IMAGING ELEMENT, IMAGING DEVICE, IMAGING SYSTEM, ANALYSIS METHOD AND MANUFACTURING METHOD THEREFOR

Abstract

One aspect of the invention relates to an imaging element (20, 20S) for analyzing a sample comprising: an electrode (201) adapted to receive the sample, a light-emitting element (202), arranged opposite the electrode (201), and separated from the electrode (201) by an insulating protective layer (203), a voltage-controlled current source (204), configured to supply the light-emitting element (202) with current and comprising a control electrode electrically connected to the electrode (201), such that said light-emitting element (202) generates a light wave in response to a voltage coming from the sample. Figure to be published with the abstract: Figure 5

Description

Title of the invention: IMAGING ELEMENT, IMAGING DEVICE, IMAGING SYSTEM, ANALYSIS METHOD AND MANUFACTURING METHOD THEREFOR TECHNICAL FIELD OF THE INVENTION

[0001] The technical field of the invention is linked to the analysis of a sample, for example a biological sample, by an imaging system.

[0002] The invention relates to an imaging element for analyzing a sample, as well as to an associated imaging device and imaging system. The invention further relates to a method for analyzing the sample using the imaging device and to a method for manufacturing the imaging device.

[0003] The invention finds application in the fields of biology and health, in particular in the field of organs on chips, or "organ-on-chip" in English. TECHNOLOGICAL BACKGROUND OF THE INVENTION

[0004] Organs-on-chips are miniaturized cell culture platforms that can reproduce the function and structure of human organs on a micrometric scale and as close as possible to their operation in the human body.

[0005] Organs on chips have the advantage of being perfectly suited to the integration of sensors, because they are manufactured with similar manufacturing technologies.

[0006] These sensors are essential for accessing information concerning cells, their interactions, their proliferation or even their response to various stimuli, for example chemical (or medicinal) stimuli, and, thus, making it possible to understand the functioning of organs and to test the effect of medicines.

[0007] Organs on chips applied to cellular models imitating the central nervous system thus offer the possibility of better understanding the functioning of the brain as well as certain neurodegenerative diseases of the brain, such as Parkinson's disease or Alzheimer's disease, which are linked to functional aberrations of neuronal networks. These organs on chips also make it possible to test in vitro the effect of targeted treatments on these diseases.

[0008] For this type of organs-on-chips, electrophysiological sensors have been developed to image the extracellular electrical activity of neurons in real time.

[0009] This extracellular activity is triggered by a temporal evolution of the intracellular voltage of a neuron, called an action potential, and is associated with ionic currents across the cell membrane. Typically, an action potential lasts between 1 and 2 milliseconds and, during this time, the inner membrane potential changes from -70mV to +30 mV, then returns to -70 mV.

[0010] A known type of electrophysiological sensor for combining imaging at the scale of a neuron (micrometric scale) and at the scale of a neural network (macroscopic scale) uses a network of transistors in a configuration called EOS (acronym for "Electrolyte Oxide Silicon" in English).

[0011] In this configuration, the neurons are in an electrolyte bath which is brought, via an electrode, to a reference potential. In addition, the transistors do not have a metal gate electrode.

[0012] The document "Electrical imaging of neuronal activity by multi-transistor-array (MTA) recording at 7.8 pm resolution" by Lambacher et al., Applied Physics A., 2004 describes an MTA matrix (acronym for "Multi-Transistor Array" in English) of 16384 field effect transistors manufactured with CMOS technology (acronym for "complementary metal oxide Silicon" in English) and covered with a thin insulating layer of titanium dioxide (TiO2). The spatial resolution is 7.8 pm, and the sensor surface is 1 mm2.

[0013] The recording principle is as follows: when a neuronal cell, adhering to the TiO2 layer opposite a transistor, emits an action potential, it produces at the junction between the cell and the TiO2 layer an extracellular potential which differs from the reference potential of the electrolyte bath. This local change in the electric field is capacitively coupled, through the insulating TiO2 layer> to the gate of the transistor and gives rise to a modulation of the source-drain current calibrated as a function of the field potential.

[0014] The paper "Signal Transmission from individual mammalian nerve cell to field-effect transistor" by Voelker et al., Small Journal, 2, 206-210, 2005 describes an improved EOS transistor array that allows recording extracellular electrical activity with a better signal-to-noise ratio. The transistors do not have a TiO2 layer, and the neurons are arranged directly on the gate oxide of the transistors.

[0015] However, this recording is very sensitive to the position of the neuronal cells on the transistors. It is not enough for a neuronal cell to be positioned opposite a transistor for it to generate a signal there.

[0016] Indeed, only a small part of the transistor defined by the gate electrode is actually a sensitive area. This part is limited by the gate length. A significant surface area of ​​the sensor therefore does not contribute to the detection of electrical activity.

[0017] There therefore remains a need for an imaging system that is less sensitive to the position of neuronal cells, thus allowing more robust contact (or connection) of these neuronal cells to it.

[0018] This need exists more broadly for the study of samples comprising at least a source capable of generating an electrical signal. Summary of the invention

[0019] In the field of sensors, the element which is in contact with the sample and provides a signal in response to an event generated by the sample is called a "receiver", and the element which receives a signal in one form and transforms it into a signal in another form is called a "transducer".

[0020] The inventors have identified that an obstacle to addressing the problem mentioned above is related to the fact that, in the state-of-the-art sensor, the receiver and the transducer are integrated into each other. This implies that the surface area of ​​the sensitive area cannot be enlarged in order to decrease the positioning sensitivity and improve the contact robustness without modifying the architecture of the transistor itself.

[0021] The invention offers a solution to the problem mentioned above by making it possible to produce an imaging element in which the receiver and the transducer are two separate elements electrically connected, so that it is possible to easily obtain, that is to say independently of the transducer, a sensitive surface of a larger size than the surface of the CMOS transistor of the state of the art.

[0022] A first aspect of the invention relates to an imaging element intended for the analysis of a sample and comprising: • an electrode suitable for receiving the sample, • an electroluminescent element, arranged opposite the electrode, and separated from the electrode by an insulating protective layer, • a voltage-controlled current source, configured to supply current to the electroluminescent element and comprising a control electrode electrically connected to the electrode, such that said electroluminescent element generates a light wave in response to a voltage coming from the sample.

