ORGANIC ELECTROCHEMICAL TRANSISTOR FOR BIOLOGICAL ELEMENT

Abstract

An organic electrochemical transistor including a source and drain connected by a conductive channel, a gate electrically connected to the conductive channel via an ionically stable layer, and a biological recognition layer in direct contact with the gate. The organic electrochemical transistor can be used to measure the concentration of a biological element in a biological sample. Also, an electronic device including the organic electrochemical transistor.

Claims

1.-12. (canceled)

13. An organic electrochemical transistor comprising source and drain connected by a conductive channel, a gate electrically connected to the conductive channel via a water immiscible ionic liquid layer, and a biological recognition layer in direct contact with the gate.

14. The organic electrochemical transistor according to claim 13, wherein the anionic part of the water immiscible ionic liquid is selected from the group of: hexafluorophosphate (PF6-), bis(trifluoro-methylsulfonyl)imide (Tf2N-), ethyl sulfate (EtSO4-), bis(trifluoromethylsulfonyl)imide (TFSI), tetrafluoroborate (BF4-), prolinate (Pro), and N-trifluoromethylsulfonyl-L-leucine (Tf-Leu).

15. The organic electrochemical transistor according to claim 13, wherein the cationic part of the water immiscible ionic liquid is selected from the group of: 1-alkyl-3-methylimidazolinium [CnMIM]; 1-propyl-3-methylpiperidinium (C3C1PIP); 3-(2-(Butylamino)-2-oxoethyl)-1-ethylimidazolium ([CH2CONHC4H9]C2IM) and tetrabutylphosphonium (P4444).

16. The organic electrochemical transistor according to claim 13, wherein the water immiscible ionic liquid is selected from the group of: 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]), 1-decyl-3-methylimidazolium bis(trifluoro-methylsulfonyl)imide ([DMIM][Tf2N]), 1-ethyl-3-methylimidazolium ethyl sulfate (C2MIM EtSo4), and 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [EMIM][TFSI].

17. The organic electrochemical transistor according to claim 13, wherein the water immiscible ionic liquid layer is in direct contact with the conductive channel.

18. The organic electrochemical transistor according to claim 13, wherein the water immiscible ionic liquid layer further comprises a solid-like matrix.

19. The organic electrochemical transistor according to claim 13, wherein biological recognition layer comprises enzymes, enzyme-based recognition systems, antibodies, antibody fragments, antibody dendrimer conjugates, nanobodies, engineered binding proteins, receptors, lectins, aptamers, aptazymes, ssDNA, dsDNA, DNA oligomers, ssRNA, dsRNA, RNA oligomers, modified RNA, DNA/RNA hybrids, peptide nucleic acids, cells, microorganisms, biological tissues or organelles.

20. The organic electrochemical transistor according to claim 19, further comprising a selective membrane over the water immiscible ionic liquid layer, over the biological recognition layer, or over both.

21. The organic electrochemical transistor according to claim 19, comprising successive layers: (a) a substrate, (b) an electric layer on the substrate, said electric layer comprising source, drain, gate and channel, wherein channel connects source and drain, (c) the biological recognition layer, the water immiscible ionic liquid layer and a hydrophobic layer comprising two recesses for receiving the biological recognition layer and the water immiscible ionic liquid layer on the electric layer, wherein the biological recognition layer is on gate, and wherein the water immiscible ionic liquid layer is on channel, (d) an encapsulation layer on hydrophobic layer to prevent damage and degradation, said encapsulation layer comprising a recess above the biological recognition layer and the water immiscible ionic liquid layer.

22. The organic electrochemical transistor according to claim 19, comprising successive layers: (a) a substrate, (b) an electric layer on the substrate, said electric layer comprising source, drain, gate and channel, wherein channel connects source and drain, (c) the biological recognition layer, the water immiscible ionic liquid layer and a hydrophobic layer comprising two recesses for receiving the biological recognition layer and the water immiscible ionic liquid layer on the electric layer, wherein the biological recognition layer is on a part of the gate, and wherein the water immiscible ionic liquid layer is on channel and on a part of gate, (d) an encapsulation layer on hydrophobic layer to prevent damage and degradation, said encapsulation layer comprising a recess above the biological recognition layer and the water immiscible ionic liquid layer.

23. An electronic device comprising an organic electrochemical transistor according to claim 13.

24. A method of measuring concentration of a biological element in a biological sample, comprising depositing a droplet of a biological sample on an organic electrochemical transistor according to claim 13.

25. The organic electrochemical transistor according to claim 1, wherein the cationic part of the water immiscible ionic liquid is a 1-alkyl-3-methylimidazolinium [CnMIM] selected from the group of: 1-ethyl-3-methylimidazolium (C2MIM), 1-butyl-3-methylimidazolium (BMIM), 1-hexyl-3-methylimidazolium (BMIM), 1-octyl-3-methylimidazolium (BMIM), 1-decyl-3-methylimidazolium (DMIM); 1-butyl-3-methylsilylimidazolium (C4(C1C1C1Si)IM); and 1, 3-diethylimidazolium (C2C2IM).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0082] FIG. 1 shows an exploded view of an organic electrochemical transistor with substrate (1), source (2S), drain (2D), gate (2G), channel (3), hydrophobic layer (4), biological recognition layer (5), ionically stable layer (6), encapsulation layer (7) and selective membrane (8).

