The document discusses medical applications of micro and nano technology. It begins with definitions of microsystems technology and nanotechnology. It then discusses various medical applications including implants and artificial organs like pacemakers, diagnostic devices like endoscopy cameras and pill cams, drug delivery systems, and microfluidics applications like lab-on-a-chip devices. The document also briefly mentions applications in genomics and proteomics.

1. Medical Applications
Micro and Nano Technology
Jan Eite Bullema

2. Medical Applications
of Micro and Nano Technology
‘It would be interesting in surgery
if you could swallow the surgeon’
Richard P. Feynman
May 28, 2014
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3. 3
Medical Applications
of Micro and Nano Technology
Micro and Nano Technology
Medical Applications
Genomics, Proteomics
Example Projects
Conclusion
TTAGGG-TTAGGG-TTAGGG-TTAGGG-TTAGGG
May 28, 2014
Jan Eite Bullema
Medical Applications

4. 4
Micro and Nano Technology
Definition: Micro Systems Technology
Microsystems technology is the technology to build a system
that can measure and respond autonomous to signals
A microsystem is a small product with functional dimensions
in the micro-meter-domain.
Sensor Processor
Energy
Source
Actuator
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5. Micro and Nano Technology
Definition: Nano Technology
The U.S. National Nanotechnology Initiative gives the following defining
features of nanotechnology:
Nanotechnology involves research and technology development at the
1 nm -to- 100nm range.
Nanotechnology creates and uses structures that have novel properties
because of their small size.
Nanotechnology builds on the ability to control or manipulate at the
atomic scale.
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6. 6
Micro and Nano Technology
The Micro and Nano meter domain
hair scale Egg celllouse
diode
Solder-
line
Digital
Mirror
Transis-
tor
Ic line
(157 nm)
pore
1 mm 0,1mm 0,01mm 1mu 0,1mu
Atom
(CO op Pt
back finger nail bacteria DNA
PCB ICTelevision
Quantum
structure
Buckey
Ball
semen
1m 0,1m 0,01mu 1nm 0,1nm0,01m
BIOLOGICAL Scale
TECHNOLOGICAL Scale
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7. Micro and Nano Technology
Biological Microsystem; T-4 Bacteriophage
1 micron(Replica made with FIB)
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Anisotropic etching of a cavity in {100} oriented Silicon
Micro and Nano Technology
Anisotropic Etching of Silicon
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9. By anisotropic etching highly precise 3D structures
can be realized in Silicon
9
Micro and Nano Technology
Realization of a pressure sensor in Silicon
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By the use of etching technology many products can be realized
simultaneously. This enables low cost manufacture of precise parts
Micro and Nano Technology
Example: Mass Micro Machining
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11. Micro and Nano Technology
Example: Pressure sensor in a package
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Silicon structure is packaged in an electronic package
The packaging significantly contributes to cost
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12. Micro and Nano Technology
Pacemaker: Typical Micro System
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13. 13
Micro and Nano Technology
Medical Applications
Micro and Nano Technology
Medical Applications
Genomics, Proteomics
Example Projects
Conclusion
TTAGGG-TTAGGG-TTAGGG-TTAGGG
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14. 14
Medical Applications
• Implants and Artificial Organs
• Diagnostic and Analytical Devices
• Drug Delivery
• Microfluidics
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15. 15
Medical Applications: Implants and Artificial Organs
The oldest example of a microsystem
The pacemaker is one of the oldest examples of a
micro system product
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Medical Applications: Implants and Artificial Organs
Pacemaker Historic Developments (1950)
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Medical Applications: Implants and Artificial Organs
Pacemaker Historic Developments (2000s)
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18. Medical Applications: Implants and Artificial Organs
Pacemaker Decreasing Dimensions
MEDTRONIC, is using micro
electronics and chip manufacturing
to shrink pacemakers
– implanted devices that regulate the
hearts rhythm. Whereas current
pacemakers are the size of a silver
dollar. Medtronics new device would
be smaller than a tic-tac. At that size
the pacemaker could be inserted
through a catheter rather than
invasive surgery
http://www.technologyreview.com/biomedicine/32436
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19. 19
Medical Applications: Implants and Artificial Organs
Implantable Hart
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20. Medical Applications: Implants and Artificial Organs
CardioMEMS: Implantable pressure sensor
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21. Medical Applications: Implants and Artificial Organs
Stents
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Medical Applications: Implants and Artificial Organs
CardioMEMS Implantable pressure sensor
CardioMEMs’ device measures blood pressure in people who
have an abdominal aortic aneurysm. Doctors can treat the
bulging artery with a stent graft, stents can fail, so aneurysm
patients require lifetime monitoring
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23. Medical Applications: Implants and Artificial Organs
Artificial Kidney project: Nephron +
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Towards a wearable blood cleansing device
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24. Medical Applications: Implants and Artificial Organs
Artificial Kidney project: Nephron +
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Towards a wearable blood cleansing device
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25. Medical Applications: Implants and Artificial Organs
Artificial Kidney project: Nephron +
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Towards a wearable blood cleansing device
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26. Medical Applications: Implants and Artificial Organs
Artificial Kidney project: Nephron +
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Current Prototype (2012)
Towards a wearable blood cleansing device
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27. Medical Applications: Implants and Artificial Organs
Artificial Kidney project: Nephron +
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Towards a wearable blood cleansing device
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28. Medical Applications: Implants and Artificial Organs
Hearing Aid
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Trend is that products become
smaller
and
smarter
This is enabled by developments
