RAPID DIAGNOSTIC TESTING OF URINARY TRACT INFECTIONS
Ronald J Rieder, President
Biosense Technologies, Inc., 4 Arrow Dr, Woburn, Ma 01801-2040
Grant 3R44DK075198-03S1 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: The continued development of a rapid diagnostic method for testing the antibiotic susceptibility of urinary tract infections in near real-time is proposed. Currently, all methods for determining antibiotic susceptibility rely exclusively on detecting changes in the bacterial population caused by cell division after exposure to an antimicrobial compound. In our Phase I effort we demonstrated a novel phenotypic approach to antibiotic susceptibility testing that provides commensurate information without measurements of growth. Technical feasibility of this method was demonstrated by measuring the antibiotic susceptibility of both sensitive and resistant strains of Escherichia coli and Pseudomonas aeruginosa treated with antibiotics having different mechanisms of action. Susceptibility results were obtained within one hour time. In addition, resistant strains were easily distinguished from sensitive strains. Because grown cultures are no longer needed to obtain results, susceptibility results can be obtained directly from urinary specimens at the point of collection within 90 minutes total reducing the time from sample collection to availability by days enabling targeted therapy, improved patient outcomes, and the reduced spread and generation of resistant organisms. The method can be realized with a disposable device that is simple, cost effective, and ideal for mass production. The proposed Phase II effort focuses on extending our investigation to include all first and second line antibiotics used to treat uropathogens and developing a prototype test instrument. Urinary tract infections (UTIs) are among the most common of all bacterial infections, occurring primarily in women, and accounting for as many as 8 million outpatient visits to doctors annually. Furthermore, UTIs have become the leading healthcare-associated infection among adults and children in the United States. However, the management of UTIs has become more complicated over the last decade due to increasing antimicrobial resistance to first-line antibiotics. Already, authorities advise the use of significantly more expensive fluoroquinolones as a first line treatment for uncomplicated UTIs when the prevailing rate of antibiotic resistance in the area rises to greater than 20 percent. The same type of resistance of E. coli in other countries has reached a shocking 70 to 100 percent. Antibiotic resistance represents a problem of increasing societal importance brought about by the overuse or inappropriate use of broad-spectrum antibiotics. The proposed rapid test is an essential tool for the responsible and prudent use of prescribed antibiotics to prevent the spread of resistant bacterial strains
Keywords: 0-11 years old; 2, 4-Imidazolidinedione, 1-(((5-nitro-2-furanyl)methylene)amino)-; 21+ years old; 3-Quinolinecarboxylic acid, 1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-; 3-Quinolinecarboxylic acid, 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-; 4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 6-((amino(4-hydroxyphenyl)acetyl)amino)-3, 3-dimethyl-7-oxo-, (2S-(2alpha, 5alpha, 6beta(S*)))-; 5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(((2-amino-4-thiazolyl)(methoxyimino)acetyl)amino)-8-oxo-3-(((1, 2, 5, 6-tetrahydro-2-methyl-5, 6-dioxo-1, 2, 4-triazin-3-yl)thio)methyl)-, (6R-(6alpha, 7beta(Z)))-; Accounting; Adult; Algorithms; Amoxicillin; Amoxicilline; Amoxil; Amoxycillin; Antibiotic Agents; Antibiotic Drugs; Antibiotic Resistance; Antibiotic susceptibility; Antibiotics; Antimicrobial Resistance; Antimicrobial resistant; Applications Grants; Area; Attention; Bacteria; Bacteria resistance; Bacteria resistant; Bacterial Infections; Bacterial resistant; Bactrim; Benzenesulfonamide, 4-amino-N-(5-methyl-3-isoxazolyl)-, mixt. with 5-((3, 4, 5-trimethoxyphenyl)methyl)-2, 4-pyrimidinediamine; Biological; Biosensing Technics; Biosensing Techniques; Businesses; Care, Health; Cefatriaxone; Ceftriaxone; Cell Count; Cell Number; Cell division; Cells; Centrin; Chemicals; Child; Child Youth; Children (0-21); Ciprofloxacin; Circulatory Collapse; Clavulanate; Clinic; Clinical; Clinical Microbiology; Collection; Cotrim; Country; D-Streptamine, O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1-6)-O-(6-amino-6-deoxy-alpha-D-glucopyranosyl-(1-4))-2-deoxy-; Detection; Development; Devices; Diagnostic; Diagnostic Method; Diagnostic Procedure; Diagnostic Technique; Diagnostic tests; Dimensions; Drugs; E coli; Electrical Impedance; Electrodes; Electronics; Elements; Enterococcus faecium; Escherichia coli; Eslectin; Event; Exposure to; FDA approved; Figs; Figs - dietary; Fluoroquinolones; Funding; Generalized Growth; Generations; Genus staphylococcus; Grant; Grant Proposals; Grants, Applications; Growth; HOSP; Healthcare; Hospitals; Hour; Housing; Human, Adult; Human, Child; Hydroxyampicillin; Impedance; Infection; Insozalin; Instrumentation, Other; Investigation; K. pneumoniae; Kanamycin; Klebsiella pneumonia bacterium; Klebsiella pneumoniae; Laboratories; Levaquin; Levofloxacin; Life; Macrobid; Macrodantin; Measurement; Measures; Medical center; Medication; Metabolic; Metabolic Pathway; Methods; Methods and Techniques; Methods, Other; Mirabilis; Miscellaneous Antibiotic; Monitor; NIDDK; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Digestive Diseases and Kidney Disorders; Nitrofurantoin; Norfloxacin; Ofloxacin, (S)-Isomer; Operation; Operative Procedures; Operative Surgical Procedures; Optics; Organism; Out-patients; Outcome; Outpatients; P. aeruginosa; P.aeruginosa; Patients; Performance; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Physiologic; Physiological; Polymox; Population; Predisposition; Procedures; Process; Production; Programs (PT); Programs [Publication Type]; Proteus mirabilis; Protocol; Protocols documentation; Pseudomonas aeruginosa; Pseudomonas pyocyanea; Quixin; Records; Research; Research Specimen; Resistance; Resistance to antibiotics; Resistance to antimicrobial; Resistance, Antibiotic; Resistant to antibiotics; S. agalactiae; S. aureus; S. faceium; S. faecium; S.agalactiae; S.aureus; S.faceium; S.faecium; SMZ-TMP; Serratia marcescens; Shock; Side; Specimen; Speed; Speed (motion); Staging; Staphylococcus; Staphylococcus aureus; Streptococcus; Streptococcus Group B; Streptococcus agalactiae; Streptococcus faceium; Streptococcus faecium; Stress; Surgical; Surgical Interventions; Surgical Procedure; Susceptibility; Suspension substance; Suspensions; TMP-SMX; Techniques; Technology; Testing; Time; Tissue Growth; Trimedin; Trimethoprim-Sulfamethoxazole; Trimethoprim-Sulfamethoxazole Combination; Trimezole; Trimox; UTI; United States; Urinary System, Urine; Urinary tract infection; Urinary tract infectious disease; Urine; Uropathogen; Utimox; Visit; Woman; Work; Wymox; ing; adult human (21+); anti-microbial; anti-microbial agent; anti-microbial drug; anti-microbial resistance; anti-microbial resistant; antibiotic resistant; antimicrobial; antimicrobial agent; antimicrobial drug; authority; bacterial disease; bacterial resistance; base; biological adaptation to stress; biosensing; children; circulatory shock; cost; cost effective; data acquisition; design and construction; drug/agent; effectiveness measure; electric impedance; experiment; experimental research; experimental study; improved; innovate; innovation; innovative; instrument; instrumentation; living system; millimeter; novel; ontogeny; overgrowth bacterial; pathogen; pathogenic bacteria; phase 1 study; phase 2 study; prevent; preventing; programs; prototype; reaction; crisis; research study; resistance to Bacteria; resistance to Bacterial; resistance to anti-microbial; resistant; resistant strain; resistant to Bacteria; resistant to Bacterial; resistant to anti-microbial; resistant to antimicrobial; sample collection; specimen collection; stress response; stress; reaction; stressor; surgery; suspension; tool; urinary; youngster
Project start date: 2010-03-05
Project end date: 2011-02-28
Budget start date: 5-MAR-2010
Budget end date: 28-FEB-2011
PFA/PA: PA-07-280
3R44DK075198-03S1 (2010): $26054
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Ronald J Rieder
Ultra-Sensitive Detection Of Protein-Ligand Interactions
Ronald J Rieder
Biosense Technologies, Inc. 4 Arrow Dr Woburn, Ma 018012040
