Methods for determining the key characteristics of fragrance blends, methods for determining the key notes of fragrance blends, and corresponding systems

Abstract

A method (100) for determining the tonality of a combination of notes includes: a step (105) of inputting at least one volatile molecule digital identifier on a computer interface, the volatile molecule digital identifier representing an aromatic volatile molecule, the input defining a formulation; a step (110) of calculating a value by a calculation system for at least one volatile molecule digital identifier of the formulation, the value representing the effect of each molecule on the activity level of an odor receptor represented by an odor receptor digital identifier, each volatile molecule digital identifier being associated with at least one odor receptor digital identifier, the association being many-to-many; and a step (115) of determining a value representing at least one tonality forming a combination of notes by a calculation system for the formulation and depending on the calculated effect of at least one odor receptor activity level and a value representing an odor receptor activation threshold, each odor receptor digital identifier being associated with a tonality digital identifier, the association being one-to-one.

Description

[0001] This invention is a divisional application of patent application No. 202080056744.9, filed on October 2, 2020, entitled "Method for determining the notes of a fragrance combination, method for determining the notes of a fragrance combination and corresponding system". Technical Field

[0002] This invention relates to a method for determining the timbre of a fragrance composition, a system for determining the timbre of a fragrance composition, and a system for determining the timbre of a fragrance composition. It is particularly applicable to the fields of fragrance design and olfaction, fragrances (cosmetic flavorings), fine fragrance flavorings, and flavorings (food flavorings). This invention is also applicable to odorless or non-fragrance compositions / compositions designed to enhance or reduce the perceptibility of specific timbre in other compositions / compositions. Background Technology

[0003] Since the initial identification of odor receptors in 1991, much work has been done to advance our understanding of olfaction and how humans perceive volatile chemicals. At the periphery of the human olfactory system, the main olfactory epithelial cells lining the nasal cavity contain millions of olfactory sensory neurons (OSNs), each expressing a single member from a family of approximately 400 complete odor (olfactory) receptor (OR) genes. Each OR can be activated by several volatile compounds, and a single volatile compound can activate multiple ORs. This results in a combination of OSN activation codes for each volatile chemical and mixtures thereof. Each receptor is randomly expressed in the OSN in a monogenic and monoallelic manner, producing an OSN type for each OR allele present in the genome. The subset of the total OSN population dedicated to each OSN type varies depending on the gene selection frequency of each OR. Each OSN type subpopulation provides discrete channels of information about one or more identities of molecules and the concentration of volatile compounds they are exposed to at any given time. The induced activity level in each OSN of each OSN type varies depending on the concentration of volatile compounds it accepts as an OR and the binding and activation parameters associated with each OR-compound pair. Furthermore, some OR-ligand pairs induce or enhance OSN activity, while others reduce or inhibit it. This can occur competitively, where compounds compete to bind ORs, or non-competitively, where more than one compound can bind an OR simultaneously. The combinatorial logic of these approximately 400 input channels (i.e., the peripheral olfactory system) is translated by subsequent downstream neural networks and results in our olfactory sensations.

[0004] The fragrance and flavor (F&F) industry is constantly looking for new ingredients, new fragrance (perfumery) and flavoring applications, improved sensory experiences, and more stable, biodegradable, and non-toxic compounds.

[0005] Because odorants or aroma molecules may interact with several olfactory receptors (ORs), it is often difficult to infer the tonality of a volatile compound based solely on its chemical structure. Conversely, because each OR may interact with several odorants and aroma molecules with different chemical structures and evoke different sets of tonality, it is often difficult to infer the nature of the information encoded by the OR.

[0006] There is still a need to predict at least one olfactory tone of a given compound or composition / combination based on OR activation, and to facilitate the discovery of new flavor and flavor components relevant to the F&F industry. Summary of the Invention

[0007] The present invention aims to overcome all or part of these shortcomings.

[0008] Therefore, according to the first aspect, the present invention aims to provide a method for determining the tone of a combination, comprising:

[0009] The step of entering at least one volatile molecule numerical identifier on a computer interface, wherein the volatile molecule numerical identifier represents an aromatic volatile molecule, and the input defines a formula.

[0010] ~ For at least one volatile molecule digital identifier of the formulation, a step of calculating a value by a calculation system, the value representing the influence of each molecule on the activity level of an odor receptor represented by an odor receptor digital identifier, each volatile molecule digital identifier being associated with at least one odor receptor digital identifier, the association being many-to-many, and

[0011] ~ For this formulation and depending on the calculated effect of at least one odor receptor activity level and a numerical value representing the odor receptor activation threshold, the step of determining a numerical value representing at least one tonality forming the combined tone by a calculation system, wherein each odor receptor digital identifier is associated with a tonality digital identifier, the association being a one-to-one association.

[0012] Such specifications allow for the automatic prediction of the tonality of dynamic input combinations. This prediction enables a more efficient and productive fragrance and flavor design cycle.

[0013] In a particular embodiment, the method of the present invention includes, downstream of the calculation step, a step of calculating, for at least one odor receptor, a total activity level associated with at least one influence of the calculated activity level by a calculation system.

[0014] Such a specification allows for the prediction of the overall effect on the perceived tonality of a given combination of tones, rather than a molecule-by-molecule approach.

[0015] In a particular implementation, the method object of the present invention includes:

[0016] ~ Steps to modify the numerical values ​​representing the fragrance notes in a fragrance blend on a computer interface.

[0017] ~ The step of calculating the modification amount of the total activity level of at least one odor receptor using a calculation system.

[0018] ~ The step of determining a set of at least one set of volatile molecule digital identifiers by a calculation system, wherein the total activity level influence value presented by this set is equal to the calculated total activity level modification.

[0019] ~ The step of providing the group to a computer interface.

[0020] Such a specification allows for the automatic modification of a formulation by fitting new molecules into the formulation or by removing input molecules from the formulation, thereby achieving a target combination of at least one tone.

[0021] In a particular embodiment, each tone is associated with a tone numerical identifier, and the method includes an automatic tone selection step that depends on the result of comparing the tone numerical identifier of the combined tone with a set of at least one predetermined tone numerical identifier, and a modification step of the numerical value of the aroma of the selected tone identifier representing the combined tone is configured to reduce the numerical value of the selected tone identifier to a reduced value, preferably to zero.

[0022] Such regulations allow for the automatic removal of tones deemed unpleasant or unnecessary.

[0023] In a particular implementation, the numerical representation of the effect of molecules, represented by numerical identifiers of volatile molecules, on the activity level of odor receptors is:

[0024] ~ Activation of the odor receptors,

[0025] ~ Inactivation of the odor receptors,

[0026] ~ Enhancement of the odor receptors, and / or

[0027] ~ Inhibition of the odorant receptors.

[0028] Such an implementation scheme allows for the precise definition of the types of effects that volatile molecules may have on odor receptors.

[0029] In a particular embodiment, the determining step is configured to provide at least one volatile molecule digital identifier that presents a numerical value representing the effect on the activity of the odor receptor associated with the tone modified in the modifying step, the effect corresponding to the enhancement or inhibition of the odor receptor.

[0030] This timbre modifier is context-dependent on the application of the fragrance. For example, adding volatile molecules that reduce the activity of odor receptors to a formulation can decrease the perception of ambient odors (applicable to toilets, cat litter, deodorants, laundromats, etc.). Similarly, using enhancers with faster release kinetics (e.g., top notes) to enhance receptor activity can allow for the selective enhancement of the base timbre earlier than typically occurs in the fragrance experience. In a particular embodiment, the method of the present invention comprises:

[0031] The step of selecting the volatile molecule digital identifier for this formula on the computer interface.

[0032] ~ The step of determining at least one set of at least one volatile molecule digital identifiers through a calculation system, wherein the set presents a numerical value representing the effect on the activity level of the odor receptor, the numerical value being equal to the numerical value representing the effect of the selected volatile molecule digital identifier on the activity level of the odor receptor, and

[0033] ~ The step of providing the group to a computer interface.

[0034] Such regulations allow for the automatic identification of alternative molecules that can be used to reformulate a product. These alternative molecules may have better environmental or cost impacts than the originally input molecules.

[0035] In a particular implementation, the method object of the present invention includes:

[0036] The step of selecting at least two volatile molecule digital identifiers for the formulation, wherein the at least two volatile molecules are associated with the activation of at least two different odor receptors called "target receptors".

