WO2006045628A1

WO2006045628A1 - Adsorption monitoring device

Info

Publication number: WO2006045628A1
Application number: PCT/EP2005/011632
Authority: WO
Inventors: Jean-Pierre Abid; Jean Olivier Gamby; Hubert Hugues Girault
Original assignee: École Polytechnique Fédérale de Lausanne
Priority date: 2004-10-28
Filing date: 2005-10-27
Publication date: 2006-05-04
Also published as: GB0423961D0

Abstract

A device for monitoring the adsorption of target molecules on a substrate, the device comprising a substrate (1), at least a portion of which is formed as a thin dielectric layer. A first, modified surface (2) of the layer has ionizable groups of the substrate material thereon. A chamber contains a sample (5) including target molecules (6) to be in contact with the first surface (2). At least two electrodes (3) each have an electrode surface arranged on a second surface of said dielectric layer (1) opposite said first surface (2). A method of making the device is also disclosed.

Description

ADSORPTION MONITORING DEVICE

Background to the Invention

[0001] This invention relates to a device for monitoring the adsorption of a target molecule on to a substrate.

[0002] For developing new sensors for the detection of ions and also ultra-low concentrations of biomolecules, an increasing effort has been devoted to the development of new techniques. For example, confocal fluorescence microscopy, surface plasmon resonance, surface second harmonic generation and impedance spectroscopy are often employed for studying the adsorption of target molecules onto solid surfaces depending on the nature of the surface.

[0003] In the case of metal or semi-conducting surfaces, information on the electrical structure at the metal/ solution interface may be obtained through the measurement of the capacitance. Based on the same concept, electrochemical impedance spectroscopy provides a thorough method of probing biomolecular interactions at conductive and semi-conductive surfaces (see E.Katz ; I. Willner, , Electroanalyis, 15 (2003) 913) with related applications in immunosensors (see C. Fernandez-Sanchez; C. J. McNeil; K. Rawson ; O. Nilsson, Analytical Chemistry, 76 (2004) 5649), DNA-sensors and enzyme biosensors. With this method, the bias of the sensing electrode potential should be controlled, and the frequency of the alternating potential difference imposed is in the kilohertz range.

[0004] Concurrently to the electrochemical methods, optical methods such as confocal fluorescence microscopy are used either when the adsorbing target molecules fluoresce or when tagged with a fluorescent probe. Non-linear optical methods such as Surface Second Harmonic Generation can be also used, but the instrumentation requires high power laser sources. Another technique called surface plasmon resonance (SPR) is widely employed for monitoring the adsorption of target biomolecules on specifically prepared glass slides containing a thin gold film (see for example, "Present and future of surface plasmon resonance biosensors", by J. Homola, Analytical and Bioanalytical Chemistry, 377 (2003) 528). Recently, a new combined technique called surface plasmon resonance (SPR)/ Love mode surface acoustic wave (SAW) has been described for studying the quantity of adsorbed biomolecules at the solid/ liquid interface (C. Zhou; J.M. Friedt; A. Angelova; K.H. Choi; W. Laureyn; F. Frederix; L.A. Francis; A. Campitelli; Y. Engelborghs; G. Borghs, Langmuir, 20 (2004) 5870). Compared with the SPR technique, a slight modification is made on the quartz substrate, which is patterned with a double-finger ihterdigitated electrode for launching a Love mode acoustic wave at a frequency of 123.5 MHz. During the process of adsorption, the modification of the phase shift can be converted to a frequency shift and thus, related to the bound mass of biomolecules. For some particular cases, it is also possible to use a quartz microbalance to follow the adsorption of biomolecules on the balance placed in the solution. In that configuration, the measurement of the changes in the resonance frequency due to the protein adsorption at the surface of the quartz crystal, allows the estimation of the quantity of biomolecules adsorbed on the sensor surface (see F. Hook; M. Rodahl; P. Brzezinski; B. Kasemo Langmuir, 14 (1998) 729 and M. Rodahl; B. Kasemo Sens. Actuators A, 54 (1996) 448). In the case of the adsorption of human immunoglobulin, these techniques have demonstrated high sensitivity with a limit of detection of 87.5 ng/mL.

