ORGANIC ELECTROCHEMICAL TRANSISTOR BASED SENSOR

Abstract

An organic electrochemical transistor, which includes a biologic detection layer and a catalytic layer, the latter being a composite material including noble metal nanoparticles and an organic conductive matrix. Also, a method for detection of a biological analyte wherein a biological fluid is contacted with such an organic electrochemical transistor.

Claims

1.-13. (canceled)

14. An organic electrochemical transistor comprising source and drain connected by a conductive channel, a gate electrode, a catalytic layer and a biologic detection layer, wherein the catalytic layer is a composite material comprising noble metal nanoparticles and a conductive matrix selected from an organic conductive polymer or a conductive allotrope of carbon, wherein the catalytic layer is in direct contact with the gate electrode, and wherein the biologic detection layer is in direct contact with the catalytic layer; wherein noble metal nanoparticles are grafted with thiophenol derivatives of formula (I): ##STR00008## wherein R moiety of thiophenol derivatives is charged or comprises at least one aromatic group.

15. The organic electrochemical transistor according to claim 14, wherein R moiety comprises a function selected from charged ternary amine, quaternary amine, sulfonate and phosphonate.

16. The organic electrochemical transistor according to claim 15, wherein R moiety is selected from 4-trimethylammonium thiophenol (IIa), 4-mercaptobenzenesulfonic acid (IIb), N-4-thiophenol-(2, 5 diamino) propenamide (IIc) and, 4-mercaptobenzenephosphonic acid (IId), ##STR00009##

17. The organic electrochemical transistor according to claim 14, wherein R moiety comprises one aromatic group selected from N-(4-mercaptophenyl)pyrene-1-carboxamide (IIIa) and 4-(tritylamino)benzenethiol (IIIb). ##STR00010##

18. The organic electrochemical transistor according to claim 14, wherein noble metal nanoparticles are platinum nanoparticles.

19. The organic electrochemical transistor according to claim 14, wherein the organic conductive polymer of the catalytic layer is selected from polythiophene derivatives, polypyrrole, polyaniline.

20. The organic electrochemical transistor according to claim 19, wherein the organic conductive polymer of the catalytic layer is poly(3,4-ethylenedioxythiophene) polystyrene sulfonate.

21. The organic electrochemical transistor according to claim 14, wherein the conductive allotrope of carbon of the catalytic layer is selected from carbon nanotubes, graphene or carbon powder.

22. The organic electrochemical transistor according to claim 14, wherein the biologic detection layer is a composite material comprising a biologic recognition element and a polymer.

23. The organic electrochemical transistor according to claim 22, wherein the polymer is selected from polyvinylpyridine derivatives, polysaccharides derivatives, chitosan derivatives or cellulose acetate derivatives.

24. The organic electrochemical transistor according to claim 14, wherein the biologic detection layer is a composite material comprising a biologic recognition element and an allotrope of carbon.

25. The organic electrochemical transistor according to claim 24, wherein the allotrope of carbon is selected from carbon nanotubes, graphene or carbon powder.

26. The organic electrochemical transistor according to claim 22, wherein the biologic recognition element is an enzyme.

27. The organic electrochemical transistor according to claim 26, wherein the biologic recognition element is Glucose oxidase or Lactate oxidase.

28. The organic electrochemical transistor according to claim 24, wherein the biologic recognition element is an enzyme.

29. The organic electrochemical transistor according to claim 28, wherein the biologic recognition element is Glucose oxidase or Lactate oxidase.

30. The organic electrochemical transistor according to claim 14, comprising: a substrate, the source electrode and the drain electrode, the channel connecting source electrode and drain electrode, the gate electrode located near the channel, the catalytic layer in direct contact with the gate electrode and comprising noble metal nanoparticles grafted with thiophenol derivatives of formula (I); and ##STR00011## the biologic detection layer in direct contact with the catalytic layer and comprising a biologic recognition element.

31. The organic electrochemical transistor according to claim 14, comprising: a polyimide polymeric substrate, the source electrode and the drain electrode, source electrode and drain electrode being gold electrodes, the channel connecting source electrode and drain electrode, channel being poly(3,4-ethylenedioxythiophene) polystyrene sulfonate polymer (PEDOT:PSS), the gate electrode located near the channel, gate electrode being a gold electrode, the catalytic layer in direct contact with the gate electrode and comprising platinum nanoparticles grafted with thiophenol derivatives of formula (I) and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate polymer (PEDOT:PSS) as organic conductive polymer; and ##STR00012## the biologic detection layer in direct contact with the catalytic layer; comprising Glucose oxidase or Lactate oxidase as biologic recognition element; and a derivative of chitosan.

