WO2025006958A2 - Methods of treating amyloidosis of the skin and rejuvenating skin using biosensors - Google Patents

Abstract

The invention relates to methods of diagnosing and/or treating a subject having, or being at risk of developing, a disease or condition that is associated with amyloidosis.

Description

METHODS OF TREATING AMYLOIDOSIS OF THE SKIN AND REJUVENATING SKIN USING BIOSENSORS

FIELD OF INVENTION

The present invention relates to methods of diagnosis and treatment of amyloidosis and amyloidosis-associated diseases of the skin, and methods of rejuvenating skin, wherein the methods include, for example, detection and modulation of neurotransmitters.

BACKGROUND OF THE INVENTION

Amyloidosis is a rare disease characterized by a buildup of abnormal amyloid deposits in the body. Amyloid deposits can build up in the heart, brain, kidneys, spleen and other parts of the body. A person may have amyloidosis in one organ or several. Amyloidosis tends to make subjects look and feel older and not fit into the modem society where outer beauty takes precedence over inner beauty.

Prior art techniques for detecting neurotransmitters in real time and in vivo fall short of the instant invention. These previous methods such as dialysis have limitations such as those described in During MJ. et al., 1993, Lancet 341 : 1607-1610; Ferrendelli JA. et al., 1986, Adv. Neurol. 44:393-400; Goldstein D S et al., 1988, J Neurochem 50:225229; Janusz W. et al., 1989, Neurosci Res 7: 144153; Kawaguchi Y. et al., 1998, J Neurosci 18:6963-6976. For example, the dialysis (microdialysis) technique has several disadvantages relative to temporal resolution. It has limited time resolution (>1 min) in comparison to voltammetry (sub-seconds). In contrast, the use of highly sensitive analytical techniques (e.g. neuromolecular imaging with the Broderick probe⁵' ) reduces sampling times to less than sub-seconds. Dialysis samples do not provide real time information regarding changes in the neurochemical environment. Also, dialysis is an invasive technique and therefore causes some damage to the tissue under study and critically, the dialysis process creates an area around the membrane in which all solutes capable of crossing the membrane are depleted. Furthermore, there are other limitations described, including ascorbic acid interference and misinterpretation of the data (Vladimir I. Chefer, Alexis C. Thompson, Agustin Zapata, and Toni S. Shippenberg, Overview of Brain Microdialysis, Curr Protoc Neurosci. 2009 Apr; C HAPTER: Unit7.1.doi: 10.1002/0471142301.ns0701s47, PMID: 19340812, NIHMSID: NIHMS236586, PMCID: PMC2953244). Techniques in the art are limited, in part, in their relative inability to monitor neural chemistry in real time in a freely behaving animal or human, which may limit their diagnostic and/or therapeutic efficacy.

Thus, there is a need for improved methods for the diagnosis and treatment of amyloidosis and amyloidosis-associated diseases.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1: Photo of Neuroimaging squalene.

Figure 2: Photo of Neuroimaging Lauric Acid.

Figure 3: Diagram of one embodiment of the Broderick*' probe.

SUMMARY OF THE INVENTION

In one aspect of the present invention, a method of diagnosing amyloidosis and/or amyloidosis-associated pathology in a subject (e.g., a person of color) in need thereof is provided. The subject can be mammalian (e.g., human) or non-mammalian subject.

The method comprises: a) generating a temporally resolved sensor scan of said subject using a sensor placed on said subject; b) determining from said scan a concentration of biogenic amines and other neurotransmitters (e.g., serotonin and/or dopamine) associated with amyloidosis in said subject; and c) comparing said amyloidosis-associated concentration to specific threshold values to determine a concentration of statistically significant differences, wherein said differences are indicative of amyloidosis-associated pathology, wherein said threshold values are derived from the sensor scan of at least one healthy cell, tissue, organ or organism. Examples of the amyloidosis-associated pathology includes primary localized cutaneous amyloidosis (PLCA) (e.g., lichen amyloidosis, macular amyloidosis, or nodular amyloidosis). In one embodiment of the method, a sensor is placed on the skin and/or under the fingernails.

In another aspect of the present invention, a method of treating amyloidosis and/or amyloidosis-associated pathology in a subject in need thereof is provided. The method comprises: a) generating a temporally resolved sensor scan of said subject using a sensor placed on said subject; b) determining from said scan a concentration of biogenic amines and other neurotransmitters associated with amyloidosis in said subject; c) comparing said amyloidosis- associated concentration to specific threshold values to determine a concentration of statistically significant differences, wherein said differences are indicative of amyloidosis-associated pathology, wherein said threshold values are derived from the sensor scan of at least one healthy cell, tissue, organ or organism; and d) administering to said subject a pharmaceutical composition or therapy that is known to treat said pathology. In one embodiment, the method includes administration by biochip under the fingernails wherein the composition penetrates the skin.

In a further aspect of the present invention, a method of rejuvenating skin in a subject in need thereof is provided, bi one embodiment, the method comprises administering to a subject a composition by a biosensor (e.g., biochip) applied topically, fit under a fingernail or used as an infrared laser, wherein the biosensor contains albumin, phosphotidyl polymer, phosphotidyl- ethanolamine, squalene or combinations thereof. In one embodiment, facial skin is rejuvenated.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to the identification, diagnosis, and treatment of amyloidosis and amyloidosis-associated diseases of the skin, using biosensors (e.g., probes, electrodes, biochips). The identifications, diagnoses and/or treatments are known as biosensing. The subject can be a mammalian (e.g., human) or non-mammalian subject.

In one embodiment, the amyloidosis is primary localized cutaneous amyloidosis (PLCA). Primary localized cutaneous amyloidosis is a condition in which clumps of abnormal proteins called amyloids build up in the skin, specifically in the wave-like projections (dermal papillae) between the top two layers of skin (the dermis and the epidermis). The primary feature of PLCA is patches of skin with abnormal texture or color. The appearance of these patches defines three forms of the condition: lichen amyloidosis, macular amyloidosis, and nodular amyloidosis.

In one aspect, the present invention provides methods to identify, diagnose and treat amyloidosis and amyloidosis-associated diseases in all skin types, for example, amyloidosis of the skin in people of color. The methods utilize biosensors (i.e., sensors) which detect the activities of biogenic amines and other neurotransmitters (e.g., dopamine and serotonin). Amyloidosis is associated with amyloid substances which are abnormal aggregates of misfolded proteins that form fibrillar structures that can accumulate and deposit in tissues. The present invention can detect amyloid substances and can diagnose and treat amyloidosis.

