EP3596461A1

EP3596461A1 - A monitoring device

Info

Publication number: EP3596461A1
Application number: EP18714350.8A
Authority: EP
Inventors: Mark Thomas O'connell
Original assignee: Probe Scientific Ltd
Current assignee: Cornel Medical Ltd
Priority date: 2017-03-17
Filing date: 2018-03-16
Publication date: 2020-01-22
Also published as: WO2018167508A1; GB201704299D0; GB2560580A

Abstract

The present invention relates to a monitoring device and methods of monitoring utilising such a device. In particular, the present invention relates to a monitoring device to detect and/or measure the amount of an analyte in a biological sample. The monitoring device for detection of and/or measuring the amount of an analyte or plurality of analytes in a fluid comprises a monitoring unit having an electroanalytical component connected to a first electrical contract; and a sensor unit having a sensor arrangement connected to a second electrical contact; wherein the monitoring unit and the sensor unit have a first cooperating attachment arrangements to hold the monitoring unit and the sensor unit together releasably in a first attached configuration, and in the first attached configuration the first and second electrical contacts are brought together in direct electrical communication with one another.

Description

1

Title: A Monitoring device

5

Description of Invention

The present invention relates to a monitoring device and methods of monitoring utilising such a monitoring device. In particular, the present 10 invention relates to a monitoring device to detect and/or measure the amount of an analyte in a biological sample.

Monitoring systems are known that detect substances and amounts of substances in a specific environment. Typically, the monitoring system 15 includes a device having a sensor for detecting an analyte, and a control/monitor unit that receives data from the sensor and presents it to the user.

There are many different types of monitoring systems for measuring different 20 analytes. The nature of the monitoring system depends on the analyte to be detected and the environment within which the system will be used.

Monitoring systems

25 Self-monitoring glucose devices that measure the approximate concentration of glucose in the blood are well known. These devices provide a snapshot of a patient's blood glucose level at the time that the blood sample is obtained. These devices can be used to monitor the need for insulin therapy for a diabetic subject. A drop of blood, obtained by pricking the skin with a lancet,

30 is placed on a disposable test strip; the test strip is inserted into a cavity of the monitoring device having a sensor that reads the test strip to calculate the blood glucose level. The test strip is impregnated with glucose oxidase

SUBSTITUTE SHEET (RULE 26) 2 amongst other components, and blood components flow along the test strip by laminar flow; this is utilised for calculating the blood glucose level. The drawbacks of these devices are that they only measure a snapshot of the blood glucose concentration at a single time point. It is difficult to gain a full 5 overview of the blood glucose level in the subject without taking multiple droplets of the blood from the subject. Moreover, these medical devices require a cavity for the test strip to be inserted into. It is difficult to ensure that the cavity remains contamination free using standard domestic cleaning techniques, such as wiping the product.

10

Advances in glucose monitoring technology include continuous glucose monitoring, which are used to monitor the glucose levels more closely. One type of continuous glucose monitors requires the insertion of a tiny electrode, called a glucose sensor, under the skin to measure glucose levels in tissue

15 fluid. The sensor is connected to a transmitter that sends information to a monitoring device. These devices can monitor the glucose levels over a continuous period of time. One of the drawbacks to these devices is that they do not directly measure the glucose level of the blood. The devices measure the mass transfer of glucose from the blood to the tissue. The mass transfer

20 measures a change in the mass transfer which could reflect a change in the blood glucose levels or it could be the result of a physiological change. Therefore, the accuracy of these devices is limited, and it is generally recommended that calibrations using standard glucose monitoring device are carried out before changing the treatment based on the results. Another

25 drawback of these devices is that they need to meet additional regulatory conditions because the sensor is positioned within the body and the fluid passing over the sensor is returned back into the body.

Other continuous monitoring devices are known that have the sensor 30 positioned outside of the body. However, these are a single unit integrated device having a microfiber connected by tubing to a sensor, the sensor being 3 wired to an electronic unit for processing the data provided by the sensor. The sensor can be connected to a pump via tubing. When the device is connected to a pump, the electronic unit is positioned remotely from the sensor and placed in the same housing as the pump and a battery. The data is then 5 transmitted from the electronic unit to an external control unit. The single integrated unit of the microfiber, sensor and electronic unit must be sterile, because the microfiber is inserted into the body of a subject. This can cause high costs during manufacture and it can be difficult and/or expensive to re- sterilise the device after use. For this reason, such devices are usually 10 disposed of after one use.

Cross -contamination

In a hospital or clinic-like environment there will be considerations when 15 determining the monitoring system to be used. In these environments, where people will have infectious conditions and medical instruments will be used on more than one patient, it is important to ensure that there is a clean environment; this is fundamental to providing safe and high quality care. A particular problem faced in hospitals and other clinic like environments is cross 20 contamination; the process by which bacteria or other microorganisms are unintentionally transferred from one patient or object to another with harmful effects. It is important that any medical instrument/devices can be readily cleaned or disposable depending upon the exact use of the instrument/device.

25 It is important that reusable medical devices can be readily cleaned. This issue can be partially addressed, whilst avoiding excessive time and costs for cleaning equipment, by making the part coming into contact with the patient disposable. For example, it is standard for an ear thermometer used in hospitals and clinic -like environments to have a disposable cover for the tip

30 of the thermometer that is placed in the patient's ear. This means that the cover can be disposed of after use with a single patient. However, it is still 4 important that any part of the instrument that will be used with more than one patient and/or comes into contact with the patient can be readily cleaned to minimise the risks of cross-contamination.

5 Although cross-contamination is less of a risk outside of the hospital and clinic like environment, it is still important that any reusable device can be readily cleaned to avoid contamination. Medical devices are increasingly being used by medical practitioners for patient home-care or by private individuals for their own personal use. It is important that such devices can be readily cleaned to 10 avoid risks of contamination.

If a device has crevices and or cavities that cannot be reached by manual cleaning methods, such as wiping the device, it is likely that bacteria and other micro-organisms will build up in these areas. Although other cleaning

15 methods, such as mechanical and ultrasonic, are known for removing contaminants from joints, crevices, lumens and other areas of a medical device that are difficult to clean by manual methods, these types of cleaning are costly and time consuming. This means that it is not practical to carry out ultrasonic or mechanical cleaning after each use. Therefore, there is a risk of

20 contamination and, in particular, cross-contamination between patients.

It is an object of the present invention to provide a monitoring system that overcomes or mitigates some or all of the above disadvantages.

25 pefinitions

For the avoidance of doubt, the following terms are intended to have the definitions as outlined below: Analyte or plurality of analytes is any component, substance or chemical or biological constituent that is of interest to be detected and/or the amount measured.

5 The casing of the monitoring unit and sensor unit, is constructed from any suitable material, such that the substantial flow of fluid or molecules is prevented through its walls in the environment within which it is intended to be used. The material of the casing must also be rigid enough to ensure the device is not easily damaged during use. Preferably, the casing is constructed 10 from high density polyethylene (HPDE) (HDPE), polyamide, carbon fibre, or similar material.

Cooperating attachment arrangements are well known in the art. They provide a mechanism to retain a close contact between the electrical contacts

15 of the respective units, i.e. the monitoring unit and the sensor unit or the monitoring unit and the battery charging unit. For example the retaining mechanism of a headphone jack and its socket, or a USB plug and its socket could be utilized. Alternatively a single or multiple retaining mechanism can be used to ensure that sensor unit/battery charging unit cannot be taken out of

20 the recess by being inadvertently pulled away or falling away from the bottom surface of the monitoring unit, and the sensor unit battery charging unit cannot be taken out of the recess by being inadvertently pulled away or falling away from the side surface of the monitoring unit.

25 An electrical contact and/or connection is an electrically conductive material, usually metal, which can pass an electrical current when touching another electrical contact. The electrical contact can have one or more connections that touch the electrical connections of a respective electrical contact to form electrical communication.

30 6

Electroanalytical component controls an electrochemical sensor. For example, the electroanalytical component is a potentiostat, coulometer or a voltmeter.

5 Electrochemical sensor is a detector that measures the concentration of a target analyte or plurality of analytes by oxidizing or reducing the target analyte or plurality of analytes at an electrode and measuring the resulting current. The electrochemical sensor has a reference electrode and at least one working electrode. Advantageously, the electrochemical sensor may 10 further comprise one or more auxiliary electrodes. The electrochemical sensor may comprise one, two, three, four, five, six, seven, eight, nine, ten or more working electrodes.

An electrode may be a working electrode, an auxiliary electrode, or a 15 reference electrode. The reference electrode is an electrode which has a stable and well-known electrode potential; and establishes the electrical potential against which other potentials may be measured. The working electrode is the electrode on which the reaction of interest is occurring. The auxiliary electrode, along with the working electrode, provides a circuit over 20 which current is either applied or measured. The potential of the auxiliary electrode is usually not measured and is adjusted so as to balance the reaction occurring at the working electrode. This configuration allows the potential of the working electrode to be measured against a known reference electrode without compromising the stability of that reference electrode by 25 passing current over it. The auxiliary electrode can provide stability to the system.

The at least one exchange aperture is a portion of the casing that exposes the adjacent portion of the fluid passageway. The exchange aperture may be an 30 opening in the external wall of the cavity. Alternatively, the exchange aperture 7 may be a porous area that permits the exchange of selected molecules to/from the fluid passageways from/to the environment external to the device.

Molecular exchange is the selective exchange of any suitable molecule or 5 composition, including but not limited to dialysis, ultra-filtration, drug delivery etc., from the device to the external environment and vice versa.

The monitoring unit has electrical components, such as an electroanalytical component, such as a potentiostat in the form of a PCB, a rechargeable

10 battery, an EEPROM (Electrically Erasable Programmable Read-Only Memory) unit for caching data, a component for transmitting the data wirelessly (e.g. via Bluetooth^®) to an external control unit, such as a personal computer, tablet or smartphone. In embodiments of the invention, these electrical components are sealed in a casing. The electroanalytical

15 component is connected to a first electrical contact for connecting to the second electrical contact of the sensor unit. The rechargeable battery is connected to a third electrical contact for connecting to the fourth electrical contact of the battery charging unit.

20 An optical sensor, the sensor has a light source for emitting illuminating light, such as LEDs or OLEDs, and a light receiving unit, such as a photodiode which feeds back to a voltmeter. In these embodiments the electrical contact provides power for the setting of the voltage, provides power for the light source to emit light, and collects the information from the photodiode. The light

25 source has a gating arrangement to achieve the desired wavelength for the analyte of interest. The gating arrangement zones out wavelengths not required. Alternatively, a laser can be used as the light source. Optical sensors have excellent long term stability. 8

A perfusate is the fluid before it has passed through the molecular exchange areas. In contrast, a dialysate a fluid that has passed through the molecular exchange area and comprises any selected exchange materials.

5 The porous area of a molecular exchange device is porous to the extent that the selective exchange of molecules across the fluid passageway is permitted. A skilled person would appreciate that different sized molecules will require different porosities to permit the selective exchange of the desired molecule, i.e. analyte or plurality of analytes.

10

A recognition substrate has selective recognition for the analyte of interest. In one embodiment, the recognition substrate binds to the analyte of interest directly or indirectly. In an alternative embodiment, the recognition substrate binds to a converted product of the analyte of interest. The recognition 15 substrate may be selected from an enzyme, an antibody, an aptamer, and/or material imprinted polymers (MIPS).

Selective recognition; for sensor systems some degree of analyte selectivity is necessary. Selective recognition or a gating mechanism is usually necessary

20 that allows the analyte of interest to react with the sensor but prevents similar analytes from doing so. Thus a glucose biosensor reacts to glucose rather than another sugar. Typical selective recognition is achieved by using antibodies to bind a specific analyte or recognises a unique molecule, or by using enzymes that demonstrate an induced-fit or lock-and-key mechanism.

25 This is well known in the art.

Sensor arrangement comprises an electrochemical sensor or an optical sensor. These are well known in the art. 9

Molecular exchange is the selective exchange of any suitable molecule or composition, including but not limited to dialysis, ultra-filtration, drug delivery etc., from the device to the external environment and vice versa.

5 The subject is any suitable environment in which the device may be applied.

For example, the subject can be a human or animal body. Alternatively, the subject could be part of an industrial, chemical or fermentation process.

Perfusion unit comprises any arrangement that can provide the fluid to the 10 monitoring device, sensor unit and/or molecular exchange device described herein. The perfusion unit may, for example, be a pump or gravity feed. For example, the pump may actively move the fluid from the fluid source to the other units/devices described. Alternatively, the gravity feed arrangement may move the fluid from the fluid source to the other units/devices by the action of 15 gravity.

Summary of the invention

20 In a first aspect of the invention there is monitoring device for detection of and/or measuring the amount of an analyte or plurality of analytes in a fluid comprising a monitoring unit having an electroanalytical component connected to a first electrical contact; and a sensor unit having a sensor arrangement connected to a second electrical contact; wherein the

25 monitoring unit and the sensor unit have a first cooperating attachment arrangement to hold the monitoring unit and the sensor unit together releasably in a first attached configuration, and in the first attached configuration the first and second electrical contacts are brought together in direct electrical communication with one another.

30

The main advantage provided by the monitoring device of the present 10 invention is that no wires are required to connect the electroanalytical component of the monitoring unit and the sensor arrangement of the sensor unit, thereby providing a more compact monitoring device. The absence of wires also reduces the overall surface area of the device for cross- contamination, and reduces the likelihood that the sensor unit will accidentally be disconnected from the monitoring unit by accidentally pulling on the wires. In a clinical environment, a patient will often be connected to other medical devices, and the absence of wires reduces the chance of the wires of the different medical devices becoming entangled. Moreover, an electrical wire can act as an aerial, which can cause interference between different medical devices. To address this issue, the wires need to be heavily shielded to RF frequency, which is costly and takes up more space. This problem is overcome by the first electrical contact of the monitoring unit and the second electrical contact of the sensor unit being in direct contact with one another in the attached configuration. Moreover, the cooperating attachment arrangements to hold the monitoring unit and the sensor unit together releasably in an attached configuration allow the sensor unit to be readily removed from the monitoring unit, such that the sensor unit can be disposed, for maintenance and/or connection to the fluid source and fluid output.

In an embodiment, the monitoring unit comprises a casing with a recess, and the first electrical contact is position in the recess; and in the first attached configuration at least a part of the sensor unit is housed in the recess and held in position by the cooperating attachment arrangement. In an advantageous embodiment, the casing is sealed.

Advantageously, the width of the casing is from 50 to 100mm, and preferably 60 to 70mm; the depth of the casing is from 30 to 50mm, and preferably 40 to 45mm; and/or the height of the casing is from 4 to 8mm, and preferably 6 to 7mm. In addition to or alternatively, the width of the 11 recess is from 8 to 25mm, and preferably 11 to 20mm; the depth of the recess is from 12 to 20 mm, and preferably 14 to 16mm; and the height of the recess is from 3 to 5mm, and preferably 3 to 4mm.

In a preferred embodiment, the casing of the monitoring unit has a top and a bottom surface and a substantially perpendicular side surface extending from the top surface to the bottom surface; and a recess having a bottom wall and side wall formed in the bottom surface and the side surface of the casing, wherein the first cooperating attachment arrangement prevents the sensor unit being removed from the base wall and side wall of the recess in the attached arrangement.

Advantageously, the walls of the recess do not include any sharp internal angles.

In an embodiment, the base wall is substantially planar and parallel to the bottom surface of the casing, and the side wall takes the form of three sides of a rectangle. The angle between the base wall and each side wall is between 90° and 175°; or the angle between the base wall and the side wall can be between 45° to 85°. Advantageously, the junctions between the base wall and the side wall have a radius.

Advantageously, the first electrical contact has one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more electrical connectors. The second electrical contact has one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more electrical connectors.

In an advantageous embodiment, at least one of the connectors of the first 12 and/or the second electrical contacts are in the form of an electrical contact pad. In an embodiment, at least one electrical pad is a spring contact, a flat plate, a flat plate with one or more spring connectors, or a flat plate with one or more concave connectors. In a preferred embodiment, one of the first and second electrical contact pads is a flat plate and the other is a spring connectors.

In advantageous embodiments, the electroanalytical component is a potentiostat, coulometer or a voltmeter.

Advantageously, the monitoring unit further comprises an Electrically Erasable Programmable Read-Only Memory (EEPROM) unit, and the data provided by the electroanalytical component is cached onto the EEPROM.

In an advantageous embodiment, the monitoring unit further comprises a component configured to wirelessly transmit the data to an external control unit

In an embodiment, the sensor unit comprises at least one flow cell housing a sensor arrangement. The sensor unit may comprise two or more flow cells.

In an advantageous embodiment, the sensor arrangement comprises an electrochemical sensor or an optical sensor.

In an embodiment, the electrochemical sensor has at least two electrodes. The electrochemical sensor has a reference electrode and at least one working electrode. Advantageously, the electrochemical sensor may further comprise one or more auxiliary electrodes. The electrochemical sensor may comprise one, two, three, four, five, six, seven, eight, nine, ten or more working electrodes. 13

In an advantageous embodiment, the sensor arrangement is an optical sensor having a light source and a receiving unit.

In an embodiment, the sensor unit comprises one, two, three, four, five, six, seven, eight, nine or more sensor arrangements.

In advantageous embodiment, the monitoring device further comprises one or more additional sensor units.

