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”
• 100.000 individuals
• 3 sample tube / individual
• 400‐600 individuals / day
• >16 aliquots (225ul) / individual
• More automated
• Pilot completing
– Full‐scale start 23/11/2010
The large-scale biobanking challenge
LifeGene
• 500.000 individuals
• And repeat samples to follow
• 7 sample tubes / individual
• 100‐200 individuals / day
• 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)
•Prostate cancer 3 (200K)
•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)
•Prostate cancer 3 (200K)
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
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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
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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