The invention includes the use of biosensors, smaller than one human hair, which contain graphite, oil and at least one type of organic biopolymer. Examples of such biosensors include Broderick biosensors (e.g., BRODERICK NANOPROBE® and BRODERICK BIOCHIP®). These biosensors can detect neurotransmitters, ions, and other molecules, providing physiological information of a targeted area. Key features of the Broderick biosensors include real-time monitoring, high sensitivity and minimally invasiveness.

Examples of organic biopolymers suitable for use with the biosensors include albumin, unsaturated fatty acids, sphingolipids, phospholipids, lauric acid, and optical opsins with retinal. An example of an unsaturated fatty acid is squalane. Examples of sphingolipids include ceramides, sphingosines, and cerebrosides. Ceramides consist of a long-chain amino alcohol called sphingosine linked to a fatty acid via an amide bond. Sphingosine is a long-chain amino alcohol. Ceramides play important roles in maintaining the structure and function of the skin barrier. Sphingosines are key components of sphingolipids, including ceramides and other sphingolipid derivatives. Cerebrosides consist of a ceramide backbone linked to a single sugar molecule. They are commonly found in nerve tissues and play roles in cell signaling and the maintenance of the nervous system. The cerebrosides are ceramides with the distinction of the latter having a composition of sphingosines and fatty acids whereas the former are primarily sphingosines. The sphingosines enable the lipid barrier of the skin to protect from dehydration as well as to enable the skin cell neurons to survive for electroactive fatty acid signals to redox neurotransmitters for younger and more supple skin.

It has been surprisingly discovered by the instant inventor that, when used in biosensors of the invention, the organic biopolymers can image biogenic amines. In particular, the biosensors of the invention create reflective images of neurotransmitters on the skin, including, for example, dopamine, serotonin and peptides.

In one embodiment, the BRODERICK NANOPROBE ® is a microelectrode comprising graphite, oil, and unsaturated fatty acids, e.g., squalane. The transformation of squalene ( i.e. , polyunsaturated hydrocarbon with a formula of C₃₀H₅₀) to squalane (i.e., saturated derivative of squalene) is important from the marketing perspective as squalane is more stable. In other embodiments, the BRODERICK NANOPROBE * is a microelectrode comprising graphite, oil, and sphingolipid, e.g., ceramides, sphingosines, and/or cerebrosides.

Dopamine and serotonin are known to provide younger and healthier skin, and provide oils and fats to supplement nutrition. These neurotransmitters have been found to be diminished in amyloidosis as compared to a healthy control. In a preferred method of the invention, a biosensor is placed on an affected area of the skin to detect levels of dopamine and/or serotonin. If the level of these neurotransmitters are below the level of a healthy control level, a diagnosis of amyloidosis and/or amyloidosis-associated diseases is suspected.

For example, BRODERICK NANOPROBE * probes can detect basal (normal, natural, endogenous or steady state) concentrations of neurotransmitters associated with amyloidosis in vivo, in situ and in vitro. They can also detect alterations in the neurotransmitters associated with amyloidosis on the skin before and after pharmaco logical manipulation with drugs or other compounds.

The invention provides a variety of methods for identification and diagnosis of amyloidosis and amyloidosis-associated pathologies of the skin, and treatment of such using biosensors. These methods include the use of, for example, microvoltammetry, and comparing BRODERICK NANOPROBE ® microvoltammograms from at least two different tissues. One of these tissues is generally a reference tissue or control. The other is tissue is that being assayed. Preferably, the reference tissue corresponds to the assay tissue with respect to, for example, tissue type, anatomical location, and/or stage of development.

In some embodiments of the invention, the comparison is performed between microvoltammograms taken from the same tissue at different times. In some embodiments, the microvoltammograms compared are taken from the same tissue before and after treatment, e.g., exposure to a material such as a pharmaceutical drug. In some embodiments, a tissue suspected of being diseased is compared with healthy tissue.

Such comparisons may make it possible to diagnose and/or treat amyloidosis and amyloidosis-associated pathologies. In one embodiment, the invention provides methods comprising exposing at least a cell to a diagnostic challenge or therapeutic treatment, contacting said cell with a BRODERICK NANOPROBE ® probe, applying a potential to said BRODERICK NANOPROBE - probe and generating a BRODERICK NANOPROBE ® probe microvoltammogram/scan. A diagnostic challenge may be designed to elicit a differential response from cells of interest, e.g,, diseased cells, from other cells, e.g., healthy cells.

Once an affirmative diagnosis is found, the biosensors of the present invention can be used to treat amyloidosis and amyloidosis-associated diseases.

In one embodiment, the biosensor treats amyloidosis and amyloidosis-associated diseases by enhancing the activities of biogenic amines and other neurotransmitters (e.g., dopamine and serotonin) and peptides (e.g. collagen). Enhancing the activities includes increasing the production of the biogenic amines, neurotransmitters and peptides. For example, a nanoprobe containing lauric acid can increase production of L-tryptophan. Enhancement of activities near affected skin areas treats disease and/or enhances beauty. For example, dopamine and serotonin make the skin more plump and moist, thus enabling the skin to have a younger look. Thus, the biosensors treat the amyloidosis by providing smoother and unwrinkled skin. For example, a nanoprobe containing lauric acid can increase production of L-tryptophan.

As another example, a BRODERICK BIOCHIP® can be applied topically, be fit under a fingernail or be used as an infrared laser. The biochips reduce amyloidosis by removing disturbing pigments, hydrating via unsaturated fatty acids, miming lipids that welcome fatty acids into the cellular matrix, enabling neuronal production of unsaturated fatty acids, using saturated fatty acids that image dopamine and serotonin to redox neurochemicals that enable healthy skin, enabling collagen, and imaging L-tryptophan to make collagen a more complete protein.

For instance, by applying a BRODERICK BIOCI 11 P containing albumin, skin becomes dramatically more supple and springy by recoiling skin muscle and innervating skin muscle in the aging skin. That is, albumin enables muscular tone where the muscle appears flexed even when it is at rest and where previously, before treatment, neurons had become clumped with alpha synuclein and various intermediates of synuclein deposits. In one embodiment, a BRODERICK PROBE* containing phosphotidyl polymer with albumin and a phosphotidylethanolamine coating, delivered by electrochemical nanotechnology, reverses aging of the skin. That is, elastin, a protein in the extracellular matrix of connective tissue, is replaced or at least the loss of elastin is ameliorated in the aging skin by the albumin biochip.

