Diamond micro system for bio-chemistry

Ž .Diamond and Related Materials 10 2001 722�730

Diamond micro system for bio-chemistry

M. Adamschika,�, M. Hinzc, C. Maier b, P. Schmida, H. Seliger c, E.P. Hoferb,E. Kohna

aDepartment of Electron De�ices and Circuits, Uni�ersity of Ulm, D-89081 Ulm, GermanybDepartment of Measurement Control and Microtechnology, Uni�ersity of Ulm, Control and Microtechnology, D-89081 Ulm, Germany

cDepartment of Polymers, Uni�ersity of Ulm, D-89081 Ulm, Germany

Abstract

This work illustrates the potential of diamond micro system technologies progressively developed in the last years for anapplication in the bio-chemical field. A diamond micro reactor system based on a novel integration concept is presented and therole of diamond in this generic system is described. It consists of reaction chambers with removable bottom and integrated microdosage elements allowing the ejection and mixture of two different fluids onto the removable bottom substrate. As an example,this system is used in a novel DNA-synthesis cycle. In this application the diamond micro reactor system combined with aspecifically designed chemistry for the DNA-synthesis enables the parallel production of DNA-chain-clusters with individual

Ž .sequence arranged in an array DNA-Chip . � 2001 Elsevier Science B.V. All rights reserved.

Keywords: Diamond micro system; Bio-chemistry; DNA; Diamond MEMS; Diamond actuators

1. Introduction

Many diamond-based sensor and actuator structures� � � �like piezoresistive- 1,2 , pressure- 3,4 , acceleration-

� � � � � �5 , temperature- 6,7 , UV-sensors 8 , micro switches� �9,10 and various micro electromechanical systemŽ . � �MEMS applications 11�13 have been reported pre-viously. Beyond these applications and the application

� �as electrochemical electrode 14�17 in the presentwork the potential of diamond for devices in the newfield of bio-chemistry and nano-chemistry shall be de-monstrated. The role of diamond in a generic chemical

� �micro reactor system 19 will be described. Chemicalmicro reactors have emerged as an essential part of all

� �bio-chemical synthesis and analysis systems 20�22 .

� Corresponding author. University of Ulm, Albert-Einstein-Allee45, D-89081 Ulm, Germany. Tel.: �49-731-502-6179; fax: �49-731-502-6155.

Ž .E-mail address: [email protected] M. Adamschik .

The system presented here consists of three main partsŽ .Fig. 1 :

1. an overlay carrier for electrical and liquid supply;2. a micro dosage unit based on the bubble jet princi-

ple combined with an integrated array of reactionchambers with open bottom; and

3. a removable substrate representing the bottom ofthe reaction chamber array.

Integrated into the micro dosage unit are individu-ally controllable diamond bubble-jet elements for pre-cise injection of two different fluids into the reactionchambers. The diamond bubble-jet element has in

� �essence already been published previously 5,18,23�25and is shown in Fig. 2. This element combines highrobustness, good chemical inertness and simple tech-nology, thus serving as a reliable work horse for inte-gration into such a system.

The bubble-jet element had already been character-

0925-9635�01�$ - see front matter � 2001 Elsevier Science B.V. All rights reserved.Ž .PII: S 0 9 2 5 - 9 6 3 5 0 0 0 0 6 1 4 - 2

( )M. Adamschik et al. � Diamond and Related Materials 10 2001 722�730 723

Fig. 1. Schematic cross-section of micro reactor system.

ized extensively, showing its outstanding properties� �27,28 . Due to the high hardness, high mechanicalstrength and chemical inertness no passivation layersare necessary on top of the diamond heater element toprevent cavitation damages or chemical attack of theheater surface resulting in high reliability, low thermalinduced stresses, small heat losses, and a simple tech-nology. The low specific heat capacity allows fast tem-perature changes from room temperature up to the

Ž � �.spinodalean limit 312�C for water 24 necessary forproper overheating and bubble nucleation of the fluids.The good electrical isolating properties of undopeddiamond combined with the high thermal conductivity