[0023] The electroluminescent element can here be understood as an element which produces monochromatic or polychromatic radiation, for example in the 400-800 nm spectral band, by conversion of electrical energy when an electric current passes through it. Light-emitting diodes or LEDs (acronym for "Light Emitting Diode" in English) and their derivatives, mainly organic light-emitting diodes or OLEDs (acronym for "Organic Light Emitting Diode" in English) are examples of electroluminescent elements.

[0024] Thus, the imaging principle is as follows: • a sample is placed on the electrode, • a variation in the electrical potential of the sample modifies the potential electrical of the electrode. • This electrical potential is used to control the current source, which in response provides a current through the electroluminescent element. This current then generates, in the electroluminescent element, a light wave whose amplitude is indicative of the action potential of the neuronal cell.

[0025] Thus, the imaging element according to the first aspect of the invention comprises a receiver (the electrode) and a transducer (the electroluminescent element) which are two distinct elements because they are separated by the protective layer, located opposite each other, and connected by an electrical connection (via the current source).

[0026] This configuration of the imaging element provides freedom of arrangement of the electrode relative to the electroluminescent element, and makes it possible to adapt the surface of the receiver, and, in any case, to increase it relative to the surface of a CMOS transistor of an MTA matrix, without modifying the transducer (here the electroluminescent element).

[0027] The device according to the first aspect of the invention may also have one or more of the characteristics below, considered individually or in all technically possible combinations.

[0028] The electroluminescent element is disposed between the protective layer and a transparent, semi-transparent support substrate.

[0029] The electrode and the protective layer are transparent or semi-transparent.

[0030] The term “transparent” designates the fact of having an optical transmission coefficient greater than 60% for at least one wavelength of the 400-800nm ​​spectral band.

[0031] The term “semi-transparent” designates the fact of having an optical transmission coefficient greater than 60% for at least one wavelength of the 400-800nm ​​spectral band.

[0032] Thus, the light wave propagates through the transparent or semi-transparent electrode, opposite which it can be visualized and / or measured, for example by an optical photodetector.

[0033] The current source comprises a transistor having: • a grid electrode constituting the control electrode of the current source; • a source electrode connected to the electroluminescent element; and • a drain electrode connected to a supply terminal.

[0034] The transistor is advantageously a simple technology allowing a potential difference to be converted into a current.

[0035] When the current source comprises a transistor, the transistor is a thin film transistor also called TFT.

[0036] The thin-film transistor has several advantages, including good compatibility with microelectronic manufacturing processes, low cost and high flexibility, which allows them to drive different types of electroluminescent elements.

[0037] The lateral dimensions of the electrode are greater than the lateral dimensions of the transistor.

[0038] Thus, the sensitive surface is increased compared to the state of the art, which allows better detection efficiency (fewer events are “missed” and the response provided by the imaging element reflects reality more faithfully).

[0039] The lateral dimensions of the electrode are preferably between 4 μm and 20 μm, and for example equal to 15 μm.

[0040] Thus, the size of the sensitive surface corresponds to the size of a neuronal cell. The imaging element is then well adapted, in size, to detect and follow the extracellular electrical activity of an individual neuronal cell.

[0041] The electroluminescent element may be an organic light-emitting diode.

[0042] Organic light-emitting diodes have a relatively simple structure based on a superposition of several organic semiconductor layers between two electrodes, at least one of which is transparent or semi-transparent. The manufacturing method is advantageous in terms of cost and complexity, since the semiconductor layers and the electrode can be deposited full plate (i.e. over the entire surface of the substrate), which avoids lithography and etching steps.

[0043] Organic light-emitting diodes also have the advantage of being available in micrometric lateral dimensions (for example 10 μm and less), of being flexible and easily connectable to an electronic control circuit, for example an electronic circuit in CMOS technology. Finally, they require a lower current than inorganic light-emitting diodes.

[0044] The light-emitting element may be an inorganic light-emitting diode, preferably an inorganic micro-light-emitting diode.

[0045] Like OLEDs, micro-light emitting diodes or microLEDs (acronym for “micro-Light Emitting Diodes” in English) have the advantage of having micrometric dimensions well adapted to the size of neuronal cells, for example dimensions between 15 pm and 20 pm.

[0046] Compared to OLEDs, microLEDs have higher luminance and longer lifetime, but they require higher drive current and are more difficult to manufacture.

[0047] The imaging element further comprises an electronic driving circuit configured to generate a control voltage for the current source, said electronic driving circuit electrically connecting the control electrode of the source current and the electrode.

[0048] By "electronic control circuit" is meant a circuit which produces a control voltage adapted to control, via the current supplied by the current source, certain emission characteristics of the electroluminescent element. These characteristics are, for example, the dynamics of light intensity, the emission duration (linked to the observation time), etc.

[0049] A second aspect of the invention relates to an imaging device comprising a plurality of imaging elements according to the first aspect of the invention.

[0050] The imaging elements are preferably arranged to have a first repeat pitch in a first direction and a second repeat pitch in a second direction intersecting the first direction.

[0051] The first repetition pitch is between 4 pm and 30 pm and preferably equal to 10 pm, and the second repetition pitch has the same dimensional characteristics as the first repetition pitch.

[0052] Thus, the repetition step is equal to or less than the size of a neuronal cell.

[0053] The imaging device then comprises a regular network, or matrix, of elements imaging.

[0054] Thus, the device combines an imaging capability at several scales: the scale of an imaging element, and the scale of the matrix.

[0055] The imaging elements are preferably distributed over an area greater than 1 cm2, for example 4 cm2.

[0056] Thus, when the imaging elements are sized to correspond to the size of a neuronal cell, the device has imaging capabilities combining micrometric spatial resolution (for example 15 pm) and a centimetric field of analysis (for example 4 cm2).

[0057] Such capabilities make it possible to simultaneously image the activity of a large number of neuronal cells and to study the correlation between this activity and the function of neural networks. It is, moreover, possible to multiplex the experimental conditions on the same sample. This avoids introducing inter-sample variations that could bias the measurements. Several drugs can thus be tested and their effects compared reliably, with a view to better predicting the effectiveness of future disease treatments.

[0058] A third aspect of the invention relates to a system for imaging a sample comprising: • an imaging device according to the second aspect of the invention, • an image sensor arranged opposite said imaging device, and adapted to form at least one image of the light wave generated by the imaging device under the effect of the sample, • a processor adapted to process the image formed by the photodetector.

