Tapered dosing, photostimulation and electrophysiological probe for neural interface

Abstract

Multi-modal fiber optic probe devices and methods of making the same are described. In one example, a multi-modal fiber optic probe apparatus may include a flexible tapered fiber optic probe structure having a microscale tip region at a first end and a macroscale connector region at a second end opposite the first end. The multi-modal fiber optic probe device may also include an optical waveguide positioned in the flexible tapered fiber optic probe structure and extending through the flexible tapered fiber optic probe structure from the micro-scale tip region to the macro-scale connector region. The multi-modal fiber optic probe device may also include a microfluidic channel formed in the flexible tapered fiber optic probe structure and extending through the flexible tapered fiber optic probe structure from the micro-scale tip region to the macro-scale connector region.

Description

[0001] Government licensing rights

[0002] This invention was completed under government grants from the National Institutes of Health (NIH) under grant numbers R01NS123069A and R21EY033080A. The government holds certain rights to this invention.

[0003] Cross-references to related applications

[0004] This application claims the benefit and priority of U.S. Provisional Application Serial No. 63 / 499,869, filed May 3, 2023, entitled “TAPERED DRUG DELIVERY, OPTICAL STIMULATION, AND ELECTROPHYSIOLOGY PROBE FOR NEURAL INTERFACING,” the entire contents of which are incorporated herein by reference. This application also claims the benefit and priority of U.S. Provisional Application Serial No. 63 / 598,801, filed November 14, 2023, entitled “TAPERED DRUG DELIVERY, OPTICAL STIMULATION, ELECTROPHYSIOLOGY PROBE, AND FABRICATION THEREOF,” the entire contents of which are incorporated herein by reference. This application also claims the benefit and priority of U.S. Provisional Application Serial No. 63 / 598,810, filed November 14, 2023, entitled “COMBINED FIBER PHOTOMETRY AND ELECTROPHYSIOLOGY PROBE AND FABRICATION THEREOF”, the entire contents of which are incorporated herein by reference. Background Technology

[0005] Our nervous system plays a vital role in every aspect of our lives, from thoughts and emotions to sensations and breathing. Technological advancements have improved our understanding of the nervous system, and a deeper understanding of the brain's inner workings is essential for the early detection and treatment of neurological disorders such as Alzheimer's, epilepsy, and substance use disorders, as well as for advancements in brain-computer interfaces that can restore sensorimotor function. Monitoring and manipulating neural activity with greater precision enables a deeper understanding of the dynamics of the nervous system. The widespread adoption of silicon-based neural probes capable of monitoring electrical activity and applying light has made significant progress in this field.

[0006] Understanding the neural basis of behavior, as well as the diagnosis and treatment of neurological diseases, requires carefully designed, highly specific protocols that monitor and manipulate combinations of physiological elements and their interactions in behavioral animals to unlock the complex and obscure mechanisms of the brain. The primary tool for this research is the neural probe. Currently, the most widely available probes are general-purpose silicon-based microelectromechanical systems (MEMS) devices. Additionally, electrophysiology is a well-established and well-understood method for monitoring neural activity at high temporal frequencies. Furthermore, fiber optic photometry involves collecting and analyzing light signals emitted from neurons affected by genetically encoded calcium indicators (GECIs). Summary of the Invention

[0007] This disclosure relates to multimode fiber optic probe devices and methods for manufacturing the same. Embodiments described herein describe a thermal taper process that can be implemented to manufacture various types of flexible multimode fiber optic neural probe devices, all of which incorporate ultrafine features of dense electrodes or tetrodes, optical waveguides, and microfluidic channels at the tip region of the device. The probe devices of this disclosure may also include a back-end connector region that allows for scalable assembly of the probe.

[0008] Aspects and advantages of embodiments of this disclosure will be set forth in part in the description which follows, or may be learned from the description or by practice of the embodiments. Other aspects and advantages of embodiments of this disclosure will be better understood with reference to the appended claims and drawings, all of which are incorporated in and constitute a part of this specification. The accompanying drawings illustrate exemplary embodiments of this disclosure and, together with the description, serve to explain the relevant concepts of this disclosure.