� �allows electrically insulating layers 29 on top of theheater surface to prevent leakage currents betweenindividual heaters during the ejection of acidic or basicsolutions. From lifetime tests over 108 nucleation cy-cles could be extracted without deterioration showingthat the heater element itself is not limiting the lifetime� �25 . Due to the material properties the diamondheaters are able to withstand power densities up to 30

2 � �GW�m 25 being 10 times that of the nucleationpower density in a normal operation. Fig. 3 shows anexample of the electrical power applied onto a 60�60-�m heater element vs. minimum heating time for nu-cleation using a water covered heater element. Herethe maximum power of 30 GW�m2 has been applied,resulting in an ultra-fast sub-microsecond nucleationtime. Fig. 4 shows the time for damage for this ex-tremely high power level, which is approximately fourtimes of that necessary for nucleation.

The new integrated diamond micro reactor systemdiscussed in the following contains two bubble-jet ele-ments in a single reaction chamber with a heater area

Ž .of 30�30 �m to overheat the liquids Fig. 5 . Thereaction chambers are arranged as an array. The microdosage unit is bonded into an overlay carrier, whichcontains the liquid and electrical connections. The openbottom of the reaction chamber array can be pressed

Fig. 2. Diamond bubble-jet ejector element.

onto the surface of a planar or patterned reactionsubstrate, which can be removed for inspection afterthe chemical reaction took place. The amount of ejectedliquid can be adjusted very precisely by sequentiallydriving the heater elements, resulting in a digital in-

� �crease by 30-pl increments per drop 24 . Thus, thesystem enables tight control of chemical exotherm orendotherm reactions, mixing, etc. Due to the chemicalinertness, the parallel arrangement of the reactionchambers, the selectively addressable heater elementsand the precisely adjustable volumes of ejected liquids,this diamond chip represents a generic building blockfor nano-chemical systems.

As a first example the synthesis of oligonucleotidesŽ .oligonucleotide�part of a DNA-chain, see Fig. 9bwill be presented and discussed. The system allows fastand parallel fabrication of oligonucleotides with indi-

Ž .vidual sequences ‘custom design’ on the surface of areaction substrate by combining a specially designed

� �chemistry 26 . Due to the aggressive nature of thechemistry all major parts of the system need to bechemically inert.

2. Technology

The heart of the system is the micro dosage unitŽ .Fig. 1, part II consisting of an array of open bottomreaction chambers with integrated bubble-jet injectors.It is fabricated from two parts as illustrated in Fig. 5a,b

� �Fig. 3. Applied electrical heating power vs. nucleation time 25 .

( )M. Adamschik et al. � Diamond and Related Materials 10 2001 722�730724

Fig. 4. Applied electrical heating power vs. time until destruction� �25 .

using two different diamond-on-Si wafers. The assem-Ž .bled part part 1 and 2 in Fig. 5 is then mounted into

the fluidic and electrical supply carrier.Each micro reaction chamber contains two ‘bubble-

jet’ injector elements as indicated above, based onŽ .highly doped diamond micro heater elements Fig. 5a .

The diamond heater elements are grown by microwaveplasma CVD onto a thermal insulation layer and aredoped by boron. After the growth step dry etching wasused for patterning.

For the supply and the distribution of the reactionfluids on this part a photosensitive and chemical resis-tant polyimide capillary wall system was used, becausethis part of the device is not thermally stressed.

The second part consists of the diamond nozzle plateŽ .and reaction chambers Fig. 5b . The rectangular reac-

tion chamber geometry was formed by anisotropic sili-con etching using KOH. In the etching process dia-mond again offers the advantage of a selective etchstop. A 5-�m thick CVD-diamond film was grown byPECVD and holes with a diameter of 30 �m wereetched by dry etching. In the last step the nozzle plate� reaction chamber part is bonded onto the top of thecapillary wall system of part 1 forming a leak-tightmicrofluidic system. To connect the micro fluidic capil-lary system with conventional tubes an overlay carrierwas fabricated into which the micro reaction chip was

bonded. It contains an integrated fluidic system, fluidicconnectors and electrical connectors. Fig. 5c representsa schematic view of a single reaction chamber of thecomplete array.

