sign in sign up
<<
Home , FinFET, Piet Bergveld, Sensor

Laboratoire d’Informatique, de Robotique et de Microelectronique´ de Montpellier

Summer Internship 2019

Field-effect based biosensing of using carbon nanotubes and monolayer MoS2

Nathan Ullberg

supervised by Aida Todri-Sanial

examined by Carla Puglia

November 24, 2019 Contents

Abstract...... 2 Acknowledgements...... 3 1 Introduction...... 4 2 Background...... 5 2.1 Field-effect (FET)...... 5 2.1.1 Brief history and overview...... 5 2.1.2 Characteristic curves...... 6 2.1.3 Transconductance, threshold voltage, and ON/OFF ratio7 2.2 Field-effect biosensing (FEB)...... 8 2.3 CNT-FETs...... 10 2.3.1 Dry CNT transistors...... 10 2.3.2 Functionalization for glucose sensing...... 11 2.4 MoS2-FETs...... 12 2.4.1 Dry MoS2 transistors...... 12 2.4.2 Biosensing applications...... 14 2.5 -FETs...... 16 3 Results...... 17 3.1 CNT devices...... 17 3.1.1 Fabrication...... 17 3.1.2 SEM and AFM characterization...... 19 3.1.3 Electrical characterization...... 22 3.2 MoS2 devices...... 24 3.2.1 Fabrication...... 24 3.2.2 Electrical characterization...... 25 4 Conclusions and next steps...... 26 Bibliography...... 32 Appendix I – Acronyms...... 33 Appendix II – Procedure Guides...... 34

1 Abstract

As part of the EU SmartVista project to develop a multi-modal wearable for health diagnostics, field-effect transistor (FET) based were explored, with glucose as the analyte, and carbon nanotubes (CNTs) or monolayer MoS2 as the semiconducting sensing layer. Numerous arrays of CNT-FETs and MoS2-FETs were fabricated by pho- tolithographic methods and packaged as integrated circuits. Functionalization of the sensing layer using linkers and enzymes was performed, and the samples were character- ized by atomic force microscopy, scanning electron microscopy, optical microscopy, and electrical 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 in a wear- able device.

2 Acknowledgements

Firstly, I would like to thank my supervisor Dr Aida Todri-Sanial. She has been very supportive in ensuring that my internship experience is something meaningful both for myself and for the group. She has guided me and has helped sharpen my skills as a scientist. 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 help from Dr BenoˆıtCharlot whose lab space and resources I was welcome to use, in addition to his advice, guidance, and help. I also thank post-doc Dr Marwa Dhifallah who helped me integrate into the environment and to understand the project, and Thierry Gil who provided help regarding 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 known as a Traineeship). I therefore extend my thanks to the providers of these funds, which enabled me to focus on my work and to be less burdened by financial difficulties. I am also grateful for EU Horizon 2020, the eight Framework Program (FP8) since 1984 supporting research in the European Research Area, which is funding the SmartVista project.1,2 For this summer project I am also receiving 15 ECTS course credits, which contribute to my current Master’s in Materials program at Uppsala University. I am grateful to the program coordinator Professor Andreas Korn for his support and advice he has given me regarding my choices. I am also grateful to my home institution advisor Professor Carla Puglia; she evaluated my report and has been advising me in general regarding my academic choices. Finally I would like to thank my parents, sister, and friends for all their support.

3 1 Introduction

The objective of this summer internship was to contribute in research and development concerning field-effect transistor (FET) based glucose sensing using carbon nanotubes (CNTs) and monolayer MoS2. This work is within the framework of the European Union Horizon 20203 project known as Smart Autonomous Multi Modal Sensors for Vital Signs (SmartVista).1,2 The SmartVista project was launched in January 2019, and is a 3-year-long contract from the EU to help reduce deaths due to cardiovascular diseases (CVD) by a multi-modal wearable sensor. A schematic of the different modules in the wearable are shown in Figure 1.

Figure 1: Modules in the SmartVista wearable.

There are multiple partners from across Europe in this project working on the different modules. The partners include Tyndall National Institute (Ireland), University College Cork (Ireland), the French National Center for Scientific Research (CNRS) (France), NovoSense AB (Sweden), Fraunhofer – Research Institution for Microsystems and Solid State Technologies (EMFT) (Germany), and Analog Devices, Inc. (Ireland).1 The laboratory that I worked at is called The Montpellier Laboratory of Computer Sci- ence, , 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 of which 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 to three 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 and MoS2-FETs were fabricated and characterized by electrical measurements, as well as by scanning electron microscopy (SEM), atomic force microscopy (AFM), and optical mi- croscopy. It should be noted that although the sensors were tested with different glucose molarities 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 sensors in “dry” conditions. The next section will be about the background, state of the art, and

