Grants

Over $2.5 million in federal funding secured and executed

About

In Vitro Diagnostic Solutions has successfully secured and executed over $2.5 million in federal funding from the National Institutes of Health and the National Science Foundation. Through these programs we have successfully demonstrated strong scientific feasibility and launched commercialization of several innovative chemistries in a universal platform that will transform the market and increase accessibility for point of care diagnostics across a wide spectrum of challenge diseases.

A User-Friendly Point of Care Device, Glucose-6-Phosphaste Dehydrogenase 

Grant Number: 1R43AI129057-01A1
Grant Agency and Type: NIH NIAID, Phase I SBIR
Amount: $191,220
Principal Investigator: Robert Harper
Disease Indication: Malaria

Overview: Malaria caused by Plasmodium vivax threatens over 2 billion people globally and sickens tens of millions annually. Radical cure for P. vivax malaria includes therapy aimed both at the acute attack (blood schizontocidal) and against future attacks (hypnozoitocidal). The only hypnozoitocide available are 8- aminoquinolines such as primaquine or tafenoquine. However, clinicians often do not prescribe 8- aminoquinolines due to the high prevalence (8%) of individuals with various levels of inherited Glucose-6- phosphate dehydrogenase (G6PD) deficiencies, because these drugs can cause life-threatening acute hemolytic anemia in patients with moderate to severe G6PD deficits. There is an urgent need to quantify both Hgb and G6PD for patients stricken with malaria or prior to the administration of 8-aminoquinilones. All current quantitative methods for G6PD determination are laboratory based spectrophotometric methods, requiring diluents, reagents, pipettes and trained personnel. There are currently no commercially available point-of-care (POC) tests that can quantify both Hgb and G6PD directly from a finger-stick sample. Developing a robust, quantitative assay for field use in low resource areas is a high priority for overall malaria control and elimination.

Technology Solution: In Vitro Diagnostic Systems (IVDS) will establish the feasibility of developing a POC test, the PreQuine Test, in which Hgb and G6PDH levels can be quantitated simultaneously from a 30 mL blood stick sample. In pilot studies, we have successfully assessed Hgb and G6PD levels using independent test strips. To develop a dual Hgb and G6PDH test strip, we propose develop a lysing protocol to maximize liberation of Hgb and G6PD from blood samples (Aim 1), optimize Hgb and G6PDH assay conditions (Aim 2) and then combine the Hgb and G6PD assays into a single test strip (Aim 3). The PreQuine Test results will be compared to results obtained with a calibrated hand-held meter; demonstration of concordance of the results from the PreQuine Test strip and calibrated meter to reference samples will indicate success.

Results and Commercialization Status: We achieved all of our Phase I Aims and filed for a Phase II application, 2R44AI129057-02A1

A User-Friendly Point of Care Device, Glucose-6-Phosphastase Dehydrogenase 

Grant Number: 2R44AI129057-02A1
Grant Agency and Type: NIH NIAID, Phase II SBIR
Amount: $1,447,330
Principal Investigator: Robert Harper
Disease Indication: Malaria

Overview: Malaria caused by Plasmodium vivax threatens over 2 billion people globally and sickens tens of millions annually. Radical cure for P. vivax malaria includes therapy aimed both at the acute attack (blood schizontocidal) and against future attacks (hypnozoitocidal). The only hypnozoitocide available are 8- aminoquinolines such as primaquine or tafenoquine. However, clinicians often do not prescribe 8- aminoquinolines due to the high prevalence (8%) of individuals with various levels of inherited Glucose-6- phosphate dehydrogenase (G6PDH) deficiencies, because these drugs can cause life-threatening acute hemolytic anemia in patients with moderate to severe G6PDH deficits. There is an urgent need to quantify both Hgb and G6PDH for patients stricken with malaria or prior to the administration of 8-aminoquinilones. All current quantitative methods for G6PDH determination are laboratory based spectrophotometric methods, requiring diluents, reagents, pipettes and trained personnel. There are currently no commercially available point-of-care (POC) tests that can quantify both Hgb and G6PDH directly from a finger-stick sample. Developing a robust, quantitative assay for field use in low resource areas is a high priority for overall malaria control and elimination.