Fig. 6a shows part 1 of the device and a detailed viewof one heater element. Fig. 7 shows part 2, the nozzleplate with integrated reaction chambers and a detailedSEM micrograph of a single nozzle. Anisotropic andsmooth sidewalls can be seen, preventing vortexes dur-ing drop ejection. Fig. 8a shows a device with 10reaction chambers in a one-dimensional array afterchip bonding of part 1 and 2. Fig. 8b depicts a top viewinto a single reaction chamber showing the nozzles, themetallization and the diamond heater elements throughthe transparent CVD-diamond nozzle plate. The com-pletely assembled system with the high-grade steel car-rier and its electrical connections can be seen in Fig.8c.

3. Application

As the first application the synthesis of oligonu-cleotides, which are a segment of a DNA-chain, isdiscussed. Such a synthesis is carried out in a cycle offour steps. The synthesis is supposed to be controlledindividually on a large number of spots. This individualcontrol for each spot is performed by the diamondmicro reactor system.

Individually addressable ejector elements in eachreaction chamber allow the fabrication of individuallysequenced oligonucleotides on practically every ap-propriately functionalized reaction substrate surfaceŽ .silicon, polypropylene, glass, etc. . Such oligonu-cleotides which are anchored on the reaction substrate,confined to small spots and arranged as an array arealso called ‘DNA-chips’. DNA-chips are presently usedin the development of new drugs, the evaluation ofgene functions, the diagnostics of diseases and in othermedical and biological applications. The fabrication ofDNA-chips is currently done either by a process similar

� �to photolithography 30,31 or by anchoring prefabri-cated DNA or oligonucleotides on a solid substrate,

Fig. 5. Technology.


Ž .Fig. 6. a Array of 10�12 heaters, metallization; capillary wallŽ . Ž .system SEM micrograph ; b enlarged part of one micro heater.

� �which may be polypropylene 32 , etc. Both methodsare relatively inflexible in respect to custom design.

To illustrate the details involved, in the following themain steps of the oligonucleotide synthesis cycle will beshortly described.

4. Oligonucleotide synthesis

DNA is a linear polymer consisting of a sugar�phos-phate backbone and four different bases attached to

Ž . Ž .the sugar moieties Fig. 9a . The succession sequenceof the bases encodes the information.

ŽSynthesis of oligonucleotides short parts of DNA.chain, see Fig. 9b is done by successive addition of

Žsugar�phosphate�base units adenine, guanine, cyto-.sine or tymine to a growing oligonucleotide chain

anchored on a solid support.To increase the chain by one base unit a synthesis

cycle with the following most important synthesis stepsŽ .has to be carried out Fig. 10 :

1. Deprotection and neutralization.Ž .2. Coupling of one base .

These two steps will be discussed in more detail inthe following. The oligonucleotide chain is madechemically inaccessible by a temporary protection groupŽ .Fig. 9b, Fig. 11a . This group is removed by an acid

Ž .Fig. 7. a Nozzle plate � reaction chamber unit, column of 10Ž .reaction chambers and 10�2 nozzles; b SEM micrograph of noz-

zle.

Ž . Ž .Fig. 8. a Micro reaction device; b top view into one reactionŽ .chamber; c complete chip with electrical leads for addressing the

heaters.

Ž .Fig. 11b followed by a neutralization with a basicŽ .solution Fig. 11c . Thus, chemically reactive functio-

nality is formed at the end of the oligonucleotide chain.To this functional site the next sugar�phosphate�base

Ž .unit is coupled in the next step Fig. 11d . To performthe coupling in the desired manner, the sugar�phos-phate�base unit has to carry the temporary protectiongroup to prevent reaction with itself and to preventmore than one coupling. To increase the oligonu-

Ž . Ž . Ž .cleotide by one further base Fig. 11e step a and b


Ž . Ž .Fig. 9. a DNA-chain; b oligonucleotide.

