presentation slides - TechConnect World

Custom Micro/Nano System Development and Production
for Telecom, Process Control, Life Sciences and Space
LioniX BV
PO Box 456
7500 AL Enschede
the Netherlands
Phone: +31 (0)53 489 3827
Fax: +31 (0)53 489 3601
Mail: info@lionixbv.nl
Website: www.lionixbv.nl
Opto-fluidic Life Marker Chip for
Extra-terrestrial Exploration
Arne Leinse, Henk Leeuwis, Albert Prak, Rene Heideman
LioniX BV
Guus Borst
Dutch Space BV
James Walker
JayWalker Technical Consulting, LLC
1

Life Marker Chip
• Goal
– Search for molecular evidence of past or present life on Mars
• How
– In situ analysis using biosensing / bio-analytical technologies
enabled by micro/nano systems technology
The life marker chip for the Exomars mission 2

• Introduction to LioniX
• Life Marker Chip on ExoMars rover
• LMC analysis subsystem
• LMC microfluidics
• LMC integrated optics
• Current challenges
• Concluding remarks
• Acknowledgements
Overview
3

LioniX Overview
Develop/produce micro/nano-based products for (OEM) customers
Customer space:
•Telecom
•Industrial Process Control
•Life Sciences
•Space Exploration
Enschede, The Netherlands
Dortmund, Germany
Core technologies:
•integrated optics
•microfluidics
•optofluidics (including surface functionalization)
•MEMS
LioniX offers ‘design for manufacturing’ and ‘horizontal integration’
by partnering with foundries and suppliers of complementary
technologies
4

ExoMars Mission Schedule
Life Marker Chip
Courtesy of ESA
5

Basis of the Life Marker Chip
each site binds a different selective fluorescent biomarker dye
parallel excitation (via integrated optics)
parallel detection via camera
Antibody microarray technology
• attachment of thousands of probes
in small area
• small reaction volumes
• higher reaction kinetics
• potential for miniaturization and
robotization
Features
1. Detect existent and extinct life
2. Parallel multi-molecular detection
3. No special external calibration
4. Detection over broad molecular
size range
5. Sensitivity: From ppb to ppt
6. Easy analysis
7. Biotechnology industry support Typical image with one
hundred different antibodies
Courtesy of Mark Sims (LU) and
Dave Cullen (CU)
as well as positive and
negative control
Present-life biomarkers
1. Whole cells,
2. Cellular debris, biofilms
3. Biopolymers
Past-life biomarkers
1. Aliphatic Hydrocarbons.
2. Monocyclic hydrocarbons.
3. Tricyclic hydrocarbons.
4. Aromatic carotenoids.
5. Hopanoids and other
pentacycic triterpanes.
6. PAHs.
7. Lipids – Steroids.
8. Porphyrins and
maleimides.
9. Aminoacids (aa) and
nucleotides.
10. Nucleotides and other
metabolites
11. Polymers
6

• Space Flight Requirements
Microsystem Challenges
Compact, low mass, low reagent and energy consumption, robust
(shock, radiation etc.)
• Complicated fluidics in small chip sandwich
Combination of innovative bellows pump and ‘hybrid’ selector valve
• Leakproof bonding of microfluidic chip with integrated
conductors and small tolerances
New bonding technique
• Integrated Laser-Induced Fluorescense system enabling
dynamic/quantitive results
Exploitation of planar waveguide evanescent field
Flexible design features of TriPleX TM
7

Analysis Sub-system
Fluid I/F
Fluid I/F
preloaded with
dry immunoassay chemistry
Analysis system
S-A1
Conductivity sensor
Assay
chambers
Single shot
valve
Buffer chamber
V-A1
0 0
1
1
S-A2
S-A3
2
2
S-A4
3
3
pad
V-A3
S-A5
V-A2
dissolution chambers
optical I/F
Bellows
pump
Late access I/F
Pad, antibodies,
lightsource
Lightsource
Front end electronics
Power/data
Mech.
I/F
Mech.
I/F
Thermal I/F
multiple chambers enable assay of
incompatible chemistries
8

Assay chambers /
Camera window
Dissolution
chambers
Conductivity
electronics
Valve motor
System Integration
Fluid I/F
Fluid I/F
Analysis system
S-A1
Conductivity sensor
Assay
chambers
Clamp for laserdiode
LMC Analysis Subsystem
Single shot
valve
Buffer chamber
V-A1
0 0
1
3
V-A3
2
S-A2
pad
dissolution chambers
S-A3
S-A4
S-A5
2
1
3
V-A2
optical I/F
Bellows
pump
Late access I/F
Pad, antibodies,
lightsource
Lightsource
Fluid storage, valve and pump
Mech.
I/F
Mech.
I/F
Thermal I/F
Front end electronics
Power/data
Rotary valve to
control liquid flow
Glass microfludics with channels,
chambers and sensors
Electronic Readout
Laser
Integrated Optics
for Assay Readout
9

