From cold to hot: Building a modern biobank for a healthy ... · Jaspal Singh Cecilia Agardh Peter...

From cold to hot:Building a modern biobank for a healthy

future

Tecan Symposium 2011: Translational Medicine

Mark Divers, Karolinska Institute & BBMRI.se

Overview• Background: the biobanking challenge

• Karolinska Institute Biobank

• Creating a large‐scale national facility

• The Impact and Value of Biobanks

• Background: the biobanking challenge

• Karolinska Institute Biobank

• Creating a large‐scale national facility

• The Impact and Value of Biobanks

A biobank is like a compound bank!

• Huge numbers of diverse samples• Sample quality essential

– Physical, scientific relevance, data

• Rapid, selective access (cherry‐picking)• Demands automation• Massive informatics opportunities

– charting scientific space: chemical or biological

• Fabulous research asset– To benefit to human health

But a biobank is not like a compound bank!

• Size– multi‐millions

• Extreme storage conditions (complex samples)– Restricts automation

• Access and usage– Access and usage technologies still emerging

• Ethics– And law

• Longer‐term investment– Decades– How do we judge the impact?

• Not a well‐established activity at large scale– yet

What do you associate with the word biobank?

But biobanking is hot!• Big interest and growing

• >>$B spend recent years

• Many biobanks in many forms

• eg ~900 in Sweden

• Advanced technologies need the best samples

• And many of them

• Very big population studies emerging

• Hunt, UK Biobank, LifeLines, LifeGene + …

• Growing impact on biomedical research

• Huge epidemiology and public health opportunity 6

Samples

•Collection•Processing•Storage•Data•Access

Samples

•Collection•Processing•Storage•Data•Access

Yet we must still keep cool!...

Donors

•Selection

•Availability

•Informed consent

Donors

•Selection

•Availability

•Informed consent

See…Wired May 2010Nature July 2011

See…Wired May 2010Nature July 2011

Quality has been a problem

• Lab, data systems, processes• Ethics and legal compliance addressed• 1st studies, incl. Twingene

Progressive growth• Capacity• Competence• Quality• Study diversity

• 1st withdrawals• Quality System and ISO acreditation• Data support to external collections

• Huge studies start • Big scale‐up• LifeGene pilot• BBMRI.se

A brief history of Karolinska Institue Biobank…a research biobank in a medical university

KI Biobank is home to >70 diverse studies

0

20000

40000

60000

80000

100000

120000

2004 2006 2008

Ulsam DNA TwinGeneTOSS komplettering Tissue Biobank KSTest-studie TCHADTBI SödertäljehjärtanStroke STARSTANLEY STAGE-ADHDSTAGE Saliva STAGESPP-Sthlm SPCSNACK SLESHEEP SCISCALE SBPSATSA8 SATSA7SATSA_twinstudy Sandra CMMSALTY Sahlgrenska CaidahlRely Genomics Rasmusen, TvillingstudienRainer CCK PROCAPPart projekt Parkinson_twinstudyparkinson PAINOptimization OLINNOAK Neurotec HSMolecular medicine, Harvest MIAMEB Employees LUFTLore LIBRO-1Lars Lind KTSKTH Kristina MelkerssonKOL IMSEHenrik G Harmony_twinstudyGlaser GEMSGallsten Första barnetFilterpappersstudien FASTEXT EurospanEuroClot EpiEkonomiskt beteende EIMS-SalivEIMS DOGSSDNA-kvalitetskontroll 1 Dennis H Astra-ZenecaDelext COSM (Oragene)CEFAM CEFALOCCK 8 CC10CATSS CAPSFAMCAPS2 CAPS1CAPS BroadBipolära Biobank_intern_1BIOAIR BeroendeBasal BAMSEALfext ALFALB Genetics AISS