[0059] Thanks to electro-optical transduction, the visualization, recording and analysis of electrical activity are carried out by an optical system (image sensor and processor) located at a distance from the imaging device and the sample.

[0060] This optical system can also be used to image the morphological details as well as the movements of this sample.

[0061] The association of these two imaging modes (electrical and morphological) makes it possible to correlate the electrical activity of a population of neuronal cells with morphological and organizational changes or with cell movements.

[0062] A fourth aspect of the invention relates to a method of analyzing a sample using the imaging device according to the second aspect of the invention, comprising the following steps: • Depositing the sample on the imaging device such that the sample is in contact with at least one of the electrodes of said imaging device, each electrode in contact belonging to a corresponding imaging element of said imaging device, • Optical detection of the electrical activity of the sample, comprising a step of collecting a light wave generated by the electroluminescent element of the imaging element corresponding to the contacting electrode, the light wave being generated in response to a voltage from the sample.

[0063] The generated light wave can be collected by an image sensor, arranged opposite the imaging device, and in which the collection step is followed by a step of acquisition, by the photodetector, of an image representative of the light wave.

[0064] The step of acquiring the image representative of the light source can be followed by a step of determining the voltage coming from the sample from the image acquired by the image sensor.

[0065] A fifth aspect of the invention relates to a method of manufacturing an imaging element intended for the analysis of a sample, comprising the following steps: • Supply of an electronic circuit comprising a connection pad and a voltage-controlled current source, the current source comprising a control electrode electrically connected to the connection pad, • Formation, on the electronic circuit, of an electroluminescent element, • Formation of a transparent, or semi-transparent, and insulating protective layer covering the electroluminescent element and the connection pad, • Formation, on the protective layer and opposite the electroluminescent element, of a transparent or semi-transparent electrode suitable for receive the sample, • Formation, through the protective layer, of a conductive via extending from the transparent or semi-transparent electrode to the connection pad.

[0066] In a preferred embodiment of this manufacturing method, the conductive via and transparent or semi-transparent electrode are formed from the same material, respectively conductive and transparent or conductive and semi-transparent.

[0067] The manufacturing method can then comprise, to form the transparent electrode and the conductive via, the following sub-steps: • Formation, by etching the protective layer, of an opening extending from the surface of the protective layer to the connection pad connected to the control electrode of the current source, • Simultaneous formation of the transparent or semi-transparent electrode and the conductive via by deposition, in a single step, of the conductive and transparent or semi-transparent material on the surface of the protective layer, opposite the electroluminescent element, and on the walls of the opening.

[0068] The invention and its various applications will be better understood upon reading the following description and examining the accompanying figures. BRIEF DESCRIPTION OF THE FIGURES

[0069] The figures are presented for information purposes only and in no way limit the invention. • [Fig.l] schematically represents in top view a preferred embodiment of an imaging device, in the form of a matrix of imaging elements, • [Fig.2] schematically represents in cross-sectional view the imaging matrix of [Fig.l] and illustrates its operating principle, • [Fig.3] schematically represents in top view an imaging element of the imaging matrix of [Fig.l], • [Fig.4] schematically represents in cross-sectional view along a section plane AA the imaging element of [Fig.3], • [Fig.5] schematically represents in cross-sectional view along a section plane BB the imaging element of [Fig.3], • [Fig.6] is an example of a simplified electrical diagram of the imaging element of [Fig.3], • [Fig.7] schematically represents in cross-sectional view along a section plane BB an alternative embodiment of the imaging element of [Fig.3], • [Fig.8] schematically represents in cross-sectional view along a section plane AA an alternative imaging element to the imaging element of [Fig.3], • [Fig.9] schematically represents in cross-sectional view along a section plane BB the imaging element of [Fig.8], • [Fig. 10] schematically represents an imaging system based on the imaging device of [Fig.l], • [Fig.l 1] is a block diagram illustrating the sequence of the main stages of a sample analysis process, • Figures 12A to 12L schematically represent in sectional view along section plane BB the steps or sub-steps of manufacturing the imaging element of [Fig.3].

[0070] Unless otherwise specified, the same element appearing in different figures has a single reference. DETAILED DESCRIPTION

[0071] As mentioned above, the present invention relates in particular to an imaging device comprising a plurality of imaging elements for detecting and visualizing the electrical activity of a sample.

[0072] In the remainder of the description, the sample will be considered to be a biological sample such as neuronal cells in culture in a culture medium.

[0073] A preferred embodiment of this imaging device is shown in Figures 1 and 2, respectively in a top view and in a sectional view.

[0074] The imaging device 1 comprises mxn imaging elements 20. m and n are non-zero positive natural integers. For example, m and n may be equal to 2000.

[0075] The imaging elements 20 are of the same type, i.e. manufactured together and in the same manner, and therefore have the same characteristics or very similar characteristics. They are preferably identical.

[0076] The imaging elements 20 are arranged in rows and columns in the form of a matrix 2. They advantageously have a first repetition pitch PI in a first direction DI and a second repetition pitch P2 in a second direction D2 intersecting the first direction. The second direction D2 is for example perpendicular to the first direction DI.

[0077] The repetition steps PI, P2 may be identical. The imaging device then comprises a regular network, or matrix, of imaging elements.

[0078] Preferably, the repetition steps PI, P2 are between 4 pm and 30 pm.

[0079] Preferably, the repetition steps PI, P2 are between 4 pm and 10 pm. Thus, PI, P2 repetition steps are equal to or less than the size of a neuronal cell.

[0080] The general operating principle of the imaging device 1 is described in relation with [Fig.2].

[0081] The device 1 is intended to receive the ECH- sample

[0082] When one of the neuronal cells Cs of this ECH sample emits an action potential, it produces an extracellular potential Vin20s on the surface of the imaging element 20S with which it is in contact which, in response, produces locally, on the surface of the device 1, a light wave O2os having at least one wavelength, for example in the spectral band 400 nm - 800 nm, and the intensity of which depends on the amplitude of the extracellular potential Vin20S.

[0083] Assuming that the other Ci cells in the ECH sample do not produce any action potentials (i.e., are inactive), the other imaging elements 20 are inactive or "off."

[0084] As the light wave O20s is localized at the level of the electrically active cell, and the intensity of this light wave varies according to the extracellular potential Vin2os, it is possible to acquire a quantitative map of the electrical activity of the sample ECh-

[0085] The imaging elements 20 are thus comparable to pixels of a screen, with the difference that the signal O20s that they deliver is controlled by, or a function of, the electrical activity Vin20s of the sample Ech.