Grant 1R43CA101460-01 from National Cancer Institute IRG: ZRG1
Abstract: The development of an evanescent wave biosensor enabling the monitoring of binding interactions of small weakly interacting bio-molecules (MW<100Da) currently not possible is proposed. This technique relies on an innovative transducer design employing a novel self-compensating interferometer capable of surface sensitivities at the level of fg/mm2 - many orders of magnitude improvement over commercially available biosensors. The device employs the novel use of microfluidic flow dynamics for high capture efficiency further reducing the time to results for high throughput and is readily integrated into a small disposable, sealed cartridge for ease of use and low cost. The Phase I effort is focused around a proof-of-principle experiment demonstrating the sensitivity of the device. The Phase II effort will focus on the development of a microfluidic flow cell and a technical demonstration of the binding of a relevant ligand-protein system.
Keywords: biomedical equipment development, biosensor, interferometry, intermolecular interaction, ligand, protein, fluid flow, monitoring device, optics, bioengineering /biomedical engineering
Project start date: 2003-04-01
Project end date: 2004-07-31
1R43CA101460-01 (2003): $100000
Rapid Diagnostic Testing Of Urinary Tract Infections
Ronald J Rieder
Biosense Technologies, Inc. 4 Arrow Dr Woburn, Ma 018012040
Grant 1R43DK075198-01 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ZRG1
Abstract: The development of a new rapid diagnostic method for testing the antibiotic susceptibility of urinary tract infections is proposed. The technical approach is based on a novel implementation of impedance sensing to monitor cellular growth with exceptional sensitivity and stability avoiding the need for grown cultures to obtain results. Susceptibility results can be obtained directly from urinary specimens at the point of care within two hours reducing the time from sample collection to availability by days enabling targeted therapy, improved patient outcomes, and the reduced spread and generation of resistant organisms. The method can be realized with a disposable device that is simple, cost effective, and ideal for mass production. Feasibility of the proposed diagnostic tool will be demonstrated with both drug susceptible and resistant strains of Escherichia coli. A follow-on effort will focus on the development of prototype instrumentation and testing of other clinically relevant multi-drug resistant organisms.
Keywords: antibiotic, biomedical equipment development, biosensor device, communicable disease diagnosis, diagnosis design /evaluation, diagnostic test, drug resistance, rapid diagnosis, urinary tract disorder diagnosis, urinary tract infection, electrical impedance, electrical measurement, urinalysis, Escherichia coli, bioengineering /biomedical engineering
Project start date: 2006-05-18
Project end date: 2007-04-30
1R43DK075198-01 (2006): $100000
Rapid Antibiotic Susceptibility Testing
Ronald J Rieder
Biosense Technologies, Inc. 4 Arrow Dr Woburn, Ma 018012040
Grant 1R43AI056707-01 from National Institute Of Allergy And Infectious Diseases IRG: ZRG1
Abstract: The development of a new method for the diagnostic testing of Mycobacterium tuberculosis having unparalleled speed and simplicity is proposed. The technical approach is based on a novel implementation of impedance sensing to monitor cellular growth with unprecedented sensitivity and stability. This enables results to be obtained directly from sputum samples within a few hours with a simple, inexpensive, and easy to use device ideally suited for mass production. This method also avoids the need for grown cultures, thus reducing the time from sample collection to complete diagnosis by weeks compared to currently used methods. The new method is also applicable to other Category A, B, and C organisms. Feasibility of the proposed diagnostic tool will be demonstrated with antimicrobial drug resistant strains of Mycobacterium smegmatis and Mycobacterium bovis BCG within a 12-month Phase I effort. A Phase II effort will be focused on the development of a prototype instrumentation and clinical testing of multi-drug resistant strains of M. tuberculosis.