32. The organic electrochemical transistor according to claim 14, wherein the organic electrochemical transistor is totally or partially encapsulated in a membrane.

33. A method for detection of a biological analyte wherein a biological fluid is contacted with an organic electrochemical transistor according to claim 14.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0067] FIG. 1 illustrates a schematic of a state of the art OECT, with equivalent electrical circuit. On a substrate (1) are disposed source electrode (2) and drain electrode (3), connected by a channel (4). A gate electrode (5) is located in the neighborhood of channel (4) and electrically connected to channel (4) through an electrolyte (not represented). A potential V.sub.DS is imposed between drain and source. Another potential V.sub.GS is imposed between gate and source.

[0068] FIG. 2 illustrates a schematic of the OECT according to the invention. A catalytic layer (6) comprising noble metal nanoparticles (7) in an organic conductive matrix (8) is in contact with gate electrode (5). A biologic detection layer (9) is in contact with catalytic layer (6) (exploded view for better understanding).

[0069] FIG. 3 shows results obtained in example 1. FIG. 3a: Drain Source current I.sub.DS (dotted line, in mA) and gate source current density j.sub.GS (continuous line, in μA.Math.cm.sup.−2) as a function of time (in seconds). FIG. 3b: stationary values of I.sub.DS (squares in mA) and j.sub.GS (triangles in μA.Math.cm.sup.−2) as a function of glucose concentration in sample (in mmol/L).

[0070] FIG. 4 shows results obtained in example 2. FIG. 4a: Drain Source current I.sub.DS (doted line, in mA) and gate source current density j.sub.GS (continuous, line in μA.Math.cm.sup.−2) as a function of time (in seconds). FIG. 4b: stationary values of I.sub.DS (squares in mA) and j.sub.GS (triangles in μA.Math.cm.sup.−2) as a function of glucose concentration in sample (in mmol/L).

[0071] FIG. 5 illustrates a schematic of a functionalized nanoparticle obtained by grafting of thiophenol derivative (I) on nanoparticle surface via a covalent bound. Typical diameter of nanoparticles is about 30 nm, while typical thickness of the thiophenol derivative crown is about 1 nm.

[0072] FIG. 6 shows results obtained in comparative example. FIG. 6a: Drain Source current I.sub.DS (in mA) for OECT-1 with platinum nanoparticles (squares, solid line) and OECT-C1 without platinum nanoparticles (triangles, dotted line) as a function of H.sub.2O.sub.2 concentration in sample (in mmol/L). FIG. 6b: Gate source current density j.sub.GS (in μA.Math.cm.sup.−2) for OECT-1 with platinum nanoparticles (squares, solid line) and OECT-C1 without platinum nanoparticles (triangles, dotted line) as a function of H.sub.2O.sub.2 concentration in sample (in mmol/L).

EXAMPLES

[0073] The present invention is further illustrated by the following examples.

[0074] Preparation of Grafted Platinum Nanoparticles

Synthesis of 4,4′-disulfanediylbis(N,N,N-trimethylbenzenamonium)

[0075] Under argon using Schlenk techniques, 4-aminophenyl disulfide (496 mg, from Aldrich) is dissolved in anhydrous DMF (10 mL) under stirring. N,N-diisopropylethylamine (2.04 mL, from Aldrich) and iodomethane (2.24 mL, from Aldrich) were added and the mixture was stirred for 48 h at room temperature. The solution was filtered, and the crude product was precipitated by adding dropwise the filtrate solution to 100 mL of vigorously stirred cold diethylether. The solution was filtered and the residual solid was purified by washing it twice with boiling acetone in a reflux apparatus for 45 min. The colorless powder was dried under high vacuum leading to the desired product (432 mg).

[0076] Synthesis of Platinum Nanoparticles with a 4-(Trimethylammonium)Thiophenolate Crown