Number of processed samples per study and year

>1.5M samples stored, tracked and accessed

• Disease‐based• Cancer• Neurology• Cardiovascular• Inflammation

• Population‐based

• Disease‐based• Cancer• Neurology• Cardiovascular• Inflammation

• Population‐based

Sample statistics 2004-2011

21 februari 2012Namn Efternamn 10

Typical biobanking studies in research

• 250 – 15.000 individuals

• Ca.2 samples / individual

• 300 – 400 samples / day

• Generate 5‐10 aliquots (0.5‐1ml) / individual

• Wide range of logistic demands and solutions

• Little automation

Breast Cancer ”Karma”

• 100.000 individuals

– And repeat samples to follow• 3 sample tubes / individual

• 300‐400 individuals / day

• 16 aliquots (225ul) / individual

• More automated

• Pilot completing

– Full‐scale start 1Q2011

Prostate Cancer ”Stockholm‐2”


• 3 sample tube / individual


• >16 aliquots (225ul) / individual

• More automated

• Pilot completing

– Full‐scale start 23/11/2010

The large-scale biobanking challenge

LifeGene


• And repeat samples to follow

• 7 sample tubes / individual


• 48 aliquots (225ul) / individual

• More automated

• Pilot complete

• Full‐scale start 101101

+ BBMRI.se• Scapis• Epi Health• Malmö Kost Cancer• …

01/11

10/01

22/11

While researchers want much better access to their assets!

• Many assets

• Long‐term safe storage

• With quick reliable access

• To exploit diverse analysis opportunities

• Many assets

• Long‐term safe storage

• With quick reliable access

• To exploit diverse analysis opportunitiesFrom this… To this…

What does this mean?

• >>>30M aliquots to store, track and search

• Massive capacity challenge

• Storage

• Retrieval

• Data management

Big change…

• Create a new large‐scale operation

• >>>30M aliquots to store, track and search

• Massive capacity challenge

• Storage

• Retrieval

• Data management

Big change…

• Create a new large‐scale operation

How to take the big leap?

• Automate

• Miniaturise

• Collaborate

• Continuous improvement

Step‐wise progress built on real needs

• Defined sample collections for defined aims

• Automate

• Miniaturise

• Collaborate

• Continuous improvement

Step‐wise progress built on real needs

• Defined sample collections for defined aims

Sounds great, but who’s going to support that?...

…And where does the money come from?

Introducing BBMRI…

• European initiative started in 2008 by ESFRI*

• Create a hub‐and‐spoke network of national competence centres, co‐operating with regional centres

* ESFRI = European Strategy Forum on Research Infrastructures

With a grand vision

•Network: connect modern biobanks!•Vision: link 300 biobanks across Europe

•Harmonise: evolve common standards!•Avoid re‐inventing wheels!!

•New technology•test and apply the best!

•Network: connect modern biobanks!•Vision: link 300 biobanks across Europe

•Harmonise: evolve common standards!•Avoid re‐inventing wheels!!

•New technology•test and apply the best!

• Now >50 members, >30 countries

• Applying for tax exemption status

• Several national hubs underway:• BBMRI.se, BBMRI.nl, BBMRI.fi, BBMRI.no, BBMRI.it, BBMRI.at

• Swedish Science Research Council + KI agreed to fund BBMRI.se

• 5 year grant

• Now >50 members, >30 countries

• Applying for tax exemption status

• Several national hubs underway:• BBMRI.se, BBMRI.nl, BBMRI.fi, BBMRI.no, BBMRI.it, BBMRI.at

• Swedish Science Research Council + KI agreed to fund BBMRI.se

• 5 year grant

Project 1 – management

BBMRI.se is a sum of parts to create a unified biobank infrastructure for Sweden

Projects 2 & 3

Collection:Input

Samples & data from

population & disease cohorts

Project 4

Analysis:Output

Interface to analysis resources

Project 8

Financing

Ensure long‐term

sustainability

Project 7

Ethics

Unified approach to ethics: expertise think‐tank

Project 6

Physical Facility

Unified large‐scale sample handling platform

Project 5

IT

Unified national

informatics platform

Distributed sample handling at local

biobanks and hospitals

Common storage and withdrawal -80° C freezers or N2 stores

~100 million tubes = “hard drive”

Automatic repicking unit -20° CFast withdrawal of tubes = “processor and RAM memory”

Where are we now?