[0009] According to one example embodiment, a multimode fiber optic probe device may include a flexible tapered fiber optic probe structure having a micro-scale tip region at a first end and a macro-scale connector region at a second end opposite the first end. The multimode fiber optic probe device may also include an optical waveguide positioned within the flexible tapered fiber optic probe structure and extending from the micro-scale tip region through the flexible tapered fiber optic probe structure to the macro-scale connector region. The multimode fiber optic probe device may also include a microfluidic channel formed within the flexible tapered fiber optic probe structure and extending from the micro-scale tip region through the flexible tapered fiber optic probe structure to the macro-scale connector region. Attached Figure Description

[0010] Many aspects of this disclosure can be better understood by referring to the following accompanying drawings. The components in the drawings are not necessarily drawn to scale, but the emphasis is on clearly illustrating the principles of this disclosure. Furthermore, the repeated use of reference numerals or numbers in the drawings is intended to indicate the same or similar features, elements, or operations in different drawings. For the sake of brevity, repeated descriptions of these repeated reference numerals or numbers have been omitted.

[0011] Figure 1 A perspective view of an example multimode fiber optic probe device according to various aspects and embodiments of the present disclosure is shown.

[0012] Figure 2A , Figure 2B and Figure 2C An example probe component arrangement of an example multimode fiber optic probe device according to various aspects and embodiments of the present disclosure is shown.

[0013] Figure 3A , Figure 3B and Figure 3C An example optical waveguide addressable mode of an example multimode fiber optic probe device according to various aspects and embodiments of this disclosure is shown.

[0014] Figure 4A An example preform manufacturing process is illustrated according to various aspects and embodiments of this disclosure.

[0015] Figure 4B An example hot stretching process is illustrated according to various aspects and embodiments of this disclosure.

[0016] Figure 4C An example thermal tapering process according to various aspects and embodiments of this disclosure is shown.

[0017] Figure 4D An example backend connectivity process is illustrated according to various aspects and embodiments of this disclosure.

[0018] Figure 5A , Figure 5B and Figure 5C Various views of another example multimode fiber optic probe device according to various aspects and embodiments of this disclosure are shown.

[0019] Figure 6A and Figure 6B An additional example probe component arrangement of another example multimode fiber optic probe device according to various aspects and embodiments of this disclosure is shown.

[0020] Figure 7A Another example preform manufacturing process is shown according to various aspects and embodiments of this disclosure.

[0021] Figure 7BAnother example of a hot stretching process is shown according to various aspects and embodiments of this disclosure.

[0022] Figure 7C Another example of a thermal taper process is shown according to various aspects and embodiments of this disclosure.

[0023] Figure 7D Another example back-end connectivity process is shown according to various aspects and embodiments of this disclosure.

[0024] Figure 8A and Figure 8B A view of another example multimode fiber optic probe device according to various aspects and embodiments of this disclosure is shown.

[0025] Figure 9A and Figure 9B A view of another example multimode fiber optic probe device according to various aspects and embodiments of this disclosure is shown.

[0026] Figure 10 A multimode fiber optic probe device manufactured according to various aspects and embodiments of this disclosure is shown.

[0027] Figure 11A and Figure 11B Various aspects and embodiments according to this disclosure are illustrated. Figure 10 Example implementation of an example multimode fiber optic probe device.

[0028] Figure 12A and Figure 12B Various aspects and embodiments according to this disclosure are illustrated. Figure 10 Additional example implementations of the example multimode fiber optic probe device.