[0037] The step of determining a volatile molecule numerical identifier, which presents a numerical value representing the effect on the activity level of each target receptor, is equal to the numerical value representing the effect of the selected volatile molecule numerical identifier on the activity level of the odor receptor, and...

[0038] ~ The step of providing the determined numerical identifiers of volatile molecules to the computer interface.

[0039] Such a rule allows for the substitution of several molecules with a single molecule, thereby optimizing the designed formulation.

[0040] In a particular embodiment, the method of the present invention includes, downstream of any determining step, estimating the number of at least one of the volatile molecule digital identifiers, the number being used for a downstream step of providing a set of at least one volatile molecule digital identifier.

[0041] Such a specification allows for the prediction of molecules to be added / removed from the formulation, as well as the quantity of such molecules to be added / removed.

[0042] In a particular implementation, an optimization rule is executed by a step of determining at least one set of at least one set of volatile molecule digital identifiers through a computational system. This rule is at least one of the following:

[0043] The first rule states that a defined set of at least one volatile molecule digital identifiers is configured to present a minimum number of volatile molecule digital identifiers.

[0044] The second rule, wherein the identified set of at least one volatile molecule digital identifiers is configured to present a minimum total quantity indicator of the corresponding volatile molecule digital identifiers,

[0045] ~ The third rule, wherein the identified set of at least one volatile molecule digital identifiers is configured to present a minimum number of negative volatile molecule digital identifiers.

[0046] The fourth rule, wherein at least one volatile molecule numerical identifier is associated with a volatile molecule delivery capability indicator, is configured to adapt a determined set of at least one volatile molecule numerical identifiers to the volatile molecule numerical identifiers in that set, depending on the volatile molecule delivery capability indicator.

[0047] ~ Rule 5, wherein a set of at least two volatile molecule numerical identifiers is configured to minimize the overlap of odor receptors activated by said set of molecules.

[0048] ~ Rule Six, wherein a set of at least two volatile molecule numerical identifiers is configured to minimize the modulation of odor receptors activated by said set of molecules,

[0049] ~ Rule 7, wherein the identified set of at least one volatile molecule numerical identifiers is configured to maximize the negative modulation or inhibition of odor receptors associated with a predetermined undesirable olfactory tone.

[0050] ~ Rule 8, wherein the identified set of at least one volatile molecular numerical identifiers is configured to maximize the positive modulation or enhancement of odor receptors associated with a predetermined desired olfactory tone, and / or

[0051] ~ Rule 9, wherein a set of at least one volatile molecule numerical identifiers is configured to minimize or maximize at least one cost function, each volatile molecule being associated with at least one numerical value representing cost.

[0052] Such an implementation scheme allows for the optimization of the formulation by following predetermined optimization rules.

[0053] In a particular embodiment, the method of the present invention includes the step of inputting a quantity of at least one volatile molecule on a computer interface, the quantity being used to: calculate a numerical value by a calculation system for at least one volatile molecule numerical identifier of the formulation, the numerical value representing the effect on the activity level of odor receptors.

[0054] This implementation scheme allows quantity to be considered as a parameter for tone prediction.

[0055] In a particular embodiment, at least one volatile molecule digital identifier is associated with a volatile molecule delivery capability indicator, and at least one of the calculation step and the determination step is performed depending on the volatile molecule delivery capability indicator associated with at least one input volatile molecule digital identifier.

[0056] Such implementation schemes allow for more accurate determination of the tonality in the combined notes generated by the input formula, or conversely, accurate determination of volatile molecules in the formula based on the input tonality.

[0057] In a particular implementation, the volatile molecule delivery capability indicator represents the substrate where the relevant volatile molecule is located.

[0058] In a second embodiment, the present invention relates to a method for determining a formulation, comprising:

[0059] ~ For at least one tonality identifier, the step of entering a numerical value on a computer interface, the numerical value representing the tonality of the combination of tones generated by the formula to be determined,

[0060] ~ For a given formulation and depending on at least one numerical value representing at least one tonality of the combined tonality, the step of determining, through a calculation system, the numerical value of the activity level of at least one odor receptor digital identifier representing an odor receptor, wherein each odor receptor digital identifier is associated with at least one tonality digital identifier, the association being one-to-one.

[0061] ~ The step of determining a formulation represented by at least one set of at least one volatile molecular digital identifiers, which presents a numerical value representing the effect on the activity level of the odor receptor digital identifier, the numerical value being equal to a determined numerical value representing the activity level of the odor receptor, each volatile molecular digital identifier being associated with at least one odor receptor digital identifier, the association being a many-to-many association.

[0062] In a particular implementation, the relationship between the volatile molecule digital identifier and the odor receptor digital identifier can be one-to-many or many-to-one.

[0063] Such a specification allows for reverse recipe design, where the user determines the desired tone and then infers the recipe as a result of the target tone.

[0064] In the third embodiment, the object of the present invention is a combined tone determination system, comprising:

[0065] ~ An organization that inputs at least one volatile molecule numerical identifier, the volatile molecule numerical identifier representing an aromatic volatile molecule, the input defining the formulation.

[0066] ~ For at least one volatile molecule digital identifier of the formulation, a mechanism for calculating a value representing the effect of each molecule on the activity level of an odor receptor represented by an odor receptor digital identifier, each volatile molecule digital identifier being associated with at least one odor receptor digital identifier, the association being many-to-many.

[0067] ~ For this combined tone, depending on the calculated influence of at least one odor receptor activity level and a numerical value representing the odor receptor activation threshold, a mechanism is established to determine the numerical value representing at least one tonality that forms the combined tone, where each odor receptor numerical identifier is associated with a tonality numerical identifier in a one-to-one manner.

[0068] Such a system offers the same advantages as the corresponding method.

[0069] In its fourth form, the present invention relates to a formulation determination system, comprising:

[0070] ~ For at least one tonality identifier, a mechanism that inputs a numerical value on a computer interface, the value representing the tonality of the combined tone generated by the formula to be determined.

[0071] For a given formulation and depending on at least one numerical value representing at least one tonality of the combined tonality, a computational system determines the numerical value of the activity level of at least one odor receptor digital identifier representing an odor receptor, wherein each odor receptor digital identifier is associated with a tonality digital identifier in a one-to-one manner.

[0072] ~ An organization that determines a formulation represented by at least one set of at least one volatile molecular digital identifiers, which presents a numerical value representing the effect on the activity level of the odor receptor digital identifier, the numerical value being equal to a determined numerical value representing the activity level of the odor receptor, each volatile molecular digital identifier being associated with at least one odor receptor digital identifier, the association being a many-to-many association.

[0073] Such a system offers the same advantages as the corresponding method. Attached Figure Description

[0074] Other advantages, objects, and specific features of the invention will become apparent from the following non-exhaustive description of at least one particular method or system that is an object of the invention, taken in conjunction with the accompanying drawings, wherein:

[0075] Figure 1 The first series of specific steps of the method subject of the present invention are schematically illustrated.

[0076] Figure 2 The second series of specific steps of the method subject of the present invention are schematically illustrated.

[0077] Figure 3 The first specific embodiment of the system subject matter of the present invention is illustrated schematically.

[0078] Figure 4 A second specific embodiment of the system subject matter of the present invention is illustrated schematically.

[0079] Figure 5 Examples of the content of the four flavor blend components (A, B, C, and D) that activate ORD1, OR8B3, and OR5AU1, along with their respective composition ratios.

[0080] Figure 6 This indicates the percentage activity level of the components that activate OR8D1, OR8B3, and OR5AU1.

[0081] Figure 7 The study demonstrated that the induced odor receptor activity was validated by modulators A and B by comparing the identified model with in vitro control experiments.

[0082] Figure 8This demonstrates the consistency between the celery spice assessment and the model's sensory predictions.

[0083] Figure 9 This indicates that the induced odorant receptor activity was verified by comparing the model with in vitro control experiments using modifiers A, C, and D.

[0084] Figure 10 This demonstrates the consistency between the hay spice assessment and the model's sensory predictions, and

[0085] Figure 11 This represents the consistency between the coconut-toned spice assessment and the model's sensory predictions. Detailed Implementation

[0086] This specification is not exhaustive, as each feature of one embodiment can be advantageously combined with any other feature of any other embodiment.

[0087] It should be noted that the accompanying drawings are not drawn to scale.

[0088] The contents of US62 / 911,096 are incorporated herein by reference.

