KINETICS OF BIOMARKER DEVELOPMENT BIOSCICON, INC. 2013 Point-of-Care Technology for Global Health NIH Conference January 2014 A MODEL INSTRUMENT TO MEASURE EFFICACY OF SMALL MOLECULES TO MODIFY METABOLIC KINETICS IN SINGLE CELLS OBTAINED FROM TUMOR TISSUES 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

FIGHTING CANCER NEEDS INNOVATIONS CANCER IS DESCRIBED AS UNSTOPABLE GROWTH OF ABNORMAL CELLS WHICH DISTROY NORMAL CELLS AND TISSUE AT POINTS OF ORIGIN, SPREAD AND METASTASES. CANCER IS A FATAL DISEASE KNOWN FROM THE BEGINNING OF THE HISTORY: ALL ATTMEPTS TO CURE THIS DISEASE, WHEN ADVANCED, HAVE FAILED; CONSEQUENTLY, REPROGRAMMING CANCER GROWTH, IF POSSIBLE, IS THE NEW TARGET OF THE OLD FIGHT AGAINST CANCER. 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

CHEMOTHERAPY IS NOT PERFECT CHEMOTHERAPY IS DESIGNED TO KILL CANCER CELLS WILE PRESERVING NORMAL TISSUES. CHEMOTHERAPY HAS CYTOCIDAL (OXYGEN RADICALS, ANTIBODIES) AND CYTOSTATIC (ANTI MITOTIC) EFFECTS; NORMAL CELLS CANNOT BE COMPLETELY PROTECTED. BY THEORY, CHEMOTHERAPY AFFECTS A PERCENT OF CANCER CELLS AND CANNOT ELIMINATE THE LAST CELL WHICH CAN GENERATE CANCER REGROWTH. 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

KINETICS OF BIOMARKER DEVELOPMENT WHY REPROGRAMMING? NORMAL CELLS ARE PROGRAMMED TO GROW, DIFFERENTIATE, MATURE AND DIE IN A CONTINUUM OF THEIR LIFE, WICH HAS SUPPORTIVE CONTROL BY THE NORMAL BODY LOGISTICS. CANCER CELLS DO NOT ABIDE TO BODY CONTROLS AND HAVE ABILITY TO ESCAPE ATTACKS FROM THE IMMUNOSURVEILLANCE AND BODY PROTECTIVE CELLS. 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

KINETICS OF BIOMARKER DEVELOPMENT IDEA! CHANGING METABOLIC PATHWAYS IN ABNORMAL CELLS COULD CAUSE: PREMATURE APPOPTOSIS (DYING) OR ELIMINATING FACTORS BLOCKING THE RESPONSE TO NORMAL GROWTH CONTROL MECHANISMS, AND LETING THEM TO CONTROL FURTHER FAITH OF MODIFIED ABNORMAL CELLS 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

IN VITRO MODEL TO TEST CELL SENSITIVITY TO DRUGS A COMBINATION OF AN OPEN WINDOWS CELL CULTURE CHAMBER, A SYSTEM FOR CONTINUOUS MONITORING/RECORDING OF INTRACELLULAR CHEMICAL REACTION, SPECIMEN SMEARED ON A GLASS WALL OF THE CHAMBER, CHROMOGENIC SUBSTRATE, A LIGHT MICROSCOPE WITH OR WITHOUT PHOTOMETER OR CAMERA TO MEASURE THE ABSORBANCE, IS MAKING THE MEASUREMENTS POSSIBLE. 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

STRUCTURE OF THE MODEL TO TEST CELL SENSITIVITY 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

SINGLE CELL METABOLIC ANALYSIS Nanoparticles buildup indicating the presence, location, size and power of bioactive molecules inside single cells. Monitoring of this reaction, or its recording as time lapse still images or a video, could be a powerful quantitative method for testing cell sensitivity to drugs and toxins and new drugs development. 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

KINETICS OF BIOMARKER DEVELOPMENT FUNCTION OF THE MODEL THE FOLLOWING VIDEO WILL PRESENT HOW THIS MODEL WORKS AND COULD BE USED IN RESEARCH A NORMAL BLOOD IS SMEARED INSIDE THE INCUBATION CHAMBER. A NORMAL PML IS FOCUSED IN THE CENTER OF A MICROSCOPIC FIELD MYELOPEROXIDASE REACTION IS INITIATED BY INTRODICING APPROPRIATE SUBSTRATS KINETICS OF THE FINAL REACTION PRODUCT DEVELOPMENT IS OBSERVED, RECORDED AND MEASURED 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

KINETICS OF BIOMARKER DEVELOPMENT VIDEO - 1982 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

KINETICS OF CATALYSIS MEASURED BY PRODUCT DEVELOPMENT S, E S + E K1 > K2 SEP K3 > K4 E + P P*P K5 > K6 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

KINETICS OF BIOMARKER DEVELOPMENT MANAGEMENT INTRODUCING INHIBITORS AND ACTIVATORS INTO THIS MODEL SYSTEM, IT WAS POSSIBLE TO MODIFY THE REACTION AND TO MEASURE THE EFFECT OF THE NEW MOLECULES TO THE KINETICS OF INTRACELLULAR METABOLISM CONFIRMING THE FEASIBILITY OF THE MODEL TO ENABLE THE MONITORING AND MEASURING THIS EFFECT WAS A SUFFICIENT EVIDENCE TO WARRANT PATENTING THE MODEL FOR THE APPLICATION IN CANCER REPROGAMMING RESEARCH 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

KINETICS OF BIOMARKER DEVELOPMENT TESTING NEW MOLECULES TARGETS OF MEDICAL INTEREST MOLECULAR FUNCTIONS TO BE TARGETED BODY SYSTEM ORGAN TISSUE CELL ORGANELLE DNK RNA ACTIVE PROTEIN K1/K2 K3/K4 K5/K6 INHIBITORS ACTIVATORS 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

CERVICAL CANCER CHALLENGE TO CONTROL CAP + HIV MARKERS POSITIVE CERVICAL CANCER CELLS 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT

KINETICS OF BIOMARKER DEVELOPMENT CONTACT Dr. NENAD MARKOVIC BIOSCICON, INC. WWW.BIOSCICON.COM info@biosicon.com Tel. 301.610.9130 9/19/2013 KINETICS OF BIOMARKER DEVELOPMENT