Nanoteknologi Muligheter og usikkerheter - - KLUBBNYTTrk25040.rotary.no/files/.../Presentasjoner/100210_Nano-teknologi.pdf · 25.02.2010 1 Microsystems and Nanotechnology 19/01-2010

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119/01-2010Microsystems and Nanotechnology

NanoteknologiMuligheter og usikkerheter

Chief Scientist Liv Furuberg

Microsystems and NanotechnologyMiNaLab

SINTEF ICT


Nano - dverg

� En milliard nanometer i en meter

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10-12

10-10

10-8

10-6

10-4

10-2

100

102

Virus Bacteria Hair ManH-atom

MEMSNanodevices Typical man-madeDevices

Lengdeskala - nanometer


Nanoski – snart slutt på smøring

� Forsiden av Dagens næringsliv 19. januar

� HVA er det som er nano??

As a result of co-operation withone of the world’s leading nanotechnologyexperts Amroy Inc,Peltonen is proud to EXCLUSIVELYannounce the world’s first crosscountryskis with HYBTONITE®nanoepoxy construction.The new ski models, Supra X and Infra Xuse the latest material technology to enchanceyour skiing experience:HYBTONITE® nanotechnology combinedwith other top features like 9-click NISplates, new XTT Extralight Carbon Tipand Tail, PRG-NANO bases with Crystal-Glide™ finish, all built up with PELTONENknow-how and quality result in a ski thatis THE choice for the most demandingskiers who want the world’s latest and

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Nanorør produksjon ved bue-utladning

� Grafitt elektroder

� Høy spenning

� Elektrisk utladning – arc discarge

� Grafittstøv – og 30% karbon nanorør


Hva med miljøet?

� Karbon nanorør kan sameliknes med asbest

� Mekanisk, spisse nåler

� Kjemi? Mange forskningsprosjekter pågår

� Sølv nanopartikler

� Sølv i elver, dreper bakterier

� SINTEF – ingen nanopartikler

� Tynne filmer på overflater, kontrollert struktur på molekylært nivå

� Nanoteknologi for rensing av f. eks vann

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MiNaLab (Mikro- and Nanoteknologi Laboratoriet i Oslo)

� Universitetet i Oslo og SINTEFSINTEF: 800 m2

Universitetet i Oslo: 600 m2

� SINTEF:

� Silicon production line with annual capacity of 10.000 150 mm wafers

� The most advanced laboratory in Norway for micro- and nanotechnology

� Situated on the campus of University of Oslo

� 240 MNOK investment in scientific equipment and laboratory


� Sensorer og aktuatorer

� Laget av silisium, glass eller polymer

� Funksjonelle filmer

� Det funksjonelle elementet harmikrometer skala

� Produseres ved å utnytteproduksjonsteknologier for integrertekretser

Hva er mikrosystemer?

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Top – downmanufacturing

Diffractive optical element

Optical filter

� Start with silicon wafer

� Lithography defines areas to be etched away

� Create 3D structures


Eksempel på komponenter: Mikro-optikk

Anesthetic gas detector

Tomra Recycling Center

Gene technology

Food quality & security

CO2-sensor for ventilation control

Diagnostics

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Prossesering i MiNaLab

Start point:

a silicon wafer


Hva gjør vi i MiNaLab?

� Produserer � Mikro-trykksensorer (for oljebrønner … hofteimplantater)

� Mikro-akselerometre (for biler, fly)

� Strålingsdetektorer (tannrøntgen, vitenskapelige eksperimenter ala CERN, materialanalyser)

� Diffraktive optiske filtre og linser – og mikro-lyspærer

� Utvikler nye produksjonsprosesser� Laboratorier på brikker

� Energihøstere -

� Fleksible linser for mobilkameraer

� In-vivo medisinsk prøvetakning

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In-vitro diagnostics

Virus diagnostics detecting mRNA in cervical cell smear

Active capsule endoscope for colon cancer

In-vivo sensors


In Vitro Diagnostics (IVD):Analysis of samples drawn from patients

� 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

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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


“MicroActive”Automatic Detection of

Disease Related Molecular Cell Activity

FP6 STREP IST-NMP-CT-2005-017319

December 2005 - January 2009Michal Mielnik, Ib-Rune Johansen, Anja Gulliksen, Lars Solli, Tobias Baier, Cara Martin,

John O’Leary, Lutz Riegger, Peter Koltay, Frank Karlsen

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The main objective for The MicroActive projectwas to develop an instrument for molecular diagnosticsintended for use in the doctor’s office

• Human Papilloma Virus • Cervical cancer• mRNA • Two microchips• Instrument• Liquid based cytology specimens in (cervical

epithelial cells) • Diagnosis on 5 HPV viruses out


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The technology platform is generic –HPVs were the viruses chosen for proof-of-principle

� Platform for groups of disease markers with similar symptoms, such as our set of mRNAs, transcribing active genes of HPV types

� Screening

� Diagnostics

� Monitoring of treatment

Microfluidics: several virus can be detected simultaneously with high

sensitivity


Human Papilloma VirusHPV 16, 18, 31, 33, 45,

39, 51, 52, 56, 58, 59, 66, 68, and 73

High to medium risk of cancer

Second most common cause of mortality due to cancer among women worldwide

� Persistent infections – cancer

� Cytology based screening of population

� If cytology ambiguous – HPV (DNA or mRNA test)

� Vaccination of young girls (HPV 16 and HPV 18)

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The sensitivity challenge of miniaturization is met

� Is it possible to miniaturize the macroscopic mRNA HPV detection?