In an advantageous embodiment, the sensing arrangement comprises a recognition substrate that has selective recognition of the analyte of interest. In one embodiment, the recognition substrate binds to the analyte of interest directly or indirectly. In an alternative embodiment, the recognition substrate binds to a converted product of the analyte of interest. The sensor arrangement may further comprise an immobilized enzyme reactor (IMER). In advantageous embodiments, the recognition substrate is selected from an enzyme, an antibody, an aptamer, and/or material imprinted polymers (MIPS).

In alternative embodiments, the sensing arrangement does not have a recognition substrate. In these embodiments, the electroactive surface of the electrode is oxidized leading to a change in the current. The sensor can be selective for a certain analyte or analytes, such as sugars, by applying a certain voltage.

In embodiments of the invention, the fluid source for the sensor unit is a molecular exchange device or a receptacle.

In an advantageous embodiment, the first cooperating attachment arrangement is in the form of a base plate releasably held against the 14 bottom surface of the monitoring unit that holds the sensor unit in the first attached configuration in the recess. The base plate may have a clip mechanism that connects to a clip mechanism on the sensor unit.

5 In an alternative embodiment, the first cooperating attachment arrangement is integral with the monitoring unit, and optionally comprises a protrusion that fits into a recess on the sensor unit.

In an embodiment, the monitoring unit has a rechargeable battery that 10 powers the monitoring device. Advantageously, the monitoring unit further compromises a component for inductive charging of the rechargeable battery. Alternatively, the device further comprises a battery charging unit for charging the rechargeable battery. The battery charging unit may be configured to be housed in the recess of the monitoring unit, when the 15 sensor unit is not in the first attached configuration.

Advantageously, the monitoring device has a third electrical contact positioned in the recess and the battery charging unit has a forth electrical contact, wherein the monitoring unit and the battery charging unit have a 20 second cooperating attachment arrangements to hold the monitoring unit and the battery charging unit together releasably in a second attached configuration, and in the second attached configuration the third and fourth electrical contacts are brought together in direct electrical communication with one another.

25

In an embodiment, the first and third electrical contacts of the monitoring unit are on the same pad. In some embodiments, the first and third electrical contacts are the same type of electrical connector as one another.

30 Advantageously, the first and second cooperating attachment arrangements are the same. 15

In an embodiment, the monitoring unit further comprises an operating button to turn on and off the monitoring device; and/or stop and start the electrochemical sensor. The button may be positioned beneath an elastic membrane bonded to the sealed casing of the monitoring unit. Advantageously, the button is positioned on the bottom surface of the monitoring unit. In addition to or alternatively, the monitoring unit comprises a component for receiving a wireless signal to turn on and off the monitoring device; and/or stop and start the electrochemical sensor.

In an advantageous embodiment, the monitoring unit further comprises a visible and/or audible signal to indicate the functioning of the device. The function of the device may be selected from: that the monitoring unit and/or sensor unit is/are on or off; that the device is taking measurements; that the device is transferring data; that the device is transferring a certain level of data; that the device is transferring a data dump; and/or that the rechargeable battery needs charged or is fully charged. Advantageously, the visible signals for different functions are distinguished by the number signals, different colour signals, and/or flashing signals. In an preferred embodiment, the visible signal is one or more LEDs.

The invention also provides a sensor unit as described above.

The invention also provides a monitoring unit as described above.

The invention also provides a battery charging unit as described above.

The invention also provides a system comprising at least one monitoring device described above; and an external control unit, a fluid source, a battery charging unit, and/or a perfusion unit. Advantageously, the fluid source is a molecular exchange device. Advantageously, the perfusion unit 16 comprises a pump or gravity feed arrangement.

The invention also provides a monitoring system comprising a receptacle for containing a fluid and adapted to allow the fluid to flow from the receptacle by the action of gravity; a molecular exchange area; a supply conduit defining a fluid path from the receptacle to a molecular exchange area; and an outlet conduit defining a fluid path from the molecular exchange area to an outlet port, and at least one monitoring device described above; wherein, in use, the receptacle is positioned above the supply conduit, molecular exchange area, outlet conduit, and monitoring device such that the fluid is transported from the receptacle to the outlet port by the action of gravity. The system can provide a continuous flow of fluid through the molecular exchange area.

In advantageous embodiments, the volume of the receptacle may be 0.0005 to 10 litres, 0.0005 to 0.75 litres, 0.25 to 8 litres, or 0.5 to 4 litres. In some embodiments, the volume of the receptacle may will be 0.005, 0.1 , 0.02, 0.05, 0.1 , 0.2, 0.25, 0.5. 0.75, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10 litres.

In preferred embodiments, the receptacle is positioned at least 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50 60, 70, 80, 90 centimetres, 1 , 2, 3, 4, 5, or more meters above the molecular exchange area.

Advantageously the systems further comprise one or more attachments to hold one or more of the receptacle(s), supply conduit, molecular exchange area, outlet conduit and/or the sensor unit in position. In a preferred embodiment the attachment is a stand, pole, and/or wall mountable arrangement. Advantageously, the attachment is extendable and/or retractable to move the position of the receptacle, supply conduit, molecular exchange area, outlet conduit and/or the sensor unit. in some embodiments, the systems further comprise one or more means to control the flow rate. The means may be selected from: a constriction element; moving the height of the receptacle with respect to the molecular exchange area; altering the size of the supply conduit, altering the internal cross-sectional area of the supply conduit. In some arrangements, the means are an adaptor that changes the size of the internal cross-sectional area of the supply conduit.

In an advantageous embodiment, the flow rate is 0.01 to 150pi/min and preferably 30 to 150μΙ/ιπίη. The flow rate may be 0,01 , 0.02, 0.03, 0.04, 0.05, 0,06, 0.07, 0.08, 0.09, 0.1 , 0.15, 0.2. 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0,7, 0.75, 0.8, 0.85, 0.9, 0.95, 1 , 1 .5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9,5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 1 10, 1 15, 120, 125, 130, 135, 140, 145 150pl/min in a preferred embodiment, the supply conduit and/or the outlet conduit is in the form of tubing. The tube can have a uniform cross-section and/or uniform wall thickness. The tube may have a a circular cross-section; and optionally have an internal diameter of 0.01 to 0.5 mm, or 0.01 , 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1 , 0.15, 0.2, 0.25, 0.3, 0,35, 0.4, 0.45, 0.5 mm; and /or an external diameter of 0.02 to 7mm, or 0.01 , 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1 , 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1 , 1 .5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7 mm.

In an advantageous embodiment, the molecular exchange area of the system is a fluid conduit having porous area. Advantageously, the molecular exchange area comprises at least one fluid passageway supported by a casing, and comprising at least one exchange aperture wherein a portion of at least one of the fluid passageways exposed by the exchange aperture is porous. In some aspects, there are two or more fluid passageways. In some embodiments of the invention, the two or more fluid passageways each run from the inlet to the outlet of the molecular exchange area. One or more of the fluid passageways has an exchange aperture. In addition to or alternatively, one exchange aperture expose two or more fluid passageways and allows molecular exchange to occur from/to each of the fluid passageways. In an alternative embodiment, the molecular exchange area is a molecular exchange device.

Advantageously, the systems further comprise a second receptacle, The second receptacle can be attached to the outlet port, A monitoring device of the invention may be positioned between the first receptacle and the molecular exchange area and/or a second monitoring deivce may be positioned between the molecular exchange area and the second receptacle. In an advantageous embodiment, the receptacle comprises two compartments that are fiuidiy sealed from one another; each receptacle compartment contains a fluid and provides the fluid to the molecular exchange area of the system by the action of gravity. The compartments may be integral with one another or separate to one another. The first compartment contains a perfusion fluid and the second receptacle compartment contains oil.

The invention further provides a method of monitoring for the presence of a molecule, the method comprising providing a receptacle containing a fluid and adapted to allow the fluid to flow from the receptacle; providing a molecular exchange area; and providing a supply conduit defining a fluid path from the container to a molecular exchange area; and an outlet conduit connected to a monitoring device; wherein the receptacle is positioned above the supply conduit, molecular exchange area, outlet conduit, and monitoring device such that the fluid is transported from the receptacle to the monitoring device by the action of gravity; and molecular exchange occurs across the molecular exchange area such that the presence of a molecule can be detected by the monitoring device. The method can use the monitoring devices described herein.

The invention further provides a method of delivering a molecule, the method comprising providing a receptacle containing a fluid and adapted to allow the fluid to flow from the receptacle; providing a molecular exchange area; providing a supply conduit defining a fluid path from the container to a molecular exchange area; and providing an outlet conduit defining a fluid path from the molecular exchange area to an outlet port; wherein the receptacle is positioned above the supply conduit and molecular exchange area such that the fluid is transported from the receptacle to the molecular exchange area by the action of gravity; and molecular exchange occurs across the molecular exchange area to deliver a molecule. The method can use the monitoring device described herein.

Figures in order that the present invention may be more readily understood, non- limiting examples thereof will now be described, by way of example, with reference to the accompanying drawings.

Figure 1 is a first embodiment of a monitoring device in accordance with the present invention, when the sensor unit and monitoring unit are in the first attached configuration; Figure 2a is an alternative view of part of the monitoring unit of the first embodiment of the monitoring device in accordance with the present invention, when the sensor unit and monitoring unit are detached from one another:

Figure 2b is an alternative view of the sensor unit of the first embodiment of the monitoring device in accordance with the present invention, when the sensor unit and the monitoring unit are detached from one another;

Figure 2c is an alternative view of part of the monitoring unit of the first embodiment of the monitoring device in accordance with the present invention, when the sensor unit and the monitoring are detached from one another;

Figure 3 is an alternative view of the first embodiment of the monitoring device in accordance with the present invention, when the sensor unit and the monitoring unit are detached from one another yet showing the two parts of the monitoring unit in an attached arrangement;

Figure 4 is alternative view of the first embodiment of the monitoring device in accordance with the present invention, when the sensor unit and monitoring unit are in the attached arrangement;

Figure 5 is alternative embodiment of the monitoring device in accordance with the present invention, when the battery charging unit and the monitoring unit are in the attached arrangement;

Figure 8 is alternative embodiment of a battery charging unit in accordance with the present invention; Figure 7 is alternative view of the battery charging unit in accordance with the present invention;

Figures 8a, 8b and 8c provide alternative embodiments of the monitoring unit in accordance with the present invention;

Figures 9a, 9c, 9e and 9g are alternative embodiments of a battery charging unit in accordance with the invention;

Figures 9b, 9d, 9f and 9h are alternative embodiments of a sensor unit in accordance with the invention;

Figure 10 is an alternative embodiment of a monitoring device in accordance with the present invention;

Figure 1 1 is an alternative embodiment of a monitoring device in accordance with the present invention;

Figure 12 is an alternative embodiment of a system in accordance with the present invention;

Figure 13 is an aiternative embodiment of a system in accordance with the present invention;

Figure 14 is an alternative embodiment of a sensor unit in accordance with the present invention;

Figure 15 is an embodiment of a system in accordance with the invention; the system comprising a monitoring device in accordance with the invention, a molecular exchange device and a perfusion unit connected to one another by fluidic tubing; Figure 17 is an overall illustration of a first embodiment of a monitoring system in accordance with the present invention;

Figure 18 is an overall illustration of a second embodiment of a monitoring system in accordance with the present invention, where the molecular exchange area is a molecular exchange device;

Figure 19 is an overall illustration of a first embodiment of a delivery system in accordance with the present invention;

Figure 20 is an illustration of a cut off view of a molecular exchange area in the form of a medical device:

Figure 21 is an illustration of a cut off view of a molecular exchange area;

Figure 6a and 6b are illustrations of a third embodiment of a monitoring system in accordance with the invention. in a first aspect of the invention there is a monitoring device for detection of and/or measuring the amount of an ana!yte or plurality of anaiytes comprising: a monitoring unit having an electroanalytica! component connected to a first electrical contact; and a sensor unit having a sensor arrangement connected to a second electrical contact; wherein the monitoring unit and the sensor unit have cooperating attachment arrangements to hoid the monitoring unit and the sensor unit together re!easably in an attached configuration, and in the attached configuration the first and second electrical contacts are brought together in direct electrical communication with one another, The main advantage provided by the monitoring device of the present invention is that no wires are required to connect the eiectroanalytical component of the monitoring unit and the sensor arrangement of the sensor unit, thereby providing a more compact monitoring device. The absence of wires also reduces the overall surface area of the device for cross- contamination, and reduces the likelihood that the sensor unit will accidentally be disconnected from the monitoring unit by accidentally pulling on the wires. In a clinical environment, a patient will often be connected to other medical devices, and the absence of wires reduces the chance of the wires of the different medical devices becoming entangled. Moreover, an electrical wire can act as an aerial, which can cause interference between different medical devices. To address this issue, the wires need to be heavily shielded to RF frequency, which is costly and takes up more space. This problem is overcome by the first electrical contact of the monitoring unit and the second electrical contact of the sensor unit being in direct contact with one another in the attached configuration. Moreover, the cooperating attachment arrangements to hold the monitoring unit and the sensor unit together reieasably in an attached configuration allow the sensor unit to be readily removed from the monitoring unit, such that the sensor unit can be disposed, for maintenance and/or connection to the fluid source and fluid output,

The monitoring device, during use, is connected to at least one fluid source and an analyte or plurality of analytes can be detected and/or the amount of the analyte or plurality of analytes can be measured in the fluid. The fluid is introduced into the sensor unit of the monitoring the device. . The fluid to be analyzed travels from the fluid source into the sensor unit via fiuidic tubing. The fluid passes over the sensor arrangement and travels out of the sensor unit. The sensor arrangement detects the presence and/or quantity of an analyte in the fluid sample introduced into the sensor unit. The sensor unst transmits the data to the eiectroana!ytica! component of the monitoring unit via their respective electncal contact: and the data is transmitted to a visual display on the monitoring unit and/or transmitted wirelessly from the electroanalytical component to an external control unit.

Advantageously, the monitoring device can continuously detect or measure the amount of an anaiyte or a plurality of analytes. in such an arrangement, the sensor unit may be connected to a molecular exchange device positioned in a subject or container. The monitoring device can detect or measure the amount of analytes that are present in the subject or the patient over a period of time.

In a preferred embodiment, the monitoring unit has a casing that fully encapsulates the electronic components of the monitoring unit to ensure that no fluids can ingress the unit, which mitigates cross-contamination. In a preferred embodiment, the casing provides a sealed unit. In such an arrangement, the unit cannot be opened without breaking the seal and damaging the unit. The casing has a recess, and the first electrical contact of the monitoring unit is positioned in the recess.

In the attached configuration, at least a part of the sensor unit is housed in a recess in the casing of the monitoring unit, such that the first electrical contact of the monitoring unit make direct contact with the second electrical contact of the sensor unit, thereby providing electrical communication between the monitoring unit and the sensor unit. The main advantage provided by this arrangement is that the electrical connection between the sensor unit and monitoring unit by way of their respective first and second electrical contacts allows the sensor unit to be easily removed from the monitoring device. This arrangement also means that a sensor unit, or a replacement sensor unit, can be readily inserted into the recess of the monitoring device. This allows the sensor unit to be a disposable unit, or removed from the monitoring unit for maintenance and/or connection to the fluid source and fluid output. The sensor unit may be used once or multiple times; or a different sensor unit may be used for a different subject or environment.

The sensor unit is held in place in the recess of the monitoring unit by the cooperating attachment arrangement. Cooperating attachment arrangements are well known in the art. They provide a mechanism to retain a close contact between the electrical contacts of the respective units. For example the retaining mechanism of a headphone jack and its socket, or a USB plug and its socket could be utilized.

The first electrical contact of the monitoring unit and/or the second electrical contact of the sensor unit have one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more electrical connectors.