Keywords: Mycobacterium tuberculosis, antibiotic, biosensor, diagnosis design /evaluation, rapid diagnosis, Mycobacterium bovis, Mycobacterium smegmatis, cell proliferation, drug resistance, electrical impedance, tissue /cell culture
Project start date: 2003-07-01
Project end date: 2004-12-31
1R43AI056707-01 (2003): $476168
RAPID DIAGNOSTIC TESTING OF URINARY TRACT INFECTIONS
Ronald J Rieder, President
Biosense Technologies, Inc., 4 Arrow Dr, Woburn, Ma 01801-2040
Grant 5R44DK075198-03 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: The continued development of a rapid diagnostic method for testing the antibiotic susceptibility of urinary tract infections in near real-time is proposed. Currently, all methods for determining antibiotic susceptibility rely exclusively on detecting changes in the bacterial population caused by cell division after exposure to an antimicrobial compound. In our Phase I effort we demonstrated a novel phenotypic approach to antibiotic susceptibility testing that provides commensurate information without measurements of growth. Technical feasibility of this method was demonstrated by measuring the antibiotic susceptibility of both sensitive and resistant strains of Escherichia coli and Pseudomonas aeruginosa treated with antibiotics having different mechanisms of action. Susceptibility results were obtained within one hour time. In addition, resistant strains were easily distinguished from sensitive strains. Because grown cultures are no longer needed to obtain results, susceptibility results can be obtained directly from urinary specimens at the point of collection within 90 minutes total reducing the time from sample collection to availability by days enabling targeted therapy, improved patient outcomes, and the reduced spread and generation of resistant organisms. The method can be realized with a disposable device that is simple, cost effective, and ideal for mass production. The proposed Phase II effort focuses on extending our investigation to include all first and second line antibiotics used to treat uropathogens and developing a prototype test instrument. Urinary tract infections (UTIs) are among the most common of all bacterial infections, occurring primarily in women, and accounting for as many as 8 million outpatient visits to doctors annually. Furthermore, UTIs have become the leading healthcare-associated infection among adults and children in the United States. However, the management of UTIs has become more complicated over the last decade due to increasing antimicrobial resistance to first-line antibiotics. Already, authorities advise the use of significantly more expensive fluoroquinolones as a first line treatment for uncomplicated UTIs when the prevailing rate of antibiotic resistance in the area rises to greater than 20 percent. The same type of resistance of E. coli in other countries has reached a shocking 70 to 100 percent. Antibiotic resistance represents a problem of increasing societal importance brought about by the overuse or inappropriate use of broad-spectrum antibiotics. The proposed rapid test is an essential tool for the responsible and prudent use of prescribed antibiotics to prevent the spread of resistant bacterial strains
Keywords: 0-11 years old; 2, 4-Imidazolidinedione, 1-(((5-nitro-2-furanyl)methylene)amino)-; 21+ years old; 3-Quinolinecarboxylic acid, 1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-; 3-Quinolinecarboxylic acid, 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-; 4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 6-((amino(4-hydroxyphenyl)acetyl)amino)-3, 3-dimethyl-7-oxo-, (2S-(2alpha, 5alpha, 6beta(S*)))-; 5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(((2-amino-4-thiazolyl)(methoxyimino)acetyl)amino)-8-oxo-3-(((1, 2, 5, 6-tetrahydro-2-methyl-5, 6-dioxo-1, 2, 4-triazin-3-yl)thio)methyl)-, (6R-(6alpha, 7beta(Z)))-; Accounting; Adult; Algorithms; Amoxicillin; Amoxicilline; Amoxil; Amoxycillin; Antibiotic