Patent Application
20210025883
This application relates to composite materials and more particularly to composite materials combining an active moiety material with a structural material and their use in supporting novel integration within micro-fluidic and nano-fluidic components and devices.
Microfluidics deals with the behaviour, precise control and manipulation of fluids that are geometrically constrained to a small, typically sub-millimeter, scale. It is a multidisciplinary field involving engineering, physics, chemistry, biochemistry, nanotechnology, and biotechnology, with practical applications in the design of systems in which low volumes of fluids are processed. Since the 1980s micro-fluidics has evolved to use within inkjet printheads, DNA chips, lab-on-a-chip technology, micro-propulsion, and micro-thermal technologies. Micro-fluidic devices may process a single fluid, or they may exploit multiplexing either with automated fluidics, self-driven fluidics, and high-throughput screening. Whilst microfluidics addresses devices that process small volumes, namely femto-liters (fL), pico-liter (pL), nano-liter (nL) and micro-liter (μL), it is also common for devices at the μL level to be referred to a microfluidic whilst devices at the fL, pL and nL level are referred to as nanofluidic. However, in each instance the devices exploit effects of the microdomain, are small, have low power consumption, and within biological and chemical sensing applications also provide high sensitivity, exploit minute amounts of samples and reagents, offer low cost, are portable and easily distributed to end-users, etc.
Typically, within microfluidic devices and systems one or more fluids are moved, mixed, separated or otherwise processed. Numerous applications employ passive fluid control techniques like capillary forces. In some applications, external actuation means are additionally used for a directed transport of the media. Examples are rotary drives applying centrifugal forces for the fluid transport on the passive chips whereas active microfluidics exploit the defined manipulation of the working fluid by active (micro) components such as micropumps or microvalves. Micropumps supply fluids in a continuous manner or are used for dosing. Microvalves determine the flow direction or the mode of movement of pumped liquids. Often processes which are normally carried out in a lab are miniaturised on a single chip (e.g. lab-on-a-chip) in order to enhance efficiency and mobility as well as reducing sample and reagent volumes.
Microfluidic devices are commonly fabricated using polydimethylsiloxane (PDMS) for the mechanical structure of the body, micro-channels etc. PDMS is the most widely used silicon-based organic polymer and is particularly known for its unusual rheological (or flow) properties, being optically clear, and, in general, inert, non-toxic, and non-flammable together with tunable elastomeric properties, gas permeability, low auto fluorescence, nano-scale precision, and easy moldability.
Accordingly, PDMS is an important structural material for the fabrication of microfluidic and nanofluidic devices for various biomedical and industrial applications where its biocompatibility and compatibility with low complexity and low-cost fabrication processes are particularly attractive.
However, its inert nature and biocompatibility mean that all of the active functionality of the microfluidic devices must be added during the fabrication process after the formation of the microfluidic structures and the structural elements. Within the prior art several attempts have been reported within the prior art to enhance the properties of PDMS. These have included reinforcing the PDMS with carbon nanotubes or embedding gold or silver nanoparticles in order to either adjust the mechanical properties of the PDMS or to provide an electrically conductive polymer for support plasmon resonance based devices or electro-mechanical applications. Alternatively, the PDMS has been made porous allowing the introduction of an active material within a hydrogel into the pores.
However, it would be beneficial to provide designers of microfluidic devices with an ability to implement active elements for the detection of one or more components within a fluid or arising within a fluid from a reaction upstream using a composite comprising a mechanical component, such as the PDMS, with the active material for the active element of the microfluidic device embedded with the PDMS as a composite. Such active elements employing a composite from by integrating an active material, reagent, into the structural matrix may support the realization of a variety of applications, including biosensing and sensing applications.
Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments of the invention in conjunction with the accompanying figures.
This application is directed to composite materials and more particularly to composite materials combining an active moiety material with a structural material and their use in supporting novel integration within micro-fluidic and nano-fluidic components and devices.
