Neural microprobe and method of manufacturing same

Abstract

A neural microprobe is disclosed. The neural microprobe comprises a stacked structure having a base layer, a core layer, a metal layer, and a ceiling layer. The base layer is formed from a first species of biocompatible polymer. The core layer is formed from a second species of biocompatible polymer deposited on the base layer. The metal layer is deposited on the core layer. The ceiling layer is formed from the first species of biocompatible polymer deposited on the metal layer and comprises a plurality of trenches etched through the ceiling layer to expose portions of the metal layer, said exposed portions defining electrodes of an electrode array of the neural microprobe. The first species of biocompatible polymer has a lower coefficient of thermal expansion than the second species. A method of manufacturing a neural microprobe comprises providing a first mask on the ceiling layer, wherein the first mask is lithographically patterned to define a plurality of gaps in the first mask; providing a second mask on the first mask; etching, with a first etchant, through the second mask and the gaps in the first mask, trenches in the ceiling layer to expose the portions of the metal layer defining the electrodes of the electrode array; and etching, with a second etchant, the stacked structure to remove any remaining portions of the first and second masks, and to release a base layer of the stacked structure from the release layer.

Description

[0001] NEURAL MICROPROBE AND METHOD OF MANUFACTURING SAME

[0002] Field of the Invention

[0003] The present invention relates to neural microprobes and particularly, to layered neural microprobes having a structure formed from layers of biocompatible polymers.

[0004] Background

[0005] Neural probes may be formed from flexible materials. Such flexible probes may be easier to manipulate by a surgeon and be less likely to induce an immune response (that could ultimately lead to the patient rejecting the probe) than a rigid probe. In particular, the flexibility may allow the prove to move with the brain tissue. However, providing a neural microprobe with improved flexibility may reduce the structural strength and integrity of the microprobe, not least because excessive curvature of an electrode array may cause the microprobe to crack or otherwise break.

[0006] There is, therefore, a need to provide neural microprobes with sufficient flexibility to be easily insertable (and to allow for the probe to conform onto convolutions and / or ridges found in brain tissue) but with sufficient structural integrity to be robust enough to survive such an implantation.

[0007] The present invention has been devised in light of the above considerations.

[0008] Summary of the Invention

[0009] In a general sense, the present invention provides a neural microprobe having a layered structure of biocompatible polymer materials in which the layers are symmetrically configured about a central plane to simultaneously provide flexibility and structural robustness / integrity. Additionally, the present invention provides a method of manufacturing such neural microprobes that follows a novel atypical protocol that is more efficient than the standard method of alternating deposition and etching steps.

[0010] In an aspect, there is provided a method of manufacturing a neural microprobe. The method comprises: providing a first mask on a ceiling layer of a stacked structure deposited on a release layer formed on a silicon wafer. The first mask is lithographically patterned to define a plurality of gaps in the first mask. The method further comprises: providing a second mask on the first mask; and etching, with a first etchant, through the second mask and the gaps in the first mask, trenches in the ceiling layer to expose portions of a metal layer underlying the ceiling layer. The exposed portions define electrodes of an electrode array of the neural microprobe. The method further comprises: etching, with a second etchant, the stacked structure to remove any remaining portions of the first and second masks. The method further comprises removing the release layer under the stacked structure to separate the stacked structure from the silicon wafer, e.g. by disengaging a base layer of the stacked structure from the release layer. This method of depositing two masks and then etching through them with two separate etchants differs from conventional fabrication methods at least in that conventional fabrication methods alternate deposition and etching steps such that a single layer is always deposited between successive etching steps. In contrast, this method involves depositing two differently structure and patterned masks consecutively without an etching operation in between, and is then followed by two consecutive etching steps (with two different etchants) with no deposition operation in between. Such a method is more efficient than the typical methods because it does not require the transfer of the stacked structure between various apparatuses to alternate between deposition and etching steps.

[0011] Etching, with the first etchant to expose portions of the metal layer underlying the ceiling layer may define the shape of the neural microprobe by etching the majority of the polymer film, leaving behind only the neural microprobes.

[0012] The first and second masks may be deposited and formed by any conventional method. For example, in some cases, the first mask may be deposited and formed using any lithographic process (e.g., a standard photolithographic process) to form an etch mask. The first mask may be made from any suitable material, for example aluminium - although other suitable materials will be well-known to the skilled person. The first mask may have a thickness suitable for surviving the first etching operation intact. For example, the first mask may have a thickness of approximately 100 nm.