[0089] As used herein, the term "volatile molecule" refers to any molecule, preferably one that exhibits flavoring or aroma properties. The terms "compound" or "ingredient" refer to the same thing as "volatile molecule".

[0090] The term "formulation" refers to a liquid, solid, or gaseous aggregate of at least one volatile molecule.

[0091] The term "composition" refers to the olfactory perception of a formulation. A composition is defined by the perceptibility of at least one tonality.

[0092] As used herein, “olfactory tonality” or “tonality” is the sensory characteristic of volatile molecules that is triggered by the activation of an orbicularis oculi (OR), which is transmitted through the olfactory bulb and processed by the central nervous system to produce a specific olfactory experience in the subject. This experience has properties that can be described verbally by the subject, often referencing everyday objects associated with the olfactory experience. Additional modifiers are usually required to capture the specificity of the tonality. When evaluated by trained experts (such as perfumers), everyday objects with characteristic “scents” often evoke experiences of multiple separable tonalities. The experience of a single tonality depends entirely on the specific OR activated in the subject; thus, a single OR produces the perception of a single tonality, while the multiple tonalities produced by everyday objects are determined by a set of ORs activated by a set of volatile molecules emitted through them. Although the mechanism differs in many important respects, the perception of olfactory tonality can be thought of as analogous to the perception of a single discernible pitch through the auditory system, even when multiple pitches are played simultaneously. Similarly, the same pitch (F-sharp, G-flat, etc.) can be described in multiple ways, and therefore the same olfactory tonality can be described in multiple ways.

[0093] Non-limiting examples of olfactory tones include earthy, coconut, celery, and hay (see Example 1 in US62 / 911,096). For example, OR11A1 agonists all share a common earthy tone, even though they elicit a whole set of different tones (see Example 2 in US62 / 911,096). Volatile molecules may have more than one tone. For example, β-ionone has a violet tone and a blondewoody tone, respectively, generated by activating OR5A1 and OR7A17 (see Example 3 in US62 / 911,096).

[0094] As used herein, “fragrance / scent” refers to the olfactory perception resulting from the sum of activation, enhancement, and inhibition (when present) of odor receptors by at least one volatile molecule. Thus, by way of illustration and not intended to limit the scope of this disclosure, “fragrance / scent” originates from the olfactory perception resulting from the sum of activation of a first volatile molecule of an OR associated with coconut notes, activation of a second volatile molecule of an OR associated with celery notes, and inhibition of a third volatile molecule of an OR associated with hay notes.

[0095] The inventors have discovered that the activation of an OR triggers a tonality perceptibility in a one-to-one relationship, such that a combined tone, as a collection of at least one tonality, can be encoded by a set of corresponding activations of OR that may have associated activation levels.

[0096] As used in this article, “note” or “olfactory note” or “fragrance note” indicates a timbre category. For example, floral notes include lily of the valley and violet notes.

[0097] The term "OR," or "olfactory receptor," or "odorant receptor," refers to one or more members of the G protein-coupled receptor (GPCR) family that are expressed in olfactory cells. OSNs (olfactory sensory neurons) can also be identified by morphology or by the expression of proteins specifically expressed in olfactory cells. Members of the OR family may have the ability to act as receptors for olfactory signal transduction.

[0098] "OR agonists" or "agonist compounds" refer to volatile compounds or ligands that bind to OR, activate OR, and induce olfactory receptor transduction cascades.

[0099] "OR antagonists" or "antagonist compounds" refer to volatile compounds or ligands that bind to OR and reduce the measured activity of olfactory receptors in the presence of an agonist.

[0100] An "enhancer" is a compound or ligand that, when bound to an agonist compound, enhances the activity of the receptor (OR) by binding to it and through a transduction cascade of olfactory receptors exposed to the agonist compound, compared to the receptor's activity in the absence of an enhancer. In one form, the non-agonist compound binds to a site on the receptor that is different from the binding site of the agonist compound.

[0101] "Potency" is a measure of receptor activity induced by the binding of an agonist (odorant) in terms of the amount or concentration required to produce a given level of activity. It indicates the receptor's sensitivity to different agonist concentrations and is typically assessed by calculating the EC50 (the agonist concentration required to achieve half-maximal receptor activity).

[0102] "Efficacy" refers to a measure of the activity level of an OR response to a given agonist, and is obtained by measuring the activation span between the constitutive baseline (in the absence of an agonist) and the agonist-induced activity.

[0103] The "receptive field" or "molecular sensing range" of an odor receptor refers to the range of volatile compounds that activate the receptor. It describes a different set of volatile compounds that can bind to the receptor, triggering an intracellular transduction cascade and thus transmitting the chemical stimulus to the brain via olfactory sensory neurons.

[0104] The "OR," or "odor receptor," or "olfactory receptor" polypeptide is considered to belong to the G protein-coupled receptor superfamily, which consists of a single exon approximately 1 kb long and seven transmembrane domains, exhibiting characteristic olfactory receptor-specific amino acid motifs. These seven domains are called the "transmembrane" or "TM" domains TM I through TM VII, connected by three "intracellular loop" or "IC" domains IC I through IC III and three "extracellular loop" or "EC" domains EC I through EC III. Motifs and their variants are defined, but not limited to, the MAYDRYVAIC motif (SEQ ID NO: 7) overlapping with TM III and IC II, the FSTCSSH motif (SEQ ID NO: 8) overlapping with IC III and TM VI, the PMLNPFIY motif (SEQ ID NO: 9) in TM VII, and the presence of three conserved C residues in EC II and highly conserved GN residues in TM I [Zhang, X. &Firestein, S. Nat. Neurosci. 5, 124–133 (2002); Malnic, B., et al. Proc.Natl. Acad. Sci. USA 101, 2584–2589 (2004)].

[0105] "Delivery capacity" refers to the factor that converts the amount of volatile molecules in a formulation into the amount delivered to the olfactory receptors in the subject's nose.

[0106] It should be understood that, in the context of this invention, two key relationships are established:

[0107] The first relationship links volatile molecules to the activation of OR, and

[0108] The second type of relationship links the activation of OR with a specific tone.

[0109] In particular, a given volatile molecule may interact with several ORs, while an OR may interact with several volatile molecules. However, the activity of an OR may correspond to a perceived tone triggered by the activity of a given OR. The perception of a single compound exhibiting several tones is caused by the activation of several ORs encoding said tone. The discovery of this "one-to-one" relationship is not insignificant and has important implications in formulation and fragrance design. In fact, in systems where only the volatile molecule-to-tone is known, it is impossible to accurately predict or estimate the tone of a combination of volatile molecules due to the lack of understanding, on the one hand, of the intermediate layer of interactions between molecules and ORs, and on the other hand, of the tone-to-OR relationship.

[0110] The first relationship can be obtained by contacting a volatile molecule sample with isolated ORs and monitoring the activity of each OR. The results of this experiment can be stored in a database that cross-references numerical identifiers of volatile molecules, representing the actual volatile molecules, and the effects of said volatile molecules on the ORs monitored during the experiment.

[0111] In such a method, OR can be used in any form in the methods or assays described herein, provided that the function of OR is not impaired. For example, OR can be used as follows: tissues or cells that inherently express OR, such as olfactory sensory neurons isolated from an organism and their culture products; olfactory cell membranes carrying OR; recombinant cells that have been genetically modified to express OR and their culture products; the membranes of the recombinant cells; and artificial lipid bilayer membranes carrying OR.

[0112] Indicators used to monitor olfactory receptor activity include, for example, fluorescent calcium indicator dyes, calcium indicator proteins (e.g., GCaMP, a genetically encoded calcium indicator), fluorescent cAMP indicators, cell flow assays, cell dynamics mass redistribution assays, label-free cell-based assays, cAMP response element (CRE)-mediated reporter proteins, biochemical cAMP HTRF assays, β-inhibitor protein assays, or electrophysiological recordings. In one particular embodiment, a calcium indicator dye is selected that can be used to monitor the activity of olfactory receptors (e.g., Fura-2 AM) expressed on the olfactory neuron membrane. Molecules can be screened sequentially, and odor-dependent changes in calcium dye fluorescence can be measured using fluorescence microscopy or fluorescence activated cell sorting (FACS).

[0113] Such methods allow for the identification of commonalities in olfactory perception between chemically and sensorily different volatile compounds based on their OR activation curves. Not intended to be limited to any particular theory, the OR activation curve represents a better predictor of the olfactory tone of a given volatile compound compared to physicochemical similarity alone. Not intended to be limited to any particular theory, physicochemical similarity may only partially predict olfactory similarity.