In another embodiment, the instant invention uses biosensors for drug delivery for nanomedicine. Medicinal agents can be in ultra-small particles and travel through the skin using nucleocapsules comprised of, for example, magnolia oil and/or hyaluronic acid (HA) or docotaxel-loaded HA, the latter then specifically providing a versatile anionic polymer that biochemically interlocks with anion/cation exchange properties of the BRODERICK NANOPROBE'® probe library of diverse inventive sensors, including the cationic properties of the BRODERICK NANOPROBE*’ probe to deliver nanomedicines heretofore unavailable to patients presenting with amyloidosis or amyloidosis-related diseases. For example, electrochemical biosensors based on nanomaterials with superior properties of charge transport, large surface area and good biocompatibility are used to deliver fatty acids transdermally. hi another embodiment, the biosensor may be pre-treated, inserted, or coated with a therapeutic biomolecule. Biomolecules include but are not limited to, pharmaceutical compounds specific for amyloidosis or amyloidosis-associated diseases, disorders, and conditions, anti-inflammatories and compositions which enhance the activities of biogenic amines and other neurotransmitters (e.g., dopamine and serotonin), neurotransmitters, neuromodulators, or combinations thereof. A preferred biomolecule for this invention is squalane. Squalane is present in the skin naturally and more squalane can penetrate the skin with the assistance of fatty acid transporters. Topical squalane fabricates more of itself by a process called autocatalysis which makes more and more squalane. Another preferred biomolecule for this invention is lauric acid. Other preferred biomolecules for this invention are ceramides, sphingosines, and/or cerebrosides.

For example, BRODERICK BIOCHIP* biochips can fit on a fingernail and have several modes of action. For example, one mode by which the biochips function is by a phenomenon called lipid biomimetics, i.e., lipids that mime and are mimed. That is, fatty acids bind to proteins and transport these proteins to the lipid membrane in cell membranes in neurons; the result is a change in lipid conformation. The process involves protein unfolding and prions. These are skin phonopathies. Further, fatty acid penetration also changes the lipid metabolism of the skin enabling or disenabling more fatty acids such as squalene to be made. The penetration is dependent on the lipophilicity of squalene and the lipophilicity-' of the skin; and both are lipophilic. Hydrophobicity is another key. The longer the chain the more hydrophobichating hydrogen. For example, see “Evaluation of Hydrophobicity for Fatty Acids Using Reversed-phase Thin Layer Chromatography” J Oleo Sei. 2019 Jul l;68(7):665-670. doi: 10.5650/jos.ess 19016. Epub 2019 Jun 10. The more the product hates hydrogen, the more long lasting is the hydration of the skin, the skin remains moistened longer. This is the advantage of the Broderick squalene biochip. Squalene traps moisture more effectively than does hyaluronic acid.

In another embodiment, if amyloidosis or an amyloidosis-associated pathology is diagnosed, a therapeutic treatment known to treat such condition is administered to the subject. Examples of such treatment includes albumin, anti-inflammatories, steroids, prednisone, colchicine, dimethylsulfoxide (DMSO), antihistamines, light therapy, stimulation therapy, carbidopa /levodopa, pramipexole, apomorphine, selegiline, Xadago, dopamine modulators, serotonin modulators, catechol-o-methyl transferase (COMT) inhibitors, monoamine oxidase (MAO) inhibitors, electrometallurgy therapy, cobalt, cobalt catalysts, antagonists of iron, magnesium, copper and the like, catalytic converters, catalysts, metal catalysts, enzymes, antibodies, pronatinib, enoxaparin fragments, serotonin, somatostatin, N-Methyl-D aspartate therapies, Co-Q-10 therapies, mitochondrial therapies, inflammation inhibitors, melatonin, indoles, alpha synuclein modulators and chelators, indole derivatives, apomorphine, dopamine auto-receptor antagonists and agonists thereof, N acetyl serotonin, precursors, kynurenine modulators, quinolinic acid inhibitors, cytokine restorative therapy, reperfusion therapies, arachidonic acid metabolites, biogenic amine therapy, indoleamine therapy, glutamine, glutamate, GABA therapy, dynorphin fragment therapy, receptor inhibitors of protein kinase 1 (RIPK1), serine, threonine, tyrosine, inhibitors, protein kinase inhibitors and combinations thereof, proline, cysteine, progeline, prolagine, antioxidants, taurine, taurine copolymers, magnesium taurate, squalene, lavender, caprylic acid, coconut oil, magnolia oil, peptides, peptide therapies, polyphenols and sugars and combinations thereof, Quinone-Tryptophan-Hybrid- Aggregation-Inhibitors, anthragen quinone blockers, G 12/13-GSK 3, G 12/13-GSK 3 beta antagonists and partial antagonists thereof, glycogen synthase kinase 3 alpha, glycogen and glycogen mediators, mitochondria pyruvate carrier 1 , hyaluronic acid (HA), docetaxel loaded HA, kami-un-tanto, kampo herbal agents, hydrolyzed collagen, collagen, elastin, bioderm, medium chain triglycerides, light chain immunoglobulins, saw palmetto, Vitamin A, retinal, retinoid, Vitamin B, thiamine, pyrithiamine, thiamine pyrophosphate, magnolia oil, dihydrotestosterone modulators, easyliance, retinylidene, Schiff base, insulin, beta cells, streptozotocin blockers, dopamine, serotonin and derivatives and precursors thereof, for example, but not limited to, 1-tryptophan, tyrosine, ceramides, sphingosines, cerebrosides, polycrystalline potash, nitrogen, zinc, phosphorus, agricultural plant products, organic/inorganic materials mining process, fertilizer, halite, sylvite, carnallite, kieserite and combinations thereof.

In some embodiments, a subject is monitored after treatment to assess whether the treatment was successful.

In one embodiment, a treatment can be assessed for its capacity to serve as a diagnostic indicator or therapeutic treatment. A diagnostic challenge or a therapeutic treatment can comprise exposing the cell(s) to a material such as a small molecule drug or drug candidate, a defined electrochemical environment (e.g. application of a potential to the cell(s)), exposure to an isotopic or nonisotopic label, activation or repression of a preselected gene, or combinations thereof.

BRODERICK NANOPROBE probes are described in more detail herein. BRODERICK NANOPROBE * probes may be in electrical contact with an auxiliary microelectrode and/or a reference microelectrode. These microelectrodes and the squalane sensor are functionally connected. This sensor may be termed the indicator microelectrode or the working microelectrode.