[0086] The operation of the imaging device 1 will be better understood with the aid of the description of the imaging element 20 below.

[0087] Figures 3 to 6 schematically represent, according to different views, a first embodiment of the imaging element 20.

[0088] Figures 8 and 9 schematically represent, in sectional views, a second embodiment of the imaging element 20.

[0089] Reference will first be made to FIGS. 6 and 9 which represent the first and second embodiments of the imaging element 20 according to the same sectional view BB.

[0090] In a manner common to these two embodiments, the imaging element 20 is intended for the analysis of the ECH sample and comprises: • an electrode 201 adapted to receive the ECH sample • an electroluminescent element 202, arranged opposite the electrode 201, and separated from the electrode by an insulating protective layer 203. By “opposite” is meant that all or part of the electroluminescent element 202 is located opposite, or in front of, the electrode 201. • a voltage-controlled current source 204, configured to supply the electroluminescent element 202 with current and comprising a control electrode (not shown in FIGS. 6 and 9) electrically connected to the electrode 201.

[0091] The electrode 201 is used as a sensitive surface, or receiver, that is to say that it is in contact with the ECH sample, more precisely with a Cs cell of this ECH sample, and collects the extracellular potential Vin20s emitted by this Cs cell in contact.

[0092] The term “suitable for receiving the ECH sample” means that the electrode is not such as to degrade this ECH sample when it is in contact with it. As the ECH sample considered is biological, the electrode 201 is biocompatible.

[0093] The electrode 201 has lateral dimensions preferably between 4 μm and 20 μm, and for example equal to 10 μm.

[0094] These size ranges are particularly well suited to the size of neuronal cells, which is generally between 10 μm or 15 μm. More precisely, these dimensions are small enough to allow the analysis of an individual neuronal cell, and large enough for the connection with this individual cell to be robust with respect to the position of this cell. The sensitive surface thus obtained is in fact notably larger than that described previously in the state of the art, which makes it possible to improve the capacity for detecting an action potential (or, in other words, the risk of missing an electrical event is reduced).

[0095] Furthermore, since the entire surface of the electrode 201 is conductive, the position of the neuronal cell on the electrode 201 is of little importance. In other words, there is no need for the sample to be positioned precisely on a certain part of the imaging element for an action potential to be detected.

[0096] The imaging element is thus well suited to the electrical imaging of an individual neuronal cell, while being, compared to the state of the art, less sensitive to the position of the sample, which increases the detection efficiency and makes it possible to obtain a more faithful (more consistent) response to the actual electrical activity of the sample.

[0097] The electroluminescent element 202 is used as an electro-optical transducer, making it possible to produce, as described previously in relation to [Fig.2], the light wave O2os in response to the extracellular potential Vin20S generated by the sample E ch and collected by the electrode 201.

[0098] The electroluminescent element 202 designates an element which produces monochromatic or polychromatic non-coherent radiation in the 400-800 nm spectral band, i.e. in the transparency spectral band, by conversion of electrical energy when an electric current passes through it.

[0099] The intensity of this radiation is advantageously proportional to the electric current.

[0100] Preferably, the electroluminescent element 202 is an organic light-emitting diode or OLED (acronym for “Organic Light Emitting Diode” in English). This is a technology that allows for easier and less expensive manufacturing and integration, and to drive the device with lower control currents than an LED (acronym for “Light Emitting Diode” in English) for example.

[0101] The internal structure of the electroluminescent element 202 is shown in particular in [Fig.4] and in [Fig.5] (for the first embodiment), and in figures 8 and 9 (for the second embodiment).

[0102] With reference to these figures 4, 5, 8 and 9, the electroluminescent element 202 comprises an organic layer 2022 disposed between two electrodes, the anode 2023 and the cathode 2021, which are transparent or semi-transparent.

[0103] The electroluminescent element 202 has lateral dimensions which are preferably close to the lateral dimensions of the transparent electrode 201. Thus, these dimensions are preferably between 10 pm and 15 pm, for example 12 pm.

[0104] Such dimensions make it possible to obtain a good spatial correspondence between the transparent electrode 201 (the receiver) and the electroluminescent element 202 (the transducer).

[0105] For this, with reference to figures 4 and 5, or 8 and 9, the cathode 2021, the organic layer 2022 and the anode 2023 of the electroluminescent element 202 are structured to have the desired lateral dimensions.

[0106] The organic layer 2022 can be formed from several layers, for example an HTL layer (acronym for “Hole Transporting Layer” in English) and an emissive layer.

[0107] According to an alternative embodiment represented by [Fig.7], compatible with both embodiments, only the anode 2023 of the electroluminescent element 202 is structured to have these dimensions. From a manufacturing point of view, this arrangement simplifies the process since the organic layer 2022 and the cathode 2021 can be formed by a single-step deposition, i.e. without a lithography and etching step.

[0108] The electroluminescent element 202 may also be an inorganic light-emitting diode (or LED acronym for “Light Emitting Diode” in English), in particular a microLED.

[0109] Like OLEDs, micro-light emitting diodes or microLEDs (acronym for “micro-Light Emitting Diodes” in English) have the advantage of having micrometric dimensions well adapted to the size of neuronal cells, for example dimensions between 15 pm and 20 pm.

[0110] Compared to OLEDs, microLEDs have higher luminance and longer lifetime, but they require higher drive current and are more difficult to manufacture.

[0111] The protective layer 203 is an encapsulation layer, which makes it possible to protect the electroluminescent element 202, and thus to guarantee its lifetime. It also makes it possible to electrically isolate the electrode 201 from the electroluminescent element 202.

[0112] It is noted that, due to the arrangement of the protective layer 203 in the imaging element 20, the electrode 201 is distinct from the electroluminescent element 202. In particular, it is distinct from the electrodes, anode 2021 and cathode 2023, of this electroluminescent element 202.

[0113] The protective layer 203 can also surround the electrode 201 when the latter does not cover the entire surface of the imaging element 20. It can also be used to separate the imaging elements 20 from each other in the imaging device 1 shown in [Fig.2]. It then forms insulating blocks separating the imaging elements 20. In these two cases, the ECH sample can also be in contact with the protective layer 203 which is then, like the electrode 201, adapted to receive the ECH sample.

[0114] The protective layer 203 may be formed from a stack of organic sub-layers and inorganic sub-layers which may be transparent.

