Patent ID: 12225955

DETAILED DESCRIPTION

Introduction

Molecular imprinting is an advancing technique in the medical device field because of its ability to mimic biologically active binding sites. Molecular imprinting uses artificial binding sites of proteins, sugars, and other biological compounds in order to capture molecules. Numerous two-dimensional and three-dimensional techniques are known in the art for imprinting of surface proteins. Techniques using silica have shown successful specificity for imprinting complex shapes such as hemoglobin. Biomedical applications have utilized molecular imprinting for ex vivo diagnostic methods such as immunoassays (antibody detection), analytical separations, and biosensors for detecting changes in blood sugar. Molecular imprinting is also used in the development of other biosensors and for diagnostic detection of viruses by interacting with antibodies.

Reference throughout this specification to “one embodiment,” “an embodiment,” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.

Furthermore, the described features, structures, or characteristics of the invention may be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided to convey a thorough understanding of embodiments of the invention. One skilled in the relevant art will recognize, however, that the invention may be practiced without one or more of the specific details, or with other methods, components, materials, and so forth. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of the invention.

FIG.1depicts an embodiment of a molecular imprinted face mask100as worn by an individual, comprising an outer surface102that holds a filtering component104securely against the front of the face over the nose and mouth and a user. The outer surface may comprise an air-permeable material including without limitation paper, woven fabric, knitted fabric, non-woven fabric, melt-blown fabric, ion-infused fabric, polymer foam, or other appropriate material as known in the art.

In various embodiments the filtering component104comprises a fabric and/or porous material for air to pass through. The surface of the threads of the fabric and/or the interior pores of the porous material may be coated with molecular imprints that capture, attenuate, neutralize, and/or detect toxic gases, toxic fumes, hazardous aerosols, or infectious pathogens. In certain embodiments a single layer of a molecular imprinted fabric, woven, or non-woven material is used as the filtering component. The fabric or other woven or non-woven material sometimes comprises more than one type of fiber or other material and/or more than one type of molecular imprint. Different types of molecular imprints sometimes attenuate and/or neutralize more than one airborne agent. Different types of molecular imprints sometimes generate a multi-step process in the woven matrix to attenuate and/or neutralize an airborne agent.

FIG.2depicts an expanded view of an embodiment of a molecular imprinted face mask100comprising a single-layered filtering component104, an outer surface102, a thin polymer film202, and molecular imprints204on surface of the polymer film202. Environmental air206passes through the filtering component104and filtered air208emerges.

In some embodiments the outer surface102is coated with the thin polymer film202. The filtering component104may comprise a molecular imprinted fabric or other porous material. The polymer film202may be a molecular imprinted polymer with imprinted sites204that in various embodiments may capture, sense, destroy, and/or release bacteria, viruses, medications, and various airborne particles.

A molecular imprinted polymer202may be created by mixing monomers of the polymer with the molecule (known as the template) to be imprinted. First, the monomers cluster and conform around the template. Second, the monomers polymerize with the template in place. Third, the template is removed from the polymer, thus leaving a mold or imprint204of the molecule in a polymer matrix. The monomers can be polymerized into nanoparticles or thin films. To create the molecular imprinted face mask100described herein, the monomers may be polymerized as a thin film202on the porous surface102of the face mask100or on the surfaces of fibers comprising a fabric or woven filtering component. Alternative, the monomers may be polymerized directly as fibers and incorporated into a fabric or woven filtering component.

Various methods for the fabrication of molecular imprinted polymers as thin films on a solid substrate are known in the art, and include spin coating, polymer brushes, dip coating using a silicon substrate, self-assembling monolayers, drop coating, spray coating, grafting, electropolymerization, and sol-gel processes. Micropatterned thin films of molecular imprinted polymers can also be manufactured using various lithography methods such as UV-mask lithography, soft lithography, micro-stereo lithography, and nanoimprint lithography.

The molecular imprinted face mask100may be fabricated in a variety of different models comprising different sets of molecular imprints204. A model could then be available for capturing various types of pathogens including bacteria and viruses such as the COVID-19 virus. In certain embodiments pathogens trapped by the molecular imprints204may also be inactivated or killed. Mechanisms may include, without limitation, chemical, biological, electrical, sonic, and UV light, applications as described above.