[0013] Similarly, the second mask may be deposited and formed using any lithographic process (e.g., a standard single-layer photolithographic process). The second mask may be made from any suitable material, for example, the second mask may also be formed from aluminium - although other suitable materials will be well-known to the skilled person. The second mask may have a thickness that will be removed during the first etching operation, while preserving the contents of the underlying layers. For example, the second mask may have a thickness of approximately 60 nm. In some examples, the thickness of the second mask may be determined based on the thickness of the ceiling layer of the stacked structure. The deposition of a mask layer typically involves the use of a developer such as tetraethylammonium hydroxide (TMAH). However, such a developer could etch through, or otherwise deteriorate the first mask. Therefore, the deposition of the second mask may preferably not involve the use of a TMAH developer or any other similar developer that has chemical properties suitable for dissolving the first mask.

[0014] In some embodiments, the etching with the first etchant may be a dry-etching process.

[0015] This dry-etching process may completely remove the second mask and etch through those portions of the ceiling layer that underly gaps in the first mask to expose the portions of the metal layer defining the electrodes of the electrode array.

[0016] The dry-etching process may use a standard dry-etching recipe such as the ICP180 oxygen recipe provided by Oxford InstrumentsR™.

[0017] In some embodiments, the method may further comprise monitoring the depth of the etching with the first etchant with an interferometer. In this way, the manufacturer of the neural microprobe may be confident that they are accurately manufacturing the neural microprobe without accidentally etching through the electrodes of the electrode array.

[0018] The use of an interferometer may be appropriate based on a judicious choice of the materials for the various layers of the stacked structure, by recognising how the strength of a signal measured by the interferometer will depend on the reflectance of the uppermost exposed material. By monitoring how the signal (and therefore the reflectance) changes, the manufacturer may be able to determine how far through the stacked structure they have etched.

[0019] In some embodiments, the etching with the second etchant may be a wet-etching process.

[0020] This wet-etching process may release the stacked structure from the silicon wafer and dissolve the release layer such that it is removed from the stacked structure.

[0021] The wet-etching process may use a standard wet-etching recipe such as TMAH or an acidic aluminium etchant to remove the remaining hard mask and the bulk of the release layer.

[0022] In some embodiments, the release layer may be formed from a material that is removable by electrolysis, and the method may further comprise: after etching with the second etchant, removing any remaining traces of the release layer from the stacked structure by electrolysis.

[0023] The electrolysis process may preferably be a standard electrolysis process. To be suitable for electrolysing, the release layer may - for example - a 50 nm layer of aluminium deposited using a standard process and machine (e.g., a beam evaporator such as the MEB550S produced by PlassysRTM). The electrolysis process may be necessary to remove those portions of the release layer that are located underneath the stacked structure. For example, the wet-etching process may only remove those areas of the release layer (which may, for example, be formed from aluminium) that are not protected by the probes. Electrolysis of the release layer may therefore be required to remove the remaining release layer, for example by connecting the silicon wafer to a power supply and immersing it in a solution of e.g., sodium chloride with a negative electrode.

[0024] In some embodiments, the stacked structure may comprise: a base layer, said base layer being formed from a first species of biocompatible polymer; a core layer formed from a second species of biocompatible polymer deposited on the base layer; the metal layer, said metal layer being deposited on the core layer; and the ceiling layer, said ceiling layer being from the first species of biocompatible polymer, and being deposited on the metal layer. The first species of biocompatible polymer may have a lower coefficient of thermal expansion than the second species.

[0025] In another aspect, there is provided a neural microprobe comprising a stacked structure. The stacked structure comprises: a base layer formed from a first species of biocompatible polymer; a core layer formed from a second species of biocompatible polymer deposited on the base layer; a metal layer deposited on the core layer; and a ceiling layer formed from the first species of biocompatible polymer deposited on the metal layer. The ceiling layer comprises a plurality of trenches etched through the ceiling layer to expose portions of the metal layer, said exposed portions defining electrodes of an electrode array of the neural microprobe. The first species of biocompatible polymer has a lower coefficient of thermal expansion than the second species.

