluid reservoir via at least one lower gas release port communicating with a lower region of the gas release chamber, and being arranged such that when the fluid reservoir is filled with a fluid sample from the sample receiving well, gas in the fluid reservoir can be discharged upward into the at least one gas release chamber.

32. The fluid device of claim 21, wherein one or more orifices are configured to pass through the top of the cover.

33. The fluid device according to claim 1 or 2, comprising a body and a base, wherein the fluid reservoir and the at least one fluid system are defined within the body of the device, and the base is connectable to the body to define a lower surface of the fluid reservoir and the fluid system.

34. The fluid device of claim 33, wherein the base is a membrane configured to be fixed to the body of the device by an adhesive or heat seal.

35. The fluid device according to claim 1 or 2, comprising at least one fluid system containing an antibiotic or a combination of antibiotics; wherein the antibiotic or combination of antibiotics is selected from the group consisting of: amoxicillin, amoxicillin / clavulanic acid, cephalexin, ciprofloxacin, ertapenem, fosfomycin, levofloxacin, mecillin, nitrofurantoin, trimethoprim, and trimethoprim / sulfamethoxazole.

36. The fluid device according to claim 1 or 2, wherein the fluid device comprises: At least one fluid system containing the antibiotic amoxicillin; At least one fluid system containing the antibiotic combination amoxicillin / clavulanic acid; At least one fluid system containing the antibiotic cephalexin; At least one fluid system containing the antibiotic ciprofloxacin; At least one fluid system containing the antibiotic ertapenem; At least one fluid system containing the antibiotic fosfomycin; At least one fluid system containing the antibiotic levofloxacin; At least one fluid system containing the antibiotic mecillin; At least one fluid system containing the antibiotic nitrofurantoin; At least one fluid system containing the antibiotic trimethoprim; and / or At least one fluid system containing the antibiotic combination trimethoprim / sulfamethoxazole; At least one fluid system that does not contain antibiotics, and / or at least one fluid system that contains an effective amount of bactericide.

37. An apparatus comprising: The fluid device according to claim 1 or 2; A drive mechanism for driving the fluid device to rotate around its central axis; as well as A controller that executes machine-readable code to enable the drive mechanism to control the flow of the fluid sample from the fluid reservoir to each fluid analysis chamber.

38. The apparatus of claim 37, further comprising an optical device, the optical device comprising: A light source configured to emit an incident light beam and illuminate the fluid sample in each of the fluid analysis chambers; as well as A photodetector configured to detect scattered light exiting each of the fluid analysis chambers.

39. The apparatus of claim 38 further includes a sample container turntable arranged to engage with the fluid device and configured to periodically align and dealign each of the fluid analysis chambers with and from an incident beam of light from the optical device.

40. The apparatus of claim 38 or 39, further comprising at least one processor configured to analyze the detected scattered light to determine one or more properties of a fluid sample contained in the at least one fluid analysis chamber.

41. The apparatus of claim 40, wherein the one or more properties are selected from: relative amount of bacteria; relative concentration of bacteria; change in relative amount of bacteria over time; change in relative concentration of bacteria over time; qualitative amount of bacteria; qualitative concentration of bacteria; actual amount of bacteria; change in relative amount of bacteria over time; or actual concentration of bacteria present in the fluid sample in the fluid analysis chamber over time.

42. A method for moving a fluid sample from a fluid reservoir through a fluid system formed in a fluid apparatus, the fluid system including a fluid analysis chamber and a fluid channel arrangement configured to provide fluid communication between the fluid reservoir and the fluid analysis chamber, the fluid channel arrangement including: A separation chamber configured to remove unwanted particles from the fluid sample before it enters the fluid analysis chamber; A first fluid channel extends radially outward from the fluid reservoir to the separation chamber and communicates with the separation chamber through a wall in the radially outer region of the separation chamber; as well as A second fluid channel is configured for fluid communication between the separation chamber and the fluid analysis chamber. The second fluid channel includes a pair of channel arms configured to allow fluid to flow in an antiparallel direction. and The method includes: The fluid device is rotated about a central axis at a first rotational speed for a first duration by a drive mechanism, thereby generating a first centrifugal force sufficient to drive the fluid sample from the fluid reservoir to a first portion of the fluid channel arrangement. A pressure opposite to the first centrifugal force is applied via a valve mechanism, which prevents the fluid sample from flowing forward from the first part of the fluid channel arrangement into the second part of the fluid channel arrangement through the valve mechanism located in the fluid path between the pair of channel arms of the second fluid channel; as well as The drive mechanism causes the fluid device to rotate around the central axis at a higher second rotational speed for a second duration, thereby generating a second centrifugal force sufficient to overcome the pressure of the valve mechanism and drive the fluid sample into the second part of the fluid channel arrangement and thus into the fluid analysis chamber.

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