[0115] The inorganic layers are for example based on aluminum oxide (A12O3) or titanium dioxide (TiO2). The organic layers are based on resin.

[0116] The thickness of the protective layer 203 is preferably between 25 nm and 1 μm, and is for example equal to 300 nm.

[0117] The current source 204 makes it possible to drive the electroluminescent element 202 in response to the electrical activity Vin2os of the sample ECh-

[0118] More precisely, the current source 204 has the effect of converting the extracellular potential Vin2os generated by the ECH sample (and collected by the electrode 201) into a current passing through the electroluminescent element 202 and capable of generating the light wave O20s in this electroluminescent element 202.

[0119] With reference to [Fig.5] (first embodiment) or [Fig.9] (second embodiment), the electrical connection between the current source 204 and the transparent electrode 201 comprises an electrical track 206, a connection pad 205, and a conductive via 211.

[0120] The electrical track 206 is for example metallic.

[0121] The connection pad 205 is for example metallic.

[0122] The conductive via 211 extends from the transparent electrode 201 to the connection pad 205.

[0123] Preferably, the conductive via 211 is formed from the same material as the transparent electrode 201. The manufacturing process is facilitated because the electrode 201 and the via 211 are formed simultaneously.

[0124] [Fig.6] is an example of a simplified electrical diagram of the imaging element 20, compatible with all embodiments of the imaging element 20.

[0125] With reference to this [Fig.6], the current source 204 preferably comprises a transistor 2041 having: • a gate electrode 2042 constituting the control electrode of the current source 204; • a source electrode 2043 connected to the electroluminescent element 202; and • a drain electrode 2044 connected to a power supply terminal.

[0126] With reference to figures 4 (first embodiment) and 8 (second embodiment), this power supply terminal can be coupled, via metallic electrical tracks 23, 24 to a voltage source (not shown in [Fig.5]).

[0127] Preferably, the transistor 2041 is a thin-film transistor also called TFT (acronym for “Thin Film Transistor” in English).

[0128] With reference to [Fig.6], the transistor 2041 provides a current iD between the drain and source electrodes 2043,2044 which is controlled by the voltage VDD applied to the supply terminal (and therefore to the drain electrode 2044) and by the electrical voltage Vc of the gate electrode 2042. In this [Fig.6], the references VSEUIL, VOFFSET, RST and RST correspond to control voltages.

[0129] Transistor 2041 operates in saturated mode.

[0130] In the absence of electrical activity of the neuronal cell Cs, the transistor 2041 is blocked. No current ID flows between the drain 2042 and source 2043 electrodes, nor through the electroluminescent element 202. The electroluminescent element 202 is therefore off and forms a “black” pixel.

[0131] When there is electrical activity of the neuronal cell C20s, the extracellular potential Vin2os modifies the voltage Vc of the gate electrode, which is then sufficient to turn on the transistor 2041. A current iD, proportional to the gate voltage Vc then passes through the electroluminescent element 202 which emits the light wave O20s with an intensity proportional to the gate voltage Vc.

[0132] In a calibration phase, the electrical potential on the transparent electrode 201 is modulated around an operating point and the variations in intensity of the light wave O20s are measured. Calibration data associated with the imaging element 20, 20S are thus obtained.

[0133] In an analysis phase, the light intensity is measured and reported, via the calibration data, to the amplitude of the extracellular potential Vin20s.

[0134] With reference to [Fig.6], the imaging element 20 preferably comprises an electronic control circuit 207 electrically connected, on the one hand, to the control electrode 2042 of the current source 204, and on the other hand, via the connection pad 205, to the transparent electrode 201.

[0135] The control circuit 207 is configured to generate, from the extracellular potential Vin20s, an electrical control voltage Vc on the control electrode 2042 of the current source 204.

[0136] For this, the control circuit 207 can comprise one or more functional blocks called stages, arranged in series.

[0137] For example, it comprises a switch stage 2071 making it possible to trigger the reading of the transparent electrode 201, and in doing so, to provide an extracellular voltage Vex from the extracellular potential Vin2os and a reference voltage V offset*

[0138] It can also comprise an amplification stage 2072 making it possible to amplify the extracellular voltage Vex so that the control voltage is greater than the threshold voltage of the transistor 2041, this threshold voltage being defined as the voltage between the gate electrode 2042 and the source electrode 2043 for which the inversion zone appears.

[0139] Thus, even extracellular potentials of low amplitude, for example 15 mV are detected and lead to the emission of the light wave O2os by the electroluminescent element 20).

[0140] It may also comprise a memory stage 2073 making it possible to ensure that the electrical voltage Vc is maintained over a certain duration on the control electrode 2042 of the current source 204. This duration is, at most, the same as the time of the neuronal activity, i.e. from 1 ms to 2 ms. Preferably, this duration is adapted to guarantee an observation time (of light background) sufficient to be measurable, for example this duration is between 10 ps and 100 ps.

[0141] Stage 2071, amplification stage 2072 and memory stage 2073 arranged, in order, in series.

[0142] The imaging element 20 which has just been described in relation to FIGS. 3 to 9 has several advantages, in particular: • It is not necessary to place the sample in an electrolyte bath, nor to polarize this electrolyte bath. • The electroluminescent element 202 makes it possible to produce an optical signal representative of neuronal electrical activity without the need to incorporate, into the cell, dyes (for example proteins) sensitive to variations in cellular voltage. The imaging is therefore non-invasive.

[0143] According to the first embodiment, illustrated in particular in figures 3, 4 and 5, the electrode 201 is transparent, or semi-transparent, as is the protective layer 203.

[0144] The term “semi-transparent” is used for any material or element which has an optical transmission coefficient greater than 60% for at least one wavelength included in the spectral band extending into the visible range, i.e. between 400 nm and 800 nm.

[0145] The term “transparent” is used for any material or element which has an optical transmission coefficient greater than 80% for at least one wavelength included in the spectral band extending into the visible range, i.e. between 400 nm and 800 nm.

[0146] Thus, the light wave O2os generated by the electroluminescent element 202 in response to the electrical activity of the sample ECH passes through the transparent or semi-transparent protective layer 203 and the transparent or semi-transparent electrode 201.

[0147] The O2os light wave is therefore generated at least partly on the same side as the ECH- sample. An advantage is that it is then relatively easy to combine, using optical systems, the image of the electrical activity with the image of the morphological details of the ECH- sample.