[0077] A solution of Platinum(IV) chloride (387.3 mg, from Aldrich) dissolved in hexylamine (95 mL, from Acros Organics) was prepared (Solution A). A solution of sodium borohydride (349.9 mg, from Aldrich) in a mixture of 25 mL distilled water and 25 mL methanol (from VWR) was prepared and 25 mL hexylamine were added (Solution B) Immediately after preparation, the solution B is combined with the solution A (Solution C). After 20 s, a solution of 4,4′-disulfanediylbis(N,N,N-trimethylbenzenamonium) (425 mg) in a mixture of 25 mL of hexylamine, 25 mL of methanol and 15 mL of distilled water was added to the solution C. After 3 min 30 s, 110 mL of distilled water were added, and the mixture was stirred at room temperature for 10 min. The reaction mixture was then transferred into a separation funnel and 150 mL of distilled water were added. The aqueous phase was isolated and concentrated under reduced pressure. The nanoparticles were dispersed in 30 mL ethanol (from VWR) and 4,4′-disulfanediylbis(N,N,N-trimethylbenzenamonium) (426 mg) and 15 mL distilled water were added. The reaction mixture was stirred overnight at room temperature. The reaction mixture was then centrifugated at 7000 rpm for 20 min. The supernatant was removed, and the residual powder was redispersed in a mixture of 25 mL ethanol and 25 mL distilled water then centrifugated at 7000 rpm for 20 min twice. Finally, the powder was redispersed in absolute ethanol (from VWR) and centrifugated at 7000 rpm for 20 min. The clear supernatant was removed, and the black powder was left to dry in air overnight and then 3 h under high vacuum to obtain the platinum nanoparticles (344 mg).

[0078] Diameter of nanoparticles is determined to be 30 nm.

[0079] Preparation of OECT-1

[0080] A substrate (1) of Kapton® HN (general-purpose polyimide film supplied by DuPont) is cut to appropriate dimensions and cleaned by successive washing with acetone, water and isopropanol, then dried and heated for 60 minutes at 180° C.

[0081] A mask is prepared according to geometry of electrodes conceived and applied on substrate. Then Gold (Au) is deposited by vacuum deposition to form drain, source and gate electrodes. A 200 nm thick layer of Gold is obtained.

[0082] By ink-jetting Orgacon™ IJ-1005 ink (supplied by AGFA), a PEDOT:PSS layer is deposited on source electrode, drain electrode and between electrodes so as to form channel (3). A thermal treatment of 60 minutes at 120° C. is applied to get conductive properties of PEDOT:PSS.

[0083] A mixture of 0.2% wt platinum nanoparticles with a 4-(trimethylammonium)thiophenolate crown in PEDOT:PSS is prepared and ink-jetted on a part of gate electrode (2G), yielding a catalytic layer (5) of thickness 3 μm.

[0084] Electrodeposition of Biologic Detection Layer

[0085] A solution comprising 1.5 wt % Chitosan (75%-85% deacetylated natural chitin, medium molecular weight, MW 190-310 kDa, from Aldrich, CAS 9012-76-4) is prepared in 0.075 M HCl, under vigorous stirring. The resulting solution is filtered over a porosity 3 glass frit to remove any undissolved material. The pH of the solution is adjusted to 5.1 with NaOH 1.0 M. 5.0 mg/mL Glucose Oxidase (Glucose Oxidase type VII from Aspergillus Niger, ≥100 kU/g, MW 160 kDa, from Aldrich) are added to the Chitosan solution under gentle stirring, and 5.0 mL of the resulting mixture are transferred to a 4-way electrochemical cell, equipped with a 3-electrodes setup (working electrode:OECT gate, prepared as previously described; counter electode:inox grid; reference electrode:Saturated Calomel Electrode, Sat'd KCl) and a magnetic stirrer. 20.0 mmol/L H.sub.2O.sub.2 (H.sub.2O.sub.2 30 wt % in H.sub.2O, from Aldrich) are added to the electrochemical cell. The working electrode is polarized at E=−0.40 V vs SCE, for 200 seconds, at room temperature and under stirring (400 rpm). The working electrode (OECT gate) is then rinsed with distilled water to remove any loosely bound material and stored in air until further use.

[0086] OECT-1 devices are thus obtained, as shown schematically on FIG. 2.

[0087] Preparation of OECT-C1

[0088] A comparative OECT device is prepared with the same protocol as OECT-1, but [0089] without electrodeposition of biologic detection layer; and [0090] without platinum nanoparticles.

[0091] Only PEDOT:PSS is ink-jetted on a part of gate electrode (2G), yielding a layer (5) of thickness 3 μm. The same amount of PEDOT:PSS is deposited in OECT-C1 and in OECT-1.

[0092] Preparation of OECT-C2

[0093] A comparative OECT device is prepared with the same protocol as OECT-1 (including electrodeposition of biologic detection layer), but a 0.2% wt platinum nanoparticles with a 4-(trimethylammonium)thiophenolate crown in ethanol is used to prepare catalytic layer (5) on gate electrode (2G). The same amount of nanoparticle solution is deposited in OECT-C2 and in OECT-1.

[0094] Preparation of OECT-2

[0095] On an OECT-1 device, an encapsulation membrane is further deposited.

