SBIR-STTR Award

In Vitro Diagnostic Solutions (IVDS) proposes to develop the only point-of-care (POC) test for the determination of L-phenylalanine (Phe) from a finger or heel-stick sample. The point-of-care test, the “PKU Now” will be used as a home monitoring device for PKU patients and for diagnostic testing in developing regions. The PKU Now will provide immediate feedback of whole blood phe concentration, allowing for stricter dietary compliance, improve the quality of life, and reduce healthcare costs. In Phase I studies, we will resolve three outstanding issues before commercializing the system, namely eliminating interferences (Aim-1), eliminating hematocrit bias in the range of 32% to 60% (Aim-2), and establishing agreement between the “PKU Now” and a laboratory reference method (Aim-3). Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. PKU is the most common disorder of amino acid metabolism, effecting 1 in 8,000 people, globally. Most cases of PKU are detected shortly after birth by newborn screening. Individuals affected by PKU must monitor and control phe levels throughout their lives to avoid neurological complications including; permanent intellectual disabilities, seizures, delayed development, behavioral problems, and psychiatric disorders. Whole blood is collected in EDTA tubes or spotted onto Dried Blood Spot (DBS) Cards by parents, patients or caregivers. These samples are sent to laboratories for measurement by tandem mass spec and results can take days to weeks. This complicated process for monitoring and controlling phe levels, results in non-compliance, a decrease in quality of life, as well as increased healthcare costs for treating complications. The PKU Now will provide real time phe levels, allowing parents and caregivers to promptly adjust their diets to help maintain optimal phenylalanine levels. In Vitro Diagnostic Systems (IVDS) has developed a prototype POC test, in which phe can be quantified from a 20 microliters of sample. Upon successful validation of “PKU Now”, Phase II will ensure linearity and precision, establish intra-day and inter-day precision, and evaluate preclinical data against tandem mass spec analysis, all following CLSI guidelines. “PKU Now” will be the only point-of-care testing device (POCT) that will allow the accurate measurement of L-phenylalanine (phe) levels from a finger or heel-stick.

Public Health Relevance Statement:
Project Narrative PKU is the most common disorder of amino acid metabolism, effecting 1 in 8,000 people, globally. Without proper monitoring and treatment, these patients can develop permanent intellectual disabilities, seizures, delayed development, behavioral problems, and psychiatric disorders. IVDS propose the development of the PKU Now as a home monitoring point-of-care device and as well a diagnostic device in developing regions where new-born screening is not available.

Project Terms:
Affect; Agreement; amino acid metabolism; Analysis of Variance; Bedside Testings; Bilirubin; Biological Assay; Birth; Blood; Caregivers; Catabolism; Color; Data; Data Set; design; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Diet; Disease; Edetic Acid; Ensure; enzyme activity; Excipients; Feedback; Fingers; Genetic Screening; Guidelines; Health Care Costs; Heel; Hematocrit procedure; Hereditary Disease; Home environment; Immobilization; improved; In Vitro; Individual; Intellectual functioning disability; Laboratories; Legal patent; Measurement; Membrane; Mental disorders; Methods; Monitor; monitoring device; Neonatal Screening; Neurologic; non-compliance; Oxides; Oxidoreductase; Parents; Pathway interactions; Patients; Phase; phase 1 study; Phenylalanine; Phenylketonurias; Plasma; point of care; Population; pre-clinical; Problem behavior; Process; prototype; Quality of life; Reagent; Sampling; Seizures; Series; Signal Transduction; Spottings; Structure; System; Testing; Time; Triglycerides; Tube; Tyrosine; Validati

