BIOELECTRONICS and nanotechnology the bridge between electronics and life sciences

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BIO-ELECTRONICS(and nanotechnology)the bridge
between electronics and life sciences

• Luc De Schepper
• Director IMO/IMOMEC

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Content

• What is bio-electronics ?
• Why bio-electronics ?
• Basic approaches
• TOP DOWN
• BOTTOM UP
• bio-electronic interconnection technology
• State of the art in bio-electronics
• A look into the future
• Conclusions

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Content

• What is bio-electronics ?
• Why bio-electronics ?
• Basic approaches
• TOP DOWN
• BOTTOM UP
• bio-electronic interconnection technology
• State of the art in bio-electronics
• A look into the future
• Conclusions

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What is bio-electronics ?

• Bio-electronics is the bridge between
• ELECTRONICS AND LIFE
  SCIENCE

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Why bio-electronics ?

• ELECTRONICS was the driving technology of the
  20th century transistor, televison, personal
  computer, mobile phone, internet
• Many people predict that LIFE SCIENCES will be
  one of the driving forces for the technological
  development in the 21th century (see
  Converging technologies for improving human
  performance, report of the NSF (USA), 2002,
  available on Blackboard)
• BIO-ELECTRONICS is intended to link the most
  succesfull technology of the 20th century with
  one of the most promising technologies for the
  21th century !

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Who is taking part in the bio-electronic research
in the tUL ?

• Partners in the bio-electronics research project
  of the tUL
• At LUC (development of new biosensor concepts)
• Institute for Materials Research (IMO) (materials
  and electronics)
• Biomedical Institute (BIOMED) (biochemistry,
  biotechnology, application in auto-immune
  diseases)
• At UM (applications of bio-electronics)
• CARIM
• NUTRIM
• AzM
• IMEC (integration of succesfull concepts in
  micro-electronic devices)

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A unique co-operation

• RESEARCH
• IMO, IMOMEC and BIOMED develop new biosensor
  concepts
• IMEC integrates succesful concepts in
  micro-electronic devices
• BIOMED, CARIM and NUTRIM define applications and
  test the biosensors for diagnostic and
  therapeutic use
• EDUCATION
• Unique multidisciplinary Master in Life Sciences
  in Flanders and the Netherlands BIO-ELECTRONICS
  AND NANOTECHNOLOGY
• (accessible for bachelors in Life Sciences,
  Physics, Chemistry, Biology)

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New biosensor concepts

• Current research focus new types of biosensors
  based on new materials

artificial diamond (CVD diamond)
Multifunctional semiconducting polymers
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Bio-elektronics is multidisciplinary
BIO-ELECTRONICS
AzM
Application
Development
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Bio-electronics and nanotechnology

• Wat is nanotechnology ?
• NANO means small
• Nanotechnology technology on a small scale

• In numbers
• 1 micrometer 1 mm 0,001 mm 1/1000
  millimeter
• 1 nanometer 1 nm O,000001 mm 1/1.000.000 mm
• 1 nanometer 1/1.000.000 mm
• 1 nanometer 1/1.000.000.000 m

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Why nanotechnology ?

• To link ELECTRONICS and biological systems we
  need to work on micrometer- or nanometer scale !
• Example on a micrometerschaal connection between
  a neuron and a neuron well in silicon

0,01 mm
0,01mm 10mm
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Why nanotechnology ?

• On nanometer scale the dimensions of electronic
  materials fit to the dimensions of individual
  biomolecules !
• ELECTRONIC MATERIAL BIOMOLECULE

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The Scale of Things
Human made
In nature
MINIATURIZATION
Objects fashioned from metals, ceramics, glasses,
polymers ...
SELF ASSEMBLY
5/20/00
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Content

• What is bio-electronics ?
• Why bio-electronics ?
• Basic approaches
• TOP DOWN
• BOTTOM UP
• bio-electronic interconnection technology
• State of the art in bio-electronics
• A look into the future
• Conclusions

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Manufacturing technologies for bio-electronics

• We want to produce structures on a micrometer or
  nanometer scale which are able to connect
  biological entities and electronic systems
• Micro- and nanometer scale structures can be made
  in two ways
• By miniaturisation TOP-DOWN
• By building up, starting from smaller building
  blocks BOTTOM UP
• TOP-DOWN use of well known techniques from
  micro-electronics (to be pushed somewhat further)
• BOTTOM-UP manipulating individual atoms new !
• BIO-ELECTRO INTERCONNECTION TECHNOLOGY new !