The electrical connectors of the first and second electrical contact are well known in the art, such as electrical connectors having male and female parts that connect to one another to establish electrical connection. Also known in the art are electrical contacts in the form of a pad, such as a pad comprising a fiat plate and/or a pad having a spring connectors. In some embodiments of the invention, the first electrical contact is in the form of a pad comprising a single flat plate with one or more spring connectors for electrical connection with the second electrical contact in the form of a pad ; or vice versa. In such an arrangement, the respective first and second electrical contacts of the monitoring unit or sensor unit can be in the form of a fiat plate, or a slightly concave connector on a substantially planar plate to ensure a good electrical connection with the spring connector on the respective pad of the respective electrical contact when the sensor unit and monitoring unit are in the attached configuration. In arrangement with multiple electric connectors for each of the respective first and second electrical contacts, each connectors can have a separate channel providing connection to the respective sensor arrangement or the eiectroanaiytical component, A channel connects the second electrical contact of the sensor unit to an electrode of the sensor arrangement, and/or a channel connects the first electrical contact of the monitoring unit to the eiectroanaiytical component (e.g. cou!ometer, potentiostat or voltmeter). in an aspect of the invention, there is a monitoring device comprising a monitoring unit having a top and a bottom surface and a substantially perpendicular side surface extending from the top surface to the bottom surface; wherein the monitoring unit has a recess found in the bottom surface and the side surface so that a sensor unit can be received in the recess; and a retaining arrangement that prevents the sensor unit being removed from the recess by being lifted directly away from the bottom surface of the recess and prevents the sensor being withdraw from the side surface of the recess; wherein the recess has a base wall and side walls that do not include any sharp internal angles, so that all parts of the recess can be accessed and cleaned when the sensor unit is not positioned within the recess,

The main advantage provided by the monitoring device in accordance with the present invention is that the arrangement of the recess being open on the bottom and the side surface, in combination with the recess having no internal angles, allows the device to be readily cleaned by manual cleaning such as wiping. This reduces the risk of contamination/cross-contamination and the costs associated with cleaning the device,

Monitoring unit

The monitoring unit has an eiectroanaiytical component, such as a potentiostat or coulometer, which determines the presence and/or amount of an analyte by measuring the potential and/or current in a sensor arrangement of the sensor unit containing the analyte, In a preferred embodiment, the electroanalyticai component is a potentiostat,

A potentiostat is a device that controls the potential between two or more electrodes while measuring the resulting current flow. In the present invention, the electrodes form part of the sensor arrangement of the sensor unit,

In an embodiment of the present invention, the analyte binds to a recognition substrate on the electrochemical sensor arrangement, which results in a change in the current. The potentiostat records the change in current, which can be used to determine the presence of an analyte in the fluid sample passing though the sensor unit, The magnitude of the change in current can be used to determine the amount of the analyte present in the fluid sample passing through the sensor unit, Alternatively, a coulometer could be utilised, Coulometers determine the presence and/or amount of an analyte by measuring the electric charge (in coulombs) passing through an electrochemical sensor arrangement, The amount of the analyte present can be determined based on the amount of a substance that accumulates on the electrodes. Again, in the present invention the electrodes from which this measurement is taken form part of the sensor arrangement of the sensor unit, In a preferred embodiment, the electroanalyticai component of the monitoring unit is a potentiostat in the form of a PCB having electrical contact pads for connection with contact pads on the sensor unit. Data is cached onto EEPROM (Electrically Erasable Programmable Read-Only Memory) unit. The data can be transmitted to an external control unit, such as a personal computer, tablet or smartphone, The data is transmitted wireiessly to the control unit, such as via Bluetooth^®. The external control unit allows data to be stored and analysed effectively, rapidly, and accurately. The monitoring unit is powered by a rechargeable battery.

In an arrangement of the monitoring device having an optical sensor, the electroanalytical component is a voltmeter in the form of a PCB having electrical contact pads for connection with contact pads of the sensor unit. Data is cached onto EEPROM (Electrically Erasable Programmable Readonly Memory) unit. The data can be transmitted to an external control unit, such as a personal computer, tablet or smartphone. The data is transmitted wirelessly to the control unit, such as via Bluetooth^®. The external control unit allows data to be stored and analysed effectively, rapidly, and accurately, The monitoring unit is powered by a rechargeable battery.

In a preferred embodiment of the invention, the monitoring unit can have a top and a bottom surface and a substantially perpendicular side surface extending from the top surface to the bottom surface; wherein the monitoring unit has a recess found in the bottom surface and the side surface so that a sensor unit can be received in the recess; and a retaining arrangement that prevents the sensor unit being unintentionally removed from the recess by being lifted directly away from the bottom surface of the recess and prevents the sensor being withdraw from the side surface of the recess; wherein the recess has a base wall and side walls that do not include any sharp internal angles so that all parts of the recess can be accessed and cleaned when the sensor unit is not positioned within the recess.

The arrangement of the recess being open on the bottom and the side surface, in combination with the recess having no internal angles, allows the device to be readily cleaned by manual cleaning such as wiping. This reduces the risk of contamination/cross-contamination and the costs associated with cleaning the device. The recess is provided in the bottom and side surface of the two part moulding. The recess houses the electric contact pad of the monitoring unit, which provides the electrical connection to the electric contact pad of the sensor unit. The first and second electrical contacts of the two units are in direct contact with one another. In a preferred embodiment the electrical contact of the monitoring unit has one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more electric connectors connected to the electroanalytica! component.

The first electrical contacts of the monitoring unit are well known in the art, such as electrical connectors having male and female parts that connect to one another to establish eiectricai connection. Also known in the art are electric contacts in the form of a flat plate and/or a spring connector. In some embodiment, a single fiat plate has one or more spring connectors for electrical connection with a respective electrical connector of the sensor unit or monitoring unit. In an arrangement with multiple electric connectors, each electrical connectors of the sensor unit can have a separate channel providing connection between each of the electrodes to an individual connector.

In an advantageous embodiment, the monitoring unit is formed of a two part moulding having a top surface, a bottom surface and a side surface extending between top and the bottom surfaces. The electronic components of the monitoring unit are fully encapsulated in the two part moulding to ensure that no fluid can ingress the unit, which mitigates cross-contamination. In a preferred embodiment, the casing provides a sealed unit. In such an arrangement, the unit cannot be opened without breaking the seal and damaging the unit.

In preferred embodiments, the width of the casing is from 50 to 100mm, and preferably 80 to 70mm; the depth of the casing is from 30 to 50mm, and preferably 40 to 45mm; and the height of the casing is from 4 to 8mm, and preferably 6 to 7mm. In preferred embodiments, the width of the recess is from 8 to 25rnm, and preferably 1 1 to 20mm; the depth of the recess is from 12 to 20 mm, and preferably 14 to 16mm; and the height of the recess is from 3 to 5mm, and preferably 3 to 4mm.

The battery can be recharged using a standard external battery charger, such as a USB or microUSB connector. However, such connectors provide a cavity in the monitoring unit that cannot be readily cleaned. Therefore, alternative charging means are preferred, such as inductive charging or electrical contacts, connectable to a mains electrical charging unit, on the external surface of the monitoring unit. These arrangements allow the external surfaces of the monitoring device to be cavity and crevice free. in a preferred embodiment, the electrical contacts of the monitoring unit for connection to the battery charging unit are positioned in the recess. This arrangement means that the sensor unit cannot be held in the attached configuration with the monitoring unit when the battery is charging. This is advantageous when the sensor unit is connected to a molecular exchange device that is position in a human or animal subject. Hence, the battery cannot be charged when the monitoring system is being used, i.e. when the system is connected to a molecular exchange device positioned in a subject. This mitigates the small risk that a current could be passed down the perfusate fluid (a salt solution) that passes from the sensor unit to the molecular exchange device along microf!uidic tubing, and into the subject.

The charging electrical contact of the battery can be one or more electrical connectors that form an electrical connection with respective one or more electric connectors of the electrical contact of the battery charging unit. The one or more electrical connectors of the monitoring unit for providing the electrical connection to the battery charging unit can be the same type of electrical connectors as the electrical connectors that provide electrical connection to the sensor unit. Alternatively, different types of electrical connectors can be utilised for each of these purposes. The monitoring device may have a series of electrical connectors for electrical connection with the electrical connectors of the battery charging unit, and a further series of electrical connectors for electrical connection with the electrical connectors of the sensor unit.

In the embodiment in which the electrical contact of the monitoring unit for electrical connection to the battery charging unit are positioned in the recess, it is advantageous for the (first) electrical contact of the monitoring unit for electrical connection with the sensor unit to be positioned in the recess such that the (third) electrical contact of the battery charging unit will not pass over them when being position in the recess for charging the battery. This will mitigate the risk of the electrical contact of the battery charging unit providing a current to these electrical contact and causing damage.

In a preferred embodiment, the monitoring unit (third) electrical contact for the battery charging unit are positioned cioser to the outer edge of the recess that the monitoring unit (first) electrical contact for the sensor unit. This arrangement means that the electrical contact of the battery charging unit will not need to pass over the monitoring unit (first) electrical contact when being placed into position in the recess for charging.

In an alternative arrangement, the monitoring unit (first) electrical contact for the battery charging unit are positioned on one side of the recess and the monitoring unit (third) electrical contact for the sensor unit are positioned on the other side of the recess; such that the electrical contact of the battery charging unit will not need to pass over the monitoring unit (first) electrical contact when being placed into position in the recess for charging. In such arrangements, the battery charging unit can have a different configuration to the sensor unit. However, it is envisaged that the battery charging unit and the sensor unit will have similar shapes and configurations to ensure allow them to form similar cooperating attachment arrangements with the monitoring unit.

The battery charging unit can be fixed to a standard wail plug for charging. Alternatively, the battery charging unit can have a standard connection, such as a micro USB or USB socket for connection to a standard medical grade charger.

In an advantageous embodiment, the monitoring unit has an operating button to turn the unit on/off and/or control the stop/start of the electrochemical sensor. This arrangement provides an independent capability to test whether the monitoring unit is on/off. In a preferred embodiment, the button is position beneath an elastic membrane bonded to the casing of the monitoring unit, so that the button can be pressed without breaking the sea! of the casing, i.e. prevent an access point for fluid to enter the unit and reduce the risk of cross- contamination. In a preferred embodiment, the operating button is position on the bottom surface of the monitoring unit to prevent unintended use.

In an alternative embodiment the monitoring unit is turned on/off and/or the electrochemical sensor is turned on/off remotely by a control unit that is wirelessly connected to the monitoring device.

In an advantageous embodiment, the monitoring unit has a visible signal, such as one or more LEDs, and/or an audible signal that can indicate various aspects of the functioning of the device. The various aspects can be an indication that the monitoring unit and/or sensor unit is on or off, that the device is taking measurements that the device is transferring data, that the device is transferring a data dump and/or that battery needs charged or is fully charged, The indication may distinguish between different levels of data transfer, i.e. the data is being transferred at different time internals and/or amounts. For example, the indictor may indicate that the data is being transferred every two seconds or that five data points are being transferred every ten seconds. The visible signal for each indicator may be one or more of a different coloured LEDs and/or flashing LEDs, wherein the flashing LEDs have different flashing sequences. The top surface of the monitoring unit may be a simple plastic surface, or it can be a display illustrating the results of the analysis.

The recess provides a seat for the sensor unit to be positioned during use of the monitoring system. The recess may be formed in both the bottom and the side surfaces of the casing of the monitoring unit. This arrangement provides that there is no cavity into which the sensor unit needs to be inserted. This means that the external parts of the monitoring unit can be formed without crevices and/or cavities, so the external services can be effectively wipes clean which helps to mitigate the risk of cross-contamination,

The recess, positioned in the bottom and side surfaces of the monitoring unit, has a base wall and at least one side wail that define the shape of the recess. In a preferred embodiment, the base wall is substantially parallel with the bottom surface of the recess and there are three side walls taking the form of three sides of a rectangle. In a preferred embodiment, the angle between the base wail and each side wall is between 90° and 175°, This arrangement provides a recess that can easily be wiped clean after use. Alternatively, the angle between the base wall and the side wail can be between 45° to 85°. This arrangement can be advantageous when the side walls form part of the retaining unit to maintain the sensor in position against the base wall of the recess.

Advantageously, the junctions between the base wall and the at least one side wall and/or the junctions between each of the side walls have a radius, to avoid any sharp internal angles that are difficult to access when the monitoring unit is wiped clean.

!n an embodiment, the base wall is substantially planar. Preferably the side walls are also substantially planar. Alternatively, the one or more side walls have a cross section that is curved, such as semi-circular or semi-oval shaped, straight, or shaped where two or more straight lines connect. Advantageously, the junctions between the two or more straight lines have a radius to avoid any sharp internal angles that are difficult to access when the monitoring unit is wiped clean.

The recess houses at least two electric contacts which provide the electrical connection to the sensor unit and the battery charging unit. Advantageously, each of the electrical contacts is in the form of a pad against which a deformabie electrical contact in the sensor unit can be aligned during use. When the sensor unit is held in the recess of the monitoring unit, the deformabie electrical contact is biased against the electrical contact housed by the recess to maintain a good electrical contact, in some embodiments, the pad has a flat surface, whilst in other arrangement the pad has a slightly raised curved surface. In these embodiments, the pad can be easily wiped clean to mitigate cross-contamination.

Alternatively, the electrical contacts of the recess can be deformabie and biased such that, when the sensor unit is held in the recess of the monitoring unit, the contact is held against an electrical contact of the sensor unit and/or electrical contact of the battery charging unit. Cooperating attachment arrangement

The cooperating attachment arrangement is required to ensure that the sensor unit can be held in p!ace during use. it is important that the first and second electrical contacts of the respective monitoring unit and sensor unit are held against one another to ensure a good electrical communication. This requires that the sensor unit cannot be taken out of the recess by being inadvertently pulled away or falling away from the bottom surface of the monitoring unit, and the sensor unit cannot be taken out of the recess by being inadvertently pulled away or falling away from the side surface of the monitoring unit. This can be achieved by the cooperating attachment arrangement in the form of a single retaining mechanism or multiple retaining mechanisms for one or both of the units. A cooperating attachment arrangement is also required to ensure that the battery charging unit can be held in place during recharging of the battery, it is important that the third and fourth electrical contacts of the respective monitoring unit and battery charging unit are held against one another to ensure a good electrical communication. This requires that the battery charging unit cannot be taken out of the recess by being inadvertently pulled away or falling away from the bottom surface of the monitoring unit, and the battery charging unit cannot be taken out of the recess by being inadvertently pulled away or falling away from the side surface of the monitoring unit. This can be achieved by the cooperating attachment arrangement in the form of a single retaining mechanism or multiple retaining mechanisms for one or both of the units. The single or multiple retaining mechanisms for holding the batter/ charging unit in place can be the same as or different to the single or multiple retaining mechanisms for holding the sensor unit in place. In one embodiment, the retaining mechanism is a single retaining unit in the form of a base plate. The base plate is an additional component to the monitoring unit that can be re!easabiy held against the bottom surface of the monitoring unit to retain the sensor unit in position, i.e. the sensor unit cannot be inadvertently pu!i or fail away from the bottom surface of the monitoring unit in the attached configuration. The base plate may also have a retainer clip mechanism that connects to a c!ip mechanism on the sensor unit to hold the sensor unit in place during use, such that it cannot be inadvertently pulled away or fail away from the side surface of the monitoring device. This arrangement is advantageous because the retaining mechanism does not form an integral part of the monitoring device. This is beneficial to ensure that the monitoring unit can be easily cleaned to reduce the risk of cross- contamination. The sensor unit and/or the base plate may be disposable single use units to help mitigate the risks of cross-contamination.

The same base plate may be used to retain the battery charging unit in place. The base plate being releasably held against the bottom surface of the monitoring unit ensures that the battery charging unit is held in place in the recess, i.e. the battery charging unit cannot inadvertently pull or fall away from the bottom surface of the monitoring unit in the attached configuration. In this arrangement, the battery charging unit has a clip mechanism that connects to a retainer clip mechanism of the base plate. In a preferred embodiment the clip mechanism of the base plate is the same clip mechanism as the clip mechanism that connects to the sensor unit, i.e. the clip mechanism of the base place can hold the sensor unit in position or the battery charging unit in position. The clip mechanism arrangement ensures holds the battery charging unit in place during charging of the battery, such that it cannot be inadvertently pulled away or fail away from the side surface of the monitoring device. The battery charging unit may be a disposable single use unit to help mitigate the risks of cross-contamination.

In a preferred embodiment, the base plate is in the form of a substantially fiat plate with reieasable clips that hold the monitoring unit in place when the base piate is placed on top, The base plate can be connected to a strap that enables the base piate to be placed on the wrist of a subject and held in place by the strap; in a watch-like arrangement. The strap can be secured by simply tying the ends of the strap together, or the strap can have a fastening mechanism, which holds the ends of the strap together. The fastening mechanism may be an attach and release fastening mechanism that are well known in the art. For example, the mechanism may be a hook and loop fastener, such as Velcro, or a side release buckle (with male and female portions that connect to one another). This embodiment is advantageous because the monitoring device can be comfortable held on the patient during use. Moreover, the base plate, rather than the monitoring unit, comes into contact with the subject which mitigates cross-contamination when the monitoring unit is re~used with different subject. The base plate can be for single person use to avoid cross-contamination,

In a preferred embodiment, the base plate has a spring clip that retains the sensor unit in position and presses the sensor unit against the monitoring unit to ensure a good electrical communication between the respective first and second electrical contacts of the two units.

In an alternative embodiment, the retainer is in the form of two retaining units; one retaining unit is in the form of a base piate as descried above without the clip mechanism and the other retaining unit is in the form of a clip. The clip is integral to the monitoring unit and holds the sensor unit in position such that it cannot be inadvertently pulled away from the side surface of the monitoring unit during use. For example, the clip may be a protrusion that fits into a recess on the sensor unit. In such an arrangement, the sensor unit can be released by applying a force. In another arrangement, the base plate is in the form of a strap having a pocket. The monitoring unit with the sensor unit position in the recess can be placed in the pocket. The pocket is shaped and sized to ensure that the sensor unit is held against the monitoring unit, such that the respective electrical contacts of the two units are placed in direct contact with one another. The strap can be formed of a band of material. The strap can be placed around a limb, including the ankle or wrist, or the waist of the subject to secure the monitoring device on the patient. In such an arrangement, the strap can be in the form of a wristband or armband.

The strap can be secured by simply tying the ends of the strap together, or the strap can have a fastening mechanism, which holds the ends of the strap together. The fastening mechanism may be an attach and release fastening mechanism that are well known in the art. For example, the mechanism may be a hook and loop fastener, such as Velcro, or a side release buckle (with male and female portions that connect to one another).

