WO2011004136A1

WO2011004136A1 - Graphene biosensor

Info

Publication number: WO2011004136A1
Application number: PCT/GB2010/001231
Authority: WO
Inventors: Owen James Guy
Original assignee: Uws Ventures Limited
Priority date: 2009-07-07
Filing date: 2010-06-23
Publication date: 2011-01-13
Also published as: GB0911705D0; GB2471672B; GB2471672A; GB201200154D0

Abstract

The present disclosure relates to a sensor for detecting the presence of at least one biological molecule and a method for the production of such a sensor. The sensor comprises: a patterned graphene structure, at least two electric contacts arranged in contact with the patterned graphene structure for determining a conductivity; and at least one linker attached to at least a portion of the patterned graphene structure, wherein the at least one linker has a binding affinity for the at least one biological molecule.

Description

Title: Graphene Biosensor

Field of the invention

[0001] The present disclosure relates to graphene biosensors and to a method for detecting biological molecules with the graphene biosensor. The present disclosure also relates to a method for the production of the graphene biosensor. In particular, the present invention relates to biosensors having a patterned and chemically functionalized graphene surface.

Background of the invention

[0002] Sensors for detecting biological molecules, termed biosensors, are widely used. A large variety of biosensors have been developed for sensing or detecting biological molecules with increasing resolution and specificity.

[0003] A biological molecule within the meaning of the present disclosure is an organic molecule produced by or occurring in living organisms. The term biological molecules includes, but is not limited to polymeric molecules occurring in nature and their analogues, such as proteins, polysaccharides, and nucleic acids as well as small molecules such as primary metabolites, secondary metabolites, and natural products.

[0004] Besides optical and other approaches, many biosensors rely on the general principle of generating an electrical signal if the presence or absence of a biological molecule is detected. Structured semiconductor materials are in some cases used to form channels or other structures at the micrometer scale (micro-scale) or nanometer scale (nano-scale). [0005] Graphene is a planar sheet of carbon atoms forming a honey-comb shaped crystal lattice and has gained increasing interests for its electronic properties. While structures that are similar to graphene, such as carbon nanotubes, graphite and fullerenes have been widely used, planar graphene sheets have only recently become of interest for micro-scale or nano-scale applications. The structuring of graphene has advanced and the chemical modification of graphene has been investigated. However, graphene is today not a preferred choice for biological applications because of its low affinity for biological molecules. The biocompatibility issues of carbon nanotubes are often reported to be related to their shape and length rather than their chemical reactivity. Since graphene occurs as flakes or on substrates, this issue of shape does not have the same implications for graphene as for carbon nanotubes.

[0006] Recently the use of graphene in bio-devices and DNA transistors has been suggested (N. Mohanty, nano letters 2008, 8 (12), 4469 - 4476, 5 November 2008). This document proposes the use of chemically modified graphenes for the detection of bacteria or DNA strands, wherein graphene sheets are disposed on a silica substrate. This graphene sheets have a flake-like structure and substantially comprise plain graphene surfaces. These plain graphene surfaces are achieved by chemically modifying the graphene surface to graphene oxide or graphene amine. This method is not selective for specific biological molecules. The method can be used to selectively detect bio-molecules if graphene-amine (GA) or graphene-oxide (GO) is modified by attaching a bio-receptor molecule. For example, Mohanty reports attachment of DNA strands to a GO surface. The DNA modified graphene surface can then be used to selectively detect its complementary pair DNA strand. Thus a device using the DNA modified graphene surface can act as a selective biosensor for the complementary DNA strand. Mohanty also states that to attach DNA to the GO surface, a linking molecule, (0-(7-azabenzoMazole-l-yl)-iV,iV,iV_r/V'- tetramethyluronium hexafluorophosphate (HATU) (an amidecoupling reagent), must be used. Mohanty does not give details on this linking process and relates to a micrometer- scale sensor.

[0007] No graphene based biosensors are known so far that allow a selective measurement of amount or concentration of biological molecules.

Summery of the invention [0008] The present disclosure relates to a sensor for detecting the presence of at least one biological molecule.