FIG.3depicts an embodiment of a multi-layer molecular imprinted face mask300in accordance with the present invention. As depicted, the multi-layer molecular face mask300comprises an outer surface102, a filtering component104, a thin polymer film202, molecular imprints204on surface of polymer film202, and an additional filtering layer302. In various embodiments of the invention, two or more layers of a molecular imprinted fabric or other material are used to generate a multi-step process to attenuate, neutralize, and/or detect toxic, hazardous, or infectious agents in the air. Two or more layers of a molecular imprinted fabric may be used to detect toxic, hazardous, or infectious airborne agents in one layer, and to attenuate and/or neutralize these agents in the other layer.

The strategically placed imprints204as shown on the molecular imprinted face mask300may be those of an antigen or binding site for a bacteria or virus such as COVID-19. Imprinting of an antigen or binding site may be accomplished through template imprinting techniques. Antigen or binding site molecules are obtained as a template by absorption onto a silicate mineral along with a buffer. The sample is heated and left to cool. Afterwards the sample is rinsed with deionized water to remove the buffer. The remaining sample may be coated with a disaccharide. A plasma deposition (hexafluoropropylene) may be deposited onto the sample where it will be placed in a plasma reactor to remove the template protein. Finally, a solvent may wash away any remains of the template protein.

In certain embodiments the thin polymer film202covers majority of mask300area for biochemically interacting with airborne particles. A pattern of molecular imprints204of different molecular species on a polymer film202may be used as described above. Molecular imprints may function as “phantom” or “virtual” molecules or binding sites to capture and immobilize pathogen molecules, to sense and report them, to kill or inactive them, and to release them during cleaning.

FIG.4depicts an embodiment of a woven filtering component400, composed of fibers with molecular imprints402, different types of molecular imprints404, positively charged conductive electrodes406, negatively charged conductive electrodes408, sensor wires, optical waveguides, and/or acoustic waveguides410. In some embodiments an electronically generated physical mechanism may release proteins from trapped on the surface of the polymer film202. Ultrasonic waves may be generated in the mask100,300or an external device702and transmitted to the mask surface102and polymer film202via waveguide principles. An acoustic waveguide410may comprise metal incorporated into the filtering component104. Such waveguide principles are identical to those used to propagate light along an optical fiber. In this manner the protective face mask100may be safely cleaned between uses and pre-loaded molecular imprints may be emptied of medication and/or other cargo.

In certain embodiments conductive wires function as interdigital electrodes406and408that enhance, modulate and/or read the binding state of the imprints204. Optical and/or acoustic waveguides410may function as sensor components in conjunction with the molecular imprints204. Optical and/or acoustic waveguides410in a fabric, woven, or non-woven material may function to attenuate or neutralize a hazardous airborne agent. For example, ultraviolet (UV) light transmitted by optical waveguides410may attenuate or neutralize a virus captured by molecular imprints202on the optical waveguides410, and/or other fiber components in the fabric, woven or non-woven matrix.

FIG.5depicts an expanded view of embodiment of an enhanced molecular imprinted filtering component500in accordance with the present invention. As depicted the electronically enhanced molecular imprinted filtering component500comprises a polymer coating202, molecular imprints204, and interdigital electrodes502embedded within the filtering component104, embedded within an air-permeable polymer support substrate such as polyurethane foam504, and/or positioned on the surface of the mask102as biosensors. Molecular imprints204may be loaded with material506comprising medications or other substances.

Biosensing molecular imprinted polymer surface technologies include surface plasmon resonance (SPR) techniques, surface-enhanced Raman spectroscopy (SERS), fluorescence quenching of semiconductor quantum dots, photoluminescence, UV-visible spectroscopy, electrochemical sensors (conductivity, capacitance, impedance, potentiometry, and voltammetry measurements), piezoelectric (quartz crystal microbalance, surface acoustic wave (SAW), pulse-echo ultrasound, through-transmission ultrasound, and phased-array ultrasound sensors, and biomimetic microchips with micropatterned imprinted polymers. The molecular imprint biofunctional devices provided herein may combine biosensors with bioactive molecular imprints and apply them to a protective face mask.

In certain embodiments the electronically enhanced molecular imprinted filtering component500detects molecules in contact with the molecular imprints204. The electronically enhanced molecular imprinted filtering component500sometimes detects specific pathogen molecules, providing information on probable exposure and the relevant venue. In various embodiments the electronically enhanced molecular imprinted filtering component500detects particles, pollutants, and gasses, and may alert the wearer to the status of the breathing environment in real time.

