A surface-enhanced raman spectroscopy (SERS) cartridge

Abstract

A Surface-Enhanced Raman Spectroscopy (SERS) cartridge (10) for use with a Raman spectrometer, the cartridge comprising a body, receiving means (20) for receiving an analyte in the form of a fluid, and a transport layer (60) for moving the analyte to a probe, the probe comprising a first nanoparticle (70) having first predefined characteristics so as to increase the detectability of Raman scattered light reflected therefrom, in use.

Description

A Surface-Enhanced Raman Spectroscopy (SERS) cartridge

[0001] The present invention relates generally to a Surface-Enhanced Raman Spectroscopy (SERS) cartridge and a method of analysing an analyte using such a cartridge.

[0002] SERS is a technique known to enhance Raman scattering by adsorbing molecules of an analyte on metal surfaces or nanostructures such as nanotubes. Known means for presenting analytes to a spectroscope are relatively basic and laboursome.

[0003] In a first aspect, the present invention provides a Surface-Enhanced Raman Spectroscopy (SERS) cartridge for use with a Raman spectrometer, the cartridge comprising a body, receiving means for receiving an analyte in the form of a fluid, and a transport layer for moving the analyte to a probe, the probe comprising a first nanoparticle having first predefined characteristics so as to increase the detectability of Raman scattered light reflected therefrom, in use.

[0004] Such a cartridge allows the presentation of an analyte in a relatively simple manner. The analyte may be added to the cartridge by a person supplying the analyte. For instance, urine or blood may be added to the cartridge in a relatively simple manner by the person.

[0005] The first nanoparticle’s characteristics may be predefined to be optimally responsive to the wavelength of laser light emitted by the Spectrometer. This range may be from 700nm to 830nm.

[0006] The first nanoparticle’s characteristics may be predefined to be optimally responsive for a specific energy produced by the laser light emitted by the spectroscope.

[0007] The first nanoparticle’s characteristics may be predefined to discriminate between diseases, and / or to be more sensitive to a specific disease. The first nanoparticle’s characteristics may be predefined to be optimal for a single target disease, or for a number of target diseases, or for disease generally. In this regard, the term ‘optimal’ may mean that the first nanoparticle’s characteristics are selected such that with an analyte, comprising a particular chemical signature, is adsorbed thereon, the resultant Raman scattered light provides an indication of the presence of the particular chemical signature. The particular chemical signature may indicate the presence of a particular disease or medical condition.

[0008] Typical materials for the nanoparticles are gold, silver and platinum, although others are contemplated. The nanoparticles may have a diameter / width of 40 to 80nm.

[0009] The transport layer may comprise nitrocellulose. In this way, an analyte, in the form of a fluid, may be “wicked” along the layer from an initial point to the first nanoparticle. The transport layer may comprise pores having a diameter of 200nm.

[0010] The cartridge may comprise a plurality of nanoparticles. These may be arranged in lines across the transport layer, and / or in one or more layers of the transport layer.

[0011] At least one of the plurality of nanoparticles may have second predefined characteristics. Likewise, at least one of the plurality of nanoparticles may have third predefined characteristics. In a similar manner, at least one of the plurality of nanoparticles may have fourth predefined characteristics. It is to be understood, that each nanoparticle may have predefined characteristics different from every other nanoparticle. Alternatively, there may be a plurality of nanoparticles with first predefined characteristics, a plurality of nanoparticles with second predefined characteristics, and so on. These groups of nanoparticles having predefined characteristics may be arranged in lines so that one line may be arranged to be optimally responsive to a first disease or medical condition, and another line may be arranged to be optimally responsive to a second disease or medical condition. In this regard, the term “medical condition” includes analysing an analyte for the presence of certain compounds such as specific hormones, cholesterol, and other biomarkers.