In micro electronics and in micro
systems technology
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Type Typical cost
Euro per unit
Behind the ear 200 - 300
In the ear 500 - 700
In the canal 700 - 1000
Completely
in the canal 1400 - 2000
Cochlear Implants 35000 - 50000
Medical Applications: Implants and Artificial Organs
Hearing Aids & Cochlear implants
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Medical Applications: Implants and Artificial Organs
Hearing Aids
Source: Phonak
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31. Medical Applications: Implants and Artificial Organs
Cochlear Implants
1985 1991 1997 1999 2000 2004
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32. Medical Applications: Implants and Artificial Organs
Additive Manufacturing of Hearing Aids
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The silent revolution in manufacturing of hearing Aid Applications
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33. Medical Applications: Implants and Artificial Organs
Additive Manufacturing of Hearing Aids
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in 2 years time change from manual production to digital shell production
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34. Medical Applications: Implants and Artificial Organs
Printing Vincents Ear
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35. Medical Applications: Implants and Artificial Organs
Printing Vincents Ear
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36. Medical Applications: Implants and Artificial Organs
Printed Electronic Ear
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37. Medical Applications: Implants and Artificial Organs
3D Printed Skull Implant
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38. Medical Applications: Implants and Artificial Organs
3D Printed Skull Implant
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Xilloc in Maastricht is producing 3D printed patient specific implant parts
Leading to a cost reduction in patient care
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39. Medical Applications: Implants and Artificial Organs
3D Printing of Stem Cells on Hip Implant
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40. Medical Applications: Implants and Artificial Organs
UTAH Electrode
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UTAH Electrodes for Contacting the nerve system
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41. Medical Applications: Implants and Artificial Organs
UTAH Electrode
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UTAH Electrodes for Contacting the nerve system
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42. Medical Applications: Implants and Artificial Organs
Deep Brain Stimulation
Sapiens in Eindhoven is developing a Deep Brain Stimulation system
primary directed at patients with Parkinsons disease
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43. 43
Medical Applications
• Implants and Artificial Organs
• Diagnostic and Analytical Devices
• Drug Delivery
• Microfluidics
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44. Medical Applications: Diagnostic and Analytical Devices
Endoscopy
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45. Medical Applications: Diagnostic and Analytical Devices
Pill Cam
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46. Medical Applications: Diagnostic and Analytical Devices
Pill Cam
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47. Medical Applications: Diagnostic and Analytical Devices
Properties of the Pill Cam
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The capsule is 11mm x 26mm (<4 grams)
Field of view is 140 degrees.
Detection of objects at a minimum size
less than 0.1 mm
In a normal (8 hr) procedure the
generates approximately 57,000 images,
at a rate of two frames / second.
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49. Medical Applications: Diagnostic and Analytical Devices
Capsule Endoscopy Image
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Eosinophilic Enteritis
visualizing folds
of the cecum
Cecum Nematodes
Pinworm in
healthy volunteer
Note thickened...
Kaposi’s Sarcoma
Patient with
cutaneous Kaposi’s
Normal ColonHemorrhagic
60 year old woman Normal vessels
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50. Medical Applications: Diagnostic and Analytical Devices
Mermaid Capsule
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The "Mermaid" capsule can swim around in the large intestine like an eel
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51. 52
Medical Applications
• Implants and Artificial Organs
• Diagnostic and Analytical Devices
• Drug Delivery
• Microfluidics
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52. Medical Applications: Drug Delivery
IntelliCap® by Medimetrics
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53. Medical Applications: Drug Delivery
IntelliCap® by Medimetrics
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54. Medical Applications: Drug Delivery
IntelliCap® by Medimetrics
Length small intestines 4-6 m
Drift velocity (due to peristalsis) in small
intestines 1 m/h
Residence time in small intestines 4-5 hrs
Length large intestines 1-1.5 m
Throughput time1-5 days
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55. Medical Applications: Drug Delivery
IntelliCap® by Medimetrics
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56. Medical Applications: Drug Delivery
IntelliCap® by Medimetrics
Dimensions length 26 mm, diameter 11 mm
Weight 3.2 gr (specific mass 1450 kg/m3)
Medication content 300 micro liter
Minimum dispensed volume 1 micro liter
Once per 20 seconds the status on temperature, pH, medication content,
battery will be transmitted to the outside of the body
Reach RF link 0.3 m in the body
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57. Medical Applications: Drug Delivery
Fantastic Voyage
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58. Medical Applications: Drug Delivery
Capsule Size
Patient comfort needs a move towards acceptable swallow size
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59. Medical Applications: Drug Delivery
Capsule Size Chart
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60. Medical Applications: Drug Delivery
3D Printed Nano Pill
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61. Medical Applications: Drug Delivery
Aerosol dispenser
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62. Medical Applications: Drug Delivery
Aerosol dispenser
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63. 66
Medical Applications
• Implants and Artificial Organs
• Diagnostic and Analytical Devices
• Drug Delivery
• Microfluidics
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64. Medical Applications: Micro Fluidics
Micro Fluidics
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The science and engineering of systems in which fluid behaviour
differs from conventional flow theory primarily due to the small
length scale of the system.