[0009] In one aspect the sensor comprises a patterned graphene structure, at least two electric contacts arranged in contact with the patterned graphene structure for determining a conductivity, and at least one linker attached to at least a portion of the patterned graphene structure, wherein the at least one linker has a binding affinity for the at least one biological molecule. [0010] In a second aspect the sensor comprises a graphene surface, at least one linker comprising an aniline, wherein the at least one linker is attached to at least a portion of the graphene surface, wherein the at least one linker has a binding affinity of the at least one biological molecule. [0011] In a third aspect the sensor comprises a graphene structure arranged on a silicon carbide substrate, wherein at least a portion of the graphene structure is functionalized, i.e. chemically functionalized, such that the functionalized portion of the graphene structure has a binding affinity for the at least one biological molecule. [0012] Two or more of these aspects may be combined in a sensor for detecting a biological molecule depending on the desired application of the sensor.

[0013] For example, the graphene structure may be chemically functionalized using at least one linker. The at least one linker may be a linker molecule or a group of molecules. The at least one linker may comprise at least one of an aniline, a diazonium ion or diozonium salt and a sensing molecule. The sensing molecule may be at least one of a biomarker, a receptor molecule, an amino acid, an enzyme, or an antibody for the at least one biological molecule. [0014] The present disclosure also relates to a method functionalizing graphene. The method may comprise chemical functionalization using at least one linker. The method -A- comprises providing a graphene surface, attaching at least one nitrobenzene molecule to the graphene surface, and reducing the nitrobenzene to an aniline.

[0015] A diazonium salt may be used to attach the at least one nitrobenzene molecule to the graphene surface. A sensing molecule, comprising at least one of a receptor molecule, an amino acid, an enzyme, or an antibody may be attached to the amine group of the aniline, which may be chosen according to their specificity or affinity for the biological molecule or group of biological molecules to be detected by the sensor. [0016] The graphene surface or graphene structure may be grown or arranged on a silicon carbide substrate, for example by epitaxial growth or sublimation growth. The graphene structure may comprise one or more epitaxial layers (multi-epitaxial layer). As an example the graphene structure may have a thickness of 1 to 10 atomic layers. [0017] The graphene structure may be patterned into a device structure. The graphene structure may comprise one or more channels or a channel network. The size of channels may be adapted to specific application and may be at the micrometer scale or nanometer scale. The graphene structure may further comprise at least two metal contacts which may be used as electrodes. Two or more metal contacts may be arranged at each channel to detect a change in at least one electrical property of the graphene, when a biological molecule attaches to the at least one linker.

Short description of the Figures [0018] The Figures illustrate examples of the present disclosure and are not intended to limit the scope of the invention as defined by the claims.

Fig. 1 shows a three-dimensional representation of a sensor comprising graphene nanochannel and nano-transitor devices.

Fig. 2 shows a cross-section of a graphene nanochannel device. Fig. 3 shows a cross-section of a graphene nanochannel device using semi-insulating SiC epitaxial layer.

Fig. 4 shows a schematic of a sensor comprising a single nanochannel.

Figs. 5a and 5b show alternative schematics of a sensor implemented as nano-transistor.

Fig. 6 shows an array of nanochannels and transistors. Fig. 7 shows an example of a manufacturing process for a patterned graphene structure. Fig. 8. shows a functionalization of a grahpene surface.

Figs. 9a and 9b show two alternatives for the attachment of a linker to a graphene surface.

Fig. 10 shows an alternative functionalization of a graphene surface.

Fig. 11 shows a functionalized graphene surface produced by plasma treatment. Detailed description of an example

[0019] Examples of the present disclosure will now be described with reference to the figures. [0020] Figure 1 shows a three-dimensional representation of a plurality of sensors arranged on a substrate 110. The substrate 110 is made from silicon carbide (SiC) on which a structured graphene pattern is arranged. The pattern comprises a plurality of graphene channels 120 of different channel widths to illustrate that the sensor according to the invention is equally applicable with different channel dimensions. A sensor usually comprises one channel and two or more metal contacts or electrodes 130. The graphene channels and thus the individual sensors are separated by a silicon dioxide (SiO₂) layer 150 providing electric insulation between the metal contacts and the graphene channels. A plurality of metal contacts or metal electrodes is arranged on or at the graphene channels. The metal contacts or metal electrodes may be silver probes or may be made from other metals such as, for example, titanium, nickel, gold or aluminium. The metal contacts may or may not be in contact with the grahpene channel, as will be explained in detail below. The electrodes may have different shapes such as triangles or squares. Some examples of the different shapes are shown in Fig. 1. The shape of the metal contacts or electrodes may be adapted to the specific needs of a specific biosensor. A measurement channel made from graphene is formed between two of the electrodes. The two electrodes are arranged at opposite ends of the channel. As an example, some of the channels may comprise a third electrode arranged at one side of the channel for operating these sensors as a lateral transistor. Fig. 1 shows an assembly of different types and examples of sensors for the detection of biological molecules. In practical applications, a sensor may comprise only one channel. [0021] Figure 2 shows a first example of a cross section of a sensor according to the present disclosure comprising a graphene channel. The sensor is formed on a SiC substrate 210. The SiC substrate 210 can be semiconducting or semi-insulating, or a combination of semiconducting or semi-insulating depending on the conductivity. The difference in conductivity arises from doping of the SiC as known in the art. If there are an excess of one type of impurity or dopant atom in the SiC, the SiC the conductivity will be increased and the SiC substrate becomes semi-conducting. If there is little or no excess, the SiC will be virtually insulating or semi-insulating.