In accordance with an embodiment there is provided a device comprising:
In accordance with an embodiment there is provided a device comprising:
In accordance with an embodiment there is provided a microfluidic device comprising:
In accordance with an embodiment there is provided a device comprising:
In accordance with an embodiment there is provided a device comprising:
In accordance with an embodiment there is provided a microfluidic device comprising:
In accordance with an embodiment there is provided a microfluidic circuit comprising:
In accordance with an embodiment there is provided a method comprising:
In accordance with an embodiment there is provided a device comprising:
In accordance with an embodiment there is provided a device comprising:
In accordance with an embodiment there is provided a device comprising:
In accordance with an embodiment there is provided a device comprising:
In accordance with an embodiment there is provided a method comprising:
In accordance with an embodiment there is provided a method comprising dissolving ninhydrin within a suitable solvent to form a ninhydrin mixture;
In accordance with an embodiment there is provided a sensing material comprising
In accordance with an embodiment there is provided a method comprising:
Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments of the invention in conjunction with the accompanying figures.
Various aspects of this disclosure are described, by way of example only, with reference to the attached Figures, wherein:
This application is directed to composite materials and more particularly to composite materials combining an active moiety material with a structural material and their use in supporting novel integration within micro-fluidic and nano-fluidic components and devices.
The ensuing description provides representative embodiment(s) only, and is not intended to limit the scope, applicability or configuration of the disclosure. Rather, the ensuing description of the embodiment(s) will provide those skilled in the art with an enabling description for implementing an embodiment or embodiments of the invention. It being understood that various changes can be made in the function and arrangement of elements without departing from the spirit and scope as set forth in the appended claims. Accordingly, an embodiment is an example or implementation of the inventions and not the sole implementation. Various appearances of “one embodiment,” “an embodiment” or “some embodiments” do not necessarily all refer to the same embodiments. Although various features of the invention may be described in the context of a single embodiment, the features may also be provided separately or in any suitable combination. Conversely, although the invention may be described herein in the context of separate embodiments for clarity, the invention can also be implemented in a single embodiment or any combination of embodiments.
Reference in the specification to “one embodiment”, “an embodiment”, “some embodiments” or “other embodiments” means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least one embodiment, but not necessarily all embodiments, of the inventions. The phraseology and terminology employed herein is not to be construed as limiting but is for descriptive purpose only. It is to be understood that where the claims or specification refer to “a” or “an” element, such reference is not to be construed as there being only one of that element. It is to be understood that where the specification states that a component feature, structure, or characteristic “may”, “might”, “can” or “could” be included, that particular component, feature, structure, or characteristic is not required to be included.
Reference to terms such as “left”, “right”, “top”, “bottom”, “front” and “back” are intended for use in respect to the orientation of the particular feature, structure, or element within the figures depicting embodiments of the invention. Such directional terminology with respect to the actual use of a device has no specific meaning as the device can be employed in a multiplicity of orientations by the user or users.
Reference to terms “including”, “comprising”, “consisting” and grammatical variants thereof do not preclude the addition of one or more components, features, steps, integers or groups thereof and that the terms are not to be construed as specifying components, features, steps or integers. Likewise, the phrase “consisting essentially of”, and grammatical variants thereof, when used herein is not to be construed as excluding additional components, steps, features integers or groups thereof but rather that the additional features, integers, steps, components or groups thereof do not materially alter the basic and novel characteristics of the claimed composition, device or method. If the specification or claims refer to “an additional” element, that does not preclude there being more than one of the additional element.
An “analyte” as used herein and throughout this disclosure may refer to, but is not limited to, a component (in clinical chemistry), chemical species, substance or chemical constituent that is of interest in an analytical procedure.
A “moiety” as used herein and throughout this disclosure may refer to, but is not limited to, a part of a molecule forming a functional group. A moiety or functional group participates in similar chemical reactions in most molecules that contain it.
A “microstructure” as used herein and throughout this disclosure may refer to, but is not limited to, the small scale structure of a material.
A “nanostructure” as used herein and throughout this disclosure may refer to, but is not limited to, a structure of intermediate size between microscopic and molecular structures. Nanostructural detail is microstructure at nanoscale.
A “microparticle” as used herein and throughout this disclosure may refer to, but is not limited to, particles between 0.1 and 100 micrometres (μm) in size.
A “nanoparticle” as used herein and throughout this disclosure may refer to, but is not limited to, particles between 1 and 100 nanometres (nm) in size with a surrounding interfacial layer. The interfacial layer is an integral part of nanoscale matter, fundamentally affecting all of its properties. The interfacial layer typically consists of ions, inorganic and organic molecules.