4 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 either switching or amplification applications. The former can be used for logical operations and therefore computing, while the latter is used for amplifying such as in a microphone. Before transistors, there were thermionic valves, also known as or vacuum tubes which were used in computer processors such as in the 1945 ENIAC—the first electronic general-purpose computer. Vacuum tubes were problematic for several reasons 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 , New Jersey in 1947.6 The mechanism of a transistor is that it is a three-terminal device where a small input current or voltage controls a separate output current. The first 1947 transistor was a current-controlled point-contact transistor, of bipolar type, meaning both electrons and holes flow in the output current. What soon followed in 1948 was the invention of the bipolar junction transistor (BJT) which also is current-controlled and uses a more elegant junction approach of differently doped blocks of connected by junctions. 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 in the semiconductor and hence controls the output current. (FETs are unipolar meaning either electrons or holes flow in the channel but not both.) One way to think of such a device is as a voltage-controlled variable .6,7 This is shown in Figure2. 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 are called insulated-gate FETs (IGFETs) since the gate may not always be a metal and the dielectric may not always be an oxide.) As mentioned, are unipolar and hence can be either n-type (meaning electrons flow in the channel) or p-type (holes flow in the channel). The modes of a FET are either enhancement-mode (where the field causes carriers 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 a single chip (called NMOS and PMOS respectively), one can create a . However the most efficient approach is to use both, which is called complementary metal-oxide- semiconductor (CMOS) integration, which was invented in 1963. CMOS technology gave rise to the (IC), and this business helped give rise to the Silicon Valley business 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 include Shockley Semiconductor Laboratory, Fairchild Semiconductor, and later .6

5 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 Figure3, and as can be seen the channel is p-doped while 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 while electrons are attracted from below, therefore the originally p-doped channel becomes effectively n-doped! This is called inversion because the p becomes inverted to n. That is 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 particular there are two current-voltage (IV ) curves which are of highest importance. The first is called transfer and is a sweep of the gate voltage Vg with the drain-source current Id being measured and the drain-source voltage Vds sometimes varied as a parameter; and the 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 curves for a standard MOSFET, this one is called IRF540N, and the data is shown in Figure

6 4. The data was obtained using an HP4156A Precision Semiconductor Parameter An- alyzer, which is a that can source voltage or current and measure the output automatically 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 turning the MOSFET to the ON-state. If the gate voltage is less than this, the channel will not conduct any electrons. And, in the output curve we see how if the device is more on, then the drain-source current is higher. Note that conventional current which is positive flows from drain to source; this means that the source is a source of electrons, which makes sense since this is an n-type transistor and so electrons flow in the channel. In a p-type MOSFET 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 units of conductance (inverse resistance or Ω−1), which is why the letter “g” is used, and takes on values usually on the order of milli-Siemens (mS). It is defined as the derivative of the transfer curve: ∂Ids gm ≡ ∂Vgs

As can be seen, it is an indication of how much output (current) is produced for the input (voltage) provided, and hence it is like the yield of the transistor. A plot of gm is shown in gray color in the left-most plot of Figure5 for an IRF540N MOSFET, where the maximum 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 vary Vds, as shown in the right-most plot. In general we also want to know what is called the ON-OFF ratio. This is basically a ratio of the ON current (Vgs > Vth) and the OFF current (Vgs < Vth). To calculate this

7 Figure 5: Calculating the transconductance gm and threshold voltage Vth from a transfer IV curve. (In this case for a IRF540N MOSFET.) it is often useful to do a log plot of the transfer curve as in Figure6.

Figure 6: Log plot of the transfer curves for a IRF540N MOSFET, where the ON-OFF ratio is calculated to be 106. As can be seen in the Figure, we have 106 ratio which is very high and we can already see how within just some tens of mV we can have a significant change in current by one million in this case. This already gives us an indication that this system exhibits ultra-high sensitivity, with just a few milli- or less we can have a significant in the (Ids).

2.2 Field-effect biosensing (FEB)

FET-based biosensing, also known as field-effect biosensing (FEB),9, 10 or sometimes BioFET, ChemFET, or ISFET (-sensitive FET) depending on the analyte and mech- anism in question, is an approach to sensing that makes use of a FET system that is tailored 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

8 materials having been explored for the semiconducting channel. The concept behind the “FET to FEB” idea is illustrated in Figure7. On the left of the figure is a thin-film transistor (TFT) in a conventional setup where an input gate voltage signal is provided. On the right, the surface of the channel has been “functionalized” with receptors (shown as “Y”s) that are selective to the analyte of interest (shown as circles). The mechanism is that when an analyte binds to the receptor it causes carriers in the channel to either accumulate or deplete, which changes the conductance/resistance of the channel, and henceforth the transconductance. The degree to which the conductance changes depends on the concentration/molarity of the analyte, and hence the system can be used as a sensor.

Figure 7: Concept of field-effect transistor based .

There are different variations of the system shown in Figure7. The FEB shown is held at a constant back-gate potential, however some devices do not employ a back-gate voltage 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 the surface.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 of the main advantages is its compatibility with the CMOS process, meaning FEBs can be integrated as a “” (SoC) for electronic digital processing, and in a miniaturized fashion. The concept of such integration for biosensors has been termed the “internet of ”.10 For the semiconductor channel, various different classes of materials have been explored, including: nanowires (NWs),16 organic (OSCs),17–20 one-dimensional (1D) materials such as CNTs,21, 22 and two-dimensional (2D) materials such as graphene23, 24 25–27 and other transition metal dichalcogenide (TMD) monolayers like MoS2. 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 which can be sensed, including: chemicals, pH, proteins, , DNA, and other com- plex molecules.14 The channel can also be sensitized by use of nanoparticles28–30 or nanopores.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.