The pocket has an open end for the device to be inserted, in some arrangements, the open end has a fastener or cover flap to close the open end and retain the device inside the pocket. In an alternative arrangement, the fabric of the strap and/or pocket is elastic to ensure that the device is retained in the pocket, in a preferred embodiment, the pocket has a transparent wall to allow the monitoring device to be visible within the pocket.

Moreover, the strap, rather than the monitoring unit, comes into contact with the subject which mitigates the use of cross-contamination when the monitoring unit is re-used with different subject. The strap can be for single person use to avoid cross-contamination. in an alternative arrangement, the cooperating attachment arrangement is integral with the monitoring unit and/or the sensor unit. For example, the side walls of the recess may be at an acute angle with respect to the base wall of the recess. This arrangement would act to hold the sensor unit in place so thai it cannot be inadvertently pulled away from the bottom surface of the monitoring unit. In a preferred embodiment, a dip in the base surface of the recess can be used to prevent the sensor unit being inadvertently pulled out of the recess. For example, the clip may be a protrusion that fits into a recess on the sensor unit. In such an arrangement, the sensor unit can be released by applying a force. This arrangement avoids the cost of manufacturing and/or cleaning a separate cooperating attachment arrangement unit,

Sensor unit

The invention provides a sensor unit having a sensor arrangement and an electrical contact for electrical communication with respective electrical contact of a monitoring unit. In an embodiment, the sensor unit comprises a flow cell having a sensor arrangement. In preferred embodiments, the sensor arrangement includes an electrochemical sensor or an optical sensor.

In one embodiment, the electrochemical sensor has a base material, such as a ceramic chip or a plastic polymer substrate, having at least two electrodes; a reference electrode and at least one working electrode. The sensor may also have one or more auxiliary electrodes.

The sensor may have two, three, four, five, six, seven, eight, nine, ten or more electrodes. For example, there may be a reference electrode, a working electrode, and optionally an auxiliary electrode. In a preferred embodiment, a working eiectrode may be used in conjunction with an auxiliary electrode, and a reference eiectrode in a three electrode system.

The reference electrode is an electrode which has a stable and well-known electrode potential; and establishes the electrical potential against which other potentials may be measured. The working eiectrode is the electrode on which the reaction of interest is occurring. The auxiliary electrode, along with the working electrode, provides a circuit over which current is either applied or measured. The potential of the auxiliary electrode is usually not measured and is adjusted so as to balance the reaction occurring at the working electrode. This configuration allows the potential of the working electrode to he measured against a known reference electrode without compromising the stability of that reference electrode by passing current over it. The auxiliary electrode can provide stability to the system.

There may be one, two, three, four, five, six, seven, eight, nine, fen or more working electrodes. The working electrode may comprise a gold, platinum, glassy carbon, or diamond doped carbon surface. A recognition substrate can be attached to the working electrode, either directly or indirectly; or positioned close by such that the electrode can register a change in the current due to the presence of the ana!yte of interest in the flow cell. Alternatively, no recognition substrate is attached to the working electrode and the surface of the electrode is oxidised by the analyte of interest and the change in current is registered. In this arrangement, a certain voltage can be applied to select for the analyte of interest. The recognition substrate may be any substrate that has selective recognition for the analyte of interest (i.e. the analyte being detected). The recognition substrate may bind to the analyte of interest directly or indirectly. Alternatively, the recognition substrate may bind to a converted product of the analyte of interest. Again, the recognition substrate may bind to directly or indirectly to the converted product. The converted product may be produced by any means known in the art. In some embodiments, the sensor arrangement includes an immobilised enzyme reactor (IMER). The IMER acts to convert the analyte to an electroactive product that can be oxidised or reduced, which changes the current. The change in current can be detected and enables the presence and/or amount of analyte to be determined. The recognition substrate can be selected from an enzyme, an antibody, an aptarner, and/or material imprinted polymers (MIPS), The recognition substrate can break away from the surface of the electrode, which can affect the sensitivity of the sensor. The sensor arrangement can be recalibrated by inserting a known concentration of the anaiyte (such as glucose), or a known concentration of the anaiyte can be inserted simply to determine that the sensor arrangement is functioning/working.

The enzyme is immobilised onto an electrode, and the function of the electrode is essentially connected with the catalytic activity of the immobilised enzyme. The electrochemical response of the electrode is based on the enzymic generation of electroactive species or on the electrochemical communication of the enzyme with the electrode, For example, in a glucose sensor, glucose oxidase is entrapped on the electrode by a dialysis membrane. The decrease in measured oxygen is proportional to the glucose concentration.

For repeated use of enzymes on such sensors, there are numerous techniques in the art for holding the enzymes in place such a providing a number of membrane layers.

In an alternative embodiment, the sensor arrangement may have one or more membrane layers on the surface of the working electrode to retain the recognition substrate in contact with the surface of the electrode. One, two, three, four, five, six, seven, or more membrane layers can be placed on top of the electrode surface. The recognition substrate is captured in the one or more layers of membrane. The membrane can act to retain the recognition substrate in place and prevent/reduce damage to the recognition substrate during use. The membrane can also act as a filter to ensure that only the desired analyte/converted product can contact the recognition substrate. The one or more layers may be cross-linked to the surface of the electrode. One or more of the layers may include a mediator material that enhances detection of the anaiyte. For example, if the analyte to be detected is glucose, the layer can include nation, which creates a charged surface that allows neutral substrates such as glucose to be absorbed, but repels charged substrates. In this arrangement, the sensor arrangement can also be recalibrated by inserting a known concentration of the analyte (such as glucose), or a known concentration of the analyte can be inserted simply to determine that the sensor arrangement is functioning/working.

In an alternative arrangement, glucose can be converted by glucose oxidase to produce hydrogen peroxide. The hydrogen peroxide can be converted by the voltage to produce hydrogen, oxygen and water. This can be achieved with a membrane arrangement on top of the working electrode, such that the first membrane provides a selective layer for selecting glucose from the perfusion fluid. The glucose binds to the recognition substrate, for example glucose oxidase, which is retained on a second membrane/layer. The glucose oxidase catalyses the oxidation of the glucose, and one of the resulting products is hydrogen peroxidase. The resulting hydrogen peroxidase passes to a third membrane/iayer where it is oxidised at the working electrode by the current set by the potentiostat. The change in current is detected by the potentiostat. in this arrangement, the third membrane/layer is on top of the working electrode, the second membrane/layer is on top of the third layer, and the first membrane/layer is on top of the second membrane/layer. In this arrangement, the layers can be over one of the working electrodes only, or on top of some or all of the other electrodes.

The electrochemical sensor arrangement of the above embodiments must have a reference electrode and one or more working electrodes. The plurality of working electrodes can detect the same and/or different analytes. Each working electrode (and the reference and auxiliary electrodes) requires a channel connected to an electric connector that can be connected to an electrical connector of the monitoring unit. Each channel can connect to an individual electrical connector. Such sensors arrangements may be prepared using Thick-Film Technology for example. The sensor unit can have multiple sensor arrangements, channels and electric connectors.

In one arrangement the multiple sensors arrangements can detect different analytes. In another embodiment, some of the sensor arrangements detect different analytes and some of the sensors detect the same anaiyte. in another arrangement, the multiple sensor arrangements detect the same anaiyte. In embodiments where some or all of the sensor arrangements detect the same anaiyte, this embodiment can be utilised to determine if one of the sensor arrangements is not working properly. If all but one of the sensor arrangements provide the same result, then if can be determined that the sensor arrangement detecting a different result is not functioning correctly. This sensor arrangement can be ignored or turned off.

In the embodiments in which the sensor arrangement is an optical sensor, the sensor has a light source for emitting illuminating light, such as LEDs or OLEDs, and a light receiving unit, such as a photodiode which feeds back to a voltmeter. In these embodiments the electrical contact provides power for the setting of the voltage, provides power for the light source to emit light, and collects the information from the photodiode. The light source has a gating arrangement to achieve the desired wavelength for the anaiyte of interest. The gating arrangement zones out wavelengths not required. Alternatively, a laser can be used as the light source. Optical sensors have excellent long term stability.

!n an advantageous embodiment, all or some of the flow cell containing the sensor arrangement is visible from the outside of the sensor unit. This means a visual check of the sensor arrangement can be made. Microfiuidic devices, such as a flow ceii, often have bubbles of gas travelling through the device. If such bubbles were to accumulate on the one or more of the electrodes and/or recognition substrates, it could affect the accuracy of the sensor arrangement. It will also be possible to visual any discoloration of the sensor arrangement that would suggest there is a problem with the sensor arrangement.

During use, a perfusion fluid is passed into the flow ceil by the action of a perfusion unit, for example a pump or gravity feed unit. The fluid travels across the sensor arrangement, and the electrochemical or optical sensor detects any target anaiyte in the perfusion fluid. This data is transmitted to the monitoring unit via the respective first and second electrical contact of the sensing unit and the monitoring unit. Fluid source

The monitoring device can utilise any fluid source that contains the anaiyte or analytes of interest. For example the fluid source can be a molecular exchange device, a fluid sample obtained from the subject or other environment.

In an advantageous embodiment, the sensor unit described above can be attached to a molecular exchange area, such as molecular exchange device, such as the device described in PCT publication WO2008038015. The molecular exchange area is a device that is implanted in a subject, which selects exchange material from the subject. When the subject is a human or animal, the molecular exchange area is a sterile device. The selected exchange material may include the target ana!yte(s). The sensor unit is connected to the molecular exchange area, such as a molecular exchange device, via a fluidic connection, such as tubing. The sensor unit itself is not inserted into the subject, which means that it can be non-sterile. During use, the perfusate fluid, transporting the selected exchange material, travels from the molecular exchange area into the sensor unit, such as a flow cell, such that the fluid passes over a sensor arrangement having one or more sensors. The flow of the fluid is controlled by a perfusion unit, such as a pump or gravity feed unit. The selected exchange material may include solute fractions present in blood that have diffused across the semi-permeable membrane of the molecular exchange area.

In preferred embodiments, the sensor unit is attached to the fluid source, such as a molecular exchange device, by a microfiuidic Luer connector or other connectors known in this field. Alternatively this connector may be a one-way valve to prevent back-flow. This detachable arrangement allows the fluid source, such as a molecular exchange device, to be disposed of or sterilised after a single use. The sensor unit and/or monitoring unit can be utilised for multiple uses. These devices do not get placed into the subject; and therefore they do not require the high level of sterility of a unit that is inserted into a subject. Sterilisation of sensors is a known problem as most common sterilisation methods cause some degree of recognition substrate inactivation, especially for a biological component. The use of MIPs goes some way to addressing this problem.

In some embodiments, the sensor unit may have two or more flow cells described above. In a preferred embodiment, the sensor unit has two flow ceils, in this arrangement, the sensor unit may be fiuidiy connected to a molecular exchange device, or other fluid source, as described above. A perfusion unit can transport perfusion fluid from a fluid source to the first flow cell and across the sensor arrangement(s). The fluid exiting the first flow cell is transported to the molecular exchange device. This arrangement is preferred for continuous monitoring of an analyte, or anaiytes, in a subject. However, in an alternative arrangement, the fluid exiting the flow cell may be put into a different system or disposed of as a waste material. Within the molecular exchange device, there is a selective transfer of materials; and the perfusion fluid containing the selected materials will then be transported from the molecular exchange device to the second flow cell of the sensor unit. The fluid flows over the sensor arrangement(s) of the second flow celi. The fluid exiting the second flow cell can be collected in the perfusion unit or left to drip into a waste receptacle. In embodiments in which the fluid exiting the second flow cell is collected in the perfusion unit, this fluid can then be transported (for example, by pumping or gravity feed) into the first flow cell, In all of these embodiments, the monitoring unit can then look at the difference in the readings of the target analyte(s) between the two flow cells. In these embodiments, the flow ceils and fluid ic tubing must be sterile because the fluid is introduced into the subject when it flows through the molecular exchange device. The second flow celi and any fiuidic tubing taking the fluid away from the molecular exchange device does not need to be sterile, provided the fluid will not be reintroduced into the first flow ceil. in an alternative embodiment, the sensor unit has two flow cells. In this arrangement, the sensor unit may be fluidly connected to a molecular exchange device as described above, A perfusion unit can transport perfusion fluid from a fluid source to the first flow cell and across the sensor arrangement(s). The fluid exiting the first flow cell is then transported to the molecular exchange device. Within the molecular exchange device, there is a selective transfer of materials; and the perfusion fluid containing the selected materials will then be transported from the molecular exchange device to the second flow cell of the sensor unit. The fluid flows over the sensor arrangement(s) of the second flow celi. Optionally, the fluid exiting the second flow cell is transported to the first flow cell to provide a closed loop arrangement. This arrangement allows the same perfusion fluid to be used. The first sensor arrangement will determine the amount of analyte present in the fluid before the fluid is reintroduced into the molecular exchange device, and the second sensor arrangement can detect the change in the amount with respect to the first sensor arrangement. The monitoring unit can then look at the difference in the readings of the target anaiyte(s) between the two flow cells. When this arrangement is used having the molecular exchange device positioned in a subject, the flow cells and fluidic tubing should be sterile because the fluid is introduced into the subject when it flows through the molecular exchange device. In an arrangement in which the molecular exchange device is not positioned in a subject, the flow cell and fluidic tubing does not The second flow cell and any fluidic tubing need to be sterile, because it is being reintroduced into the first flow ceil.

!n an alternative arrangement, a monitoring system has two monitoring devices of the invention described herein. In this arrangement, a first sensor unit may be fluidly connected to a molecular exchange device as described above. A perfusion unit can transport perfusion fluid from a fluid source to the first sensor unit, of the first monitoring device, and across the sensor arrangement(s). The fluid exiting the first sensor unit is then transported to the molecular exchange device. Within the molecular exchange device, there is a selective transfer of materials; and the perfusion fluid containing the selected materials will then be transported from the molecular exchange device to the second sensor unit of the second monitoring unit. The fluid flows over the sensor arrangement(s) of the second sensor unit. Optionally, the fluid exiting the second sensor unit can be transported to the first sensor to provide a closed loop arrangement. This arrangement allows the same perfusion fluid to be used. The first sensor unit will determine the amount of analyte present in the fluid before the fluid is reintroduced into the molecular exchange device, and the second sensor unit can detect the change in the amount with respect to the first sensor unit. The monitoring unit can then look at the difference in the readings of the target analyte(s) between the two sensor units. In embodiments in which the molecular exchange device is position in a human or animal subject, the flow cells and fiuidic tubing must be sterile because the fluid is introduced into the subject when it flows through the molecular exchange device. The second flow cell and any fiuidic tubing need to be sterile, because it is being reintroduced into the first sensor.

It is advantageous to have a sensor unit that is reieasable from the monitoring unit, it means that the sensor unit can be disposed of after a single use to mitigate any contamination, or it can be reused.

The flow ceil of the sensor unit ensures that measurements can be derived from a flowing measurement driven by a pump or gravity, rather than through capillary action. This ensures that a continuous reading of the anaiyte concentration in a subject can be achieved if desired.

Continuous monitoring includes continuous measurements being taken, or measurements taken at regular intervals. For example, continuous monitoring may mean that measurements are taken every 30 seconds, one minute, two minutes, etc. In some embodiments, the measurements will be taken at regular intervals with a flushing of the sensor between some or ail of the measurements.

Gravity feed monitoring or delivery system

In an alternative arrangement, the fluid source connected to the sensor unit is a receptacle for containing a fluid. The receptacle provides fluid to the sensor unit by the action of gravity; and is adapted to allow the fluid to flow from the receptacle.

The main advantage provided by gravity feed of the fluid through the device avoids the need for a powered or motorized action to transport the fluid through the monitoring device. This provides a simple and cost effective monitoring device, which does not require any additional arrangements to use the monitoring device, in particular, no expensive pumps, electricity, or other powered or motorized arrangements are required to transport fluid through the system. This simplifies the requirements and reduces the cost of manufacturing the monitoring device, and reduces the cost of running and maintaining the monitoring device. It can also improve the safety of the monitoring device. in an additional embodiment of the gravity feed arrangement, the arrangement further includes a molecular exchange device; a supply conduit defining a fluid path from the receptacle to a molecular exchange device; and an outlet conduit defining a fluid path from the molecular exchange device to an outlet port, the outlet port adapted to be connected to the sensor unit; wherein, in use, the receptacle is positioned above the supply conduit, molecular exchange area, outlet conduit, and sensor unit such that the fluid is transported from the receptacle to the sensor unit by the action of gravity. To achieve the flow of fluid through the system by the action of gravity, the receptacle providing the fluid to the rest of the system must be in an elevated position compared to the other components of the system. This would be appreciated by those of skill in the art. In an alternative embodiment of the gravity feed arrangement, a monitoring system has two monitoring devices of the invention described herein, in this arrangement, a first receptacle is fluidly connected to a first sensor unit, the first sensor unit is fluidly connected to a molecular exchange device as described above. Gravity transports the perfusion fluid from the first receptacle to the first sensor unit, of the first monitoring device, and across the sensor arrangement(s). The fluid exiting the first sensor unit is then transported to the molecular exchange device by gravity. Within the molecular exchange device, there is a selective transfer of materials; and the perfusion fluid containing the selected materials will then be transported by gravity from the molecular exchange device to the second sensor unit of the second monitoring unit. The fluid flows over the sensor arrangement(s) of the second sensor unit. Optionally, the fluid exiting the second sensor unit can be transported by gravity to a second receptacle. The second receptacle can be used to switch with the first receptacle, such that the fluid collected in the second receptacie is transported to the first sensor unit by- gravity, which provides a closed type of arrangement. This arrangement allows the same perfusion fluid to be used. The first sensor unit will determine the amount of analyte present in the fluid before the fluid is reintroduced into the molecular exchange device, and the second sensor can detect the change in the amount with respect to the first sensor. The monitoring unit can then look at the difference in the readings of the target analyte(s) between the two sensor units. In embodiments in which the molecular exchange device is position in a human or animal subject, the sensor unit and fluidic tubing must be sterile because the fluid is introduced into the subject when it flows through the molecular exchange device. The second sensor unit and any fluidic tubing need to be sterile, because it is being reintroduced into the first sensor unit.