One means for electrochemically measuring the concentration of one or more biogenic amines (i.e., neurotransmitters) include, for example, circuits of square wave, amperometric semidifferential/semiderivative, voltammetric, linear scan, differential pulse, double differential pulse, and chronoamperometric circuits.

It will be apparent to those of ordinary skill in the art, particularly in view of the cited patent documents, that "BRODERICK NANOPROBE ® probe" is a term that relates to a number of electrodes that vary by composition and the type of circuit in which it is employed and that these variations give rise to differences in detection properties.

BRODERICK NANOPROBE ^R> probes are miniature carbon-based sensors that are able to detect electrochemical signals for a vast number of biogenic amines and other neurotransmitters, neuromodulators and metabolites, including neuropeptides, hormones, vitamins, and the like (Broderick P A, 1989, U.S. Pat. No. 4,883,057; Broderick P A, 1995, U.S. Pat. No. 5,433,710; Broderick P A, 1997, EP 0487647 Bi; Broderick P A, 1999, U.S. Pat. No. 5,938,903; Broderick P A, 1999, Hong Kong, HK # 1007350). These probes have made it possible to routinely and selectively detect in discrete neuroanatomic substrates of living human and animal brain, the monoamines, DA, NE, and 5-HT, in addition to the precursor to 5-HT, 1 -tryptophan (1-TP), ascorbic acid (AA) and uric acid (UA) (Broderick P A, 1988, Neurosci. Left. 95:275-280; Broderick P A, 1989, Brain Res. 495: 115-121; Broderick P A, 1990, Electroanalysis 2:241-251; Broderick P A, 2000, Epilepsia 41 (Suppl. ):91; Broderick P A et al., 2000, Brain Res. 878:49-63). It is also possible to differentiate catecholamines, DA and NE, electrochemically using these probes (Broderick P A, 1988, Neurosci. Lett. 95:275- 280; Broderick P A, 1989, Brain Res. 495:115-121; Broderick P A, 1990, Electroanalysis 2:241 -251 ; Broderick P A, 2000, Epilepsia 41 (Suppl. ):91 ; Broderick P A et al., 2000, Brain Res. 878:49-63). More recently, it has been found that these probes are also capable of electrochemical detection of somatostatin and dynorphin A (Broderick P A, 2000, Epilepsia 41(Suppl.):91).

The BRODERICK NANOPROBE ® probes, as used herein, can be prepared in a wide range of sizes and formulations each with different detection capabilities. In particular, one embodiment of the BRODERICK N ANOPROBE ® probes comprises a construction and indicator portion. The BRODERICK NANOPROBE ® probes are useful for intraoperative recordings and continuous recordings with data logging and telemetry.

The sensor is partially or fully encased in an encasement, where the encasement is made of a conducting, semi-conducting, or non-reactive material, such as, for example, metals, polymers, or blends thereof, for example, but not limited to, polytetrafluoroethylene, fluorinated ethylene -propylene, perfluoroalkoxy polymer resin, polymethylmethacrylate, polyethylethacrylate, steel, stainless steel, silicon, germanium, silver, platinum, gold, or combinations thereof. The shape of the encasement may be a hollow three-dimensional surface, where there is an opening on either or both ends of the sensor which allows contact of the indicator with the neural cells, body, blood, or urine. The shape of the encasement, and thereby sensor, has an end face in the shape of any geometric shape. By end face is meant the ends of the encasement. For example, if the encasement is in the shape of a hollow cylinder, then the circle faces are the end faces of the sensor. Non-limiting examples of geometric shapes include: a circle, a triangle, a quadrilateral, a rhombus, a parallelogram, a rectangle, or a polygon of any number of sides, pentagonal, hexagonal, or octagonal.

The encasement may be an inverted well or the like, having the inventive sensor material, i.e., the squalane, ceramides, sphingosines, and/or cerebrosides. The partially or fully encased sensor may be, but not limited to, flat, horizontal or vertical. The sensor material may be fitted into, for example, an electroencephalographic (EEG) grid, strip, or depth electrodes for recordings for ictal, interictal, intracranial imaging, for image-guided surgery and gammaknife surgery in epilepsy or tumor patients, and the like. Sensors may also, for example, be fitted into stimulating electrodes for thalamic and globus pallidus recordings and the like.

The construction portion of the probe has a conducting and/or semi-conducting material, including, for example, a conducting metal or semi-conducting metal, or combinations thereof. Non-limiting examples of the construction include: steel, stainless steel, silicon, germanium, silver, platinum, or gold, or combinations thereof.

The indicator portion of the probe has at least one form of carbon, or combinations thereof, and at least one lipid or entity having a lipid, or combinations thereof. Carbon comes in several forms, including but not limited to, graphite, fullerenes, cylindrical fullerenes, buckminsterfullerenes, buckyballs, nanotubes, probing tubes, cold form carbon steel, white carbons, dioxosilane, diamonds, or combinations thereof.

The indicator portions of the inventive sensors also have some type of lipid, fat, or oil. These are water-insoluble substances of plant, animal, or mineral origin, which are mainly comprised of glycerol esters of fatty acids or glycerides. Lipids are greasy oily substances which also contain glycerol. The word, "fat" is commonly used to refer to triglycerides that are solid or semi-solid at ordinary temperatures; the word "oil" connotes triglycerides in the liquid phase. The terminologies "fat" and "oil" are often interchanged. Therefore, a triglyceride is a condensation product of one molecule of glycerol and three molecules of fatty acid. A mixed triglyceride contains two different fatty acids and has four isomeric fonns. Monoglycerides and diglycerides contain only one or two fatty acids respectively and consequently have two or one free hydroxyl groups. Monoglycerides and diglycerides do not occur naturally in appreciable quantities except in fats that have undergone partial hydrolysis. Animal and vegetable fats can have similar composition and thus, we must realize the importance of glyceride composition in determining the physical properties of fats and oils. In preferred embodiments of this invention, squalane, lauric acid, ceramides, sphingosines, and/or cerebrosides are used.