Agents; Antibiotic Drugs; Antibiotic Resistance; Antibiotic susceptibility; Antibiotics; Antimicrobial Resistance; Antimicrobial resistant; Applications Grants; Area; Attention; Bacteria; Bacteria resistance; Bacteria resistant; Bacterial Infections; Bacterial resistant; Bactrim; Benzenesulfonamide, 4-amino-N-(5-methyl-3-isoxazolyl)-, mixt. with 5-((3, 4, 5-trimethoxyphenyl)methyl)-2, 4-pyrimidinediamine; Biological; Biosensing Technics; Biosensing Techniques; Businesses; Care, Health; Cefatriaxone; Ceftriaxone; Cell Count; Cell Number; Cell division; Cells; Centrin; Chemicals; Child; Child Youth; Children (0-21); Ciprofloxacin; Circulatory Collapse; Clavulanate; Clinic; Clinical; Clinical Microbiology; Clinical Trials, Phase I; Clinical Trials, Phase II; Collection; Cotrim; Country; D-Streptamine, O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1-6)-O-(6-amino-6-deoxy-alpha-D-glucopyranosyl-(1-4))-2-deoxy-; Detection; Development; Devices; Diagnostic; Diagnostic Method; Diagnostic Procedure; Diagnostic Technique; Diagnostic tests; Dimensions; Drugs; E coli; Early-Stage Clinical Trials; Electrical Impedance; Electrodes; Electronics; Elements; Enterococcus faecium; Escherichia coli; Eslectin; Event; Exposure to; FDA approved; Figs; Figs - dietary; Fluoroquinolones; Funding; Generalized Growth; Generations; Genus staphylococcus; Grant; Grant Proposals; Grants, Applications; Growth; HOSP; Healthcare; Hospitals; Hour; Housing; Human, Adult; Human, Child; Hydroxyampicillin; Impedance; Infection; Insozalin; Instrumentation, Other; Investigation; K. pneumoniae; Kanamycin; Klebsiella pneumonia bacterium; Klebsiella pneumoniae; Laboratories; Levaquin; Levofloxacin; Life; Macrobid; Macrodantin; Measurement; Measures; Medical center; Medication; Metabolic; Metabolic Pathway; Methods; Methods and Techniques; Methods, Other; Mirabilis; Miscellaneous Antibiotic; Monitor; NIDDK; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Digestive Diseases and Kidney Disorders; Nitrofurantoin; Norfloxacin; Ofloxacin, (S)-Isomer; Operation; Operative Procedures; Operative Surgical Procedures; Optics; Organism; Out-patients; Outcome; Outpatients; P. aeruginosa; P.aeruginosa; Patients; Performance; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Phase 1 Clinical Trials; Phase 2 Clinical Trials; Phase I Clinical Trials; Phase I Study; Phase II Clinical Trials; Physiologic; Physiological; Polymox; Population; Predisposition; Procedures; Process; Production; Programs (PT); Programs [Publication Type]; Proteus mirabilis; Protocol; Protocols documentation; Pseudomonas aeruginosa; Pseudomonas pyocyanea; Quixin; Records; Research; Research Specimen; Resistance; Resistance to antibiotics; Resistance to antimicrobial; Resistance, Antibiotic; Resistant to antibiotics; S. agalactiae; S. aureus; S. faceium; S. faecium; S.agalactiae; S.aureus; S.faceium; S.faecium; SMZ-TMP; Serratia marcescens; Shock; Side; Specimen; Speed; Speed (motion); Staging; Staphylococcus; Staphylococcus aureus; Streptococcus; Streptococcus Group B; Streptococcus agalactiae; Streptococcus faceium; Streptococcus faecium; Stress; Surgical; Surgical Interventions; Surgical Procedure; Susceptibility; Suspension substance; Suspensions; TMP-SMX; Techniques; Technology; Testing; Time; Tissue Growth; Trimedin; Trimethoprim-Sulfamethoxazole; Trimethoprim-Sulfamethoxazole Combination; Trimezole; Trimox; UTI; United States; Urinary System, Urine; Urinary tract infection; Urinary tract infectious disease; Urine; Uropathogen; Utimox; Visit; Woman; Work; Wymox; ing; adult human (21+); anti-microbial; anti-microbial agent; anti-microbial drug; anti-microbial resistance; anti-microbial resistant; antibiotic resistant; antimicrobial; antimicrobial agent; antimicrobial drug; authority; bacterial disease; bacterial resistance; base; biological adaptation to stress; biosensing; children; circulatory shock; cost; cost effective; data acquisition; design and