“LIGA” as used herein and throughout this disclosure may refer to, but is not limited to, a fabrication technology for the formation of high aspect ratio microstructures. Derived from the German acronym Lithographie, Galvanoformung, Abformung the process comprises three main processing steps of Lithography, Electroplating, and Molding. Common LIGA fabrication technologies are X-ray LIGA and UV LIGA.
An “optical source” as used herein and throughout this disclosure may refer to, but is not limited to, a light emitting diode (LED), a laser diode (LD), a diode pumped solid state source (DPSS), and a dye laser. Dye lasers may be formed within the microfluidic circuit as these generally employ liquid dyes. An optical source may be narrow linewidth, e.g. distributed feedback laser (DFB); narrowband, e.g. Fabry-Perot laser; wideband, e.g. LED; filtered; unfiltered; fixed wavelength; tunable wavelength; continuous wave; pulsed; and modulated.
An “optical detector” as used herein and throughout this disclosure may refer to, but is not limited to, a photodiode, a phototransistor (or light dependent resistor), an avalanche photodetector (APD), a reverse biased LED, and a quantum dot photodetector.
A “lock-in amplifier” as used herein and throughout this disclosure may refer to, but is not limited to, an amplifier capable of extracting a signal with a known carrier wave from an extremely noisy environment. Generally comprising a homodyne detector followed by low-pass filter, which may be static where a fixed carrier wave frequency is employed or adjustable in cut-off frequency and filter order in other instances where the carrier frequency modulating the signal being detected may be referenced from an external modulation source or generated by the lock-in amplifier itself. Analog lock-in amplifiers exploit analog frequency mixers and RC filters for the demodulation whereas digital lock-in amplifiers implement and perform both steps implemented by fast digital signal processing, for example, on a Field Programmable Gate Array.
“SU8” as used herein and throughout this disclosure refers to an epoxy-based negative photoresist. SU8 being composed of Bisphenol A Novolac epoxy dissolved in an organic solvent (for example gamma-butyrolactone (GBL) or cyclopentanone) and a photoacid generator (for example, up to 10 wt % of mixed triarylsulfonium/hexafluoroantimonate salt).
Referring to
Microfluidic devices may exploit different “actuation” mechanisms for the transport of the one or more fluids within the microfluidic device. These are divided into actuation mechanisms that are internal (or integrated) to the microfluidic device or external to the microfluidic device within the overall microfluidic system. Those external to the microfluidic device are typically one of the multiple designs of fluidic pump known within the prior art including, but not limited to, positive displacement and centrifugal type such as rotary-type positive displacement, reciprocating-type positive displacement, linear-type positive displacement, impulse pumps, gravity pumps, velocity pumps, etc.
Of the many internal—integrated microfluidic systems developed for POC these include, but are not limited to:
As will become evident from the discussion below embodiments of the invention are compatible with any microfluidic devices exploiting these microfluidic actuators exploiting one or more active material structural composites either as the main structure of the microfluidic device or within selective areas such as described below.
Further, one or more active material structural composites may be employed either as the main structure of the microfluidic device or within selective areas of the microfluidic component. Further, due to the nature of composites according to embodiments of the invention they may be employed within powered and self-powered, self-regulated microfluidic devices and may be employed in forming one or more capillary elements within the microfluidic circuit including, but not limited to:
B1: Host Material
Within the embodiments described and depicted in respect of
Optionally an elastomer and/or polymer according to an embodiment may comprise one or more of polydimethylsiloxane (PDMS), poly(methyl methacrylate) (PMMA), polystyrene (PS), polyvinyl chloride (PVC), polytetrafluoroethylenes (PTFE), cellulose derivatives such as ethyl cellulose, SU8, and cyclic olefin copolymer (COC)/cyclic olefin polymer (COP).
Optionally, the PDMS may according to embodiments of the invention comprise polydimethylsiloxane (PDMS) and a polysiloxane sealant formulation comprising from 85.0-100 wt % of hydroxy-terminated polydimethylsiloxane, from 7.0-13.0 wt % of amorphous fumed silica, and from 1.0-5.0 wt % of methyltriacetoxysilane. Optionally, the PDMS may be employed in conjunction with a curing agent suitable for curing PDMS.
Optionally, embodiments of the invention may exploit an initial base elastomer and/or polymer, which may for example be a substantially non-electrically conductive, silicone-based base elastomer and/or polymer, in combination with one or more active materials.
