Laboratoire d’Informatique, deRobotique et de Microelectronique de

Montpellier

Summer Internship 2019

Field-effect transistor basedbiosensing of glucose using carbonnanotubes and monolayer MoS2

Nathan Ullberg

supervised by

Aida Todri-Sanial

examined by

Carla Puglia

November 24, 2019

Contents

Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.1 Field-effect transistors (FET) . . . . . . . . . . . . . . . . . . . . 52.1.1 Brief history and overview . . . . . . . . . . . . . . . . . 52.1.2 Characteristic curves . . . . . . . . . . . . . . . . . . . . 62.1.3 Transconductance, threshold voltage, and ON/OFF ratio 7

2.2 Field-effect biosensing (FEB) . . . . . . . . . . . . . . . . . . . . 82.3 CNT-FETs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2.3.1 Dry CNT transistors . . . . . . . . . . . . . . . . . . . . 102.3.2 Functionalization for glucose sensing . . . . . . . . . . . 11

2.4 MoS2-FETs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122.4.1 Dry MoS2 transistors . . . . . . . . . . . . . . . . . . . . 122.4.2 Biosensing applications . . . . . . . . . . . . . . . . . . . 14

2.5 Graphene-FETs . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

3.1 CNT devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173.1.1 Fabrication . . . . . . . . . . . . . . . . . . . . . . . . . 173.1.2 SEM and AFM characterization . . . . . . . . . . . . . . 193.1.3 Electrical characterization . . . . . . . . . . . . . . . . . 22

3.2 MoS2 devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243.2.1 Fabrication . . . . . . . . . . . . . . . . . . . . . . . . . 243.2.2 Electrical characterization . . . . . . . . . . . . . . . . . 25

4 Conclusions and next steps . . . . . . . . . . . . . . . . . . . . . . . . . . 26Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32Appendix I – Acronyms . . . . . . . . . . . . . . . . . . . . . . . . . . . 33Appendix II – Procedure Guides . . . . . . . . . . . . . . . . . . . . . . . 34

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Abstract

As part of the EU SmartVista project to develop a multi-modal wearable sensor for healthdiagnostics, field-effect transistor (FET) based biosensors were explored, with glucose asthe analyte, and carbon nanotubes (CNTs) or monolayer MoS2 as the semiconductingsensing layer. Numerous arrays of CNT-FETs and MoS2-FETs were fabricated by pho-tolithographic methods and packaged as integrated circuits. Functionalization of thesensing layer using linkers and enzymes was performed, and the samples were character-ized by atomic force microscopy, scanning electron microscopy, optical microscopy, andelectrical measurements. ON/OFF ratios of 102 p-type and < 102 n-type were acheived,respectively, and the work helped survey the viability of realizing such sensors in a wear-able device.

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Acknowledgements

Firstly, I would like to thank my supervisor Dr Aida Todri-Sanial. She has been verysupportive in ensuring that my internship experience is something meaningful both formyself and for the group. She has guided me and has helped sharpen my skills as ascientist.

I have been working closely with post-doc Dr Abhishek Dahiya. His expertise, input,and patience have been invaluable to my internship experience. I also received much helpfrom Dr Benoıt Charlot whose lab space and resources I was welcome to use, in additionto his advice, guidance, and help. I also thank post-doc Dr Marwa Dhifallah who helpedme integrate into the environment and to understand the project, and Thierry Gil whoprovided help regarding electronics aspects.

This internship was funded by the laboratory through my supervisor, as well as by a Eu-ropean Union (EU) Erasmus+ Student Mobility of Placement (SMP) grant (also knownas a Traineeship). I therefore extend my thanks to the providers of these funds, whichenabled me to focus on my work and to be less burdened by financial difficulties. Iam also grateful for EU Horizon 2020, the eight Framework Program (FP8) since 1984supporting research in the European Research Area, which is funding the SmartVistaproject.1,2

For this summer project I am also receiving 15 ECTS course credits, which contribute tomy current Master’s in Materials Physics program at Uppsala University. I am grateful tothe program coordinator Professor Andreas Korn for his support and advice he has givenme regarding my choices. I am also grateful to my home institution advisor ProfessorCarla Puglia; she evaluated my report and has been advising me in general regarding myacademic choices.

Finally I would like to thank my parents, sister, and friends for all their support.

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1 Introduction

The objective of this summer internship was to contribute in research and developmentconcerning field-effect transistor (FET) based glucose sensing using carbon nanotubes(CNTs) and monolayer MoS2. This work is within the framework of the European UnionHorizon 20203 project known as Smart Autonomous Multi Modal Sensors for Vital SignsMonitoring (SmartVista).1,2

The SmartVista project was launched in January 2019, and is a 3-year-long contract fromthe EU to help reduce deaths due to cardiovascular diseases (CVD) by a multi-modalwearable sensor. A schematic of the different modules in the wearable are shown in Figure1.

Figure 1: Modules in the SmartVista wearable.