[0026] In other words, the degree of thermal expansion exhibited by the base and ceiling layers of the stacked structure is less than that exhibited by the core layer. In this way, the base and ceiling layers provide a symmetric profile (in terms of thermal expansion) that reduces the risk of the stacked structure undergoing curvature that makes the electrode array or another component of the neural microprobe more difficult to manipulate. Therefore, the symmetric profile makes the overall microprobe easier to accurately and reliably implant.

[0027] In some examples of either aspect, the metal layer may be formed by a lithographic lift-off process to define the electrode of the electrode array.

[0028] The lithographic lift-off process may be any suitable lithographic process, for example a bilayer photoresist photographic lift-off procedure.

[0029] The metal layer may be formed from any suitable biocompatible metal having suitable conductive properties.

[0030] In some embodiments, the metal layer may be at least partly formed from titanium and / or platinum and / or an alloy of titanium and platinum.

[0031] Titanium and platinum are metals having suitable conductivity and biocompatibility properties for use in neural implants.

[0032] A bilayer of titanium and platinum may be particularly beneficial because titanium can be used as a biocompatible adhesion layer, while platinum is particularly suitable for use as an electrode material due to its conductive properties.

[0033] In some embodiments, the metal layer may have a thickness of less than 200 nm.

[0034] It may be preferable for the electrodes to be thin relative to the other layers of the stacked structure so that the metal layer does not negatively impact the structural properties of the stacked structure.

[0035] In a preferred example, the metal layer may be formed as a bilayer of metal with a 10 nm layer of titanium deposited on the core layer, and a 90 nm layer of platinum deposited on the layer of titanium. This bilayer of metal may, for example, be patterned with a bilayer of photoresist.

[0036] In some embodiments, one or more of the base layer, core layer and ceiling layer are formed by spincoating and curing the corresponding biocompatible polymer on a corresponding underlying layer.

[0037] Any suitable spin-coating and curing process may be used. For example, the corresponding biocompatible polymer may be deposited using a spin-coating machine with a revolution rate of 2000 revolutions per minute. The spun-coated polymer may subsequently me cured at a temperature of at least 300 °C, using a conventional apparatus, for example a nitrogen oven.

[0038] In some embodiments, the stacked structure may be connected to a microelectromechanical system on a silicon chip. In some, said microelectromechanical system may comprise a microprocessor for controlling the neural microprobe.

[0039] In some examples, the microelectromechanical system may comprise recording hardware.

[0040] The silicon chip may take the form of a printed circuit board suitable for connection with e.g., recording hardware.

[0041] In some embodiments, the coefficient of thermal expansion of the first species may be greater than the coefficient of thermal expansion of silicon.

[0042] In this way, in the context of a stacked structure connected to a microelectromechanical system (MEMS) on a silicon chip, the coefficient of thermal expansion of the first species effectively provides a bridge between that of silicon and that of the second species to minimise the effect of mismatch between the thermal expansions of the second species of biocompatible polymer and silicon. In other words, by providing the first species with a coefficient of thermal expansion between that of silicon and the second species, the base and ceiling layers of the stacked structure effectively provide a thermal bridge to reduce the risk of the stacked structure cracking or otherwise being damaged as a result of thermal mismatch.

[0043] In some embodiments, one or more of the first and second species of biocompatible polymer may be a polyimide polymer.

[0044] In some embodiments, the first species of biocompatible polymer may be polyimide polymer PI-2545.

[0045] PI-2545 is a proprietary polyimide polymer available from HD MicrosystemsR™.

[0046] In some embodiments, the second species of biocompatible polymer may be polyimide polymer HD- 4110.

[0047] HD-4110 is also a proprietary polyimide polymer available from HD MicrosystemsR™.

[0048] Typically, PI-2545 is used only as a release layer and not as part of a stacked structure of a neural microprobe. However, the inventors have found that the properties of PI-2545, relative to (and in conjunction with) those of HD-4110, is particularly beneficial.

[0049] Firstly, HD-4110 provides the necessary structural stability but PI-2545 is particularly useful for providing a thermal bridging effect between the HD-4110 core layer and silicon in a MEMS.

[0050] This is because the coefficient of thermal expansion of silicon is approximately 3 x 10-6K-1, while the coefficients of thermal expansion of PI-2545 and HD-4110 are 1 .3 x 10-5K-1and 3.5 x 10-5K-1.

[0051] In some embodiments, the ceiling layer may be etched to have a surface roughness suitable for adhering to tissue cells of a person into which the neural microprobe is implanted.