Optionally, embodiments of the invention may exploit an initial base elastomer and/or polymer, which may for example be a substantially non-electrically conductive, base elastomer and/or polymer, in combination with one or more active materials.
Optionally, embodiments of the invention may exploit an initial base elastomer and/or polymer in combination with one or more active materials wherein the one or more active materials are at least one of employed together within a region of a microfluidics device, within multiple regions of the microfluidic device with a different active material in each region, and within multiple regions of the microfluidic device with varying subsets of the one or more active materials in each region.
Optionally, the active material composition according to embodiments of the invention may also employ a particulate filler comprising at least one of electrically non-conductive particles and electrically conductive particles in combination with at least one of the active material composite and a structural material of the microfluidics device.
Optionally, the active material composition according to embodiments of the invention may also employ a polymer additive comprising at least one an electrically conductive polymer additive and an electrically non-conductive polymer additive in combination with at least one of the active material composite and a structural material of the microfluidics device.
Optionally, one or more regions of the microfluidics device comprising at least one electrically conductive polymer additive and an electrically non-conductive polymer additive may, within embodiments of invention, be disposed within regions of the microfluidics device to provide modified structural properties. Said regions may be where the active material composite is employed, adjacent to other regions where the active material composite is employed, or in other regions.
An electrically conductive polymer additive according to embodiments of the invention may comprise one or more of: ethylenedioxythiophene (EDOT); poly(3,4-ethylenedioxythiophene) (PEDOT); PEDOT doped with poly(styrenesulfonate) (PEDOT/PSS); polyaniline; poly(pyrrole); poly(acetylene); poly(thiophene); poly(p-phenylene sulfide); poly(para-phenylene vinylene) (PPV); polyindole; polypyrene; polycarbazole; polyazulene; polyazepine; polynaphthalene; other conjugated polymers and derivatives of these materials.
The particulate filler according to embodiments of the invention may comprise of one or more of metal-based microparticles, metal-based nanoparticles, carbon-based microparticles, carbon-based nanoparticles, silica nanoparticles, alumina nanoparticles, and zirconia nanoparticles.
Carbon-based microparticles and nanoparticles according to embodiments of the invention may comprise one or more of single walled carbon nanotubes, multi-walled carbon nanotubes, carbon nanorods, graphene, graphite and fullerene. Said carbon-based microparticles and nanoparticles may within embodiments of invention be disposed within regions of the microfluidics device to provide modified structural properties. Said regions may be where the active material composite is employed, adjacent to other regions where the active material composite is employed, or in other regions.
Metal based microparticles and nanoparticles according to embodiments of the invention may comprise one or more silver, gold, platinum, copper, nickel, aluminum, zinc, molybdenum, cadmium, scandium, titanium, vanadium, chromium, manganese, iron, cobalt, yttrium, zirconium, niobium, tantalum, tungsten, lead, indium tin oxide, terfenol-D, manganin and constantan. Said metal-based microparticles and nanoparticles may within embodiments of invention be disposed within regions of the microfluidics device to provide modified structural properties. Said regions may be where the active material composite is employed, adjacent to other regions where the active material composite is employed, or in other regions.
The nanoparticles composite with analytes can also change the electrical impedance of the regions comprising the active material composite. As a result, bioimpedance would vary with the sensing and interaction with analyte which can be measured through electrical impedance and/or electrical impedance spectroscopy.
B2: Active Material Options
Within the embodiments described and depicted in respect of
Active materials in each instance have properties, optical or electrical for example, that are affected by various analytes. The analytes detected may be primary analytes, e.g. directly measured within the sample being analysed, or be second analytes, e.g. analytes established based upon chemical reaction of a primary analyte wherein the second analyte is measured to derive the presence and/or concentration etc. of the primary analyte.
