The improvements generally relate to apparatuses for implantation into biological tissue, and more specifically relate to apparatuses which interact with such biological tissue when so-implanted.
An implantable apparatus may interact with the biological tissue into which it is implanted by sensing and/or stimulating the surrounding biological tissue. For instance, the implantable apparatus can interact with the biological tissue by sensing an electrical activity of the biological tissue. Additionally or alternatively, the implantable apparatus can interact with the biological tissue by electrically stimulating the biological tissue. Other forms of interaction may include electrochemical sensing or stimulation, optical sensing or stimulation, and sampling or delivery of biological materials including drugs, ions, molecules, metabolites, and other fluids. Although existing implantable apparatuses are satisfactory to a certain degree, there remains room for improvement.
It is often desirable for an implantable apparatus to include many biological interaction elements in order to increase the spatial resolution and/or control of the interaction. However, it can be difficult to fabricate such an implantable apparatus, especially when the implantable apparatus has a high density of such biological interaction elements. An implantable apparatus with many biological interaction elements may also be large and rigid, resulting in poor compatibility with the biological tissue into which it is implanted.
There is described an implantable apparatus for interacting with biological tissue. The implantable apparatus has a base, strands each having an elongated body with a proximal end fixed to the base and a distal end opposite the proximal end. As will be discussed below, the strands are entwined with one another to form a thread of entwined strands. For instance, the strands can be twisted with one another, braided with one another, woven with one another, self-assembled via capillary forces and/or surface tension forcing the strands to partially or wholly contact one another along their elongated bodies when pulled out of a liquid, or otherwise manipulated in any other suitable fashion. Biological interaction devices extending between the base and the entwined strands are also provided. Each biological interaction device has one or more biological interaction elements located along the elongated body of a corresponding strand which interacts with surrounding biological tissue when the thread of entwined strands is implanted into the biological tissue.
When the biological interaction devices of the implantable apparatus are interactingly coupled to an actuation apparatus, thereby forming a biological interaction system, biological tissue can be sensed and/or stimulated as desired. For instance, the actuation apparatus can sense electrical signal(s), optical signal(s), and/or biological fluid(s) originating from the biological tissue surrounding the implantable apparatus, and/or stimulate the surrounding biological tissue with electrical signal(s), optical signal(s), and/or external fluid(s) containing chemical(s), drug(s), molecule(s), metabolite(s), ion(s), water or any combination thereof.
In accordance with a first aspect of the present disclosure, there is provided an implantable apparatus for interacting with biological tissue, the apparatus comprising: a base; a plurality of strands each having an elongated body with a proximal end fixed to said base and a distal end opposite the said proximal end, the plurality of strands being entwined with one another to form a thread of entwined strands; and a plurality of biological interaction devices extending between the base and the plurality of strands, the biological interaction devices each having a biological interaction element located along the elongated body of a corresponding one of the plurality of strands and interacting with surrounding biological tissue when the thread of entwined strands is implanted into the biological tissue.
Further in accordance with the first aspect of the present disclosure, at least one of the plurality of biological interaction devices can for example have a conductive pad at the base, and a conductive trace running within the elongated body of a corresponding one of the plurality of strands and electrically connecting the biological interaction element of the at least one of the plurality of biological interaction devices to the conductive pad, the elongated body being made of an electrically insulating material.
Still further in accordance with the first aspect of the present disclosure, the biological interaction element can for example have at least one of an an electrode, a transistor, an electromagnetic coil, an antenna, an electrical transmitter, and an electrical detector.
Still further in accordance with the first aspect of the present disclosure, the electrically insulating material can for example be a polymeric material.
Still further in accordance with the first aspect of the present disclosure, at least one of the plurality of biological interaction devices can for example have an optical port at the base, an optical waveguide running within the elongated body of a corresponding one of the plurality of strands and optically connecting the biological interaction element of the at least one of the plurality of biological interaction devices to the optical port.
Still further in accordance with the first aspect of the present disclosure, the biological interaction element can for example have at least one of an opening along or at the end of the optical waveguide, a reflective surface, a focusing lens, a collecting lens and an optical filter.
Still further in accordance with the first aspect of the present disclosure, at least one of the plurality of biological interaction devices can for example have a microfluidic port at the base, a microfluidic channel running within the elongated body of a corresponding one of the plurality of strands and fluidically connecting the biological interaction element of the at least one of the plurality of biological interaction devices to the microfluidic port.
