SBIR-STTR Award

"StressSmart" Repeated exposures to psychosocial stress are associated with several human diseases (e.g., cancer, drug addiction, heart disease, depression) of tremendous public health burden. However, our progress is limited by the lack of a portable device that can enable rapid, reliable, non-invasive and continuous measurement of personal exposure to psychosocial stress in real-time, as experienced by individuals in their natural environments. In this interdisciplinary project, we propose to develop a new test called InstaCortisol(tm) that can be used to reliably, selectively and rapidly quantify personal exposures to stress by measuring Cortisol levels of subjects in their natural environments. Cortisol is the primary steroid produced and secreted by the adrenal cortex and is used as a reliable indicator of stress. This rapid test is based on immunoelectrochemical method where the reaction signal is measured by using cyclic voltammetry, when Cortisol sandwiches between the capture and the detector antibody, which is attached to Alkaline Phosphatase enzyme. There are four specific aims of this project. First is Sensor Fabrication: We will fabricate multiple Cortisol sensors in first two months. Second is Sensor Evaluation: we will test the sensors for sensitivity, specificity, enzyme/antibody stability, detection limit, linearity, accuracy, dynamic range, repeatability, precision, accuracy, interference, cross-reactivity, drift, and sensor calibration. We anticipate changing and/or optimizing fabrication methods to achieve benchmarks in each of these categories. Third is sensor performance: Establish sensor performance against commercially available Cortisol sensors. We aim to meet or exceed, given the need for continuous performance benchmarks of readily available Cortisol sensors. Fourth would be to Design integration feasibility experiments: A virtual evaluation of Cortisol sensor chip and its integration into a compact easy to use design. Relevance: The InstaCortisol(tm) test (being developed during Phase I), which will be part of StressSmart(tm) device during Phase II, will enable researchers to quantify personal exposure to psychosocial stress, as experienced by individuals in real-life situations. Such a capability will advance our understanding of how exposures to psychosocial stress interact with genetic factors in the etiology of prevalent human diseases of tremendous public health burden.

Public Health Relevance:
We are proposing to make a rapid test for detecting Cortisol, called "InstaCortisol", which will make real-time and continuous measurements of personal exposure to psychosocial stress quantitatively, selectively, objectively, reliably, and securely by detecting Cortisol in interstitial fluid (ISF). ISF will be harvested using our proprietary minimally invasive device called "LightAccess". The proposed product involves the integration of several cutting edge technologies. The product would require virtually no action on the part of the subject or patient thereby greatly reducing error associated with improper use. These innovations would provide a significantly improved method for assessing a molecule that plays an important role in many biological processes and disease states.

Public Health Relevance Statement:
Project Narrative for PA-06-471-Phase I We are proposing to make a rapid test for detecting Cortisol, called "InstaCortisol", which will make real-time and continuous measurements of personal exposure to psychosocial stress quantitatively, selectively, objectively, reliably, and securely by detecting Cortisol in interstitial fluid (ISF). ISF will be harvested using our proprietary minimally invasive device called "LightAccess".

NIH Spending Category:
Behavioral and Social Science; Bioengineering; Mental Health; Nutrition