There are multiple partners from across Europe in this project working on the differentmodules. The partners include Tyndall National Institute (Ireland), University CollegeCork (Ireland), the French National Center for Scientific Research (CNRS) (France),NovoSense AB (Sweden), Fraunhofer – Research Institution for Microsystems and SolidState Technologies (EMFT) (Germany), and Analog Devices, Inc. (Ireland).1

The laboratory that I worked at is called The Montpellier Laboratory of Computer Sci-ence, Robotics, and Microelectronics (LIRMM) and is part of CNRS. The semiconduct-ing materials that were explored fall within a class of so-called 1D/2D materials, some ofwhich include carbon nanotubes, graphene, and transition metal dichalcogenides (TMDs)like MoS2. These kinds of materials have attracted a lot of attention in the last two tothree decades due to their various extraordinary and useful properties.4,5

For the internship the use of CNTs and monolayer MoS2 as the semiconducting chan-nel in the FET were explored for glucose sensing. Numerous arrays of CNT-FETs andMoS2-FETs were fabricated and characterized by electrical measurements, as well as byscanning electron microscopy (SEM), atomic force microscopy (AFM), and optical mi-croscopy. It should be noted that although the sensors were tested with different glucosemolarities to detect changes in FET current, such measurements were not successful be-cause the devices were shorted by an ionic current or damaged during functionalization.Therefore for this report the data discussed will be regarding the quality of the sensorsin “dry” conditions. The next section will be about the background, state of the art, and

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mechanism for these kinds of sensors, followed by the results and data that were obtained,and finally a conclusion and discussion of the next steps for realizing these sensors.

2 Background

2.1 Field-effect transistors (FET)

2.1.1 Brief history and overview

A transistor is a type of solid-state electronic device which conventionally is used in eitherswitching or amplification applications. The former can be used for logical operationsand therefore computing, while the latter is used for amplifying signals such as in amicrophone. Before transistors, there were thermionic valves, also known as triodes orvacuum tubes which were used in computer processors such as in the 1945 ENIAC—thefirst electronic general-purpose computer. Vacuum tubes were problematic for severalreasons however, such as that they consumed a lot of power and were not very stable.The solid-state transistor was superior, and was first fabricated at AT&T Bell Labs, NewJersey in 1947.6

The mechanism of a transistor is that it is a three-terminal device where a small inputcurrent or voltage controls a separate output current. The first 1947 transistor wasa current-controlled point-contact transistor, of bipolar type, meaning both electronsand holes flow in the output current. What soon followed in 1948 was the invention ofthe bipolar junction transistor (BJT) which also is current-controlled and uses a moreelegant junction approach of differently doped blocks of semiconductor connected byjunctions.

The first field-effect transistor was fabricated in 1953, and is a voltage-controlled transis-tor, where the electric field from the voltage causes charge to accumulate or deplete inthe semiconductor and hence controls the output current. (FETs are unipolar meaningeither electrons or holes flow in the channel but not both.) One way to think of such adevice is as a voltage-controlled variable resistor.6,7 This is shown in Figure 2.

There are many different types of FETs, but the most common is a metal oxide semi-conductor FET (MOSFET), which was first fabricated in 1959. (More broadly these arecalled insulated-gate FETs (IGFETs) since the gate may not always be a metal and thedielectric may not always be an oxide.) As mentioned, MOSFETs are unipolar and hencecan be either n-type (meaning electrons flow in the channel) or p-type (holes flow in thechannel). The modes of a FET are either enhancement-mode (where the field causescarriers to accumulate) or depletion-mode (where the field depletes the channel of carri-ers). By very-large-scale integration (VLSI) of either n-type or p-type MOSFETs on asingle chip (called NMOS and PMOS respectively), one can create a processor. Howeverthe most efficient approach is to use both, which is called complementary metal-oxide-semiconductor (CMOS) integration, which was invented in 1963. CMOS technology gaverise to the integrated circuit (IC), and this business helped give rise to the Silicon Valleybusiness culture, so-called since silicon is the most common semiconductor used in transis-tors. Some of the Silicon Valley companies that were involved in the early stages includeShockley Semiconductor Laboratory, Fairchild Semiconductor, and later Intel.6

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Figure 2: Basic circuits for a (current-controlled) NPN bipolar junction transistor (BJT)and a (voltage-controlled) NPN metal oxide semiconductor field-effect transistor (MOS-FET).

An n-type MOSFET is shown in Figure 3, and as can be seen the channel is p-dopedwhile the drain and source terminals are n-doped; hence the name “NPN” transistor.When a positive gate voltage is applied, the holes in the channel region are repelled whileelectrons are attracted from below, therefore the originally p-doped channel becomeseffectively n-doped! This is called inversion because the p becomes inverted to n. Thatis why this is an n-type transistor even though the channel is actually p-doped.7,8

Figure 3: Diagram of NPN MOSFET transistor.

2.1.2 Characteristic curves

There are various relevant quantities to consider when it comes to FETs. In particularthere are two current-voltage (IV ) curves which are of highest importance. The first iscalled transfer and is a sweep of the gate voltage Vg with the drain-source current Idbeing measured and the drain-source voltage Vds sometimes varied as a parameter; andthe second is called the output which is a sweep of Vds with Vg as a parameter.

In order to have a control and sturdy example of such sweeps, I measured the IV curvesfor a standard MOSFET, this one is called IRF540N, and the data is shown in Figure

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4. The data was obtained using an HP4156A Precision Semiconductor Parameter An-alyzer, which is a machine that can source voltage or current and measure the outputautomatically and is programmable.

Figure 4: Characteristic transfer and output curves for an IRF540N n-type MOSFET.

In the transfer sweep we see that there is a threshold voltage Vth involved for turningthe MOSFET to the ON-state. If the gate voltage is less than this, the channel will notconduct any electrons. And, in the output curve we see how if the device is more on, thenthe drain-source current is higher. Note that conventional current which is positive flowsfrom drain to source; this means that the source is a source of electrons, which makessense since this is an n-type transistor and so electrons flow in the channel. In a p-typeMOSFET it is the opposite; the conventional current flows from source to drain.