[0148] The association of these two imaging modes (electrical and morphological) makes it possible to correlate the electrical activity of a population of neuronal cells with morphological and organizational changes or with cell movements.

[0149] The transparent or semi-transparent electrode 201 is formed from a transparent, or respectively semi-transparent, and conductive material.

[0150] Preferably, this material is chosen from the following materials: Poly(3,4-ethylenedioxythiophene) (or PEDOT), indium tin oxide (or ITO for "Indium Tin Oxide" in English), tin dioxide (SnO2), zinc oxide (ZnO) or aluminum-doped zinc oxide (or AZO).

[0151] The transparent or semi-transparent electrode 201 can also be formed from a thin layer, between 5 nm and 100 nm, of aluminum (Al), silver (Ag), or chromium (Cr).

[0152] The electrode 201 is transparent when it has a thickness of between 5 nm and 30 nm.

[0153] The electrode 201 is semi-transparent when it has a thickness of between 5 nm and 100 nm.

[0154] Advantageously, the anode 2023 of the electroluminescent element is an optical reflection surface. Thus, the light wave O20s is generated essentially in the direction of the transparent or semi-transparent electrode 201. This configuration avoids optical losses, and makes it possible to improve the sensitivity limit of the imaging element 20.

[0155] With reference to [Fig.5], the voltage-controlled current source 204 is part of an electronic circuit 22. This circuit 22 is for example coupled to the electroluminescent element 202 on the side of the anode 2023 of this electroluminescent element 202. The electronic circuit 22 also serves as a substrate, or support for the imaging element 20, and more broadly for the imaging device 1 illustrated in [Fig.l].

[0156] The electrical track 206 is preferably integrated into the electronic circuit 22.

[0157] The connection pad 205 is preferably integrated into the electronic circuit 22. It is for example arranged so as to be flush with the surface of the circuit 22. It can also be arranged as a projection (not shown in [Fig.6]).

[0158] It will be noted that when the same material is used to form the electrode 201 and the conductive via 211, a transparent or semi-transparent via 211 is then available, making it possible to avoid certain optical phenomena (parasitic reflections) which could disturb the propagation of light beam O20s.

[0159] According to the second embodiment, illustrated in FIGS. 8 and 9, the electroluminescent element 202 is arranged between the protective layer 203 and a transparent or semi-transparent substrate 200.

[0160] As a result, the luminous flux O2os generated by the electroluminescent element 202 in response to the electrical activity of the ECH sample passes through this transparent or semi-transparent substrate 200.

[0161] Being able to collect this O20s light wave on the side opposite the electrode 201 makes it possible to free up space above the ECh sample, this space being able to be used to carry out other types of measurements on this sample.

[0162] The transparent or semi-transparent substrate 200 serves as protection and support for the electroluminescent element 202. It may be glass.

[0163] The electrode 201 and the protective layer 203 are not necessarily transparent or semi-transparent.

[0164] They may be opaque. In this case, the electrode 201 may be formed of a metal, for example aluminum (Al), silver (Ag) or chromium (Cr).

[0165] Advantageously, the electrode 201 is a reflection surface. The metal used to form this electrode 201 can then be argon (Ag). This makes it possible to optimize the optical power passing through the substrate 200, and therefore to improve the detection limit of the imaging element 20.

[0166] The cathode 2021 of the electroluminescent element may also be a reflective surface.

[0167] With reference to [Fig.8], the connection of the current source 204 to the metal tracks 23 and 24 is, similarly, arranged so as not to block the passage of light source O20s through the substrate 200.

[0168] With reference to [Fig.9], the current source 204, as well as the connection elements 205, 206, 211 and the electronic circuit 207 are arranged so that they do not block the passage of light emitting element O20s through the substrate 200. For example, they may be arranged, at least in part, between the electrode 201 and the electroluminescent element 202.

[0169] Regardless of the embodiment of the imaging element 20, the arrangement in superimposed levels of the current source 204, the electroluminescent element 202, the protective layer 203 and the transparent electrode 201 makes it possible to obtain a compact imaging element 20, integrating all the reception / transduction functions.

[0170] This makes it possible to produce, in the imaging device 1 shown in [Fig.l], the matrix 2 of imaging elements 20 with a high density, for example more than 6000 electrodes per mm2, and a large surface area, for example 2x2 cm2.

[0171] The imaging device 1 thus has imaging capabilities combining a micrometric spatial resolution, between 4 pm and 10 pm, and a centimetric analysis field, for example 4 cm2, greater than the state of the art.

[0172] Such capabilities make it possible to simultaneously image the activity of a large number of neuronal cells and to study the correlation between this activity and the function of neural networks. It is, moreover, possible to multiplex the experimental conditions on the same sample. This avoids introducing inter-sample variations that could bias the measurements. Several drugs can thus be tested and their effects compared reliably, with the aim of better predicting the effectiveness of future disease treatments.

[0173] Another aspect of the invention relates to an imaging system 3, represented in [Fig.3], using the imaging device 1.

[0174] This system 3 makes it possible to acquire an image of the O2os light wave generated by the imaging device 1 under the effect of the ECH sample, then to carry out, from this image, an optical detection of the electrical activity of the ECH sample.

[0175] The imaging system 3 comprises for this purpose the imaging device 1, an image sensor 4, and a processor 5.

[0176] The image sensor 4 is formed of a matrix of pixels and thus adapted to form, and acquire, at least one image of the light wave O2os generated by the imaging device 1 under the effect of an ECH- sample

[0177] The image sensor 4 is arranged relative to the imaging device 1 so as to collect the light wave O20s generated by one or more of the imaging elements 20S of the imaging device 1. In other words, it is arranged on the side of the face of the device 1 which is crossed by the light wave O20s-

[0178] In [Fig. 10], the imaging device 1 integrates the imaging elements 20 according to the first embodiment (in which the electrode 201 and the protective layer 203 are transparent or semi-transparent). Thus, the photodetector 4 is arranged on the side of the electrodes 201 of these imaging elements 20, and therefore on the side of the sample Ech. Naturally, when the imaging elements are produced according to the second embodiment, the photodetector 4 is arranged on the side opposite the electrodes 201 and the sample ECh-

[0179] This image sensor 4 can be coupled with the face of the imaging device crossed by the light wave O2os by focusing optics, such as optical lenses, objectives, etc.

[0180] The image sensor 4 can be integrated into a microscope.