[0022] A graphene layer 220, as shown in Fig. 2, is grown, for example by epitaxial growth or sublimation growth, on the SiC substrate. The growth process will be described below with respect to Fig. 7.

[0023] The graphene layer 220 may, for example have the shape of a graphene channel as illustrated in Fig. 1 and described in further detail with respect to Figs. 4, 5 and 6 below. Two metal contacts 231 and 232 are arranged on top of the graphene layer 220 and form end points of the graphene channel 220. The metal contacts 231, 232 may be electrodes and can be made of silver material or any other material known in the art. The graphene channel 220 is separated from other structures or other devices that may be arranged on the SiC substrate 210 by an insulating silicon dioxide (SiO₂) layer 250. A metallic back electrode 240 can be provided on the back surface of the SiC substrate 210. The back electrode 240 may be of the same material as the metal contacts 231 and 232.

[0024] Figure 3 shows an alternative example of a sensor comprising a graphene channel. The sensor comprises a SiC substrate 310 with a back side electrode 340 as described with respect to figure 2. A semi-insulating SiC layer 360 is arranged on the silicon carbide substrate 310 and a graphene layer 320 is arranged (i. e. grown) on top of the semi- insulating SiC layer 360. The semi-insulating layer electrically isolates the highly conductive graphene layer from the SiC substrate 310. If the SiC substrate 310 is conductive, some of the current in any graphene device could potentially travel through the SiC substrate 310. Semi-insulating SiC can also be used as the SiC substrate 310. Metal contacts 331 and 332 are arranged on top of the graphene layer 320.

[0025] It is obvious to a person skilled in the art that the examples shown in figure 2 and 3 may be combined and that a semi insulating SiC layer may be used in combination with a SiO₂ layer. The graphene layers 220 and 320 may have different patterns and layouts may be modified according to the requirements of the application of the sensor. In particular, the graphene layers may be channels or channel networks at the micrometer scale or nanometer scale.

[0026] Figure 4 shows an example of a graphene structure in a top view. A graphene channel 420 is arranged between two metal contacts 431 und 432. The two metal contacts or electrodes 431 und 432 in the graphene channel 420 are otherwise insulated by a SiO₂ layer 450. The sensor or channel arrangement is seen from the top and may be formed on a SiC substrate (not shown). The graphene channel 420 may be in direct contact with the SiC substrate. The graphene channel 420 may have a thickness or channel width about 20 nm to about 200 nm. The length of the channel may vary from about 200 nm to 10 μm. The structured graphene channel 420 may therefore be termed a "nano-channel". However, for some applications, the graphene channel 420 may be made larger and thus be at the micrometer scale or sub- millimeter scale. The graphene channel 420 may be open at the topside to allow access of biological molecules to the graphene channel 420.

[0027] The two metal contacts or metal electrodes 431 and 432 may be much larger in size compared to the width of the graphene channel 420. The dimension of the metal contacts or metal electrodes 431, 432 may have a surface area of, for example, about 20 to 50 μm². However, different electrode sizes can be used. Using a back electrode as shown in Figs. 2 and 3 allows the operation of the graphene channel 420 as a field effect transistor. However, the electric properties of the graphene channel 420 may also be determined by measuring the electrical resistance of, a current passing through, the impedance of other parameters of the graphene channel 420. The measurement of the electrical property can rely on the principle that the electrical property changes if a biological molecule or a plurality of biological molecules binds to the graphene channel 420. This change in the electrical property may be detected as an electrical signal which can be further amplified. A back electrode may be omitted depending on the electrical property to be detected and the type of sensor that is to be used. The graphene channel 420 is functionalized to enable the binding or attachment of specific biological molecules. The functionalization of the graphene will be explained in detail with respect to Fig. 7. [0028] Fig. 5a shows a top view of another example of a sensor with a graphene channel. As described with respect to Fig. 4, a graphene channel 520 is arranged on top of a SiC substrate and terminated by metal contacts or electrodes 531 and 532. The metal contacts or electrodes 531, 532 are in direct electrical contact with the graphene channel 520 which again is functionalized to allow binding of specific biological molecules. In addition to the structure shown and described with respect to Fig. 4, a third gate contact 535 is arranged at one side of the graphene channel 520. The gate contact 535 may be a silver electrode and may be of the same material as the other electrodes 531 and 532. As shown, the gate contact 535 is not in direct contact with the graphene channel 520. For example, a gap of between about 5 nm to about 100 nm will be left between the graphene channel 520 and the gate contact 535. Using the gate contact 535 as gate electrode, the sensor may be operated as a lateral field effect transistor, which changes its electrical properties when one or more biological molecules attach to the graphene channel 520. A back electrode may be omitted.