Žhave to be repeated again together with other additio-.nal steps .

The step, where the spots on the reaction substrateare individually addressed, are the deprotection and

Ž .neutralization step Fig. 11b,c . This is performed bythe diamond micro reactor system, which provides and

Žinjects the necessary aggressive chemicals acid and. Ž .base . A reaction synthesis substrate made of po-

lypropylene represents the bottom of the reactionchamber and contains the anchored oligonucleotides.

During the deprotection step the micro dosage unitand the reaction substrate are pressed together to formthe chamber for the confined fluid and are disassem-bled after the reaction took place. The neutralizationŽ .Fig. 11c is necessary to prevent unwanted deprotec-tion due to residual acid on the reaction substrateduring the rinse in the sugar�phosphate�base solutionŽ . ŽFig. 11d which contains one sugar�base pair either

.adenine, guanine, thiamine or cytosine . This means

Fig. 10. Synthesis cycle.

that after neutralization the micro dosage unit is re-moved from the reaction substrate and the substrate is

Ž .rinsed in a sugar�phosphate�base solution Fig. 11dto increase the deprotected oligonucleotides by onebase.

5. Performance of the technological building blocks ofthe micro dosage unit

To verify the functionality of the micro dosage unitwe first visualized the bubble nucleation of the micro

Ž .heater elements area �30�30 �m in the ‘openŽ .mode’ without capillary wall system and nozzle plate

applying the pseudo-cinematographic visualizationmethod.

Accordingly in this investigation the measurementhas been performed with the reaction fluids used in thesynthesis cycle. Here collidine, a basic solution, and

Ž .Fig. 11. Synthesis with diamond micro reaction system: a oligonu-Ž .cleotide before synthesis cycle with three bases; b acid injection and

Ž . Ž .removal of protecting group; c neutralization with base; d cou-Ž .pling of one base by rinsing in nucleotide solution; e oligonu-

cleotide after synthesis cycle with four bases.


Fig. 12. Pseudo cinematographic recording of nucleation in ‘open mode’ of collidine: P �2.3 W, t �5 �s, f �3 kHz.el pulse repetion

Fig. 13. Pseudo cinematographic recording of nucleation in ‘open mode’ of TCA: P �2.3 W, t �5 �s, f �3 kHz.el pulse repetion

Ž .trichloro acetic acid TCA , both solved in an organicsolution are applied for the deprotection and neutral-ization step.

In the open mode all relevant properties like dy-namic bubble nucleation, the necessary electrical powerfor nucleation, chemical or mechanical attack of theheater surface or the metallization can be investigatedand extracted. Nucleation with water and ink have

� �already been published previously 18 .Fig. 12 shows the bubble nucleation of collidine. Due

to the high temperature stability of diamond the powerdensity of 2.6 GW�m2 could be applied on 30�30 �mheater elements far below thermal breakdown resultingin a very fast nucleation time of approximately 1.5 �s.The maximum nucleation frequency was limited by theaverage thermal heating of the substrate to approxi-mately 40 kHz. No mechanical or chemical damage ofthe diamond heater surface or the metallization couldbe detected showing that indeed no passivation layer isnecessary on top of the diamond heater.

Fig. 13 shows a comparable experiment with TCA.

Here again, no corrosion or other chemical or mechan-ical damage of the heater element and metallizationcould be observed.

After approximately 3 �s the bubble collapse beginsfor both liquids.

To measure and visualize the drop ejection for aclosed ejection system a real time cinematographicrecording set-up has been used. The reaction fluid inthis case was an organic solvent resulting in dropejections as shown in Fig. 14.

The liquid amount per drop can be estimated toapproximately 30 pl allowing very precise control of theejected liquid and thus mixing ratios.

To prove the functionality of the system and toinvestigate the drop impact and the mixing behavior oftwo drops onto the reaction substrate a dual dropejection experiment onto a transparent substrate hasbeen performed. A pulse sequence has been appliedonto the two heater elements resulting in a successivelyincreasing amount of liquid onto the reaction substrateas shown in Fig. 15. For the first 10 drops the drops still

� �Fig. 14. Real time cinematographic recording of drop ejection; medium: organic solvent 19 .