Still further in accordance with the first aspect of the present disclosure, the biological interaction element can for example have at least one of a fluidic entry port, a fluidic exit port, a nozzle and a valve.
Still further in accordance with the first aspect of the present disclosure, the elongated bodies of the plurality of strands can for example have a similar length.
Still further in accordance with the first aspect of the present disclosure, the entwined strands can for example be twisted with one another.
Still further in accordance with the first aspect of the present disclosure, the implantable apparatus can for example comprise one or more gaps within the entwined strands of the thread.
Still further in accordance with the first aspect of the present disclosure, the elongated bodies of the entwined strands of the thread can for example be in contact with one another.
Still further in accordance with the first aspect of the present disclosure, at least some of the plurality of biological interaction devices can for example extend between the base and one of the plurality of strands, with biological interaction elements being longitudinally spaced-apart from one another along the elongated body of the one of the plurality of strands.
Still further in accordance with the first aspect of the present disclosure, at least some of the biological interaction elements of the biological interaction devices of different strands can for example be longitudinally aligned with one another.
Still further in accordance with the first aspect of the present disclosure, said at least some of the biological interaction elements of the biological interaction devices can for example be located at the distal ends.
Still further in accordance with the first aspect of the present disclosure, said interacting can for example include at least one of electrically interacting, optically interacting and fluidically interacting with said surrounding biological tissue.
In accordance with a second aspect of the present disclosure, there is provided a method of interacting with biological tissue, the method comprising: entwining a plurality of strands to one another, thereby obtaining a thread of entwined strands each having an elongated body extending between a proximate end and an opposite distal end, a plurality of biological interaction elements being disposed along the elongated bodies of the entwined strands; implanting the thread of entwined strands within the biological tissue via the distal ends of the entwined strands of the thread; and the biological tissue surrounding the thread interacting with the plurality of biological interaction elements of the entwined strands.
Further in accordance with the second aspect of the present disclosure, said interacting for example comprise at least one of transmitting a signal to the surrounding biological tissue and receiving a signal from the surrounding biological tissue.
Still further in accordance with the second aspect of the present disclosure, said signal can for example be one of an electrical signal and an optical signal.
Still further in accordance with the second aspect of the present disclosure, said interacting can for example comprise at least one of injecting a fluid into the surrounding biological tissue and drawing a fluid from the surrounding biological tissue.
Still further in accordance with the second aspect of the present disclosure, said entwining can for example comprise at least one of twisting and braiding the plurality of strands with one another.
Still further in accordance with the second aspect of the present disclosure, said implanting can for example comprise implanting said thread of entwined strands into at least one of a central nervous system and a peripheral nervous system of a patient.
Still further in accordance with the second aspect of the present disclosure, the distal ends can for example be removably attached to a sacrificial member, said entwining comprising manipulating the sacrificial member relative to the proximal ends and removing the sacrificial member after said entwining.
The implantable apparatus is designed to address at least some shortcomings of some existing implantable apparatuses in terms of fabrication, implantation, ability to scale up the density of biological interaction elements, biocompatibility, and the ease of connectivity with any type of actuation apparatus, for instance. Broadly described, the implantable apparatus can be used for scientific, therapeutic, and/or diagnostic purposes including sensing electrical, optical, fluidic, metabolic, ionic, and/or chemical activity originating from cells, stimulation of cells in biological tissue, nervous system interfaces and brain-machine interfaces. More specifically, the implantable apparatus can be designed to sense or stimulate neural activity in cortex, hippocampus, or other areas of the brain to track activity of hundreds to thousands of neurons simultaneously or sequentially, individually or in groups, over a given period of time. The implantable apparatus can be designed to sense or stimulate neural activity in the peripheral nervous system as the thread of entwined strands can be sewn into a nerve fiber bundle to enable sensing and/or stimulating at a range of depths within the nerve fiber. The implantable apparatus can be designed to allow for sensing of specific metabolites or other biomarkers to allow for simultaneous or sequential sensing of one or more biomarkers in the surrounding biological tissue.
Many further features and combinations thereof concerning the present improvements will appear to those skilled in the art following a reading of the instant disclosure.
In the figures,
As illustrated, the implantable apparatus 102 has a base 108, and strands 110 fixed to the base 108 at an end thereof. More specifically, each strand 110 has an elongated body 112 with a proximal end 114 fixed to the base 108 and a distal end 116 opposite to the proximal end 114. As shown, the strands 110 are entwined with one another to form a thread 118 of entwined strands 110. The thread 118 of entwined strands 110 thereby has a fixed end and an opposite free end to be implanted in the biological tissue 106. The thread 118 of entwined strands 110 can be designed to be biocompatible, and also flexible with cellular-size dimensions to reduce foreign-body response.