[0005] The introduction of capillary electrophoresis in 1979 involved the development of new systems for the detection of ions in solution using silica capillaries. A well-known method is oscillometry, which has recently been applied as a detection method in capillary electrophoresis (J.A. Fracassi da Silva and CL. do Lago Anal Chent. 70 (1998) 4339). The non-contact configuration consists of a system in which the electrodes are located outside the conductivity cell and are therefore not directly in contact with the electrolyte solution. Using a Plexiglas ® cell in a contactless mode, it has been possible to detect a concentration of few micromolar for tetrabutylammonium and tetraethylammonium cations (see J. Tanyanyiwa; P.C. Hauser Analytical chemistry, 74: (2002) 6378). Due to the advantages of this non-contact technique, an increasing interest has been observed in several fields.

[0006] In medicine, harmlessness to the human body was an important factor for the development of this technique for the diagnosis of lesions and tumors. For example, electrical impedance tomography is often used to measure the contractility of the heart (MIC: Minnesota Impedance Cardiograph), preventing periventicular intraventicular hemorrhage in low birth weight infants (150Og), diagnosing cardiovascular diseases and monitoring vascular hemodynamics in the limb segments of patients during operations, monitoring pulmonary ventilation and imaging the brain activity (see W.G. Kubicek; F.J. Kottke; M.U. Ramos; R.P. Patterson; D.A. Witsoe; J.W. Labree; W. Remol ; T.E. Layman; H. Schoening; J.T. Garamela Biomed.Eng. 9 (1974) 410; B.H. Brown; D.C. Barber ; A.D. Seagar CZm. Phys. Physiol. Meas. 6 (1985) 109; H.M. Carim Encyclopedia of medical devices and instrumentation, J. G. Webster, New-York, John Wiley, 1988; and Y. Kim ; H.W. Woo ; J.T. Brooks ; S.O. Elliott /. Clin. Eng. 12 (1987) 221). The configuration, consists of 4 to 100 electrodes dispatched on the body, a low AC current (4 mA RMS) is applied between two electrodes and the voltage is measured between the two others electrodes. In that configuration, any modification of the body composition will influence the total resistivity of the probed part. For example, electrical impedance tomography can be used to determine the change in fluid volume within the lung, which could be related to the changes in the thoracic impedance. In fact, the phenomenon involves air (80%) and fluid (5%). During maximal inspiration, the lungs are filled with air and hence the impedance is maximal whereas during the expiration process, the amount of air decreases and the impedance follows a similar way. In that way, impending pulmonary oedema could be detected. The concept can be used for imaging the brain activity where the electrodes are usually settled at the surface of the low conducting bony shell, which acts like an insulator. In this way, the collected impedance signal is mainly influenced by the activity of the brain tissue. The same concept is frequently used for imaging tumors, lesions or oedemas in each part of the human body (see Y.Kim; J.G. Webster; WJ. Tompkins J.Microwave Power 18 (1983) 245; J.M. Porter; LD. Swain /. Biomed. Eng. 9 (1987) 222 and A. Wexler Clin. Phys. Physiol. Meas. 9 suppl. A (1988) 29). The non-contact configuration has the advantage to avoid any cumbersome occlusion for monitoring oedema, lesions or cancers.

[0007] Finally, the non-contact concept has some applications in the engineering field for detecting gas bubbles in pipes and estimating the mineral resources (see D. Murphy and P. Rolfe Phys. Physiol. Meas. 8 suppl. A (1988) 5). In the latter configuration, the electrical impedance system is usually employed in petroleum exploration in order to identify potential reservoirs in rocks (porosity and permeability). The implemented configuration consists of four electrodes: two electrodes are used as transmitters and the other two as the voltage receivers. By moving this configuration along the earth's surface and recording the changes in the resistivity, it is possible to detect subsurface objects and relate these to geological structures.

[0008] In contactless conductivity cells or impedance tomography, the devices are designed to ensure the capacitive coupling between the electrodes and the solution (or the body fluids) whilst keeping the capacitive admittance lower than the resistive component that is measured.

