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pHealth2009
June 25. 2009, Session 1:
Medical sensors and sensor systems
In vitro diagnostic platforms of the future;
technological possibilities and challenges
Stig Morten Borch and Liv Furuberg,
Microsystems and Nanotechnology,
SINTEF ICT, Oslo, Norway
www.sintef.no/microsystems
Stig Morten Borch, pHealth2009 ICT 1
In Vitro Diagnostics (IVD):
Analysis of samples drawn from patients
Microorganisms, Proteins, DNA/RNA, Lipids, Nutrients, Drugs, Hormones,…
Blood
Whole Blood, Serum or Plasma
Urine
Stool
Secretion fluids
Saliva
Gastric juice
Mucous secretion
Tissue samples
Tissue fluids
Spinal fluid
Synovial fluid
Mucous membranes
Stig Morten Borch, pHealth2009 ICT 2
Point of Care IVD platforms
Doctors offices
Nursing homes
Remote testing
In field / off shore
Ambulance
Home testing
Hospitals;
Children’s clinics
Bedside
Emergency wards
Acute care
Surgery rooms
Stig Morten Borch, pHealth2009 ICT 3
Clinical use of PoC IVD products:
Clinical use Examples
Risk screening Cancer, Cardio vascular disease,…
Detection Ongoing inflammations, Fibrinolysis,..
Specific diagnosis Diabetes, Infections, Cardio vascular disease /
AMI, Cancer,…
Disease / treatment Anticoagulant therapy, Diabetes, Rheumatic
monitoring disease, Cancer,..
Relapse Infections, Cancer,..
Stig Morten Borch, pHealth2009 ICT 4
Many POC IVD systems at the market
Cartridge + Instrument
Stig Morten Borch, pHealth2009 ICT 5
Critical features of PoC IVD platforms for the future:
Compactness Broad application platform – menu
(Cartridge + apparatus) + high sensitivity parameters
Minimal room for storage Flexibility:
Assay principles and sensitivity range.
Completely self-contained system
Robustness
Ease of use Physical
Integrated sample processing Chemical (e.g. room temp storage)
Automated processing and
measurements Reliability and safety:
Performance = Ref-.lab. Assay
Minimally invasive samples
Fingerprick blood, saliva, urin Low cost
Simple three steps procedure; Built in auto-calibration and fail safes
Add sample - Push button - Read result
Safe and adequate read out,
Result < 5 minutes interfaces, communication, data
storage and connectivity.
Stig Morten Borch, pHealth2009 ICT 6
Bioanalytical platforms.
Integrated multi-disciplinary systems.
Chemistries
Cartridges Detection
Sample + reagents systems
storage and processing
Instruments
Stig Morten Borch, pHealth2009 ICT 7
Lab-on-a-chip
Allows for:
Completely self-contained system
Disposable cassettes with all reagents included.
Chemistries
Sealed compact format.
Cartridges Detection
Micro-channels. Sample + systems
assay processing
High accuracy in liquid handling
Operates small sample volumes Instruments
Very little reagent necessary
Low cost production
Fast assays
Robustness
..
SINTEF equipment for polymer chip moldings (prototyping)
Stig Morten Borch, pHealth2009 ICT 8
Microfluidics allow for controlled liquid handling:
Reagent integration
Excellent, liquid and gass barriers
ThinXXS design kit slides:
microBUILDER Lysis buffer
Sample (blood)
Sample storage loop
Mixer 1 (11µl)
Washing buffer 1
Washing buffer 2
Connections to
Splitting Elution buffer silicon chip
Product
Waste
Incubation chamber
(21 µl)
Ethanol
Microfluidic functionalities are readily Mixer 2
Mixing combined with a variety of sensor and Storage chamber
(31µl)
actuator systems as well as a variety surface Multifunctional slide for
modifications (Bio-functional layers) DNA extraction
Exact
metering
Silicon based microchips
OD- measurements
Filtering and Cuvette cavities
active porous membranes COC: excellent optical features
www.microbuilder.org
Stig Morten Borch, pHealth2009 ICT 9
Chemistries and reagents:
Biotechnology,
Immobilized biomolecules: Nanotechnology,
• Micro-cavity walls
• Beads
Surface modification:
• Porous membrane Small volumes and fast assays =>
• Microchip surfaces Very fast interaction between reactants:
COC (Cyclic Olefin
Reagent stability:
Copolymer )
OC2H5
OH C2H5O Si OH
Room temperature storage
OC2H5
Methanol / Water , 18h
Liquid and dried reagents formulations
COC (Cyclic Olefin
OC2H5
Copolymer )
Si OH
OC2H5
Chemistries
Cartridges Detection
Sample + assay systems
processing
Instruments
Stig Morten Borch, pHealth2009 ICT 10
Lab-on-a-chip cartridges may be operated by compact
(handheld) instruments:
Chemistries
Cartridges
Sample +
Detection Signal read out:
systems
assay processing
Instruments
• Optics
• colours (OD), fluorescence,
Liquid processing: chemiluminescence
• Capillary forces • Functionalized MEMS sensors
• Pumps (Integrated or external)
• Centrifugal forces
• Electrochemical sensors
• Electro-osmosis • Integrated optical sensors
• …….
Fluorescent readout of 10 chambers
Stig Morten Borch, pHealth2009 ICT 11
SINTEF; Cover all fields of competence necessary
for developing reliable IVD platforms of the future:
• Assay design
• Reagents preservation
• Surface modification
• Biotechnology
Lab-on-a-chip / -disc Chemistries Micro-sensors
• Microfluidics design Detection Micro-optics
• Prototype molding Cartridges High and low sensitivity
• High speed fluidic control
systems
Wide range
• Sample + reagents processing Instruments
• Integration
• Automation
• Miniaturation
• Communication
SINTEF seek to utilize our broad and unique competences to further develop
technologies in this field by direct collaboration with industry partners and
through international collaborative projects.
Through the microBUILDER consortium we have a network of volume
production partners.
Stig Morten Borch, pHealth2009 ICT 12