C1: Background
Ammonia is present almost everywhere in the atmosphere at a low concentration, in the range of sub-parts per billion (ppb) levels. Ammonia is a compound present in environmental samples such as aquaculture effluents, industrial wastewaters, plants and soil, and in pharmaceutical formulations for example. The majority of the ammonia present in atmosphere arises from human activities among which agricultural activities such as livestock and fertilizers are the most prominent sources of ammonia. Other sources of ammonia include on-road vehicles, industrial chemical plants and silver chemicals. However, extensive exposure to ammonia is harmful to both animals and humans. Ammonia at a level of 24-50 parts per million (ppm) can irritate the nose and the throat whilst at a moderate and higher exposure of typically above few hundreds of ppm of exposure to only a few minutes can cause severe irritation in the respiratory tract, spasms, and rapid suffocation. Accordingly, the acceptable threshold limit value (TLV) for ammonia gas with an exposure longer than 8 hours is around 25 ppm: and short-term exposure is 35 ppm for 15 minutes in order to serious health issues.
Accordingly, it is important to be able to detect ammonia in air at low concentrations (ppm level) for controlling pollution and in industrial processes such as food technology, fertilizers, and: especially, in environments where refrigeration processes are carried out. Several methods have been reported within the prior art for the determination of ammonia including spectrophotometry, solid-phase extraction, diffuse reflectance spectroscopy, electrochemical methods, ion-chromatography, spectrofluorimetry, capillary coulometric titration using the hypochlorite luminol chemiluminescence reaction, potentiometry with a differential system or indirect methods: for example, by amperometric detection of ammonium ions. Usually, the spectrophotometric method is used for the detection of ammonia and it is based on the adaptation of classical methods such as the Nessler or Berthelot reactions.
The major application areas of ammonia sensors are gas sensing and analysis in automotive industry, chemical industry and biomedical industry. Ammonia sensors having high sensitivity can be used as disease diagnostic tool as the ammonia is natural body product and its detection arid measurement can precisely predict the health conditions of various internal organs such a kidney and liver where breath ammonia detection can be used as fast diagnostic technique for patients having a kidney disorder or a stomach ulcer.
Within the prior art ammonia sensors have been reported and are generally categorized into five main types, each with its own advantages and disadvantages. These being metal oxide semiconductor devices, catalytic ammonia sensor, conducting polymer gas sensors, optical gas sensing, and indirect gas analyzers. Many of the classical analytical techniques used for the detection of ammonia suffer from drawbacks and are not suitable for the miniaturization into convenient POC sensors.
At present there is increased demand for miniaturized ammonia sensors due to several benefits such as faster analysis, low cost, easy integration with PEDs, FEDs, and other instruments and easy integration with miniaturized air vehicles such as drones in order to map the presence of ammonia, for environmental or industrial safety monitoring etc.
Accordingly, considering the prior art then several sensing principles for measuring ammonia in air have been reported but typically exploit infrared gas analyzers which are large and expensive, and not suitable for miniaturization and integration in a chip either as a discrete ammonia sensor or in combination with sensors for other materials and/or environment. Methods, more suitable for miniaturization are those based on the semiconductor properties of metal thin films (such as tin oxide or molybdenum oxide) or conducting polymer film gas sensors. However, their detection limits are not low enough and the selectivity of the methods is poor for many applications. In addition, the sensors lifetime has been found limited together with restrictions concerning their reproducibility, stability, sensitivity, and selectivity.
Other methods are based on the absorption of ammonia into a liquid and the subsequent detection of the ammonium ions by using an electrolyte conductivity detector. However, these techniques are bulky, measure cumulative ammonia and whilst electrochemical methods are sensitive and selective the instruments are quite expensive, and the presence of an experienced operator is either required for fast turnaround or samples must be sent for analysis.
More recently approaches have been reported for the fabrication of optical gaseous ammonia sensors which utilize the reaction of ammonia vapor with either a pH-dependent dye material or a pH-sensitive film which undergoes a suitable color change or an absorption change In general, these sensing mechanisms are based on monitoring the absorption or fluorescence characteristics of indicator dyes/sensing films entrapped within a membrane, deposited onto a wave guiding substrate or an optical fiber as substituted cladding. The targeted ammonia molecules interact with the immobilized indicator, resulting in changes in their absorbance or emission spectra, which are monitored using a proper detector module, via an optical fiber or optical waveguide.
C2: Concept for Optical Detection of Ammonia Using Ninhydrin-PDMS Composite
In order to demonstrate the active material polymer composite according to an embodiment the inventors established a composite comprising 2,2-dihydroxyindane-1,3-dione (known as ninhydrin) for the detection of ammonia within polydimethylsiloxane (hereinafter referred to as Ninhydrin-PDMS composite). Referring to
Now referring to
The device is powered by 3V DC power supply wherein the LED is biased via a first resistor R1 (1 kΩ) and the phototransistor 350 via a second resistor R2 (10 kΩ). The voltage across the photoresistor 350 was measured in order to quantify the amount of ammonia reacting with film and accordingly quantifies the concentration of ammonia.