Technology Solution: To complete development of the PreQuine System, we will: (1) Finalize Assay Development by Assessing Bioactive Components. Three commercially available diaphorases will be tested to ensure (1) a high degree of activity at the optimal pH (2) long-term stability; and (3) no inhibition in the presence of maleimide; (2) Transition from Hand Assembly to Semi-Automated Assembly of Test Strips. This will be achieved by optimizing process capabilities of coating, slitting and laminating the strips into 5-up card stock.; (3) Incorporate a Temperature Correction Factor (TFC). The PreQuine system must be enable function in a working temperature of 18°C to 40°C. The TFC will be incorporated into the software and correct for temperature differences. Finally, (4) Validation of the PreQuine System. Validation for G6PD and Hgb levels will demonstrate concordance between the manufactured test strips and reference methods. Once validated and commercialized, the PreQuine System will provide point of care diagnostic tool to identify G6PD deficient individuals who can or cannot tolerate 8-aminoquinoline treatment, which will transform malaria treatment strategies and aid in the eradication of P.vivax and P. oval malaria.

Results and Commercialization Status:

G6PD Analytical Range: 0.8-13 U/g Hgb , PreQuine System versus Pointe Scientific G6PD Spec Assay. Data reveals excellent agreement across the analytical range for G6PD for samples provided by PATH https://www.path.org/about/

Combined with samples spike with G6PD.

Third-degree Polynomial of Spectrophotometric Concentration of G6PD vs % Refectances

First-order Linear Regression Spectrophotometric Concentration of G6PD vs PreQuine Meter Output Calculation

A Point-Of-Care Device for Phenylalanine Determination 

Grant Number: 1R43GM126593-01A1
Grant Agency and Type: NIH NIGMS, Phase I SBIR
Amount: $224,700
Principal Investigator: Robert Harper
Disease Indication: Phenylketonuria

Overview: 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. 

Technology Solution: 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-microliter sample. “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. The point-of-care test, the “PKU Now” will be used as a home monitoring device for PKU patients and for diagnostic testing. 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).

Results and Commercialization Status: We achieved all of our Phase I Aims and filed for a Phase II application. Whole-blood spiked samples vs tandem mass spec.

First-order Linear Regression of Tandem Mass Spectral Analysis (U of Wisconsin) vs PKU Now results.

Plot reflects IVDS “Suppression Technology” of Tyrosine Interference on Phenylalanine Dehydrogenase, Patent Pending

Bland-Altman Plot of Amino Acid Analysis versus PKU Now results 60 determinations spike PHE Samples.

PKU Now Test Kit;  Meter, Capillary holder, Vial of test Strips, Vial of 20 mL capillary tubes.

A Point-Of-Care Device for the Determination of the Bilirubin, the BiliNow 

Grant Number: 1R43HD095727-01
Grant Agency and Type: NIH NICHD, Phase I SBIR
Amount: $224,700
Principal Investigator: Robert Harper
Disease Indication: Kernicterus

Overview: Neonates with high bilirubin levels can develop a fatal disorder known as Kernicterus. Kernicterus has a death rate of 2-3% and causes brain damage and serious long-term complications. High bilirubin levels are the leading cause for readmission of newborns to the hospital in the first 2 weeks of life. Current laboratory analyzers require a venipuncture for neonates, which is difficult for the care-provider, patient and parent. “With the onset of illness, it is not uncommon for neonates lose 15-30% of circulating blood volume to laboratory testing.” A NICHD workshop on NICUs concluded that there is a urgent need for metabolic analysis methods that require minimal volumes of blood, can measure analytes in parallel, and are accurate, reliable, and cost-effective. A recent report by Market Research Future, states that by 2024 the Bilirubin Testing market will reach 2.5 billion dollars. 

Technology Solution: In Vitro Diagnostic Solutions (IVDS) proposes the development of the first and only point-of-care (POC) system, the “BiliNow”, for the determination of bilirubin from a finger or heel-stick. The “BiliNow” will be used in the Neonatal Intensive Care Unit (NICU), emergency room (ER), intensive care units (ICU) and clinician’s office providing immediate feedback to expedite treatment. The BiliNow utilizes a microfluidic chip format that is minimally invasive, requiring only 30 microliters of whole blood, which is collected from a heel-stick or fingerstick. In Phase I studies, we will: 1) Test solubilizing agents to ensure complete solubility of unconjugated bilirubin; 2) Test and eliminate hematocrit bias in the neonatal range of 32 to 60%; and 3) Evaluate a dose response of bilirubin with whole blood samples. Microchips will be dosed and dried with chromophore-sensors specific for conjugated and unconjugated bilirubin. Whole blood will be spiked with each conjugated and unconjugated bilirubin, over the analytical ranges. Plasma will be separated, in-situ, and the end-color of each sensing-well will be quantitated using percent reflectance and calculated mg/dL, via a hand-held, portable analyzer, similar to the glucose model. The BiliNow provides results for both conjugated and unconjugated bilirubin in a single step within 3 minutes. The BiliNow technology has a clear advantage in the neonatal blood chemistry market as no other device can measure bilirubin, from a single drop of blood.