[0052] For example, in embodiments where the ceiling layer is formed from PI-2545, etching may cause the ceiling layer to have a surface roughness profile that is inherently more suitable for engaging with and adhering to tissue cells than an etched surface of HD-4110 (which is more typically used as the body of a structure in a neural microprobe). In some examples, there may be a thin (nanometre-scale) aluminium layer between each layer of biocompatible polymer to provide an interface between the two different species of biocompatible polymer.

[0053] In some embodiments, the base layer and the ceiling layer may have a same first thickness, and the core lay may have a second thickness that is larger than the first thickness.

[0054] For example, the base layer and the ceiling layer may have a thickness of 5 pm, and the core layer may have a thickness of 20 pm.

[0055] In this way, the base layer and the ceiling layer may provide the stacked structure with the necessary symmetry to inhibit unwanted curvature of the stacked structure while the thicker core layer may provide the necessary robustness to preserve the structural integrity of the neural microprobe.

[0056] The neural microprobe may preferably be dimensioned to be suitable for implantation in the head of a patient as a neural implant.

[0057] In some embodiments, the neural microprobe may have a length of less than 15 mm.

[0058] For example, in a preferred example, the length of the neural microprobe may be 12 mm.

[0059] In some embodiments, the neural microprobe may have a width of less than 200 pm.

[0060] For example, in a preferred example, the width of the neural microprobe may be 100 pm.

[0061] In some embodiments, the neural microprobe may comprise at least four electrodes.

[0062] In some examples, the number of trenches etched through the ceiling layer is the same as the number of electrodes.

[0063] In some examples, each of the electrodes may be formed as an individual finger-like structure in the metal layer, formed by a lithographic process.

[0064] In a preferred example, the neural microprobe may comprise eight electrodes.

[0065] In some examples, the electrode array of the neural microprobe may have a diameter between 20 pm and 30 pm.

[0066] In some examples, the distance between electrodes may be between 40 pm and 70 pm.

[0067] In some examples, the area of the electrode array may be between 314 pm2and 706 pm2.

[0068] In some examples, the stacked structure may have a thickness of less than 50 pm.

[0069] For example, in a preferred example, the stacked structure may have a thickness of 30 pm.

[0070] In some embodiments, the neural microprobe may be adapted to be flexible such that the neural microprobe can be bent through an angle of 90 degrees without breaking.

[0071] Such flexibility may make it possible to implant the neural microprobe into parts of the brain that have previously been difficult to access using typical microprobe structures. In some embodiments, the neural microprobe may be configured to be implantable in the CA3 sub-region of the ventral hippocampus.

[0072] The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.

[0073] Summary of the Figures

[0074] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0075] Figure 1 shows a silicon wafer upon which the stacked structure of the neural microprobe of the present invention may be manufactured.

[0076] Figure 2 shows the silicon wafer of Figure 1 having a release layer deposited thereon.

[0077] Figure 3a shows a schematic illustration of a spin-coating and curing apparatus system for use in depositing biocompatible polymers on the stacked structure of Figure 2.

[0078] Figure 3b shows the stacked structure of Figure 2 having a base layer deposited thereon.

[0079] Figure 3c shows the stacked structure of Figure 3a having a core layer deposited thereon.

[0080] Figure 4a shows a schematic illustration of a lithographic deposition and lift-off process for use in depositing metal on the stacked structure of Figure 3c.

[0081] Figure 4b shows the stacked structure of Figure 3c having a photoresist bilayer deposited thereon.

[0082] Figure 4c shows the stacked structure of Figure 4b after undergoing photolithographic patterning.

[0083] Figure 4d shows the stacked structure of Figure 4c after deposition of the metal layer.

[0084] Figure 4e shows the stacked structure of Figure 4d after lift-off to define the metal layer.

[0085] Figure 5a shows a schematic illustration of a spin-coating and curing apparatus system for use in depositing a biocompatible polymer on the stacked structure of Figure 4b.

[0086] Figure 5b shows the stacked structure of Figure 4b having a ceiling layer deposited thereon.

[0087] Figure 6a shows a schematic illustration of hard etch masks for deposition on the stacked structure of Figure 5b.

[0088] Figure 6b shows the stacked structure of Figure 5b having a first and second mask deposited thereon.

[0089] Figure 7a shows a schematic illustration of a dry-etching process.