9 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 such nanowire 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 level with foundry-fabricated modular graphene FET (GFET) chips available on the market for sensing a variety of analytes,10 however the use of graphene as the channel has the drawback of it being a semimetal and thus leaking current. The most popular graphene- 15, 44–47 like alternative is the TMD monolayer MoS2, which has a direct bandgap of 1.8 eV.48, 49 Research is still on-going and although the focus has been on high surface-to-volume-ratio materials 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 they are 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 SmartVista the 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 up into 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 valence electron 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 be visualized by the cited Wolfram Demonstrations Project.51 Furthermore, CNTs can be grown to be either single-walled (SWCNT) or multi-walled (MWCNT).52 In the internship single-walled were used. In general, when fabricating a CNT-FET, it will exhibite transistor p-type behavior. The channel will hence only be enhanced by a negative gate voltage, and depleted by a positive one. An example of transfer curves from the literature are shown in Figure9, and is from a 2009 CNT-FET sensor review paper.53 Note the sharp kink in the curve, which is an indication of a good Schottky barrier between the semiconductor-CNT and metal contact interface,7 as opposed to a more ohmic interface which would display more linear tendency at the “kink”-point and smoothen out that portion of the curve. Under some conditions such as cryogenic, CNT-FETs can actually exhibit ambipolar behavior as shown in Figure9. 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-FET displays better sensitivity, as shown in Pujad´o’s2012 Figure 10.54 Finally some typical output curves for a CNT-FET is shown in Figure 11.

10 Figure 8: Example of CNT-FET transfer curves for the case of a gas sensor, where the effect 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 either holes or electrons can be made to conduct across the channel. Usually CNT-FETs can only 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 explain how a CNT-FET is functionalized to serve the purpose of glucose sensor. The key is to immobilize glucose oxidase enzyme (GOx) molecules on the surface of CNTs, by help of an intermediate linker called 1-pyrenebutanoic acid succinimidyl ester (Pbase). (See Figure 13 for a decomposition to constituent parts.) The idea of immobilizing molecules by help of the intermediate linker Pbase was first introduced in 2001 by Chen et al.55 The immobilization of GOx specifically was introduced in 2003 by Besteman et al.42 Figure 12 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. This is a non-covalent binding, it is relatively weak and is due to asymmetric distributions of charge (dipole moments) providing a net electrostatic force. It is ideal for this system that it is non-covalent because that means that the electronic properties (which are described by the band structure) of CNTs remain essentially the same. In other words, the CNT isn’t becoming like a new material/molecule by some strong binding of another molecule to it. For the GOx, an amide bond is formed with the Pbase by replacing its succinimidyl

11 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 the reaction of glucose to gluconic acid and peroxide (H2O2), where the latter in turn reacts to form proton and electrons. The electrons, by help of a liquid gate voltage (usually held around -1.5 V) are transferred to the channel and actually enhances it by attracting holes to the channel which increases degree of p-doping. A diagram of the setup from the same paper is also shown in Figure 15, as well as the physical setup and change in output curves from the different glucose molarities in phosphate-buffered saline (PBS).

2.4 MoS2-FETs

2.4.1 Dry MoS2 transistors

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

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

12 Figure 12: Functionalization of semiconducting single-walled CNT with glucose oxidase enzyme (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 is possible 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 Wang et al. 2012.48 As can be seen it is shows n-type behavior, and will not accumulate holes as charge carriers in the channel by a negative potential. Ambipolar behavior can be seen however by use of a electric double-layer transistor (EDLT) and a liquid gate. 10 Anyway as a dry transistor MoS2 can exhibit current on/off ratios of up to 10 which is quite impressive. Also, MoS2 is relatively abundant on Earth, and although it is hard to compete with III-V semiconductors, it could be a promising material for low-power electronics.48

13 Figure 14: Sensing mechanism of a GOx-enzyme coated CNT-FET glucose sensor. Figure modified 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 the phosphate-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- 44, 45, 49 sors. However there exist several papers in the literature for MoS2-FET sensors. 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, also known as “”) 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 the case 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 can be said to be operating in “depletion-mode”. A crucial aspect when designing these sensors is to passivate the source/drain electrodes.

14 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 data of transfer curves.

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

What this means, is to ensure that they are not exposed to the solution but rather isolated from it. Otherwise there can be an ionic current between the electrodes which short the semiconducting channel, and this is not what we want to measure; we want to measure current purely through our semiconductor. One way to do this is by depositing a thin high-κ dielectric on top of both the electrodes 46 and the channel, for example HfO2. This was done for example by Sarkar et al. and Wang 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 is not necessary for the channel to have a dielectric layer, the device will still work as a sensor.15

Finally I discuss the one paper that currently exists on glucose sensing using an MoS2- 57 FET: Shan et al. 2018. The group exfoliated bulk MoS2 directly onto electrode array patterns that had been fabricated by UV lithography. No functionalization was per- formed, but rather the different glucose molarities in PBS buffer were combined with GOx. I believe their data to be a bit dubious because the source drain gold electrodes are exposed to the solution so very likely they are measuring an ionic current and not purely the current in the channel.