[0114] For example, olfactory neurons activated by targeted agonists, such as molecules with specific olfactory tones, are isolated using glass microelectrodes or FACS machines connected to a micromanipulator. Mouse olfactory sensory neurons are screened using Ca2+ imaging, similar to the procedure previously described. Malnic, B., et al. Cell 96, 713-723 (1999); Araneda, RC et al. J. Physiol. 555, 743-756 (2004); and WO2014 / 210585. In particular, the number of cells that can be screened per experiment is increased to at least 1,500 using a motorized movable microscope stage. Since there are approximately 1,200 different olfactory receptors in mice, and each olfactory sensory neuron expresses only one of the genes for olfactory receptors out of the 1,200, this screening capability covers almost the entire mouse odor receptor repertoire. In other words, the combination of calcium imaging for high-throughput screening of olfactory sensory neurons results in the identification of almost all odor receptors that respond to specific odor signatures. In one morphology, odor receptors that respond to a target agonist, such as those with a specific olfactory tone, can be isolated for receptor recognition. For example, at least one neuron is isolated for receptor recognition.

[0115] The second type of relationship can be obtained by linking at least one olfactory tone to an OR, which is done by screening chemically and sensorily distinct libraries of volatile compounds for the OR to identify at least one common olfactory tone among the volatile compounds that act as activators of the screened OR.

[0116] This method of associating at least one olfactory tone with an olfactory receptor can be performed by: providing an OR, contacting the OR with a volatile molecule having at least one known tone, determining whether the compound activates at least one olfactory receptor, repeating the contact and determination steps with different compounds having at least one known tone, classifying a subset of compounds that activate the OR, identifying at least one known tone common to the subset of compounds, and associating the identified at least one known tone with the OR.

[0117] By comparing the overall descriptions of compounds and identifying common descriptors among activators, it is possible to correlate the common olfactory tones of compounds that activate a given receptor. It should be understood that this olfactory tone can be semantically described in several ways, such as by a perfumer. Examples of such semantic similarities that capture the same olfactory tone include, for instance: ocean, water, and ozone; soil, humus, and moss; hay, coumarins, and tonka; celery, fenugreek, and maple; lily of the valley and lily of the valley.

[0118] The results of such experiments can be stored in a database that cross-references OR numeric identifiers, representing the actual ORs, and information representing the tones associated with the activation of these ORs.

[0119] Figure 1 A series of specific steps of the object method 100 of the present invention are illustrated. This combined tone determination method 100 includes:

[0120] Step 105 involves entering at least one volatile molecule digital identifier on a computer interface, the volatile molecule digital identifier representing an aromatic volatile molecule, the input defining the formulation.

[0121] ~ For at least one volatile molecule digital identifier of the formulation, step 110 involves calculating a value through a calculation system, the value representing the effect of each molecule on the activity level of an odor receptor represented by an odor receptor digital identifier, each volatile molecule digital identifier being associated with at least one odor receptor digital identifier, the association being many-to-many.

[0122] ~ For this formulation and depending on the calculated effect of at least one odor receptor activity level and a value representing the odor receptor activation threshold, step 115, by calculating the value representing at least one tonality that forms the combined tone, each odor receptor digital identifier is associated with a tonality digital identifier, the association being a one-to-one association.

[0123] Step 105 can be performed using any type of computer interface, such as a keyboard, mouse, or touchscreen. Such an interface may also include a graphical user interface (GUI) that allows user interaction and input, which is part of software running on a computing device such as a personal computer or computer server. In derivative embodiments, the computer interface is inherently logical, and the input corresponds to commands received via an electronic network or cable and originating from a command mechanism.

[0124] Figures 1 to 4 The specific architecture of the computing system used is not important to this invention. That is, such a computing system can be distributed, integrated, using a client-server architecture, or using local and / or remote computing resources. The data stored and accessed can be stored in a traditional database, computer memory, or a distributed database.

[0125] During step 105, the user can select one or more volatile molecule numerical identifiers to add to the recipe. These volatile molecule numerical identifiers can be, for example, icons, text labels, or numbers. These identifiers preferably correspond to entries in computer memory or a database.

[0126] The formulation may further contain a certain amount of volatile molecules, expressed in liquid, solid, or gaseous quantities. Such amounts may be measured in parts per million (ppm) or as a measure of the headspace concentration of the molecules in the gas phase, for example, mol / m³. 3 To express.

[0127] The resulting collection of tones perceived from the evaporation and / or gaseous form of volatile molecules, as well as the transport of volatile molecules, is called composite tone.

[0128] Calculation step 110 is performed, for example, by a computing system configured to run dedicated software. During this calculation step 110, each input volatile molecule numerical identifier is matched with the corresponding activated OR. If an OR is activated or enhanced, the effect on that OR is positive. If an OR is deactivated or its activation is inhibited, the effect on that OR is negative. A volatile molecule numerical identifier can simultaneously activate / enhance / deactivate / inhibit several ORs.

[0129] This calculation step 110 may include the step of accessing an information storage (e.g., a database or computer memory) and retrieving the information (not shown), which stores the effect of volatile molecule digital identifiers on at least one referenced OR.

[0130] This calculation step 110 is described in embodiment n°2 of U.S. Patent Application No. 62 / 911,096.

[0131] Step 115 is performed, for example, by a computing system configured to run dedicated software. During step 115, information related to tonality (which is associated with at least one OR activated by at least one volatile molecule) is generated. Such information may be the presence of the tonality or the efficacy of the OR on the tonality.

[0132] This means that the numerical value representing tone might represent:

[0133] ~ The perceptibility of one or more tones,

[0134] ~ The quantification of perceptibility

[0135] ~ The suppression of the tone,

[0136] ~ The increase in the perceptibility of the tonality, and / or

[0137] ~ The reduction in tone.

[0138] This determining step 115 may include the step of accessing an information storage (e.g., a database or computer memory) and retrieving the information (not shown), the information storage containing tone information to be generated for at least one OR.

[0139] Step 115 may include calculating a numerical value associated with the total activity of at least one OR, wherein the at least one numerical value represents a quantification of the stored tonality. For example, such a numerical value may indicate whether an associated tonality is retrieved, the intensity of the perceived tonality, or the probability that the tonality is perceived by the subject.

[0140] For example, such information can be obtained by reading it from a suitable information storage device, or it can be the result of calculation by a computing system.

[0141] Preferably, an OR activation level threshold is used to determine a numerical value representing the tone, such as those disclosed above. In such a derivative scheme, the activation threshold may be common to all ORs or determined individually for each OR, and the threshold is observed and recorded empirically. Such a threshold is, for example, 20% of the average maximum activation level of the ORs. For example, these thresholds are stored in an activation threshold database used during step 115.

[0142] OR activity depends on the potency and efficacy of any given agonist for that OR, obtained from receptor screening experiments. With this information, one can determine the minimum amount of material (based on potency data) required to produce sufficient activity (based on efficacy data) to generate perception of the corresponding tone. The amount of compounds that inhibit or enhance ORs can be similarly obtained from receptor screening data. This quantification can be tailored to the target outcome for each OR presented as a mixture (or formulation) of compounds (the presence of the desired tone, reduction of unwanted tone).

[0143] The output of step 115 may be provided as result information on a computer interface such as a computer screen.

[0144] In a particular implementation, for example Figure 1 According to the embodiment shown, the object method 100 of the present invention includes, downstream of the calculation step 110, a step 120, calculating, for at least one odor receptor, a total activity level related to at least one influence of the calculated activity level by a calculation system.

[0145] Calculation step 120 is performed, for example, by a computing system configured to run dedicated software. During this calculation step 120, the sum of the individual effects of activation / enhancement / inhibition / inactivation ORs is obtained, and the result is then used to provide information during determination step 115.

[0146] In a particular implementation, for example Figure 1 The embodiment shown, the object method 100 of the present invention includes:

[0147] Step 125: Modify the numerical values ​​representing the aroma notes of the formula on the computer interface.

[0148] Step 130: Calculating the modification amount of the total activity level of at least one odor receptor using a calculation system.

[0149] ~ Step 135: Determining a set of at least one set of volatile molecule digital identifiers through a calculation system, wherein the total activity level influence value presented by this set is equal to the calculated total activity level modification.

[0150] ~ Step 140: Providing the group to the computer interface.