2-D coded microtubes are our new currency

From this To this

Standard cryo‐tubes• manual boxed

• Conventional barcode• Screw caps

Standard cryo‐tubes• manual boxed

• Conventional barcode• Screw caps

Micro‐tubes• 96‐format racks

• 2‐D barcode• Foil sealed

Micro‐tubes• 96‐format racks

• 2‐D barcode• Foil sealed

10/10/2010

21

Mark Divers

Large-scale sample input now a reality

22

New DNA banking service is taking shape

• Magnetic bead technology

• Early technical problems solved

• >20.000 DNA samples so far

• Improving processes

• 3 systems installed

• goal 1000 extracts / day

• Stable yield

• Avoid normalisation

• Good quality

• Magnetic bead technology

• Early technical problems solved

• >20.000 DNA samples so far

• Improving processes

• 3 systems installed

• goal 1000 extracts / day

• Stable yield

• Avoid normalisation

• Good quality23

Getting samples out:the first step in biobank value

• 1st retrieval in our new systems

• 6K DNA samples, breast cancer study

• Cancer SNP profile

• Prostate cancer retrieval autumn

• 2.5K selected DNA samples

• Based on PSA values

• LifeGene retrieval planned 1Q2012

• Call for research proposals autumn

• 1st retrieval in our new systems

• 6K DNA samples, breast cancer study

• Cancer SNP profile

• Prostate cancer retrieval autumn

• 2.5K selected DNA samples

• Based on PSA values

• LifeGene retrieval planned 1Q2012

• Call for research proposals autumn

24

Development continues…3 critical strategic goals 2011-12

Retrieval

National network

Enriching the sample collection

25

Automated retrieval:the challenge and the plans…

(=how do we help Anna?)

26

•Pilot develop with new auto‐picker•Install big DNA auto‐store

•‐20°C; 400K samples; ~5MSEK

•Plan a multi‐million ‐80°C auto‐store

•Pilot develop with new auto‐picker•Install big DNA auto‐store

•‐20°C; 400K samples; ~5MSEK

•Plan a multi‐million ‐80°C auto‐store

Create a shared BBMRI.se operationCreate a shared BBMRI.se operation

•Multi‐million aliquots

•‐20, ‐80 or ‐190°C•Instant access•Cost!!

•Multi‐million aliquots

•‐20, ‐80 or ‐190°C•Instant access•Cost!!

We can’t do this alone!

Creating BBMRI.se national network

28

Progressive build up

• Göteborg node• launch Jan 2012

• 1st project: Scapis

• Malmö node

• launch 1H2012

• 1st projects: EpiHealth, MKC, MFM

• Linköping?• launch 2H2012

• project identified

•Others to follow

Progressive build up

• Göteborg node• launch Jan 2012

• 1st project: Scapis

• Malmö node

• launch 1H2012

• 1st projects: EpiHealth, MKC, MFM

• Linköping?• launch 2H2012

• project identified

•Others to follow

Co‐ordinated:•Facilities•Equipment & consumables•IT system•Staffing•Process

Co‐ordinated:•Facilities•Equipment & consumables•IT system•Staffing•Process

Enriching the BBMRI.se bank2010-2012

Population cohorts

•LifeGene (500K)

•Prostate cancer 2 (100K)

•Breast cancer (100K

•Epi Health N (150K)

•EpiHealth S (150K)

•Scapis CV (30K)

•Malmö Diet & Cancer (18K)

•Malmö Preventative Medicine (22K)


•LifeGene (500K)


•Breast cancer (100K

•Epi Health N (150K)

•EpiHealth S (150K)

•Scapis CV (30K)

•Malmö Diet & Cancer (18K)

•Malmö Preventative Medicine (22K)


National disease collections

•Multiple Sclerosis

+ Quality register‐based:

•Rheumatoid Arthritis

•Bipolar disease

•Blood cancers

•Multiple Sclerosis

+ Quality register‐based:

•Rheumatoid Arthritis

•Bipolar disease

•Blood cancers

29

Emerging pipeline (possibilities):• North Pop (Norrland)• IDEFICS (West Sweden)

Why are we doing this?...… to advance medical research!