[0090] Figure 7b shows the stacked structure of Figure 6b after undergoing a dry-etching process to remove the second mask and etch trenches in the ceiling layer.

[0091] Figure 7c shows a graph plotting the reflectance of the various layers of the stacked structure when subject to an interrogation signal from an interferometer. Figure 8a shows a schematic illustration of materials used for a wet-etching process and electrolysis.

[0092] Figure 8b shows the stacked structure of Figure 7b after undergoing a wet-etching process and electrolysis to release the stacked structure from the silicon wafer, and to remove the first mask and release layer.

[0093] Figure 9 shows the stacked structure of Figure 8b after undergoing a process (e.g., electrolysis) to remove the structure from a silicon wafer.

[0094] Figure 10a shows a depiction of the surface roughness of polymer HD-4110.

[0095] Figure 10b shows a depiction of the surface roughness of polymer PI-2545.

[0096] Figure 11a shows a schematic illustration of a released neural microprobe.

[0097] Figure 11b shows an image of a neural microprobe bent and implanted into the CA3 sub-region of a ventral hippocampus.

[0098] Detailed Description of the Invention

[0099] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference.

[0100] Figure 1 shows a silicon wafer 100 upon which the neural microprobe described herein may be manufactured. The silicon wafer is preferably cleaned and dried with a standard solvent to prepare it for deposition.

[0101] After providing the wafer 100 upon which the neural microprobe is to be manufacture, a release layer 102 is deposited on the wafer 100. This structure is shown in Figure 2.

[0102] The release layer 102 may be formed from any suitable release material, for example aluminium. The release layer may be deposited by any suitable process, for example vapour deposition to form a 50 nm thick layer of aluminium on the silicon wafer 100.

[0103] Once the preliminary structure has been formed, the components of the stacked structure of the neural microprobe may be deposited to manufacture the microprobe.

[0104] Figure 3a shows a schematic illustration of a spin-coating and curing apparatus system for use in depositing biocompatible polymers on the stacked structure of Figure 2.

[0105] In a first spin-coating process, a base layer 104 is deposited on the release layer 102, as shown in Figure 3b.

[0106] The base layer 104 may be formed from a first species of suitable biocompatible polymer such as a polyimide polymer - e.g., PI-2545. This base layer 104 may be deposited on the preliminary structure by spin-coating at a revolution rate of 2000 revolutions per minute to deposit a base layer 104 of PI-2545, having a thickness of 5 pm. This deposited layer is then set solid by curing at a temperature of at least 300°C, for example using a nitrogen oven.

[0107] Subsequent to the deposition of the base layer 104, a core layer 106 may be deposited on the base layer 104 using a second-spin coating process, as shown in Figure 3c.

[0108] The core layer 106 may be formed from a second species of suitable biocompatible polymer such as a polyimide polymer - e.g., HD-4110. This core layer 106 may be deposited on the base layer 104 by spincoating at a revolution rate of 2000 revolutions per minute to deposit a core layer 106 of HD-4110, having a thickness of 20 pm. This deposited layer is then set solid by curing at a temperature of at least 300°C, for example using a nitrogen oven.

[0109] Importantly, as discussed below, the coefficient of thermal expansion of the first species of biocompatible polymer (defining the base layer 104) is lower than the coefficient of thermal expansion of the second species of biocompatible polymer (defining the core layer 106).

[0110] Figure 4a shows a schematic illustration of a lithographic deposition and lift-off process for use in depositing a metal layer on the stacked structure of Figure 3c.

[0111] For example, a metal layer 108 may be deposited on the core layer 106 through the use the of a bi-layer photoresist using a standard photolithographic lift-off procedure, as shown in Figures 4b to 4e.

[0112] As shown in Figure 4b, a photoresist bilayer 108 may be deposited on the core layer 106. The bilayer may be formed from two photoresists, for example a first of the bilayers 108a may be formed from photoresist S1818, while a second of the bilayers may be formed from photoresist LOR3A, each being a proprietary photoresists available from Shipley ®.

[0113] Further, as shown in Figure 4c, the photoresist bilayer may be patterned using a lithographic (e.g., a photolithographic process).

[0114] Following the (photo) lithographic patterning, the metal layer 110 may be deposited, as shown in Figure 4d.