Receptacle

The receptacle can be in any form that allows fluid to flow from the receptacle by the action of gravity. The receptacle could be a glass bottle, plastic bottle or a bag. The receptacie may be formed from an e!astomeric material, such as rubber, plastic, silicon or other suitable material that can be filled with a volume of fluid. For example, the receptacle could be an elastomeric bag, such as standard fusion/!V bag that are normally utilised for intravenous medical use. Such bags are usually formed from two heat sealed sheets of an e!astomeric material, If the receptacle is not formed from an elastomeric material, a vent will be required to equalise the pressure within the receptacle.

In an aspect of the invention, the receptacle is a closed receptacle. The receptacle may be prefilled and/or re-fi!lab!e. The receptacle may further comprise a valve that allows the receptacle to be refilled with fluid. The receptacle may be sterile or non-sterile depending on its intended utility. For a re-fillabie receptacle, it may be necessary to control sterility in the environment in a different way. in an aspect of the invention, the volume of the receptacle may be 0,0005 to 10 litres, 0.0005 to 0,75 litres, 0.25 to 8 litres, or 0.5 to 4 litres. The volume of the receptacle may be 0.005, 0.1 , 0.02, 0.05, 0.1 , 0.2, 0.25, 0,5, 0,75, 1 , 2, 3, 4, 5, 8, 7, 8, 9, 10 litres (I). The actual volume of the receptacle wiiS depend on the intended utility of the device. For example, for drug delivery, a volume of 0, 5I may be sufficient. In contrast, for use on a production line to monitor analyses for quality control purposes a receptacle with a 2I volume may be appropriate.

The receptacle must be positioned above the molecular exchange area during use, to ensure that there is a proper elevation to provide consistent pressure for the supply of the fluid into the supply conduit. This allows the monitoring system to work by gravity feed of the fluid to the molecular exchange area.

In one aspect of the invention, the receptacle is positioned at least 5, 8, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 80, 70, 80, 90 centimeters, 1 , 2, 3, 4, 5, or more meters above the molecular exchange

<3ΓΘ3.

The exact elevation of the receptacle with respect to the molecular exchange area will depend on many factors such as the cross-sectional area of the fluid path of the supply conduit, the thickness of the walls defining the fluid path of the supply conduit, the volume of the fluids being supplied and the desired flow rate of the fluid through the system/molecular exchange area. Moreover, the required elevation will depend on the intended utility of the monitoring system.

Stationary/portable device

In one aspect of the invention, the monitoring system may further include one or more attachments to hold one or more of the receptacle, supply conduit, molecular exchange area, outlet conduit and/or the sensor unit in position. One of the attachments may hold two or more of the receptacle, supply conduit, molecular exchange area, outlet conduit and/or the sensor unit in position relative to one or more of the receptacle, supply conduit, molecular exchange area, outlet conduit and/or the sensor unit in position. Two or more attachments may hold two or more of the receptacle, supply conduit, molecular exchange area, outlet conduit and/or the sensor unit in position with respect to one or more of the receptacle, supply conduit, molecular exchange area, outlet conduit and/or the sensor unit in position.

The attachment may be a stand, pole, and/or wall mountable arrangement. The attachment, such as a stand, pole or wall mounted, may be moveable from one position to the other. The attachment, such as a stand or pole, may be extendable/retractable to allow the position of the receptacle, supply conduit, molecular exchange area, outlet conduit and/or the sensor unit to be moved. For example, the receptacle may be held by an extendable/retractable attachment that changes the height of the receptacle with respect to the molecular exchange area. This arrangement would allow different flow rates to be achieved and/or accommodate different utilities of the monitoring system. In some aspects of the invention, at least one of the one or more attachments is adapted to be portable from one location to different location. For example the attachment_., such as a pole or a stand can be on wheels.

Flow rate

In one aspect of the invention, during use, it is preferable that the supply conduit is maintained in a fixed position to provide a constant perfusion rate. In some aspects of the invention, this is achieved by using an attachment, such as a pole or stand that maintains the position of the supply conduit during use.

In some aspects of the invention, the flow rate of the fluid through the molecular exchange area can be altered by constricting the receptacle. This creates a pressure within the receptacle and forces the fluid out of the receptacle. The receptacle may be constricted by hand and/or by placing a constriction eiement around the receptacle to create pressure within the receptacle. in, some aspects of the invention, the flow rate of the fluid through the molecular exchange area can be altered by moving the height of the receptacle with respect to the molecular exchange device. in some aspects of the invention, the flow rate can be altered by altering the size of the supply conduit.

In some aspects of the invention, the flow rate is 0.01 to 150pl/min and preferably 30 to 150pl/min. The flow rate may be 0.01 , 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1 , 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0,55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1 , 1.5, 2, 2,5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6,5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 80, 65, 70, 75, 80, 85, 90, 95, 100, 105, 1 10, 1 15, 120, 125, 130, 135, 140, 145 150μΙ/min .

The supply and outlet conduits

The supply conduit defines a fluid path from the receptacle to a molecular exchange area. The outlet conduit defines a fluid path from the molecular exchange area to the outlet port. The supply and outlet conduits can be any arrangement that can carry fluid (by the action of gravity) from the receptacle to the molecular exchange area or the molecular exchange area to the outlet port, For example, the supply and/or outlet conduits may be in the form of tubing. The tube can have a uniform cross-section and/or uniform wall thickness. The tube can have a circular cross-section, or any other shaped cross-section that allows the passage of a fluid along the tubing. A tube with a circular cross section may, for example, have an internal diameter of 0.01 to 0.5 mm, or approximately 0,25mm. The internal diameter of the tubing may be 0.01 , 0,02, 0.03, 0.04, 0.05, 0.08, 0.07, 0.08, 0.09, 0,1 , 0,15, 0.2, 0.25, 0.3, 0.35, 0,4, 0.45, 0.5 mm. The tubing may have an external diameter of 0,02 to 7mm or approximately 1 mm. The tubing may have an external diameter 0,01 , 0.02, 0.03, 0.04, 0.05, 0,06, 0.07, 0,08, 0.09, 0.1 , 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0,45, 0.5, 0.55, 0,6, 0,65, 0,7, 0.75, 0.8, 0.85, 0.9, 0.95, 1 , 1 .5, 2, 2,5, 3, 3,5, 4, 4.5, 5, 5.5, 6, 6.5, 7 mm.

In some aspects of the snvention, the supply conduit and/or outlet conduit may be standard IV drip tubing.

In some aspects of the invention, the rate of flow of the fluid can be controlled by changing the internal cross-sectional area of the supply conduit, in an aspect of the invention, a plurality of supply conduits having different internal cross-sectional areas can be provided and/or utilised within the same monitoring system. This can be utilized alone to control the flow rate or in combination with the receptacle being constricted to create pressure within the receptacle, either by hand, placing a constriction element around the receptacle and/or or using an infusion pump to create pressure within the receptacle.

An adaptor may be provided that can allow supply conduits having different internal cross-sectional areas to be used with the same molecular exchange area of the monitoring system. For example the adaptor may be circular in shape with a plurality of openings around the external periphery of the adaptor. The adaptor can be rotated so that each of the openings is positioned over the inlet of the molecular exchange device, and a supply conduit having the desired cross-sectional area can be attached to the molecular exchange area via the adaptor.

In some aspects of the invention, the monitoring system may further comprise a valve arranged to occlude the supply conduit. The valve for example may be a roller valve or a pinch valve. When the valve is closed it occludes the supply conduit it prevents fluid being transported along the supply conduit to the molecular exchange device. When the valve is open it allows fluid to be transported from the receptacle to the sensor unit. The supply conduit may have a first port connected to the receptacle and a second port. The second port may be used to introduce an additional fluid into the molecular exchange area.

In some aspects of the invention, the monitoring device is positioned in an outlet of the outlet conduit, a container, for example a bucket or toilet bowl, and/or a sensor apparatus. In the online arrangement, the monitoring device may be connected to the outlet port, or positioned between the molecular exchange area and the outlet port. In the latter arrangement the outlet conduit is in two parts; one part linking the molecular exchange area and the sensor unit, and the other part linking the sensor unit and the outlet port.

In some aspects of the gravity feed system, a second receptacle may be present after the monitoring device, after the molecular exchange area, and/or a second monitoring device may be present before the molecular exchange area. In such an arrangement, there would exist a first receptacle to allow a fluid to flow through the sensor unit of the first monitoring device, and then on to the molecular exchange area and from there through the sensor unit of the second monitoring device, and into a second receptacle. In such a manner, the presence of the analyte can be measured in the perfusate and dialysate and the difference between these two represents the effect of the environment. In such an arrangement, the flow can be reversed by lifting the second receptacle above the molecular exchange area, and lower the first receptacle to promote flow through the molecular exchange area by the action of gravity.

The arrangement having two sensor units can be utilised to determine the difference in the concentration of an analyte During use, a perfusion fluid is passed into the flow cell by the action of gravity feed unit. The fluid travels across the sensor arrangement, and the electrochemical or optical sensor detects any target analyte in the perfusion fluid. Additional sensor unit and/or flow cells

In some embodiments, the system can have one or more sensor units; and each sensor unit can have one or more flow cells,

In an embodiment of the invention, the sensor unit has two flow ceils. In this arrangement, the fluid is transported by gravity from the receptacle into the first flow cell and across the sensor arrangement(s). The fluid exiting the first flow ceil is transported to the molecular exchange area. Within the molecular exchange area, there is a selective transfer of materials; and the perfusion fluid containing the selected materials will then be transported from the molecular exchange area to the second flow cell of the sensor unit. The fluid flows over the sensor arrangement(s) of the second flow cell, The fluid exiting the second flow ceil can be collected in in a waste receptacle, in these embodiments, the electroanalytical component of the sensor unit (or a monitoring unit electrically connected to the sensor unit) can detect the difference in the readings of the target analyte(s) between the two flow cells. In these embodiments, the first flow cell and fluidic tubing should be sterile if the fluid is introduced into a human or animal subject when it flows through the molecular exchange area. The second flow ceil and any fluidic tubing taking the fluid away from the molecular exchange device does not need to be sterile, provided the fluid will not be reintroduced into the first flow cell. In an alternative embodiment, the monitoring system has two sensor units of the invention described herein. Each sensor unit can be in direct electrical contact with a monitoring unit as described above. Alternatively, each sensor unit can be in direct electrical contact with the same monitoring unit. In this arrangement, a first receptacle is fiuidiy connected to a first sensor unit, the first sensor unit is f!uidly connected to a molecular exchange device as described above. Gravity transports the perfusion fluid from the first receptacle to the first sensor unit, and across the sensor arrangement(s). The fluid exiting the first sensor unit is then transported to the molecular exchange area by gravity. Within the molecular exchange area, there is a selective transfer of materials; and the perfusion fluid containing the selected materials will then be transported by gravity from the molecular exchange area to the second sensor unit, The fluid flows over the sensor arrangement(s) of the second sensor unit.

The first sensor unit will determine the amount of analyte present in the fluid before the fluid is reintroduced into the molecular exchange device, and the second sensor unit can detect the change in the amount with respect to the first sensor unit. The monitoring unit(s) can then look at the difference in the readings of the target ana!yte(s) between the two sensor units. This can provide a more sensitive reading,

Optionally, the fluid exiting the second sensor unit can be transported by gravity to a second receptacle. The second receptacle can be switched with the first receptacle (i.e. positioned at a height above the other components of the system). This arrangement allows the same perfusion fluid to be used.

In embodiments in which the molecular exchange area is positioned in a human or animal subject, the sensor unit and fluidic tubing must be sterile because the fluid is introduced into the subject when it flows through the molecular exchange area. The second sensor unit and any fluidic tubing need to be sterile, because it is being reintroduced into the first sensor unit.

It is advantageous to have a sensor unit that is releasable from the monitoring unit, it means that the sensor unit can be disposed of after a single use to mitigate any contamination, or it can be reused. Continuous monitoring includes continuous measurements being taken, or measurements taken at regular intervals. For example, continuous monitoring may mean that measurements are taken every 30 seconds, one minute, two minutes, etc. In some embodiments, the measurements will be taken at regular intervals with a flushing of the sensor between some or ail of the measurements.

In an embodiment of the delivery system, a sensor unit is positioned after the molecular exchange area. A known concentration of a composition, such as a drug, can be introduced into the receptacle. The composition is carried from the receptacle to the drug via the supply conduit. The composition is then delivered across the molecular exchange area. The sensor unit can measure the amount of the composition in the fluid being carried from the molecular exchange area. The difference between the measure amount and the known concentration of the composition can be utilised to determine the amount of the composition that has been delivered.

Additional receptacles In some embodiments, the monitoring system further comprises one or more additional receptacles. In a preferred arrangement, the monitoring system has two receptacles. The first receptacle contains a fluid and is adapted to allow the fluid to flow from the first receptacle to a molecular exchange area, via the supply conduit; and from the molecular exchange area to the second receptacle, via the outlet conduit. The second receptacle is connected to the outlet port. The first receptacle is positioned above the supply conduit, molecular exchange area, outlet conduit, and second receptacle such that the fluid is transported from the first receptacle to the second receptacle by the action of gravity, in an alternative arrangement, the second receptacle is positioned above the supply conduit, molecular exchange area, outlet conduit, and first receptacle such that the fluid is transported from the second receptacle to the first receptacle by the action of gravity. The elevation of first and second receptacles can be switched between the two arrangements.

In an advantageous arrangement, the system further comprises a first and second sensor unit. The first sensor unit position between the first receptacle and molecular exchange area. The second sensor unit position between the molecular exchange area and the second receptacle. The first sensor detects one or more analytes present in the fluid transported from the first receptacle to the molecular exchange device; or the fluid transported from the molecular exchange area to the first receptacle. The second sensor detects one or more analytes present in the fluid transported from the molecular exchange area to the second receptacle; or the fluid transported from the second receptacle to the molecular exchange device.

In the molecular exchange area, selective transfer of materials can occur across the porous area. In the arrangement in which the first receptacle is elevated, the first sensor unit determines the amount of analyte present in the fluid before the fluid is introduced into the molecular exchange area, and the second sensor unit determines the amount of analyte present in the fluid after the fluid has travelled through the molecular exchange area. The difference in the readings of the target analyte(s) between the two sensor units can be utilised to determine the change in the amount of the analyte.

In the arrangement in which the first receptacle is elevated, i.e. the second receptacle has been switched with the first receptacle, the second sensor unit determines the amount of analyte present in the fluid before the fluid is introduced into the molecular exchange area, and the second sensor unit determines the amount of analyte present in the fluid after the fluid has travelled through the molecular exchange area. The difference in the readings of the target analyte(s) between the two sensor units can be utilised to determine the change in the amount of the analyte. This arrangement allows the same fluid to be utilised to monitor a change in the amount of an analyte in the subject in which the molecular exchange area is positioned.

In some embodiments, the system can comprise additional receptacles that the collect the fluid that has been transported through the system. The receptacle can then be removes so that the collected fluid can be analysed and/or otherwise disposed of.

The molecular exchange area is any arrangement that enables the selective exchange of material from a subject. For example, the molecular exchange area may be a fluid conduit having porous area across which selective molecular exchange can take place. This may be a hollow fibre in a casing having a porous area. Alternatively, the molecular exchange area may be part of a molecular exchange device, such as the device described in PCT publication WO2008038015. The molecular exchange device is a device that is implanted in a subject, which selects exchange material from the subject. When the subject is a human or animal, the molecular exchange device is a sterile device. The exchange material may pass over a porous area of the molecular exchange device. The selected exchange material may include the target anaiyte(s). The selected material may be a compopsiiton to be delivered to the subject, such as a drug.

The sensor unit of the monitoring device is connected to the molecular exchange device via a fiuidic connection, such as tubing. The sensor unit is not inserted into the subject, which means that it can be non-sterile. During use, the perfusate fluid, transporting the selected exchange material, travels from the molecular exchange device Into the sensor unit, such as a flow cell, such that the fluid passes over one or more sensor arrangements.

The selected exchange material may include solute fractions present in blood that have diffused across the semi-permeable membrane of the molecular exchange device.

In some aspects of the invention, the molecular exchange area comprises at least one fluid passageway supported by a casing, and comprising at least one exchange aperture wherein a portion of at least one of the fluid passageways exposed by the exchange aperture is porous.

The casing supports and protects the fluid passageways. The casing fuslher ensures that the porous portion of the passageway will not fragment in use, whilst ensuring that the passageway maintains its shape and maximises the flow of fluid therein.