In some embodiments the molecular imprinted protective face mask is configured for a specific type of pathogen, a specific type of pollutant, a specific type of allergen, a specific environment or condition and/or is customized to a specific user or set of users. The electronically enhanced molecular imprinted filtering component sometimes comprises a triggerable reservoir of airborne medication504which may comprise a loaded molecular imprints202and/or other storage medium. The specific user or set of users sometimes comprises persons with compromised lung function. The biosensor may sense restricted air flow through the mask and trigger release of a bronchodilator and/or other lung treatment. In certain embodiments the biosensor is tuned to sense specific volatile organic compounds (VOCs) in the exhaled breath of the user and to trigger an alert and/or release of an appropriate medication. Non-limiting examples of using the molecular imprinted face mask to sense VOCs in exhaled breath to diagnose, monitor, and/or treat medical conditions include asthma, hyperglycemia in diabetic patients, disease progression in patients with renal failure, and cancer.

FIG.6depicts an expanded section view of an embodiment of an electronically enhanced molecular imprinted face mask500in accordance with the present invention. As depicted, the electronically enhanced molecular imprinted face mask is comprised of a fabric or woven filtering component402with simply structured molecular imprinted fibers602, with molecular imprints on the surface of the fiber604and electronically enhanced with interdigital electrodes502. Alternatively, complexly structured molecular imprinted fibers may be used with surface molecular imprints604combined with internal electrical components602,606,610,618, and624. These complexly structured fibers include those with a conductive electrode core608, a coaxial conductive core612and conductive shield616, a conductive electrode core622surrounded by quantum dots620, and/or multiple conductive cores626. As depicted, fibers with multiple conductive cores may be configured as a ribbon624, increasing the surface area of the fiber and thereby the density of molecular imprints604.

In one embodiment the electronically enhanced molecular imprinted face mask500comprises a polymer film202, molecular imprints604, an embedded semiconductor or piezoelectric polymer614, embedded quantum wires626, or nanoparticle quantum dots620. In some embodiments, quantum dots620underneath the molecular imprints604are used to configure the imprints604. In certain embodiments the quantum dots620or wires626are custom-engineered to produce unique electron wave function configurations that modulate the response of the molecular imprints604. The quantum dots620, or wires626may be used to dynamically reconfigure the electron charge distribution within the molecular imprints604, thereby creating a tunable molecular imprint604at the quantum level. Such charge distribution may influence processes such as the capture, sensing, reporting, deactivation, or destruction of pathogens or other molecules.

For non-limiting example, static electric fields (also known as direct-current or DC fields) have been shown to repel, attract, or capture airborne molecules, particles, or gases. Such static electric fields are sometimes generated on the surface of the electronically enhanced molecular imprinted face mask500, with the use of interdigital electrodes502deposited onto or into the surface of an insulating material (e.g. polyurethane foam), but lying beneath the polymer film202or molecular imprinted fabric402, and corresponding molecular imprints604.

In various embodiments electric fields, ultrasonic waves, electromagnetic waves, or quantum dots provide additional energy to free molecules from the imprint binding sites. This may function in the fabrication of the molecular imprints and in re-activation of the binding function of imprint sites that have been de-activated by the bonding of free molecules to the imprints.

In certain embodiments high frequency ultrasonic waves (10 MHz-10 GHz) or light (infrared to ultraviolet) may impact pathogens or other materials bound to the molecular imprints204. The ultrasonic or light waves may be generated in the electronically enhanced molecular imprinted face mask500or in an attachment and conducted to the face mask500via waveguide principles, including without limitation an acoustic waveguide or optical fibers embedded into the face mask500. The electronically enhanced molecular imprinted face mask500sometimes comprises a semiconductor. In certain embodiments the semiconductor comprises silicon into which ultrasonic transducers or lasers are fabricated on microchips and embedded into the filtering component104to locally excite the molecular imprints.

In certain embodiments high-frequency ultrasonic waves (10 MHz-10 GHz) are generated locally in the electronically enhanced molecular imprinted face mask500by embedded piezoelectric elements and conductive electrodes612,614, and616. In some embodiments an ultrasonic wave is generated on the electronically enhanced molecular face mask component500that mechanically agitates bound protein molecules or other materials and induces their separation from the imprints204. Piezoelectric elements may include but are not limited to fibers and thin films.