[0012] The nanoparticles may be arranged in a predefined pattern on a substrate. For example, lines or bands, shapes such as squares, triangles, etc. For instance, the nanoparticles may be arranged in a grid with 2 to 5mm spacing between the nanoparticles.

[0013] The substrate may be the transport layer. Alternatively, another material may be arranged on, or adjacent, the transport layer, on which the at least one nanoparticle is arranged.

[0014] The cartridge may further comprise one or more standard reference materials (SRM) for calibrating the spectroscope. Each SRM may have a known Raman response and may be arranged on the cartridge such that the spectroscope may submit them to laser light and analyse the resulting reflected light rays. The response may be compared, either automatically, or manually, to the known response, so as to provide an indication as to the accuracy of the spectroscope. The response may also be used to adjust the spectroscope so as to calibrate it.

[0015] The receiving means may be a well. In this regard the term “well” may include a depression, or other arrangement for temporarily holding an analyte. The receiving means is in contact with the transport layer so as to allow the analyte to be wicked to the at least one nanoparticle.

[0016] The cartridge may further comprise one or more filters for filtering the analyte before it reaches the transport layer. The one or more filters may be arranged to filter out material that is not required; for instance, filtering out solids above a certain size, from a fluid. Example filter sizes may be 60 microns (a wire mesh), 10 microns (cellulose material), 4 microns (micro-glass fibre material).

[0017] The one or more filters may be arranged to split the analyte into sub-analytes each for a different analysis by the nanoparticles. Each sub-analyte may be directed to different nanoparticles or groups of nanoparticles, each having different predefined characteristics for different analyses.

[0018] This may be effected by the cartridge comprising more than one transport layer. In other words, the filter sizes may be different for each transport layer.

[0019] The cartridge may further comprise a tab projecting from end, the tab arranged to receive the analyte and transport it to the transport layer. In this regard, the tab may be integral with the transport layer such that it wicks the fluid to the nanoparticles. Alternatively, the tab may be separate from, but in contact with, the transport layer so that the fluid may pass from one to the other, in use.

[0020] The cartridge may further comprise a drying means for drying the analyte. This may take the form of a heater, such as an electrically, or chemically powered heater, or hygroscopic materials, such as silica beads; or a metal heat transfer layer arranged to permit heat to be indirectly applied to, for instance, the transport layer.

[0021] The cartridge may further comprise a temperature sensor arranged to provide data relating to the temperature of the analyte. The temperature sensor may be arranged to sense ambient temperature, and / or the temperature of the analyte. The temperature may be sensed at the time at which the analyte is added to the cartridge, and / or at any other predetermined time, such as the time of analysis by the spectroscope.

[0022] The cartridge may further comprise an indicator to provide an indication that data relating to the temperature of the analyte does not meet predefined temperature criteria. For instance, if a temperature has been sensed at any time from the initial addition of the analyte to the cartridge to the time of analysis by a spectroscope, which exceeds a predefined temperature criteria, and thus reduces the likelihood of a meaningful, or accurate, Raman response, then an indication may be provided. The indication may take the form of an audible, visual, or haptic indication such as a buzzer, a light or a vibration, or change in colour or status. Alternatively, a chemical strip indicator may be provided which visually records the maximum and / or minimum ambient temperature.

[0023] The cartridge may further comprise a humidity sensor arranged to provide data relating to the humidity of the filter and / or transport layer. The humidity sensor may be arranged to sense ambient humidity around the cartridge. The humidity may be sensed at the time at which the analyte is added to the cartridge, and / or at any other predetermined time, such as the time of analysis by the spectroscope.

[0024] The cartridge may further comprise an indicator to provide an indication that data relating to the humidity of the analyte does not meet predefined humidity criteria. For instance, if a humidity has been sensed at any time from the initial addition of the analyte to the cartridge to the time of analysis by a spectroscope, which exceeds a predefined humidity criteria, and thus reduces the likelihood of a meaningful, or accurate, Raman response, then an indication may be provided. The indication may take the form of an audible, visual, or haptic indication such as a buzzer, a light or a vibration. Alternatively, a chemical strip indicator may be provided which visually records the maximum and / or minimum ambient humidity.