Project Terms:
1,2-Benzenediol, 4-(1-hydroxy-2-(methylamino)ethyl)-, (R)-; 3beta-Hydroxyandrost-5-en-17-one; 4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol; 5-Androsten-3-beta-hydroxy-17-one; AIDS; Acquired Immune Deficiency; Acquired Immune Deficiency Syndrome; Acquired Immuno-Deficiency Syndrome; Acquired Immunodeficiency Syndrome; Addiction, Drug; Adrenal Cortex; Adrenaline; Aeroseb-HC; Age; Aged 65 and Over; Alkaline Phosphatase; Androst-5-en-17-one, 3-hydroxy-, (3beta)-; Androstenolone; Anti-Cancer Agents; Anti-Tumor Agents; Anti-Tumor Drugs; Antibodies; Antineoplastic Agents; Antineoplastic Drugs; Antineoplastics; Antiproliferative Agents; Antiproliferative Drugs; Assay; Behavior; Behavioral Sciences; Benchmarking; Best Practice Analysis; Bioassay; Biologic Assays; Biological Assay; Biological Function; Biological Process; Biosensor; Blood Pressure, High; Bone; Bone and Bones; Bones and Bone Tissue; Calibration; Cancer Drug; Cancers; Cardiac Diseases; Cardiac Disorders; Categories; Causality; Cell Communication and Signaling; Cell Signaling; Cetacort; Chemical Dependence; Chemotherapeutic Agents, Neoplastic Disease; Chemotherapy-Hormones/Steroids; Clinical; Cort-Dome; Cortef; Cortenema; Cortex of adrenal gland; Cortisol; Cortispray; Cortril; DHEA; Data; Data Collection; Dehydroisoandrosterone; Dependence, Drug; Dermacort; Detection; Devices; Diabetes Mellitus; Diet; Digestion; Disease; Disorder; Drug Addiction; Drug Dependency; Eldecort; Elderly; Elderly, over 65; Endocrine Gland Secretion; Environment; Enzymes; Epi; Epinephrine; Error Sources; Etiology; Evaluation; Exercise; Exercise, Physical; Exposure to; Frequencies (time pattern); Frequency; Genetic; Hand; Harvest; Healed; Health; Heart Diseases; Hormones; Hour; Household; Housing; Human; Human, General; Hydrocortisone; Hydrocortone; Hypertension; Hytone; Immune system; Immunologic Deficiency Syndrome, Acquired; Individual; Intercellular Fluid; Intermediary Metabolism; Interstitial Fluids; Intervention; Intervention Strategies; Intracellular Communication and Signaling; Investigators; Learning; Life; Life Style; Lifestyle; METBL; Major Depressive Disorder; Malignant Neoplasms; Malignant Tumor; Man (Taxonomy); Man, Modern; Marketing; Measurement; Measures; Metabolic Processes; Metabolism; Methods; Monitor; Muscle; Muscle Tissue; Natural regeneration; Nicotine; Normal Cell; Nutracort; Obesity; Operation; Operative Procedures; Operative Surgical Procedures; Orthophosphoric-monoester phosphohydrolase (alkaline optimum); Osteoporosis; Participant; Patient Self-Report; Patients; Pattern; Performance; Phase; Physical environment; Physiologic; Physiological; Play; Prasterone; Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-; Process; Proctocort; Production; Psychosocial Stress; Public Health; Pyridine, 3-(1-methyl-2-pyrrolidinyl)-, (S)-; Reaction; Regeneration; Research; Research Personnel; Researchers; Role; Salivary; Sampling; Self-Report; Sensitivity and Specificity; Signal Transduction; Signal Transduction Systems; Signaling; Sleep; Smoker; Social Interaction; Socio-economic status; Socioeconomic Status; Sports Medicine; Status, Socioeconomic; Steroid Compound; Steroids; Stress; Surgical; Surgical Interventions; Surgical Procedure; Survey Instrument; Surveys; System; System, LOINC Axis 4; Technology; Testing; Therapeutic Dehydroepiandrosterone; Therapeutic Epinephrine; Therapeutic Hormone; Therapeutic Hydrocortisone; Time; Transmission; Tumor-Specific Treatment Agents; Vascular Hypertensive Disease; Vascular Hypertensive Disorder; Weight Gain; Weight Increase; Wireless Technology; Wrist; adiposity; advanced age; alkaline phosphomonoesterase; anticancer agent; anticancer drug; base; biological signal transduction; biomarker; body system, allergic/immunologic; body weight gain; body weight increase; bone; corpulence; corpulency; corpulentia; cross reactivity; dehydroepiandrosterone; depression; design; designing; detector; diabetes; disease causation; disease etiology; disease/disorder; disease/disorder etiology; disorder etiology; elders; experience; experiment; experimental research; experimental study; field study; geriatric; glycerophosphatase; healing; heart disorder; human disease; hyperpiesia; hyperpiesis; hypertensive disease; improved; innovate; innovation; innovative; interventional strategy; late life; later life; major depression; malignancy; meetings; minimally invasive; neoplasm/cancer; obese; obese people; obese person; obese population; older adult; older person; organ system, allergic/immunologic; physical conditioning; psychosocial; public health medicine (field); public health relevance; regenerate; research study; senior citizen; sensor; sensor (biological); social role; strength training; stressor; surgery; transmission process; virtual; wireless; wt gain