[0115] The metal layer 110 may be formed as a bi-layer, having a 10 nm layer of titanium deposited on the core layer 106 / photoresist 108b, and a 90 nm layer of platinum deposited on the titanium layer. The photolithographic lift-off process may be used to define a plurality of electrodes (for example eight electrodes) in this metal layer, the electrodes being the parts of the metal layer 110 in contact with the core layer 106. The separation between adjacent electrodes (equivalently referred to as the interelectrode distance) may be between 40 pm and 70 pm. The overall electrode area may be between 314 pm2and 706 pm2. In this way, the bulk of the electrode may be defined as fingers of platinum electrodes.

[0116] The formation of the electrodes as part of the metal layer 110 may be finalised by a lift-off procedure that removes the remaining photoresist bilayer 108a, 108b.

[0117] Figure 5a shows a schematic illustration of a spin-coating and curing apparatus system for use in depositing biocompatible polymers on the stacked structure of Figure 4b. In a spin-coating process, a ceiling layer 112 may be deposited on the metal layer 110, as shown in Figure 5b.

[0118] The ceiling layer 112 is formed from the same first species of biocompatible polymer as the base layer 104. The ceiling layer 112 may therefore be formed from polyimide polymer PI-2545. This ceiling layer 112 may be deposited on the metal layer 108 by spin-coating at a revolution rate of 2000 revolutions per minute to deposit a ceiling layer 110 of PI-2545, having a thickness of 5 pm. This deposited layer is then set solid by curing at a temperature of at least 300°C, for example using a nitrogen oven.

[0119] Figure 6a shows a schematic illustration of hard-etch masks for deposition on the stacked structure of Figure 5b.

[0120] For example, as can be seen in Figure 6b, the stacked structure may have a first mask 114 deposited on the ceiling layer 112, and a second mask 116 deposited on the first mask 114.

[0121] The first mask 114 may, for example, be a standard 100 nm-thick aluminium mask patterned using a standard photolithographic process. Finger-like structures may be machined into the first mask 114 , the gaps between each finger overlaying an electrode of the metal layer 110.

[0122] Meanwhile, the second mask 116 may also be an aluminium mask (this time only 60 nm thick) deposited using single-layer photoresist photolithography. Importantly, no TMAH developer (or any other aluminium- dissolving developer) is used in the deposition of the second mask 116 as this could risk dissolving the first mask 114.

[0123] Following the deposition of both masks 114, 116, a dry-etching process may be implemented as schematically illustrated in Figure 7a.

[0124] This dry-etch may be a conventional dry-etching process, for example using a standard ICP180 oxygen recipe, as provided by Oxford InstrumentsR™.

[0125] As can be seen from Figure 7b, the dry-etching process may remove the second mask 116 and etch trenches 202, 204, 206 through the ceiling layer 112 to expose the electrodes in the metal layer 110. In the case of the dry-etch, the thicker first mask 114 may protect the portions of the ceiling layer 112 underlying the first mask 114 from being removed from the stacked structure.

[0126] The extent to which the trenches are etched through the ceiling layer 112 may be monitored by the manufacturer using interferometric techniques. As can be seen from Figure 7c, each different material constituting the various layers of the stacked structure has a characteristic reflectance in response to an optical interferometric signal.

[0127] For example, as can be seen in Figure 7c, HD-4110 in particular is almost entirely absorbent - i.e., it has a very low reflectance.

[0128] Meanwhile, the (optional) aluminium interfaces between the PI-2545 and HD-4110 layers have (expectedly) very high reflectance levels. By analysing how much of an interferometric interrogation signal is reflected back to the interferometer, the manufacturer is therefore able to infer how far through the stacked structure the first (dry) etchant has etched.

[0129] Following the dry etching process by the first (dry) etchant, a wet-etching process - for example using an acid (second) etchant - may be performed, as schematically indicated in Figure 8a.

[0130] The wet-etching process may be a conventional wet-etching process, for example using TMAH or an acidic aluminium etchant to remove any remaining traces of the second mask 116, and to release the release layer 102 from the silicon wafer 100 to release the neural microprobe from the silicon wafer 100.

[0131] Following the wet-etching process, an electrolysis operation may be performed to remove any remaining aluminium mask (of either mask 114, 116) on top of the ceiling layer 112 and any aluminium release layer 102 remaining attached to the base layer 104.

