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

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MIRACLE (FP7 – 257743)

CRISTINA DE JONCHEERE LIESBET LAGAE, TIM STAKENBORG, CHENGXUN LIU

MAGNETIC ISOLATION AND MOLECULAR ANALYSIS OF SINGLE CIRCULATING AND DISSEMINATED TUMOR CELLS ON CHIP

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OVERVIEW

 Miracle aim  Importance  Challenge  Miracle overview  Market considerations

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MIRACLE OVERVIEW

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Buffer reservoirs Multiplex amplification DNA detection Cell isolation with sieve

 AIM: A smart miniaturized system

for the isolation, counting and molecular characterization of occult tumor cells directly from clinical samples.

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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

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1 AACR 2008 2 M. Campion, J. Voss, and K. Halling, 2011, Comunique

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CIRCULATING TUMOR CELLS FOR CANCER DIAGNOSIS AND PROGNOSIS

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• 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

(Giatromanolaki et al., 2004) CTC in Breast Cancer

Prediction of Recurrence

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WHY USE CTCS?

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Minimally invasive diagnosis Less toxic Better Prognosis Reduced mortality Less side effects Therapy response monitoring Acurate Therapy Decision Reduced healthcare cost Automated Single Cell Capture & Molecular Analysis On chip For CTC identification User interface Data mining Patient Records

Novel cancer markers Improved Cancer therapies

Clinical evaluation Cancer society Create awareness Promote acceptance Biotech Industry Clinicians Patients User interface

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Here? THE CHALLENGE

1 Tumor cell 105-107 peripheral blood mononuclear cells What defines a CTC?

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CURRENT APPROACHES FOR CTC DETECTION

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Nature Reviews Cancer 8, 329-340 (May 2008)

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CURRENT APPROACHES

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Veridex, a J&J company

High throughput cell sorter (FACS)

Immunomagnetic separation of Epcam positive cells using functionalized magnetic nanoparticles Microscopic evaluation of morphology

Problem: Only EpCAM

Single laser, single detector based sorting

Problem: Sensitivity

100,000 analysis events per second

Moflo Beckman&Coulter

Circulating tumor cell separation system

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MIRACLE OVERVIEW

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 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

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MIRACLE OVERVIEW

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Buffer reservoirs Multiplex amplification DNA detection Cell isolation with sieve

Immunomagnetic purification Cell sorting, counting & lysis Detection & read-out RT-PCR & DNA multiplex amplification Hybridization

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MIRACLE OVERVIEW

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Probe immobilizatio n DNA hybridization HRP labeling and detection

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MIRACLE OVERVIEW

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Microfluidic s Clinical validation Integrated circuits Molecular biology Nano- particles

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ADDRESSING A MEDICAL NEED

Time Mammography Biopsy Surgery Pain Death Xray, CT

radiotherapy chemotherap y

Nothing is analyzed, no test exists !!!

Relapse

Therapy monitoring Companion diagnostics

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 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

SCIENTIFIC IMPACT (MIRACLE)

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THE WORLD IS WATCHING

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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

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MARKET?

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Lead products Number

• f

cases Number

• f

tests 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, 42nd annual oak ridge conference 2010

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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?

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ACKNOWLEDGEMENTS

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