Bp ususally 120/80Doppler Ultrasonography:Pregnancies associated with an abnormal uterine Doppler after 24 weeks of gestation are associated with a more than six fold increase in the rate of preeclampsiaNon stress test or biophysical profile:Check if baby is getting sufficient O2 and nutrientsResponse of baby’s heart rate relative to baby’s movement
. For the following reasons, we are intending to release our product. The first12% maternal death is caused by preeclampsiaIts globally prevalent which we’ve previously shown, but its more in developing countries.Bringing together all the aspects of market need. 76,000 maternal deaths each year across the globe as a result of preeclampsia.500,000 foetuses and newborns die annually because of the disease, mostly in lower- and middle-income countries,(WHO).An estimate of 13,000 women get preeclampsia each year in Canada 6.4 Million Women Get Pregnant Each Year in the USIt is Estimated That Preeclampsia Costs the Global Health Care System US $3 Billion Per Year. Source: US Department of Health and Human Services, National Center for Health Statistics 99% per cent of preeclampsia maternal deaths occur in lower- and middle-income countries and result from delays in diagnosis, transport and treatment. “What this project is designed to do is target all pregnant women in their communities, in lower- and middle-income countries and provide potentially a way to prevent the condition, or [allow] early identification”. Route to MarketGlobal Partnering (EU /USA, Africa, Asia) Independent Market research research has identified potential major international diagnostic companies.
Wat we’ll b looking at is specification of the product which we have developed
Target molecule:Analyte to be detectedReading system:How the test result will be seen - naked eye or use of dedicated equipment
Reading system:How the test result will be seen - naked eye or use of dedicated equipmentReproducibility near clinical threshold:Gives some idea of the chance of correctly classifying borderline specimens By testing a panel of well characterized and representative clinical samples close to the clinical thresholdTEST PROCEDURENumber of timed steps:Use of different reagents/incubation stepsPrecision pipetting:Need to use a precise volume of sample/reagent
Sample preparation:Need to process the sample prior to performing the testThroughput :Number of tests to be done per working dayADDITIONAL FEATURESHeat stability :Temperature at which the test should remained stable for a defined length of timeStorage conditions:Specific conditions for the test to be transported and stored prior utilizationEnd user profile:Level of education of the person in charge of the testBiosafety requirement:Level of protection to be made available for the staff and the samplesTraining needs:Time dedicated to training session for end users
automated : faster and more accurate and reliablePoint of care approach: portable and more accessible and user- friendlyHuge market demand: of high rate of pre-eclampsia, and high maternal mortality rate. The physicians feel the need for a method that’s more reliable and faster to detect the preeclampsia.
A blood protein marker for the early detection of pre- eclampsia
A BLOOD PROTEIN MARKER FOR THE EARLYDETECTION OF PRE- ECLAMPSIA A G7 DIAGNOSTICS PRESENTATION Helena Gwani Ayotunde Awosusi Daniel Igwe Priyesh Waghmare Srishti Jain Vinie Varkey T
OUTLINE Pre- eclempsia: What is it? Causes of maternal death Global maternity mortality Pre-eclempsia distribution Current diagnosis Market need Product specifications Conclusion
Pre- EclampsiaGlobally, Causes: Symptoms:•10% of all •Damage to the •Rising High bloodpregnancies blood vessels pressure •Insufficient blood •High protein levels•12% of maternal flow to the uterus in the urinedeaths •Severe headache•1/3rd of pre maturebirths •Visual Disturbances •Vomiting and abdominal pain
RISK FACTORS Medical problems First time pregnancy Family history Previous case of pre-eclampsia 40 years or older Obesity Multiple birth Source: http://jalesknowsbabiesrock.blogspot.com/2010/10/annotated- webliography-of-preeclampsia.html
PRE-ECLAMPSIA DISTRIBUTION (EXTRAPOLATEDFIGURES) Source: http://www.cureresearch.com/p/preeclampsia/stats-country.htm
CURRENT DIAGNOSISMethod Description LimitationsBlood pressure (>140/90) • Time consumingProtein concentration in urine (>300mg/dL) •Complex •Low reliabilityBlood tests: liver, kidneys, plateletsnumber. •Late diagnosis •Rate of falseUterine artery Doppler ultrasound positive result is high.