FIG.7depicts an embodiment of a system for an electronically enhanced molecular imprinted protective face mask in accordance with the present invention, the system comprising an electronically enhanced molecular imprinted protective face mask500, an attachment702, a supply tube704, a medication repository706, a power supply component708, and a detection component710. The attachment702may be connected to the face mask500either physically or remotely. In certain embodiments electric current, light waves, sound waves or other energy is generated in the attachment702by a power supply component and conducted to the face mask500via wires, tape, channels, optical waveguides, or other conduit712. In some embodiments the attachment702is a triggering device that communicates with the mask500to generate an energetic response within the mask500. In various embodiments the attachment702comprises a triggerable repository for inhalable or other appropriate medication706. Medication may be supplied to the mask500via a tube704or other channel. The medication repository706may be located on the attachment702or in any convenient location on the face mask500.

In some embodiments, the attachment702contains a detection component710to electronically process sensor signals received from the mask500via wires, tape, channels, optical waveguides, wireless radio-frequency communication, or other conduit712. In some embodiments, the detection component710also provides a readable output to the mask wearer on the level and/or type of hazardous substance or infectious pathogen detected by the face mask500. In certain embodiments, the detection component710generates a triggering signal based on sensor input from the mask500. The triggering signal is communicated via electrical wires714to the medication repository706, where it triggers the release of medication. In certain embodiments, the triggering signal from the detection component710is communicated via electrical wires714to the power supply component708, where it triggers at least one of fine-tuning the molecular imprint to enhance its response to a range of molecules, providing electrical energy to free molecules from the imprinted binding site, re-activating the specific molecule capture function of the imprint site, and interacting with the molecular imprint to function as a biosensor.

The detection component may contain at least one of a photodetector to convert optical signals from optical fibers to electrical signals, an ultrasound transducer to convert acoustic signals from acoustic waveguides to electrical signals, a spectrometer to analyze optical signals with molecular spectroscopy (for example surface plasmon resonance, surface-enhanced Raman, quantum dot fluorescence quenching, photoluminescence, and UV-VIS-IR spectroscopy), a multiplexer for a plurality of sensor channels, an amplifier to amplify sensor signals, a rectifier for radio-frequency signals such as ultrasonic signals, an electronic filter and/or discriminator to separate signals from noise, and a trigger signal generator.

FIG.8depicts an embodiment of a system for a molecular imprinted protective face mask, comprising a face mask802, one or more layers of molecular imprints804, an electronic enhancement806, outside air808, filtered or treated air810, a medication repository812, a power source and detection module814, communication module816, a receiving module818, a transmitting module820, a tracking module822, a remote connection824, a remote data and communications manager826, and a database828.

Communication between the electronic enhancement of the mask806and a database828provides the ability of the molecular imprinted face mask to selectively adapt to changing environmental hazards, specifically to detect, analyze, and counter a plurality of airborne threats. An example of the mask's adaptive ability is the following:

First, the environment is analyzed for a range of hazardous agents and pathogens by sending a sequence of control signals from the database828to the mask802via a communications manager826, a remote connection824, and a receiving module818. Examples of a remote connection824include but are not limited to ethernet, wireless, and/or optical fiber connections The control signals electronically tune the wave functions of the molecular imprints804through the electronic enhancement806, and they sweep the sensitivity range of the imprints across different molecular or pathogen species. The electronic enhancement806is then used in combination with the molecular imprints804to sense the presence and concentration of hazardous molecules and/or pathogens. The sensor data is processed by the detection component814. The processed sensor data is transmitted back to the database by means of a transmitting module820, remote connection824, and communications manager826.

Second, the mask is tuned to selectively capture, attenuate, and/or neutralize the principal hazardous molecule or pathogen in the environment. A control signal is sent from the database828to the mask802via a communications manager826, a remote connection824, and a receiving module818. The control signal electronically tunes the wave functions of the molecular imprints804through the electronic enhancement806to selectively interact with the principal hazardous molecule or pathogen.

Another function of the sensing and communication capabilities of the molecular imprinted protective face mask system is to use the sensor data from one or more masks to map the spatial extent and time-dependent changes of a hazardous molecule or pathogen in the environment. This data would be particularly valuable to the epidemiological monitoring of a disease such as COVID-19, for example to identify disease hotspots (geographically localized increases of infection), and spikes or surges in the infection rate (acceleration of infection rates).