[0151] Modification step 125 is similar to input step 105, and may be performed, for example, by collecting user input via a human-machine interface, the input representing a modification to the flavor profile of the formula representing the initial input. The modification may be part of a formula modification command received electronically via a computing system.

[0152] A change in tonality can be a decrease in the perceived level of a given tonality or an increase in the perceived level of a given tonality.

[0153] Calculation step 130 is performed, for example, by a computing system configured to run dedicated software. During this calculation step 130, modifications affecting at least one tone are translated into modifications to the activity level of one or more base ORs.

[0154] Step 135 is performed, for example, by a computing system configured to run dedicated software. During step 135, modifications to the activity levels of one or more ORs calculated during step 130 are translated into modifications to the volatile molecular inputs of said one or more ORs that activate / enhance / inhibit / inactivate them.

[0155] It should be understood that the total activity level effect value, which is equal to the calculated total activity level modification, is interpreted as a value within an acceptable range representing the exact equation.

[0156] This modification might correspond to:

[0157] Removing volatile molecules from a formula is equivalent to removing the corresponding numerical identifiers from the formula.

[0158] The addition of volatile molecules to the formulation is converted into the addition of corresponding numerical identifiers in the formulation, and / or

[0159] Modifications to the number of volatile molecules in a formulation are converted into modifications to indicators representing the corresponding number of numerical identifiers in the formulation.

[0160] Given that the effect of volatile molecules on OR activity is many-to-many, and the effect of OR activity on tone perception ability is one-to-one for each OR and the corresponding tone, there are several combinations of calculation steps 130 and determination steps 135.

[0161] To determine the optimal solution for these steps, it is preferable to set optimization solution rules. Such solution rules might be:

[0162] The first rule states that a defined set of at least one volatile molecule digital identifiers is configured to present a minimum number of volatile molecule digital identifiers.

[0163] The second rule, wherein the identified set of at least one volatile molecule digital identifiers is configured to present a minimum total quantity indicator of the corresponding volatile molecule digital identifiers,

[0164] ~ The third rule, wherein the identified set of at least one volatile molecule digital identifiers is configured to present a minimum number of negative volatile molecule digital identifiers.

[0165] The fourth rule, wherein at least one volatile molecule numerical identifier is associated with a volatile molecule delivery capability indicator, is configured to adapt a determined set of at least one volatile molecule numerical identifiers to the volatile molecule numerical identifiers in that set, depending on the volatile molecule delivery capability indicator.

[0166] ~ Rule 5, wherein a set of at least two volatile molecule numerical identifiers is configured to minimize the overlap of odor receptors activated by said set of molecules.

[0167] ~ Rule Six, wherein a set of at least two volatile molecule numerical identifiers is configured to minimize the modulation of odor receptors activated by said set of molecules,

[0168] ~ Rule 7, wherein the identified set of at least one volatile molecule numerical identifiers is configured to maximize the negative modulation or inhibition of odor receptors associated with a predetermined undesirable olfactory tone.

[0169] ~ Rule 8, wherein the identified set of at least one volatile molecular numerical identifiers is configured to maximize the positive modulation or enhancement of odor receptors associated with a predetermined desired olfactory tone, and / or

[0170] ~ Rule 9, wherein a set of at least one volatile molecule numerical identifiers is configured to minimize or maximize at least one cost function, each volatile molecule being associated with at least one numerical value representing cost.

[0171] The fourth rule can represent the availability of volatile molecules in the headspace to produce the desired level of activation. These rules take into account nonlinear factors related to the delivery of combinatorial modulosomes, which affect the amount reaching the OR. Examples of these factors are deposition on the substrate, evaporation from the substrate, the rate of adsorption into the mucus, the transport of specialized molecules in the mucus, and the biodegradation of molecules in the mucus.

[0172] In a particular embodiment, at least one volatile molecule digital identifier is associated with a volatile molecule delivery capability indicator, and calculation step 110 is performed depending on the volatile molecule delivery capability indicator associated with at least one input volatile molecule digital identifier.

[0173] For example, volatile molecule delivery capability indicators are stored in a volatile molecule delivery capability indicator database and determined empirically.

[0174] In one example, to determine the delivery capability indicator, a formulation containing at least one volatile molecule is administered at a given concentration to a relevant substrate, such as fabric, bare skin, kitchen tiles, cat litter, or directly atomized into the air, placed under relevant environmental conditions, such as in a room with certain temperature, pressure, and humidity, and left for a relevant period of time. A known volume of air can be sampled in the room for a known period of time using suitable equipment (e.g., adsorbent tubes or fibers), and subsequently analyzed by quantitative chemical analysis instruments (e.g., gas chromatography-mass spectrometry), and the vapor phase concentration of at least one molecule can be determined.

[0175] In another example, the known vapor phase concentration of at least one volatile molecule representing the formulation can be established by using a known volume of liquid substrate, such as a viscous liquid, in a suitable chamber with a known surface area including the interface, under appropriate pressure, temperature, and humidity for a specified time. The concentration of at least one molecule can then be determined by applying the liquid substrate sample to a quantitative analytical chemistry instrument, such as a liquid chromatography-mass spectrometry (LC-MS).

[0176] In the third example, more complex delivery capability indicators can be calculated by combining the previous two examples and / or by measuring physicochemical constants (such as the Henry constant) through established methods and combining them with relevant physical models.

[0177] For example, calculation step 110 can be configured to calculate the loss due to the molecular delivery capability indicator, the loss effect representing a value of the tone determined in determination step 115.

[0178] In embodiments where a numerical value representing the tone is set, the determination step 135, 155, or 165 may be performed depending on the molecular delivery capability indicator. In such embodiments, the loss due to the molecular delivery capability indicator for a given volatile molecule numerical identifier can be compensated, for example, by increasing the amount of the volatile molecules in the formulation.

[0179] In a particular implementation, the volatile molecule delivery capability indicator represents the substrate where the relevant volatile molecule is located.

[0180] For example, the base is a fabric, a food product, or there is no base, such as when perfume aerosols are released into the air.

[0181] Additional rules related to external parameters can be formulated. In the derived scheme, each volatile molecule's numerical identifier is associated with a cost, which can be environmental, financial, or other.

[0182] In the first example of such an additional rule, the corresponding rule could be used to configure a determined set of at least one set of volatile molecule digital identifiers to present a minimum cost value.

[0183] In a second example of such additional rules, the corresponding rule could be used to configure a determined set of at least one set of volatile molecule digital identifiers to present cost values ​​that are below or above a predetermined threshold.

[0184] In a third example of such additional rules, the corresponding rule could be used to configure a determined set of at least one set of volatile molecule digital identifiers to represent the minimum sum of cost values, where at least two types of costs are considered.

[0185] Step 140, which provides the result of determining step 135, corresponds to the provision step 140 discussed above.

[0186] In a particular implementation, for example Figure 1 In the illustrated embodiment, each tone is associated with a tone numerical identifier. The method includes an automatic tone selection step 145, which depends on the result of comparing the tone numerical identifier of the recipe with a set of at least one predetermined tone numerical identifier. A modification step 125, representing the aroma value of the selected tone identifier of the recipe, is configured to reduce the value of the selected tone identifier to a reduced value, preferably to zero.

[0187] Automatic tone selection step 145 is performed, for example, by a computing system configured to run dedicated software. During this automatic tone selection step 145, the objective is to remove unpleasant tones from the combined tones. Such unpleasant tones may correspond to specific predetermined tone identifiers stored in computer memory or a database. During this automatic tone selection step 145, the tones determined during determination step 115 can be matched against the predetermined unpleasant tone identifiers, and during modification step 125, at least one of the matched tones is modified to a reduced value, preferably reduced to zero.

[0188] In a particular implementation, for example Figure 1 The embodiment shown, the object method 100 of the present invention includes:

[0189] Step 150: Select the volatile molecule digital identifier for the formulation on the computer interface.

[0190] ~ Step 155: Determining a set of at least one set of volatile molecule digital identifiers through a computational system, this set presents a numerical value representing the effect on the activity level of odor receptors, which is equal to a numerical value representing the effect of the selected volatile molecule digital identifiers on the activity level of the odor receptors, and

[0191] ~ Step 140: Providing the group to the computer interface.

[0192] Selection step 150 can be performed, for example, in a manner similar to input step 105. This selection step 150 can be performed manually or automatically as a result of a selection command sent to the computing system. The selection criteria can be arbitrary or follow an algorithmic solution based on information associated with each volatile molecule's numerical identifier, such as the cost value of each volatile molecule's numerical identifier.