[0029] Figure 13 A multimode fiber optic probe device manufactured according to various aspects and embodiments of the present disclosure is shown, along with an example implementation thereof. Detailed Implementation

[0030] Understanding the neural basis of behavior requires monitoring and manipulating the combination and interactions of physiological elements in behavioral animals. As mentioned above, the widespread adoption of silicon-based neural probe devices capable of monitoring electrical activity and applying light has led to significant progress in the monitoring and manipulation of neural activity. However, a problem with these existing probe devices is that other biological factors, such as neurochemistry, are intertwined with electrical activity and need to be studied simultaneously, which is impractical for such probe devices.

[0031] Another problem with existing silicon-based neural probe devices is the time-consuming and expensive fabrication process. Therefore, thermo-fiber stretching is often used to produce scalable fiber devices. This involves manufacturing such devices using methods commonly used in industry to produce optical fibers. Specifically, macroscopically sized multi-material preforms are heated to soften and stretched into fibers hundreds of meters long, as thin as a human hair. This rapid and simple manufacturing process utilizes economical machinery and soft materials, resulting in an inexpensive, robust, and biocompatible device. Therefore, thermo-stretching is a promising process. However, a problem with fiber devices produced by this thermo-stretching process is that the back-end connections of micron-sized fibers pose a major challenge limiting the practicality of optical fibers in neural applications.

[0032] This disclosure provides solutions to the aforementioned problems commonly associated with monitoring and manipulating neural activity, as well as problems associated with existing neural probes. To overcome these limitations, examples of this disclosure include multimodal neural fiber probe devices capable of interacting with the mammalian brain across multiple modalities. The multimodal neural fiber probe device can be embodied as a polymer-based fiber probe device, referred herein as a cone-dose administration, photostimulation, and electrophysiology (T-DOpE) probe device. Additionally, some examples include a thermal tapering process that can be implemented to fabricate the multimodal neural fiber probe device. Furthermore, examples include a rear-end connector region of the multimodal neural fiber probe device that can be approximately 10 to 30 times (e.g., 20 times) the connector region of an existing fiber neural probe.

[0033] T-DOpE probe devices and thermal tapering processes offer several technical benefits and advantages. For example, an exemplary T-DOpE probe device can be embodied as a single-neuron-level device that enables high-fidelity electrophysiological recording, local drug delivery, and photostimulation. T-DOpE probe devices allow for the study of highly complex neural circuits, such as the hippocampus of behavioral mice. T-DOpE probe devices can include a tapered geometry and relatively small and / or angled tips (e.g., as small as 50 micrometers (μm)), which can allow for minimal tissue damage. Additionally, T-DOpE probe devices can include a relatively large back-end connector region (e.g., approximately 20 times larger than existing fiber-optic-based neural probes), which allows for scalable assembly of the T-DOpE probe device and its direct integration with industrial-grade connectors. Furthermore, a thermal tapering process can be implemented to fabricate the T-DOpE probe device and / or back-end connection in a relatively fast and inexpensive manner.

[0034] Furthermore, the back-end connection process and the back-end connector region of the T-DOpE probe device described herein allow for the fabrication of microprobes with greater complexity, while increasing the scalability of the back-end connections. For example, the back-end connection process and the back-end connector region of the T-DOpE probe device can allow for semi-automated connection processes, thereby reducing connection time, labor, and cost. Moreover, existing fiber-optic-based neural probe devices and connection processes only allow connection to the outer layers of the device. In many conventional devices and processes, it remains difficult or impossible to connect channels near the center of the device without damaging the external channels. This limits the complexity of such existing devices. In contrast, the back-end connection process and the back-end connector region of the T-DOpE probe device described herein allow for easy connection of electrical, optical, and chemical modes throughout the device, thereby enabling the scalable fabrication and distribution of the T-DOpE probe device of this disclosure.

[0035] Electrophysiology is a well-established and well-known method for monitoring neural activity at high temporal frequencies. However, its spatial resolution is relatively poor. Due to the largely extracellular nature of electrical recordings, it is difficult to distinguish signals from different neurons, and the process typically requires considerable post-recording signal processing. In contrast, fiber photometry involves collecting and analyzing light signals emitted from neurons affected by genetically encoded calcium indicators (GECIs). GECIs can be engineered to respond to or emit light of different wavelengths and bind neurotransmitters with high specificity. This, combined with transgenic or viral infection, allows GECIs to affect specific brain regions and cell types, resulting in fiber photometry with high spatial resolution. However, fiber photometry suffers from poor temporal resolution due to the inherent randomness of photon emission and detection.