2.1.3 Transconductance, threshold voltage, and ON/OFF ratio

A quantity that is of critical importance is the transconductance (or transfer con-ductance) also known as mutual conductance and is denoted by gm. It has the unitsof conductance (inverse resistance or Ω−1), which is why the letter “g” is used, and takeson values usually on the order of milli-Siemens (mS). It is defined as the derivative of thetransfer curve:

gm ≡ ∂Ids∂Vgs

As can be seen, it is an indication of how much output (current) is produced for theinput (voltage) provided, and hence it is like the yield of the transistor. A plot of gm isshown in gray color in the left-most plot of Figure 5 for an IRF540N MOSFET, where themaximum value gm (max) is of particular interest, as indicated by the blue slope. And,the x-intercept is the voltage threshold Vth. Both of these quantities change as we varyVds, as shown in the right-most plot.

In general we also want to know what is called the ON-OFF ratio. This is basically aratio of the ON current (Vgs > Vth) and the OFF current (Vgs < Vth). To calculate this

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Figure 5: Calculating the transconductance gm and threshold voltage Vth from a transferIV curve. (In this case for a IRF540N MOSFET.)

it is often useful to do a log plot of the transfer curve as in Figure 6.

Figure 6: Log plot of the transfer curves for a IRF540N MOSFET, where the ON-OFFratio is calculated to be 106.

As can be seen in the Figure, we have 106 ratio which is very high and we can alreadysee how within just some tens of mV we can have a significant change in current byone million in this case. This already gives us an indication that this system exhibitsultra-high sensitivity, with just a few milli-volts or less we can have a significant in thesignal (Ids).

2.2 Field-effect biosensing (FEB)

FET-based biosensing, also known as field-effect biosensing (FEB),9,10 or sometimesBioFET, ChemFET, or ISFET (ion-sensitive FET) depending on the analyte and mech-anism in question, is an approach to sensing that makes use of a FET system that istailored for biosensing applications.11,12

The use of FETs in biosensing began in 1970 with the invention a NaCl ISFET sensor.12,13

FET biosensing as a discipline has continued to grow since then, with a wide variety of

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materials having been explored for the semiconducting channel. The concept behind the“FET to FEB” idea is illustrated in Figure 7.

On the left of the figure is a thin-film transistor (TFT) in a conventional setup wherean input gate voltage signal is provided. On the right, the surface of the channel hasbeen “functionalized” with receptors (shown as “Y”s) that are selective to the analyteof interest (shown as circles). The mechanism is that when an analyte binds to thereceptor it causes carriers in the channel to either accumulate or deplete, which changesthe conductance/resistance of the channel, and henceforth the transconductance. Thedegree to which the conductance changes depends on the concentration/molarity of theanalyte, and hence the system can be used as a sensor.

Figure 7: Concept of field-effect transistor based biosensor.

There are different variations of the system shown in Figure 7. The FEB shown isheld at a constant back-gate potential, however some devices do not employ a back-gatevoltage but rather a liquid-gate voltage. Others have both, or even none at all.14 Also,if selectivity of analyte is not a must, then one need not immobilize receptors to thesurface.15 Mere adsorption or other kinds of sorption can vary the conductance.

The potential of FET biosensing is very significant for a number of reasons. One ofthe main advantages is its compatibility with the CMOS process, meaning FEBs canbe integrated as a “system on a chip” (SoC) for electronic digital processing, and in aminiaturized fashion. The concept of such integration for biosensors has been termed the“internet of biology”.10

For the semiconductor channel, various different classes of materials have been explored,including: nanowires (NWs),16 organic semiconductors (OSCs),17–20 one-dimensional (1D)materials such as CNTs,21,22 and two-dimensional (2D) materials such as graphene23,24

and other transition metal dichalcogenide (TMD) monolayers like MoS2.25–27

Given such a wide array of options for channel material, and in addition dozens of differ-ent techniques for functionalization, there exist many different kinds of analytes whichcan be sensed, including: chemicals, pH, proteins, antibodies, DNA, and other com-plex molecules.14 The channel can also be sensitized by use of nanoparticles28–30 ornanopores.31–33

FEB devices provide selectivity, stability, ultra-high sensitivity, low power operation,label-free sensing, scalability, and notably can be fabricated on flexible substrates,34–37

which all are factors making FEBs compelling for wearable health monitoring technolo-gies, and hence are part of the focus of the SmartVista project.

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Regarding channel material, much of early research with FEBs focused on nanowires16,38,39

such as SiNWs,40,41 and on nanotubes like CNTs.21,22,42 However, fabricating suchnanowire and nanotube devices has proven challening in many regards such as in align-ment.43 Graphene has been a popular choice and has even reached the commercial levelwith foundry-fabricated modular graphene FET (GFET) chips available on the marketfor sensing a variety of analytes,10 however the use of graphene as the channel has thedrawback of it being a semimetal and thus leaking current. The most popular graphene-like alternative is the TMD monolayer MoS2,

15,44–47 which has a direct bandgap of 1.8eV.48,49

Research is still on-going and although the focus has been on high surface-to-volume-ratiomaterials for higher sensitivity, bulk technologies like FinFET and silicon-on-insulator(SOI) FET biosensors are also in the spotlight and may be promising especially since theyare less brittle; an aspect which is important for wearable health monitoring technology.50

In any case 1D/2D materials have not lost their appeal however, and within SmartVistathe intention is to make use of CNTs and MoS2 as the channel material.

2.3 CNT-FETs

2.3.1 Dry CNT transistors

Carbon nanotubes (CNTs) are made of carbon, and are basically graphene rolled upinto tubes. Hence their surface is a hexagonal network of sp2 bonded carbon atoms.Interatomic bonds are σ covalent and hence very strong, while from the remaining valenceelectron it forms a delocalized π-network. CNTs are either metallic or semiconducting,depending on how they are cut, which is called the chirality of the tube. This can bevisualized by the cited Wolfram Demonstrations Project.51 Furthermore, CNTs can begrown to be either single-walled (SWCNT) or multi-walled (MWCNT).52 In the internshipsingle-walled were used.

