manufactured? • microstructure, nanostructure, colour t bl t i l ( hiti ) t li • stable material (chitin), not alive • reproducibility • ease of manufacturing • low cost • … and what is the blueprint for it?
manufactured? d h t i th bl i t f it? •… and what is the blueprint for it? • … how to get from molecular biology to structure? • … how to get discrete size, structure • … how to engineer by self assembly? g y y
manufactured? d h t i th bl i t f it? •… and what is the blueprint for it? • … how to get from molecular biology to structure? • … how to get discrete size, structure • all 3 have identical genome g
a substrate dev ce de o subs e • using clean room technology • target: chemistry biology medical use • target: chemistry, biology, medical use • containing channels, reactors etc t i d t t h t t • may contain detectors, heaters, etc.
glass‐glass silicon‐silicon glass‐silicon silicon‐silicon pmma‐pmma glass gold glass glass‐silicon glass‐gold‐glass glass‐laminate‐glass glass‐silicon‐glass d l l i l d d pdms‐glass ordyl multi‐layer glass pdms‐copper pdms‐silicon pdms‐pdms pdms‐silicon‐pdms quartz‐quartz • substrate materials used
spider single channel central bed, ch around single channel 1 loop central ch array, tree central bed, ch around tree, spider central ch array, tree binary branching structure non‐binary branching well central chamber, frit, tree single channel 1 loop network central chamber, single ch • topology • spider, tree, loop, network, etc p p
large holes, thick glass cover eppendorf pipets open eppendorf pipets, open flat metal plates eppendorf pipets, open fused silica tubing don't know, not used plastic tubing ‐ glue fused silica tubing plastic tubing ‐ glue flat metal plates large holes, thick glass cover flat plastic plates large holes thick pdms cover don't know, not used large holes, thick pdms cover • interfacing type • (“chip to world interface”) p
separation d t ti separation biology detection reaction biology reaction basics application pumping pumping sample prep detection • what is the chip used for?
chip, design 1989, fab 1989 mettler imt switzerland g g p g • manz, harrison, fettinger, verpoorte, lüdi, widmer, proc. transducers 1991 san francisco, 939-941, 1991
chip, design 1992, fab 1992 mettler imt switzerland g g p g • burggraf, manz, effenhauser, verpoorte, de rooij, widmer, j.high resolut.chromatogr. 16, 594-596, 1993
o p c p e • high speed separation • commercial product • commercial product • market needs just 2x faster electrophoresis ( h di i ti !) • (…. how disappointing!)
oil – (RT) PCR conducted on a PCR Oi glass cover slip – Micromachined heater/sensor Sample Oi l B are separated from the sample – Cover slip is disposable – Small sample volume makes system very fast Mirror reflection
glass placed on a LENGTH LINK SENSOR micromachined silicon – Heater integrated with LINK temperature sensor – Heating rate: thermal mass, available power with PID control – Cooling rate: (thermal time constant) H T G P G H ;
Real-Time RT- PCR 0 .6 2 ature (V) • Melting Curve Analysis • 8 minutes for RNA detection 0 1 Tempera 8 utes o N detect o 0 .3 -2 -1 e (V) V irusD etected H ot S tart P C R 100 150 10-2 cence (mV) uorescence (V/cycle) -3 uorescence V irus D etected R T 0 50 10-3 Fluoresc Differential Flu Critical Threshold 22.3 0 2 4 6 8 1 0 12 0 .0 -5 -4 Flu 0 10 20 30 40 10-4 Cycle Number T im e (m in)
without boiling! PCR Oi without boiling! Sample Oi l B experiment mirror reflection no boiling of aqueous solutions at 240 °C for more than 30 min!!! limited by thermal decomposition of surrounding oil y p g temperature x exposure time = applied energy 64
resistance against: - dryness y - toxic substances - other aggressive substances substances - aging - heat: dry: 150 °C ca. 1 h boiling: ca 5 h boiling: ca. 5 h electron microscope cross section of a spore of Bacillus electron microscope cross-section of a spore of Bacillus subtilis, showing the cortex and coat layers surrounding the core (dark central area). spore is 1.2 µm across. (Picture: S. Pankratz, Berkeley University of California) 65