The base can take many forms. In some embodiments, the base can be flat, with the strands all connected to one or more edges of the flat base. In some other embodiments, the base can have a cube-like body, with the strands connected to one or more sides of the cube-like body in a two dimensional array. Other embodiments may apply.
It is intended that the thread 118 of entwined strands 110 can have one or more gaps 120 separating some portions of two or more adjacent strands 110, which may advantageously increase the contact surface with the biological tissue 106 and bodily fluids, as fluids and cells can move into and through the thread 118 via the gaps 120. Moreover, it is noted that the thread 118 of entwined strands 110 can be more flexible than existing implantable apparatuses with the same number of biological interaction elements thanks to at least part of the gaps 120 between the entwined strands 110. In some other embodiments, the elongated bodies 112 of the strands 110 may be in contact with one another along their entire lengths. Accordingly, the density of the thread 118 of entwined strands 110 can be adjusted to allow both densely packed threads as well as loosely packed threads, i.e., structures with physical space between the strands 110 that may be equal to one or more strands. The implantable apparatus 102 can also be configured to allow for expansion of the thread 118 once it is implanted into the biological tissue 106 in order to allow for the penetration of cellular structures and other biological media. In any case, the thread 118 of entwined strands 110 can be formed such that it maintains its original form following implantation.
The number of strands 110 can vary from one embodiment to another. However, in some embodiments, the implantable apparatus 102 can have at least two strands 110, at least ten strands 110, or more, and so forth, depending on the embodiment. The strands 110 may be straight or with curves and turns in some embodiments. The length of the entwined strands 110 can vary as well. For instance, the entwined strands 110 of the thread 118 can share a similar length to one another in some embodiments whereas the entwined strands 110 of the thread 118 can have different lengths in some other embodiments. In some embodiments, the length of the strands 110 can range between 1 mm and 1 m, preferably between 5 cm and 500 cm, and most preferably between 1 cm and 10 cm. The strands 110 can be thin, with widths and depths each varying between 0.1 μm and 1 mm, preferably between 25 μm and 500 μm and most preferably between 50 μm and 100 μm. The strands 110 can have cross-sectional areas varying between 1 μm2 and 1 cm2, preferably between 10 μm2 and 0.9 cm2, and most preferably between 100 μm2 and 0.5 cm2. It was found that in embodiments where the width of the thread 118 of entwined strands 110 corresponds to the cell dimension associated to the biological tissue, rejection of the implantable apparatus 102 may be less likely.
As shown in the depicted embodiment, biological interaction devices 122 extend between the base 108 and the strands 110. Each biological interaction device 122 has one or more biological interaction elements 124 located along the elongated body 112 of a corresponding strand 110 of the thread 118. The biological interaction elements 124 are configured to interact with surrounding biological tissue 106 when the thread 118 of entwined strands 110 is implanted into the biological tissue 106.
In this specific embodiment, the interaction between the implantable apparatus 102 and the biological tissue 106 is of electrical nature, as the biological interaction devices 122 are configured for sensing electrical activity of the surrounding biological tissue 106 and/or electrically stimulating the surrounding biological tissue 106. However, as described below with reference to
Still referring to
It is envisaged that the electrical interaction with the biological tissue 106 may be performed only via the biological interaction elements 124. For instance, the biological interaction elements 124 can include an electrode, a transistor, an electromagnetic coil or antenna, or some other electrical transmitter or detector. In some embodiments, the transistor can be a regular transistor for sensing or delivering electrical activity. However, in some other embodiments, the transistor can be configured to sense chemical activity, for example by coating an exposed surface of the transistor with one or more chemically sensitive materials or enzymes. Additionally or alternately, the biological interaction elements 124 can have a circular shape, a rectangular shape, or any other suitable shape, with dimensions suitable for measuring single cell activity (e.g., 10 μm×10 μm) or for interacting with groups of a few or many cells together.
The type of electrical components included in each biological interaction element 124 can differ from one biological interaction device 122 to another. For instance, some of the biological interaction elements 124 can include electrical transmitters whereas some other of the biological interaction elements 124 can include electrical detectors. It is intended that the type of electrical components of the biological interaction elements 124 dictate the construction of the actuation apparatus 104.