[0132] As can be seen from Figure 8b, the wet-etching and electrolysis processes may result in a completed stacked structure with a metal layer 110 defining the electrodes on top of a core layer 106, with both of these layers sandwiched between the base and ceiling layers 104, 112.

[0133] By providing the core layer 106 as a HD-4110 polyimide polymer, the stacked structure may provide the neural microprobe with the necessary robustness to survive implantation in a patient.

[0134] Meanwhile, noting that the neural microprobe is preferably connected to a silicon-based MEMS, by providing the base and ceiling layers 104, 112 as a PI-2545 polyimide polymer, the thermal stress of the stacked structure may be reduced as a result of the coefficient of thermal expansion of PI-2545 being disposed between the coefficients of thermal expansion of silicon and HD-4110 respectively.

[0135] Moreover, the PI-2545 polyimide polymer may be deposited as a thinner layer than an HD-4110 layer (the ceiling layer 112, for example, having a thickness of only 5 pm. In this way, the depth of the trench in the ceiling layer may be reduced when compared with a traditional structure made from only HD-4110. This may improve the performance of the neural microprobe because the distance between any tissue and the electrodes is significantly reduced (this can be seen for example, from the fact that the thickness of the core layer 106 is 20 pm - four times thicker than either the base or ceiling layers 104, 110).

[0136] Importantly, the base layer 104 is made from the same material as the ceiling layer 112 to ensure that the stacked structure has the required symmetry to reduce the risk of thermally induced curvature.

[0137] PI-2545 is also a suitable polymer for the base and ceiling layers 104, 112 because of its particular surface properties following a wet-etch. This is illustrated in Figures 9a and 9b.

[0138] The stacked structure depicted in Figure 8b may be released from the silicon wafer 100 and the release layer 102 by electrolysis.

[0139] As discussed above, the electrolysis process may preferably be a standard electrolysis process. To be suitable for electrolysing, the release layer may - for example - a 50 nm layer of aluminium deposited using a standard process and machine (e.g., a beam evaporator such as the MEB550S produced by PlassysRTM). The electrolysis process may be necessary to remove those portions of the release layer that are located underneath the stacked structure. For example, the wet-etching process may only remove those areas of the release layer (which may, for example, be formed from aluminium) that are not protected by the probes. Electrolysis of the release layer may therefore be required to remove the remaining release layer, for example by connecting the silicon wafer to a power supply and immersing it in a solution of e.g., sodium chloride with a negative electrode.

[0140] The resulting (completed) stacked structure following release of the structure from the release layer 102 and silicon wafer 100 is depicted in Figure 9

[0141] Figure 10a shows a depiction of the surface roughness of polymer HD-4110 after wet-etching.

[0142] Figure 10b shows a depiction of the surface roughness of polymer PI-2545 after wet-etching.

[0143] As can be seen from these figures, HD-4110 has a higher average surface roughness than PI-2545 (165 nm compared to 29 nm). However, the qualitative nature of the surface roughness of the two different species is significantly qualitatively different.

[0144] In particular, while the average deviations (seen in Figures 10a and 10b) may be higher in HD-4110, there is a smaller number of peaks when compared with PI-2545. The greater number of shallower peaks in PI-2545 after wet-etching makes PI-2545 more surprisingly more suitable than HD-4110 for engaging with tissue cells that the stacked structure is brought into contact with.

[0145] Figure 11a shows a schematic illustration of a released probe 300. Figure 11 b shows a scan of the probe having been inserted into the CA3 sub-region of a ventricular hippocampus.

[0146] The stacked structure of Figure 9 is housed in the trapezoidal region depicted at the end of the neural microprobe 300. The microprobe 300 may be inserted into the hippocampus using a titanium guidewire or other suitable flexible implanting process. As can be seen from Figure 11 b, the neural microprobe 300 can be subject to bends as extreme as 90° without comprising the structural integrity of the microprobe 300.