� Dilution series experiments showed:� Sample prep chip: extracts

from down to 5 cell linecells (CaSki) is amplifiable

� NASBA chip: down to 1.25 cell line cells (Caski) per droplet amplifiable

20 ul

20 ul

500 nl

3 mlout of 20 ml


We compared chip results with commercial macroscopic results, using clinical specimens

Voyager sample preparation instrument

Qiagen M48 BioRobot

NASBA amplification & detection instrument

NorChip PreTect HPV Proofer

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A sample preparation chipwas manufactured

� Purification of nucleic acids

� Start material (3 ml): liquid based cytology

� Output (40 µl): mRNA suitable for NASBA amplification

� Functions

� Cell filter

� Lysis buffer, wash buffers, elution buffer

stored on-chip

� Nucleic acid capture filters

Macro: Qiagen M48

MicroActive chip (IMM)


A NASBA amplification and fluorescent detection chiphas been manufactured

Input: 20 µl of purified nucleic acids

Split fluid volume into 10 droplets of 500 nl

Dried reagents stored on chip

3 droplet stop positions controlled by hydrophobic patches in channels

Metering

Dissolution of reagents

Dissolution of reagents and detection

SINTEF injection molded chip

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Biofunctional layers for polymer, silicon dioxide and gold

� Patterned or non-patterned surfaces for specific binding of

� proteins (e.g. antibodies)

� DNA probes

� Surface anchors (e.g. silanization, thiol)

� Attach biotin-ylated antibodies, DNA probes

� Anti-binding of proteins

K.W. Wee et al. 2005


Tilbake til nanoskiene!!!Hydrophobic Patterning: Coating

� Superhydrophobic surface, very good visibility in restrictions

� Preferred solution for the hydrophobic patterning

chip patterning DI-water droplet on Teflon-CB

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NASBA of HPV-16 mRNA in 500 nlplugs in microchip� Optimization of drying

agents� Wall roughness� Wall coating� Re-hydration of dried

reagents

� NASBA amplification in sample plugs using dried enzymes

Instrument� Pump

� Heating (for amplification)

� Fluorescent readout of 10 chambers


Conclusion MicroActive

� First time mRNA analysis of clinical specimen using microchip sample preparation and microchip amplification

� Proof-of-principle: on-chip NASBA based diagnostics is possible!

� A molecular marker based cancer diagnostics

� That has higher specificity (and higher PPV) than DNA based methods (and cytology)

� That is possible to miniaturize

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New: Sensor principles based on detecting non-labeled biomolecules

SINTEF: Piezoelectric

resonance shift

Electrical:Impedance

Electrochemical

SINTEF: Piezoresistive

mechanical stress

SINTEF: Photonic crystal: refractive index change


Translating biomolecular recognition into nanomechanicsScience 288, 2000

Bulk silicon micromachining

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Detection of prostate cancer

� Detection of Prostate Specific Antigen, PSA, in blood

� Cantilever composed of SiNx

� Au added on the top side of the cantilever

� Cantilever 1: 200 x 20 x 0,5

� Background 1 mg/ml HSA

� Deflection 20 nm

� 6 ng/ml

� Cantilever 2: 600 x 20 x 0,65

� Background 1 mg/ml BSA

� Deflection 20 nm

� 0,2 ng/ml

Ref.: G. Wu et al. Nature Biotechnology 19 (2001)


Photonic crystal biosensor – new!

� 200 nm sized holes forming a lattice

a) b) c) d)

e) f) g) h)

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In-vivo sensors and actuatorsImportant:- Low energy

consumption- Robust- Biocompatible


Smart Microsystems for Diagnostic Imaging in Medicine (SMIDA)

� En ultralyd-probe som kan gåinn i en blodåre

� Man antar at 80% av plutselige hjerteattak skyldes skadelig plakk (avleiringer) i blodårer som løsner og gir en blodpropp

� Genererer ultralyd ca 30MHz (elektrostatisk) og leser ut reflektert lyd (kapasitivt) med et array av små nitridmembraner

m/NTNU

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VECTORVersatile Endoscopic Capsule for gastrointestinal

TumOr Recognition and therapy

FP6 ICT Integratedproject

SINTEF ICT og Helse i samarbeid med 19 partnere i Europa

SINTEF MiNaLab: Utvikle ultralydprobe som detekterer cancer i tykktarmen ved ultralyd

Utfordring: Trådløs pille, energi minimalisering

SINTEF Helse, medisinsk teknologi: navigasjonskontroll


Pressure sensor can be integrated in stentgraft for monitoring functionality of stent

� AAA: Abdominal Aortic Aneurism

� Mission - improving the long term reliability of AAA stent grafts

� The Product - introducing an add-on to the AAA stent grafts to enable a real time monitoring device to alert for possible sudden rupture and endo-leaks

Orhere

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Nano- og mikroteknologi

Mikroteknologi er allerede i mange produkter

De kan få nye funksjoner med nanometer tynne lag påoverflaten

Miljøfarer for nanopartikler blir nå utforsket

Teknologien kan også brukes i rensesystemer

Små komponenter krever mindre ressursbruk, mindre energi etc..

Documents

Nanoteknologi Muligheter og usikkerheter - - KLUBBNYTTrk25040.rotary.no/files/.../Presentasjoner/100210_Nano-teknologi.pdf · 25.02.2010 1 Microsystems and Nanotechnology 19/01-2010