MOLECULA R A NALYSIS OF SINGLE C IRCU L ATING AND DISSEMINATED TUMOR - PowerPoint PPT Presentation

M AGNETIC I SOLATION AND MOLECULA R A NALYSIS OF SINGLE C IRCU L ATING AND DISSEMINATED TUMOR C E LLS ON CHIP CRISTINA DE JONCHEERE LIESBET LAGAE, TIM STAKENBORG, CHENGXUN LIU MIRACLE (FP7 – 257743) FP-7 MIRACLE

OVERVIEW  Miracle aim  Importance  Challenge  Miracle overview  Market considerations FP-7 MIRACLE 2

MIRACLE OVERVIEW Cell isolation with sieve Buffer reservoirs Multiplex amplification DNA detection  AIM : A smart miniaturized system for the isolation, counting and molecular characterization of occult tumor cells directly from clinical samples. FP-7 MIRACLE 3

IMPORTANCE IS CLEAR  13 Million cases of cancer worldwide 1  8 Million cancer related deaths 1  ~50% of cancer patients present with distant or local metastasis 2  Tumors shed approximately 1 million circulating tumor cells per gram of tumor tissue 2 1 AACR 2008 FP-7 MIRACLE 4 2 M. Campion, J. Voss, and K. Halling, 2011, Comunique

CIRCULATING TUMOR CELLS FOR CANCER DIAGNOSIS AND PROGNOSIS CTC in Breast Cancer Prediction of Recurrence ( Giatromanolaki et al ., 2004 ) • Breast cancer tumor cells in blood has diagnostic and prognostic value • BUT: Detection of rare tumor cells in circulation (few in 5 ml of blood) on routine basis is not straightforward 5 FP-7 MIRACLE

WHY USE CTCS? Biotech Industry Less toxic Novel cancer Better Prognosis markers Reduced mortality Improved Cancer Less side effects therapies Clinical evaluation Therapy response monitoring Minimally invasive diagnosis User interface Data mining Patient Records Clinicians Patients Automated Single Cell Capture & Molecular Analysis On chip Create awareness For CTC identification Promote acceptance Acurate Therapy Decision Reduced healthcare cost Cancer society User interface 6 FP-7 MIRACLE

THE CHALLENGE What defines a CTC? 1 Tumor cell 10 5 -10 7 peripheral blood mononuclear cells Here? FP-7 MIRACLE 7

CURRENT APPROACHES FOR CTC DETECTION Nature Reviews Cancer 8 , 329-340 (May 2008) FP-7 MIRACLE 8

CURRENT APPROACHES Circulating tumor cell separation system Immunomagnetic separation of Epcam positive cells using functionalized magnetic nanoparticles Microscopic evaluation of morphology Veridex, a J&J Problem: Only EpCAM company High throughput cell sorter (FACS) Single laser, single detector based sorting Problem: Sensitivity Moflo 100,000 analysis events per Beckman&Coulter second FP-7 MIRACLE 9

MIRACLE OVERVIEW  Key Challenges  Key objective: Complete integrated platform  Using Clinical samples  Direct processing of clinical samples  Assay robustness, sensitivity, (blood & bone marrow) specificity  Single cell sensitivity (macro to micro  Flexibility towards downstream interface) processing  Multi-type assays (cell assay, RT- PCR and multiplex DNA  Use in hospital setting amplification, DNA detection array) Hetero-integration (combining silicon  & polymer technology)  Continuous clinical evaluation / design / integration FP-7 MIRACLE 10

MIRACLE OVERVIEW Immunomagnetic purification Cell sorting, counting & lysis Cell isolation with sieve RT-PCR & DNA multiplex amplification Buffer reservoirs Hybridization Multiplex amplification DNA detection Detection & read-out FP-7 MIRACLE 11

MIRACLE OVERVIEW HRP Probe DNA labeling immobilizatio hybridization and n detection FP-7 MIRACLE 12

MIRACLE OVERVIEW Clinical Microfluidic validation s Molecular biology Integrated circuits Nano- particles FP-7 MIRACLE 13

ADDRESSING A MEDICAL NEED Mammography Biopsy Surgery Relapse Pain Xray, CT Death Therapy monitoring Nothing is analyzed, no test Companion exists !!! diagnostics chemotherap radiotherapy y Time FP-7 MIRACLE

SCIENTIFIC IMPACT (MIRACLE)  Recent invited publication :  Recent invited lectures :  May 2010 (Dublin, Ireland) : Single Cell Analysis Congress  Sept 2010 (Buenos-Aires, Argentina) : IEEE – Engineering in Medicine and Biology Society  Sept 2010 (Espoo, Finland) : Microfluidics in Bioanalytical Research and Diagnostics International Scientific Conference  February 2011 (Leiden, the Netherlands) : Circulating Tumor Cell Isolation and Diagnostics ... LET ´ S KEEP IT THAT WAY FP-7 MIRACLE 15