C3: Fabrication of the Ninhydrin-PDMS Composite Film
Within the initial proof of concept device depicted within
Within the initial prototype devices sensing films of 100-1,000 μm were fabricated although other thicknesses may be exploited either per element or in overall combination within the optical path from the optical source, e.g. LED, to optical detector.
Synthesis of the ninhydrin-PDMS composite started by mixing the PDMS and a curing agent, e.g. at 10:1 wt %. Separately, the ninhydrin was dissolved in ethanol, e.g. 0.5 g in 5 ml, and stirred until all the ninhydrin had dissolved. The ninhydrin solution was added to the PDMS mixture and stirred for about 5 minutes. Immediately after adding the ninhydrin solution, the PDMS mixture appears to a low viscosity, then slowly, the PDMS mixture becomes viscous. At this point the mixture was degasified to remove any air bubbles. The film was fabricated by spinning, e.g. 300 rpm for 30 seconds, onto a carrier wafer, e.g. a silicon wafer. The silicon wafer was silanized prior to coating to promote the easy removal of the Ninhydrin-PDMS composite film. After spinning the Ninhydrin-PDMS composite film was baked at 85° C. for 2 hours and then peeled off from the wafer.
First and second images 400A and 400B in
Now referring to
Now referring to
C4: Fabrication Assembly of Device for Ninhydrin-PDMS Composite Film
Now referring to
Accordingly, a PDMS platform containing the channel and slots for guiding the gas were bonded onto a glass substrate using oxygen plasma bonding. The plastic horn shaped tubes, which were used as the guiding assembly for the gas to the sensing film, were then fixed in the slots at the input and output points. The LED and photoresistor were then integrated into PDMS in their respective locations opposing one another with the central channel and slot between them. The Ninhydrin-PDMS Composite film was cut to 3×6 mm and affixed on a flat PDMS substrate with a groove in this substrate which would become the top lid of the PDMS platform. The lid was then placed over the PDMS platform with the Ninhydrin-PDMS Composite film in the slot and the lid attached.
C5: Testing of Prototype Ninhydrin-PDMS Composite Film Based Microfluidic Device
Once assembled the microfluidic device with Ninhydrin-PDMS Composite film then
Subsequently, the inventors carried out tests with varying thickness of the Ninhydrin-PDMS composite film and found that the response time can be reduced to a lower value, by reducing the thickness of the film. The limit of detection in the present case was found to be as low as 2 ppm. In each case the composite was spun on a silicon wafer to obtain various thicknesses and the response time was investigated.
Having demonstrated the ammonia sensing capabilities of the Ninhydrin-PDMS composite film the inventors proceeded to investigate the feasibility of detecting amino acids with the developed Ninhydrin-PDMS composite. In these experiments the inventors employed glycine as the amino acid being detected. As with the ammonia sensor the absorbance spectrum of the Ninhydrin-PDMS composite was measured when it reacted with glycine. As the reaction of the glycine with the Ninhydrin-PDMS composite is very slow at the room temperature the composite was annealed at 100° C. for 5 minutes. The heating process resulted in a faster reaction of composite with the glycine arid the color of the composite changed to slightly blue. Accordingly, thin film composites may be locally heated within the microfluidic device through thin film heaters, power resistors disposed adjacent, etc.
The resulting absorption peak as evident from
The embodiment of the invention may be employed to detect an analyte with an NxHy group.
Some active materials, e.g. ninhydrin, exhibit a shift of absorbance peak which varies with the amine group species absorbed. Accordingly, a microfluidic circuit employing a ninhydrin-PDMS composite in combination with a tunable wavelength optical system allows for the species-specific detection of any amine group by using spectroscopy. The tunable wavelength optical system may comprise a tunable laser with broadband optical detectors or a broadband optical source in combination with a tunable filter and broadband optical detector.