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

2.5 Graphene-FETs

Although for the internship I did not work with graphene FET sensors, it is relevant to note that field-effect biosensing devices involving the use of graphene have been researched quite a deal,10, 23, 24, 35, 36, 58 ever since the material was successfully isolated by A. Geim and K. Novoselov in 2004 at the University of Manchester, U.K. by mechanical exfoliation using the scotch-tape method.59, 60 Graphene has generated a lot of excitement in the last decade and a half, both for the interesting physics behind it such the presence of relativistic carriers (massless Dirac fermions), and for technological applications such as its potential for next-generation electronics. However the transition from scientific academic laboratory to industry has been a bit slow, however scalable graphene technologies have begun to emerge, such as in Huawei’s new Mate 20 X phone which uses graphene film cooling technology.61, 62 Notably the company Nanomedical Diagnostics (parent company Cardea) have created an impressive and exciting array of graphene FEB products for sensing a wide variety of analytes. There is an electronic digital processing unit called Agile which can be plugged into a computer by USB, and then the user inserts a GFEB chip module into it for sensing. An image of the product is shown in Figure 19a. In Figure 19b we have side-view of the system, where the functionalized graphene channel can be seen and is exposed to the analyhte solution. Two-step lithography was used to isolate the solution from the Pt electrodes to prevent an ionic current. It is exciting that foundry-fabricated graphene FEBs exist on the market as a commercial product, however it will be interesting to see whether graphene based technologies will win 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. 2014 who pointed out 74% better sensitivity for their MoS2-FEBs are compared with graphen- FEBs.46

16 Figure 19: (a) The digital processing unit called “Agile” accompanied by the graphene FEB modules which are inserted and can selectively sense a specific analyte. (b) Diagram of their device with functionalized graphene channel, where two-step UV lithography of SiN protects the Pt electrodes to prevent an ionic current from shorting the graphene channel 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 summarized here, but a more thorough procedure guide can be found in Appendix II. A diagram of the 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 basis of a micro/nano-electronic device. The base Si is highly p-doped and hence can conduct current. The oxide (500nm thick in this case) will serve as an oxide for the transistor, as well as providing suitable optical contrast for being able to identify and image the CNTs

17 under an optical microscope at relatively low magnification. Following this, a powder of semiconducting CNTs are dispersed in ethanol at a concentration of 0.1 µg/mL, and by use of a probe-type sonicator which generates high-frequency pulses at rate of about 1 Hz, for about 45 minutes, to disperse the CNTs and prevent conglomoration and clumps from forming (see Figure 21a). Then, extract about 20 mL using a micro-pipette and drop-cast onto a chip which is waiting on a 40◦ C hot-plate. After drop-cast, let the chip 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 is visible and as can be seen in Figure 21b, there are large clusters, medium clusters, and small clusters. The small clusters are more desirable because the large clusters have too many CNTs and are more entangled, exhibiting metallic behavior.

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

The next step is UV photolithography for creating a resist pattern where metal contacts will 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 develop the pattern using AZ726 and rinse. Now, the sample is ready for metal deposition. It is best to use electron-beam physical vapor deposition (EBPVD), which involves firing electrons onto metal pellets in a crucible, causing metal vapor to rise to the top where the sample is mounted and rotated. This method can be fine-tuned very well to deposit thicknesses with nanometer precision. For these CNT devices, 10/100 nm Cr/Au layers were deposited. The Cr functions to help the gold adhere better. Without the Cr the gold would not stick enough to the SiO2. The chip post-metal deposition is shown in Figure 22. (An alternative to EBPVD is sputtering, but this method is more coarse albeit less expensive.) The design of the mask was such as to be able to channel as many CNTs as possible between the gold fingers. The result is CNT channels connected as in parallel between each pad. Ideally it is better to align CNTs across each channel, such as by dielectrophoresis (DEP), and actually a lot of research is being done concerning this, but no trivial procedure exists for this at the moment, hence our starting point is to use a randomly dispersed CNT network. As also seen in Figure 22, there is an array of devices and each can be tested and will have different 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

18 curves, using probe-tips with micro-controllers for fine positioning onto the pads. After this, the functionalization procedure should be performed, with IV curves being measured along 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 by Lee 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 on the chemicals, see previous section on CNT-FET functional- ization.) Some parts of the functionalization aspects are shown in Figure 23. Following the functionalization, the chip is glued to an integrated circuit (IC) to facilitate handling of the electrical measurements for the device. One first scratches off the few nm native oxide 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 also known 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 -bond the pads to the connections on the DIL or PCB, which ultimately connect to other pins or metal contacts which can be soldered or put on a breadboard for straight-forward electrical measurements. After the wire-bonding, UV-cured resin is placed on the to prevent ionic current, and also as a way to protect them from breaking. The UV-cured glue is also used to place a plastic cylinder over the chip to enable testing with analyte solution.

3.1.2 SEM and AFM characterization

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

19 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 from Aspergillus niger. (c) Immobilization of GOx enzyme to Pbase/CNT channel.