Repetitive exposures to psychosocial stress are associated with several human diseases (e.g., cancer, drug addiction, heart disease, depression) of noteworthy public health burden. However, our progress is limited by the lack of a portable device that can enable rapid, dependable, non-invasive and continuous measurement of personal exposure to psychosocial stress in real-time, as experienced by individuals in their natural environments. Although reliable methods to assess exposure to psychosocial stress in clinical settings exist, these intermittent assessments do not accurately portray timing, duration, frequency, or intensity of exposure. Currently there are more than 3600 registered endocrinologists in the US and on an average they refer five patients per day for cortisol tests. This test is ordered by sending patient's samples to the lab. Therefore, there is a grave need to develop a rapid test for cortisol so a ""No-Stress Stress Measuring Device"" can be developed. In this interdisciplinary Phase II project, we propose to develop a new device called ""StressSmartTM"", which will house a rapid test for cortisol developed during Phase I, namely InstaCortisolTM. Cortisol is the primary steroid produced and secreted by the adrenal cortex and is used as a reliable indicator of stress. Our rapid test is based on immunoelectrochemical method where the reaction signal is measured by using dithiobissuccinimidyl propionate (DTSP) self assembled monolayer (SAM) based immunosensor for cortisol. Detection is being facilitated using impedance measuring technique. There are six specific aims of this project. First is further refining and optimizing the cortisol sensor fabrication and sensor evaluation, including sensitivity, specificity, detection limit, linearity, accuracy, dynamic range, repeatability, precision, accuracy, interference, cross-reactivity, drift, and sensor calibration. Second is the development of microfluidic architecture system. The third aim would be the design, fabrication, integration and development of a microfluidic valves. Several such valves will be needed as parts of the three disposable cartridges. Fourth and fifth aim being the development of a reliable vacuum microfluidics pump, followed by cortisol sensor housing development as part of the device. Throughout the program, some other efforts will also include cortisol sensor clotting mitigation, cortisol sensor electronic Interface board development, cortisol sensor miniaturization efforts, clinical validation and the design integration feasibility. A virtual evaluation of cortisol sensor chip and its integration into a compact easy to use design will be carried out in parallel. A virtual evaluation of cortisol sensor chip and its integration into a compact easy to use design will also be carried out throughout the Year 2 budget period. Relevance: The InstaCortisolTM test (developed during Phase I), which will be part of StressSmartTM device during Phase II, will enable researchers to quantify personal exposure to psychosocial stress, as experienced by individuals in real-life situations. Cortisol production follows a circadian rhythm, and moreover it is affected by stimulatory events or nutrient intake, so it important to measure the trend of cortisol in a person versus taking a single measurement in one day as is done traditionally. Recent research surveys have revealed that the minimal number of samples needed in a day for an accurate assessment of cortisol is five. Our current disposable cartridge is designed to collect four measurements over 24 hours for the proof of concept. However, this device can be easily re-designed to include any other clinically relevant requirements. Availability of such a non-invasive and rapid cortisol measuring device will allow patients to be able to monitor their cortisol levels over 24 hours and professionals to be able to modify dosing regiments at multiple points throughout the day.

Public Health Relevance:
We are proposing to make a tool for rapid detection of cortisol, called StressSmartTM. ""InstaCortisolTM"" (a rapid cortisol test developed during Phase I), will be integrated in StressSmart device to develop a portable test for real-time measurement of personal exposure to psychosocial stress via detecting cortisol in interstitial fluid (ISF). The new minimally invasive tool will enable researchers to quantify personal exposure to psychosocial stress, as experienced by individuals in real-life situations. This device will be capable of measuring cortisol quantitatively, selectively, objectively, reliably, and securely.