A lipid is any of a group of organic compounds, including fats, oils, waxes, sterols, and triglycerides, that are insoluble in water but soluble in non-polar organic solvents. Nonlimiting examples of lipids, or entities having lipids, include fats, oils, animal fats or oils, plant fats or oils, mineral oils, nujol oil, glycerol containing lipids, membrane lipids, soaps or detergents, waxes, cells, cell components, stem cells, electroplaques, lipoproteins, fatty acids, glycerides, monoglycerides, diglycerides, triglycerides, artificial or synthesized fats or oils, heifer fats, ox-depot fats, Valeria indica fats, tallow, red tallow, Malabar tallow, vegetable tallow, cocoa butter, soybean oil, safflower oil, sesame oil, peanut oil, coconut oil, linoleic acid, linoleic acid in vegetable oil, soybean oil, cottonseed oil, corn oil, or poppy seed oil, lauric acid, lauric acid in coconut oil, cholesterol, phosphotidylcholine, phosphotidylethanol- amine, sphingomyelin, lecithin, lysolecithin, steroids, isoprenoids, eicosenoids, sodium alkyl benzene sulfonate, sodium lauryl sulfate, jejoba wax comprised of gadoleic acid, N-stearoyl- cerebroside, N- stearoylsphingosine, cardiolipin, or combinations thereof. In preferred embodiments of this invention, squalane, lauric acid, ceramides, sphingosines, and/or cerebrosides are used.

The sensors of the invention may be used in any or all methods described herein. In some embodiments, the size of the sensor is from less than about 1 nanometer to about 10 millimeters in width, and from less than about 1 nanometer to about 10 millimeters in length. The indicator portion having some form of carbon may be present in a useful amount ranging from about 1 microgram to about 100 grams, while the lipid which is incorporated, coated, or inserted in the carbon, is in an amount from about 1 microgram to about 100 grams.

BRODERICK NANOPROBE ® probes do not promote bacterial growth either before or after sterilization with gamma irradiation. Gamma irradiation treatment was performed by Sterigenics International, Inc., Haw River. N.C.

The probes of the instant invention can include, for example, micro-voltammetry, nanotechnology, spectrometry, laser, photonic, surgical, stimulation, robotic, implant and devices thereof for microprocessor systems and the like to image biogenic amines and other neurotransmitter activity. This imaging can occur while the subject(s) is walking, anesthetized, conscious and/or in altered states of consciousness presenting and/or at risk of amyloidosis and/or amyloidosis-related diseases.

The present invention further includes devices and methods of use thereof for determining the presence and concentration of biogenic amines and other neurotransmitters (e.g.. dopamine and serotonin) associated with amyloidosis/amyloidosis-related diseases in a cell, tissue, organ or organism. The invention includes, inter alia, semiderivative voltammetric measurements and chronoamperometric, amperometry, differential pulse, double differential pulse, square wave, fiber optic, voltaic photosensitive, as well as but not limited to, use as adjunct to resonance imaging including magnetic, functional magnetic, nuclear magnetic, Raman Spectroscopy, computerized axial tomography (CAT), electroencephalographic, dry electroencephalographic, electrocorticographic, measurements of chemicals and/or molecules to identify, diagnose, and/or treat amyloidosis-associated pathologies. Microvoltammetric indicator microelectrodes pass small but measurable currents while neurotransmitters and metabolites close to the microelectrode surface undergo oxidation and/or reduction (Adams R N et al., 1982, Handbook of Psychopharmacology, pp. 1-74). When an electrode is placed in contact with a solution a phase boundary is created that separates identical solutes into two different types. They are (a) molecules that are at a distance from the microelectrode and (b) those molecules that are close enough to participate in mutual interactions between the surface of the microelectrode and the sample solution interface (Kissinger P T et al., 1996, Laboratory Techniques in Electroanalytical Chemistry, pp. 11-50). Collectively, these interactions are called electrochemistry.

Microvoltammetric circuits using several types of carbon paste microelectrodes have been developed and refined (Broderick P A, 1995, U.S. Pat. No. 5,433,710; Broderick P A, 1996, EP 90914306.7; Broderick P A, 1999, U.S. Pat. No. 5,938,903). Reliable separation and quantification of neurotransmitters including norepinephrine, serotonin, and dopamine as well as some of their precursors and metabolites is now possible (Broderick P A, 1989. Brain Res. 495: 115-121 ; Broderick P A, 1988, Neurosci. Lett. 95:275-280; Broderick P A, 1990, Elcctroaiialysis 2:241245).

Extensive refinements to microelectrodes and to in vivo electrochemistry have been made (Broderick P A, 1990, Electroanalysis 2:241-245). The recent development of a stearatecarbon paste probe along with an electrode conditioning process has resulted in reliable separation and detection of norepinephrine, dopamine, and serotonin (Broderick P A, 1996, EP 90914306.7; Broderick P A, 1999, U.S. Pat. No. 5,938,903). In addition, other types of niicroelectrodes with increased sensitivity and reliability continue to be developed (Broderick P A, 1996, EP 90914306.7; Broderick P A, 1999, U.S. Pat. No. 5,938,903).

Without wishing to be bound by a theory, it is believed that between the surface of the sensor and the biomolecule per se, weak covalent bonds are formed by adsorption of the biomolecule onto the surface of the instant inventive sensor, which is also comprised of adsorptive carbon or carbon allotropes. Although weak covalent bonding may provide a rationale for the memory or reflective image of the biomolecule produced by the sensor, it is plausible that a number of other interactions may occur between the biomolecule and the instant inventions. Chemisorption is an adsorptive interaction between a molecule and a surface in which electron density is shared by the adsorbed molecule or molecules and the sensor surface. Physisorption is another plausible explanation for the reflective adsorptive image on the instant inventions. In this mechanism, a biomolecule does not actually undergo a specific chemical bonding. Physisorption involves an electrostatic attraction or dipole-dipole interaction but no real chemical bonds are made. Instead, there is a sharing of electrons between the biomolecule and the instant inventive sensor material, that is to say, as the adsorbate, i.e., the biomolecule migrates closer to the surface of the sensor, the dipole moment of the adsorbate induces an image dipole. Since dipoles attract each other and generate an electromagnetic field on the surface, the electromagnetic field may factor into reflection or imaging of the biomolecule or biomolecules on the part of the instant sensor invention.