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

Figure 24: SEM images of CNTs dispersed on a SiO2/Si chip, showing (a) large cluster and (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 have been ideal as a control for comparison. Such images were also acquired by for example Besteman et al. 2003.42 Image comparisons are shown in Figure 25. Profiles across electrodes are shown in Figure 26, including a 3D representation as well as a line-scan profile. This reveals the height of the fingers as being about 100 nm (from adding 60 nm + 40 nm) which is what the EBPVD recipe was chosen to be, and hence testifies to the accuracy and reliability of this form of metal deposition; however the surfaces are rather rough. Regarding diameter of the tubes it can be estimated from the figures as roughly 10-20 nm depending on the tube, which is a bit large, likely due to some 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 sample and the “atomic force” response is registered by a which receives a signal from a laser which is reflected off of the cantilever. This mode is one of the more subtle modes in AFM, contrasting for example “contact mode” which may damage the sample. The

20 Figure 25: (a) No AFM data was acquired before CNT functionalization. (b) AFM data after functionalization, possibly revealing GOx enzyme features. (c) and (d) are for from Besteman et al. 2003 paper.42 main draw-back with tapping mode however is that the micrograph is more prone to displaying artifacts resulting from certain tapping resonances. There are many different modes which exist for AFM. One can for instance carry out electrical measurements by methods that include and/or combine Scanning Kelvin Probe Microscopy (SKPM), electrical force microscopy (EFM), conductive AFM (C-AFM), and Nap 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, and IC-packaging, which can introduce many different contaminations since one has to spin different polymers, etc. Such electrical AFM measurements may be carried out by the group later in the future.

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

21 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, see Appendix II.) For transistor measurements (characteristic output and transfer curves), there are three connections for Drain (forced voltage), Source (ground), and Gate. Figure 27 shows all the devices that were fabricated. For each package, two of the connections go to the back plate that the chips are glued on with Ag paste, enabling application of the gate voltage which charges the back up like a , creating an electric field which either enhances or depletes the semiconductor channel of charge carriers; hence it is like a voltage-controlled “effective doping” of the channel. (To read more about the transistor characterization, 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 the arrays of devices created are usually like a matrix with three rows, the middle row is interconnected to act as the Source for all devices and hence only one connector will be needed. 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 like the final step where you have your device and you characterize it and when you perform sensing 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 for a representative sample shown in Figure 28. Admitidley this was the best device fabricated, where many others were either damaged or exhibited significant leakage currents through the oxide and hence were did not yield such nice curves. A linear and log plot of the transfer curve for Vds = 3.0 V is shown in Figure 29 where the ON/OFF ratio is calculated to be somewhere between 101 and 102, depending on if the OFF state is taken to be at zero back-gate voltage or at forced depletion with the positive gate voltage. Functionalization was carried out, as explained previously, however the devices died after the functionalization process, for unknown reasons. This will be investigated further by another post-doc in the group. Therefore although reasonably good dry CNT-FET devices were fabricated during the internship, no sensing data for glucose was successfully obtained.

22 Figure 28: Characteristic output and transfer curves obtained for one of the fabricated CNT-FETs. Although there is a leakage current Igs between gate and source, this is not affecting 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 the fabricated CNT-FETs, revealing an ON/OFF ratio of about 102.

23 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 flakes were grown by chemical vapor deposition (CVD). One of the ways to grow large highly 64 impermeable monolayer MoS2 triangles is described by Lloyd et al. 2016.

Lloyd explains that a common method is to use MoOx and S precursor , but that the following slightly modified method is better: first, place MoS2 powder in the tube of 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; these molecules flow downstream to react with the substrate. Such procedure or a similar one was likely used by the vendor that we purchased from.

65 Figure 30: MoS2 transfer procedure, based on Ma et al. 2017.

In order to fabricate multiple FET devices from the purchased flakes, we carried out about eight or so transfers of the flakes to other substrates. There is a lot in the literature on transferring 2D materials like MoS2 and graphene, and many of them involve multiple laborious steps in the processes like polymer-spinning, baking, and micropositioning. We used a rather straight-forward procedure published by Ma et al. in 2017.65 Figure 30 illustrates 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, the water starts to evaporate. As this is happening, one should exposure a PDMS film for 3-7 seconds, and then place the film on the source substrate gently by a reverse-peeling touch-down. Gently prizing with tweezers, then peeling off and positioning on target substrate which also is on the 120 ◦C hot-plate. Wait about 30 seconds and then place it on a cool wipe followed by a peel-off. The transfer is finished. This is also shown in Figure 31a and 31b. As can be seen in (b), our transfers were not optimal since on the target substrate the flakes are slightly cracked. Following transfer, we patterned multiple substrates both with the previously mentioned pads-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 to a channel consisting of resistors in parallel. For metal deposition, we used 10/100 nm Ti/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 extracting MoS2 flakes to transfer. (b) Flakes before and after transfer. (c) MoS2-FET device after photolithography, metal deposition, and lift-off. overnight acetone baths as opposed to a quicker Remover-PG solution which we found lifted 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 IC to 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 only three becaues the rest of them were damaged during lift-off. The two on the left are transferred devices, while the right-most device is from the original donor substrate, and should hence in theory have the best performance. Unfortunately the donor device was not 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 transfer logarithmic plot reveals an ON/OFF ratio which is a bit less than 102. This is far lower than 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 the fabrication process. A better result could be obtained by evaporating contacts using a shadow mask, which is a polymer-free fabrication process. Most likely our group will go ahead to perfect the photolithographic process to create better devices however, as photolithography generally allows for better patterning and other advantages. Following dry transistor measurements, testing with glucose analyte in DI water was carried out, based on the Shan et al. 2018 paper.57 This is a first-principles approach since there is no functionalization, disallowing for selectivity among other analytes. The method involves simply mixing together the glucose oxidase enzyme (GOx) together with the analyte, to catalyze a reaction which leads to doping of the channel as a function of the glucose molarity. This approach was tested, but since the channel had on the order of MΩ resistance, in addition to the source/drain electrodes being also exposed to the solution, there was an ionic current which shorted the channel.