[0029] Fig. 5b shows an alternative example of the graphene sensor of Fig. 5a, wherein the gate contact 535 comprises and additional graphene gate contact 536 as graphene gate electrode. The graphene gate contact is in electrical contact with the gate contact 535. The spacing between the graphene gate contact 536 and the graphene channel 520 may be about 2 ran to about 100 nm. [0030] The examples of the graphene channels 420, 520 shown and explained with respect to Figs. 4, 5a and 5b are purely illustrative and more complex structures and different sizes may be used. Figure 6 shows an array of different structure types and sizes that may be used as examples of the present invention. While Fig. 6 shows different types of sensors that are arranged close to each other, a sensor according to the present disclosure may comprise only one channel.

[0031] The channel structures shown as examples in Figs. 1 to 6 may be formed as graphene layer or multi-epitaxial layer graphene grown using a epitaxial growth. The layer thickness may be between one and about 10 atomic layers or more.

[0032] Figs 7a-h show an example of growth and fabrication processes process that may be applied in the manufacture of a patterned graphene structure of the present disclosure. The growth process involves sublimation growth of graphene on SiC substrate 710. The SiC substrate 710 may be a commercially available SiC wafer. The growth process comprises sublimation of silicon from the first few surface layers of the SiC substrate. Carbon atoms left behind after silicon sublimation, reconstruct themselves into a hexagonal graphene structure. The growth process involves heating the SiC substrate at between about 1000 and 1300⁰C under vacuum conditions, for example ultra high vacuum conditions with pressures lower than 10^"9 mbar. An alternative growth process involves higher temperatures (for example up to about 1500 to 1700⁰C or more) and higher pressures. For example, an epitaxial graphene layer 720 is grown on the SiC substrate 710 by annealing SiC under ultra high vacuum (UHV) conditions, for example for about 10 minutes at about 125O⁰C. The temperature and time duration may be varied to control the thickness of the graphene layer 720.

[0033] The graphene layer is then patterned by depositing a layer of electron beam resist (Fig. 7a) and subsequently patterning using electron beam lithography (Fig 7b). The resist is developed (Fig. 7c) and the exposed graphene is then etched away using an oxygen plasma etch (Fig. 7d). After striping the remaining resist (Fig. 7e), graphene channels remain on the SiC substrate. The metal electrodes can then be fabricated by depositing a thin film of metal from 100 run to 1 μm in thickness (Fig. 7f). A Photoresist is then deposited on top of the metal layer and patterned using a standard photolithography process (Fig 7g). Finally the thin film of metal is etched, leaving behind the final device structures (Fig. 7h).

[0034] Figs. 8 to 11 show an examples of how the graphene structures, i. e. the graphene channels may be chemically functionalized to have a binding affinity for the biological molecule. The binding affinity may be specific for the biological molecule to be detected with the sensor. The biological molecule to be detected is also termed target molecule.

[0035] Fig. 8 shows an example of the attachment of a linker 870, 880 to a graphene surface 820. A possible mechanism for nitrobenzene attachment to graphene and subsequent electrochemical reduction to aniline is the attachment of a diazonium salt

to the graphene surface 820 in order to attach a nitrobenzene or a nitrobenzene derivate to the graphene surface 820 as illustrated in Fig. 9a and 9b. The nitro group of the nitrobenzene may than be reduced to an amine as shown in Fig. 9a. The resulting aniline 870 has an amine group that can be used as such as a linker.

[0036] A possible mechanism for benzoic acid attachment to graphene is the attachment of a diazonium salt, 4-benzoic acid diazonium tetrafluoroborate (COOHC₆H₄N₂BF₄), to the graphene surface 820 in order to attach a benzoic acid or benzoic acid derivative to the graphene surface 820 as illustrated in Fig. 9b.