The inlet to the molecular exchange area is attached to the supply conduit and the outlet of the molecular exchange area is attached to the outlet conduit.

In an advantageous embodiment of the invention, the molecular exchange area is a hollow fibre in a casing having a porous area along the casing.

In some aspects of the invention there are two or more fluid passageways, In some embodiments of the invention, the two or more fluid passageways each run from the inlet to the outlet of the molecular exchange area, One or more of the fluid passageways has an exchange aperture. In addition to or alternatively, one exchange aperture expose two or more fluid passageways and allows molecular exchange to occur from/to each of the fluid passageways. In an alternative embodiment of the invention, the molecular exchange area is a molecular exchange device.

The molecular exchange device comprising a casing, extending from a proximal end to a distal end, supporting at least two fluid passageways extending from the proximal end to the distai end; the casing comprising at least one exchange aperture between the distal end and the proximal end, wherein a portion of the fluid passageway exposed by the exchange aperture is porous.

In an advantageous embodiment of the present invention, a separator extends along the casing for at least the length of the exchange aperture, separating the at least two fluid passageways. In a further advantageous embodiment, the separator extends along substantially the entire length of the casing, from the distal end to the proximal end, separating the at least two fluid passageways. Preferably, the separator extends along the central axis of the casing. The separator provides the advantage of ensuring that there is no exchange of fluid between two or more fluid passageways, thereby improving dialysis efficiency. The separator also provides support to the two or more fluid passageways, particularly at the porous portion of the passageway. The separator may or may not be integral with the casing.

Advantageously, the two fluid passageways may be arranged on aligning sides of the central separator. Advantageously, two or more fluid passageways may be arranged around the central separator. Preferably pairs of fluid passageways in fluid communication with one another may be arranged around the central separator to permit multiple sets of molecular exchange in one device. The molecular exchange may be for analysis, dialysis, delivery, recovery and extraction of substances etc.. During use in a subject, for example, one set of fluid passageways may deliver a drug to the external environment of the device, whereas another set of fluid passageway may be used for recovery, extraction or analysis of a substance from the environment surrounding the device into the passageway to measure the overall drug content, it is envisaged that each set of fluid passageways will be selected for a particular function.

In an advantageous embodiment the at least two fluid passageways are at least partially defined by the casing and/or separator, Alternatively, the at least two fluid passageways are not at least partially defined by the casing and/or separator. For example, the fluid passageways are at least one tube held within the casing, in one embodiment of the invention the porous region of the fluid passage way is a porous membrane bonded within the casing at the proximal and distal ends of the exchange aperture. Preferably, the at least one tube is a porous membrane. More preferably, the porous membrane is a dialysis membrane.

In an embodiment of the invention, substantially the entire area of the tube is porous. In this embodiment, the tube can be made of a single type of material, which obviates the need for forming a separate porous portion in the conduit adjacent to the exchange aperture and makes the molecular exchange device even cheaper to manufacture. This embodiment also provides the advantage that the porous portion does not need to be carefully- aligned with the at least one exchange aperture of the casing. As the hollow tube is only exposed to the external environment at the exchange aperture of the casing, molecular exchange will only occur at these desired points of the casing.

In a preferred embodiment the at least one tube extends from the proximal end to the distal end of the casing, folds back on itself at the distal end and extends from the distal end to the proximal end of the casing, providing two fluid passageways. Advantageously, the at least one tube has a circular or non-circu!ar shaped cross section. This enables the hollow tube to be positioned in the correct orientation within the casing. For example, the cross section may have one or more straight edges or be D-shaped or be profiled to orientate the hollow tube in such a way as to optimise its efficiency for exchange. in preferred embodiments the fluid may be supplied to one of the fluid passageways and drawn from other fluid passageway to ensure flow of fluid within the device.

Advantageously, the exchange aperture is an opening in the casing, preferably formed by removing, such as by cutting, an area of the casing, in an alternative embodiment, the exchange aperture is a porous area, preferably formed by treating the casing to render a portion of the casing porous. in a preferred embodiment, more than one exchange aperture exposes the same fluid passageway. In one embodiment, the porous portions of the more than one exchange aperture have different porosities. The porosity of each porous portion will depend upon the intended function of the specific porous portion.

In a preferred embodiment having two or more of fiuid passageways or two or more porous portions on one fiuid passageway, the porous portions have different porosities from one another. The use of porous portions and/or fiuid passageways having different porosities enables different selections of molecular exchange at different exchange apertures along the casing. For example, when the device is being used to deliver a drug into the bloodstream of a subject and monitor the concentration of the drug in the bloodstream, at least one porous portion will require a porosity that enables the drug to pass through the porous area into the bloodstream and at least one porous portion that has a porosity allowing the drug bound to a carrier, such as a plasma protein, for exampie albumin, to pass through the hollow area into the respective fluid passageway. The latter porous portion, located further downstream to other porous portion with respect to the fiow of fluid within the at least two fluid passageways, will need to have a porosity that allows the passage of larger particles, i.e. the drug bound to a carrier as opposed to the drug alone. A skilled person will appreciate that the desired porosity of the porous portion of a fluid passageway will depend upon the size of the molecule that is intended to be exchanged across the porous portion adjacent to the exchange aperture. This arrangement will enable both the free (unbound to carrier) concentration and the total (unbound and bound to carrier) concentration of the drug to be determined,

In a preferred embodiment, the at least two fluid passageways have aligned exchange apertures, in use, an exchange aperture may rest against the internal walls of the vessel preventing access to the porous portion of the fluid passageway adjacent to the exchange aperture, as it is often the case that the device is not inserted Into centre of the vessel, By providing aligned exchange apertures, it is more likely that at least one of the exchange apertures will be in contact with the fiow of fluid within the vessel.

Alternatively, the exchange apertures may be positioned along the respective fluid passageway so that the apertures are not aligned. Such an arrangement is advantageous when the exchange apertures are intended to be used for different purposes.

In a preferred embodiment, the casing supports the at least two fluid passageways in the form of a tube, which are separated by the central separator along the length of the exchange aperture. The separator provides support to the tubing, whilst enabling a substantially large extent of exposure to the fluid passageway. In such an embodiment exchange of molecules may occur over substantially the entire circumference of the exposed tube, thereby providing a maximum surface area and increasing the efficiency of the exchange of molecules.

In a preferred embodiment of the invention, the at least two fluid passageways are held away from the separator in the porous section as a consequence of the hollow tubes being sealed where they enter and exit the porous section, thereby enabling substantially 100% of the circumference of the porous portion of the fluid passageway to be exposed. This provides the advantage of maximising the surface area of the porous region in contact with the environment external to the device. Preferably, the at least two fluid passageways are sealed by glue.

Advantageously, the distal end of the device comprises a plug in the end of the casing. More advantageously in this embodiment, the separator extends to the distal end of the casing and contains a fluid aperture to allow flow from one of the fluid passageway to another fluid passageway.

Alternatively, the distal end of the casing is formed as a tip containing a flow chamber to allow flow from the end of at least one of the fluid passageways info the end of another fluid passageway. Advantageously, the ends of the fluid passageways are within the flow chamber, such that any bond between the end of the fluid passageway and the distal end of the casing is remote from the exchange aperture to avoid fragmentation of the tube/porous membrane attached to the inside of the casing. in an arrangement, the flow chamber has a sensor arrangement for detecting a substance. For example, the sensor arrangement is a fibre optic and a reflector, wherein the fibre optic and reflector are positioned at the distal end of the device to enable spectro!ogical measurements, for example, spectrophotometric measurement. Alternatively the sensor arrangement is a wave guide, conductor, photoelectric, electro-active or electrochemical sensor.

In an advantageous embodiment, the fluid transported along the at least one of the fluid passageways carries a composition, such as a drug, to be delivered; and it is delivered via molecular exchange across the exchange aperture. Advantageously, the molecular exchange device further comprises a channel leading from the proximal end of the casing to the distal end of the casing to provide additional materials to the interior and/or exterior of the distal end of the casing. Preferably, the channel is integral with the separator. More preferably, the channel is formed within the central axis of the separator.

The channel may supply fluid through to the distal end of the casing, in particular, into the flow chamber. In such an embodiment, the fluid can then pass into one or more of the fluid passageways. Of course, the reverse is possible, with fluids being passed along the fluid passageways into the distal end of the casing and then drawn out through the channel to the proximal end of the casing.

In an advantageous embodiment, the channel delivers a composition to activate a particular drug being administered by the device.

The channel may also be used to receive an additional component. For example, a guide wire may be inserted for positioning the molecular exchange device into the desired position within a subject. Advantageously, a probe may be provided within the channel, such as electrical, sonic or optical probes, that may be used for detection and/or analysis. In a preferred embodiment, the channel may be exposed to the environment external to the device, to enable such a probe to have direct contact with the external environment. For example, a fibre optic or light source could be provided at the distal end of the molecular exchange device to allow guidance of the device during insertion into a subject.

Preferably, the proximal end of the casing is adapted for attachment to a catheter or cannulas", to accommodate insertion of the molecular exchange device into the subject. Insertion of the device using a catheter or cannular is a minimally invasive procedure.

More preferably, the proximal end of the casing is a lockable-mating arrangement or anchoring member for connecting to an invasive port, in a medical application, it is possible that the subject will already have an existing invasive port inserted, Therefore, preferably, the proximal end is a lockable- mating arrangement or anchoring member for connecting to an existing invasive port, which reduces damage caused by insertion of the molecular exchange device into the subject.

More preferably, the proximal end of the casing is adapted for attachment to a pump. The pump allows fluid to be pumped into the fluid passageways and/or drawn from the fluid passageways, to ensure flow of the fluid through the device. Fluid may flow in both directions through the fluid passageways of the device. The intended use of the individual fluid passageway will determine whether the pump provides fluid flow through the fluid passageway in one direction or both directions, As will be appreciated, when the device has two or more of fluid passageways, the supply to and/or return of fluid from each of the fluid passageways will depend upon its required function.

Advantageously, the proximal end of the casing is adapted for attachment to an external device. More advantageously, the proximal end of the casing is adapted for attachment to two or more of external devices, The one or more external devices may be attached directly to the ends of the fluid passageways at the proximal ends of the device or indirectly attached to the fluid passageways via connecting tubing.

In a preferred embodiment, the externa! devices analyse the composition of the fluid drawn from one or more of the fluid passageways. Advantageously, the external device determines the presence of one or more molecules in the fluid from the fluid passageways and/or measures the amount/concentration of one or more molecules in the fluid. More advantageously, the external devices control delivery of a drug into the patient through the molecular exchange device.

In an advantageous embodiment, the device can provide a self-maintaining mechanism for drug delivery, to maintain the concentration of the drug at a predetermined level.

In another arrangement of the invention, the system has a receptacle having first and second compartments which are fiuid!y sealed from one another; each compartment contains a fluid and provides the fluid to the molecular exchange area of the system by the action of gravity. The compartments can be integral with one another or separate to one another. The first compartment contains a perfusion fluid and the second compartment contains oil. in this arrangement, the flow rate of each fluid is controlled so that each fluid is introduced as continuously flowing droplets. Each fluid droplet has a fixed volume. The fluids have a reciprocal arrangement that allows them to feel into the molecular exchange device and subsequently the sensor unit in a desired arrangement, i.e. one droplet of oil followed by one droplet of perfusion fluid etc. This arrangement disperses the perfusion fluid and allows rapid detection of an analyte in the perfusion fluid. Alternating aqueous and oil droplets allows for sample segregation and later on allows reaction substances to the added to one or other drop so, for example, a coiour reaction can occur and be detected by an optical system. Sample

Any fluid sample potentially containing the ana!yte of interest can be introduced into the flow ceil having the electrochemical sensor.

In a preferred embodiment, the flow ceil will be connected to a molecular exchange device to enable continuous measurements to be taken from a subject. The fiuid sample travelling into the flow cell is a perfusate sample rather than blood itself. This means that the fluid does not need to be returned into the body; which is safer and mitigates the risk of contamination.

Perfusion fluid may be a sterile and/or isotonic fluid. The exact form of the perfusion fluid will depend upon the intended use of the monitoring system,

Perfusion unit

The perfusion fiuid can be transported to/from the flow cell of the sensor unit using a perfusion fluid, such as a pump or gravity feed system as described above. Those skilled in the art would appreciate pumps that can be utilized for this purpose. For example, the following pumps could be utilized:

Medtronic Paradigm™ pump, B. Braun Perfusor^ pump, AMV Medical Technic pump, Codan Argus infusion pump.

The perfusion fluid can be transported from and/or collected in a perfusion unit. The fluid will be held in a fiuid receptacle of the perfusion unit, in some arrangements, the pump and/or the receptacle of the gravity feed system is present in the perfusion unit. The perfusion unit and/or pump can be present in a container that is attached to the monitoring device. For example, the container may be attached the monitoring device in a clam shell arrangement. The container has a fastening mechanism to attach it to the monitoring unit. The fastening mechanism could, for example, be spring clips or a side release buckle. The fastening mechanism could also provide the retaining mechanism that holds the sensor unit in place against the monitoring unit.

The monitoring device and/or systems of the invention, as described above, can be utilized in a wide variety of environments and for a wide number of purposes. The monitoring device and system of the invention can be used to analyze water quality, for example in a factory setting. The factory water, for example, can switch from hard to soft, which may require changes to other parameters within the factory. It is known to use water cartridges to control the amount of calcium in water. Water cartridges are expensive and are thrown away after a defined volume (for example, 10,000 litres) of water have gone through them. This safety mechanism ensures that the filter is thrown away before it stops functioning correctly. To get as much use out of the filter as possible, the monitoring system of the invention can be used to measure the amount of calcium in the water that has passed through the filter, if the amount of calcium increases, this indicates that the filter is not functioning correctly and the filter can be replaced. This allows an accurate assessment of the functioning of the filter rather than a simply basing it on the volume of water that has flown through the filter. The monitoring system of the invention may also be used to detect a faulty filter, so it can be fixed or replaced. The monitoring device and/or delivery system of the invention can be used to deliver perfusion drugs to a human or animal subject. This is of maximum benefit in situations when a pump to deliver a perfusion drug is too expensive and. /or there is no power to drive the pump.

The monitoring device and/or delivery system of the invention can be used to deliver drugs into solid tumour. The selective transfer of the drug into the tumour can reduce the potential damage caused to cells in the surrounding environment.

The monitoring device and/or system of the invention can be used for quality control purposes, for example on a production line in a factory or other environment. The monitoring system can detect and/or quantify the amount of any substance that can cross membrane. For example, in a production line utilizing milk, the monitoring system can be uses to detect the lactate concentration to ascertain if the milk has gone off.

The monitoring device and/or system of the invention can be used to determine if a cow, or other milk producing mammal, is pregnant. The monitoring system can measure ieutinising hormone in combination with estradiol in cow's milk to determine if the cow is pregnant. This is currently achieved by taking a blood sample. The molecular exchange area of the monitoring system of the invention can be dipped into the milk to be tested.

The monitoring device and/or system of the invention can be used in a medical/domestic facility. For example, the monitoring system can be used to detect for the presence of an analyte in urine, in this arrangement, the molecular exchange area can be positioned in the toilet bowl (or other container) and the sensor unit and/or monitoring unit can wireiessiy transmit the data to an external control unit, such as via Bluetooth©. The external control unit, such as a mobile phone, may be programmed to turn the sensor and/or monitoring unit on when it is in close proximity. The perfusate fluid is well buffered so flushing or cleaning the toilet bowl will have no detrimental effect to the molecular exchange. For example, the monitoring system can be used to test for diabetes or pregnancy. When testing for diabetes, for example in a diabetes clinic, the anaiyte detected by the sensor unit is glucose. When testing for pregnancy, for example in a doctors' surgery, maternity unit or in at home, the anaiyte to be detected is beta subunit of human chorionic gonadotropin; or leutinising hormone in combination with estradiol.

The monitoring device and/or system of the present invention can also be used for a colorimetric assay to detect an anaiyte present in a non- transparent fluid. Colorimetric assays use reagents that undergo a measurable color change in the presence of the anaiyte. However, colorimetric assays cannot usually be used if the anaiyte is present in a non-transparent fluid, because the colour change may not be visible. For example, a colour change cannot readily be determined when the fluid is liquid or blood. However, perfusion fluid is transparent, is the anaiyte of interest can be selected from the subject and a colorimetric assay can be used. Colorimetric tests are well known in the art. These could be used to test for toxicity, such as aspirin or paracetamol, present in blood or urine, or simply used in a setting where there is not sufficient funding for a pump or battery, such as a developing country.

JBcamjg|e§

As illustrated in figure 1 , a first embodiment of a monitoring device (1 ) for detection of and/or measuring the amount of an anaiyte or plurality of ana!ytes in a fluid, according to the present invention, comprises a monitoring unit (2) having an eiectroanaiyticai component (3) connected to a first electrical contact; and a sensor unit (4) having a sensor arrangement (5) connected to a second electrical contact, wherein the monitoring unit (2) and the sensor unit (4) have a first cooperating attachment arrangements to hold the monitoring unit (2) and the sensor unit (4) together releasably in a first attached configuration, and in the first attached configuration the first and second electrical contacts are brought together in direct eiectrical communication with one another, in this embodiment, and as shown in Figure 2a, the monitoring unit has a casing (6) that fully encapsulates the electronic components of the monitoring unit (2) to form a sealed unit. The casing (6) forms a monitoring unit (2) having top surface (13), a bottom surface (14) and a substantially perpendicular side surface (15) extending from the top surface (13) to the bottom surface (14). The recess (7) of the monitoring unit (2) is positioned in the bottom surface (14) and the side surface (15). A first electrical contact (1 1 ), having three electrical connectors in the form of pads, is positioned in the recess. The sensor unit (4) is partially placed in the recess (7), when it is in its first attached configuration.