Figure 33: Output and transfer curves for the device (MoS2–6), revealing an ON/OFF ratio 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 transistor curves, there is still much work remaining to the group to perfect the fabrication procedure and to better tailor the system for glucose sensing. This continuation will be carried out by 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 sensing module of the SmartVista project, together with my colleagues, by fabricating CNT-FET sensor arrays, as well as MoS2-FET sensor arrays, establishing the ground-work for the module. In addition I also wrote four procedure guides, included in Appendix II, and contributed 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 carried out. The representative CNT-FET curves showed the expected p-type behavior, with an 2 ON/OFF ratio around 10 . The representative MoS2-FET curves showed the expected n-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 sensing data, both with CNTs and MoS2. Following this, other factors need to be addressed, some

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

27 Bibliography

[1] SmartVista website. https://www.smartvista.eu. Accessed 2019-09-16. [2] European Comission – Project Information SmartVista. https://www.cordis. europa.eu/project/rcn/219915/factsheet/en. Accessed 2019-09-16. [3] European Commission – What is Horizon 2020. https://ec.europa.eu/ programmes/horizon2020/en/what-horizon-2020. Accessed 2019-09-16. [4] Ruben Mas-Balleste, Cristina Gomez-Navarro, Julio Gomez-Herrero, and Felix Zamora. 2D materials: to graphene and beyond. Nanoscale, 3(1):20–30, 2011. [5] Erik T Thostenson, Zhifeng Ren, and Tsu-Wei Chou. Advances in the science and technology of carbon nanotubes and their composites: a review. Composites science and technology, 61(13):1899–1912, 2001. [6] Walter Isaacson. The Innovators: How a Group of Inventors, Hackers, Geniuses and Geeks Created the Digital Revolution. Simon and Schuster, 2014. [7] Ben G. Streetman and Sanjay Banerjee. Solid state electronic devices. Pearson Education, 7th edition, 2015. [8] . Modern semiconductor devices for integrated circuits, volume 2. Pren- tice Hall Upper Saddle River, NJ, 2010. [9] Nanomed – How does Field Effect Biosensing (FEB) work? https://www. nanomedical.com/field-effect-biosensing. Accessed 2019-09-16. [10] Brett R Goldsmith, Lauren Locascio, Yingning Gao, Mitchell Lerner, Amy Walker, Jeremy Lerner, Jayla Kyaw, Angela Shue, Savannah Afsahi, Deng Pan, et al. Digital biosensing by foundry-fabricated graphene sensors. Scientific reports, 9(1):434, 2019. [11] Yu-Cheng Syu, Wei-En Hsu, and Chih-Ting Lin. Field-Effect Transistor Biosens- ing: Devices and Clinical Applications. ECS Journal of Solid State Science and Technology, 7(7):Q3196–Q3207, 2018. [12] Matthew S Makowski and Albena Ivanisevic. Molecular analysis of with micro- /nanoscale field-effect-transistor biosensors. small, 7(14):1863–1875, 2011. [13] . Development of an ion-sensitive solid-state device for neurophysi- ological measurements. IEEE Transactions on Biomedical Engineering, (1):70–71, 1970. [14] Matti Kaisti. Detection principles of biological and chemical FET sensors. Biosensors and Bioelectronics, 98:437–448, 2017.

28 [15] Joonhyung Lee, Piyush Dak, Yeonsung Lee, Heekyeong Park, Woong Choi, Muham- mad A Alam, and Sunkook Kim. Two-dimensional layered MoS2 biosensors enable highly sensitive detection of biomolecules. Scientific Reports, 4:7352, 2014. [16] Qian Li, Na Lu, Lihua Wang, and Chunhai Fan. Advances in Nanowire Transistor- Based Biosensors. Small Methods, 2(4):1700263, 2018. [17] Sandeep G Surya, Harshil N Raval, Rafiq Ahmad, Prashant Sonar, Khaled N Salama, and V Ramgopal Rao. Organic field effect transistors (OFETs) in environmental sensing and health monitoring: A review. TrAC Trends in Analytical , 2018. [18] Luisa Torsi, Maria Magliulo, Kyriaki Manoli, and Gerardo Palazzo. Organic field- effect transistor sensors: a tutorial review. Chemical Society Reviews, 42(22):8612– 8628, 2013. [19] SM Goetz, CM Erlen, H Grothe, B Wolf, P Lugli, and G Scarpa. Organic field-effect transistors for biosensing applications. Organic Electronics, 10(4):573–580, 2009. [20] Francesco Maddalena, Marjon J Kuiper, Bert Poolman, Frank Brouwer, Jan C Hum- melen, Dago M de Leeuw, Bert De Boer, and Paul WM Blom. Organic field-effect transistor-based biosensors functionalized with protein receptors. Journal of Applied Physics, 108(12):124501, 2010. [21] Jianping Lei and Huangxian Ju. Nanotubes in biosensing. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2(5):496–509, 2010. [22] G Gruner. Carbon nanotube transistors for biosensing applications. Analytical and bioanalytical chemistry, 384(2):322–335, 2006. [23] Anindya Nag, Arkadeep Mitra, and Subhas Chandra Mukhopadhyay. Graphene and its sensor-based applications: A review. Sensors and Actuators A: Physical, 270:177–194, 2018. [24] Martin Pumera. Graphene in biosensing. Materials today, 14(7-8):308–315, 2011. [25] Chengzhou Zhu, Dan Du, and Yuehe Lin. Graphene-like 2D nanomaterial-based biointerfaces for biosensing applications. Biosensors and Bioelectronics, 89:43–55, 2017. [26] Padmanathan Karthick Kannan, Dattatray J Late, Hywel Morgan, and Chan- dra Sekhar Rout. Recent developments in 2D layered inorganic nanomaterials for sensing. Nanoscale, 7(32):13293–13312, 2015. [27] Kateryna Shavanova, Yulia Bakakina, Inna Burkova, Ivan Shtepliuk, Roman Viter, Arnolds Ubelis, Valerio Beni, Nickolaj Starodub, Rositsa Yakimova, and Volodymyr Khranovskyy. Application of 2D non-graphene materials and 2D oxide nanostruc- tures for biosensing technology. Sensors, 16(2):223, 2016. [28] Shun Mao, Ganhua Lu, Kehan Yu, and Junhong Chen. Specific biosensing using car- bon nanotubes functionalized with gold nanoparticle–antibody conjugates. Carbon, 48(2):479–486, 2010.