[0096] A solution comprising 64.0 mg/mL poly-(4-vinylpyridine) (average Mw 160 kDa, from Aldrich) is prepared in a mixture of absolute ethanol and distilled water (90/10 v/v) (solution A). A solution comprising 64.0 mg/mL poly-(sodium 4-styrenesulfonate) (average Mw 1000 kDa, from Aldrich) is prepared in distilled water (solution B). A solution comprising 4.0 mg/mL poly(ethylene glycol) diglycidyl ether (PEGDE, average Mw 500 g/mol, from Aldrich) is prepared in a mixture of absolute ethanol and distilled water (80/20 v/v) (solution C). Solutions A and B are combined with a 90/10 v/v ratio (solution D). Solutions D and C are combined with an 80/20 v/v ratio (solution E). 35.5 μL/cm.sup.2 of solution E are drop cast onto the channel and gate of the OECT. The resulting drop is left to dry at room temperature, and under an ethanol/water saturated atmosphere, for 18 to 24 h.

[0097] OECT-2 device is thus obtained.

[0098] Mode of Operation of OECT—Performances.

[0099] OECTs are connected to usual electric device for control of filed effect transistor.

Example 1: OECT-1

[0100] V.sub.GS and V.sub.DS are set to +0.5V and −0.6V respectively.

[0101] A sample containing controlled concentration of glucose in Phosphate Buffer Solution (pH=7.4) is brought in contact with OECT-1. I.sub.DS and j.sub.GS are measured. Then sample is replaced with a sample more concentrated in glucose.

[0102] FIG. 3a shows I.sub.DS current and j.sub.GS (current density) as a function of time, in an experiment in which glucose concentration is varied from 0 mmol/L (blank) to 2 mmol/L in phosphate buffer solution (0.01 M) at 310 K, by successive increments every 200 seconds. Time response is quick, lower than 30 seconds leading to stationary values of current associated with each increment of glucose concentration.

[0103] FIG. 3b shows these stationary values of I.sub.DS and j.sub.GS as a function of glucose concentration. Currents linearly vary with glucose concentration, enabling to define sensibility of the OECT in said operating conditions. Actually, a linear fit defines J.sub.GS=10.14+45.75 [Glucose] and I.sub.DS=—15.85+4.15 [Glucose] over range 0-2 mmol/L of glucose.

Example 2: OECT 2

[0104] Setup of example 1 is reproduced, but using OECT-2 device and with following conditions.

[0105] FIG. 4a shows I.sub.DS current and j.sub.GS (current density) as a function of time, in an experiment in which glucose concentration is varied from 0 mmol/L (blank) to 30 mmol/L in phosphate buffer solution (0.01 M) at 310 K, by successive increments every 200 seconds. Time response is quick, lower than 30 seconds leading to stationary values of current associated with each increment of glucose concentration.

[0106] FIG. 4b shows these stationary values of I.sub.DS and j.sub.GS as a function of glucose concentration. Currents linearly vary with glucose concentration, enabling to define sensibility of the OECT in said operating conditions. Actually, a linear fit defines J.sub.GS=18.53+1.40 [Glucose] and I.sub.DS=—20.13+0.07 [Glucose] over range 0-30 mmol/L of glucose.

Example 3: Determination of Glucose Concentration in a Sample

[0107] A sample of unknown concentration of glucose is used.

[0108] OECT is configured in conditions of example 1, then sample is brought in contact with OECT. After few seconds, I.sub.DS and j.sub.GS becomes stationary. Using sensibility of OECT defined in example 1, real concentration of glucose in sample is determined.

Comparative Example

[0109] A comparative experiment has been conducted to demonstrate the efficiency of the composite material used in catalytic layer in this disclosure.

[0110] OECT-C1 has been used on one hand. In this OECT, there is no biologic detection layer. As a consequence, OECT-C1 is not designed to measure a concentration of glucose, but only a concentration of hydrogen peroxide H.sub.2O.sub.2.

[0111] On the other hand, OECT-1 has been prepared, but without biologic detection layer.

[0112] OECT-C1 and OECT-1 have been contacted with H.sub.2O.sub.2 solutions having a concentration varying from 0.1 mmol/L to 2 mmol/L.

[0113] FIG. 6a shows the stationary values of drain source current I.sub.DS (in mA) as a function of H.sub.2O.sub.2 concentration for OECT-1 (squares, solid line) and OECT-C1 (triangles, dotted line).

[0114] FIG. 6b shows the stationary values of gate source current density j.sub.GS (in μA.Math.cm.sup.−2) as a function of H.sub.2O.sub.2 concentration for OECT-1 (squares, solid line) and OECT-C1 (triangles, dotted line).

[0115] It is clear that the composite material comprising platinum nanoparticles and a PEDOT:PSS conductive matrix has improved sensitivity has compared to PEDOT:PSS conductive matrix alone.