THE WORLD IS WATCHING 9/1/2010 EETimes Europe European project MIRACLE to deliver cancer diagnosis lab-on-chip system 9/1/2010 Leuven Inc. European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/7/2010 EETimes Asia Team research to develop lab-on-chip system vs cancer underway 9/2/2010 News Medical MIRACLE project to develop lab-on-chip system for diagnosing cancer 9/1/2010 Azonano imec Launches European Seventh Framework Project MIRACLE 9/6/2010 Elektronik & Data Lab-on-chip skal hjælpe cancerdiagnose 9/3/2010 Bionity.com en European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/3/2010 European Hospital Cheap and fast cancer diagnosis 9/6/2010 Bionity.com de "Lab-on-Chip" zur schnellen Krebsdiagnose: EU-Projekt MIRACLE wird von IMEC koordiniert 9/13/2010 Elektronik Informationen Lab-on-Chip zur schnellen Krebsdiagnose 9/2/2010 CORDIS Nachrichten MIRACLE-Projekt bringt Krebsbehandlung voran 9/2/2010 Elektronik Praxis Schnelle Krebsdiagnose mit "Lab-on-Chip" 9/2/2010 Tech Whack Imec European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/8/2010 EETimes India Lab-on-chip system project to detect cancer cells takes off 9/3/2010 PC's Semiconductor Blog European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/2/2010 CORDIS News MIRACLE project to advance cancer care 9/6/2010 EuroAlert.net MIRACLE's advanced LOC system, a step further towards better diagnosis of cancer 9/7/2010 Medical Device Network IMEC to Develop Lab-on-Chip Cancer Device 9/2/2010 Medi Lexicon European Collaborative Research To Develop Lab-on-chip System For Cheap And Fast Cancer Diagnosis 9/3/2010 MTB Europe MIRACLE project launched to develop lab-on-chip for cancer diagnosis 9/2/2010 Medical News Today European Collaborative Research To Develop Lab-on-chip System For Cheap And Fast Cancer Diagnosis 9/3/2010 Medical News Today Imec European Collaborative Research To Develop Lab-on-chip System For Cheap And Fast Cancer Diagnosis 9/1/2010 Alpha Galileo European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/2/2010 Today's Healthy News Imec European Collaborative Research To Develop Lab-on-chip System For Cheap And Fast Cancer Diagnosis 9/3/2010 New Electronics Lab on chip research aims to accelerate detection of cancer 9/3/2010 Drug Discovery World Research To Develop Lab-on-chip System 9/1/2010 Electronic Specifier European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/2/2010 Semiconductor Packaging News Lab-on-chip project aims to diagnose cancer faster 9/1/2010 Electro IQ (Small Times) Lab-on-chip project aims to diagnose cancer faster 9/1/2010 NanotechWire European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/1/2010 Nanowerk European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/2/2010 Med Tech Insider European Collaborative Research to Develop Lab-on-Chip System for Cancer Diagnosis 9/1/2010 PR ZOOM European Collaborative Research to Develop Lab-on-Chip System for Cheap and Fast Cancer Diagnosis 9/2/2010 Healthcare Technology Online imec European Collaborative Research To Develop Lab-On-Chip System For Cheap And Fast Cancer Diagnosis 9/2/2010 EETimes News & Analyses IMEC launches cancer lab-on-chip project 9/2/2010 Nanotechnology Now Imec European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/2/2010 Genome Web Daily News European Collaboration Launches Effort to Develop Lab-on-Chip for Cancer Dx 9/2/2010 EDA Café Imec European collaborative research to develop lab-on-chip system for cheap and fast cancer diagnosis 9/8/2010 Semiconductor Packaging News Imec to develop lab-on-chip system for fast cancer diagnosis 9/1/2010 Newswire Today European Collaborative Research to Develop Lab-on-Chip System for Cheap and Fast Cancer Diagnosis 9/1/2010 HPC Wire Imec's European Collaborative Research to Develop Lab-on-Chip System for Cancer Diagnosis 9/2/2010 Opto IQ (Laser Focus World) European researchers team to develop lab-on-a-chip for cheaper cancer diagnosis FP-7 MIRACLE 16

MARKET? Lead products Number of Number of Cost per test Market size cases tests USA World CTC prostate 370 000 1 480 000 $300 $444M $11B CTC breast 126 370 505 480 $300 $151M $3.6B CTC colon 74 940 299 760 $300 $90M $2.6B CTC pancreas 37 170 111 510 $300 $33M $792M Urine 870 000 1 740 000 $50 $82M $2B Preclinical drug 100 000 100 000 $300 $30M $90M development Clinical drug 33 600 134 400 $300 $40M $80M development Total 1 612 080 4 371 150 - $870M $20B * Data from Dr. R.J. Cote, 42 nd annual oak ridge conference 2010 FP-7 MIRACLE 17

HOW TO CAPITALIZE ON THIS MARKET?  Selling Components Vs. Selling System  Regulatory Requirements and Clinical Validation  How to cater to all levels of the value chain, or which to prioritize? FP-7 MIRACLE 18

ACKNOWLEDGEMENTS FP-7 MIRACLE 19