29 [29] Sung Myung, Aniruddh Solanki, Cheoljin Kim, Jaesung Park, Kwang S Kim, and Ki-Bum Lee. Graphene-encapsulated nanoparticle-based biosensor for the selective detection of cancer . Advanced Materials, 23(19):2221–2225, 2011. [30] Xing Chen, Zheng Guo, Gui-Mei Yang, Jie Li, Min-Qiang Li, Jin-Huai Liu, and Xing- Jiu Huang. Electrical nanogap devices for biosensing. Materials Today, 13(11):28–41, 2010. [31] Joyeeta Basu and Chirasree RoyChaudhuri. Graphene Nanoporous FET Biosensor: Influence of Pore Dimension on Sensing Performance in Complex Analyte. IEEE Sensors Journal, 18(14):5627–5634, 2018. [32] Yue Wang, Qiuping Yang, and Zhimin Wang. The evolution of nanopore sequencing. Frontiers in genetics, 5:449, 2015. [33] Ren Ren, Yanjun Zhang, Binoy Paulose Nadappuram, Bernice Akpinar, David Klen- erman, Aleksandar P Ivanov, Joshua B Edel, and Yuri Korchev. Nanopore extended field-effect transistor for selective single-molecule biosensing. Nature communica- tions, 8(1):586, 2017. [34] Meng Xu, Dora Obodo, and Vamsi K Yadavalli. The design, fabrication, and appli- cations of flexible biosensing devices–a review. Biosensors and Bioelectronics, 2018. [35] Yeon Hwa Kwak, Dong Soo Choi, Ye Na Kim, Hyeongkeun Kim, Dae Ho Yoon, Sang-Sik Ahn, Ji-Woon Yang, Woo Seok Yang, and Sungkyu Seo. Flexible glu- cose sensor using CVD-grown graphene-based field effect transistor. Biosensors and Bioelectronics, 37(1):82–87, 2012. [36] Oh Seok Kwon, Seon Joo Park, Jin-Yong Hong, A-Reum Han, Jun Seop Lee, James S Lee, Joon Hak Oh, and Jyongsik Jang. Flexible FET-type VEGF aptasen- sor based on nitrogen-doped graphene converted from conducting polymer. ACS Nano, 6(2):1486–1493, 2012. [37] Dongjin Lee and Tianhong Cui. Low-cost, transparent, and flexible single- walled carbon nanotube nanocomposite based ion-sensitive field-effect transistors for pH/glucose sensing. Biosensors and Bioelectronics, 25(10):2259–2264, 2010. [38] Fernando Patolsky and Charles M Lieber. Nanowire . Materials today, 8(4):20–28, 2005. [39] Eric Stern, Aleksandar Vacic, and Mark A Reed. Semiconducting nanowire field- effect transistor biomolecular sensors. IEEE Transactions on Electron Devices, 55(11):3119–3130, 2008. [40] Guo-Jun Zhang and Yong Ning. Silicon nanowire biosensor and its applications in disease diagnostics: a review. Analytica Chimica Acta, 749:1–15, 2012. [41] Yanli Wang, Tianyu Wang, Peimei Da, Ming Xu, Hao Wu, and Gengfeng Zheng. Silicon nanowires for biosensing, energy storage, and conversion. Advanced materials, 25(37):5177–5195, 2013. [42] Koen Besteman, Jeong-O Lee, Frank GM Wiertz, Hendrik A Heering, and Cees Dekker. Enzyme-coated carbon nanotubes as single-molecule biosensors. Nano let- ters, 3(6):727–730, 2003.