Fig. 15. Dual drop impact onto a transparent reaction substrate.

remain separated flowing together after approximately20 drops corresponding to a volume of approximately 1nl.

This experiment has been successfully performedwith water, 1-2-propanol, collidine and TCA, however,due to the best optical contrast water was used in theexperiment shown in Fig. 15. In the oligonucleotidesynthesis the reaction fluids show different wettingbehavior on the surface due to different surface ten-sions. This is one reason, why in this case polypropy-

Ž .lene not transparent has been selected. Good mixingof the fluids and good confinement of the fluids ontothe reaction substrate could be observed.

To validate the chemistry in the micro system and toinvestigate sealing between the bottom of the reactionchambers and the reaction substrate, a micro fluidiccapillary system in the geometry of a meander insteadof the diamond micro reactor system with square reac-tion chambers has been pressed onto a planar po-lypropylene substrate. The meander was connected withexternal tubes and successively provided with all neces-sary fluids for the chemical synthesis of oligonu-cleotides.

Sealing could be obtained by proper surface termina-tion of both surfaces and exploiting capillary effects.Fig. 16 shows the result of the synthesis. Good con-finement even without substrate patterning is seen.

The area of synthesized oligonucleotides can beidentified after attaching a color marker to the oligonu-cleotides.

6. Conclusion

A novel versatile diamond micro reaction system for

chemical reactions has been presented. The systemconsists of a micro dosage unit based on the bubble-jetprinciple, integrated reaction chambers with open bot-tom, a reaction substrate and an overlay carrier forliquid and electrical connections. The system is chemi-cally inert due to the application of CVD-diamondfilms on decisive locations like the micro heater ele-ments, the nozzle plate and the reaction chamber sur-face.

Each reaction chamber contains two ejection ele-ments supplied by two different fluids allowing preciseinjection and mixing of the chemicals. After the chemi-cal reaction the synthesis substrate may be taken offfor inspection. The reaction chambers are arranged inan array and each heater element is selectively address-able.

The performance of the system has been investigatedby visualization of the bubble nucleation and dropejection of an organic solvent, acidic and basic solution.Power densities up to 30 GW�m2 resulting in sub-mi-crosecond nucleation times could be applied to thediamond heater elements without thermal breakdown.No chemical or mechanical attack on the heater sur-face could be observed.

As an example, the synthesis of oligonucleotidesŽ .part of a DNA-chain has been discussed. The dia-mond micro reaction system allows parallel and highlyflexible fabrication of ‘custom-design’ oligonucleotide

Ž .arrays DNA-chips by selective deprotection ofoligonucleotides anchored on a reaction substrate. Inthe future it seems feasible to still complement thesystem with sensors to monitor and control the reac-tion. Such a sensor may be the recently proposed

� �diamond based pH-sensor 33 , the ion-sensitive ISFET

Fig. 16. Polypropylene substrate with synthesized oligonucleotids.


� �34 or electrodes for cyclic electro voltammetry makingthe system a true ‘lab-on-chip’.

Acknowledgements

We thank A. Kaiser and Y. Men of the University ofUlm for the support at the device fabrication and themeasurements of the bubble nucleation in the ‘openmode’. We would also like to thank A. Hildebrandt fordeveloping electronic components for driving the dia-mond micro heaters. We acknowledge the cooperationwith P. Gluche and A. Floter for providing diamond-¨on-Si substrates. This work is supported by the GermanBMBF and DECHEMA under the classification num-ber 03D00693.

References

� �1 M. Werner et al., Review on Diamond Based PiezoresistiveSensors, ISIE’98, Proceedings, pp. 147�152.

� �2 I. Taher et al., Piezoresistive microsensors using p-type CVDŽ .diamond films, Sensors Actuators A 45 1994 35�43.