In general, when fabricating a CNT-FET, it will exhibite transistor p-type behavior. Thechannel will hence only be enhanced by a negative gate voltage, and depleted by a positiveone. An example of transfer curves from the literature are shown in Figure 9, and is froma 2009 CNT-FET gas sensor review paper.53 Note the sharp kink in the curve, whichis an indication of a good Schottky barrier between the semiconductor-CNT and metalcontact interface,7 as opposed to a more ohmic interface which would display more lineartendency at the “kink”-point and smoothen out that portion of the curve.

Under some conditions such as cryogenic, CNT-FETs can actually exhibit ambipolarbehavior as shown in Figure 9.54 This is usually not the case however.

The CNT-FET sensor we are interested in is for the case of glucose sensing application.In this case a liquid gate is used, and actually operating a liquid gate on a CNT-FETdisplays better sensitivity, as shown in Pujado’s 2012 Figure 10.54

Finally some typical output curves for a CNT-FET is shown in Figure 11.

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Figure 8: Example of CNT-FET transfer curves for the case of a gas sensor, where theeffect of exposure to gas on the curve are shown as well. From Bondavalli et al. 2005.53

Figure 9: Ambipolar behavior of a CNT-FET under special conditions, meaning eitherholes or electrons can be made to conduct across the channel. Usually CNT-FETs canonly accumulate holes by a gate-voltage.54

2.3.2 Functionalization for glucose sensing

Now that intrinsic CNT-FET characteristics have been discussed, I proceed to explainhow a CNT-FET is functionalized to serve the purpose of glucose sensor. The key isto immobilize glucose oxidase enzyme (GOx) molecules on the surface of CNTs, by helpof an intermediate linker called 1-pyrenebutanoic acid succinimidyl ester (Pbase). (SeeFigure 13 for a decomposition to constituent parts.) The idea of immobilizing moleculesby help of the intermediate linker Pbase was first introduced in 2001 by Chen et al.55 Theimmobilization of GOx specifically was introduced in 2003 by Besteman et al.42 Figure12 illustrates this and was modified from the Chen et al. 2001 paper.

The pyrene groups of the Pbase binds with van der Waals to the surface of the CNT. Thisis a non-covalent binding, it is relatively weak and is due to asymmetric distributions ofcharge (dipole moments) providing a net electrostatic force. It is ideal for this system thatit is non-covalent because that means that the electronic properties (which are describedby the band structure) of CNTs remain essentially the same. In other words, the CNTisn’t becoming like a new material/molecule by some strong binding of another moleculeto it. For the GOx, an amide bond is formed with the Pbase by replacing its succinimidyl

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Figure 10: CNT-FET linear transfer plot showing better sensitivity for liquid gate com-pared to back-gate.54

Figure 11: Typical output curves for a CNT-FET.22

group.

Now, regarding the actual mechanism involved for how the CNT channel receives an“effective gate voltage” as function of the analyte molarity, the diagram by Lee et al.2010 provides a useful picture,37 which I have modified in Figure 14. GOx catalyzes thereaction of glucose to gluconic acid and hydrogen peroxide (H2O2), where the latter inturn reacts to form proton ions and electrons. The electrons, by help of a liquid gatevoltage (usually held around -1.5 V) are transferred to the channel and actually enhancesit by attracting holes to the channel which increases degree of p-doping. A diagram ofthe setup from the same paper is also shown in Figure 15, as well as the physical setupand change in output curves from the different glucose molarities in phosphate-bufferedsaline (PBS).

2.4 MoS2-FETs

2.4.1 Dry MoS2 transistors

Monolayer molybdenum disulfide (MoS2), a type of transition metal dichalcogenide (TMD),has emerged as a interesting and useful 2-dimensional material.44,48 Bulk MoS2 is alreadywell-known and is often used as a lubricant. The bulk form is metallic however but as amonolayer a (direct) band-gap emerges, which is 1.8 eV.

Monolayer MoS2 can be mechanically exfoliated from bulk MoS2 using scotch-tape, orgrown on a substrate, even SiO2/Si, by chemical vapor deposition (CVD). Such growth

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Figure 12: Functionalization of semiconducting single-walled CNT with glucose oxidaseenzyme (GOx) by use of the intermediate linker 1-pyrene butanoic acid succinimidyl ester(Pbase). Figure modified from Chen et al. 2001.55

Figure 13: Pbase linker decomposed into its constituent parts.

processes is typically of type Volmer–Weber meaning it forms islands when it grows. It ispossible however to extend the growth process so that these islands form a thin film.