30 [43] Kannan Balasubramanian. Challenges in the use of 1D nanostructures for on-chip biosensing and diagnostics: A review. Biosensors and Bioelectronics, 26(4):1195– 1204, 2010. [44] Shaswat Barua, Hemant Sankar Dutta, Satyabrat Gogoi, Rashmita Devi, and Raju Khan. Nanostructured MoS2-based advanced biosensors: a review. ACS Applied Nano Materials, 1(1):2–25, 2017. [45] Varnika Yadav, Shounak Roy, Prem Singh, Ziyauddin Khan, and Amit Jaiswal. 2D MoS2-Based Nanomaterials for Therapeutic, Bioimaging, and Biosensing Applica- tions. Small, 15(1):1803706, 2019. [46] Deblina Sarkar, Wei Liu, Xuejun Xie, Aaron C Anselmo, Samir Mitragotri, and Kaustav Banerjee. MoS2 field-effect transistor for next-generation label-free biosen- sors. ACS Nano, 8(4):3992–4003, 2014. [47] Hongsuk Nam, Bo-Ram Oh, Pengyu Chen, Jeong Seop Yoon, Sungjin Wi, Mikai Chen, Katsuo Kurabayashi, and Xiaogan Liang. Two different device physics princi- ples for operating MoS2 transistor biosensors with femtomolar-level detection limits. Applied Physics Letters, 107(1):012105, 2015. [48] Qing Hua Wang, Kourosh Kalantar-Zadeh, Andras Kis, Jonathan N Coleman, and Michael S Strano. Electronics and optoelectronics of two-dimensional transition metal dichalcogenides. Nature , 7(11):699, 2012. [49] Kourosh Kalantar-zadeh and Jian Zhen Ou. Biosensors based on two-dimensional MoS2. ACS Sensors, 1(1):5–16, 2015. [50] Sara Rigante, Paolo Scarbolo, Mathias Wipf, Ralph L Stoop, Kristine Bedner, Elizabeth Buitrago, Antonios Bazigos, Didier Bouvet, Michel Calame, Christian Sch¨onenberger, et al. Sensing with advanced computing technology: fin field-effect transistors with high-k gate stack on bulk silicon. ACS Nano, 9(5):4872–4881, 2015. [51] Jessica Alfonsi. Wolfram Demonstrations Project – Elec- tronic Structure of a SWCNT in Tight-Binding Wannier Representation. https://www.demonstrations.wolfram.com/ ElectronicStructureOfASingleWalledCarbonNanotubeInTightBindi, 2010. Accessed 2019-09-16. [52] Joseph Wang. Carbon-nanotube based electrochemical biosensors: A review. Elec- troanalysis: An International Journal Devoted to Fundamental and Practical Aspects of Electroanalysis, 17(1):7–14, 2005. [53] Paolo Bondavalli, Pierre Legagneux, and Didier Pribat. Carbon nanotubes based transistors as gas sensors: state of the art and critical review. Sensors and Actuators B: Chemical, 140(1):304–318, 2009. [54] Merc`ePacios Pujad´o. Carbon nanotubes as platforms for biosensors with electro- chemical and electronic transduction. Springer Science & Business Media, 2012. [55] Robert J Chen, Yuegang Zhang, Dunwei Wang, and Hongjie Dai. Noncovalent side- wall functionalization of single-walled carbon nanotubes for protein immobilization. Journal of the American Chemical Society, 123(16):3838–3839, 2001.

31 [56] Lu Wang, Ye Wang, Jen It Wong, Tom´asPalacios, Jing Kong, and Hui Ying Yang. Functionalized MoS2 nanosheet-based field-effect biosensor for label-free sensitive detection of cancer marker proteins in solution. Small, 10(6):1101–1105, 2014. [57] Junjie Shan, Jinhua Li, Xueying Chu, Mingze Xu, Fangjun Jin, Xiaojun Wang, Li Ma, Xuan Fang, Zhipeng Wei, and Xiaohua Wang. High sensitivity glucose detection at extremely low concentrations using a MoS2-based field-effect transistor. RSC Advances, 8(15):7942–7948, 2018. [58] Mayra S Artiles, Chandra Sekhar Rout, and Timothy S Fisher. Graphene-based hybrid materials and devices for biosensing. Advanced drug delivery reviews, 63(14- 15):1352–1360, 2011. [59] Kostya S Novoselov, Andre K Geim, Sergei V Morozov, D Jiang, Y Zhang, Sergey V Dubonos, Irina V Grigorieva, and Alexandr A Firsov. Electric field effect in atomi- cally thin carbon films. science, 306(5696):666–669, 2004. [60] NobelPrize.org – Press release – Graphene 2010. https://www.nobelprize.org/ prizes/physics/2010/press-release/. Accessed 2019-09-16. [61] Graphene-info – Huawei’s new Mate 20 X uses graphene film cooling technology. https://mail.graphene-info.com/ huaweis-new-mate-20-x-uses-graphene-film-cooling-technology, 2018. Accessed 2019-09-16. [62] GRAPHITE STOCK NEWS – Huawei Uses Super Cool Graphene System in Latest Phone. https://graphitestocknews.com/ huawei-uses-super-cool-graphene-system-in-latest-phone, 2019. Accessed 2019-09-16. [63] Nanomed website. https://www.nanomedical.com. Accessed 2019-09-16. [64] David Lloyd, Xinghui Liu, Jason W Christopher, Lauren Cantley, Anubhav Wadehra, Brian L Kim, Bennett B Goldberg, Anna K Swan, and J Scott Bunch. Band gap engineering with ultralarge biaxial strains in suspended monolayer MoS2. Nano letters, 16(9):5836–5841, 2016. [65] Xuezhi Ma, Qiushi Liu, Da Xu, Yangzhi Zhu, Sanggon Kim, Yongtao Cui, Lan- lan Zhong, and Ming Liu. Capillary-force-assisted clean-stamp transfer of two- dimensional materials. Nano Letters, 17(11):6961–6967, 2017.

32 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

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

33 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.

34