construction; drug/agent; effectiveness measure; electric impedance; experiment; experimental research; experimental study; improved; innovate; innovation; innovative; instrument; instrumentation; living system; millimeter; novel; ontogeny; overgrowth bacterial; pathogen; pathogenic bacteria; phase 1 study; phase 1 trial; phase 2 study; phase 2 trial; phase I trial; phase II trial; prevent; preventing; programs; protocol, phase I; protocol, phase II; prototype; reaction; crisis; research study; resistance to Bacteria; resistance to Bacterial; resistance to anti-microbial; resistant; resistant strain; resistant to Bacteria; resistant to Bacterial; resistant to anti-microbial; resistant to antimicrobial; sample collection; specimen collection; stress response; stress; reaction; stressor; study, phase II; surgery; suspension; tool; urinary; youngster
Project start date: 2006-05-18
Project end date: 2010-04-30
Budget start date: 1-MAY-2009
Budget end date: 30-APR-2010
PFA/PA: PA-07-280
5R44DK075198-03 (2009): $344871
MONITORING PHYSIOLOGICAL STRESS: A NOVEL BIOPHYSICAL APPROACH FOR THE RAPID DETEC
Ronald J Rieder, President
Biosense Technologies, Inc., 4 Arrow Dr, Woburn, Ma 01801-2040
Grant 1RC3HL103273-01 from National Heart, Lung, And Blood Institute
Abstract: Platelet transfusion is the leading cause of transfusion related bacterial sepsis. Despite the mandated testing of platelet concentrate (PC) for contaminant bacteria, limitations in currently used testing methods continue to result in a significant number of false-negative results from systematic errors associated with sampling at times when bacterial numbers are low. This was recently underscored by the abrupt termination of the PASSPORT, a study designed to assess extending the transfusable lifespan of PCs. This occurred because a high incidence of bacterial contamination was detected even though the PC was previously tested. One approach for addressing this problem is effective testing just prior to transfusion when contaminant bacteria have had time to grow to more easily detectable numbers. BioSense Technologies proposes to continue the development of a prototype instrument for the rapid bacterial testing of PCs that is sensitive, rapid, and easy to implement - all of the criteria needed for acceptance in hospital blood banks. The technical approach is based on monitoring the stress developed by bacteria growing in PC in the presence of a chemical stressor using a novel sensing modality that assesses their absence or presence. The approach is applicable to both whole blood-derived and aphaeresis PCs and all bacterial species. Although the technical feasibility of this approach has been demonstrated, its integration into a practical instrument has not yet been done which has posed an obstacle to investment. BioSense proposes to develop a fully automated prototype instrument and to validate it through independent testing at leading hospital blood banks. In the United States, bacterial contamination is detected in approximately 1 of every 2000 units of platelets produced and the overall incidence may be even higher. It is also the leading cause of transfusion related bacterial sepsis. The availability of an effective bacterial test for use just prior to transfusion will 1) Detecting all bacterial species with high sensitivity within the same assay will provide a safer blood supply; 2) Doubling the transfuseable lifespan of PC will reduce pressure on the availability of platelets and the nation´s blood supply; and 3) Increase public confidence in the nation´s blood supply at a time when emerging infectious diseases are continuously undermining this confidence