Summary of the Invention

[0009] The invention seeks to provide a contactless device for monitoring the adsorption of target molecules (which term includes biomolecules, supramolecular assemblies and derivatized nanoparticles) on a substrate, and hence to assess the concentration of the target molecules in a sample. [0010] From one aspect, the invention provides a device for monitoring the adsorption of target molecules on a substrate, the device comprising a substrate, at least a portion of which is formed as a thin dielectric layer, a first surface of said layer having ionizable groups of the substrate material thereon; a chamber for containing a sample including target molecules to be in contact with said first surface having said ionizable groups; and at least two electrodes each having an electrode surface arranged on a second surface of said dielectric layer opposite said first surface.

[0011] From another aspect, the invention provides a device for monitoring the adsorption of target molecules on a substrate, the device comprising two substrates, each substrate having a portion formed as a thin dielectric layer, a first surface of at least one of the two dielectric layers having ionizable groups of the substrate material thereon; a chamber between the substrates for containing a sample including target molecules to be in contact with said first surface having said ionizable groups; and each substrate having an electrode arranged on a second surface of said dielectric layer opposite said first surface.

[0012] Such electrodes have a large dielectric/ electrode contact area and little or no direct mutual capacitive coupling when an AC signal is applied between them. When such a signal is applied between the two electrodes, a capacitive coupling between the electrodes and the first surface having said ionizable groups is established. The admittance of the device is found to be a direct measure of the adsorption process.

[0013] Unlike ISFET (ion-selective field effect transistor) sensors (MJ. Schόrύng; A. Poghossian, Analyst 127 (2002) 1137), EIS (electrolyte-insulator- semiconductor) sensors (D. Rolka; A. Poghossian; MJ. Schoning, Sensors 4 (2004) 84) and EMIS (electrolyte-membrane-insulator-semiconductor) devices (Yu. Mourzina; Th. Mai; A. Poghossian; Yu. Ermolenko; T. Yishinobu; Yu. Vlasov; H. Iwasaki; MJ. Schoning, Electrochimica Acta, 48 (2003) 3333), the substrate of the - S -

present invention does not require semiconducting material. Furthermore, ISFET, EIS and EMIS devices all require the use of a reference electrode in the analyte solution. Thus, these known devices are restricted to use with a solution, whereas the device of the present invention can be used with either a liquid or a gas phase sample.

[0014] The substrate(s) may in particular be of a polymer, such as polyethylene terephthalate (PET), said first surface being modified to create ionizable groups such as -OH and -COOH. Many other polymers are also suitable, but not polytetrafluoroethylene. The substrate may alternatively be of glass - the ionizable groups comprising silanol groups - or of a ceramic oxide such as mesoporous alumina.

[0015] The thin dielectric layer may be less than 50 μm thick and in particular less than 30 μm thick.

[0016] The electrodes may be of metal, conductive ink or an assembly of conductive particles.

[0017] The first surface may be coated with nanoparticles, such as silica nanoparticles or such as gold nanoparticles, in particular coated with ionized or ionizable groups, such as 3-aminopropanethiol. Alternatively or additionally the first surface may be coated with a mesoporous layer, for example of polyvinylidine fluoride (PVDF). The first surface may additionally or alternatively be coated with adsorbed polyelectrolytes. It will therefore be understood that the contact between the sample of target molecules and the first surface of the dielectric layer is not necessarily direct contact.

[0018] The chamber may comprise a microchannel and the device may comprise a flow cell or part of a flow cell.

[0019] The invention also provides a method of making a device for monitoring the adsorption of target molecules on a substrate, comprising the steps of forming at least a portion of a substrate as a thin dielectric layer with ionizable groups on a first surface of said layer; forming thin planar electrodes on a second surface of said dielectric layer opposite said first surface; and causing said substrate to form a wall of a chamber for containing a sample of target molecules to be in contact with said first surface having said ionizable groups.

[0020] As a preliminary step, said first surface may be modified to generate said ionizable groups, the modification comprising, for example, one of plasma etching, illumination with UV light, such as UV laser light, and chemical reaction, for example oxidation with a caustic solution.

[0021] The step of forming the electrodes may comprise formation, e.g. photoablation, of a recess in the substrate and filling said recess with a conductive substance such as carbon ink. Alternatively the electrodes may be formed by screen printing, by chemical vapor deposition, by sputtering or by photolithography.