[0036] This disclosure also provides solutions to address the aforementioned problems associated with electrophysiology and fiber photometry in existing devices and methods. To overcome such limitations, some examples of this disclosure describe multimodal neural fiber probe devices capable of simultaneously performing electrophysiological and fiber photometry operations, and some examples describe thermally charged cone-shaped interruption methods for fabricating such devices. The multimodal neural fiber probe device can be embodied herein as a fiber probe device referred to herein as a fiber photometry, drug delivery, photostimulation, and electrophysiology (P-DOpE) probe device.

[0037] The simultaneous electrophysiological and photometric applications facilitated by P-DOpE probe devices enable cross-referencing of electrical and optical signals, resulting in high spatial and temporal resolution that researchers leverage to investigate previously intractable problems. The P-DOpE probe devices described herein feature both high spatial and temporal resolution and are capable of simultaneously (e.g., synchronously) detecting electrical and chemical signals. P-DOpE probe devices are relatively inexpensive probes capable of both electrophysiological and fiber photometric measurements, and the thermally charged cone-shaped interruption method allows for rapid and easy back-end connection without the bulky back-ends of other cone-shaped methods. Furthermore, similar to the thermally charged cone method used to fabricate the T-DOpE probe devices described herein, the thermally charged cone-shaped interruption method is also a modular manufacturing process, thus allowing for the customization of rapid and cost-effective devices to meet a variety of unique requirements.

[0038] Hippocampal circuit activity is crucial for episodic and spatial memory. Hippocampal theta (~6–10 Hz), gamma (~35–80 Hz), and sharp wave-ripple (SPW-R, ~100–250 Hz) oscillations all contribute to the circuit's mnemonic function. In rodents, these oscillations are disrupted after systemic pharmacological activation of cannabinoid receptors by compounds such as Δ-9-tetrahydrocannabinol (Δ9-THC) or cannabinoid receptor agonists (CB1R). This is believed to be the mechanism underlying cannabinoid-related memory impairment in rodents and humans. CB1R activation is thought to impair memory by altering the activity of CB1R-expressing hippocampal neurons and their synaptic partners in local hippocampal circuits.

[0039] Synthetic cannabinoid CP-55,940 is a useful tool for studying the role of CB1R activation in rodent models. Previously, systemic administration of CP-55,940 has been shown to most significantly reduce theta oscillations and SPW-R in rats. Importantly, systemic administration of the cannabinoid does not exclude the interaction of CA1 with other brain regions. The same study also found that intrahippocampal delivery of CP-55,940 eliminated SPW-R in urethane-anesthetized rats, suggesting that the effect of systemic administration may be mediated by changes in intrahippocampal CB1R signaling. The effects of focal CA1 CB1R agonism have never been studied in behavioral animals, and because the only intrahippocampal administration was performed under anesthesia, the neuronal substrates and mechanisms by which CB1R controls hippocampal rhythms remain unknown. By using the T-DOpE probe device described herein, the role of CA1 CB1R in hippocampal field potential activity can be studied through simultaneous optogenetic manipulation of CA1 neuronal excitability and pharmacological intervention in CB1R agonism.

[0040] Acute and chronic implantation of the T-DOpE probe device in mouse hippocampal CA1 revealed typical neuronal activity at the local field potential and spiking levels. Utilizing the triple functionality of the T-DOpE probe device, local field potentials were monitored by simultaneously manipulating the endogenous type 1 cannabinoid receptor (CB1R; delivered via microfluidic agonist) and the CA1 pyramidal cell membrane potential (opogenetic activation). Electropharmacological experiments revealed that focal infusion of the CB1R agonist CP-55,940 in dorsal CA1 downregulated theta and sharp wave ripple oscillations. Furthermore, using the complete electropharmacological optical signature set of the T-DOpE probe device, it was determined that CB1R activation reduces sharp wave ripples (SPW-R) by weakening the inherent SPW-R generation capacity of the CA1 circuit. These are just some examples of the applications of the T-DOpE probe device described herein.

