Urine is an attractive biospecimen for point-of-care diagnostics because it can be collected in large quantities with noninvasive procedures. Urine-based lateral flow assays (LFAs) are low-cost devices suitable for point-of-care testing, particularly in low-resource settings. However, many urine-based LFAs exhibit sensitivity levels well below diagnostic utility due to the low concentration of diagnostic biomarkers present in urine. This is the case with LFAs for tuberculosis (TB) diagnostics and is a major barrier to rapid TB testing and treatment in endemic areas. Mainstream clinical and laboratory tests for diagnosing active TB, including bacterial culture, sputum smear microscopy and nucleic acid amplification tests, present limitations in speed, sensitivity, accessibility, respectively. These tests also require sputum samples that present additional difficulty and exposure risks for healthcare staff during the collection procedure. To address this, we developed an osmotic processor that statically and spontaneously concentrates urinary biomarkers for use in LFAs. Urea and small molecules that can interfere with downstream assays are removed in the concentration process. Using human chorionic gonadotropin (hCG) protein as a model analyte, we showed near 100-fold concentration of a 20 mL sample in an early prototype. By exploiting the principles of osmosis, recent prototypes developed by the company show promise in significantly reducing processing time to within 30 minutes. With its simplicity and flexibility, the device demonstrates a great potential to be interfaced with existing LFAs to enable highly sensitive detection of dilute target analytes in urine, while still retaining a diagnostic time suitable for point-of-care diagnostics. The project aims to validate molecule concentration quantitatively with mass spectrometry in newer prototypes, perform spike-and-recovery tests with simulated urine and lab-based LAM, and then test qualitatively with TB-positive clinical samples and LFAs. If awarded the Phase I SBIR grant, the team will hire another full time research scientist, register our device as a General Controls Device through the FDA, continue business collaborations with companies developing LFAs, research other applications of the device to process other biomarkers for diagnostic, disease monitoring and therapeutic purposes, and plan scale-up of device production for commercial distribution in preparation of Phase II.
Public Health Relevance Statement: PROJECT NARRATIVE Current diagnostic methods for tuberculosis (TB) either require sputum, take days to weeks to return results, or require high cost equipment that is not available in low-resource areas where TB is endemic. Lateral flow assays (LFAs) to test urine for TB exist; however, they are too low-sensitivity to be approved for clinical use due to low-concentrations of TB biomarkers in urine. OsmoProcessor is currently producing prototypes for a device which can rapidly concentrate urine samples and interface with LFAs without a power-source or special equipment, enabling a potential standardized point-of-care diagnostic for TB.
Project Terms: South Africa; Mass Spectrum Analysis; Mass Photometry/Spectrum Analysis; Mass Spectrometry; Mass Spectroscopy; Mass Spectrum; Mass Spectrum Analyses; Sputum; Standardization; Temperature; Testing; Time; Tuberculosis; M tuberculosis infection; M. tb infection; M. tuberculosis infection; M.tb infection; M.tuberculosis infection; MTB infection; Mycobacterium tuberculosis (MTB) infection; Mycobacterium tuberculosis infection; TB infection; disseminated TB; disseminated tuberculosis; infection due to Mycobacterium tuberculosis; tuberculosis infection; tuberculous spondyloarthropathy; Ultracentrifugation; Ultrafiltration; Urea; Carbamide; Elaqua XX; Urea Carbamide; Ureaphil; Urine; lipoarabinomannan; Measures; Businesses; health care; Healthcare; improved; Procedures; Nucleic Acid Testing; Nucleic Acid Amplification Tests; Area; Surface; Clinical; Phase; Training; Individual; Recovery; Collaborations; Letters; Therapeutic; With laterality; Diagnostic; Specimen; Research Specimen; Scientist; Diagnostic Procedure; Diagnostic Method; Diagnostic Technique; mycobacterial; Nucleocapsid Proteins; Equation; experience; Membrane; membrane structure; Performance; success; Speed; Devices; Excision; Abscission; Extirpation; Removal; Surgical Removal; resection; Modeling; Sampling; hCG; Human Chorionic Gonadotropin; Urea Nitrogen; preventing; prevent; small molecule; Address; Data; Detection; Collection; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Special Equipment; Monitor; Preparation; preparations; Process; urinary; point of care; cost; designing; design; scale up; innovate; innovative; innovation; prototype; commercialization; TB therapy; TB treatment; tuberculosis therapy; tuberculosis treatment; bio-markers; biologic marker; biomarker; Biological Markers; commercial scale manufacturing; manufacturing ramp-up; scale up batch; scale up production; upscale manufacturing; manufacturing scale-up; point-of-care diagnostics; flexible; flexibility; diagnostic marker; diagnostic biomarker; TB diagnostics; tuberculosis diagnostics; infection risk; 2019 novel corona virus; 2019 novel coronavirus; COVID-19 virus; COVID19 virus; CoV-2; CoV2; SARS corona virus 2; SARS-CO-V2; SARS-COVID-2; SARS-CoV-2; SARS-CoV2; SARS-associated corona virus 2; SARS-associated coronavirus 2; SARS-coronavirus-2; SARS-related corona virus 2; SARS-related coronavirus 2; SARSCoV2; Severe Acute Respiratory Coronavirus 2; Severe Acute Respiratory Distress Syndrome CoV 2; Severe Acute Respiratory Distress Syndrome Corona Virus 2; Severe Acute Respiratory Distress Syndrome Coronavirus 2; Severe Acute Respiratory Syndrome CoV 2; Severe Acute Respiratory Syndrome-associated coronavirus 2; Severe Acute Respiratory Syndrome-related coronavirus 2; Severe acute respiratory syndrome associated corona virus 2; Severe acute respiratory syndrome coronavirus 2; Severe acute respiratory syndrome related corona virus 2; Wuhan coronavirus; coronavirus disease 2019 virus; coronavirus disease-19 virus; hCoV19; nCoV2; 2019-nCoV; lateral flow test; lateral flow assay; detection limit; point of care testing; Resource-limited setting; Low-resource area; Low-resource community; Low-resource environment; Low-resource region; Low-resource setting; Resource-constrained area; Resource-constrained community; Resource-constrained environment; Resource-constrained region; Resource-constrained setting; Resource-limited area; Resource-limited community; Resource-limited environment; Resource-limited region; Resource-poor area; Resource-poor community; Resource-poor environment; Resource-poor region; Resource-poor setting; diagnostic value; diagnostic ability; diagnostic capability; diagnostic power; diagnostic utility; Affect; immunogen; Antigens; Award; Biological Assay; Assay; Bioassay; Biologic Assays; Buffers; Centrifugation; Centrifugation Fractionation; Cessation of life; Death; Diagnosis; Diffusion; diffused; diffuses; diffusing; diffusions; Disease; Disorder; Enzyme-Linked Immunosorbent Assay; ELISA; enzyme linked immunoassay; Equipment; Exhibits; Grant; Human; Modern Man; Immunoassay; Industry; Interview; Kinetics; Laboratories; Mainstreaming; Educational Mainstreaming; achievement Mainstream Education; Marketing; Methods; Microscopy; Persons; Noise; Osmosis; Polymers; polymer; polymeric; Power Sources; Power Supplies; Production; Proteins; Research; Risk; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Solubility