Brief Description of the Drawings

[0022] The invention will now be described in more detail, by way of example only, with reference to the accompanying drawings, in which:

[0023] Figure 1 is a schematic sectional view showing the principle of a single- substrate device according to the invention;

[0024] Figure 2 is a schematic sectional view showing the principle of a device with two substrates according to the invention;

[0025] Figure 3 is a schematic sectional view of a device according to an embodiment of the invention;

[0026] Figures 4a and 4b are schematic sectional and top views respectively of a device according to an alternative embodiment; [0027] Figure 5 shows a circuit including a device according to the invention;

[0028] Figure 6 shows a frequency response obtained using the device of Figure 3 when filled with phosphate buffered saline (PBS) solution;

[0029] Figure 7a shows a frequency response obtained using the device of Figure 3 when the phosphate buffer saline solution contains poly-L-lysine, superimposed on the response of Figure 6;

[0030] Figure 7b shows the difference between the two frequency responses of Figure 7a;

[0031] Figure 8a shows a frequency response obtained using the device of Figure 3 when filled with phosphate buffered saline (PBS) solution but where the first surface having ionizable groups has firstly been coated by gold nanoparticles derivatized by 3-aminopropanethiol, superimposed on the response of Figure 6;

[0032] Figure 8b shows the difference between the two frequency responses of Figure 8a;

[0033] Figure 9 schematically shows a PET surface coated for protein adsorption detection; here the protein is beta-lactoglobulin;

[0034] Figure 10a shows frequency responses for different concentrations of beta-lactoglobulin for the device illustrated in Figure 9;

[0035] Figure 10b is a plot of the maxima of the responses of Figure 10a;

[0036] Figure 11 shows the temporal change in admittance of the device of Figure 3 during adsorption of an antibody under flow conditions;

[0037] Figure 12 is a plot showing the response at 430 kHz for different concentrations of antigen on an antibody coated surface; and [0038] Figure 13 shows the temporal change in admittance of the device of Figure 4 during adsorption of poly-L-lysine.

Detailed Description of Particular Embodiments

[0039] Figure 1 schematically shows a device comprising an ultrathin dielectric substrate 1, with a thickness preferably smaller than 30 μm, made of a material such as glass (silicon oxide), another ceramic oxides or a polymer. In the case of a polymer, a first surface 2 of the dielectric is physically and/ or chemically modified to generate ionizable groups such as -OH or -COOH. Whilst different modification routes can be used, surface oxidation - by techniques such as plasma etching, ultraviolet light and chemical oxidation with caustic solutions - has proved particularly efficient. Two thin and planar electrodes 3 are placed in contact with the substrate on its unmodified side. The size of the electrodes and their spacing are important parameters. The contact area between the substrate 1 and the electrodes 3 should be as large as feasible, and the electrodes should be thin enough and/ or far enough from each other to avoid direct capacitive coupling. Two connectors 4 are used to electronically connect the electrodes 3 to an admittance-measuring instrument. When the modified surface 2 is placed in contact with a solution 5 or a gas phase sample including target molecules, the ionizable groups on the surface lead to the creation of surface charges, for example O-. Upon adsorption of target molecules 6 from the solution to the substrate, those surface charges are altered and the admittance of the device is modified.

[0040] When an AC voltage is applied between the two electrodes, a capacitive coupling takes place between the electrodes 3 and the substrate/ solution interfaces directly above each electrode. The electrode geometry is such that the electrode area capacitively coupled to the substrate is much larger than the electrode cross-section facing each other to minimize the possible direct capacitive coupling between the two electronic conductors. For these reasons, the electrodes are thin and planar.

[0041] Figure 2 schematically shows a device similar to that of Figure 1 but comprising two substrates 1. Each of the substrates has a modified first surface 2 and an electrode 3 on its unmodified side. Operation of the device is similar to that of the device of Figure 1.

[0042] Figure 3 shows a device according to the invention coupled to a flow cell.