[0037] To increase sensitivity and specificity of the sensor, a sensing molecules 880 can be attached to the amine group of the aniline 870 or to the carboxyl group of the benzoic acid. The sensing molecules 880 may comprise a biomarker, a receptor, an antibody, an amino acid, an enzyme or any other biological molecule appropriate for specifically binding a target molecule 890. It is preferred that the receptor molecule 880 has a high affinity to the target molecule 890 (the biological molecule to be detected with the sensor). A known specific interaction between the sensing molecule 880 and the target molecule 890 can be used if the sensing molecule 880 is attached to the aniline 870. For example, an antibody or enzyme as the sensing molecule 880 may be attached to the aniline linker 870 having a high affinity for the target molecule 890 that is to be detected. As the receptor molecule 880 is highly specific to the target molecule 890, only these target molecules 890 will bind to the sensing molecule 880 and thus to the graphene surface 820, thereby changing the electrical properties of the graphene surface 820. As illustrated with respect to Figs. 1 to 6, the graphene surface 820 may be the surface of a graphene channel. Other biological molecules or any other molecule coming into contact with the graphene surface 820 or the receptor molecule 880 will not bind to the graphene surface 820 or the sensing molecule 880 and have no effect on the electrical properties of the graphene surface 820.

[0038] The high specificity of the sensor may be shown using a quantum dot 895 or other fluorescent probes attached to the target molecules 890 as shown in Fig. 8c. In this way the high specificity or the sensor can be shown using fluorescents or other optical techniques known in the art. [0039] It is obvious to a person skilled in the art that this sensor can be made specific to any desired biological target molecule that is to be detected if a corresponding specific receptor is known which can be attached to the linker molecule 870 attached to the graphene surface of the sensor of the present disclosure.

[0040] Figs. 9a and 9b show the functionalization of the graphene surface using nitrobenzene, aniline, benzoic acid or other benzene derivate that is attached to the graphene surface. The nitrobenzene or nitrobenzene derivate is then electrochemically reduced to an amine 870.

[0041] The graphene may also be functionalized using ethandiamine for the linker 870 as illustrated in Fig. 10. The ethandiamine may be attached to carboxylated graphene or graphene oxide to give amine functionalised graphene to which a sensing molecule 880 can be bound.

[0042] The graphene may also be functionalized by a NH₃ plasma treatment of the graphene surface as illustrated in Fig. 11. A sensing molecule 880 can be bound to the resulting functionalized graphene amine. [0043] A person skilled in the art may make the appropriate amendments to optimize the sensor for specific applications and make the appropriate modification to the functionalization and the shape and dimensions of the graphene structures. For example, a higher sensitivity may be reached if smaller graphene channels are used. [0044] The invention covers not only individual embodiments discussed but also combinations of the embodiments that have been described.

Claims

1. A sensor for detecting the presence of at least one biological molecule (890), the sensor comprising:

- a patterned graphene structure (120; 220; 320; 420; 520, 536);

- at least two electric contacts (130; 231, 232; 331, 332; 431, 432; 531, 532, 535, 536) arranged in contact with the patterned graphene structure for determining a conductivity; and

at least one linker (870, 880) attached to at least a portion of the patterned graphene structure,

wherein the at least one linker has a binding affinity for the at least one biological molecule (890).

2. The sensor of claim 1 , wherein the patterned graphene structure comprises at least one (three dimensional) channel.

3. The sensor of claim 2, wherein the at least one channel has a length of about 100 μm or less.

4. The sensor of claim 2 or 3, wherein the at least two electric contacts

(microelectrodes) are arranged on opposite sides of the at least one channel.

5. The sensor of any of the preceding claims, wherein the at least one linker comprises a diazonium salt.

6. The sensor of any of the preceding claims, wherein the at least one linker comprises an amine group.

7. The sensor of any of the preceding claims, wherein the at least one linker comprises an aniline (870).

8. The sensor of any of the preceding claims, wherein the at least one linker comprises at least one of a receptor molecule, an amino acid, an enzyme, or an antibody for the at least one biological molecule.

9. The sensor of any of the preceding claims, wherein the patterned graphene structure is arranged on a silicon carbide substrate.

10. The sensor of any of the preceding claims, wherein the patterned graphene structure has a thickness of about 10 atomic layers of graphene or less.