In the illustrated embodiment, the actuation apparatus 104 has an electrical signal generator 130 which is electrically connected to at least some of the electrical pads 126 at the base 108, and an electrical signal detector 132 which is electrically connected to some other of the electrical pads 126 at the base 108. Some or all of the electrical pads 126 at the base 108 may also be connected to both the electrical signal generator 130 and the electrical signal detector 132 for bidirectional interaction with the biological tissue. In such an embodiment, the biological tissue 106 may be electrically stimulated by the electrical signal generator 130 generating an electrical signal to be propagated along some of the conductive traces 128 via the electrical pads 126, before or after which, or at the same time as, the biological interaction elements 124 may transmit corresponding electrical signals to the surrounding biological tissue 106. Understandably, the electrical activity of the surrounding biological tissue 106 may be picked up by the biological interaction elements 124 only to be communicated to the electrical signal detector 132 via the conductive traces 128 and the electrical pads 126 for sensing purposes. Wires of the actuation apparatus 104 can be electrically connected to the electrical pads 126 using simultaneous electrical connection methods, including, but not limited to, zero-insertion-force connectors, flexible ribbon cable bonding, and the like.
Of course, the actuation apparatus 104 can differ from the one illustrated in
The biological interaction element(s) 124 can be positioned at any longitudinal position along the elongated body 112 of a strand 110. Additionally or alternatively, the biological interaction elements 124 of different strands 110 may be longitudinally aligned with or spaced-apart from one another. For instance, in some embodiments, the biological interaction element 124 may be located at the distal ends 116 of the elongated bodies 112 of the strands 110, thereby providing electrical interaction at a tip 134 of the thread 118.
The stands 110 may be entwined with one another in any suitable manner. For instance, in some embodiments, the strands 110 are entwined with one another by twisting the strands 110 to one another. In these embodiments, one or more sacrificial members 136 may be attached to the distal ends 116 of the strands 110 such as shown in
The implantable apparatus can be fabricated using a variety of approaches, including standard microfabrication techniques.
The openings 148 at the electrical pads and biological interaction elements 124 can be made by selective deposition of the insulating material (e.g., photolithography, printing, chemical vapor deposition), by selective removal of the insulating material (e.g., wet or dry etching, laser ablation), or by some combination of the two. The electrically insulating material between the conductive traces 128 for the portion of the implantable apparatus that forms the strands 110 would be removed by a similar means either concurrently or subsequently. Such a fabrication can be done such that a thin layer of insulation is maintained on all sides of the conductive traces 128 within a strand 110. A thin coating of bioresorbable or other material may be applied to the thread 118 of entwined strands 110 at any point in the above methods in order to help maintain the desired formation. Other methods of fabricating the strands 110 can be performed in some other circumstances.
In some embodiments, each strand 110 may have one or more biological interaction elements 124.
The method of implanting the implantable apparatus 202 into biological tissue can differ from one embodiment to another. The implantable apparatus 202 can be implanted into the biological tissue directly without the need for a shuttle or other indirect implanting means. In some embodiments,
As illustrated, the implantable apparatus 302 has a base 308, and strands 310 fixed to the base 308 at an end thereof. More specifically, each strand 310 has an elongated body 312 with a proximal end 314 fixed to the base 308 and a distal end 316 opposite to the proximal end 314. As shown, the strands 310 are entwined with one another to form a thread 318 of entwined strands 310. The thread 318 of entwined strands 310 thereby has a fixed end and an opposite free end to be implanted in the biological tissue 306. In this specific embodiment, the biological interaction devices 322 each have an optical port 326 at the base 308, and an optical waveguide 328 running within the elongated body 312 of a corresponding strand 310, thereby optically connecting the biological interaction element 324 of the corresponding strand 310 to the corresponding optical port 326 at the base 308. Examples of such optical waveguide 328 can include, but not limited to, fiber(s), strip waveguide(s) and the like. In such embodiments, the elongated bodies 312 of the strands 310 are made of a material preventing any undesired optical interaction between the optical waveguides 328 and the biological tissue 306 surrounding the strands 310.
It is envisaged that the optical interaction with the biological tissue 306 may be performed only via the biological interaction elements 324. For instance, the biological interaction elements can include an opening along or at the end of optical waveguide 328, a reflective surface, a focusing lens, a collecting lens and an optical filter.
The type of electro-optical components included in each biological interaction element 324 can differ from one biological interaction device 322 to another. For instance, some of the biological interaction elements 324 can include optical transmitters whereas some other of the biological interaction elements 324 can include electrical detectors. It is intended that the type of electro-optical components of the biological interaction elements 324 dictate the construction of the actuation apparatus 304.