A typical transfer curve for an MoS2-FET are shown in Figure 16, adopted from Wanget al. 2012.48 As can be seen it is shows n-type behavior, and will not accumulateholes as charge carriers in the channel by a negative potential. Ambipolar behavior canbe seen however by use of a electric double-layer transistor (EDLT) and a liquid gate.Anyway as a dry transistor MoS2 can exhibit current on/off ratios of up to 1010 whichis quite impressive. Also, MoS2 is relatively abundant on Earth, and although it is hardto compete with III-V semiconductors, it could be a promising material for low-powerelectronics.48

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Figure 14: Sensing mechanism of a GOx-enzyme coated CNT-FET glucose sensor. Figuremodified from Lee et al. 2010.37

Figure 15: (a) Physical setup of CNT-FET glucose sensor, (b) circuit diagram of system,(c) output curves being altered as a result of adding different glucose molarities in thephosphate-buffered saline (PBS). All from Lee et al. 2010.37

2.4.2 Biosensing applications

Most research thus far has focused on using MoS2 nanostructures for electrochemical sen-sors. However there exist several papers in the literature for MoS2-FET sensors.44,45,49

Some analytes that have been explored include prostate-specific antigen (PSA) by func-tionalization with PSA anti-body,15,46,56 streptavidin by functionalization with biotin,46

TNF-α protein by functionalization with TNF-α anti-body,47 immunoglobulin (IgG, alsoknown as “antibody”) with no func.,15 and glucose by use of GOx catalyst.57

Two examples of functionalized MoS2-FET devices are shown in Figure 17. And, for thecase of TNF-α sensing, transfer curves for different molarities are shown in Figure 18.Note that greater molarity depletes the channel of electrons. Hence the FET-sensor canbe said to be operating in “depletion-mode”.

A crucial aspect when designing these sensors is to passivate the source/drain electrodes.

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Figure 16: Example of typical transfer curves from MoS2-FET device, from Wang et al.2012.48 (a) Visual diagram of device, (b) real data of transfer curves, (c) simulated dataof transfer curves.

Figure 17: (a) Sarkar et al. 2014 MoS2-FET functionalized with biotin for streptavidinsensing,46 (b) Nam et al. 2015 MoS2-FET functionalized with TNF-α anti-bodies forsensing of TNF-α.47

What this means, is to ensure that they are not exposed to the solution but rather isolatedfrom it. Otherwise there can be an ionic current between the electrodes which short thesemiconducting channel, and this is not what we want to measure; we want to measurecurrent purely through our semiconductor.

One way to do this is by depositing a thin high-κ dielectric on top of both the electrodesand the channel, for example HfO2. This was done for example by Sarkar et al.46 andWang et al.56 One can also isolate them through other means like two-step lithography,10

or by a fluidic channel. Also, electrode-isolation aside, Lee et al. showed that it isnot necessary for the channel to have a dielectric layer, the device will still work as asensor.15

Finally I discuss the one paper that currently exists on glucose sensing using an MoS2-FET: Shan et al. 2018.57 The group exfoliated bulk MoS2 directly onto electrode arraypatterns that had been fabricated by UV lithography. No functionalization was per-formed, but rather the different glucose molarities in PBS buffer were combined withGOx. I believe their data to be a bit dubious because the source drain gold electrodesare exposed to the solution so very likely they are measuring an ionic current and notpurely the current in the channel.

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Figure 18: Transfer curves of Nam et al. 2015 MoS2-FET TNF-α sensor, which operatesin depletion-mode.47

2.5 Graphene-FETs

Although for the internship I did not work with graphene FET sensors, it is relevant tonote that field-effect biosensing devices involving the use of graphene have been researchedquite a deal,10,23,24,35,36,58 ever since the material was successfully isolated by A. Geimand K. Novoselov in 2004 at the University of Manchester, U.K. by mechanical exfoliationusing the scotch-tape method.59,60

Graphene has generated a lot of excitement in the last decade and a half, both for theinteresting physics behind it such the presence of relativistic carriers (massless Diracfermions), and for technological applications such as its potential for next-generationelectronics. However the transition from scientific academic laboratory to industry hasbeen a bit slow, however scalable graphene technologies have begun to emerge, such as inHuawei’s new Mate 20 X phone which uses graphene film cooling technology.61,62

Notably the company Nanomedical Diagnostics (parent company Cardea) have createdan impressive and exciting array of graphene FEB products for sensing a wide varietyof analytes. There is an electronic digital processing unit called Agile which can beplugged into a computer by USB, and then the user inserts a GFEB chip module intoit for sensing. An image of the product is shown in Figure 19a. In Figure 19b we haveside-view of the system, where the functionalized graphene channel can be seen and isexposed to the analyhte solution. Two-step lithography was used to isolate the solutionfrom the Pt electrodes to prevent an ionic current.

It is exciting that foundry-fabricated graphene FEBs exist on the market as a commercialproduct, however it will be interesting to see whether graphene based technologies willwin over other 2D materials such as transition metal dichalcogenides (TMDs) like MoS2

which could provide better sensitivity and device operation by having a direct bandgap,which graphene lacks, being a semimetal. This was brought up by Sarkar et al. 2014who pointed out 74% better sensitivity for their MoS2-FEBs are compared with graphen-FEBs.46

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Figure 19: (a) The digital processing unit called “Agile” accompanied by the grapheneFEB modules which are inserted and can selectively sense a specific analyte. (b) Diagramof their device with functionalized graphene channel, where two-step UV lithography ofSiN protects the Pt electrodes to prevent an ionic current from shorting the graphenechannel current.10,63

3 Results

3.1 CNT devices

3.1.1 Fabrication

The procedure for the fabrication of CNT-FET glucose sensor arrays will be summarizedhere, but a more thorough procedure guide can be found in Appendix II. A diagram ofthe end-result post-fabrication is shown in Figure 20.

Figure 20: Final product of CNT-FET glucose sensor after fabrication, at different scales.