HOW CAN WE APPROACH THE PROBLEM? The ideal Screening test: Simple Noninvasive Rapid Inexpensive Early detection Highly sensitivity & predictive
MARKET NEED12% of maternal deaths Global prevalence of pre-eclampsiaOur market research reveals: There is no clinically useful screening test to predict the development of preeclampsia in either low-risk or high-risk populations.
PRODUCT SPECIFICATIONS Intended uses of the test: early detection pre-eclempsia Target population/patient: Pregnant women (first trimester) Health facility where the test will be used: clinics, health centers and hospitals
Biomarker: A biological indicator whose presence, absence or abnormal concentration reflects the severity or presence of a disease.S.No. Biochemical Marker Plasma Concentration Manifest Trimester 1 Trimester 2 Preeclampsia1. sflt-1 (Soluble fms- like -- high Early increase tyrosine kinase)2. Soluble Endoglin (sEng) -- high Early increase3. Placental Growth Factor low low further decrease (PlGF)
Sample Port Blood Filter Cells are separated from Reaction plasma Chamber A small fraction ofthe Plasma sample Timegate mixes with the dried reagents Hyrdrophobic surface – ensures Three Internal Controls reaction time Independent Positive High – and low – control Assay Zones zones and a nonspecific binding Fluoroscent control tagged antibodies on Waste nano particles Reservoir are captured Excess sample collected in the on separate periphery zones
PRIORITY FEATURES Target molecule •Placental Growth Factor(PlGF), •Soluble Isoforms of flt-1 (sflt-1), •Soluble Endoglin (sEng) Sensitivity 94.5% Specificity 95% Type of analysis Nano particles based Fluoro- Immuno Assay (FIA) Reading system Automated Sample type Blood
REPRODUCIBILITY Reading system Automated Reproducibility near 95% clinical thresholdTEST PROCEDURE Number of timed steps One step Time to result 15 minutes
SAMPLING Volume of sample 550µL required Throughput 90 testsADDITIONAL CHARACTERISTICS Heat stability 15°C- 30°C Storage conditions 20°C End user profile Can be guided by the manual Bio-safety requirement Low Shelf-life of Disposable strip reagents/device Training needs No training required
CONCLUSIONS The product is superior compared to the existing technologies for the detection of pre- eclempsia: Three independent biomarkers increase reliability of result Automated A Point of Care approach Huge market demand
SCIENTIFIC EVIDENCE Nanoparticle based protein estimation: Jiang et al (2009) He et al (2010)
REFERENCES: Jiang, X., Weise, S., Hafner, M., Röcker, C., Zhang, F., Parak, W.J. and Nienhaus, G. U. (2009) Quantitative analysis of the protein corona on FePt nanoparticles formed by transferrin binding J R Soc Interface 7, S5-S13 He, Y., Li, Y. and Hun, X. (2010) Polymer nanoparticles as fluorescent labels in a fluoroimmunoassay for human chorionic gonadotropin Microchimica Acta 171:393–398
SCREENING TESTS AND THEIR LIMITATIONS Current Diagnosis Measuring blood pressure (>140/90) protein concentration in urine (>300mg/dL) Blood tests: liver, kidneys, platelets number. Uterine artery Doppler ultrasound Non stress test or biophysical profile: Check if baby is getting sufficient O2 and nutrients Response of baby’s heart rate relative to baby’s movement Limitations : Time Consuming Tendency of false positive result is high
MOST RECENT – ALERE This technique uses immuno fluorescence. It is based on the PlGF marker Launched in Europe in January 2011.