[0193] Step 155 is performed, for example, by a computing system configured to run dedicated software. This step 155 can be performed in a manner similar to step 135 described above. Such a step 155 can follow the optimization rules described above.

[0194] This determination step 155 allows volatile molecules in the formulation to be replaced with at least one other volatile molecule represented by one or more corresponding numerical identifiers.

[0195] Step 140, which provides the result of determining step 155, corresponds to the provision step 140 discussed above.

[0196] In a particular implementation, for example Figure 1 The embodiment shown, the object method 100 of the present invention includes:

[0197] Step 160: Selecting at least two volatile molecule digital identifiers for the formulation, wherein the at least two volatile molecules are associated with the activation of at least two different odor receptors, referred to as "target receptors".

[0198] Step 165 involves determining a volatile molecule numerical identifier that presents a numerical value representing the effect on the activity level of each target receptor, equal to the numerical value representing the effect of the selected volatile molecule numerical identifier on the activity level of the odor receptor, and...

[0199] ~ Step 140: Providing the determined numerical identifier of the volatile molecule to the computer interface.

[0200] Such an implementation scheme aims to simplify the formulation in terms of the amount of volatile molecules used.

[0201] Selection step 160 can be performed, for example, in a manner similar to input step 105. This selection step 160 can be performed manually or automatically as a result of a selection command sent to the computing system. The selection criteria can be arbitrary or follow an algorithmic solution based on information associated with each volatile molecule's numerical identifier, such as the cost value of each volatile molecule's numerical identifier.

[0202] Step 165 is performed, for example, by a computing system configured to run dedicated software. This step 165 is designed to select a volatile molecule numerical identifier that performs the same function as the at least two volatile molecule numerical identifiers selected during step 160. In this case, the function is defined by the effect of the volatile molecule on at least two ORs. In other words, the OR effect characteristics of the identified volatile molecules should correspond to the OR effect characteristics of the selected volatile molecules.

[0203] This determination step 165 can follow optimization rules, such as those discussed above for other determination steps 135 or 155.

[0204] Step 140, which provides the result of determining step 165, corresponds to the provision step 140 discussed above.

[0205] In a particular implementation, for example Figure 1 The embodiment shown, the object method 100 of the present invention includes a step 170 downstream of determining step 135, 155 or 165, estimating the number of at least one of the volatile molecule digital identifiers, the number being used for a downstream providing step 140.

[0206] The estimation step 170 is performed, for example, by a computing system configured to run specialized software. This estimation step 170 uses, for example, an influence function that correlates the amount of volatile molecules with the activity level of the OR. The influence function may be general for all volatile molecules or specific to each volatile molecule.

[0207] Volatile molecules may compete for binding to odor receptors and may subsequently activate them. In these cases, the relative number of molecules, their respective binding coefficients, and their tendency to induce activation determine the total activation of the odor receptor (OR).

[0208] The activation of an OR by a single molecule is logarithmically dependent on the concentration of the molecule in contact with the receptor. To determine this dependence, those skilled in the art will expose a given molecule to different concentration levels and record the activation level of the OR. By increasing the concentration of the molecule and determining the range of activation levels of the OR using a sigmoid fitting function, a resulting formulation can be obtained to approximate the final activation level of the OR from any concentration value.

[0209] The activation of an receptor (OR) by multiple molecules is a nonlinear function of the ratio of their binding coefficients, the logarithm of the concentration of different molecular species, and their individual tendency to activate the receptor. In another mode of operation, two or more volatiles can bind to the receptor non-competitively and influence the binding affinity and / or activation tendency of other binding molecules unidirectionally or mutually. The total activity of the receptor is then a nonlinear combination of the logarithm of the concentration, the binding coefficient, the activation tendency, and the modulation coefficients of the binding coefficient and activation tendency. In all these cases, the resulting total activity can be directly measured in experimental assays and used to determine a function relating the number of volatile molecules to the total activity.

[0210] This function is used in a regression manner to determine the number of corresponding volatile molecules based on a given influence.

[0211] Such implementations can trigger additional optimization rules based on the amount of volatile molecules, such as those discussed above.

[0212] In a particular implementation, for example Figure 1 The embodiment shown, the object method 100 of the present invention includes a step 175 of inputting a quantity of at least one volatile molecule on a computer interface, the quantity being used for: a step 110 of calculating a value by a calculation system for at least one volatile molecule digital identifier of the formulation, the value representing the effect on the activity level of odor receptors.

[0213] Input step 175 is performed, for example, in a manner similar to input step 105. In such an input step 175, where the input represents a numerical value indicating the number of input molecules, the numerical value representing the number of volatile molecules is the input during input step 105.

[0214] Calculation step 110 can use an influence function that correlates the quantity of volatile molecules with the activity level of the OR. This influence function can be general for all volatile molecules or specific to each volatile molecule. The input quantity allows for the calculation of the influence of the volatile molecules, which in turn allows for the determination of the perceptible degree of the formulation's character.

[0215] Figure 2 A series of specific steps of the object-oriented method 100 of the present invention are illustrated. This formulation determination method 200 includes:

[0216] ~ For at least one tonality identifier, step 205 involves entering a numerical value on a computer interface, the value representing the tonality of the combined tone generated by the formula to be determined.

[0217] ~ For the formulation to be determined and depending on at least one numerical value representing at least one tonality of the combined tonality, step 210 involves, through a calculation system, determining numerical values ​​for the activity levels of at least one odor receptor digital identifier representing an odor receptor, wherein each odor receptor digital identifier is associated with at least one tonality digital identifier, and the association is a one-to-one association.

[0218] ~ Step 215: Determining a formulation represented by at least one set of at least one volatile molecular digital identifiers, the set presenting numerical values ​​representing the influence on the activity level of the odor receptor digital identifiers, the numerical values ​​being equal to the determined numerical values ​​representing the activity level of the odor receptors, each volatile molecular digital identifier being associated with at least one odor receptor digital identifier, the association being many-to-many.

[0219] Enter step 205 to discuss with about Figure 1 The input step 105 described is performed in a similar manner. According to the usage of the invention, this step can be manual or automatic. During this input step 205, it is not as... Figure 1 Instead of inputting volatile molecule identifiers as in the previous example, input tone numerical identifiers. Such tone numerical identifiers can correspond to the presence of a tone in the formulation or to the perceptibility of that tone.

[0220] Step 210 is determined, for example, by a computing system configured to run dedicated software. This determination step 210 is configured to... Figure 1 The determination step 115 is performed in reverse, because the impact on OR activity can be determined based on the given tone identifier input. This determination step 210 functions similarly to step 130, which calculates the total activity level modification, except that it is not limited to the modification amount but rather to the entire impact assessment.

[0221] Determining step 215 is performed, for example, by a computing system configured to run dedicated software. This determining step 215 functions in a similar manner to determining step 135.

[0222] The output of step 215 can be a computer interface. Such output is similar to... Figure 1 Step 140 is publicly provided.

[0223] In a particular embodiment, step 140 is configured to provide relevant data to a corresponding actuator, such as a formulation assembly mechanism configured to integrate a formulation corresponding to a determined quantity (or a standard quantity) of volatile molecules provided. In such an embodiment, the assembly mechanism may include a sample of volatile molecules and a reactor configured to receive all or part of the sample, the volatile molecules being fed into the reactor according to the formulation obtained from method 100 or 200.

[0224] Figure 3 A specific embodiment of the object system 300 of the present invention is shown. This combined tuning determination system 300 includes:

[0225] ~ An organization 305 inputs at least one volatile molecule numerical identifier, the volatile molecule numerical identifier representing an aromatic volatile molecule, the input defining the formulation.

[0226] For at least one volatile molecule digital identifier of the formulation, a calculation mechanism 310 calculates a value representing the effect of each molecule on the activity level of an odor receptor represented by an odor receptor digital identifier, each volatile molecule digital identifier being associated with at least one odor receptor digital identifier in a many-to-many relationship.

[0227] ~ For the combined tone, depending on the calculated influence of at least one odor receptor activity level and a numerical value representing the odor receptor activation threshold, an organization 315 determines a numerical value representing at least one tonality that forms the combined tone, each odor receptor numerical identifier being associated with a tonality numerical identifier in a one-to-one manner.