[0041] Regarding the context, Figure 1 A perspective view of an example multimodal fiber optic probe device 100 (or "probe device 100") according to various aspects and embodiments of the present disclosure is shown. Probe device 100 can be designed, embodied, and implemented as a flexible multimodal nerve fiber probe device according to the examples described herein. For example, probe device 100 can be designed, embodied, and implemented as a cone-shaped drug delivery, photostimulation, and electrophysiology (T-DOpE) probe device as described herein. Compared to existing fiber-based probe devices, probe device 100 offers relatively higher complexity at the tip region while simplifying the connection between the rear connector region and external electronics that can be coupled to probe device 100.

[0042] Figure 1 The illustrated probe device 100 includes a tapered fiber optic probe structure 110. The tapered fiber optic probe structure 110 can be embodied and implemented as a flexible tapered fiber optic probe structure as described in the examples herein. The tapered fiber optic probe structure 110 may include one or more optical waveguides 120 (or "multiple optical waveguides 120"), one or more microfluidic channels 130 (or "multiple microfluidic channels 130"), one or more electrodes 140 (or "multiple electrodes 140"), or any combination thereof. For clarity, in Figure 1Only a single optical waveguide 120, microfluidic channel 130, and electrode 140 are indicated. The optical waveguide 120, microfluidic channel 130, and electrode 140 can be formed in a tapered fiber probe structure 110 such that they are juxtaposed around the longitudinal axis of the tapered fiber probe structure 110 and extend along the longitudinal axis of the tapered fiber probe structure 110 from a first end (e.g., a first distal end) to a second end (e.g., a second distal end). For example, the optical waveguide 120, microfluidic channel 130, and electrode 140 can be formed in the tapered fiber probe structure 110 such that they are positioned at the same or different radial distances from the longitudinal axis (e.g., the center) of the tapered fiber probe structure 110.

[0043] The first end of the tapered fiber probe structure 110 can be embodied as a microscale region with a diameter ranging from, for example, about 50 micrometers (μm) to about 300 μm. In one embodiment, the first end of the tapered fiber probe structure 110 can have a diameter of about 150 μm. The first end of the tapered fiber probe structure 110 can include or be embodied as a microscale tip region, wherein at least one of the optical waveguide 120, microfluidic channel 130, or electrode 140 has one or more exposed portions or surfaces with microscale dimensions. The second end of the tapered fiber probe structure 110 can be embodied as a macroscale region with a diameter ranging from, for example, about 1.5 millimeters (mm) to about 2.50 mm or in some cases larger. In one embodiment, the second end of the tapered fiber probe structure 110 can have a diameter of about 2 mm. The second end of the tapered fiber probe structure 110 may include or be embodied as a macroscale connector region, wherein at least one of the optical waveguide 120, microfluidic channel 130 or electrode 140 has one or more exposed portions or surfaces whose macroscale size or cross-sectional area is approximately 10 to 30 times (e.g., 20 times) the corresponding size or cross-sectional area of ​​the component at the first end of the tapered fiber probe structure 110.

[0044] In the example shown, the tapered fiber optic probe structure 110 is embodied as having a cylindrical shape and a circular cross-section. In various embodiments, the cross-section of the first end of the tapered fiber optic probe structure 110 and the corresponding cross-section of the second end of the tapered fiber optic probe structure 110 are both embodied as circular cross-sections. For example, the cross-section perpendicular to the longitudinal axis of the tapered fiber optic probe structure 110, taken at or near the first end of the tapered fiber optic probe structure 110, and the corresponding cross-section also perpendicular to the longitudinal axis of the tapered fiber optic probe structure 110, taken at or near the second end of the tapered fiber optic probe structure 110, are both circular cross-sections in the example shown.