[0025] The cartridge may further comprise a time measuring device arranged to provide data relating to a period of time since an analyte was received in the receiving means.

[0026] The cartridge may further comprise an indicator to provide an indication that data relating to the period of time does not meet predefined time period criteria. For instance, if a time period between the initial addition of the analyte to the cartridge to the time of analysis by a spectroscope, exceeds a predefined time period criteria, the likelihood of a meaningful, or accurate, Raman response, may be reduced. Accordingly, an indication may be provided. The indication may take the form of an audible, visual, or haptic indication such as a buzzer, a light or a vibration. Alternatively, a chemical strip indicator may be provided which visually records the time period.

[0027] The cartridge may further comprise memory means for storing data. For instance, any one or more of the temperature, humidity and time measuring devices may provide digital information to the memory means. The cartridge may further comprise processing means for processing data. For instance, the processing means may use the temperatures, measured by the temperature measuring device, to determine if the predefined criteria have been met. The processing means may also control the indication means.

[0028] The cartridge may further comprise communication means. This may be used to communicate the data stored in the memory means to a remote processor, the spectroscope, or some other device. The communication means may be used to receive data and / or instructions so as to control an indication means.

[0029] The cartridge may further comprise RFID means. This may be used to provide identity data relating to the cartridge to the processor, the spectroscope or some other interrogating device.

[0030] The cartridge may further comprise a chemical indicator for providing an indication that the analyte is wet, or is dry, or has been wet but is now dry.

[0031] In a second aspect, the invention provides a method of analysing an analyte using Surface-Enhanced Raman Spectroscopy (SERS) comprising the steps of providing a cartridge according to the first aspect, adding an analyte to the receiving means, and introducing the cartridge to a spectroscope for analysis using Surface-Enhanced Raman Spectroscopy.

[0032] The above and other characteristics, features and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention. This description is given for the sake of example only, without limiting the scope of the invention. The reference figures quoted below refer to the attached drawings.

[0033] is a perspective view of a Surface-Enhanced Raman Spectroscopy (SERS);

[0034] is a cross-sectional side view of the cartridge of;

[0035] is a plan view of part of the cartridge of Figures 1 and 2; and

[0036] is a cross-sectional side view of another cartridge.

[0037] The present invention will be described with respect to certain drawings but the invention is not limited thereto but only by the claims. The drawings described are only schematic and are non-limiting. Each drawing may not include all of the features of the invention and therefore should not necessarily be considered to be an embodiment of the invention. In the drawings, the size of some of the elements may be exaggerated and not drawn to scale for illustrative purposes. The dimensions and the relative dimensions do not correspond to actual reductions to practice of the invention.

[0038] Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequence, either temporally, spatially, in ranking or in any other manner. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that operation is capable in other sequences than described or illustrated herein. Likewise, method steps described or claimed in a particular sequence may be understood to operate in a different sequence.

[0039] Moreover, the terms top, bottom, over, under and the like in the description and the claims are used for descriptive purposes and not necessarily for describing relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that operation is capable in other orientations than described or illustrated herein.

[0040] It is to be noticed that the term “comprising”, used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. It is thus to be interpreted as specifying the presence of the stated features, integers, steps or components as referred to, but does not preclude the presence or addition of one or more other features, integers, steps or components, or groups thereof. Thus, the scope of the expression “a device comprising means A and B” should not be limited to devices consisting only of components A and B. It means that with respect to the present invention, the only relevant components of the device are A and B.

