MAGNETIC ISOLATION AND MOLECULAR ANALYSIS OF SINGLE CIRCULATING AND DISSEMINATED TUMOR CELLS ON CHIP CRISTINA DE JONCHEERE LIESBET LAGAE, TIM STAKENBORG, CHENGXUN LIU MIRACLE (FP7 257743)
OVERVIEW Miracle aim Importance Challenge Miracle overview Market considerations 2
MIRACLE OVERVIEW Cell isolation with sieve Buffer reservoirs DNA detection Multiplex amplification AIM: A smart miniaturized system for the isolation, counting and molecular characterization of occult tumor cells directly from clinical samples. 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 2 M. Campion, J. Voss, and K. Halling, 2011, Comunique 4
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
WHY USE CTCS? Biotech Industry Novel cancer markers Improved Cancer therapies Less toxic Better Prognosis Reduced mortality Less side effects Clinical evaluation Therapy response monitoring Automated Single Cell Capture & Molecular Analysis On chip For CTC identification User interface Data mining Patient Records Create awareness Promote acceptance Cancer society Clinicians Minimally invasive diagnosis Acurate Therapy Decision Reduced healthcare cost Patients User interface 6
THE CHALLENGE What defines a CTC? Here? 1 Tumor cell 10 5-10 7 peripheral blood mononuclear cells 7
CURRENT APPROACHES FOR CTC DETECTION Nature Reviews Cancer 8, 329-340 (May 2008) 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 Moflo Beckman&Coulter Problem: Sensitivity 100,000 analysis events per second 9
MIRACLE OVERVIEW Key Challenges Using Clinical samples Assay robustness, sensitivity, specificity Flexibility towards downstream processing Use in hospital setting Key objective: Complete integrated platform Direct processing of clinical samples (blood & bone marrow) Single cell sensitivity (macro to micro interface) Multi-type assays (cell assay, RT- PCR and multiplex DNA amplification, DNA detection array) Hetero-integration (combining silicon & polymer technology) Continuous clinical evaluation / design / integration 10
MIRACLE OVERVIEW Immunomagnetic purification Cell isolation with sieve Cell sorting, counting & lysis Buffer reservoirs RT-PCR & DNA multiplex amplification DNA detection Multiplex amplification Hybridization Detection & read-out 11
MIRACLE OVERVIEW Probe immobilizatio n DNA hybridization HRP labeling and detection 12
MIRACLE OVERVIEW Clinical validation Microfluidic s Integrated circuits Molecular biology Nanoparticles 13
ADDRESSING A MEDICAL NEED Mammography Biopsy Surgery Relapse Pain Xray, CT Nothing is analyzed, no test exists!!! radiotherapy chemotherap y Death Therapy monitoring Companion diagnostics Time
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 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 NewsLab-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 NewsImec 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 16
MARKET? Lead products Number of cases Number tests of Cost per test Market size 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 development 100 000 100 000 $300 $30M $90M Clinical drug development 33 600 134 400 $300 $40M $80M Total 1 612 080 4 371 150 - $870M $20B * Data from Dr. R.J. Cote, 42 nd annual oak ridge conference 2010 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? 18
ACKNOWLEDGEMENTS 19