� �3 J.L. Davidson et al., CVD Diamond for Components andEmitters, 7th International Conference on New Diamond Sci-ence and Technology, Book of Abstracts, No. 16.1, City Univer-sity of Hong Kong, Hong Kong, 23�28 July 2000.

� �4 D.R. Wur, J.L. Davidson, W.P. Kang, D.L. Kinser, Polycrys-Ž .talline diamond pressure sensor, J. Micromech. Syst. 4 1995

34�41.� �5 E. Kohn, P. Gluche, M. Adamschik, Diamond MEMS � a new

Ž .emerging technology, Diamond Relat. Mater. 8 1999 934�940.� �6 G.S. Yang et al., Single-structure heater and temperature sen-

sor using a p-type polycrystalline diamond resistor, IEEE Elec-Ž .tron Dev. Lett. 17 1996 250�252.

� �7 M. Aslam, G.S. Yang, A. Masood, Boron-doped vapor-de-posited diamond temperature microsensors, Sensors Actuators

Ž .A 45 1994 131�137.� �8 R.D. McKeag, R.B. Jackman, Diamond UV photodetectors:

sensitivity and speed for visible blind applications, DiamondŽ .Relat. Mater. 7 1998 513�518.

� �9 M. Adamschik, S. Ertl, P. Schmid, E. Kohn, ElectrostaticDiamond Micro Switch, Transducers ’99, 10th Int. Conf. onSolid-State Sensors and Actuators, Digest of Technical Papers,vol. 2, 1999, pp. 1284�1287.

� �10 S. Ertl, M. Adamschik, P. Schmid, P. Gluche, A. Floter, E.¨Kohn, Surface Micromachined Microswitch, Proc. of 10th Int.Conf. on Diamond, Diamond-Like Materials, Carbon Nan-otubes, Nitrides&Silicon Carbide, Diamond 1999, PragueHilton Atrium, Czech Republic, 12�17 September 1999, pp.970�974.

� �11 T. Shibata, Y. Kitamoto, K. Unno, E. Makino, Micromachiningof diamond film MEMS applications, J. Microelectromech.

Ž . Ž .Syst. 9 1 2000 47�51.� �12 E. Kohn, M. Adamschik, P. Schmid, S. Ertl, A. Floter, Dia-¨

mond Electro-Mechanical Micro Devices � Technology andPerformance, 7th International Conference on New DiamondScience and Technology, Book of Abstracts, City University ofHong Kong, Hong Kong, 23�28 July 2000, p. 3

� �13 P. Schmid, M. Adamschik, S. Ertl, P. Gluche, E. Kohn, Model-ing approach for CVD-Diamond based mechanical structures,

2nd Internat. Conf. on Modeling and Simulation of Microsys-tems, San Juan, April 1999, Proc. 636�639.

� �14 J.C. Angus, H.B. Martin, U. Landau, Y.E. Evstefeeva, B. Miller,N. Vinokur, Conducting diamond electrodes: applications inelectrochemistry, New Diamond Front. Carbon Technol. 9Ž .1999 175�187.

� �15 N. Vinokur, B. Miller, Y. Avyigal, R. Kalish, Electrochemicalbehavior of boron-doped diamond electrodes, J. Electrochem.

Ž . Ž .Soc. 143 10 1996 238�240.� �16 J.S. Foord, C.H. Goeting, F. Marken, R.G. Compton, K. Holt,

Electrochemical Studies at Diamond Interfaces, The PhysicsCongress, Brighton, UK, Abstract Book, DIAM. 7.3, 27�28March 2000.

� �17 A. Perret, Ch. Comninellis, D. Gandini, W. Haenni, P. Nieder-mann, N. Skinner, Diamond Electrodes and Microelectrodes,192nd and 48th Annual Joint Int. Meeting, Electrochemical Soc.and Int. Soc. of Electrochemistry, Paris, 31 August�5 Septem-ber 1997, Abstract No. 1689.