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Content

• What is bio-electronics ?
• Why bio-electronics ?
• Basic approaches
• TOP DOWN
• BOTTOM UP
• bio-electronic interconnection technology
• State of the art in bio-electronics
• A look into the future
• Conclusions

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TOP-DOWN TECHNOLOGY
TOP DOWN - MINIATURISATION
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Top-down technology

• Standard manufacturing technology for
  micro-electronics (chips or integrated circuits)
• To be discussed next week
• IMEC is a world leading lab in developing proces
  modules

• TYPICAL FEATURE SIZE
• 1 micrometer 1000 nanometer STANDARD
• 0,1 micrometer 100 nanometer STATE OF THE
  ART
• 0,01 micrometer 10 nanometer 2010

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Top-down technology pentium chips on a wafer
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Top-down technology packaging of a chip in a
DIL package
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The packaged PENTIUM chip
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Nano is very small How can we visualise the
structures on a chip ?

• Conventional light microscopes cannot be used in
  the submicron range (resolving power is too low)
• electron microscopes !

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Scanning electron microscope (SEM)
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Metal interconnects in an IBM 233 MHz processor
(SEM image)
0.0,5 mm 500nm
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Content

• What is bio-electronics ?
• Why bio-electronics ?
• Basic approaches
• TOP DOWN
• BOTTOM UP
• bio-electronic interconnection technology
• State of the art in bio-electronics
• A look into the future
• Conclusions

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BOTTOM-UP TECHNOLOGY
BOTTOM UP
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BOTTOM-UP

• Some people say this is the only real form of
  NANOTECHNOLOGY
• Nanotechnology is the technology based on the
  manipulation of individual atoms and molecules to
  build structures to complex atomic
  specifications.
• To make nanometer scale structures via bottom-up
  techniques we must be able
• to manipulate INDIVIDUAL ATOMS/MOLECULES
• To tell the individual atoms/molecules to
  organise themselves in a predefined structure
  (SELF ASSEMBLY)

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Manipulating indivual atomscan it be done ?
Richard Feynmann
The principles of physics, as far as I can see,
do not speak against the possibility of
maneuvering things atom by atom. It is not an
attempt to violate any laws... but in practice,
it has not been done because we are too
big. RICHARD FEYNMANN, 1959
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Visualising and manipulating atoms with an STM
(Scanning Tunneling Microscope)

• Tunneling current between a very fine tip and a
  surface can be used to visualise individual atoms
• A potential difference between the tip and the
  surface can be used to pick up individual atoms

STM image of a Si surface
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Example The IBM logo written with 35 Xenon
atoms !

• STM image

1 nm
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Bottom-up technology self assembly

• Manipulation of individual atom with STM is slow
  and is not applicable to all kinds of atoms
• Alternative SELF ASSEMBLY of atoms/molecules
  atoms or molecules organise themselves to form a
  particular programmed structure
• Nature can do it ! All living creatures are
  self-assembled structures.
• Can we do it ? First steps

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Bottom-up programmed self assembly of
biomolecules (state of the art)

• A programmed self-assembly of DNA molecules
  between synthetic membranes
• Blue DNA
• Green/white hydrophylic end of the artificial
  cell membrane molecules
• Yellow/brown hydrofobic tails of the articial
  cell membrane molecules
• The distance between the DNA molecules can be
  programmed to be between 2.5 and 6 nm
• J. Rädler, Science, 275, 810 (1997)

3 nm
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Bottom-up self-assembly of polymers (state of
the art)

• Ss(Shimizu, Univ. South
• Carolina, 2000)

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Bottom-up self assembly (state of the art)

• Self assembly of a polymer and a gold-thiol
  complex

Nature 404, 746, April 2000
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Bottom-up self assembly(science fiction)

• Building molecular machines
• Nanobots (see next week !)

Molecular precision controller
Molecular pump
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Content

• What is bio-electronics ?
• Why bio-electronics ?
• Basic approaches
• TOP DOWN
• BOTTOM UP
• bio-electronic interconnection technology
• State of the art in bio-electronics
• A look into the future
• Conclusions

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How to interconnect electronics and bio-entities
?

• Bio-entity biomolecule, cell, neuron,
• Electronic system semiconducting surface, chip,
  integrated cicuit
• To capture individual target molecules we need
  BIOCHEMICAL PROBES for ANCHORING target molecules
• In many cases we need LINKING LAYERS (e.g. to
  connect the biochemical probes to the
  semiconducting surface)

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Interconnecting bio-entities to an electonic
system
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Some self-assembly may be required
SOME SELF-ASSEMBLY MAY BE REQUIRED FOR EFFICIENT
ANCHORING
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Examples of biochemical probes and linking
layers (state of the art for Si)

• Linking layer silanes on siliconoxide or thiols
  on gold
• Biochemical probes antibodies, DNA fragments

Y
Biochemical probes
Biochemical probes
silanes
thiol
Si-oxide
gold
Si based electron. system
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Content

• What is bio-electronics ?
• Why bio-electronics ?
• Basic approaches
• TOP DOWN
• BOTTOM UP
• bio-electronic interconnection technology
• State of the art in bio-electronics
• A look into the future
• Conclusions

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State of the art in bio-electronics

• Top-down based technologies on micrometer scale
  are in use today
• Biosensors
• Micro-electromechanical systems
• Bottom-up technologies in early research state