[0083] FIG. 2 shows an organic electrochemical transistor in contact with a blood droplet (Sam). Blood droplet is in contact with biological recognition layer as well as with ionically stable layer and establishes electric connection between electrodes. Hydrophobic layer, encapsulation layer and selective membrane are omitted.

[0084] FIG. 3 shows a variant in which gate (2G) is partly covered with biological recognition layer (5) under a blood droplet (Sam) and partly covered with ionically stable layer (6). Hydrophobic layer, encapsulation layer and selective membrane are omitted.

EXAMPLES

[0085] The present invention is further illustrated by the following examples.

[0086] Preparation of OECT—Electrodes (2D), (2S) and (2G):

[0087] A glass substrate (1) is cleaned with acetone for 10 minutes then with isopropanol for 10 minutes then dried.

[0088] OECT-1: An ink containing silver (50-60% in weight of nanoparticles in tetradecane—Supplier Sigma Aldrich—Reference 736511) is deposited on glass substrate with a dimatix printer, according to drain (2D), source (2G) and gate (2G) geometry. Ink is then baked at 450° C. for 1 hour. Three electrodes are obtained. Distance between drain and source is 300 micrometer.

[0089] OECT-2: A polymeric mask is applied on glass substrate, so as to define drain (2D), source (2G) and gate (2G) geometry. Then, a 10 nm thick layer of Chromium (Cr) is evaporated under vacuum, followed by a 100 nm thick layer of Gold (Au).

[0090] Preparation of OECT—Channel (3):

[0091] An ink comprising 95.5% wt of PEDOT:PSS, 0.5% wt of dodecylbenzenesulfonic acid (DBSA) and 4% wt of ethylene glycol is prepared. With an ink-jet printer, ink is deposited on source (2D), between source (2D) and drain (2D), and on drain (2D) forming the channel (3). After printing, ink is baked at 120° C. for 1 hour. A channel having a length of 500 micrometers (on and between source and drain) and width of 4 mm.

[0092] Preparation of OECT—Hydrophobic Layer (4):

[0093] A hydrophobic ink is ink-jetted to yield the expected geometry. Thickness of hydrophobic layer is 5 micrometer.

[0094] Hydrophobic layer (4) defines two recesses. One recess corresponds to gate (2G) of OECT. The second recess corresponds to channel (3) of OECT.

[0095] Preparation of OECT—Biological Recognition Layer (5)

[0096] 10 mM of a solution A consisting of 10:1 molar ratio of 3-mercaptopropionic acid (3-MPA) and 11-mercaptoundecanoic acid (11-MUA) in ethanol is prepared.

[0097] Gate of OECT-2 device is cleaned then immersed in solution A for 18 hours at 22° C., in the dark and under flux of nitrogen. Then gate of OECT-2 is rinsed several times with ethanol and deionized water, then dried with the flux of nitrogen. A self-assembled monolayer (SAM) is thus obtained on gate of OECT-2.

[0098] A solution B consisting of 0.2 mol/L 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and 0.05 mol/L N-Hydroxysulfosuccinimide sodium salt (Sulfo-NHS) in water is prepared. EDC act as a temporary functionalization

[0099] Gate of OECT-2 covered with SAM is immersed in solution B for 2 hours at 25° C., then rinsed with Phosphate Buffer Solution. EDC reacts with free acid groups of SAM and brings a temporary functionalization.

[0100] A solution C consisting of 100 μg/mL anti-C reactive protein in Phosphate Buffer Solution (pH=7.4) is prepared.

[0101] Functionalized gate of OECT-2 is immersed in solution C for 2 hours at 25° C., then rinsed with Phosphate Buffer Solution. Anti-C reactive protein replaces EDC and binds to SAM.

[0102] A solution D consisting of 1 mol/L ethanolamine in Phosphate Buffer Solution (pH=7.4) is prepared.

[0103] Antibody functionalized gate of OECT-2 is immersed in solution D for 1 hour at 25° C., then rinsed with Phosphate Buffer Solution. Ethanolamine replaces EDC on acid sites which were not functionalized with anti-C reactive protein.

[0104] A solution E consisting of 1.5 μmol/L Bovine Serum Albumin (BSA) in Phosphate Buffer Solution (pH=7.4) is prepared.

[0105] Antibody functionalized gate of OECT-2 is immersed in solution E for 1 hour at 25° C., then rinsed with Phosphate Buffer Solution. BSA covers now all surface of OECT which was not functionalized with anti-C reactive protein. This step ensures that biological recognition layer will bind exclusively C reactive proteins. Other biological elements will not be able to accumulate on the surface and generate noise or artefacts in measures.

[0106] In all immersion steps, hydrophobic layer (4) sets limits to contact area of gate (2G) with solutions A to E.

[0107] Preparation of OECT—Water Immiscible Ionic Liquid Layer (6):

[0108] Channel of OECT-2 device is cleaned then 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) is deposited so as to form a 5 μm thick layer (same thickness as hydrophobic layer).

[0109] Preparation of OECT—Encapsulation Layer (7):

[0110] A Kapton® layer is used as encapsulation layer.

[0111] Measurements:

[0112] A solution of C-reactive protein at concentration of 100 mg.Math.mL.sup.−1 is prepared. A droplet of this solution is deposited on OECT, as shown in FIG. 2. The current-voltage response of OECT is measured with state-of-the-art electrical devices.