DEPArrayTM: Progettazione, prototipazione e fabbricazione di un sistema per l'individuazione, la...

8/9/2019 DEPArrayTM: Progettazione, prototipazione e fabbricazione di un sistema per l'individuazione, la manipolazione ed il sorting di singole cellule

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Silicon Biosystems Spa Bologna ITALY

www.siliconbiosystems.com

NI Medical Innovation Summit Modena 8th June 2010

DEPArray: Progettazione, prototipazione e

fabbricazione di un sistema per l'individuazione, lamanipolazione ed il sorting di singole cellule

Ing. Gianni Medoro (Silicon Biosystems)Dott. Davide Ramanand (Skytechnology)


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Agenda

Company Introduction

DEPArray Technology

Cell Manipulation by Dielectrophoresis

Uniqueness of Performances

DEPArray Applications

Oncology: Personalized Therapy

Prenatal Diagnosis: Non Invasive Approach

Partnership Network Synergy with National Instruments and Sky Technology


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10 Years from Technology Concept to MatureProduct with Applications

1999 Company founded by 4 scientists at Bologna University

Core patent on Moving DEP Cages filed

2000-2005 DEPArray technology Proof-of-concept developed under EU,Government and Regional funding (> 5M total)

2006 1st fund raising round (1.5M)

DEPArray technology and NIPD application development

2007 2nd fund raising round (5.5M)

Direct & Indirect Gov funding: (~ 2.5 M)

2008 3rd fund raising round (3.5M)

Oncology application development started

2009 CE Mark for DEPArrayStart of marketing activities

2010 4th fund raising round (5M)

Head count ~24 FTE, 27 patents filed

NIPD and Oncology Applications close to Pilot Trial


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DEPArray Cell Sorting


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Silicon Biosystems Patented Technology:Moving DEP Cages

+ + + +--

-

nDEP Cage nDEP Cage

+ +++ --

Non-uniform electric field generated by the chipelectrodes (cross section)

Cell trapping by DEP cages

cage-move


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Sorting of Fluorescent Cells with DEPArray


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Moving DEP Cages Enables OutstandingPerformance in Single-Cell Sorting

Mainchamber

ParkingRecovery

1. Inject, trap and image all cells2. Move all cells of interest into

Parking chamber

3. Move separately to Recoverychamber and flush

Features Multiparametric image-based

sorting

Single cell resolution

Small cell loads

Gentle on cells No a priori thresholds choose

bestcells

Sorting based on slow kinetics(10-100s minutes) possible
http://images.google.it/imgres?imgurl=http://www.daigger.com/assets/product_images/4251a.jpg&imgrefurl=http://www.daigger.com/catalog/department/d-Centrifuge%2BBottles/Centrifuge%2BBottles&usg=__kuzQNmnRy8W2udK-XSyG6PfJZrQ=&h=200&w=151&sz=3&hl=it&start=2&tbnid=uzoYmfsRbgU3tM:&tbnh=104&tbnw=79&prev=/images%3Fq%3DEPPENDORF%2Btube%26gbv%3D2%26hl%3Dit%26sa%3DXhttp://images.google.it/imgres?imgurl=http://www.daigger.com/assets/product_images/4251a.jpg&imgrefurl=http://www.daigger.com/catalog/department/d-Centrifuge%2BBottles/Centrifuge%2BBottles&usg=__kuzQNmnRy8W2udK-XSyG6PfJZrQ=&h=200&w=151&sz=3&hl=it&start=2&tbnid=uzoYmfsRbgU3tM:&tbnh=104&tbnw=79&prev=/images%3Fq%3DEPPENDORF%2Btube%26gbv%3D2%26hl%3Dit%26sa%3DXhttp://deparray-a300k-beta4.wmv/


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Individual Cell Sorting with DEPArray A300K

Click on image to start movie
http://deparray-a300k-beta4.wmv/http://deparray-a300k-beta4.wmv/http://deparray-a300k-beta4.wmv/http://deparray-a300k-beta4.wmv/


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DEPArray is the Last Milefor AutomaticRare-Cells Sorting in High-Value Applications

We bridge the gap betweenenrichment and single-cell analysis

BiologicalSample

Enriched Cells

Pure Cells

Enrichment / Sample-Prep

DEParray Sorting

Downstream Analysis

1/1,000,000,000

1/1,000-10,000

1/1


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Targeting Unmet Medical Needs with DEPArray

Oncology: Circulating Tumor Cells Isolation From prognosis (based on enumeration of CTC) to personalized

therapy (based on isolation of CTC)

Prenatal Diagnosis: Circulating Fetal Cells Isolation From Amniocentesis and Villocentesis to Non-Invasive Prenatal

Diagnosis (based on Circulating Fetal Cells)

Life-Science Research

Stem-cells Immunology

Single-cell biology


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Cancer Personalized Therapy

with DEPArray


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Rare, but Important: The Role of CTC in theCreation of Metastasis

Image From:

The bone marrow niche: habitat tohematopoietic and mesenchymal stem cells, and

unwitting host to molecular parasites

Y Shiozawa, A M Havens, K J Pienta and R S Taichman


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Personalized Oncology Treatment: genetic detection to

identify addressable patients

Silicon Biosystems tests for genetic profiling enables to

determine effectiveness and allows targeting of treatment Cell growth inhibitor treatment is fastest growing class of cancer

drugs from $9.5bn in 2005 to $22bn in 2010 at a CAGR of 18% Cell growth inhibitor treatment is expensive (monthly cost

ranging from $3,000 to $10,000), with significant side-effects

0

200,000

400,000

600,000

800,000

1,000,000

1,200,000

Breast Co lo rectal Lun g Sto mach Pan creas Ovary Pro state Head &Neck

Bladder

Annual courses of treatment EU, US, Japan by type of cancer

# treatments for secondrecurrence of malignancy

# treatments fo r first

recurrence of malignancy# undergoing initialintervention

Colorectal and Lungrepresent ca 1mcourses of treatmentrequiring monitoring

each year


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CTC genetic profiling: dramatic improvement inpatient life

CTC molecular analysis allowsselection of most effectivedrugs

Longer & Better life for patient

Cost saving for healthcaresystem

A market paradigm switch:from prognosis

to personalized therapy


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DEPArray Enables the Isolation of Circulating

Tumor Cells and their Molecular Analysis

Codon 12G>T; Gly2Val

Sample CTC36-2

Genome-wide detection of chromosomalunbalances

Detection of point mutations (e.g. KRAS)

CTCs (CK-green/DAPI-blue) isolatedwith DEPArray from a metastatic

breast cancer patient

CTCs isolated withDEPArray from a

metastatic colorectalcancer patient

e.g. KRASmutation testing

is required topredict efficacyof treatment

with Ceutximabor Panitumumab


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Non Invasive Prenatal

Diagnosis with DEPArray


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Amniocentesis and chorionic villus sampling:high-risk of miscarriages and unpleasant procedures

Amniocentesis Chorionic Villus Sampling

Mothers

ageRisk Need

20 years 1 in 1,600 Low

25 years 1 in 1,300

Medium30 years 1 in 1,000

35 years 1 in 365

High40 years 1 in 90

45 years 1 in 30

Risk of fetal loss 0.5-1.5%

DEPA E bl th I l ti f Ci l ti


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DEPArray Enables the Isolation of Circulating

Fetal Cells and their Molecular Analysis

Detection and Sorting of fetal cells frommaternal blood

Genetic Analysis

Fetal

Cells

Mother

male

M P

AMXY D21S11 HPRT

Example of Fetal Cell isolated withDEPArray from peripheral blood of a

pregnant woman:

nRBC (-Globin-red/DAPI-blue)


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Sizeable and highly predictable market for NIPD

2.0m high-risk pregnancies in EU, US and Japan, but only24% adoption of amniocentesis test which has a risk ofmiscarriage


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Partnership Network


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DEPArray System

Equipment Lab-on-a-Chip

Software


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Network of Competences

Chip

Manufacturing

Partner

Mixed Analog-Digital I/O

Image Processing

Heat Management

Software &

Firmware IVD

Support

Power RF Design

Equipment

Manufacturing

Partner


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Network of Competences

Chip

Manufacturing

Partner

Heat Management Power RF Design

Equipment

Manufacturing

Partner


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Partnership goals

Application

Tech Concept

Prototyping

Validation

Ingegnerizzazione

Feedback

(Internal users,

Research institutes,Customers,

Market researches

& analysis) Maximum

Flexibility

Time-to-

market

Partnership had to

address all arosen

necessities, especiallythose below:

Iterative

process


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Needs

Flexibility

Time-to-market

Proven success (on specific items)

Qualified support

Future development support

Robustness

Maintainbility


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Why NI - 1

Worldwide player Products wide choice (Time-to-market, Support)

Ease of integration (HW with SW) (Time-to-Market, Flexibility)

Local & central branches (Support)

Corporate support R&D - upon agreement (Support)

Product Development (Future development)

Alliance Partner Network Services Firm (Support, Robustness)

Integrators (Support , Robustness)

Large Libraries Collection(Time-to-market, Support, Robustness)

Long-Term Support (Maintenability (& Evolution as well))

LabVIEW real-time (Robustness)


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Why NI - 2

Try-n-buy operation (Time-to-Market, Support (NI Italy+corporate))

Openness Integration with Silicon Biosystems proprietary service infrastructure (Time-to-

Market, Robustness)

Integration with third-parties instrumentation drivers (Time-to-Market)

Integration with third-parties imaging algorithmics (Time-to-Market, Robustness)

Wide COTS offering Cost optimization path support ((near!) Future development) (FlexRIO?)

Runtime changes can be easily managed (Flexibility, Time-to-market)

Certified/Supported COTS Widely used COTS as a facilitating element in regulated markets certification

achievement (Support, Robustness)

In our experience, NI is a dynamic reality putting much attention onmarket evolutions, interested in supporting strategic partnerships.


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Conclusions

Technically: an outstanding exercise! The machine involves knowledge and requirements necessitating many

different aspects and corresponding knowledge

Ethically: biomedical devices are of undiscussed ethic value Thinking in terms of machine intended use is a great motivational point

But overall: great team work! All involved parties have really pushed far beyond the usual

Integration issues couldnt be surpassed without all actors stronginvolvment

So, looking forward to next meeting to share with you future evolutions!


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www.siliconbiosystems.com

www.ni.com/it

www.skytechnology.it

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