65. Medical Applications: Micro Fluidics
Lab on a Chip (micro array)
By capillary action the sample is pulled to the reactive spots
Small sample volume + large number of analysis simultaneously
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66. 69
Medical Applications: Micro Fluidics
Lab on a Disk
Gyros: Lab-on-a-Disk
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67. S H A P I N G Y O U R I D E A S
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68. • Smallest features 50 x 50µm (width x depth)
• Roughness bottom channels 0,08µm Ra
• Roughness optical read out area’s 2nm Ra
• Thickness distribution total disc < 10µm
• Warpage total disc < 1˚
Injection moulded DVD-like substrate
S H A P I N G Y O U R I D E A S
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69. Point Of Care Diagnostics
Big things in little channels!
• Care from central lab to a house doctors practice
• Results in 10min.
• Just using one drop of blood (5µl)
S H A P I N G Y O U R I D E A S
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70. Medical Applications: Micro Fluidics
Lab on a Disk: Spin It Reader
Source: Axxicon, 2014
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71. Medical Applications: Micro Fluidics
Lab on a Chip: Magnotech
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Magnotech: Philips’ magnetic biosensor platform
designed for point-of-care testing (e.g. troponin)
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72. Medical Applications: Micro Fluidics
Lab on a Chip: m Chip CE
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Micro Capillary Electrophoreses for
detection of ions in whole blood
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73. Medical Applications: Micro Fluidics
Organ-on-a-chip
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soon to replace animal testing
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74. Medical Applications: Micro Fluidics
Organ-on-a-chip: e.g. Lung-on-a-Chip
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75. Medical Applications: Micro Fluidics
Organ-on-a-chip: e.g. Lung-on-a-Chip
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76. 79
Micro and Nano Technology
Medical Applications
Micro and Nano Technology
Medical Applications
Genomics, Proteomics
Example Projects
Conclusion
TTAGGG-TTAGGG-TTAGGG
May 28, 2014
Jan Eite Bullema
Medical Applications