The first step is to prepare some 1cmx1cm SiO2/Si chips. Such chips often form the basisof a micro/nano-electronic device. The base Si is highly p-doped and hence can conductcurrent. The oxide (500nm thick in this case) will serve as an oxide for the transistor, aswell as providing suitable optical contrast for being able to identify and image the CNTs

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under an optical microscope at relatively low magnification. Following this, a powder ofsemiconducting CNTs are dispersed in ethanol at a concentration of 0.1 µg/mL, and byuse of a probe-type sonicator which generates high-frequency pulses at rate of about 1Hz, for about 45 minutes, to disperse the CNTs and prevent conglomoration and clumpsfrom forming (see Figure 21a). Then, extract about 20 mL using a micro-pipette anddrop-cast onto a chip which is waiting on a 40 C hot-plate. After drop-cast, let thechip be for 45-60 seconds which will allow the ethanol to evaporate. After this, about 50“clusters” per mm2 should be present on the chip. Under an optical microscope this isvisible and as can be seen in Figure 21b, there are large clusters, medium clusters, andsmall clusters. The small clusters are more desirable because the large clusters have toomany CNTs and are more entangled, exhibiting metallic behavior.

Figure 21: (a) Probe-type sonicator for dispersing CNT powder in ethanol. (b) Opticalimages of CNTs on SiO2/Si chip.

The next step is UV photolithography for creating a resist pattern where metal contactswill be deposited. Hence, first spin AZ2020 negative resist and bake, followed by hard-contact 3.5 sec UV exposure using a coarse aligner, followed by post-bake. Then developthe pattern using AZ726 and rinse. Now, the sample is ready for metal deposition. Itis best to use electron-beam physical vapor deposition (EBPVD), which involves firingelectrons onto metal pellets in a crucible, causing metal vapor to rise to the top wherethe sample is mounted and rotated. This method can be fine-tuned very well to depositthicknesses with nanometer precision. For these CNT devices, 10/100 nm Cr/Au layerswere deposited. The Cr functions to help the gold adhere better. Without the Cr the goldwould not stick enough to the SiO2. The chip post-metal deposition is shown in Figure22. (An alternative to EBPVD is sputtering, but this method is more coarse albeit lessexpensive.)

The design of the mask was such as to be able to channel as many CNTs as possiblebetween the gold fingers. The result is CNT channels connected as resistors in parallelbetween each pad. Ideally it is better to align CNTs across each channel, such as bydielectrophoresis (DEP), and actually a lot of research is being done concerning this, butno trivial procedure exists for this at the moment, hence our starting point is to use arandomly dispersed CNT network.

As also seen in Figure 22, there is an array of devices and each can be tested and will havedifferent resistances, usually in the range of 1-100 kΩ. Following the metal deposition,one should perform automated sweeps to obtain the characteristic transfer and output

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curves, using probe-tips with micro-controllers for fine positioning onto the pads. Afterthis, the functionalization procedure should be performed, with IV curves being measuredalong each step of the functionalization.

Figure 22: (a) Chip after metal deposition and lift-off. (b) Optical images at 2.5x mag-nification. (c) At 100x the CNTs between the fingers can be faintly seen.

The functionalization procedure is as follows and is based on the concentrations used byLee et al. 2010:37

(1) 2.3 mg/mL Pbase/DMF for 2h with magnetic stirring

(2) wash clean with DMF

(3) 10 mg/mL GOx/DI for 18h

(4) DI water for 6h

(For more information on the chemicals, see previous section on CNT-FET functional-ization.) Some parts of the functionalization aspects are shown in Figure 23. Followingthe functionalization, the chip is glued to an integrated circuit (IC) to facilitate handlingof the electrical measurements for the device. One first scratches off the few nm nativeoxide that is on the bottom of the p-doped Si chip, and then uses a conducting silver(Ag) paste as the glue to a metal back-gate on the IC. These ICs in this context are alsoknown as dual in-line packages (DIL or DIP or DILP) or printed circuit-board (PCB)depending on the exact type of IC. After the chip is glued, it is necessary to wire-bondthe pads to the connections on the DIL or PCB, which ultimately connect to other pinsor metal contacts which can be soldered or put on a breadboard for straight-forwardelectrical measurements. After the wire-bonding, UV-cured resin is placed on the wiresto prevent ionic current, and also as a way to protect them from breaking. The UV-curedglue is also used to place a plastic cylinder over the chip to enable testing with analytesolution.

3.1.2 SEM and AFM characterization

Scanning electron microscopy (SEM) images were acquired after dispersing CNTs ontothe chip, revealing both the larger clusters and smaller clusters. Figure 24a shows alarge cluster on the chip, which is undesirable for a channel because it will will behave

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Figure 23: (a) Chip exposed to a Pbase/DMF stirring solution, to bind Pbase inter-mediate linkers to the CNT surface. (b) GOx enzyme in powder form, extracted fromAspergillus niger. (c) Immobilization of GOx enzyme to Pbase/CNT channel.

more metallically, with low resistance, and not as a semiconductor. Less dense clustersas in Figure 24b are the kinds to aim for when aligning the photolithographic maskaligner.

Figure 24: SEM images of CNTs dispersed on a SiO2/Si chip, showing (a) large clusterand (b) small cluster which is more favorable for the channel.

After functionalization, some atomic force microscopy (AFM) images were also obtained,both on individual CNTs as well as some profilings across the finger source/drain elec-trodes which consist of 10/100 nm Cr/Au and the channel network in between. Un-fortunately no AFM images were acquired before functionalization, which would havebeen ideal as a control for comparison. Such images were also acquired by for exampleBesteman et al. 2003.42 Image comparisons are shown in Figure 25.

Profiles across electrodes are shown in Figure 26, including a 3D representation as wellas a line-scan profile. This reveals the height of the fingers as being about 100 nm (fromadding 60 nm + 40 nm) which is what the EBPVD recipe was chosen to be, and hencetestifies to the accuracy and reliability of this form of metal deposition; however thesurfaces are rather rough. Regarding diameter of the tubes it can be estimated from thefigures as roughly 10-20 nm depending on the tube, which is a bit large, likely due tosome tip convolution as well as bundling of multiple tubes, making them larger.