� �18 P. Gluche, R. Leuner, A. Vescan et al., Actuator � sensortechnology on electronic grade diamond films, Microsyst. Tech-

Ž .nol. 5 1998 38�43.� �19 M. Adamschik, P. Schmid, C. Maier et al., Micro Dosage

Controlled Micro Reactor Based on CVD-Diamond, 4th Int.Conf. on Microreaction Technology, Atlanta, GA, Topical Con-ference Proceedings, 5�9 March 2000, pp. 114�120.

� �20 H. Loewe, W. Ehrfeld, V. Hessel, Th. Richter, J. Schiewe,Micromixing Technology, 4th Int. Conf. On MicroreactionTechnology, AlChE Spring National Meeting, Atlanta, GA,Topical Conference Proceedings, 5�9 March 2000, pp. 31�47.

� �21 D.J. Quiram, K.F. Jensen, M.A. Schmidt et al., Development ofa Turnkey Multiple Microreactor Test Station, 4th Int. Conf.On Microreaction Technology, AlChE Spring National Meet-ing, Atlanta, GA, Topical Conference Proceedings, 5�9 March2000, pp. 55�61.

� �22 R.J. Jackman, T.M. Floyd, R. Ghodssi, M.A. Schmidt, K.F.Jensen, Integrated Microchemical Reactors Fabricated by bothConventional and Unconventional Techniques, 4th Int. Conf.On Microreaction Technology, AlChE Spring National Meet-ing, Atlanta, GA, Topical Conference Proceedings, 5�9 March2000, pp. 62�67.

� �23 P. Gluche, R. Leuner, C. Rembe, A. aus der Wiesche, E.P.Hofer, E. Kohn, Novel Thermal Microactuator Based onCVD-Diamond Films, Int. Electron Devices Meeting, SanFrancisco, CA, Technical Digest, 1998, pp. 483�486.

� �24 E.P Hofer, C. Maier, C. Rembe et al., A New Diamond MicroHeater for Inkjet Printheads, International Conference onDigital Printing Technologies, IS&Ts NIP 14, 1998, p. 72.

� �25 E.P Hofer, C. Maier, C. Rembe, S. aus der Wiesche, E. Kohn,M. Adamschik, Realistic Performance Tests of a DiamondPrinthead by High Speed Visualization, International Confer-ence on Digital Printing Technologies, IS&Ts NIP 15, 1999,pp. 66�69.

� � Ž .26 S.L. Beaucage, M.H. Caruthers, Tetrahedron Lett. 24 19811859.

� �27 M. Werner, S. Klose, F. Szucs et al., High temperature Young’s¨modulus of polycrystalline diamond, Diamond and Relat. Mater.Ž .6 1997 344�347.

� �28 P. Gluche, M. Adamschik, A. Vescan et al., Application ofŽ .highly oriented, planar diamond HOD films of high mechani-

cal strength in sensor technologies, Diamond Relat. Mater. 7Ž .1998 779�783.

� �29 A. Floter, H. Guttler, G. Schulz et al., Properties of Thin¨ ¨Highly Oriented Diamond Films and Their Use in ElectronicApplications; ISDED-2, 1998, Proc. 47�51.


� �30 A.C. Pease, D. Solas, E.J. Sullivan, M.T. Cronin, C.P. Holmes,Ž .S.P.A. Fodor, Proc. Natl. Acad. Sci. U.S.A. 91 1994 5022.

� � Ž .31 M.C. Pirrung, G. McGall, J. Org. Chem. 63 1998 241.� �32 Nature Genetics, 21, No. 1, Supplement, 1999.� �33 A. Denisenko, A. Aleksov, E. Kohn, pH Sensor Based on

Surface Boron Doped Diamond, Diamond 2000, paper 10.4.

� �34 K. Kitatani, N. Seto, T. Ogawa, H. Kawarada, Ion SensitiveField Effect Transistor on Hydrogen-terminated PolycrystallineDiamond Surfaces, 10th European Conference on Diamond,Diamond-Like Materials, Carbon Nanotubes, Nitrides & Sili-con Carbide, Abstract Book, No. 4.4, Prague, Czech Republic,12�17 September 1999.

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Diamond micro system for bio-chemistry