p o s itiv e c o n tro l n e g a tiv e c o n tro l 1 0 0 1 0 tensity s p o re s o lu tio n s p o re s a fte r p re tre a tm e n t s p o re s a fte r s u p e rh e a tin g 1 0 -1 1 0 scence int 1 0 -2 1 0 Fluore 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 1 0 C yc le N u m b e r 68
bi t f l l Cellular level Cells are made up of molecules. 1 2 Cardiovascular system Atoms combine to form molecules. Tissue level Smooth muscle tissue 3 system Tissues consist of similar types of cells. Blood vessel (organ) Heart Blood vessels Connective tissue Smooth muscle tissue Organ level Epithelial tissue 4 Organ level Organs are made up of different types of tissues. Organ system level Organism level 4 5 6 g y Organ systems consist of different organs that work together closely. Organism level The human organism is made up of many organ systems. 6
and B. A. Parviz,in Evolvable Hardware 2004, Seattle, WA, 2004 Y H Jhang et al Organic Electronics Y.-H. Jhang et al., Organic Electronics, 13(10), pp. 1865-1872, 2012 K. Hosokawa, I. Shimoyama, and H. Miura, S & A t t A 57 117 125 1996 T. L. Breen et al., Science, 284, pp. 948-951, Sensors & Actuators A, 57, pp. 117-125, 1996 1999
5, pp. 1147, 2008 S A St th d B A P i PNAS 103(38) C. Lin, Y. Liu, and H. Yan, biochemistry, 48(8), pp. 1663-1674, 2009 S. A. Stauth and B. A. Parviz, PNAS, 103(38), pp. 13922-13927, 2006
asymmetric pattern by logical sequence • morphology-based assembly (non chemical functionalization) ) • capillary force as driving force • tripods as building blocks • tripods as building blocks • assembly at fluidic interface
decreased P. Singh et al., Soft Matter, 2010, 6, 4310-4325 As approaching each other, the contact angle is decreased and laterally attractive capillary force is increased
The dimension of tripods: L 500 μm Material Densit (g/cm3) Yo ng’s mod l s(GPa) • The dimension of tripods: L~ 500 μm Material Density (g/cm3) Young’s modulus(GPa) Silicon 2.33 130-188 SU-8 1.19 4.02 PDMS 0.965 0.0018 Polyimide 1.43 3.2
as releasing Fabrication Procedure of SU-8 Tripods 1. Omnicoat is used as releasing agent of SU-8 microstructure. 2. The stress of the structure should Coating omnicoat and SU-8 2050 on the wafer be minimized (RT curing, no sudden thermal-process) 3 Th t th th t i d 3. The way to gather the tripods without stacking each other is necessary Curing at RT and patterning necessary patterning Filtration for obtaining SU-8 tripods Releasing the tripods by dipping in the Remover PG
sample 3. Release of tripods from the wafer 4. Placement of the filter paper on the filter 5. Configuration of the filtration system with vacuum pump 6. Filtration 7. Washing with D.I. water 8. Vacuum- drying of the 9. Observation with microscope 10. The petridish with floating tripod thoroughly filter paper elements
Elimination of local Elimination of local Elimination of local Elimination of local minimum minimum A Elimination of local Elimination of local - - Elimination of local Elimination of local minimum minimum - - Round tip for Round tip for p p minimizing the minimizing the interacting area interacting area i i i i i i - - Sliding gradient Sliding gradient B
The attractive force is not strong enough to make them assembled because them assembled because the smaller size leads to smaller bond number and interfacial deformation
manufacturing ill i i d i l • still curiosity driven, very early stage • concepts for selective hierarchical • concepts for selective hierarchical assembly needed y
Neuzil, PhD Matthias Altmeyer PhD Matthias Altmeyer, PhD Eric Castro, PhD Adam Pribylka V Al id In Korea: Vanessa Almeida Per Arvid Loethman Seung Jae Lee Tae Song Kim, KIST Seoul, Korea Seungwon Jung KIST Seoul Korea Mi Jang Himani Sharma Jukyung Park Seungwon Jung , KIST Seoul, Korea Min Cheol Park , KIST Seoul, Korea Pavithra Sukumar , KIST Seoul, Korea Christian Ahrberg Tim Mehlhorn Camila Madeira Campos Ca a ade a Ca pos Marc Pichel