The AFM mode used was “tapping mode”, where a cantilever literally taps on the sampleand the “atomic force” response is registered by a photodiode which receives a signal froma laser which is reflected off of the cantilever. This mode is one of the more subtle modesin AFM, contrasting for example “contact mode” which may damage the sample. The

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Figure 25: (a) No AFM data was acquired before CNT functionalization. (b) AFM dataafter functionalization, possibly revealing GOx enzyme features. (c) and (d) are for fromBesteman et al. 2003 paper.42

main draw-back with tapping mode however is that the micrograph is more prone todisplaying artifacts resulting from certain tapping resonances.

There are many different modes which exist for AFM. One can for instance carry outelectrical measurements by methods that include and/or combine Scanning Kelvin ProbeMicroscopy (SKPM), electrical force microscopy (EFM), conductive AFM (C-AFM), andNap mode. Such mode would enable to user to for instance perform IV curve measure-ments directly on the sample, instead of first fabricating electrodes, wire-bonding, andIC-packaging, which can introduce many different contaminations since one has to spindifferent polymers, etc. Such electrical AFM measurements may be carried out by thegroup later in the future.

Figure 26: AFM image showing source/drain electrodes, (a) in 3D and (b) line-scan.

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3.1.3 Electrical characterization

Electrical measurements were carried out using the 1993 HP4156A Precision Semicon-ductor Parameter Analyzer. (For more information about this parameter analyzer, seeAppendix II.) For transistor measurements (characteristic output and transfer curves),there are three connections for Drain (forced voltage), Source (ground), and Gate. Figure27 shows all the devices that were fabricated. For each package, two of the connections goto the back plate that the chips are glued on with Ag paste, enabling application of thegate voltage which charges the back up like a capacitor, creating an electric field whicheither enhances or depletes the semiconductor channel of charge carriers; hence it is like avoltage-controlled “effective doping” of the channel. (To read more about the transistorcharacterization, see the Background section.)

Figure 27: All CNT-FET devices that were fabricated, packaged in ICs.

The other connections go to the Source or Drain pads for the various devices. Since thearrays of devices created are usually like a matrix with three rows, the middle row isinterconnected to act as the Source for all devices and hence only one connector will beneeded. It is by switching Drains that one can choose which device to measure.

Much of the work in the internship consisted of the electrical measurements, it is likethe final step where you have your device and you characterize it and when you performsensing measurements it is indeed the electrical signal that you probe with such an ana-lyzer. Many of the CNT-FET arrays were tested, and the output and transfer curves fora representative sample shown in Figure 28.

Admitidley this was the best device fabricated, where many others were either damagedor exhibited significant leakage currents through the oxide and hence were did not yieldsuch nice curves. A linear and log plot of the transfer curve for Vds = 3.0 V is shownin Figure 29 where the ON/OFF ratio is calculated to be somewhere between 101 and102, depending on if the OFF state is taken to be at zero back-gate voltage or at forceddepletion with the positive gate voltage.

Functionalization was carried out, as explained previously, however the devices died afterthe functionalization process, for unknown reasons. This will be investigated furtherby another post-doc in the group. Therefore although reasonably good dry CNT-FETdevices were fabricated during the internship, no sensing data for glucose was successfullyobtained.

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Figure 28: Characteristic output and transfer curves obtained for one of the fabricatedCNT-FETs. Although there is a leakage current Igs between gate and source, this is notaffecting the performance so much since it is not mirroring the Ids curves.

Figure 29: Showing both linear and logarithmic scales for the transfer curve of one of thefabricated CNT-FETs, revealing an ON/OFF ratio of about 102.

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3.2 MoS2 devices

3.2.1 Fabrication

As with the CNT devices, the MoS2 devices were fabricated based on the thin-film tran-sistor (TFT) model. We purchased two SiO2/Si substrates, where monolayer MoS2 flakeswere grown by chemical vapor deposition (CVD). One of the ways to grow large highlyimpermeable monolayer MoS2 triangles is described by Lloyd et al. 2016.64

Lloyd explains that a common method is to use MoOx and S precursor gases, but thatthe following slightly modified method is better: first, place MoS2 powder in the tubeof the CVD furnace, and the SiO2/Si substrate downstream in a slightly cooler location.Use Ar as the carrier gas at 60 sccm, with 0.1 sccm O2 and 1 sccm H2 gas, at 900 C.The mechanism is that O2 reacts to form either MoO2 or MoO3 which liberates 2S; thesemolecules flow downstream to react with the substrate. Such procedure or a similar onewas likely used by the vendor that we purchased from.

Figure 30: MoS2 transfer procedure, based on Ma et al. 2017.65

In order to fabricate multiple FET devices from the purchased flakes, we carried out abouteight or so transfers of the flakes to other substrates. There is a lot in the literature ontransferring 2D materials like MoS2 and graphene, and many of them involve multiplelaborious steps in the processes like polymer-spinning, baking, and micropositioning. Weused a rather straight-forward procedure published by Ma et al. in 2017.65 Figure 30illustrates the procedure. The first step is to fill a 100 mL beaker by half with DI water,and then to heat it on a 120 C hot-plate. When the water is around 60 to 65 C, thewater starts to evaporate. As this is happening, one should exposure a PDMS film for3-7 seconds, and then place the film on the source substrate gently by a reverse-peelingtouch-down. Gently prizing with tweezers, then peeling off and positioning on targetsubstrate which also is on the 120 C hot-plate. Wait about 30 seconds and then placeit on a cool wipe followed by a peel-off. The transfer is finished. This is also shown inFigure 31a and 31b. As can be seen in (b), our transfers were not optimal since on thetarget substrate the flakes are slightly cracked.