[0147] ***

[0148] The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

[0149] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

[0150] For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations. Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0151] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0152] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example + / - 10%. Reference Numerals

[0153] 100 Silicon wafer

[0154] 102 Release layer

[0155] 104 Base layer

[0156] 106 Core layer

[0157] 108a First photoresist bilayer

[0158] 108b Second photoresist bilayer

[0159] 110 Metal layer

[0160] 112 Ceiling layer

[0161] 114 First mask

[0162] 116 Second mask

[0163] 202 Trench

[0164] 204 Trench

[0165] 206 Trench

[0166] 300 Neural microprobe

Claims

Claims1 . A neural microprobe comprising a stacked structure, the stacked structure comprising: a base layer formed from a first species of biocompatible polymer; a core layer formed from a second species of biocompatible polymer deposited on the base layer; a metal layer deposited on the core layer; and a ceiling layer formed from the first species of biocompatible polymer deposited on the metal layer, wherein the ceiling layer comprises a plurality of trenches etched through the ceiling layer to expose portions of the metal layer, said exposed portions defining electrodes of an electrode array of the neural microprobe, and wherein the first species of biocompatible polymer has a lower coefficient of thermal expansion than the second species.

2. The neural microprobe according to claim 1 , wherein the metal layer is formed by a lithographic lift-off process to define the electrodes of the electrode array.

3. The neural microprobe according to claim 1 or 2, wherein the metal layer is formed at least partly from titanium, platinum, or an alloy of titanium and platinum.

4. The neural microprobe according to any preceding claim, wherein the metal layer has a thickness of less than 200 nm.

5. The neural microprobe according to any preceding claim, wherein one or more of the base layer, core layer and ceiling layer are formed by spin-coating and curing the corresponding biocompatible polymer on a corresponding underlying layer.

6. The neural microprobe according to any preceding claim, wherein the stacked structure is connected to a microelectromechanical system on a silicon chip.

7. The neural microprobe according to any preceding claim, wherein the coefficient of thermal expansion of the first species is greater than the coefficient of thermal expansion of silicon.

8. The neural microprobe according to any preceding claim, wherein one or more of the first and second species of biocompatible polymer is a polyimide polymer.

9. The neural microprobe according to claim 8, wherein the first species of biocompatible polymer is polyimide polymer PI-2545.

10. The neural microprobe according to claim 8 or 9, wherein the second species of biocompatible polymer is polyimide polymer HD-4110.11 . The neural microprobe according to any preceding claim, wherein the ceiling layer is etched to have a surface roughness suitable for adhering to tissue cells of a person into which the neural microprobe is implanted.

12. The neural microprobe according to any preceding claim, wherein the base layer and the ceiling layer have a same first thickness, and the core layer has a second thickness that is larger than the first thickness.

13. The neural microprobe according to any preceding claim, wherein the neural microprobe has a length of less than 15 mm.

14. The neural microprobe according to any preceding claim, wherein the neural microprobe has a width of less than 200 pm.

15. The neural microprobe according to any preceding claim, wherein the neural microprobe comprises at least four electrodes.

16. The neural microprobe according to any preceding claim, wherein the electrode array of the neural microprobe has a diameter between 20 and 30 pm.

17. The neural microprobe according to any preceding claim, wherein the stacked structure has a thickness of less than 50 pm.

18. The neural microprobe according to any preceding claim, wherein the neural microprobe is adapted to be flexible such that the neural microprobe can be bent through an angle of 90 degrees without breaking.

19. The neural microprobe according to any preceding claim, wherein the neural microprobe is configured to be implantable in the CA3 sub-region of the ventral hippocampus.

20. A method of manufacturing a neural microprobe, the method comprising: providing a first mask on a ceiling layer of a stacked structure deposited on a release layer formed on a silicon wafer, wherein the first mask is lithographically patterned to define a plurality of gaps in the first mask; providing a second mask over the first mask and the plurality of gaps; etching, with a first etchant, through the second mask, trenches in the ceiling layer to expose portions of a metal layer underlying the ceiling layer, said exposed portions defining electrodes of an electrode array of the neural microprobe; etching, with a second etchant, the stacked structure to remove remaining portions of the first and second masks; andremoving the release layer under the stacked structure to separate the stacked structure from the silicon wafer.21 . The method according to claim 20, wherein the etching with the first etchant is a dry- etching process.

22. The method according to claim 20 or 21 , further comprising monitoring the depth of the etching with the first etchant with an interferometer.

23. The method according to any of claims 20 to 22, wherein the etching with the second etchant is a wet-etching process.

24. The method according to any of claims 20 to 23, wherein the release layer is formed from a material that is removable by electrolysis, and wherein removing the release layer under the stacked structure is done by electrolysis.

25. The method according to any of claims 20 to 24, wherein the manufactured neural microprobe is as claimed in any of claims 1 to 19.

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