[0045] although Figure 1The tapered fiber probe structure 110 shown is embodied in having a cylindrical shape and a circular cross-section, but the scope of this disclosure is not limited thereto. In other examples, the tapered fiber probe structure 110 may be embodied such that it has a rectangular cross-section, an annular cross-section, a triangular cross-section, a square cross-section, or a cross-section with other geometries. In some embodiments, the cross-section of the first end of the tapered fiber probe structure 110 and the corresponding cross-section of the second end of the tapered fiber probe structure 110 are both embodied in a rectangular cross-section, an annular cross-section, a triangular cross-section, a square cross-section, or a cross-section with other geometries.

[0046] The tapered fiber optic probe structure 110 can be formed using one or more preform materials for fabricating fiber optic probe structures, and therefore may include one or more preform materials for fabricating fiber optic probe structures, such as at least one of polymer materials or polycarbonate (PC) materials. In some examples, the tapered fiber optic probe structure 110 can be formed using a polymer or polycarbonate rod having grooves or channels into which optical waveguides and electrodes can be inserted, and wherein microfluidic channels can be formed as described in the examples herein. In some cases, one or more polymer or polycarbonate films can be wrapped around such polymer or polycarbonate rods and around optical waveguides, microfluidic channels, and electrodes positioned within the rods to form a preform of the tapered fiber optic probe structure 110. This preform can then be fabricated into micropreforms that can be used to produce the tapered fiber optic probe structure 110, as further described in the examples herein.

[0047] Optical waveguides 120 can be configured independently or collectively and are operable to control optogenetics. In some examples, any or all of the optical waveguides 120 may be embodied in or comprise a polymer material. In other examples, any or all of the optical waveguides 120 may be embodied in or comprise a polycarbonate material. In some cases, any or all of the optical waveguides 120 may comprise a polycarbonate (PC) core and a poly(2-methyl methacrylate) cladding. In one example, any or all of the optical waveguides 120 may comprise a PC core with a refractive index of n=1.586 and a poly(2-methyl methacrylate) cladding with a refractive index of n=1.49. Any or all of the optical waveguides 120 may have a diameter ranging, for example, from about 5 μm to about 300 μm, but in some cases may depend on an additional diameter outside this range. In the example shown, each of the optical waveguides 120 of the probe device 100 may have a diameter of about 10 μm.

[0048] Microfluidic channels 130 can be configured independently or collectively and are operable to allow local drug infusion. In some cases, any or all of the microfluidic channels 130 can be formed, or be formed by, one of the aforementioned grooves or channels in a polymer or polycarbonate rod. The polymer or polycarbonate rod can then be used to fabricate a preform of the tapered fiber probe structure 110, a micropreform of the tapered fiber probe structure 110, and ultimately the tapered fiber probe structure 110. In other examples, any or all of the microfluidic channels 130 can be formed, or be formed by, a tube inserted into one of the aforementioned grooves or channels in such a polymer or polycarbonate rod. The polymer or polycarbonate rod can then be used to fabricate a preform, a micropreform, and ultimately the tapered fiber probe structure 110 as described herein. For example, any or all of the microfluidic channels 130 can be formed, or be formed by, a polycarbonate tube. Any or all of the microfluidic channels 130 may have a diameter ranging from, for example, about 5 μm to about 100 μm, but in some cases may depend on another diameter outside this range. In the example shown, each of the microfluidic channels 130 of the probe device 100 may have a diameter of about 25 μm.