11. A method for detecting the presence of at least one biological molecule (890) using a sensor with a patterned graphene structure (120; 220; 320; 420; 520, 536) having at least one linker (870, 880) attached to at least a portion of the patterned graphene structure, the method comprising:

- measuring the conductivity between the at least two electrical contacts;

- exposing the sensor to an environment with the at least one biological molecule such that the at least one biological molecule binds to the at least one linker;

- measuring a change in the conductivity, wherein the change in the conductivity is caused cause by the binding of the at least one biological molecule.

12. A sensor for detecting the presence of at least one biological molecule (890), the sensor comprising:

- a graphene surface (120; 220; 320; 420; 520; 820);

at least one linker comprising at least one of an aniline (870) or a benzoic acid (870), wherein the at least one linker is attached to at least a portion of the graphene surface,

wherein the at least one linker has a binding affinity of the at least one biological molecule.

13. The sensor of claim 12, wherein the at least one linker comprises at least one diazonium salt for attachment of the linker at the graphene surface.

14. The sensor of claim 12 or 13, wherein the at least one linker comprises least one of a receptor molecule, an amino acid, an enzyme, or an antibody for the at least one biological molecule.

15. The sensor of anyone of claims 12 to 14, further comprising a patterned graphene structure comprising the graphene surface.

16. The sensor of anyone of claims 12 to 15, further comprising at least two electric contacts arranged in contact with the graphene surface.

17. A method for functionalizing graphene, the method comprising:

- providing a graphene surface (120; 220; 320; 420; 520; 820);

- attaching at least one nitrobenzene molecule to the graphene surface; and

- reducing the nitrobenzene to an aniline.

18. The method of claim 17, further comprising using at least one diazonium salt for attaching the at least one nitrobenzene molecule.

19. The method of claim 17 or 18, further comprising attaching at least one of a receptor molecule, an amino acid, an enzyme, or an antibody to the aniline.

20. The method of anyone of claims 17 to 19, wherein the providing of the graphene surface comprises growing a graphene layer.

21. The method of claim 20, wherein the growing of the graphene layer comprises epitaxial growth.

22. The method of claim 20 or 21, wherein the growing of the graphene layer is carried out on a silicon carbide substrate.

23. The method of any of claims 17 to 22 in combination with a sensor of any of claims 1 to 16.

24. A sensor for detecting the presence of at least one biological molecule (890), the sensor comprising a graphene structure (120; 220; 320; 420; 520; 536) arranged on a silicon carbide substrate (110; 210; 310, 710), wherein at least a portion of the graphene structure is functionalized such that the functionalized portion of the graphene structure has a binding affinity for the at least one biological molecule.

25. The sensor of claim 24, wherein the graphene structure comprises one or more epitaxial-layers.

26. The sensor of claim 24 or 25, wherein the graphene structure is a patterned graphene structure comprising at least one channel.

27. The sensor of claim 26, wherein at least two electric contacts are arranged on opposite sides of the at least one channel.

28. The sensor of anyone of claims 24 to 27, wherein the graphene structure is functionalized using at least one linker attached to at least a portion of the graphene structure.

29. The sensor of claim 28, wherein the at least one linker comprises a diazonium salt.

30. The sensor of claim 28 or 29, wherein the at least one linker comprises at least one of an aniline or benzoic acid.

31. The sensor of anyone of claims 28 to 30, wherein the at least one linker comprises at least one of a receptor molecule, an amino acid, an enzyme, or an antibody for the at least one biological molecule.

32. The sensor of anyone of claims 24 to 31, wherein the graphene structure has a thickness of about 10 atomic layers of graphene or less.

33. A method for producing a sensor for detecting biological molecules (890), the method comprising:

- growing a graphene structure (120; 220; 320; 420; 520; 536) on a silicon carbide substrate (110; 210; 310, 710),;

- functionalizing at least a portion of the graphene structure such that the portion of the graphene structure has a binding affinity for at least one biological molecule.

34. The method of claim 33, wherein growing the graphene structure comprises epitaxial growth graphene.

35. The method of claim 33 or 34, further comprising patterning the graphene structure.

36. The method of claim 35, wherein patterning the graphene structure comprises forming at least one channel in the graphene structure.

37. The method of anyone of claims 33 to 36, wherein functionalizing at least the portion of the graphene structure comprises attaching at least one linker to the graphene structure.

38. The method of claim 37, wherein the at least one linker comprises at least one of a nitrobenzene, diazonium salt, aniline, benzoic acid, a receptor molecule, an amino acid, an enzyme, or an antibody.