Confluence of Microfluidics, Biotech, and Integrated Optics
• Antibody microarray
- competition assay format (3 chemistries)
- predosed dried chemicals
- single-use
- 4 modules of 10x10 spots
Analysis system
Single shot
valve
Buffer chamber
V-A1
Fluid I/F
S-A1
Conductivity sensor
1
3
V-A3
2
S-A2
Fluid I/F
S-A4
Assay
chambers
0 0
pad
dissolution chambers
S-A3
S-A5
2
1
3
V-A2
optical I/F
Bellows
pump
Late access I/F
Pad, antibodies,
lightsource
Lightsource
Front end electronics
Power/data
Mech.
I/F
Mech.
I/F
Thermal I/F
• Microfluidics based core system
- micro channels: fluidic connections
- micro chambers: reagents, array, buffer
- micro sensors: electricial conductivity
- planar optical waveguides: excitation of dyes
- micro system integration: compact subsystem
- hybrid selector valve
• Integrated planar waveguides
- Laser Induced Fluorescence (LIF)
- excitation by ‘manifold’ substrate
10

Microfluidic Chip
1G-prototype
52 mm
16
mm
Dry reagent chambers
Liquid front (EC) sensor
Assay (reaction) chambers
Buffer chamber
Selection valve axis
Liquid ports
Contact pads
EC sensors
11

Buffer chamber
(250 µm, 14.2 µL)
Microfluidic Chip Sandwich Structure
Etched micro
channels (50 µm)
chambers for
reagent fiber pads
(250 µm, 2.4 µL)
Feed through
(powder blasted)
Specialized
Wafer bond
Fused silica
top plate
Fused silica
bottom plate
Viton seal
Waveguide
plate
Selector
valve axis
Valve seat
with channels
Pre-processed
sample input
Assay chamber Clamping
with reaction spots screws
(0.8 µL)
Waveguide
with assay spots
Total volume
fluidic chip
(32.7 µL)
12

Fluidic Chip
- electrodes and valve
Valve rotor
Fluidic chip with details of the access hole to the
buffer chamber and a fluid front sensor
Assembled valve
13

Laser Induced Fluorescence (LIF) Detection
Reaction Chamber
array of 10x10 spots
each spot functionalized for a specific target
optically coupled with TriPleX TM waveguides
Evanescent-field excitation
of bound fluorescent dyes
Parallel detection by camera electronics
upper cladding is removed enabling strong
evanescent field interaction
14

TriPleX TM Waveguide Technology
• low loss
• small bending radius
• good fiber coupling
• transparancy from 400nm – 2500nm
~100 nm
2 m
Si 3 N 4 : red layer
SiO 2 : blue layer
~1 m
~1 m
‘sensing’ geometry
for Lab-on-a-Chip
‘fiber-like’ geometry for data/telecom
(polarization independent)
Core of TriPleX TM :
Si 3 N 4 / SiO 2 / Si 3 N 4
‘design by geometry’
15

Optical Chip and Fiber Connections
• Multimode Interferometer
• Core thickness tapering
- 3 areas
60/125 fiber
(monitor)
Monitor
waveguide
8 mW laserdiode,
635 nm
Sensing windows
9/125 fiber
(input)
FAU
(fiber array unit)
Input
waveguide
MMI (1 x 11 splitter)
Tapered area
16

Concluding Remarks
• Convergence of microfluidics-integrated optics-bio
• Low-loss, wavelength-flexible waveguides enable
compact, large-count fluorescent marker assay array
• Surface functionalization is a key issue
• Future developments in functionalization of microarrays
will enable more application opportunities
• LMC is an enabler for terrestrial applications
17

Acknowledgements
• Funding
– Netherlands Space Office (NSO)
– European Space Agency (ESA)
Netherlands Space Office
• LMC Team Leaders
– Mark Sims, Leicester Univ. (UK)
– Dave Cullen, Cranfield Univ. (UK)
• LMC Instrument Team
– Dutch Space (NL), Leicester University, Cranfield
University, Magna Parva (UK), Kayser Italia, SSTL
(UK), and Imperial College (UK)
The life marker chip for the Exomars mission 18