As shown in Figure 2a, the recess (7) has a base wall (20) and side wail (21 ) that do not include any sharp internal angles so that ail parts of the recess (7) can be accessed and cleaned.

As illustrated in Figures 1 , and 2c, the first cooperating attachment arrangement is in the form of a base plate (8). Two clip mechanisms (9) attach the base plate (8) to the monitoring unit (2), and a third clip mechanism (10) attaches the base plate (8) to the sensor unit (4) when the sensor unit is positioned in the recess in the first attached configuration. The base plate (8) is held against the bottom surface of the monitoring device (2).

Figure 3 further illustrates the monitoring unit (2) and sensor unit (4) in a detached arrangement. As can be seen in figure 2b and 3. a part (42) of the sensor unit (4) is shaped to fit into the recess (7) of the monitoring unit (2), and be held against the third clip mechanism (10) of the base plate (8) when in the first attached configuration. As illustrated in Figure 2a, the monitoring unit (2) has a first electrical contact (1 1 ) housed in the recess (7). The portion of the sensor unit (4), which is positioned in the recess (7) of the monitoring unit (2) when in the first attached configuration, houses a second electrical contact (12), as shown in Figure 3, When the sensor unit (4) is in the attached configuration, the first electrical contact (1 1 ) of the monitoring unit (2) and the second electrical contact (12) of the sensor unit (4) are in direct contact with one another. This arrangement ensures that there Is good electrical communication between a first electrical contact (1 1 ) of the monitoring unit (2) and a second electrical contact (12) of the sensor unit (13).

3n this embodiment, the first electrical contact (1 1 ) has three connectors, each in the form of a contact pad, and the second electrical contact (12) has three connectors, each in the form of a spring clip. Each of the pads (1 1 ) is in direct contact with one of the spring clips (12), when the monitoring unit (2) and the sensor unit (4) are in the first attached configuration.

In this embodiment, the base plate is attached to a strap (19) to allow the monitoring device (1 ) to be held on the patient, such as a wrist strap, or being held in position in a different environment.

The monitoring device of this embodiment has a rechargeable battery within the sealed casing. As shown in Figure 5, the monitoring unit (2) and the battery charging unit (17) have a second cooperating attachment arrangements to hold the monitoring unit (2) and the battery charging unit (17) together releasably in a second attached configuration, in this embodiment, the base piate (8) also forms part of the second cooperating attachment arrangement. The same c!ip mechanisms (9) attach the base plate (8) to the monitoring unit (2), and the battery charging unit (17) has a protrusion (10) that forms part of the third clip mechanism with the base plate (8). This arrangement holds the battery charging unit (17) in the recess (7) of the monitoring unity in the second attached configuration.

As shown in figure 2a, the recess (7) houses a third electrical contact (16), having two connectors in the form of contact pads, that form direct contact with a fourth electrical contact (18) of a battery charging unit (17), as shown in Figure 7. in the second attached configuration the third and fourth electrical contacts (16; 18) are brought together in direct electrical communication with one another, in this embodiment, the sensor unit (4) and the battery charging unit (17) cannot be positioned in the recess (7) of the monitoring unit (2) at the same time, because they have the same size and configuration that fills the entire space of the recess (7),

Moreover, as shown in figure 2a, the three connectors of the first electrical contact (11 ) are positioned in the recess (7) further away from the outer edge of the recess than the two connectors of the third electrical contact (18). This arrangement means that the two connectors of the fourth electrical contact (18) of the battery charging unit will not need to pass over the three connectors of the first electrical contact (1 1 ) when being placed into position in the recess (7) for charging.

In an alternative arrangement, shown in figures 8a and 8b, the first and third electrical contacts (11 ; 16) positioned in the recess (7) of the monitoring unit (2) can be positioned on opposite sides of the recess (7); such that the three connectors of the fourth electrical contact (18) of the battery charging unit (17) will not need to pass over the three connectors of the first electrical contact (1 1 ) when being placed into position in the recess (7) for charging. The skilled person would appreciate that a number of arrangements, such as those shown in figures 8a to 8c can be used to achieve the function of ensuring that the fourth electrical contact (18) of the battery charging unit (17) will not pass over the first electrical contact (1 1 ) when being placed into the recess (7) of the monitoring unit (2). For example, in figure 8c, the pattern of the three connectors of the first electrical contact (1 1 ) with respect to the three connectors of the third electrical contact (16) ensures that the three connectors of the fourth electrical contact (18) of the battery charging unit (17) will not need to pass over the three connectors of the first electrical contact (11 ), when the battery charging unit (17) is placed into the recess (7) of the monitoring unit (2). As shown in figures 9a to 9h, the three connectors of the second electrical contact (12) of the sensor unit (4) and the three connectors of the fourth electrical contact (18) of the battery charging unit (17) are positioned so that they can make an electrical connection with their respective connectors of the first and third electrical contacts (1 1 ; 16) in the recess (7) of the monitoring unit (7). The battery charging unit (17) shown in figure 9a and the sensor unit (2) shown in figure 9b can be used with the monitoring device shown in figure 2a, The battery charging unit (17) shown in figure 9c and the sensor unit (2) shown in figure 9d can be used with the monitoring device shown in figure 8a, The battery charging unit (17) shown in figure 9e and the sensor unit (2) shown in figure 9f can be used with the monitoring device shown in figure 8b. The battery charging unit (17) shown in figure 9g and the sensor unit (2) shown in figure 9h can be used with the monitoring device shown in figure 8c. In this arrangement, and as shown in figures 1 , 2b, 3 and 4, the sensor unit (2) has a flow cell (26) having a fluid input (22) and a fluid output (23), The fluid input (22) is attached to a fluid source, present for example in a perfusion unit, via fluidic tubing. The perfusion fluid may travel from the perfusion unit to a molecular exchange device prior to entering the sensor unit. The fluid output (22) is attached to a fluid receptacle via fluidic tubing.

The sensing arrangement (5) is has an electrochemical sensor. The electrochemical sensor has a base layer, such as a ceramic chip, having three electrodes; a reference electrode, a sensing electrode and an auxiliary electrode. The electroana!ytical component (3) of the monitoring unit (2) is a potentiostat.

The electrochemical sensor comprises a substrate recognition molecule that has selective recognition for the analyte of interest (i.e. the analyte being detected). The recognition substrate may bind to the analyte of interest directly or indirectly, or bind to a converted product of the analyte of interest, directly or indirectly. The binding of the recognition substrate to an analyte or converted product creates an oxidized or reduced product which changes the current at the working electrode. The change in current is detected by the potentiostat, which enables the presence and/or amount of analyte to be determined in the fluid. in this embodiment, the fluid is pumped from the fluid source to the sensor unit (4) via the fluidic tubing. The fluid passes over the sensor arrangement and travels out of the sensor unit via the fluid outlet (23) and along the fluid tubing to a receptacle. The sensor arrangement (5) detects the presence and/or quantity of an analyte in the fluid sample introduced into the sensor unit (2). The sensor unit (4) transmits the data to the electroanaiyticai component (3) of the monitoring unit (2) via their respective first and second electrical contacts (1 1 ; 12); and the data is transmitted to a visual display on the monitoring unit (2) and/or transmitted wireiessly from the electroanaiyticai component (3) to an external control unit. Figure 10 illustrates a system having a monitoring unit (2) and sensor unit (4); the sensor unit (4) having two flow cells (26). In this arrangement, each flow cell (26) has a sensor arrangement (5) connected to the same electroanalytica! component (3) of a single monitoring unit (2). The flow cells (26) each have a fluid inlet (22) and a fluid outlet (23). The flow cells (28) can be connected to the same or a different fluid source via their respective fluid inlets (22), and connected to the same or different fluid receptacles via their outlets (23). The different sensor units (4) can be used to detect or measure the amount of the same anaSyte and/or different anaiytes. in an alternative embodiment shown in figure 1 1 , there is a system having a monitoring unit (2) and sensor unit (4); the sensor unit (4) having two flow ceils (26). In this arrangement, each flow cell (26) has a sensor arrangement (5) connected to the same electroanaiytical component (3) of a single monitoring unit (2). The flow cells (26) each have a fluid inlet (22) and a fluid outlet (23). The flow cells (28) are arranged in fluid communication with one another, such that the fluid outlet (23) of one of flow cells (28) is connected to the fluid inlet (22) of the of the other flow cell (26). In this way, the flow cells have a single fluid source and a single fluid outlet receptacle; and the fluid transported through one of the flow cells (26) is then transported into the next flow ceil (26) via fluidic tubing. The different flow cells (26) can be used to detect or measure the amount of the same analyte and/or different anaiytes. The system can have additional flow cells arranged in fluid communication with one another. The system can also have additional flow ceils not in fluid communication with one another, as described above and shown in figure 10.

In an alternative arrangement shown in figure 12, the system has a single monitoring unit (2) and two sensor units (4); each sensor unit (4) has at least one flow cell (26), as described above, with a sensor arrangement (5) connected to the same electroanalytical component (3) of a single monitoring unit (2). In the arrangement shown in figure 12, each sensor unit (4) has a flow cell (26) having a sensor arrangement (5) connected to the same electroanalytical component (3) of a single monitoring unit (2), The sensor units (4) each have a fluid inlet (22) and a fluid outlet (23). The sensor units (4) are arranged in fluid communication with one another, such that the fluid outlet (23) of one of sensor units (4) is connected to the fluid inlet (22) of the of the other sensor unit (4). In this way, the sensor units have a single fluid source and a single fluid outlet receptacle; and the fluid transported through the flow cell (28) of one of the sensor units (4) is then transported into the flow cell (26) of the next sensor unit (4) via fiuidic tubing. The different sensor units (4) can be used to detect or measure the amount of the same analyte and/or different analytes.

Figure 13 illustrates a system having two monitoring devices; each monitoring device having a monitoring unit (2) and a sensor unit (4) as described above with respect to figures 1 to 12. In the arrangement shown in figure 13, each sensor unit (4) has a flow cell (26) having a sensor arrangement (5) connected to the respective electroanalytical component

(3) of their monitoring unit (2), i.e. the sensor arrangements are connected to different electroanalytical components. The sensor units (4) each have a fluid inlet (22) and a fluid outlet (23). The sensor units (4) are arranged in fluid communication with one another, such that the fluid outlet (23) of one of sensor units (4) is connected to the fluid inlet (22) of the of the other sensor unit (4). In this way, the sensor units have a single fluid source and a single fluid outlet receptacle; and the fluid transported through the flow cell (26) of one of the sensor units (4) is then transported into the flow cell (26) of the next sensor unit (4) via fiuidic tubing. The different sensor units

(4) can be used to detect or measure the amount of the same analyte and/or different analytes. Each of the sensor units can have one or more additional flow cells arranged in fluid communication with one another as described in figure 1 1 and/or one or more additional flow cells not in fluid communication with one another as shown in figure 10, In all of the arrangements shown in the figures 1 to 4 and 8 to 13, each of the sensor units and/or flow cells can have more than one sensing arrangements. Each of the sensing arrangements is connected by a channel to a separate working electrode. Each sensing arrangement can detect or measure the amount fo the same anaSyte and/or a different analyte.

Figure 14 illustrates the parts of a sensor unit (4) in accordance with the invention. The sensor unit (4) has a two part outer casing; a lower casing (27) and an upper casing (28). The lower and upper casing (27; 28) are held together by four screws in the region of the flow cell, and a clip arrangement (30) at the end of the sensor unit (4) that is inserted into the recess (7) of the monitoring unit (2). In a preferred embodiment, the clip arrangement (30) is formed of non-metal materials to avoid any metal components going over the first electrical contact (1 1 ) of the monitoring unit (2) and prevent any potential damage to the electrical contact. In this embodument, the clip arrangement is a snap fit clip arrangement, but other clip arrangements are known in the art.

The sensor unit (4) is put together by placing the electrochemical sensor in the form of a ceramic chip (31 ) inside the lower casing (27), The ceramic chip (31 ) has three electrodes; a reference electrode, a working electrode and an auxiliary electrode. Each electrode (32; 33; 34) has a channel (35) for connection with the electrical contact (12) of the sensor unit for electrical connection with the electrical contact (1 1 ) of the monitoring unit (2)_s which connect to the potentiostat. The electrical contact (12), having three connectors, are placed on top of the ceramic chip such that they are aligned with cut-outs (36) in the upper casing (28). When the lower and upper casings (27; 28) are held together, the three electrical connectors (12) are partially pushed through one the three cut-outs so that they are in position to make an electrical connection with the electrical contact (11 ) of the monitoring unit (2), when they are in their attached arrangement.

In this arrangement, the recognition substrate is positon on the working electrode. A first O ring is placed on top of the electrodes; and a flow ceil unit (38) is placed on top of the O ring. This arrangement The flow cell unit (38) is formed of any suitable material, such as Plexiglas®. This arrangement minimised the amount of material that needs to be used to minimise cost. The flow ceil unit (38) has four screw holes aligned with the screw holes in the lower and upper casing (27; 28) such that the sensing arrangement is held together by the screws (29) when the lower and upper casing (27; 28) are held together. The flow cell unit has a fluid input (22) and a fluid output (23) for fluid to ingress and egress the flow cell. Fluidtc tubing (39) can be inserted into the fluid input and output (22; 23) to carry fluid from the fluid source to the waste receptacle.

The bottom of the flow cell unit (38) has an opening which sits on top of the O ring and seals the flow cell. Any fluid passing into the fluid input (22) and out through the fluid output (23) passes over the electrodes (32; 33; 34), and hence the recognition substrate. There are to second O rings that are positioned around the inlet (22) and outlet (23), and fit into grooves of the lower and upper casing (27; 28) to provide a seal when the casings are held together. The upper casing (28) is placed on top of this arrangement; the clip mechanism (30) clips together and the screws (29) are screwed through the lower casing (27), the flow cell unit (38) and into the upper casing (28); which holds the sensor unit in position. The top of the upper casing (28) has an opening such that the top of the flow ceil unit (38) is visible when the casings (27; 28) are held together. The flow celi unit (38) is made of a transparent material. This means that the sensing arrangement within the flow celi is visible.

Figure 15 illustrates a system having a monitoring device (1 ) as described above, connected via fluidic tubing (39) to a molecular exchange device (43), which is connected via fluidic tubing (39) to the fluid source (47) positioned in a perfusion unit (49).

The perfusion unit (49) houses the fluid source (47) and pump (48). In this arrangement, the fluid source is in the form of a perfusion fluid filled syringe. The pump (48) compresses the piston of the syringe to transport perfusion fluid into the fluidic tubing (39) connected to the inlet (45) of the molecular exchange device (43), The fluid travels down a fluid passageway to the tip (45) of the molecular exchange device (43), The tip (45), which is positioned in the patient or an environment during use has a porous area over which molecular exchange can occur, i.e. an anaiyte to be detected and/or measured can enter the perfusion fluid from the patient or environment in which it is positioned, The fluid is then transported to the outlet (44) of the device (43) and transported to the fluid inlet (22) of the sensor unit (4) via fluid tubing (39), The fluid passes through the flow cell of the sensor unit (2) which houses the sensor arrangement (5) and out through the fluid outlet (23) of the sensor unit (4). In this arrangement, the sensor unit (4) of the monitoring device (1 ) is positioned in the recess (7) of the monitoring unit (2) and held in position by a base plate (8),

The anaiyte to be detected and/or measured is present in the subject or environment in which the molecular exchange device (43) is positioned, The anaiyte passes through the porous area of the molecular exchange device (43) via molecular exchange, The anaiyte is detected by the sensing arrangement (5) of the sensor unit (4), which results in a change in the current. The potentiostat of the monitoring unit (2) records the change in current, via the first and second electric contacts (1 1 ; 12) of the monitoring unit (2) and the sensor unit (4), The change in current can be used to determine the presence of an anaiyte in the fluid sample passing though the sensor unit (4). The magnitude of the change in current can be used to determine the amount of the anaiyte present in the fluid sample passing through the sensor unit (4). The data is transmitted to a visual display (50), which in this embodiment is present on the perfusion unit. The data is transmitted wirelessly by Bluetooth©. The data can also be transmitted to an externa! control unit, such as a persona! computer, tablet or smartphone (not shown). The external control unit allows data to be stored and analysed effectively, rapidly, and accurately. The monitoring unit (4) is powered by a rechargeable battery.

Figure 16 illustrates the system illustrated in Figure 15 being used on a human patient. The tip (not shown) of the molecular exchange device (43) is positioned in the arm (51 ) of a patient. The monitoring device (1 ) has a strap (9) attached to the base unit (8), which allows the monitoring device (1 ) to be held in place by positioning the strap (9) around the arm (51 ) of the patient. The perfusion unit (49) that provides perfusion fluid to the molecular exchange device (43) via the fluidic tubing (39) is not shown in figure 16.