Other possible explanations are provided by interactions which occur in unsaturated fatty acids which have double or triple bonds. In this interaction, memory or reflective image may occur in the instant inventive sensor by the formation of pi bonds. Such a pi-bond interaction may occur between the surface of the instant inventive sensor and biomolecules which are aromatic, benzene-like and molecules which contain a phenyl or phenyl groups such as those which are cited in the embodiment of the instant inventive sensors. Pi- bonds may account for the detection of straight chain amino acid compounds, such as acetylcholine, and benzene-like compounds, such as monoamines, with the instant inventive sensors. (Adamson, A.W., Textbook of Physical Chemistry, Academic Press, New York, 1973; Kissinger, P.T., Heineman, W. R., (Editors) Laboratory Techniques in Electroanalytlc Chemistry, Second Edition, Marcel Dekker, Inc. New York, 1996; Kamat, P.V., Asmus, K.D., "What's all the excitement about?" Interface, The Electrochemical Society, Volume 5 (number 1), 1996; Dohnalek, Z., Kim, H., Bondarchuk, O., White, J.M., Kay, B.D., Physisorption of N2,Oi,and CO on fully oxidized TiO2 (110) J. Phys. Chem..B Condens Matter Mater Surf Interfaces Biophys. 110 (12): 6629-6635, 2006; Mattil, K. F., Norris, F.A., Stirton, A. J., Swern, D., Bailey's Industrial Oil and Fat Products, (Edited by Swern, D.) Interscience Publishers, a Division of John Wiley & Sons, Inc., Third Edition, 1964; and Hui, Y. H. (Editor), Bailey's Industrial Oil and Fat Products, Edible Oil and Fat Products: Oil and Oil Seeds, A Wiley-Interscience Publication, Volume 2, Fifth Edition, 1996, all of which are incorporated herein by reference).

In one embodiment, the sensor may be in the form of a miniature stainless steel flat, circular disk construction in which the indicator comprises graphite incorporated or coated with squalane. The graphite can also be coated with cerebrosides, stearoyl, lauric acid, or the like, or combinations thereof. The indicator is further incorporated or coated with biomolecules including but are not limited to, pharmaceutical compounds, pharmaceutical compounds specific for amyloidosis or amyloidosis-associated diseases, neurotransmitters, neuromodulators, hormones, surfactants, soaps, detergents, pramipexole, topiramate, clozapine, dopamine, serotonin, norepinephrine, acetylcholine, adenosine, estrogen, vitamins, vitamin A, vitamin E, brain lipids, phosphotidylethanolamine, tallow, sodium lauryl sulfate, N-acetyl-D-aspartate, choline, lactate, uric acid, stabilizing proteins, amyloid proteins, ascorbic acid, y- aminobutyric acid, glutamate, neurotensin, somatostatin, dynorphin, homovanillic acid, nucleic acids, tryptophan, tyrosine, nitrous oxide, nitric oxide, or combinations thereof, are completely or partially encased in polytetrafluoroethylene.

Changing the surface of the sensor changes the capacitance of the surface of the sensor. The surface of the indicator electrode is a capacitance diffuse double layer (Cat) that allows potential to accumulate on its surface. Capacitance is a critical aspect of charging (background) current. Charging current is a current pulse that flows through the Cat to allow faradaic electron transfer to begin. Accumulation of potential on the surface of the indicator electrode is necessary for faradaic electron transfer. Charging current is proportional to electrode surface area; therefore, these miniature sensors (200 microns and less in diameter) minimize charging current effects.

BRODERICK NANOPROBE ^E probes or sensors can be used in conjunction with classical electrical circuits used in electrochemistry such as chronoamperometry, differential pulse voltammetry and double differential voltammetry. Another electrical circuit for providing an output signal having a mathematical relationship in operation to an input signal can be semiderivative or semidifferential. These two terms are used interchangeably here, although these two circuits have some technical differences. Semiderivative electroanalysis diminishes non-faradaic cun-ent by the addition of analysis time. In the present studies, a CV 37 detector (BAS, West Lafayette, Ind.) was equipped with a semiderivative circuit. This circuit uses a linear scanning methodology as its basis. Semiderivative treatment of voltammetric data means that the signals are recorded mathematically as the first half derivative of the linear analog signal. A semiderivative circuit combines an additional series of resistors and capacitors, called a "ladder network" (Oldham, K, 1973, Anal. Chem. 45:39-50) with the traditional linear scanning technology which then allows more clearly defined waveforms and peak amplitudes of electrochemical signals than was previously possible with linear scanning methodology.

BRODERICK NANOPROBE ^!< probes microvoltammograms/scans may be plotted as current versus time or as current versus applied potential. Other renderings are also possible. The concentration of biogenic amines and other materials may be deduced from these microvoltammograms, e.g. according to the Cottrell equation. According to the invention, a microvoltammogram is broadly defined as any rendering of the signals from a Broderick probe susceptible to human perception including, but not limited to, paper, electronic, and virtual representations of the Broderick probe signal. An individual of sufficient skill in the art to perceive a Broderick probe signal in real-time, e.g. from a visual display screen, is also within the contemplation and scope of this definition.

The main strength of in vivo microvoltammetry (electrochemistry) is that it allows the study of the neurochemical time course of action of normal neurochemistry, as well as the neurochemistry after an administered drug regimen. Temporal resolution is fast, in seconds and milliseconds. Moreover, the attendant microspatial resolution is superior (availability of discrete areas of brain without disruption). Both highly sensitive temporal and spatial resolution makes these studies ultimately most efficient for mechanism of action studies.

The basic in vivo electrochemistry experiment involves the placement of an indicator electrode or sensor on the skin of a subject, the application of a potential to that electrode or sensor, the oxidation or reduction of the selected neurochemical or biomolecule and the recording of the resultant current. In essence, the potential is applied between the indicator or sensor, and the reference electrode; the reference electrode provides a relative zero potential to sense the amount of current produced by the flow of electrons from the biomolecule through the indicator. This is an electrochemical technique with which information about neurotransmitters (e.g., dopamine and serotonin) associated with amyloidosis, an analyte, or its metabolite, including its concentration, is derived from an electrochemical current as a function of a potential difference. This potential difference is applied to the surface of an electrochemical electrode. Additionally, an auxiliary electrode provides an electrical ground.

In microvoltammetry, each neurotransmitter (e.g., dopamine and serotonin) associated with amyloidosis, or its metabolite, etc. is identified by the peak oxidation potential, or half-wave potential at which the neurochemical generates its maximum current. Using the Broderick Probe⁸ stearic acid electrode inserted in NAcc, the oxidation potential at which DA generates its maximum current in vivo (physiological pH, 37.5°C) was empirically determined to be +0.140 V (SE ± 0.015 V) in over one thousand studies. The oxidation potential at which serotonin generates its maximum current under the same conditions was empirically determined to be +0.290 V (SE ± 0.015 V) in over one thousand studies.

What matters in microvoltammetry is that each of these biogenic amines have amine groups that are protonated at neutral pH and therefore, exist as cations, whereas metabolites of the monoamines are deprotonated at neutral pH and exist as anions (Coury LA et al., 1989, Biotechnology 11:1-37).