[0181] The processor 5 communicates with the image sensor 4. It is for example a microprocessor. It makes it possible to process the image formed by the image sensor, that is to say to carry out operations for determining characteristics of the image, etc.

[0182] Another aspect of the invention relates to a method of analyzing the ECH sample using the imaging device 1.

[0183] This analysis method 100 is described in relation to [Fig.l 1]. It comprises the main steps S101, S102 and S103.

[0184] The analysis method 100 begins with step S101 consisting of depositing the sample Ech on the imaging device 1, in contact with at least one of the electrodes 201 of this imaging device 1. Each electrode 201 in contact with the sample belongs to a corresponding imaging element 20 of said imaging device 1, and is associated with the electroluminescent element of said imaging element 20.

[0185] The analysis method 100 continues with step S102, which consists of carrying out an optical detection of the electrical activity of the sample ECh-

[0186] This optical detection comprises a step S1021 of collecting a light wave O2os generated by the electroluminescent element (202) of the imaging element corresponding to the electrode in contact, this light wave O20s being formed in response to a voltage Vin20S coming from the sample ECH-

[0187] Optical detection can be carried out using the image sensor 4 of the imaging system 3 (see [Fig. 10]).

[0188] In this case, the collection S1021 of the light wave O20s is carried out by the image sensor 4. The collection step S1021 can then be followed by an acquisition step S1022, by the image sensor 4, of an image representative of the light wave O20s formed on the image sensor 4.

[0189] This acquisition step S1022 can then continue with a determination step S1023 of the electrical activity of the sample, precisely of the voltage V in2os coming from the sample ECH from the image acquired by the image sensor 4.

[0190] This determination step S1023 is carried out by the processor 5 of the imaging system 3 (see [Fig. 10]). It may comprise: • a step of determining the characteristics of the acquired image, such as determining a region of interest corresponding to the active (i.e. luminous) imaging elements, and determining a value average intensity (of gray levels) on this region of interest, and • a step of correlating said determined characteristics with the extracellular potential generated by the ECH sample, using the calibration characteristics. These calibration characteristics are established by implementing the optical detection step S102, using a “standard” sample consisting of applying a known electrical potential modulated around an operating point on the transparent electrode 201.

[0191] Another aspect of the invention relates to a method of manufacturing the imaging element 20.

[0192] Figures 12A to 12L illustrate the steps and sub-steps of this manufacturing method 900 for manufacturing the imaging element 20 according to the first embodiment (illustrated in Figures 3, 4 and 5). It will be considered that this first embodiment comprises that the protective layer 203 and the electrode 201 are transparent.

[0193] Generally, the method 900 comprises the following steps: • Provision of the electronic circuit 22 comprising the connection pad 205 and the voltage-controlled current source 204, the current source 204 comprising a control electrode (not shown) electrically connected to the connection pad 205, • Formation, on the electronic circuit 22, of the electroluminescent element 203, • Formation of the transparent and insulating protective layer 203 covering the electroluminescent element 202 and the connection pad 205, • Formation, on the protective layer 203 and opposite the electroluminescent element 202, of the transparent electrode 201 adapted to receive the sample, • Formation, through the protective layer 203, of the conductive via 211 extending from the transparent electrode 201 to the connection pad 205 connected to the control electrode of the current source 204.

[0194] In a particular embodiment, the method 900 comprises the steps S901, S902, S903, S904, S905, S906, S907, S908, S909, S910, S911 and S912 illustrated respectively in [Fig.l2A], in [Fig.l2B], in [Fig.l2C], in [Fig.l2D], in [Fig.l2E], in [Fig.l2F], in [Fig.l2G], in [Fig.l2H], in [Fig.l21], in [Fig.l2J], in [Fig.l2K], and in [Fig.l2L].

[0195] In this particular embodiment, the transparent electrode 201 and the contact connection to the electronic circuit through the via 211 are formed simultaneously by depositing the same transparent and conductive material.

[0196] With reference to [Fig.l2A], the method 300 begins with step S901, which consists of providing the electronic circuit 22.

[0197] This circuit 22 includes the connection pad 205 and the current source 204 voltage-controlled. The current source 204 comprises the control electrode 2042 (not shown in [Fig.l2A]) electrically connected to the connection pad 205 via the electrical track 206. The circuit 22 further comprises the electronic control circuit 207.

[0198] Step S902, illustrated in [Fig.l2B], is performed after step S901 and consists of forming, on the electronic circuit 22, the electroluminescent element 202.

[0199] In the case of an OLED type electroluminescent element, this step S902 comprises the following successive sub-steps: • Formation of the anode 2023 of the electroluminescent element 202, • Formation of the organic 2022 layer, • Formation of the cathode 2023.

[0200] These sub-steps are carried out by a succession of deposition, photolithography and etching steps.

[0201] Step S903, illustrated in [Fig.l2C], follows step S902 and consists of encapsulating the electroluminescent element 202 by the transparent protective layer 203 (or encapsulation layer). This protective layer 203 covers the electroluminescent element 202 and the connection pad 205.

[0202] Steps S904, S905, S906 and S907 which follow step S903 aim to prepare the formation of the conductive via 211 by forming an opening 210 at the level of an area adjacent to the area 2024 (cf. [Fig. 12F]) of the electroluminescent element, this opening 210 extending from the surface 2031 of the protective layer 203 to the connection pad 205.

[0203] Step S904, illustrated in [Fig.l2D], is a step of depositing a first sacrificial layer 208 on the surface 2031 of the protective layer 203. The sacrificial layer 208 is preferably a photosensitive resin layer.

[0204] Step S905, illustrated in [Fig.l2E], is a step of forming a first opening 209 through the first sacrificial layer 208 in the area adjacent to the area 2024, typically by exposing and developing the photosensitive resin. The opening 209 opens onto the protective layer 203.

[0205] Step S906, illustrated in [Fig. 12F] consists of forming a second opening 210 in the extension of the first opening 209, up to the electronic circuit 22, by vertical etching of the protective layer 203 through the first sacrificial layer 208. In other words, the first sacrificial layer 208 acts as an etching mask.

[0206] Step S907, illustrated in [Fig.l2G], consists of removing the first sacrificial layer 208.

[0207] Steps S908, S909, S910, S911 and S912 are for forming the transparent electrode 201 and the conductive via 211. The transparent electrode 201 and the conductive via 211 are advantageously formed by deposition, photolithography and etching of the same layer of transparent and conductive material 201a.