Following transfer, we patterned multiple substrates both with the previously mentionedpads-fingers mask used for the CNT-FET fabrication, as well as a mask which had a more“trivial” design in order to have a single film between Source and Drain—as opposed toa channel consisting of resistors in parallel. For metal deposition, we used 10/100 nmTi/Au layers. These devices were much more sensitive in the lift-off process, requiring

24

Figure 31: (a) PDMS with water vapor in contact with source substrate for extractingMoS2 flakes to transfer. (b) Flakes before and after transfer. (c) MoS2-FET device afterphotolithography, metal deposition, and lift-off.

overnight acetone baths as opposed to a quicker Remover-PG solution which we foundlifted off the flakes, destroying the device. A final device is shown in Figure 31c.

Following lift-off, the chips were glued to integrated circuit (IC) printed circuit boards(PCBs), and wire-bonds were implemented, connecting the Source/Drain pads to the ICto enable straight-forward electrical characterization.

3.2.2 Electrical characterization

All the MoS2-FET devices that were fabricated are shown in Figure 32. There are onlythree becaues the rest of them were damaged during lift-off. The two on the left aretransferred devices, while the right-most device is from the original donor substrate, andshould hence in theory have the best performance. Unfortunately the donor device wasnot functioning, because some pieces of gold shorted the channel.

Figure 32: All MoS2-FET devices that were fabricated.

The dry characteristic curves of a device are shown in Figure 33, where the transferlogarithmic plot reveals an ON/OFF ratio which is a bit less than 102. This is far lowerthan what is reported in the literature, and there is also a lot of noise. This is likely

25

due to damage in the transfer process, and also due to having spun various films in thefabrication process. A better result could be obtained by evaporating contacts using ashadow mask, which is a polymer-free fabrication process. Most likely our group willgo ahead to perfect the photolithographic process to create better devices however, asphotolithography generally allows for better patterning and other advantages.

Following dry transistor measurements, testing with glucose analyte in DI water wascarried out, based on the Shan et al. 2018 paper.57 This is a first-principles approachsince there is no functionalization, disallowing for selectivity among other analytes. Themethod involves simply mixing together the glucose oxidase enzyme (GOx) together withthe analyte, to catalyze a reaction which leads to doping of the channel as a function ofthe glucose molarity. This approach was tested, but since the channel had on the orderof MΩ resistance, in addition to the source/drain electrodes being also exposed to thesolution, there was an ionic current which shorted the channel.

Figure 33: Output and transfer curves for the device (MoS2–6), revealing an ON/OFFratio a bit less than 102. (Leakage current is minimal, on the order of nA.)

Therefore, although MoS2-FET devices were fabricated and yielded n-type transistorcurves, there is still much work remaining to the group to perfect the fabrication procedureand to better tailor the system for glucose sensing. This continuation will be carried outby some other members of the group.

4 Conclusions and next steps

For this summer internship, I contributed to the early stages of the chemical FET sensingmodule of the SmartVista project, together with my colleagues, by fabricating CNT-FETsensor arrays, as well as MoS2-FET sensor arrays, establishing the ground-work for themodule. In addition I also wrote four procedure guides, included in Appendix II, andcontributed to the writing of a review paper.

For the devices that were fabricated, characterization by electrical measurements, opti-cal microscopy, atomic force microscopy, and scanning electron microscopy were carriedout. The representative CNT-FET curves showed the expected p-type behavior, with anON/OFF ratio around 102. The representative MoS2-FET curves showed the expectedn-type behavior, albeit noisy, with a relatively low ON/OFF ratio of less than 102.

The next steps for this module will be to obtain high-performance first-principles sensingdata, both with CNTs and MoS2. Following this, other factors need to be addressed, some

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of which include scalability, stability, cost-reduction, integration with digital processingmodules, integration on flexible substrates/polymers, and sensing selectivity amongstother analytes. It will be exciting to follow the progress of the SmartVista project and itsgoal of helping reduce deaths and healthcare costs associated with cardiovascular diseases,while at the same time furthering our fundamental understanding 1D/2D materials. Newsassociated with the project can be found at www.smartvista.eu.

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Appendix I – Acronyms

The following is a table of some of the acronyms used in the report.

FET Field-effect transistor

FEB Field-effect biosensor

TFT Thin-film transistor

MOSFET Metal-oxide-semiconductor field-effect transistor

CNT Carbon nanotube

GOx Glucose oxidase enzyme

Pbase 1-pyrene butanoic acid succinimidyl ester

PBS Phosphate-buffered saline

MoS2 Molybdenum disulfide

TMD Transition metal dichalcogenide (aka TMDC)

IC Integrated circuit

PMOS P-type metal-oxide-semiconductor

PCB Printed circuit board

DIL dual in-line package (aka DIP or DILP)

EU European Union

SmartVista Smart Autonomous Multi Modal Sensors for Vital Signs Monitoring

CVD cardiovascular diseases

CVD chemical vapor deposition

PVD physical vapor deposition

EBPVD electron-beam physical vapor deposition

EMFT Research Institution for Microsystems and Solid State Technologies

ECG electrocardiograph

AFM Atomic force microscopy

SEM Scanning electron microscopy

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Appendix II – Procedure Guides

I wrote four procedure guides for my internship, including

• CNT-FET glucose sensor fabrication

• MoS2-FET glucose sensor fabrication

• HP4156A parameter analyzer

• Clean-room probe-station automated sweeps setup

They can be found in separate PDF files.

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