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Biosensors state of the art

• Working principle
• immobilisation (anchoring) of targeted
  biomolecules on the sensor surface
• Immobilisation causes the transducer to send a
  signal tot the electronic interface
• User reads the concentration on a display

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Biosensors different tranducer types (state of
the art IMEC)
Nanoscaled IDE Sensors
CMOS Integrated Multiparameter Sensors
Microphysiometer
Acoustic Wave Sensors

• DNA
• antibody/antigen
• immunosensing

• Bloodgas sensor
• pCO2, pO2, pH

• HTDS
• Calorimetric (D heat)

• antibody/antigen
• immunosensing
• liquid identification

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Biosensors state of the art

• In vitro detection of very low concentrations of
  biomolecules (e.g. Glucose in blood)
• DNA chips recognition of DNA fragments and genes
• Detection limit better dan 1 ng per ml

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Biosensors commercial systems
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Micro-electromechanical systems (MEMS)

• MEMS are top-down made components which combine
  ELECTRONIC en MECHANICAL functions
• State of the art micrometer scale
• Medical MEMS are (or will be) used for
• minimal invasive diagnostics and surgery
• smart implants
• Local drug deposition

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MEMS integration of mechanics and electronics

• Micromotor and -gears

50mm
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Medical MEMS today

• PACEMAKER

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Cochlear implant

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Implanted defibrillator
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Heart pump Jarvik 2000
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Medical MEMS today
Blood pressure sensors to be build in in a
catheder
multifinger microrobot for surgery
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Medical MEMS today

• Implants to stimulate specific nerves in the
  brain (application Parkinson and epilepsy)

Vagus Nerve Stimulation system (CYBERONICS)
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Content

• What is bio-electronics ?
• Why bio-electronics ?
• Basic approaches
• TOP DOWN
• BOTTOM UP
• bio-electronic interconnection technology
• State of the art in bio-electronics
• A look into the future
• Conclusions

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A look into the future

• Top-down further development of intelligent
  medical MEMS for implantation (e.g. articial eye
  and ear, implantable glucosesensor, .
• Bottom-up early research stadium. Self-assembled
  nanomachines are not for the next decade.
• bio-electronic interconnection technology
  rapidly advancing field for biomolecules, cells
  and neurons. The neuro-electronic synapse seems
  to be possible, brain implants will become a
  reality.

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Medical MEMS the future (5 years)

• Retinal implants to give blind patients a limited
  view
• Example for patients with damaged fotoreceptors
  in the retina (but undamaged optical nerve)
• A mini camera is mounted on glasses and sends
  digitised images via a laser to the implanted
  chip (stmulation circuit). The chip transforms
  the images into electrical pulses which are sent
  to an electrode array fixed on the retina.

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Medical MEMS science fiction

• Nanomachines are injected into the blood stream
  and carry out a number of different tasks
  (reparing damaged cells, killing cancer cells,)

red blood cell
nanomachine
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Neuro-electronic synapse

Neuron on a matrix of 128x128 Transistors (P.
Fromherz)
Rat neuron on an array of Transistors (P.
Fromherz)
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Neuro-electronic synapsescience fiction

• Based on direct coupling of electronics to
  neurons
• Implantation of neural implants that directly
  communicate with a large number of brain cells
  (within 30 year ?)
• Dramatic increase in brain capacity
• Brain and implant think together
• Learning could be replaced by implanting a
  module

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Neuro-electronische synapse brain power versus
chip power

• Calculating power of a 1.000 PC versus a brain
  as a function of time
• 2000 PC calculating power equal to the brain of
  an insect
• 2040 equal to the brain of a human
• 2060 equal to the cumulative brain capacity of
  the world population

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Content

• What is bio-electronics ?
• Why bio-electronics ?
• Basic approaches
• TOP DOWN
• BOTTOM UP
• bio-electronic interconnection technology
• State of the art in bio-electronics
• A look into the future
• Conclusions

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Conclusions

• Bio-electronics realises the link between
  electronics and biological entities
  (biomolecules, neurons, cells)
• This is realised on a micrometer or nanometer
  scale
• (1 nm 1/1.000.000 mm)
• Micro- and nanometer scale structures can be
  manufactured in two ways
• TOP-DOWN (conventional miniaturisation as used in
  micro-electronics)
• BOTTOM-UP (manupulation of individual
  atoms/molecules or self-assembly)
• Interconnecting electronics and bio-entities
  requires specific technologies neuro-electronic
  synapse, biochemical probes, linking layers,

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Conclusions

• What can we expect in the future ?
• Top-down technology further down scaling of
  litography based technology (towards 45 nm and 32
  nm).
• Bottom-up technology first steps are made in
  fundamental research. Bottom-up made nanomachines
  will not be realised on a short time scale !
• Neuro-electronic synapse the principle has been
  demonstrated, but practical applications are not
  for the near future