Results and Commercialization Status: Results showed excellent agreement with spiked blood samples for both conjugated and unconjugated bilirubin. IVDS will be applying for a Phase II application in Q1 of 2021. We are finalizing our Phase I data.

A User-Friendly Point-of-Care Device for Simultaneous G6PD and Hemoglobin Determination

Grant Number: 1746309
Grant Agency and Type: National Science Foundation, Phase I SBIR
Amount: $225,000
Principal Investigator: Robert Harper
Disease Indication: Malaria

Overview: This SBIR Phase I project seeked to develop and optical detection system to quantitate Hgb and G6PD from a test strip. This to transform treatment regimens for individuals suffering from malaria infections. Malaria particularly caused by Plasmodium vivax (P. vivax) and Plasmodium ovale  (P. ovale) remain a potential cause of morbidity and mortality amongst the 2.85 billion people living at risk of infection. The only drug currently available for treatment therapy for P. vivax and P. oval eis primaquine, which can cause life-threatening anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Clinicians often do not prescribe primaquine due to the high prevalence (8%) of individuals who are born with G6PD deficiency. The World Health Organization (WHO) and the Program for Appropriate Technology in Health (PATH) are urgently searching for a reliable assay for the diagnosis of G6PD deficiency to effectively treat patients and aid in the eradication of P. vivax and P. ovale malaria. This novel assay proposed will quantify G6PD and hemoglobin (Hgb) concentration simultaneously from a finger stick sample. This system comprises a single test strip coupled with a new prototype reflectance-based meter and cell phone application with Bluetooth connectivity to incorporate a patient’s I.D., test results, global tracking, and history of treatment. It is projected that this point-of-care assay will be used to screen >23 million people for G6PD within 5 years.

Technology Solution: The proposed novel platform will quantify both Glucose-6-Phosphate Dehydrogenase (G6PD) and hemoglobin (Hgb) concentrations simultaneously from a single finger stick sample using a point-of-care (POC) new, prototype reflectance-based meter. There is currently no such device on the market, which is urgently needed to screen patients being treated for P. vivax and P. oval malaria. A significant portion (8%) of the world population is G6PD deficient, which places these individuals at risk for life-threatening anemia after treatment with current therapeutics such as primaquine against malaria. The POC assay utilizes a novel lysis and reagent layer membrane platform to enable a reflectance-based meter to measure non-over lapping wavelengths to quantify G6PD and Hgb concentrations. In this proposal, a functional prototype reflectance-based meter and data collection software will be constructed and compared to readings obtained using the current gold standard Konica Minolta spectrophotometer. Secondly, the POC assay will be validated through performance testing using a G6PD-deficient whole blood specimen bank provided by the Program for Appropriate Technology in Health (PATH). Concordance of the data obtained from 20 samples for the proposed assay will be compared to the World Health Organization’s (WHO) approved spectrophotometric method for measuring G6PD and an FDA approved method for measuring Hgb. Success will be indicated by an R2 > 0.95, which demonstrates linear equivalency, as well as a demonstration that 90% of the data points fall within 2 sigma of each value. A POC assay that can simultaneously screen patients for both G6PD deficiency and Hgb levels will allow clinicians to treat patients with P. vivax and P. oval malaria infections effectively and aid in the eradication of malaria.

Results and Commercialization Status: IVDS is currently developing a reflectance-based meter with 3 LEDs with 3 positions to read 3 analytes. The meter is 2” x 3” in width and length. The meter will have blue tooth connectivity, QAR code and a cell phone allocation.

In Vitro Diagnostic Solutions is extremely grateful for the strong commercialization support provided by both the National Institute of Health and National Science Foundation Small Business Innovative Research Programs.

ABOUT IVDS
In Vitro Diagnostic Solutions (IVDS) develops novel testing technologies for the healthcare, veterinary, and consumer markets. IVDS scientists have helped bring 10 FDA-approved products to market over their careers in diagnostics.
CONTACT INFO
  • In Vitro Diagnostic Solutions
    900 N. Lenola Rd., Bldg. 7, Unit L
    Moorestown, NJ 08057
  • (856)-343-5098
  • Robert@ivd.solutions