[0041] Similarly, it is to be noticed that the term “connected”, used in the description, should not be interpreted as being restricted to direct connections only. Thus, the scope of the expression “a device A connected to a device B” should not be limited to devices or systems wherein an output of device A is directly connected to an input of device B. It means that there exists a path between an output of A and an input of B which may be a path including other devices or means. “Connected” may mean that two or more elements are either in direct physical or electrical contact, or that two or more elements are not in direct contact with each other but yet still co-operate or interact with each other. For instance, wireless connectivity is contemplated.

[0042] Reference throughout this specification to “an embodiment” or “an aspect” means that a particular feature, structure or characteristic described in connection with the embodiment or aspect is included in at least one embodiment or aspect of the present invention. Thus, appearances of the phrases “in one embodiment”, “in an embodiment”, or “in an aspect” in various places throughout this specification are not necessarily all referring to the same embodiment or aspect, but may refer to different embodiments or aspects. Furthermore, the particular features, structures or characteristics of any one embodiment or aspect of the invention may be combined in any suitable manner with any other particular feature, structure or characteristic of another embodiment or aspect of the invention, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments or aspects.

[0043] Similarly, it should be appreciated that in the description various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Moreover, the description of any individual drawing or aspect should not necessarily be considered to be an embodiment of the invention. Rather, as the following claims reflect, inventive aspects lie in fewer than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this invention.

[0044] Furthermore, while some embodiments described herein include some features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form yet further embodiments, as will be understood by those skilled in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.

[0045] In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the invention may be practised without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.

[0046] In the discussion of the invention, unless stated to the contrary, the disclosure of alternative values for the upper or lower limit of the permitted range of a parameter, coupled with an indication that one of said values is more highly preferred than the other, is to be construed as an implied statement that each intermediate value of said parameter, lying between the more preferred and the less preferred of said alternatives, is itself preferred to said less preferred value and also to each value lying between said less preferred value and said intermediate value.

[0047] The use of the term “at least one” may mean only one in certain circumstances. The use of the term “any” may mean “all” and / or “each” in certain circumstances.

[0048] The principles of the invention will now be described by a detailed description of at least one drawing relating to exemplary features. It is clear that other arrangements can be configured according to the knowledge of persons skilled in the art without departing from the underlying concept or technical teaching, the invention being limited only by the terms of the appended claims.

[0049] shows a cartridge 10 comprising a cuboid body having a depression, or well, 20 in the upper surface towards one end. This depression 20 allows for the introduction of an analyte in the form of a fluid. An indicator 92 is shown on the upper surface, as described below.

[0050] shows a cross-sectional side view of the cartridge 10, with the depression or well 20 visible top right. The base 30 of the well 20 has an inclined surface 30 so as to drain any introduced fluid towards an exit point 35 in the base.

[0051] Introduced fluid may pass through this exit point 35 (by gravity) and pass into a first chamber where the fluid passes through a first filter 40. The fluid having passed through this first filter 40 is then directed (by gravity) to another chamber comprising a second filter 50. The fluid then passes through this second filter 50. An exit point 55 is arranged within the second chamber beneath the second filter 50 directing the fluid to the transport layer 60. Nanoparticles 70, 80 are arranged on, and / or in, this transport layer 60. In use, molecules within the analyte may be adsorbed onto the surfaces of these nanoparticles.

[0052] The cartridge may comprise any one or more 90 of a temperature sensor, humidity sensor, time measurement device, memory means, processor, drying means, and communication means, such as RFID. The indicator 92 may be used to provide a visual or aural indication of predefined criteria having been met, or not having being met. Such criteria may be assessed on-board with an on-board processor which collects data from the various sensors and devices described herein. For instance, if the humidity of the analyte falls within acceptable predefined criteria (i.e. it is not too dry) then a green light may be provided.

[0053] In use, the cartridge may then be subjected to light in particular known wavelengths such that enhanced Raman scattering occurs from the nanoparticle / adsorbed molecules for analysis thereof.