[0228] The specific implementation scheme of System 300 has been discussed above. Figure 1 and Figure 2 The functional steps described are described in the description.

[0229] Input mechanism 305 may be, for example, a keyboard, mouse, and / or touchscreen suitable for interacting with a computing system, in order to collect user input. In derivative embodiments, input mechanism 305 may be logical in nature, such as a network port of a computing system configured to receive electronically transmitted input commands. Such input mechanism 305 may be associated with a GUI or API (Application Programming Interface) displayed to the user.

[0230] The computing mechanism 310 and the determining mechanism 315 may be, for example, a computing system configured to run dedicated software responsible for executing the corresponding algorithm.

[0231] Figure 4 A specific embodiment of the object system 400 of the present invention is shown. This fragrance formulation determination system 400 includes:

[0232] ~ For at least one tonality identifier, a mechanism 405 inputs a numerical value on a computer interface, the value representing the tonality of the combined tone generated by the formula to be determined.

[0233] For a given formulation and depending on at least one numerical value representing at least one tonality of the combined tonality, a calculation system, mechanism 410, determines the numerical value of the activity level of at least one odor receptor digital identifier representing an odor receptor, wherein each odor receptor digital identifier is associated with a tonality digital identifier in a one-to-one manner.

[0234] ~ An organization 415 that determines a formulation represented by at least one set of at least one volatile molecular digital identifiers, the set presenting a numerical value representing the effect on the activity level of the odor receptor digital identifier, the numerical value being equal to a determined numerical value representing the activity level of the odor receptor, each volatile molecular digital identifier being associated with at least one odor receptor digital identifier, the association being a many-to-many association.

[0235] Input mechanism 405 is similar to about Figure 3 The input mechanism 305 is described.

[0236] Determining mechanism 410 and determining mechanism 415 may be, for example, a computing system configured to run dedicated software responsible for executing the corresponding algorithm.

[0237] As should be understood from the foregoing description, a formulation defined by selecting at least one volatile molecule can be encoded into a set of activated OR indicators, where each OR corresponds to a perceived tone. This encoding system offers a variety of applications in formulation optimization or performance prediction. Figures 5 to 11 Examples of OR activity modeling and its impact on tone prediction are provided.

[0238] For example, in Figure 5 The spice blend shown (blend A) contains ingredients that activate odor receptors OR8B3 (contributing hay notes), OR8D1 (contributing celery notes), and OR5AU1 (contributing lactone coconut notes), as well as three slightly modified blends (blends B through D). For simplicity, ingredients that do not activate any of the three target ORs are summarized and... Figure 5 The term is described as "other ingredients". Using receptor screening data for each OR (as described in Example 1 of US62 / 911,096), alternative activators can be used to replace ingredients present in the original formulation. This approach allows for the preferential use of preferred ingredients to optimize for a variety of factors, including cost reduction, improved biodegradability, or the use of compounds with environmentally friendly properties.

[0239] Computing systems are used to... Figure 6 Determined from the nonlinear combination of empirically determined information of a single volatile molecule, as shown. Figure 5 The total receptor activity level of the modulator shown is verified with... Figure 7 and Figure 9 The empirical mixture responses shown were matched. Activity levels were normalized to the maximum cellular response to trichodin, a known pharmacologically known transduction cascade activator, which served as an anchor for data comparison purposes. The blend activities predicted by the model were compared with cell-based data generated using the same blends (as described in Example 2 of US62 / 911,096). Consistent activity levels were observed between the model and in vitro data, validating the model. Activity predictions generated between the original and modified blends were used for sensory predictions based on OR activity changes (i.e., more or less active) and inferred corresponding tone changes (i.e., more or less intense). Sensory predictions were validated by a sensory panel of spice experts, who were asked to blind-taste three tones of interest for each blend: hay, celery, and lactone coconut.

[0240] Regarding OR8D1 activity, the composition / combination adjustment where cyclotone is removed and replaced with 5-ethyl-3-hydroxy-4-methyl-2(5H)-furanone is as follows: Figure 5 As shown (compare blends A and B). The target activity level of OR8D1 was set below the original level. Figure 7 The model showed that the predicted activity levels, normalized to 100% trichosin response, were compared with in vitro validation of the receptor. A corresponding decrease in the perception of celery tones was predicted, a finding confirmed by the expert panel's assessment. Figure 8 As shown.

[0241] Regarding OR8B3 and OR5AU1 activity, combinations / combinations that remove nonanolide and replace it with coumarin are as follows: Figure 5 As shown (compare blends A and C). In this case, the target activity level of OR8B3 was set higher than the original level, while OR5AU1 was null. Figure 9 The model-predicted activity levels, normalized to 100% trichodin responses, were shown compared to in vitro validation of both receptors. A corresponding increase in perception of hay tone and a loss of lactone coconut tone were predicted, a finding confirmed by the expert panel's assessment, such as... Figure 10 As shown.

[0242] Figure 5 One composition / combination modifier is shown in which nonanolide is replaced with coumarin and dihydro-4-methyl-5-pentenyl-2(3H)-furanone (tuberolide) is added to produce the desired OR8B3 and OR5AU1 activities (compared to modifiers A, C, and D). The target activity level of OR8B3 is set to be the same in modifier D as in modifier C, and OR5AU1 is restored to the level of modifier A by modifier D. Figure 9 The model-predicted activity levels were shown compared to in vitro validation of the two receptors, normalized to 100% trichodin responses. The predicted recovery of coconut tone perception and maintenance of increased hay tone perception due to restored OR5AU1 activity were confirmed by expert panel assessments. Figure 11 As shown.

[0243] These embodiments of flavor blend modification capture the system's ability to simulate receptor activity of complex mixtures using only single-compound input data (as obtained in Examples 1-3 of US62 / 911,096) before and after compound removal and replacement. The system's ability to predict sensory outcomes based on calculated or measured receptor activity allows for: maintaining perception of a specific desired tone using different combinations of tones; adjusting the concentration or proportion of compounds in the mixture to decrease or increase the desired tone; and adding compounds to rebalance the combined tone by restoring the desired tone lost during modification. These embodiments clearly demonstrate that a desired set of perceived tones (representing the target tone) can be set in the computational system, and possible groups of compounds and their concentrations that will produce the desired total OR activity can be determined, or conversely, the combined tone can be modified as needed, and the final effect on the perceived tone can be determined by the calculated OR activity, or further, a desired or measured set of receptor activity levels, and the resulting perceived tone, and a calculated reasonable number of combined tones can be input.

Claims

1. A method for determining the tone of a combination (100), characterized in that, include: The step (105) involves inputting at least one volatile molecule digital identifier on a computer interface, the volatile molecule digital identifier representing an aromatic volatile molecule, the input defining the formulation. ~ For at least one volatile molecule digital identifier of the formulation, the step (110) involves calculating a value by a calculation system, the value representing the effect of each molecule on the activity level of an odor receptor represented by an odor receptor digital identifier, each volatile molecule digital identifier being associated with at least one odor receptor digital identifier, the association being many-to-many. ~ For this formulation and depending on the calculated effect of at least one odor receptor activity level and a value representing the odor receptor activation threshold, the step (115) involves determining, via a calculation system, a value representing at least one tonality forming the combined tone, wherein each odor receptor numerical identifier is associated with a tonality numerical identifier, the association being one-to-one. ~ Steps to modify the numerical values ​​representing the fragrance notes of the blend on the computer interface (125) ~ Step (130) of calculating the modification amount of the total activity level of at least one odor receptor by a calculation system. ~ Step (135) of determining a set of at least one set of numerical identifiers for volatile molecules by a computational system, wherein the total activity level influence value presented by this set lies within an acceptable deviation from the exact equation, and ~ The step of providing the group to the computer interface (140).

2. The method (100) according to claim 1, wherein at least one modification corresponds to: Removing volatile molecules from a formula is equivalent to removing the corresponding numerical identifiers from the formula. The addition of volatile molecules to the formulation is converted into the addition of corresponding numerical identifiers in the formulation, and / or Modifications to the number of volatile molecules in a formulation are converted into modifications to indicators representing the corresponding number of numerical identifiers in the formulation.

3. The method (100) according to claim 1 or 2, comprising, downstream of the calculation step (110), a step (120) of calculating, for at least one odor receptor, a total activity level relating to at least one influence of the calculated activity level by a calculation system.