As illustrated in figure 17, there is a first embodiment of a monitoring system (52) comprising a receptacle (53) for containing a fluid and adapted to allow the fluid to flow from the receptacle (53); a molecular exchange area (55); a supply conduit (56) defining a fluid path from the receptacle (53) to a molecular exchange area (55); and an outlet conduit (56) defining a fluid path from the molecular exchange area (55) to an outlet port (57), the outlet port (57) adapted to be connected to a sensor unit (4) of the monitoring device (1 ) of figures 1 to 16; wherein, in use, the receptacle (52) is positioned above the supply conduit (54), molecular exchange area (55), outlet conduit (56), and monitoring device (1 ) such that the fluid is transported from the receptacle (53) to the sensor unit by the action of gravity.

In use, fluid contained in the receptacle (53) will be transported to the supply conduit, by the action of gravity, to provide a continuous flow of fluid to the molecular exchange area. The molecular exchange area has an exchange aperture (58) having a porous membrane across which the analyte to be detected will cross from the external environment into the molecular exchange area. The fluid will be transported from the molecular exchange area (55) to the outlet (57) of the outlet conduit (56), and into the sensor unit. The sensor unit may be any form of arrangement that enables defection of the analyte.

As illustrated in figure 18, there is a second embodiment of a monitoring system where the molecular exchange area (55) is in the form of a molecular device. The monitoring system (52) comprises a receptacle (53) for containing a fluid and adapted to allow the fluid to flow from the receptacle (53) by the action of gravity; a molecular exchange area(55); a supply conduit (54) defining a fluid path from the receptacle (53) to a molecular exchange area (55); and an outlet conduit (58) defining a fluid path from the molecular exchange area (55) to an outlet port (56), the outlet port (57) adapted to be connected to a sensor unit; wherein, in use, the receptacle (53) is positioned above the supply conduit (54), molecular exchange area (55), and outlet conduit (56) such that the fluid is transported from the receptacle (53) to the sensor unit by the action of gravity,

The molecular exchange area in the form of a device has a casing (65) supporting two fluid passageways (64a, 64b) extending from the proximal end to the distal end; two aligned exchange apertures, between the proximal end and the distal end of the casing, exposing the fluid passageways (64a, 64b). The portion of the fluid passageways (64a, 64b) exposed by the opposed exchange apertures are porous. The fluid passageways (64a, 64b) provide a single path of fluid through the device.

In use, fluid contained in the receptacle (53) will be transported to the supply conduit by the action of gravity to provide a continuous flow of fluid to the molecular exchange area, The fluid flows from the supply conduit (54) into the fluid passageway (64a) from the proximal end to the distal end; and returns from the distal end to the proximal end through fluid passageway (64b) to the outlet conduit (66). The molecular exchange device has an exchange aperture (58a, 58b) that expose the fluid passageways (64a, 64b) across which the anaiyte to be detected will cross from the external environment into the molecular exchange area (55). The fluid will be transported from the molecular exchange area (55) to the outlet (57) of the outlet conduit (56), and into the sensor unit. The sensor unit may be any form of arrangement that enables detection of the anaiyte.

As illustrated in figure 19, there is a first embodiment of a delivery system (12) comprising a receptacle (2) for containing a fluid and adapted to allow the fluid to flow from the receptacle (2) by the action of gravity; a molecular exchange area (4); and a supply conduit (3) defining a fluid path from the receptacle (2) to a molecular exchange area (4); wherein, in use, the receptacle (2) is positioned above the supply conduit (3) and molecular exchange area (4) such that the fluid is transported from the receptacle (2) to the sensor unit by the action of gravity. !n use, fluid contained in the receptacle (2) will be transported to the supply conduit by the action of gravity to provide a continuous flow of fluid to the moiecular exchange area. The molecular exchange area has an exchange aperture (7) across which the substance to be delivered will cross from molecular exchange area into the external. The exchange aperture (7) is porous to allow the transfer of a substance from the molecular exchange area (4) into the external environment.

Figure 20 illustrates an embodiment of a molecular exchange area in the form of a device that may be part of the monitoring system or the delivery system discussed above, and/or in combination with the monitoring device described above and illustrated in figures 1 to 16. The molecular exchange device has a casing (65) supporting two fluid passageways (64a, 64b) extending from the proximal end to the distal end; two aligned exchange apertures, between the proximal end and the distal end of the casing, exposing the fluid passageways (84a, 64b). The portion of the fluid passageways (64a, 64b) exposed by the opposed exchange apertures are porous. The fluid passageways (64a, 64b) provide a single path of fluid through the device.

In use, fluid contained in the receptacle (53) will be transported to the supply conduit by the action of gravity to provide a continuous flow of fluid to the molecular exchange area. The fluid flows from the supply conduit (54) into the fluid passageway (64a) from the proximal end to the distal end; and returns from the distal end to the proximal end through fluid passageway (64b) to the outlet conduit (58).

Figure 21 illustrates an embodiment of a molecular exchange area that may be part of the monitoring system or the delivery system discussed above, and/or in combination with the monitoring device described above and illustrated in figures 1 to 16. The molecular exchange device has a casing (65) supporting a fluid passageways (64) extending through the molecular exchange area, such that one end can connect to the supply conduit and the other end can connect to the outlet conduit; and an exchange aperture exposing the fluid passageway (64). The portion of the fluid passageway (64) exposed by the opposed exchange apertures are porous. The fluid passageway (64) provides a single path of fluid through the molecular exchange area.

Figure 22a and figure 22b illustrates an embodiment of the monitoring system (52) comprising a first receptacle (53) for containing a fluid and adapted to allow the fluid to flow from the receptacle (53); a molecular exchange area (55); a supply conduit (54) defining a fluid path from the receptacle (53) to a molecular exchange area (55); and an outlet conduit (56) defining a fluid path from the molecular exchange area (53) to an outlet port (57), the outlet port (57) connected to a second receptacle (59). There is a first sensor unit (60), which is part of a monitoring device as described above and illustrated in figures 1 to 16, which is positioned between the first receptacle (53) and the molecular exchange area (55); connected via the supply conduit (54). There is a second sensor unit (61 ), which is part of a monitoring device as described above and illustrated in figures 1 to 16, which is positioned between the molecular exchange area (55) and a second receptacle (59); connected via the outlet conduit (56). The second receptacle (59) is attached to the outlet port (57).

In the arrangement shown in figure 22a, the first receptacle (2) is in an elevated position with respect to the other components of the system. The fluid can flow from the first receptacle (2) along the supply conduit (3), through the sensor unit (9), and from the first sensor unit (9) to the molecular exchange area (4) via the supply conduit (3); through the molecular exchange area (4); where selective transfer of materials can occur across the porous exchange aperture (7); and the fluid containing the selected materials is then taken through the second sensor unit (10) to the second receptacle (8) via the outlet conduit (5). The transport of the fluid is driven by gravity. In the arrangement of figure 22a, the first sensor unit (60) determines the amount of analyte present in the fluid before the fluid is introduced into the molecular exchange area (55), and the second sensor unit (81 ) determines the amount of analyte present in the fluid after the fluid has travelled through the molecular exchange area (55). The difference in the readings of the target analyte(s) between the two sensor units (60; 61 ) can be utilised to determine the change in the amount of the analyte.

In the arrangement shown in figure 22b, the second receptacle (59) has been switched with the first receptacle (53), in that the second receptacle (59) is in an elevated position with respect to the other components of the system. The same fluid can flow from the second receptacle (59) along the outlet conduit (56) (acting as a supply conduit), through the second sensor unit (61 ), and from the sensor unit (61 ) to the molecular exchange area (55) via the outlet conduit (56); through the molecular exchange area (55), where selective transfer of materials can occur across the porous exchange aperture (58); and the fluid containing the selected materials is then taken through the first sensor unit (9) to the first receptacle (53) via the in!et conduit (54) (acting as an outlet conduit). The transport of the fluid is driven by gravity.

In the arrangement of figure 22b, the second sensor unit (61 ) determines the amount of analyte present in the fluid before the fluid is introduced into the molecular exchange area (55), and the second sensor unit (60) determines the amount of analyte present in the fluid after the fluid has travelled through the molecular exchange area (55). The difference in the readings of the target analyte(s) between the two sensor units (61 ; 60) can be utilised to determine the change in the amount of the analyte. This arrangement allows the same fluid to be utilised to monitor a change in the amount of an anaSyte in the subject in which the molecular exchange area (55) is positioned.

When used in this specification and claims, the terms "comprises" and "comprising" and variations thereof mean that the specified features, steps or integers are included. The terms are not to be interpreted to exclude the presence of other features, steps or components.

The features disclosed in the foregoing description, or the following claims, or the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for attaining the disclosed result, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

Claims

1 . A monitoring device for detection of and/or measuring the amount of an analyte or plurality of analytes in a fluid comprising:

a monitoring unit having an electroanalytical component connected to a first electrical contact; and

a sensor unit having a sensor arrangement connected to a second electrical contact;

wherein the monitoring unit and the sensor unit have a first cooperating attachment arrangements to hold the monitoring unit and the sensor unit together releasably in a first attached configuration, and in the first attached configuration the first and second electrical contacts are brought together in direct electrical communication with one another.

2. A monitoring device according to claim 1 , wherein the monitoring unit comprises a casing with a recess, and the first electrical contact is position in the recess; and in the first attached configuration at least a part of the sensor unit is housed in the recess and held in position by the cooperating

attachment mechanism.

3. A monitoring device according to claim 2, wherein the casing is sealed.

4. A monitoring device according to any one of claims 2 to 3, wherein the width of the casing is from 50 to 100mm, and preferably 60 to 70mm; the depth of the casing is from 30 to 50mm, and preferably 40 to 45mm; and/or the height of the casing is from 4 to 8mm, and preferably 6 to 7mm.

5. A monitoring device according to any one of claims 2 to 4, wherein the width of the recess is from 8 to 25mm, and preferably 1 1 to 20mm; the depth of the recess is from 12 to 20 mm, and preferably 14 to 16mm; and the height of the recess is from 3 to 5mm, and preferably 3 to 4mm.

6. A monitoring device according to any one of claims 2 to 5, wherein the casing of the monitoring unit has a top and a bottom surface and a

substantially perpendicular side surface extending from the top surface to the bottom surface; and a recess having a bottom wall and side wall formed in the bottom surface and the side surface of the casing, wherein the first

cooperating attachment arrangement prevents the sensor unit being removed from the base wall and side wall of the recess in the attached arrangement.

7. A monitoring device according to claim 6, wherein the walls of the recess do not include any sharp internal angles.

8. A monitoring device according to any one of claims 6 to 7, wherein the base wall is substantially planar and parallel to the bottom surface of the casing, and the side wall takes the form of three sides of a rectangle.

9. A monitoring device according to any one of claims 6 to 8, wherein the angle between the base wall and each side wall is between 90° and 175°; or the angle between the base wall and the side wall can be between 45° to 85°.

10. A monitoring device according to any one of claims 6 to 8, wherein the junctions between the base wall and the side wall have a radius.

1 1 . A monitoring device according to any one of the preceding claims, wherein the first electrical contact has one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more electrical connectors .

12. A monitoring device according to any one of the preceding claims, wherein the second electrical contact has one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more electrical connectors .

13 A monitoring device according to any one of the preceding claims, wherein at least one of the connectors of the first and/or the second electrical contacts are in the form of an electrical contact pad.

14. A monitoring device according to claim 8, wherein the at least one electrical pad is a spring connector, a flat plate, a flat plate with one or more spring connector, or a flat plate with a one or more connectors.

15. A monitoring device according to any one of the preceding claims, wherein one of the first and second electrical contact pads is a flat plate and the other is a spring connector.

16. A monitoring device according to any one of the preceding claims, wherein the electroanalytical component is a potentiostat, coulometer or a voltmeter.

17. A monitoring device according to any one of the preceding claims, wherein monitoring unit further comprises an Electrically Erasable

Programmable Read-Only Memory (EEPROM) unit, and the data provided by the electroanalytical component is cached onto the EEPROM.

18. A monitoring device according to claim 17, wherein the monitoring unit further comprises a component configured to wirelessly transmit the data to an external control unit

19. A monitoring device according to any one of the preceding claims, where the sensor unit comprises at least one flow cell housing a sensor arrangement.

20. A monitoring device of claim 19, wherein the sensor unit comprises two or more flow cells.

21 . A monitoring device according to any one of the preceding claims, wherein the sensor arrangement comprises an electrochemical sensor or an optical sensor.

22. A monitoring device according to claim 21 , wherein the electrochemical sensor has at least two electrodes.

23. A monitoring device according to any one of claims 21 to 22, wherein the electrochemical sensor has a reference electrode and at least one working electrode.

24. A monitoring device according to any one of claims 22 to 23, wherein the electrochemical sensor further comprises one or more auxiliary

electrodes.

25. A monitoring device according to any one of claims 21 to 23, wherein the electrochemical sensor comprises one, two, three, four, five, six, seven, eight, nine, ten or more working electrodes.

26. A monitoring device according to claim 21 , wherein the sensor arrangement is an optical sensor having a light source and a receiving unit.

27. A monitoring device according to any one of the preceding claims, wherein the sensor unit comprises one, two, three, four, five, six, seven, eight, nine or more sensor arrangements.

28. A monitoring device of any one of the preceding claims, further comprising one or more additional sensor units.

29. A monitoring device according to any one of the preceding claims, wherein the sensing arrangement comprises a recognition substrate that has selective recognition of the analyte of interest.

30 A monitoring device according to claim 29, wherein the recognition substrate binds to the analyte of interest directly or indirectly.

31 . A monitoring device according to claim 29, wherein the recognition substrate binds to a converted product of the analyte of interest.

32. A monitoring device according to any one of the preceding claims, wherein the sensor arrangement further comprises an immobilised enzyme reactor (IMER).

33. A monitoring device according to claim 32, wherein the recognition substrate is selected from an enzyme, an antibody, an aptamer, and/or material imprinted polymers (MIPS).

34. A monitoring device according to any one of the preceding claims, wherein the fluid source for the sensor unit is a molecular exchange device or a receptacle.

35. A monitoring device according to any one of the preceding claims, wherein the first cooperating attachment arrangement is in the form of a base plate releasably held against the bottom surface of the monitoring unit that holds the sensor unit in the first attached configuration in the recess.

36. A monitoring device according to claim 35, wherein the base plate has a clip mechanism that that connects to a clip mechanism on the sensor unit.

37. A monitoring device according to any one of claims 1 to 34, wherein the first cooperating attachment arrangement is integral with the monitoring unit, and optionally comprises a protrusion that fits into a recess on the sensor unit.

38. A monitoring device according to any one of the preceding claims, wherein the monitoring unit further comprises a rechargeable battery that powers the monitoring device.

39. A monitoring device according to claim 38, further compromises a component for inductive charging of the rechargeable battery.

40. A monitoring device according to claim 38, further comprising a battery charging unit for charging the rechargeable battery.

41 . A monitoring device according to claim 40, wherein the battery charging unit is configured to be housed in the recess of the monitoring unit, when the sensor unit is not in the first attached configuration.

42. A monitoring device according to any one of claims, 40 to 41 , wherein the monitoring device has a third electrical contact positioned in the recess and the battery charging unit has a forth electrical contact, wherein the monitoring unit and the battery charging unit have a second cooperating attachment arrangements to hold the monitoring unit and the battery charging unit together releasably in a second attached configuration, and in the second attached configuration the third and fourth electrical contacts are brought together in direct electrical communication with one another.

43. A monitoring device according to claim 42, wherein the first and third electrical contacts of the monitoring unit are positioned in the recess of the monitoring unit.

44. A monitoring device according to any one of claims 42 to 43, wherein the first and second cooperating attachment arrangements are the same as one another.

45. A monitoring device according to any one of the preceding claims, wherein the monitoring unit further comprises an operating button to turn on and off the monitoring device; and/or stop and start the electrochemical sensor.

46. A monitoring device according to claim 45, wherein the button is positioned beneath an elastic membrane bonded to the sealed casing of the monitoring unit.

47. A monitoring device according to claim 46, wherein the button is positioned on the bottom surface of the monitoring unit.

48. A monitoring device according to any one of the preceding claims, wherein the monitoring unit comprises a component for receiving a wireless signal to turn on and off the monitoring device; and/or stop and start the electrochemical sensor.

49. A monitoring device according to any one of the preceding claims, wherein the monitoring unit further comprises a visible and/or audible signal to indicate the functioning of the device.

50. A monitoring device according to claim 49, wherein the function of the device is selected from: that the monitoring unit and/or sensor unit is/are on or off; that the device is taking measurements; that the device is transferring data; that the device is transferring a certain level of data; that the device is transferring a data dump; and/or that the rechargeable battery needs charged or is fully charged.

51 . A monitoring device according to claim 49, wherein the visible signals for different functions are distinguished by the number signals, different colour signals, and/or flashing signals.

52. A monitoring device according to any one of claims 49 to 51 , wherein the visible signal is one or more LEDs.

53. A sensor unit according to any one of claims 1 to 52.

54 A monitoring unit according to any one of claims 1 to 52.

55 A system comprising:

at least one monitoring device of any one of claims 1 to 52;

an external control unit;

a fluid source;

a battery charging unit; and/or

a perfusion unit. A system according to claim 55, wherein the fluid source is a molecular