Generally, quantitation of neurochemistry is described as a percentage of a few data points, over hours, used as "control” in microdialysis studies. However, Broderick probes are easily calibrated and concentrations are interpolated from calibration curves (Broderick P A et al., 2000, Brain Res. 878:49-63).

In one embodiment, the BRODERICK NANOPROBE “ probes is a nanosensor, which includes an imaging component that uses photonic energy to generate a photocurrent that represents a molecular parameter, wherein the imaging device includes a photosensitive material and at least one of a laser diode and/or photodiode; and a memory component that stores a representation of the molecular parameter, wherein the memory component includes at least one of a vitamin, lipid, carbon allotrope, and/or carbon tetra fluoride. Such a probe is described in WO 2017/117223 Al.

The photosensitive material may include at least one of a protein, glycoprotein, protease, peptide, amino acid, opsin, retinal, retinoic acid, retinol, rhodopsin, bathorhodopsin, lumirhodopsin, metarhodopsin 1 , metarhodopsin 11 , lumirhodopsin, trans-retinal, purple membrane proton pump protein microbe from a class of helobacteria, eukaryote, prokaryote, vitamin. The memory component may transduce a memory profile of a half wave of a molecule, and provide a peak signature associated with the molecule in an excited state proton transfer (ESPT). The electroactive photonic polymer sensing device may include a potentiostat monitoring electrochemical current derived from the electrochemical imaging component, and a spectrometer detecting and representing light energy derived from the spectral imaging component. The laser diode may provide low wattage, such as but not limited to hundreds of watts or less, near infrared energy configured to extend approximately 30 mm into the skin surface or neuroanatomy of a brain, and the imaging component may include at least one of a conducting or a semiconducting component. The conducting component may include at least one of a silica-containing material, piezoelectric material, and the semiconducting component may include tetrafluoromethane. The imaging component may include rhodopsin, the memory device may include carbon fullerene, and the rhodopsin and carbon fullerene may be disposed in a polymer shell.

The embodiments disclosed herein further include a computer-readable medium comprising instructions that, when executed by a processing device perform a method of sensing polymers, which includes converting, using an imaging component, photonic energy into electrochemical energy to generate a photocurrent that represents a molecular parameter, wherein the imaging component includes at least one of a laser diode, photodiode, and/or photosensitive material; and storing, using a memory component, a representation of the molecular parameter, wherein the memory device includes at least one of a vitamin, lipid, carbon allotrope, and/or carbon tetra fluoride.

In one embodiment, a probe/sensor of the present invention enhances memory in certain parts of the brain such, for example, the hippocampus. For example, a BRODERICK NANOPROBE * sensor comprising lauric acid, the amyl form of lauric acid, and/or laurate induces fragrances as to enhance the rewarding functions of the brain such as in the ventral tegmentum. Included in the present invention are beauty products made by the BRODERICK NANOPROBE ⁸ biosensor comprising lauric acid, the amyl form of lauric acid, and/or laurate. Empirical data in the Broderick Laboratory have proven that the sensor images beauty products enabling the manufacture and sales of a myriad of products sought for in today’s anti-aging market. The prior art does not disclose that lauric acid detects and images biogenic amines and other neurotransmitters to provide healthier skin and fragrances to add beauty products to the market via the BRODERICK NANOPROBE ⁸ probes and sensors.

The contents of all patents, patent applications, published PCT applications and articles, books, references, reference manuals and abstracts cited herein are hereby incorporated by reference in their entirety to more fully describe the state of the art to which the invention pertains.

As various changes may be made in the above-described subject matter without departing from the scope and spirit of the present invention, it is intended that all subject matter contained in the above description, or defined in the appended claims, be interpreted as descriptive and illustrative of the present invention. Many modifications and variations of the present invention are possible in light of the above teachings.

EXAMPLES

The BRODERICK PROBE®) albumin biochip recoils skin muscle and innervates skin muscle in the aging skin to make the skin dramatically more supple and springy. Albumin enables muscular tone where the muscle appears flexed even when it is at rest and where previously, before treatment, neurons had become clumped with alpha synuclein and various intermediates of synuclein deposits. Indeed, other perhaps unhealthy molecules, toxins, such as the orthoquinones, are detected instead because of the presence of these toxins in air. By removing oxygen ( deaeration) to enable the detection of the healthy neurotransmitters of the skin, such as dopamine, serotonin, L-tryptophan and ceramides, albumin was tested for “unmasking” the healthy neurotransmitters and precursors. Toward this goal, nitrogen was inserted into the custom-made calibration cell to remove the toxins by deaeration during studies of the albumin biochip for detection of healthy nemotransmitters in the skin organ. Albeit, oxygen and water (H2O) are different molecules, deaeration also propels removal of water in addition to the oxygen molecules. The end result is a decrease in inflammation that is derived from oxidative stress or proxies thereof. Thus, the data report that it is the bovine serum protein, albumin, within the inventive art of the Broderick phosphotidyl polymer with albumin and phosphotidylethanolamine coating, that provides at least one of the necessary elements or an element delivered by electrochemical nanotechnology to reverse aging of the skin. Thus, the elastin, a protein in the extracellular matrix of connective tissue, is replaced or at least the loss of elastin is ameliorated in the aging skin by the albumin biochip. Without wanting to be bound by a mechanism, the advantage of albumin appears to be its donor role for flexibility in its solubility in the skin. That is, the role of albumin as an antioxidant assists in reducing swelling because albumin is a powerful tool in modulation of oncotic pressure. Albumin provides an advantage for topical usage which data then can be gleaned with or without the laser part of the BRODERICK PROBE¹' nanoprobe. It is noteworthy that albumin and phosphotidylethanolamine allow studies of the simulated brain. Comparison of the constituents of the simulated brain provide the data that albumin, although not electroactive, increases dopamine and serotonin in the simulated brain and the enhancement of albumin is specific for the medium chain versus the long chain fatty acids. Comparison of the stearate and the laurate nanoprobes, as regards the deposition of albumin, is provided in Tables A-D.

Current Responses for the K-Laurate and J-Stearate Fatty Acid Broderick Nanoprobe

Note'. K, laurate; J, stearate; DA, dopamine; 5-HT, serotonin; PEA, phosphotidy lethanolamine; BSA, bovine serum albumin.