[0054] shows a plan view of the transport layer 60 where nanoparticles 70, 80 are shown arranged in lines, oriented transversely across its width. An arrow 62 at the righthand end of the transport layer indicates that the analyte / fluid travels from right to left along the transport layer meeting, and interacting with, as previously described, various nanoparticles on its way.

[0055] A cross-sectional side view of an alternative cartridge 110 is shown in. The cartridge has a depression, or well, 120 and an outlet 135 from the well leading to the transport layer 160. On, or in, the transport layer 160 are nanoparticles 70, 80, as previously described. In this example, a tab 165 extends outwardly from the body of the cartridge. Analyte may be introduced to the tab 165, for instance by dipping it into a container of fluid. Alternatively, fluid may be poured onto the tab, in use. In the Figure, the tab 165 is show as being integral with the transport layer 160 such that fluid wicks along the tab and then along the transport layers to reach the nanoparticles 170. In another example, not shown, the tab 165 and transport layer 160 are separate but fluidly connected.

[0056] No sensors or other electronics are shown in this example but it is to be understood that they may also be present.

Claims

A Surface-Enhanced Raman Spectroscopy (SERS) cartridge for use with a Raman spectrometer, the cartridge comprising a body, receiving means for receiving an analyte in the form of a fluid, and a transport layer for moving the analyte to a probe, the probe comprising a first nanoparticle having first predefined characteristics so as to increase the detectability of Raman scattered light reflected therefrom, in use.The cartridge of claim 1, wherein the transport layer comprises nitrocellulose.The cartridge of either one of claims 1 and 2, comprising a plurality of nanoparticles.The cartridge of claim 3, wherein at least one of the plurality of nanoparticles has second predefined characteristics.The cartridge of either one of claims 3 and 4, wherein at least one of the plurality of nanoparticles has third predefined characteristics.The cartridge of any one of claims 3 to 5, wherein the nanoparticles are arranged in a predefined pattern on a substrate.The cartridge of claim 6, wherein the substrate is the transport layer.The cartridge of any preceding claim, further comprising one or more standard reference materials for calibrating the spectroscope.The cartridge of any preceding claim, wherein the receiving means is a well.The cartridge of any preceding claim, further comprising one or more filters for filtering the analyte before it reaches the transport layer.The cartridge of any preceding claim, further comprising a tab projecting from end, the tab arranged to receive the analyte and transport it to the transport layer.The cartridge of any preceding claim, further comprising more than one transport layer.The cartridge of claim 12, wherein the cartridge has more than one filter being arranged such that the filter sizes are different for each transport layer.The cartridge of any preceding claim, further comprising a drying means for drying the analyteThe cartridge of any preceding claim, further comprising a temperature sensor arranged to provide data relating to the temperature of the analyte.The cartridge of claim 15, further comprising an indicator to provide an indication that data relating to the temperature of the analyte does not meet predefined temperature criteria.The cartridge of any preceding claim, further comprising a humidity sensor arranged to provide data relating to the humidity of the filter and / or transport layer.The cartridge of claim 17, further comprising an indicator to provide an indication that data relating to the humidity of the analyte does not meet predefined humidity criteria.The cartridge of any preceding claim, further comprising a time measuring device arranged to provide data relating to a period of time since an analyte was received in the receiving means.The cartridge of claim 19, further comprising an indicator to provide an indication that data relating to the period of time does not meet predefined time period criteria.The cartridge of any one of claims 15 to 20, further comprising memory means for storing data.The cartridge of any one of claims 15 to 21, further comprising processing means for processing data.The cartridge of any preceding claim, further comprising RFID means.The cartridge of any preceding claim, further comprising a chemical indicator for providing an indication that the analyte is wet, or is dry, or has been wet but is now dry.A method of analysing an analyte using Surface-Enhanced Raman Spectroscopy (SERS) comprising the steps of providing a cartridge according to any preceding claim, adding an analyte to the receiving means, and introducing the cartridge to a spectroscope for analysis using Surface-Enhanced Raman Spectroscopy.

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