Referring to
Further, the microcontroller and associated electronics for power, power management, optical source/optical detector control, data acquisition and analysis may be implemented within an overall device with the microfluidic circuit. Accordingly, embodiments of the invention may include, but not be limited to:
Referring to
Embodiments of the invention may also be designed and implemented to provide sensitivities in the parts per billion (ppb) range. Further, initial embodiments of the invention have been operated over initial temperature ranges of −4° C. to +100° C. with responses times of seconds over this temperature range. These initial embodiments have also been demonstrated to be independent of humidity effects through experiments performed with water based ammonia solutions and ammonia vapour alone.
G1: Electronics and Reference Elements
Within the prototype devices exploiting an embodiment as discussed and described with respect to
Optionally, the front-end amplifier may be replaced with an instrumentation amplifier or a fully-differential instrumentation amplifier. Optionally, the front-end electronics may provide a lock-in amplifier function either with analog signal processing or digital signal processing wherein depending upon the dynamic range of the electronics signals up to 106 times smaller than noise components within the received signal can be detected.
Accordingly, embodiments of the invention may support detection at parts per billion (ppb) levels of the analyte.
G2: Microfluidic Circuit Design
Within the initial prototype described and depicted supra in respect of
Referring to
Now referring to
Now referring to
Optionally, the active material composite may be employed within other microfluidic circuit elements including, but not limited to, symmetric capillary pumps; asymmetric programmable capillary pumps; microchannels; serpentine flow resistors; capillary pumps; reservoirs; and flow routers. Accordingly, active material composite sensors may be employed at different points within a microfluidic circuit.
G3: Nano-Structured and Micro-Structured Composites
Within the embodiments described and depicted supra in respect of
However, within other embodiments of the invention the active material composite may include microparticles and/or nanoparticles (hereinafter referred to as microparticles) in order to adjust the optical properties of the active material composite or to provide additional aspects such as increased interfaces, mechanical integrity, etc. Optionally, these microparticles may be also embedded into other regions of the microfluidic circuit to adjust mechanical integrity, adjust optical properties etc. Microparticles may be metallic, dielectric, semiconductor, magnetic, non-magnetic, ceramic, polymeric, etc. according to the target characteristics of the material and not impeding the sensing functionality of the active material where they are deployed within the active material composite. The microparticles may be solid, semi-solid, or soft. For example, clay microparticles into polymer matrices increase reinforcement, leading to stronger plastics, verifiable by a higher glass transition temperature and other mechanical property tests. Zinc oxide microparticles can provide UV blocking properties.
Accordingly, referring to
G4: Fluorescent Based Active Material Composite Sensors
Within the embodiments described and depicted supra in respect of
However, within other embodiments an active material composite may be employed exploiting fluorescence with the active material being a fluorescent sensor material. Such a fluorescence based system 1900 may comprises a fluorescent material 1910 embedded within a polymer material 1980. The fluorescent material 1910 as depicted comprising a capture material 1960 and a fluorescent material 1970. According to the analyte being sensed capture material may be a luminophore 1920, enzyme 1930, antibody 1940 or aptamer 1950. In the instance that the capture material is itself a luminophore 1920 and hence luminescent itself the fluorescent material 1970 may be omitted. Although in other instances wherein the luminophore 1920 is more akin to a phosphor a fluorescent material 1970 may be employed to shift the detection wavelength to a region away from the optical probe wavelength exciting the measurement system. As depicted in
Considering, luminophore 1920 then this can be divided into two subcategories, fluorophores and phosphors. The difference between luminophores belonging to these two subcategories is derived from the nature of the excited state responsible for the emission of photons. Some luminophores, however, cannot be classified as being exclusively fluorophores or phosphors and exist in the gray area in between. Such cases include transition metal complexes whose luminescence comes from an excited (nominally triplet) metal-to-ligand charge transfer (MLCT) state, but which is not a true triplet-state in the strict sense of the definition; and colloidal quantum dots, whose emissive state does not have either a purely singlet or triplet spin. Most luminophores consist of conjugated pi systems or transition metal complexes. In addition, purely inorganic luminophores, such as zinc sulfide doped with rare earth metal ions, rare earth metal oxysulfides doped with other rare earth metal ions, yttrium oxide doped with rare earth metal ions, zinc orthosilicate doped with manganese ions, etc.