Keywords: Address; Algorithms; Apheresis; Assay; Bacteria; Bioassay; Biologic Assays; Biological; Biological Assay; Biosensing Technics; Biosensing Techniques; Bizzozero`s corpuscle/cell; Blood; Blood Banks; Blood Cells; Blood Component Removal; Blood Platelet Transfusion; Blood Platelets; Boston; Capacitance, Electrical; Cell Communication and Signaling; Cell Signaling; Cell division; Cells; Chemicals; City of Boston; Clinic; Clinical; Communicable Diseases, Emerging; Complex; Data Set; Dataset; Deetjeen`s body; Detection; Development; Electric Capacitance; Electronics; Emerging Communicable Diseases; Environment; Event; Exposure to; Figs; Figs - dietary; Generalized Growth; Growth; HOSP; Hayem`s elementary corpuscle; Hemapheresis; Hospitals; Housing; Human; Human, General; Incidence; Infectious Diseases, Emerging; Intracellular Communication and Signaling; Investigation; Investments; Length of Life; Life; Longevity; Man (Taxonomy); Man, Modern; Marrow platelet; Measurable; Measurement; Metabolic Pathway; Methods; Modality; Monitor; Monitoring, Physiologic; Monitoring, Physiological; Outcome; Performance; Peripheral Blood Cell; Pheresis; Physiologic; Physiologic Monitoring; Physiological; Platelet Transfusion; Platelets; Plts; Population Growth; Pressure; Pressure- physical agent; Process; Property; Property, LOINC Axis 2; Publishing; Research Design; Reticuloendothelial System, Blood; Reticuloendothelial System, Platelets; Sampling; Sepsis; Signal Transduction; Signal Transduction Systems; Signaling; Site; Source; Speed; Speed (motion); Stress; Study Type; Suspension substance; Suspensions; System; System, LOINC Axis 4; TRNSF; Technology; Testing; Thrombocytes; Time; Tissue Growth; Transfusion; United States; Vascular blood supply; WHBLOOD; Whole Blood; Woman; base; biological adaptation to stress; biological signal transduction; biosensing; blood supply; bloodstream infection; capacitance; data acquisition; design; designing; instrument; life span; lifespan; meetings; novel; ontogeny; pressure; prototype; public health relevance; reaction; crisis; response; stress response; stress; reaction; stressor; study design; surveillance study; suspension; thrombocyte/platelet; vascular supply
Relevance: In the United States, bacterial contamination is detected in approximately 1 of every 2000 units of platelets produced and the overall incidence may be even higher. It is also the leading cause of transfusion related bacterial sepsis. The availability of an effective bacterial test for use just prior to transfusion will: 1) Detecting all bacterial species with high sensitivity within the same assay will provide a safer blood supply; 2) Doubling the transfusable lifespan of PC will reduce pressure on the availability of platelets and the nation´s blood supply; and 3) Increase public confidence in the nation´s blood supply at a time when emerging infectious diseases are continuously undermining this confidence
Project start date: 2010-06-15
Project end date: 2012-05-31
Budget start date: 15-JUN-2010
Budget end date: 31-MAY-2012
PFA/PA: RFA-OD-09-008
1RC3HL103273-01 (2010): $1998687
RAPID DETECTION OF BACTERIAL CONTAMINATION IN PLATELETS
Ronald J Rieder, President
Biosense Technologies, Inc., 4 Arrow Dr, Woburn, Ma 01801-2040
Grant 5R44HL090636-03 from National Heart, Lung, And Blood Institute
Abstract: A new approach for detecting pathogenic bacteria in platelet concentrates rapidly is proposed. Technically, the approach is based on an unconventional implementation of impedance sensing to monitor cellular metabolic responses with exceptional sensitivity and stability. This enables the detection of small numbers of viable aerobic and anaerobic microorganisms in near-real time without the need for grown cultures significantly reducing the time from sample collection to detection results by several days compared to currently in use methods. Feasibility of the approach was successfully demonstrated as part of the Phase I investigation with representative Gram-negative and Gram-positive species commonly implicated in platelet- associated bacterial sepsis. In addition, the ability to make decisive measurements in short time enables the bacterial testing of platelets just prior to transfusion ensuring the safety of the patient