[0208] Step S908, illustrated in [Fig.l2H], follows step S907 and consists of depositing the transparent and conductive material 201a over the entire surface 2031 of the protective layer 203 and in the second opening 210.

[0209] Steps S909, S910, S911 and S912 aim in particular to delimit the transparent electrode 201 so that it has the desired shape and dimensions.

[0210] Step S909, illustrated in [Fig. 121], consists of depositing a second sacrificial layer 212 (typically a layer of photosensitive resin) on the layer of conductive and transparent material 201a deposited previously.

[0211] Step S910, illustrated in [Fig.l2J], is a step of localized removal of the second sacrificial layer 212 (typically by insolation and development of the photosensitive resin layer). The removal is carried out in an area 2011 located around the area of ​​the electroluminescent element 202.

[0212] Step S911, illustrated in [Fig.l2K], is a step of etching the transparent and conductive material layer 201a through the second sacrificial layer 212 (the second sacrificial layer 212 acts as an etching mask).

[0213] Step S912, illustrated in [Fig.l2L], is a step of removing the remaining portion of the second sacrificial layer 212. On the protective layer 2031, the conductive and transparent material 201a forms the transparent electrode 201, and on the walls of the second opening 210, it forms the conductive via 211.

[0214] At the end of step S912, the imaging element 20 is formed.

[0215] The imaging device 1 can be manufactured according to a manufacturing method derived from the manufacturing method of the imaging element 20 which has just been described.

Claims

Claims

1. Imaging element (20, 20S) intended for the analysis of a sample (ECH) and comprising: - an electrode (201) adapted to receive the sample (ECH), - a light-emitting element (202), arranged opposite the electrode (201), and separated from the electrode by an insulating protective layer (203), - a voltage-controlled current source (204), configured to supply the light-emitting element (202) with current and comprising a control electrode (2042) electrically connected to the electrode (201), so that said light-emitting element (202) generates a light wave (O2os) in response to a voltage (Vin20s) coming from the sample (ECH)-

2. The imaging element (20, 20S) of claim 1, wherein the light-emitting element (202) is disposed between the protective layer (203) and a transparent or semi-transparent support substrate (200).

3. Imaging element (20, 20S) according to one of claims 1 to 2, wherein the electrode (201) and the protective layer (203) are transparent or semi-transparent.

4. Imaging element (20, 20S) according to one of claims 1 to 3, wherein the current source (204) comprises a transistor (2041) having: - a gate electrode (2042) constituting the control electrode of the current source; - a source electrode (2043) connected to the electroluminescent element; and - a drain electrode (2044) connected to a power supply terminal.

5. The imaging element (20, 20S) of claim 4, wherein the transistor (2041) is a thin film transistor also called a TFT.

6. Imaging element (20, 20S) according to one of claims 4 to 5, wherein the lateral dimensions of the electrode (201) are greater than the lateral dimensions of the transistor (2041).

7. An imaging element (20, 20S) according to one of claims 1 to 6, wherein the light-emitting element (202) is an organic light-emitting diode.

8. An imaging element (20, 20S) according to one of claims 1 to 6, wherein the light-emitting element (202) is an inorganic light-emitting diode, preferably a micro-inorganic light-emitting diode.

9. Imaging element (20, 20S) according to one of claims 1 to 8, further comprising an electronic control circuit (207) configured to generate a control voltage (Vc) of the current source (204), said electronic control circuit (207) electrically connecting the control electrode (2042) of the current source (204) and the electrode (201).

10. An imaging device (1) comprising a plurality of imaging elements (20, 20S) according to one of claims 1 to 9.

11. An imaging device (1) according to claim 10, wherein the imaging elements (20, 20S) are arranged to have a first repetition pitch (P1) in a first direction and a second repetition pitch (P2) in a second direction intersecting the first direction.

12. System (3) for imaging a sample (ECH) comprising: - an imaging device (1) according to one of claims 10 to 11, - an image sensor (4) arranged opposite said imaging device (1) and adapted to form at least one light background image (O2os) generated by the imaging device (1) under the effect of the sample (ECH), - a processor (5) adapted to process the image formed by the photodetector (4).

13. Method (100) for analyzing a sample (Ech) using the imaging device (1) according to claims 10 to 11, comprising the following steps: - Depositing (S101) the sample (Ech) on the imaging device (1) so that the sample (ECH) is in contact with at least one of the electrodes (201) of said imaging device (1), each electrode (201) in contact belonging to a corresponding imaging element (20) of said imaging device (1), - Optical detection (S 102) of the electrical activity of the sample (ECh), comprising a step of collecting (S1021) a light wave (O2os) generated by the electroluminescent element (202) of the imaging element corresponding to the electrode in contact, Light wave (O2os) being generated in response to a voltage (Vin20S) coming from the sample (ECH)*

14. Analysis method (100) according to claim 13, in which the generated light wave (O20s) is collected by an image sensor, arranged opposite the imaging device (1), and in which the collection step (S 1021) is followed by an acquisition step (S 1022), by the photodetector (4), of an image representative of the light wave (O 2 Os)*

15. Analysis method (100) according to claim 14, wherein the step of acquiring (S1022) the image representative of the light wave (O 2os) is followed by a step of determining (S 1023) the voltage coming from the sample (ECH) from the image acquired by the photodetector (4).

16. Method (900) for manufacturing an imaging element (20) intended for analyzing a sample (ECH), comprising the following steps: - Providing (S901) an electronic circuit (22) comprising a connection pad (205) and a voltage-controlled current source (204), the current source (204) comprising a control electrode (2042) electrically connected to the connection pad (205), - Forming (S902), on the electronic circuit (22), an electroluminescent element (202), - Forming (S903) a transparent, or semi-transparent, and insulating protective layer (203) covering the electroluminescent element (202) and the connection pad (205), Forming (S904, S905, S906, S907, S908, S909, S910, S911, S912), on the protective layer (203) and opposite the electroluminescent element (202), a transparent or semi-transparent electrode (201) adapted to receive the sample (ECH), Formation (S904, S905, S906, S907, S908, S909, S910, S911, S912), through the protective layer (203), of a conductive via (211) extending from the transparent or semi-transparent electrode (201) to the connection pad (205).

17. Manufacturing method (900) according to claim 16, wherein the conductive via (211) and transparent or semi-transparent electrode (201) are formed from the same material (201a) which is respectively conductive and transparent, or conductive and semi-transparent.

Images