77. 80
Genomics, Proteomics
The original Watson and Crick’s paper
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78. Genomics, Proteomics
Watson and Crick
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79. 82
Genomics, Proteomics
Cells: Natures Micro Systems
Humans: 60 trillion (1012) cells 320 cell types
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80. 83
Genomics, Proteomics
Basis of molecular biology
hierarchy of relationships
genome
gene 1 gene 3gene 2 gene X
protein 1 protein 2 protein 3 protein X
function 1 function 2 function 3 function X
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81. 84
Genomics, Proteomics
Polymerase Chain Reaction (PCR)
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82. Genomics, Proteomics
Polymerase Chain Reaction (PCR)
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Genomics, Proteomics
Micro machined silicon PCR chamber
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84. 87
Genomics, Proteomics
Fluid injection and separation
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steps in a miniature DNA capillary electrophoresis system
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Genomics, Proteomics
Example: Pulsed Field Gel Electrophorese
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86. Genomics, Proteomics
The Sequencing Explosion: Learning Curve
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http://www.economist.com/node/18304268
Developments in sequencing enable the trend from generic and curative
medical treatment towards, individual and preventive medical care
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87. Genomics, Proteomics
Graig Venter sequenced the human genome
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88. Genomics, Proteomics
Individual Human Genome Sequencing
within 6 hrs @ 900 USD
Oxford Nanopore Technologies claims it will accomplish this feat
using a device that can plug into your computer’s USB port
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89. Genomics, Proteomics
Personalised Medicine
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Optimised patient treatments through advanced diagnostics and
personalised medicine
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90. Genomics, Proteomics
Personalised Medicine
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Response rates of patients to a major drug for a selected group of
therapeutic areas
Therapeutic Area Efficacy Rate (%)
Alzheimers 30
Asthma 60
Diabetes 57
Incontinence 40
Oncology 25
Osteoporose 48
Rheumatoid Arthritis 50
Schizophrenia 60
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Micro and Nano Technology
Medical Applications
Micro and Nano Technology
Medical Applications
Genomics, Proteomics
Example TNO Projects
Conclusion
TTAGGG-TTAGGG
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92. 96
Example TNO Projects
STELLA Project: Stretchable Electronics
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Example TNO Projects
STELLA Project: Stretchable Electronics
Stretchable 3 % to 20 %
Biocompatible
Breathable
Chemical resistant
Comfortable, painless
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Example TNO Projects
STELLA Project: Stretchable Electronics
Chronic wounds = non healing wounds
Chronic wounds reduce quality
of life and may lead to infections,
amputations and even death !
Increasing with ageing population.
Common chronic wounds
- diabetic foot Ulcers,
- Pressure ulcers,
- Leg ulcers (venous stasis ulcers),
- Burns.
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95. 99
Example TNO Projects
STELLA Project: Stretchable Electronics
Smart Shoe:
(1) monitoring of the
correct size of childrens’
shoes,
(2) diabetic feet care
(3) step detection
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96. Example TNO Projects
PLACE IT: Application Flexible Electronics
Philips explores
opportunities to
integrate for light
therapy into the
baby's blanket.
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97. Example TNO Projects
PLACE IT: Application Flexible Electronics
BlueTouch Pain Relief Patch
LED-in-textile platform enables effective, safe light therapies
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98. Example TNO Projects
PLACE IT: Application Flexible Electronics
The BlueTouch Pain Relief
Patch works through
- Direct Heat Sensation
- Nitric Oxide Release
- Deep Heat Penetration
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99. Example TNO Projects
PLACE IT: Application Flexible Electronics
Ohmatex has recently
developed an Oedema sock
which wirelessly
measures the change in
volume in the lower leg
The volume in the lower leg
is an indirect measure of hart
decompression and can be
used to predict a hart attack.
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100. Example TNO Projects
Lab on a Chip: PCR for Bacteria Detection
Chip material: glass, silicon, viton sealing.
Integrated heaters and temperature sensors.
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101. 105
Example TNO Projects
SmartHEALTH: Diagnostics for Healthcare
Goal:
On-chip point-of-care cancer diagnostics
Application area: cancer diagnostics
Fast, point of care
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102. Example TNO Projects
SmartHEALTH: Diagnostics for Healthcare
• Assay development
• Geometry design
• Biocompatible coating
+ material technology
• Thermal control
• Contamination control
• Optical detection
• Prototyping
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103. Example TNO Projects
SmartHEALTH: Diagnostics for Healthcare
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3D Printing of a Lab on a Chip
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104. Jan Eite Bullema
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Example TNO Projects
HydroChip: Diatom Monitoring
Source: TNO 2014 / Trouw March 19, 2014
The Hydrochip analysis 200 samples simultaneously. Type specific
DNA for more tha 100 Algae. In half a day.
The ‘classic’ method would take > 100 days for 200 samples
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Example TNO Projects
SAMPREP: Sample Preparation
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Extraction of DNA from Cells for Amplification
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106. Example TNO Projects
SAMPREP: Sample Preparation
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107. 111
Example TNO Projects
SAMPREP: Sample Preparation
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108. MicroFluidicManufacturing

109. Example TNO Projects
MicroFluidic Manufacturing
MFManufacturing: European initiative for the standardization and
manufacturability of complex micro-fluidic devices
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110. Example TNO Projects
Organ on a Chip
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111. Example TNO Projects
Organ on a Chip
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A group at the German Fraunhofer IGB Institute has created blood
vessels, by printing artificial biological molecules with a 3D inkjet
printer and zapping them into shape with a laser.

112. Example TNO Projects
Organ on a Chip: Student Projects @ TNO
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3D Printing of 3D Capillary Structures
3D Printing of Biocompatible Materials
3D Printing of Specific Surface Structures to promote Cell Adhesion
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113. 117
Micro and Nano Technology
Medical Applications
Micro and Nano Technology
Medical Applications
Genomics, Proteomics
Example Projects
Conclusion
TTAGGG
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114. 118
Conclusions
Medical Applications of
Micro and Nano technologies
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- Fascinating emerging micro and nano technologies
e.g. 3D Printing, Bio Printing
- Smaller products mean often better products
e.g. smart drug delivery pills, smart diagnostic pills
- Personalised Medicine and Point of Care Diagnostics
are very attractive markets

115. Questions ?
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