EXAMPLES

Example 1: The Manufacture of a Molecular Imprinted Face Mask

A procedure for creating molecular imprints on face mask comprises the following steps. (1) Molecules of a specific airborne molecule (for example, COVID-19 virus) or a specific protein that functions as an antigen, antibody, or binding site for the airborne molecule are absorbed onto the surface of a thin mica sheet. (2) A buffer is added to neutralize the pH of the mica-protein surface. (3) The mica sheet-buffer solution is heated and subsequently cooled. (4) The mica sheet is rinsed with deionized water and spin cast with a disaccharide to allow coating.

The hydroxyl groups on the disaccharide molecules, combined with the surface polar residues of the protein molecules, facilitate the formation of hydrogen bonds during dehydration. Hydrogen bonds are vital for molecular recognition in biological signaling. The disaccharide coating also protects the protein molecules from dehydration and damage during the following plasma deposition process, thus preserving the fidelity of the imprinted cavities.

(5) A thin fluoropolymer film is deposited onto the mica surface using radio-frequency glow-discharge plasma deposition and hexafluoropropylene. (6) The fluoropolymer film is removably attached to a temporary support surface. The surface provides mechanical support for the fluoropolymer film. (7) The mica sheet is peeled from the supported fluoropolymer film. (8) The protein molecules are removed from the fluoropolymer film using a solvent wash, leaving behind molecular imprints of the protein. (9) The fluoropolymer film is incorporated into a woven or non-woven air-permeable surface.

For the synthesis of molecular imprinted fibers, silica capillaries are used as molds to replace the mica sheet. As in the procedure above, the target molecules are absorbed onto the interior surface of the capillary. The support polymer is then introduced into the capillary and polymerized. The capillaries are then etched away to free the imprinted polymer fibers. Another approach for the synthesis of molecular imprinted fibers is to use silica fibers as a permanent substrate for the molecularly imprinted polymer. The silica fibers are coated with a thin layer of the molecularly imprinted polymer and the polymer is then polymerized.

The above procedures may be utilized to molecularly imprint a set of diverse proteins onto a face mask in a specific spatial pattern. Non-limiting examples of proteins and other macromolecules that could be used for each molecular-imprinted polymer region on the face mask include the following: (1) angiotensin-converting enzyme 2 (ACE-2), which functions as the entry point into cells for the COVID-19 virus and other coronaviruses; (2) complex sugar chains (glycans) such as sialic acids of various chemical forms, which function as the entry point into cells for influenza viruses; and (3) receptor molecules in the immunoglobulin superfamily (IgSF), which function as entry points into cells for the measles virus and rhinovirus (common cold).

In the event that certain molecular imprints do not function similarly to their protein molecule counterparts, molecular “outprints” can be created by a stamping method that first creates the molecular imprints on nanoparticles. A polymer film is then stamped with these molecularly imprinted nanoparticles, creating a negative image of the molecular imprint, or an outprint. These molecular outprints will have the same positive shape as the original molecule, and may, therefore, have a functionality more similar to the original molecule.

Example 2: Detection of Virus Proteins

Protein-based molecular imprints have additionally been explored for the detection of virus proteins and even whole viruses. In some cases, a polymer is cross-linked and co-polymerized in the presence of a target molecule or protein. This target acts as a template for creating a cast. Once the cast is removed, it creates space for an active binding site. Molecular imprinting is supported by extensive research in the last decade, yet the application of imprinting protein-binding sites on dry surfaces for capture, sensing, activation and deactivation of airborne molecules remains to be investigated.

Previous studies have demonstrated the binding of influenza viruses to molecular imprints using aqueous solutions of viruses in contact with an imprinted polymer. In the event that an aqueous environment may be necessary for the binding of viruses to molecular imprints, evidence supports a mechanism for the capture, sensing, activation and deactivation of airborne viruses by a molecular imprinted face mask. This evidence includes the fact that many pathogenic viruses such as influenza and COVID-19 are primarily spread by microscopic airborne droplets (microdroplets) that are dispersed from an infected person by coughing, sneezing, singing, and/or speaking. Upon passing through a molecular imprinted face mask, the microdroplets are trapped by the fibers402and/or pores504in the mask's filtering component104, and simultaneously come into contact with molecular imprints604on the fiber and/or pore surfaces. Consequently, the viruses are brought into contact with the molecular imprints in the aqueous environment of the microdroplets.

The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.