Enzymes 1930, like catalysts, work by lowering the activation energy for a reaction, thus dramatically increasing the rate of the reaction. Enzymes are very selective and speed up only a few reactions, which given that enzymes are known to catalyze about 4,000 biochemical reactions, implies the number of potential enzymes available is large. A few RNA molecules called ribozymes also catalyze reactions, with an important example being some parts of the ribosome. Additionally, synthetic molecules called artificial enzymes also display enzyme-like catalysis adding to the pool of available capture molecules to operate in conjunction with the fluorescent material to establish optical activity in dependence of the process they are monitoring, controlling, or accelerating.
An antibody 1940, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen. Though the general structure of all antibodies is very similar, the small region at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures, or antigen binding sites, to exist. This region is known as the hypervariable region. Each of these variants can bind to a different target. Accordingly, there is enormous diversity in the antibodies which can be exploited.
Aptamers 1950 are oligonucleic acid or peptide molecules that bind to a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist in riboswitches. Aptamers can be used for both basic research and clinical purposes as macromolecular drugs. Aptamers can be combined with ribozymes to self-cleave in the presence of their target molecule. More specifically, aptamers can be classified as either DNA or RNA aptamers in that they consist of (usually short) strands of oligonucleotides or peptide aptamers in that they consist of short variable peptide domains, attached at both ends to a protein scaffold.
Accordingly, a wide range of materials can be employed as capture material and bound within a matrix allowing fluorescent based optical sensors to be integrated with a compact footprint and low cost. Whilst generally different capture materials would be employed for different analytes multiple capture materials may also be employed for a single analyte, such as for example to provide an increased dynamic range of measurement than is achievable with a single capture material.
Referring to
In first step 2000A an uncrosslinked SU-8 layer 2010 is deposited upon a substrate. Next in step 2000B this uncrosslinked SU-8 layer 2010 is exposed through optical lithography defining crosslinked SU-8 regions 2020. This process is repeated in steps 2000C and 2000D to provide two layers of cross-linked SU-8. SU-8 being an epoxy-based negative photoresist that is very viscous polymer and can be spun over thicknesses ranging from up to and still be processed with standard contact lithography. The uncrosslinked SU-8 material is removed in step 2000E wherein the resulting crosslinked SU-8 2020 forms the basis for a molding of hydrophobic PDMS based active material composite 2030 which may be spun or poured to form the molded element. Next in step 2000F the hydrophobic PDMS based active material composite 2030 is processed to provide hydrophilic PDMS based active material composite 2040 and vent holes are formed. Next in step 2000G a sealing substrate 2050 is attached to form the microfluidic circuit. Optionally, vent holes may be implemented within the sealing substrate 2050 or the PDMS based active material composite. Optionally, sample loading points, inlet ports, and outlet ports may be provided within the PDMS based active material composite and/or sealing substrate 2050. Within embodiments the sealing substrate 2050 may me a PDMS substrate formed with features via a similar process as that depicted within
The photolithographic patterning process described and depicted in respect of
Optionally, a photolithography, deposition and etching process may be employed to removed cured active material composite or solid active material composite. Optionally, photolithography, deposition and etching processes may be employed to structure passive or inert materials to form the upper and/or lower portions of the microfluidic circuit within materials such as silicon, silica, fused quartz, alumina, glass etc. onto which the one or more regions of active material composite are formed.
Optionally, other manufacturing processes within the semiconductor processing industry may be employed to form, pattern the active material composite and/or passive materials. Optionally, the active material composite may be stamped, molded, etched, machined, etc. according to the manufacturing process or processes employed. Stamping may, for example, employ LIGA techniques to create high-aspect-ratio stamps for the microstructures.
The foregoing disclosure of the exemplary embodiments has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many variations and modifications of the embodiments described herein will be apparent to one of ordinary skill in the art in light of the above disclosure. The scope of the invention is to be defined only by the claims appended hereto, and by their equivalents.
Further, in describing representative embodiments, the specification may have presented the method and/or process of the present invention as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims. In addition, the claims directed to the method and/or process of the present invention should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the present invention.
This application claims the benefit of priority as a national phase entry application of World Intellectual Property Office Application PCT/CA2019/000039 filed 28 Mar. 2019 which itself claims the benefit of priority from U.S. Provisional Patent Application 62/649,405 filed 28 Mar. 2018, the entire contents of each being incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/CA2019/000039 | 3/28/2019 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62649405 | Mar 2018 | US |