[0049] Electrodes 140 may be configured independently or collectively and are operable to record extracellular voltage. In some cases, any or all of electrodes 140 may be formed using a bismuth-tin (BiSn) alloy, a nickel-chromium (NiCr) alloy, a stainless steel alloy, gold or a gold alloy, platinum or a platinum alloy, tungsten or a tungsten alloy, another material or alloy, or any combination thereof. In some examples, each of electrodes 140 is formed using the same one or more materials. In other examples, at least one of electrodes 140 may be formed using a material different from any material used to form at least one of the other electrodes 140. Any or all of electrodes 140 may have a diameter ranging, for example, from about 5 μm to about 100 μm, but in some cases may depend on another diameter outside this range. In the example shown, each of the electrodes 140 of the probe device 100 may have a diameter of about 25 μm.

[0050] The probe device 100 also includes a tip region 150 positioned at a first end (e.g., a first distal end) of the tapered fiber probe structure 110. The tip region 150 may include or be embodied as a microscale tip region, wherein at least one of the optical waveguide 120, microfluidic channel 130, or electrode 140 has one or more exposed portions or surfaces with microscale dimensions. The tip region 150 may include a tip that can be formed in various geometries (e.g., shape or surface shape), configurations (e.g., arrangement of probe components exposed on the tip surface), orientations (e.g., cut angles), and microscale dimensions (e.g., microscale cross-section of the probe component exposed on the tip surface), as described in the examples herein. As referenced herein, a “probe component” may include at least one of, for example, an optical waveguide, a microfluidic channel, an electrode, a tetraode, or another neural probe component. In the example shown, the tip of the tip region 150 is embodied as an angled tip 155. Either or both of the tip region 150 and the angled tip 155 may be defined and formed by a crosscut of at least one of the tapered fiber probe structure 110, the optical waveguide 120, the microfluidic channel 130, or the electrode 140. For example, the crosscut may be an angled crosscut that is formed at a set angle (θ) relative to the cross-section of the tip region 150 or the longitudinal axis of the tapered fiber probe structure 110. In the example shown, the angled tip 155 may be formed at such a set angle (θ) relative to the cross-section of the tip region 150 or the longitudinal axis of the tapered fiber probe structure 110.

[0051] In some examples, the tip of the tip region 150 may be a flat tip rather than an angled tip. In these examples, either or both of the tip region 150 and its tip may be defined and formed by a straight cross-section of at least one of the tapered fiber probe structure 110, optical waveguide 120, microfluidic channel 130, or electrode 140. For example, the tip region 150 may be cross-sectioned at an angle perpendicular to the longitudinal axis of the tapered fiber probe structure 110. In some cases, the tip of the tip region 150 may be a multi-angled tip with multiple outer (e.g., exposed) surfaces that are cross-sectioned at different cutting angles relative to the cross-section of the tip region 150 or the longitudinal axis of the tapered fiber probe structure 110. In these examples, one or more exposed surfaces of any one or all of the tapered fiber probe structure 110, optical waveguide 120, microfluidic channel 130, or electrode 140 may be formed at at least one of these different cutting angles at the tip of the tip region 150.

[0052] The tip region 150, the angled tip 155, or both can be formed in various predetermined dimensions, such as, for example, a predetermined diameter. In one example, the tip region 150, the angled tip 155, or both can be formed in a diameter of approximately 50 μm. In another example, the tip region 150, the angled tip 155, or both can be formed in a diameter ranging from 50 μm to 150 μm. In yet another example, the tip region 150, the angled tip 155, or both can be formed in a diameter of approximately 150 μm. In some cases, the tip region 150, the angled tip 155, or both can be formed in a diameter less than 50 μm or greater than 150 μm. Other dimensions may be used.

[0053] The probe assembly 100 also includes a back-end connector region 160 located at or near a second end (e.g., a second distal end) of the tapered fiber probe structure 110. The back-end connector region 160 may include or be embodied as a macroscale connector region, wherein at least one of the optical waveguide 120, microfluidic channel 130, or electrode 140 has one or more exposed portions or surfaces whose macroscale dimensions or cross-sectional areas are approximately 10 to 30 times (e.g., 20 times) larger than the corresponding dimensions or cross-sectional areas of the components at the tip region 150. The back-end connector region 160 may be configured and operable to connect one or more probe components of the tapered fiber probe structure 110 to one or more devices external to and separate from the probe assembly 100. In the example shown, the back-end connector region 160 may be configured and operable to provide connection of one or more of the optical waveguide 120, microfluidic channel 130, and electrode 140 to one or more devices external to and separate from the probe assembly 100.