Thesaurus Terms:
1,2-Benzenediol, 4-(1-Hydroxy-2-(Methylamino)Ethyl)-, (R)-;3beta-Hydroxyandrost-5-En-17-One;4-(1-Hydroxy-2-(Methylamino)Ethyl)-1,2-Benzenediol;5-Androsten-3-Beta-Hydroxy-17-One;Addison's Disease;Adrenal Cortex;Adrenaline;Aeroseb-Hc;Affect;Algorithms;Androst-5-En-17-One, 3-Hydroxy-, (3beta)-;Androstenolone;Anti-Bacterial Agents;Anti-Cancer Agents;Antibacterial Agents;Antineoplastic Agents;Antineoplastic Drugs;Antineoplastics;Assay;Autoimmune Diseases;Award;Behavioral Sciences;Bioassay;Biologic Assays;Biological;Biological Assay;Biological Function;Biological Process;Biosensor;Budgets;Calibration;Cancer Drug;Cardiac Diseases;Cardiac Disorders;Cell Communication And Signaling;Cell Signaling;Cetacort;Chemical Dependence;Chemotherapy-Hormones/Steroids;Circadian Rhythms;Clinical;Clotting;Coagulation;Coagulation Process;Collection;Communities;Cort-Dome;Cortef;Cortenema;Cortisol;Cortispray;Cortril;Cushing Syndrome;Cushing's Basophilism;Dhea;Data;Data Collection;Dehydroisoandrosterone;Dermacort;Detection;Development;Devices;Diet;Disease;Disorder;Diurnal Rhythm;Dose;Drug Addiction;Drug Dependence;Drug Dependency;Eldecort;Electrical Impedance;Electronics;Endocrine Gland Secretion;Endocrinologist;Environment;Epinephrine;Evaluation;Event;Exercise;Exposure To;Frequencies (Time Pattern);Frequency;Goals;Harvest;Heart Diseases;Hormones;Hour;Housing;Human;Hydrocortisone;Hydrocortone;Hytone;Impedance;Individual;Intake;Intercellular Fluid;Interstitial Fluids;Intervention;Intervention Strategies;Intracellular Communication And Signaling;Investigation;Investigators;Loinc Axis 4 System;Learning;Life;Man (Taxonomy);Measurement;Measures;Mental Depression;Methods;Microfluidic;Microfluidics;Miniaturisations;Miniaturization;Modern Man;Monitor;Mothers;Neoplastic Disease Chemotherapeutic Agents;Nicotine;Nutracort;Nutrient;Nyctohemeral Rhythm;Obesity;Ptsd;Participant;Patients;Performance;Persons;Phase;Physical Exercise;Physical Environment;Pilot Projects;Position;Positioning Attribute;Post-Traumatic Neuroses;Post-Traumatic Stress Disorders;Posttraumatic Neuroses;Posttraumatic Stress Disorders;Prasterone;Pregn-4-Ene-3,20-Dione, 11,17,21-Trihydroxy-, (11beta)-;Primary Adrenal Insufficiency;Primary Adrenocortical Insufficiency;Primary Hypoadrenalism;Process;Proctocort;Production;Propionates;Psychosocial Stress;Public Health;Publishing;Pump;Pyridine, 3-(1-Methyl-2-Pyrrolidinyl)-, (S)-;Reaction;Research;Research Personnel;Researchers;Sampling;Sensitivity And Specificity;Signal Transduction;Signal Transduction Systems;Signaling;Sleep;Smoker;Source;Sports Medicine;Steroid Compound;Steroids;Stress;Survey Instrument;Surveys;System;Techniques;Testing;Therapeutic Dehydroepiandrosterone;Therapeutic Epinephrine;Therapeutic Hormone;Therapeutic Hydrocortisone;Time;Transmission;Tumor-Specific Treatment Agents;Twenty-Four Hour Rhythm;Vacuum;Vacuum Pumps;Validation;Veterans;Work;Adiposity;Adrenal Gland Cortex;Anti-Bacterial;Antibacterial;Anticancer Agent;Anticancer Drug;Autoimmune Disorder;Base;Biological Signal Transduction;Biomarker;Circadian;Circadian Process;Clinical Relevance;Clinically Relevant;Corpulence;Corpulency;Corpulentia;Cross Reactivity;Daily Biorhythm;Dehydroepiandrosterone;Depression;Design;Designing;Developmental;Disease/Disorder;Diurnal Variation;Electric Impedance;Experience;Field Study;Heart Disorder;Human Disease;Interventional Strategy;Meetings;Minimally Invasive;Monolayer;Novel;Obese;Obese People;Obese Person;Obese Population;Pilot Study;Pituitary Basophilism;Programs;Public Health Medicine (Field);Rapid Detection;Resistance Training;Sensor;Sensor (Biological);Strength Training;Stressor;System Architecture;Tool;Transmission Process;Traumatic Neurosis;Trend;Virtual