and potentially extending platelets shelf life. The proposed Phase II effort focuses on the development of a prototype instrument and testing of contaminated platelets in a realistic setting. The described approach may also be applicable to the detection of bacteria in other blood products. Bacterial contamination is detected in approximately one of every 2000 units of platelets and is implicated as the cause of severe or fatal sepsis in an estimated 150 patients per year in the United States. The proposed rapid test will enable the detection of viable contaminant bacteria in platelet supplies in near-real time both insuring their safe use and extending their useable life-span
Keywords: Aerobic; Anaerobic Bacteria; Animal Model; Animal Models and Related Studies; Applications Grants; Assay; Attention; Bacteria; Bacteria, Anaerobic; Behavior; Bioassay; Biologic Assays; Biological Assay; Biosensing Technics; Biosensing Techniques; Biosensor; Bizzozero`s corpuscle/cell; Blood; Blood Platelet Transfusion; Blood Platelets; Blood leukocyte; Businesses; Capacitance, Electrical; Cell Count; Cell Number; Cell Survival; Cell Viability; Cells; Circulatory Collapse; Compatible; Condition; Cytolysis; Deetjeen`s body; Detection; Development; Devices; Diagnostic; Dimensions; Distress; Electric Capacitance; Electrical Impedance; Electrodes; Electronics; Elements; Ensure; FDA; Food and Drug Administration; Food and Drug Administration (U.S.); Generalized Growth; Goals; Grant Proposals; Grants, Applications; Growth; Hayem`s elementary corpuscle; Heat Shock; Heat-Shock Reaction; Heat-Shock Response; Housing; Impedance; Instrumentation, Other; Investigation; Laboratories; Length of Life; Leukocytes; Life; Longevity; Lysis; Marrow leukocyte; Marrow platelet; Measurement; Measures; Medical Directors; Medicine; Metabolic; Methods; Methods and Techniques; Methods, Other; Microorganisms, General; Monitor; NaN3; Numbers; Operation; Operative Procedures; Operative Surgical Procedures; Optics; Patients; Performance; Phase; Physician Executives; Platelet Transfusion; Platelets; Plts; Preparation; Procedures; Process; Production; Programs (PT); Programs [Publication Type]; Proteins; Protocol; Protocols documentation; Reaction; Reading; Records; Recovery; Research; Reticuloendothelial System, Blood; Reticuloendothelial System, Leukocytes; Reticuloendothelial System, Platelets; Rhode Island; Sampling; Science of Medicine; Sepsis; Shock; Side; Sodium Azide; Speed; Speed (motion); Staging; Standards; Standards of Weights and Measures; Stream; Stress; Stress Tests; Surgical; Surgical Interventions; Surgical Procedure; Suspension substance; Suspensions; TRNSF; Techniques; Technology; Testing; Thrombocytes; Time; Tissue Growth; Transfusion; Triton X 100; Triton X100; USFDA; United States; United States Food and Drug Administration; White Blood Cells; White Cell; Work; anaerobe; base; biological adaptation to stress; biosensing; bloodstream infection; capacitance; circulatory shock; concept; cost; data acquisition; day; design; design and construction; designing; dielectric property; electric impedance; experiment; experimental research; experimental study; gene product; innovate; innovation; innovative; instrument; instrumentation; laptop; life span; lifespan; microorganism; millimeter; model organism; new approaches; novel; novel approaches; novel strategies; novel strategy; ontogeny; pathogenic bacteria; patient safety; programs; prototype; rapid detection; rapid method; rapid technique; reaction; crisis; research study; response; sample collection; sensor (biological); septic; size; specimen collection; stress response; stress; reaction; surgery; suspension; thrombocyte/platelet; white blood cell; white blood corpuscle
Project start date: 2004-04-01
Project end date: 2010-05-31
Budget start date: 1-JUN-2008
Budget end date: 31-MAY-2010
PFA/PA: PA-06-120
5R44HL090636-03 (2008): $0
3R44HL090636-03S1 (2008): $0
9R44HL090636-02 (2007): $365793