In Vitro Diagnostic Solutions (IVDS) proposes to develop the first and only FDA-approved point-of-care test (POCT) for the determination of L-phenylalanine (Phe) from a finger or heel-stick sample. The PKU Now will serve as a lifelong home monitoring device for PKU patients as well as a diagnostic testing device in lesser- developed regions. It will provide immediate feedback on blood Phe levels, which will enable stricter dietary compliance, substantially improve the quality of life for PKU patients and reduce healthcare costs. In Phase I studies, we successfully resolved three critical issues. We eliminated tyrosine interference that could obscure the measurement of Phe (Aim-1), eliminated hematocrit bias in the range of 32% to 60% (Aim-2) and established concordance between the “PKU Now” and a laboratory reference method, Amino Acid Analysis (AAA), in terms of accuracy and precision (Aim-3). PKU is the most common amino acid disorder, affecting 1 in 10,000 people. Most cases of PKU are detected by newborn screening in developed countries. PKU patients must monitor and control their Phe levels throughout their lives to avoid severe neurological complications, permanent intellectual disabilities and delayed development. Currently, Phe levels are measured at laboratories via blood collection or blood spotted onto Dried Blood Spot Cards and sent for mass spec analysis. This complicated process for monitoring Phe makes real time measurements impossible resulting in non-compliance. “Currently, results from DBS testing can take days to weeks. This situation endangers the health and well-being of tens of thousands of people with PKU. Such a device will open the way for newborn screening of PKU in developing countries. Of all babies born around the world, more than 2/3 won’t be tested for PKU” (PKU.org). IVDS’s proposed POCT, the “PKU Now”, will provide real-time blood Phe levels, thereby enabling immediate intervention and improving the quality of life of thousands of people. To complete development of the PKU Now, we will: Aim-1: Finalize assay development by evaluating bioactive components; Aim-2: Transition from hand assembly to semi-automated assembly of test strips; Aim-3: Develop and test synthetic controls; Aim-4: Validate the PKU Now using spiked blood samples (following potential changes from Aim-1); and Aim-5: In two Blind Studies, we will establish concordance between the data obtained from the PKU NowTM and data obtained from AAA using PKU patient samples. These studies will be conducted under approved IRBs’ and will follow all HIPPA guidelines. Once commercialized, the PKU NowTM will be the first POC diagnostic tool and home monitoring device for PKU patients, enabling real-time intervention and treatment.

Public Health Relevance Statement:
Project Narrative PKU is the most common disorder of amino acid metabolism, effecting 1 in 10,000 people, globally. Without proper monitoring and treatment, PKU patients can develop permanent intellectual disabilities, seizures, behavioral problems and psychiatric disorders. IVDS proposes to complete the development of the PKU NowTM, a point-of-care device that will be used for in home monitoring as well as newborn screening in developing regions.

Project Terms:
Affect; Aging; amino acid metabolism; Amino Acids; assay development; Automation; Bedside Testings; Biological; blind; Blood; Blood specimen; Classical phenylketonuria; Clinic; Clinical Laboratory Improvement Amendments; Collection; Color; Country; Data; Developed Countries; Developing Countries; Development; Devices; Diagnostic; Diagnostic tests; Diet; dihydrolipoamide dehydrogenase; Disease; Excipients; FDA approved; Feedback; Fingers; Formulation; Freezing; Glucose; Goals; Guidelines; Hand; Harvest; Health; Health Care Costs; Heel; Hematocrit procedure; Heparin; Hereditary Disease; Home environment; improved; In Vitro; Institutional Review Boards; Intellectual functioning disability; Intervention; Joints; Laboratories; Letters; Measurement; Measures; Medical; medical specialties; Membrane; Mental disorders; meter; Methods; Modeling; Monitor; monitoring device; Neonatal Screening; Neurologic; non-compliance; Oxidoreductase; Patients; Personal Satisfaction; Phase; phase 1 study; Phenylalanine; Phenylketonurias; Plasma; point of care; point-of-care diagnostics; Polymers; Problem behavior; Process; Quality of life; Reagent; Sampling; Seizures; Sensitivity and Specificity; Sodium Azide; Specificity; Spottings; stability testing; System; Temperature; temporal measurement; Testing; Time; tool; Training; Tube; Tyrosine; Venous; Vial device; wa