•enable advanced biological analysis•systematic

•with statistical power

•Huge potential for public health•Realise some dreams

•Personalised medicine

•Predictive healthcare

… to advance medical research!

•enable advanced biological analysis•systematic

•with statistical power

•Huge potential for public health•Realise some dreams

•Personalised medicine

•Predictive healthcare

Study publications

GALLSTEN 4

PAIN 2

BAMSE 8

SCALE 15

Ekonomiskt beteende 2

TwinGene & Euroclot 13

HARMONY & SATSA

12

KTS 1

CAPS 40

Totalt 97Emerging highlights• Multiple Sclerosis• TwinGene• Broad• Influenza Like Illnesses

• Prostate Cancer

What is the value of biobanking?...

Multiple sclerosis studies give a good example*

• ~17K MS cases in Sweden

• Many represented in KI biobank

• New therapy, Tysabri™

• Monoclonal antibody

• Very effective, very expensive

• But critical side effects in some (viral cross‐reacton)

• Screen MS biobank for virus

• Save big drug cost

• Save lives

• ~17K MS cases in Sweden

• Many represented in KI biobank

• New therapy, Tysabri™

• Monoclonal antibody

• Very effective, very expensive

• But critical side effects in some (viral cross‐reacton)

• Screen MS biobank for virus

• Save big drug cost

• Save lives31

*T Olsson et al

Several other great examples

• Human Papilloma Virus and cervical cancer

• Vaccination scheme

• Biobanked serum samples from 1969

(Sigstad et al, Br J Cancer 2002;87:175–180)

• Abacavir® anti‐HIV therapy

• Identify genetic hypersensitivity sub‐population

(Hansson M, Personalized Med,2010;7(1): 75‐85)

• Human Papilloma Virus and cervical cancer

• Vaccination scheme

• Biobanked serum samples from 1969

(Sigstad et al, Br J Cancer 2002;87:175–180)

• Abacavir® anti‐HIV therapy

• Identify genetic hypersensitivity sub‐population

(Hansson M, Personalized Med,2010;7(1): 75‐85)

This is a development!

Still in the early phase!

= lärdom

•Technology•Partnerships with researchers

•Communication och culture

•Collaboration•Evolution not revolution

35

Lab OperationsCarita RaskJaspal Singh

Cecilia AgardhPeter ArnerlövAnci CarmanPia Hillelson

Camilla LagerbergVian OsmanAmina Said

Anette SelanderJohanna Smith

Eva ÅströmEmma RidellWilliam Day

Valentina Novak

Biobank ITAnders BrinneStaffan Bergh

Olle BäckUlrika Bohlin

Bengt-Erik FröbergJohan Steninger

Scarab ITEva Büren*

Daniel EricsonJosé TapiaAnni Åsberg

Biobank DevelopmentGunnel Tybring

QualityAnette Petersson

Mirja Larsson

Acknowledgements

The LifeGene Crewincluding

Jens MattssonKicki KjaergaardMats ThurmanCamilla Björk

Thomas Bergman

The BBMRI CrewJoakim DillnerJan-Erik LittonMats Hansson

Göran HallmansUlf LandegrenJoakim Galli

Lars-Olof HanssonJoyce Carlsson

Lisen Arnheim-DahlströmSofie PetterssonMartin FranssonLoreana Norlin

Maria Anderberg

Others @ KIHenrik GrönbergNancy PedersenRune FransonOla Steinberg

Buisness consultantPer Spångeus

Customer RelationsTove Rylander-Rudqvist

Cecilia Björkdahl

The Biobank Crew

More infohttp://ki.se/kibiobankwww.bbmri.sewww.lifegene.se

That was a quick overview!

Don’t hesitate to make contact for more info!

http://ki.se/kibiobankwww.bbmri.se

From cold to hot: Building a modern biobank for a healthy ... · Jaspal Singh Cecilia Agardh Peter...

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