4. The method (100) according to claim 1 or 2, wherein each tone is associated with a tone numerical identifier, the method comprising an automatic tone selection step (145) depending on the result of comparing the tone numerical identifier of the combined tone with a set of at least one predetermined tone numerical identifier, wherein a modification step (125) representing the aroma value of the selected tone numerical identifier of the combined tone is configured to reduce the value of the selected tone numerical identifier to a reduced value, preferably to zero.

5. The method (100) according to claim 1 or 2, wherein the numerical representation of the effect of the molecule represented by the numerical identifier of the volatile molecule on the activity level of the odor receptor is: ~ Activation of the odor receptors, ~ Inactivation of the odor receptors, ~ Enhancement of the odor receptors and / or ~ Inhibition of the odorant receptors.

6. The method (100) according to any one of claims 5 and 1 or 2, wherein the determining step (135) is configured to provide at least one volatile molecule digital identifier that presents a numerical value representing the effect on the activity of the odor receptor associated with the tone modified in the modifying step (125), the effect corresponding to the enhancement or inhibition of the odor receptor.

7. The method (100) according to claim 1 or 2, comprising: ~ Step (150) of selecting the volatile molecule digital identifier for the formula on the computer interface. ~ Step (155) of determining at least one set of at least one volatile molecule digital identifiers by a calculation system, the set presenting a numerical value representing the effect on the activity level of the odor receptor, the numerical value being equal to the numerical value representing the effect of the selected volatile molecule digital identifier on the activity level of the odor receptor, and ~ The step of providing the group to the computer interface (140).

8. The method (100) according to claim 1 or 2, comprising: ~ Step (160) of selecting at least two volatile molecule digital identifiers for the formulation, wherein the at least two volatile molecules are associated with the activation of at least two different odor receptors called "target receptors". ~ Step (165) of determining a volatile molecule numerical identifier, which presents a numerical value representing the effect on the activity level of each target receptor, equal to the numerical value representing the effect of the selected volatile molecule numerical identifier on the activity level of the odor receptor, and ~ The step of providing the determined volatile molecule digital identifier to the computer interface (140).

9. The method (100) according to claim 1 or 2, comprising (170) downstream of any determining step (135, 155, 165) estimating the number of at least one of the volatile molecule digital identifiers, the number being used for a downstream providing step (140).

10. The method (100) according to claim 1 or 2, wherein the step (135, 155) of determining at least one set of at least one set of volatile molecule digital identifiers by a computing system executes an optimization rule, which is at least one of the following rules: The first rule states that a defined set of at least one volatile molecule digital identifiers is configured to present a minimum number of volatile molecule digital identifiers. The second rule, wherein the identified set of at least one volatile molecule digital identifiers is configured to present a minimum total quantity indicator of the corresponding volatile molecule digital identifiers, ~ The third rule, wherein the identified set of at least one volatile molecule digital identifiers is configured to present a minimum number of negative volatile molecule digital identifiers. The fourth rule, wherein at least one volatile molecule numerical identifier is associated with a volatile molecule delivery capability indicator, is configured to adapt a determined set of at least one volatile molecule numerical identifiers to the volatile molecule numerical identifiers in that set, depending on the volatile molecule delivery capability indicator. ~ Rule 5, wherein a set of at least two volatile molecule numerical identifiers is configured to minimize the overlap of odor receptors activated by said set of molecules. ~ Rule Six, wherein a set of at least two volatile molecule numerical identifiers is configured to minimize the modulation of odor receptors activated by said set of molecules, ~ Rule 7, wherein the identified set of at least one volatile molecule numerical identifiers is configured to maximize the negative modulation or inhibition of odor receptors associated with a predetermined undesirable olfactory tone. ~ Rule 8, wherein the identified set of at least one volatile molecular numerical identifiers is configured to maximize the positive modulation or enhancement of odor receptors associated with a predetermined desired olfactory tone, and / or ~ Rule 9, wherein a set of at least one volatile molecule numerical identifiers is configured to minimize or maximize at least one cost function, each volatile molecule being associated with at least one numerical value representing cost.

11. The method (100) according to claim 1 or 2, comprising the step (175) of inputting at least one quantity of volatile molecules on a computer interface, the quantity being used for: calculating a numerical value by a calculation system for at least one volatile molecule digital identifier of the formulation, the numerical value representing the effect on the activity level of odor receptors.

12. The method (100) according to claim 1 or 2, wherein at least one volatile molecule digital identifier is associated with a volatile molecule delivery capability indicator, and at least one of the calculation step (110) and the determination step (135, 155, 165) is performed depending on the volatile molecule delivery capability indicator associated with at least one input volatile molecule digital identifier.

13. The method (100) of claim 12, wherein the volatile molecule delivery capability indicator represents the substrate where the associated volatile molecule is located.

14. A method for determining a formula (200), characterized in that, include: ~ For at least one tonality identifier, the step (205) of entering a numerical value on a computer interface, the numerical value representing the tonality of the combined tone generated by the formula to be determined, ~ For the formulation to be determined and depending on at least one numerical value representing at least one tonality of the combined tone, the step (210) involves determining, by calculation system, the numerical value of the activity level of at least one odor receptor digital identifier representing an odor receptor, wherein each odor receptor digital identifier is associated with at least one tonality digital identifier, and the association is a one-to-one association. The step (215) of determining a formulation represented by at least one set of at least one volatile molecular digital identifiers, which presents a numerical value representing the effect on the activity level of the odor receptor digital identifier, the numerical value being equal to a determined numerical value representing the activity level of the odor receptor, each volatile molecular digital identifier being associated with at least one odor receptor digital identifier, the association being many-to-many. ~ Steps to modify the numerical values ​​representing the fragrance notes of the blend on the computer interface (125) ~ Step (130) of calculating the modification amount of the total activity level of at least one odor receptor by a calculation system. ~ Step (135) of determining a set of at least one set of numerical identifiers for volatile molecules by a computational system, wherein the total activity level influence value presented by this set lies within an acceptable deviation from the exact equation, and ~ Step (140) of providing the group to the computer interface.

15. A combined tone determination system (300), characterized in that, include: ~ An organization (305) inputs at least one volatile molecule numerical identifier, said volatile molecule numerical identifier representing an aromatic volatile molecule, said input defining the formulation. ~ For at least one volatile molecule digital identifier of the formulation, a calculation mechanism (310) calculates a value representing the level of activity of each molecule on the activity level of an odor receptor represented by an odor receptor digital identifier, each volatile molecule digital identifier being associated with at least one odor receptor digital identifier, the association being many-to-many. ~ For this combined tone, depending on the calculated influence of at least one odor receptor activity level and a numerical value representing the odor receptor activation threshold, an organization (315) determines the numerical value representing at least one tonality forming the combined tone, wherein each odor receptor numerical identifier is associated with a tonality numerical identifier, the association being one-to-one. ~ Steps to modify the numerical values ​​representing the fragrance notes of the blend on the computer interface (125) ~ Step (130) of calculating the modification amount of the total activity level of at least one odor receptor by a calculation system. ~ Step (135) of determining a set of at least one set of numerical identifiers for volatile molecules by a computational system, wherein the total activity level influence value presented by this set lies within an acceptable deviation from the exact equation, and ~ The step of providing the group to the computer interface (140).

16. A formula determination system (400), characterized in that, include: ~ For at least one tonality identifier, a mechanism (405) inputs a numerical value on a computer interface, the value representing the tonality of the combined tone generated by the formula to be determined. ~ For a given formulation and depending on at least one numerical value representing at least one tonality of the combined tonality, an apparatus (410) calculates the numerical value of the activity level of at least one odor receptor digital identifier representing an odor receptor, wherein each odor receptor digital identifier is associated with a tonality digital identifier in a one-to-one manner. ~ An organization (415) determines a formulation represented by at least one set of at least one volatile molecular digital identifiers, which presents a numerical value representing the effect on the activity level of the odor receptor digital identifier, the numerical value being equal to a determined numerical value representing the activity level of the odor receptor, each volatile molecular digital identifier being associated with at least one odor receptor digital identifier, the association being many-to-many. ~ Steps to modify the numerical values ​​representing the fragrance notes of the blend on the computer interface (125) ~ Step (130) of calculating the modification amount of the total activity level of at least one odor receptor by a calculation system. ~ Step (135) of determining a set of at least one set of numerical identifiers for volatile molecules by a computational system, wherein the total activity level influence value presented by this set lies within an acceptable deviation from the exact equation, and ~ The step of providing the group to the computer interface (140).

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