[0043] In order to manufacture the device of Figure 3, a PET substrate 1 is used. This substrate has an initial thickness of 100 μm and is available from Dupont (Geneva, Switzerland). The PET sheet is photoablated, Le. rnicromachined, using an UV excimer laser (Argon Fluor Excimer at 193 nm; Lambda Physik LPX 2051, Gόttingen, Germany) to fabricate the two microband electrodes 7 and a flow channel 8.

[0044] To form the electrodes, two microchannels 9 are photoablated in one side of the substrate 1. The microchannels run "into the paper" as viewed in Figure 3. Each microchannel has a trapezoidal cross-section shape with a depth of 45 μm, a width of 100 μm and a length of 1400 μm. The separation distance between the two microchannels is 200 μm centre to centre in this example, but can be from 40 to 1000 μm. After each photoablation, the debris produced by the laser ablation is removed by cleaning with isopropanol. The two microchannels 9 are then filled with a commercial carbon ink, Electra ® (ED 5000 series) with a surface resistivity value of 12 to 25 Ω per square, obtainable from Electra Polymers (England) with gold nanoparticles added to decrease its electrical resistance. The ink is cured at 60 °C for 4 hours. The resulting microband electrodes 7 are thermally laminated at 135 ⁰C at a pressure of 2 bar with a polyethylene/ polyethylene terephthalate (PE/PET) 35 μm thick film (Morane, Oxon, UK). [0045] On the other side of the substrate, a flow microchannel 8 is photoablated perpendicularly to the microband electrodes 7. The flow microchannel obtained has a trapezoidal cross-section shape with a depth of 45 μm, a width of 100 μm and a length of 1400 μm. Inert sealing layers 10 are laminated on either side of the substrate 1.

[0046] Figures 4a and 4b show a screen printed device. Two thin planar band electrodes 3 are screen printed on an inert supporting layer 10. The assembly is then covered by a thin dielectric layer 1. A first surface 2 of this dielectric layer is modified as specified above to generate ionizable groups. This device can be used directly to monitor the adsorption of target molecules onto the modified surface 2. Additionally, an Immun-Blot™ polyvinylidine fluoride (PVDF) membrane 11, 0.2 μm pore size, obtained from Bio-Rad, can be applied to the first surface 2 .

[0047] To measure the admittance of devices according to the invention, a frequency response analyzer or a lock-in amplifier could be used. For simplicity, we prefer to use the detector circuit shown in figure 5, comprising a simple operational amplifier 12 and a rectifier R. A wave generator 14 provides an AC voltage with a' frequency ranging from 0.2 Hz to 1 MHz and an amplitude ranging from 0.1 to 0.5 Volts to the device D of the invention. The output signal is a DC voltage corresponding to the magnitude of the admittance of the device.

[0048] A typical frequency response of the device of figure 3, filled with a phosphate buffer saline (PBS) solution, is shown in figure 6. A response of triangular shape can be observed. In the rising part of the signal, the frequency response is a direct measure of the admittance of the device. In the decreasing part of the signal, the frequency response is dominated by the bandwidth of the operational amplifier. We therefore record the peak of the triangle as the device response. Adsorption of poly-L-lysine on UV oxidized PET

[0049] Poly-L-lysine and phosphate buffer saline (PBS) tablets were purchased from Sigma- Aldrich. A 10 mM PBS solution was prepared and titrated to pH 7 with solutions of NaOH and HCl.

[0050] For all the experiments, water and PBS solution are used so that no effect is due to the modification of the solution resistance.

[0051] In the results, shown in Figures 7a and 7b, there is a clear increase of the admittance modulus at 430 kHz while the maximum output (290 mV) is shifted to 460 kHz due to the change in frequency resonance in the system upon adsorption of the poly-L-lysine on the surface having ionizable groups.

Adsorption of charged nanoparticles on oxidized PET

[0052] An aqueous solution of gold nanoparticles stabilized with 3- aminopropanethiol with an average size of 19 (±2) ran is dried in the microchannel 8 for 4 hours. After that period, the channel is filled with phosphate buffer solution (PBS), which is taken as a reference for all the experiments. The amplitude of the applied voltage was fixed at 0.4 V. The measurements after the adsorption of the gold nanoparticles at the PET surface show clearly an increase of the output voltage as shown in figures 8a and 8b. The analysis of the admittance measurements shows a major difference over the frequency range 10² to 10⁶ Hz compared to the bare surface for a similar solution (Millipore water). The modification of the channel walls with gold nanoparticles allows an enhancement of the admittance (320 mV). Such "tunability" of the surface charge allows improvements in the detection of biomolecules with low concentration. In this way, we have found it possible to study the adsorption of polycations and biomolecules on the gold-modified PET substrate. The principal aim was the estimation of the limit of detection in the case of low concentration of proteins.