In the illustrated embodiment, the actuation apparatus 304 has an optical signal generator 330 which is optically connected to at least some of the optical ports 326 at the base 308, and an optical signal detector 332 which is optically connected to some other of the optical ports 326 at the base 308. Some or all of the electrical pads 326 at the base 308 may also be connected to both the optical signal generator 330 and the optical signal detector 332. In such an embodiment, the biological tissue 306 may be optically stimulated by the optical signal generator 330 generating an optical signal to be propagated along some of the optical waveguides 328 via the optical ports 326, before or after which, or as the same time as, the biological interaction elements 324 may transmit corresponding optical signals to the surrounding biological tissue 306. Understandably, the optical activity of the surrounding biological tissue 306 may be picked up by the biological interaction elements 324 only to be communicated to the optical signal detector 332 via the optical waveguides 328 and the optical ports 326 for sensing.
As illustrated, the implantable apparatus 402 has a base 408, and strands 410 fixed to the base 408 at an end thereof. More specifically, each strand 410 has an elongated body 412 with a proximal end 414 fixed to the base 408 and a distal end 416 opposite to the proximal end 414. As shown, the strands 410 are entwined with one another to form a thread 418 of entwined strands 410. The thread 418 of entwined strands 410 thereby has a fixed end and an opposite free end to be implanted in the biological tissue 406. In this specific embodiment, the biological interaction devices 422 each have a fluidic port 426 at the base 408, and a microfluidic channel 428 running within the elongated body 412 of a corresponding strand 410, thereby fluidically connecting the biological interaction element 424 of the corresponding strand 410 to the corresponding fluidic port 426 at the base 408. In some embodiments, there can be several biological interaction elements 424 sharing a single microfluidic channel 428 and/or sharing a fluidic port 426 at the base 408. Examples of such microfluidic channels 428 can have, but not limited to, a circular cross-section, a rectangular cross-section and the like. In such embodiments, the elongated bodies 412 of the strands 410 are made of a material preventing any undesired fluidic interaction between the microfluidic channels 428 and the biological tissue 406 surrounding the strands 410.
In addition, in some embodiments, the biological interaction devices 422 are configured to control the biological interaction elements 424. For instance, to open and/or close one or more fluidic ports of the strands 410. Accordingly, the biological interaction devices 422 can have a combination of fluidic channels 428 for the fluid exchange and of electrical traces for communicating control signals.
It is envisaged that the fluidic interaction with the biological tissue 406 may be performed only via the biological interaction elements 424. For instance, the biological interaction elements can include a fluidic entry port, a fluidic exit port, a nozzle and a valve.
The type of fluidic components included in each biological interaction element 424 can differ from one biological interaction device 422 to another. For instance, some of the biological interaction elements 424 can include fluid pushing nozzles whereas some other of the biological interaction elements 424 can include fluid drawing nozzles. It is intended that the type of fluidic components of the biological interaction elements 424 dictate the construction of the actuation apparatus 404.
In the illustrated embodiment, the actuation apparatus 404 has a number of fluidic pumps, either acting as fluidic delivery or fluidic retrieval actuators 430 and 432, e.g., syringe pumps, which are fluidically connected to at least some of the fluidic ports 426 at the base 408. The fluidic pumps can push fluid into the biological tissue 406 and/or draw fluid from the biological tissue 406, depending on the embodiment. Some or all of the fluidic port 426 at the base 408 may also be connected to both the fluidic delivery and fluidic retrieval actuators 430 and 432. In such an embodiment, the biological tissue 406 may be fluidicly stimulated by the fluidic delivery actuator 430 pushing an external fluid to be conveyed along some of the microfluidic channels 428 via the fluidic ports 426, before or after which, or at the same time as, the biological interaction elements 424 may convey corresponding external fluid to the surrounding biological tissue 406. In some embodiments, the external fluid can contain chemical(s), drug(s), molecule(s), metabolite(s), ion(s), water or any combination thereof. Understandably, the fluidic activity of the surrounding biological tissue 406 may be picked up by the biological interaction elements 424 only to be retrieved by the fluidic retrieval actuators 432 via the microfluidic channels 428 and the fluidic ports 426 for sensing purposes.
As can be understood, the examples described above and illustrated are intended to be exemplary only. The scope is indicated by the appended claims.
Filing Document | Filing Date | Country | Kind |
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PCT/IB2019/001282 | 10/31/2019 | WO | 00 |
Number | Date | Country | |
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62755086 | Nov 2018 | US |