Claims

CLAIMS:

1. A method of diagnosing amyloidosis and/or amyloidosis-associated pathology in a subject in need thereof, said method comprising: a) generating a temporally resolved sensor scan of said subject using a biosensor placed on said subject; b) determining from said scan a concentration of biogenic amines and, optionally, other neurotransmitters associated with amyloidosis in said subject; and c) comparing said amyloidosis-associated concentration to specific threshold values to determine a concentration of statistically significant differences, wherein said differences are indicative of amyloidosis-associated pathology, wherein said threshold values are derived from the sensor scan of at least one healthy cell, tissue, organ or organism.

2. The method of Claim 1 , wherein the amyloidosis-associated pathology is primary localized cutaneous amyloidosis (PLCA).

3. The method of Claim 2 wherein the PLCA is lichen amyloidosis, macular amyloidosis, or nodular amyloidosis.

4. The method of Claim 1 , wherein the subject is a human.

5. The method of Claim 1, wherein the neurotransmitter is serotonin and/or dopamine.

6. The method according to Claim 1 , wherein the biosensor is a biochip placed on the skin and/or under the fingernail, wherein the biochip comprises albumin.

7. The method according to Claim 1, wherein the biosensor comprises albumin, lauric acid, laurate, squalane, ceramides, sphingosines, cerebrosides and combinations thereof.

8. A method of treating amyloidosis and/or amyloidosis-associated pathology in a subject in need thereof, said method comprising: a) generating a temporally resolved sensor scan of said subject using a biosensor placed on said subject; b) determining from said scan a concentration of biogenic amines and, optionally, other neurotransmitters associated with amyloidosis in said subject; c) comparing said amyloidosis-associated concentration to specific threshold values to determine a concentration of statistically significant differences, wherein said differences are indicative of amyloidosis-associated pathology, wherein said threshold values are derived from the sensor scan of at least one healthy cell, tissue, organ or organism; and d) administering to said subject a pharmaceutical composition or therapy that is known to treat said pathology.

9. The method of Claim 8. wherein the amyloidosis-associated pathology is primary localized cutaneous amyloidosis (PLCA).

10. The method of Claim 9 wherein the PLCA is lichen amyloidosis, macular amyloidosis, or nodular amyloidosis.

11. The method of Claim 8, wherein the subject is a human subject.

12. The method of Claim 8, wherein the neurotransmitter is serotonin and/or dopamine.

13. The method according to Claim 8, wherein the biosensor is placed on the skin and/or under the fingernails.

14. The method of Claim 8, wherein the composition or therapy is selected from the group consisting of albumin, lauric acid, laurate, anti-inflammatories, steroids, prednisone, colchicine, dimethylsulfoxide (DMSO), antihistamines, light therapy, stimulation therapy, carbidopa /levodopa, pramipexole, apomorphine, selegiline, Xadago, dopamine modulators. serotonin modulators, catechol-o-methyl transferase (COMT) inhibitors, monoamine oxidase (MAO) inhibitors, electrometallurgy therapy, cobalt, cobalt catalysts, antagonists of iron, magnesium, copper, catalytic converters, catalysts, metal catalysts, enzymes, antibodies, pronatinib, enoxaparin fragments, serotonin, somatostatin, N-Methyl-D aspartate therapies, Co- Q-10 therapies, mitochondrial therapies, inflammation inhibitors, melatonin, indoles, alpha synuclein modulators and chelators, indole derivatives, apomorphine, dopamine auto-receptor antagonists and agonists thereof, N acetyd serotonin, precursors, kynurenine modulators, quinolinic acid inhibitors, cytokine restorative therapy, reperfusion therapies, arachidonic acid metabolites, biogenic amine therapy, indoleamine therapy, glutamine, glutamate, GABA therapy, dynoiphin fragment therapy, receptor inhibitors of protein kinase 1 (RIPK1), serine, threonine, tyrosine, inhibitors, protein kinase inhibitors and combinations thereof, proline, cysteine, progeline, prolagine, antioxidants, taurine, taurine copolymers, magnesium taurate, squalene, lavender, caprylic acid, coconut oil, magnolia oil, peptides, peptide therapies, polyphenols and sugars and combinations thereof, Quinone-Tryptophan-Hybrid- Aggregation-Inhibitors, anthragen quinone blockers, G 12/13-GSK 3, G 12/13-GSK 3 beta antagonists and partial antagonists thereof, glycogen synthase kinase 3 alpha, glycogen and glycogen mediators, mitochondria pyruvate earner 1 , hyaluronic acid (HA), docetaxel loaded HA, kami-un-tanto, kampo herbal agents, hydrolyzed collagen, collagen, elastin, bioderm, medium chain triglycerides, light chain immunoglobulins, saw palmetto, Vitamin A, retinal, retinoid, Vitamin B, thiamine, pyrithiamine, thiamine pyrophosphate, magnolia oil, dihydrotestosterone modulators, easyliance, retinylidene, Schiff base, insulin, beta cells, streptozotocin blockers, dopamine, serotonin and derivatives and precursors thereof, polycrystalline potash, nitrogen, zinc, phosphorus, agricultural plant products, organic/inorganic materials mining process, fertilizer, halite, sylvite, carnallite, kieserite and combinations thereof.

15. The method of Claim 14 wherein the composition is squalene, lauric acid, laurate, ceramides, sphingosines, cerebrosides, albumin or combinations thereof.

16. The method of Claim 12 wherein administration is by biochip under thefingernails and the composition penetrates the skin.

17. A method of rejuvenating skin in a subject in need thereof, said method comprising administering to said subject a composition by a biochip applied topically, fit under a fingernail or used as an infrared laser, wherein the biochip comprises albumin, phosphotidyl polymer, phosphotidylethanolamine, squalene or combinations thereof.

18. The method of Claim 17, wherein facial skin is rejuvenated.

19. A method of treating amyloidosis and/or amyloidosis-associated pathology in the skin of a subject of color, in need thereof, said method comprising: a) generating a temporally resolved sensor scan of said subject using a biosensor placed on said subject, wherein the biosensor comprises of organic biopolymers of phospholipids and optical opsins with retinal; b) determining from said scan a concentration of biogenic amines and, optionally, other neurotransmitters associated with amyloidosis in said subject; c) comparing said amyloidosis-associated concentration to specific threshold values to determine a concentration of statistically significant differences, wherein said differences are indicative of amyloidosis-associated pathology, wherein said threshold values are derived from the sensor scan of at least one healthy cell, tissue, organ or organism; and d) administering to said subject a pharmaceutical composition or therapy that is known to treat said pathology.

20. The method of Claim 19, wherein the biosensor is a biochip applied topically, fit under a fingernail or used as an infrared laser, wherein the biochip comprises albumin.