Adsorption of proteins on surfaces modified by adsorbed nanoparticles

[0053] As portrayed in figure 9, the device of figure 3 is modified by an initial adsorption of derivatized gold nanoparticles 20 on the modified substrate 2. This surface modification was achieved by adsorption of gold nanoparticles coated with cetyltrimethylammonium onto the substrate and then by reaction with carboxy terminated thiol molecules such as 3-mercapto propanoic acid 21. Finally, poly-L-lysine 22 was adsorbed. Samples of Beta-lactoglobulin 23 with concentration ranging from 5.47xlO^~6to 5.47xl(T^I4 M were used and the evolution of the admittance with respect to the concentration in solution was recorded. As shown in figures 10a and 10b, an increase of the amplitude of the admittance was observed, reaching a maximal value at a bulk concentration of 5.47xlO"⁹ M. The experimental measurements show a very good reproducibility with negligible variation of the signal. These results emphasize the possibility of detecting the adsorption of traces of biomolecules with femtomolar concentration. We believe that the interaction of any type of biomolecule with the surface of the PET channel or the nanoparticle coating can be detected at a similar concentration.

[0054] Figure 11 shows the time evolution of the adsorption of the antibody on the device of Figure 3 under flow conditions. Prior to the experiments, the surface of the channel is coated with gold nanoparticles. First, the buffer flows in the channel. A solution of antibody is then passed for 400 seconds followed by a further flow of the buffer. We obtain a sensogram, similar to those obtained by SPR measurements, which enable the measurement of the kinetic parameters relative to the adsorption of the antibody on the modified substrate. Antigen-antibody recognition on surfaces modified by adsorbed antibodies

[0055] Further experiments show that the sensitivity of the technique is not limited to one particular biomolecule, due to the fact that the response is inherent in the interface charge. To support these observations, antibody- antigen systems have been probed using the device of figure 3. The system consists of an initial adsorption of gold nanoparticles followed by the binding of antibodies (PET/ gold nanoparticle/ antibody). After a period of one hour, the microchannel is filled with PBS solution and the admittance measurement is performed. Similarly to the case of Beta-Lactoglobulin B, a very low concentration (6.6xlO-¹⁵ M) of attached antigens on antibodies has been detected. The admittance maximum at 430 kHz decreases for an increasing concentration of antigen added into the flow microchannel 8. The results are shown in figure 12 and reveal that admittance measurements can be employed as a probe tool for studying antibody-antigen interactions.

Adsorption of poly-L-lysine using screen printed electrodes

[0056] Similar experiments have been performed using the device of figure 4, having a PVDF membrane (0.8cm x 0.9cm) in contact with a screen printed device. The typical device consists of two carbon electrodes 3 separated by 1 mm (length: 42mm, width: 3mm) printed on a PET layer 10 doped with ΗO2 and then covered with a 35 μm thick PET/PE film 1. Prior to use, the PVDF membrane is wetted in methanol to increase its hydrophilicity. After each wetting, a droplet (25 μL) of poly-L-lysine in a mixture of water and methanol is dried on the PVDF membrane. Time-dependent experiments are performed by following the admittance at 432 kHz and applying a 20 mV r.m.s. AC voltage. During the process of drying, the admittance measurement follows a sigmoid shape (figure 13). Concurrently to the phenomenon of adsorption of the poly-L- lysine on the membrane, a process of drying is observed, which causes a loss of contact between the membrane and the substrate. In this configuration, the modification of the membrane composition with polycations OΪ nanomaterials can also help to lower the limit of detection.

Claims

1. A device for monitoring the adsorption of target molecules on a substrate, the device comprising a polymer substrate, at least a portion of which is formed as a thin dielectric layer, a first, modified surface of said layer having ionizable groups of the substrate material thereon; a chamber for containing a sample including target molecules to be in contact with said first surface having said ionizable groups; and at least two electrodes each having an electrode surface arranged on a second surface of said dielectric layer opposite said first surface.

2. A device for monitoring the adsorption of target molecules on a substrate, the device comprising two polymer substrates, each substrate having a portion formed as a thin dielectric layer, a first, modified surface of at least one of the two dielectric layers having ionizable groups of the substrate material thereon; a chamber between the substrates for containing a sample including target molecules to be in contact with said first surface having said ionizable groups; and each substrate having an electrode arranged on a second surface of said dielectric layer opposite said first surface.

3. A device according to any claim 1 or 2, wherein the or each substrate is of polyethylene terephthalate (PET) yielding ionizable groups such as OH and COOH.

4. A device according to claim 1, 2 or 3, wherein the first surface is coated with a mesoporous layer.

5. A device according to claim 1, 2, 3 or 4, wherein the first surface is coated with nanoparticles.

6. A device for monitoring the adsorption of target molecules on a substrate, the device comprising a substrate, at least a portion of which is formed as a thin dielectric layer, a first surface of said layer having ionizable groups of the substrate material thereon and being coated with nanoparticles or a mesoporous layer; a chamber for containing a sample including target molecules to be in contact with said first surface having said ionizable groups; and at least two electrodes each having an electrode surface arranged on a second surface of said dielectric layer opposite said first surface.

7. A device for monitoring the adsorption of target molecules on a substrate, the device comprising two substrates, each substrate having a portion formed as a thin dielectric layer, a first surface of at least one of the two dielectric layers having ionizable groups of the substrate material thereon and being coated with nanoparticles or a mesoporous layer; a chamber between the substrates for containing a sample including target molecules to be in contact with said first surface having said ionizable groups; and each substrate having an electrode arranged on a second surface of said dielectric layer opposite said first surface.

8. A device according to claim 6 or 7, wherein the or each substrate is of a ceramic oxide such as glass or mesoporous alumina.

9. A device according to any one of claims 5 to 8, wherein said nanoparticles are selected from gold and silica.

10. A device according to any one of claims 5 to 9, wherein said nanoparticles are coated with ionizable groups.

11. A device according to any preceding claim, wherein the thin dielectric layer is less than 50 μm thick and in particular less than 30 μm thick.

12. A device according to any preceding claim, wherein the electrodes are selected from metal electrodes, conductive ink electrodes and electrodes formed from an assembly of conductive particles.

13. A device according to any preceding claim, wherein the first surface is coated with adsorbed polyelectrolytes.

14. A device according to any preceding claim, wherein the chamber comprises a microchannel.

15. A device according to any preceding claim, comprising at least part of a flow cell.

16. A method of making a device for monitoring the adsorption of target molecules on a substrate, comprising the steps of forming at least a portion of a polymer substrate as a thin dielectric layer with ionizable groups on a first surface of said layer; forming thin planar electrodes on a second surface of said dielectric layer opposite said first surface; and causing said substrate to form a wall of a chamber for containing a solution of target molecules to be in contact with said first surface having said ionizable groups.

17. A method according to claim 16, wherein as a preliminary step, said first surface is modified to generate said ionizable groups.

18. A method according to claim 17, wherein said first surface is modified by a modification step selected from plasma etching, illumination with UV light and chemical reaction.

19. A method according to claim 18, wherein said modification step comprises illumination with UV laser light.

20. A method of making a device for monitoring the adsorption of target molecules on a substrate, comprising the steps of forming at least a portion of a substrate as a thin dielectric layer with ionizable groups on a first surface of said layer; coating said first surface with nanoparticles or a mesoporous layer; forming thin planar electrodes on a second surface of said dielectric layer opposite said first surface; and causing said substrate to form a wall of a chamber for containing a solution of target molecules to be in contact with said first surface having said ionizable groups.

21. A method according to any one of claims 16 to 20, wherein the step of forming the electrodes comprises formation of a recess in the substrate and filling said recess with a conductive substance.

22. A method according to any one of claims 16 to 21, wherein the electrodes are formed by one of screen printing, chemical vapor deposition, sputtering and photolithography.