[0054] The back-end connector region 160 may include one or more optical fibers 125 (or "multiple optical fibers 125"). In the illustrated example, the back-end connector region 160 includes multiple optical fibers 125 respectively (e.g., optically, communicatively, operably) coupled to the optical waveguide 120 at or near the second end of the tapered optical fiber probe structure 110. In various examples, each optical fiber 125 may be coupled to a rear-end portion (e.g., an exposed rear-end portion) of the optical waveguide 120 at or near the second end of the tapered optical fiber probe structure 110, such that the tip portion of the optical waveguide 120 at the first end of the tapered optical fiber probe structure 110 can be coupled to an external device (e.g., optically, communicatively, operably). For example, each optical fiber 125 may be coupled to a rear-end portion of the optical waveguide 120 at or near the second end of the tapered optical fiber probe structure 110, such that the exposed cross-sectional surface of the optical waveguide 120 at the angled tip 155 can be coupled to an external device (e.g., optically, communicatively, operably). In the example shown, each fiber 125 is directly coupled to one of the multiple optical waveguides 120 at or near the second end of the tapered fiber probe structure 110.

[0055] In some examples, any or all of the optical fibers 125 may be embodied in or comprise a polymer material. In other examples, any or all of the optical fibers 125 may be embodied in or comprise a polycarbonate material. In some cases, any or all of the optical fibers 125 may be embodied in an optical fiber or a cable. In one example, any or all of the optical fibers 125 may be embodied in a polymer optical waveguide (e.g., a PC core with a poly(2-methyl methacrylate) cladding). In another example, any or all of the optical fibers 125 may be embodied in a polymer optical waveguide with a diameter of 200 μm (e.g., a PC core with a poly(2-methyl methacrylate) cladding). In other examples, the rear connector region 160 may also include one or more optical fiber connectors. In one example, any or all of the optical fiber connectors may be embodied in a stainless steel fiber ferrule. For example, any or all of the optical fiber connectors may be embodied in a stainless steel fiber ferrule with an outer diameter of 1.25 mm. In one example, each of the optical fiber connectors may be coupled to one of the optical fibers 125.

[0056] The rear connector region 160 may also include one or more microfluidic tubes 135 (or "multiple microfluidic tubes 135"). In the illustrated example, the rear connector region 160 includes multiple microfluidic tubes 135 that are respectively coupled to the microfluidic channel 130 at or near the second end of the tapered fiber probe structure 110 (e.g., fluidly and operatively). In various examples, each microfluidic tube 135 may be coupled to the rear portion of the microfluidic channel 130 at or near the second end of the tapered fiber probe structure 110, such that the tip portion of the microfluidic channel 130 at the first end of the tapered fiber probe structure 110 can be coupled to an external device (e.g., fluidly and operatively). For example, each microfluidic tube 135 may be coupled to the rear portion of the microfluidic channel 130 at or near the second end of the tapered fiber probe structure 110, such that the open cross-section of the microfluidic channel 130 at the angled tip 155 can be coupled to an external device (e.g., fluidly and operatively).

[0057] In the illustrated example, each microfluidic tube 135 is at least partially inserted into the microfluidic channel 130 at the second end of the tapered fiber probe structure 110. In one example, any or all of the microfluidic tubes 135 may be embodied as polycarbonate (PC) tubes. For example, any or all of the microfluidic tubes 135 may be embodied as PC tubes having an outer diameter (OD) of 150 μm and an inner diameter (ID) of 75 μm, although other OD and / or ID dimensions may be required in some cases. In other examples, the rear connector region 160 may also include one or more fluid connectors. In one example, each fluid connector may be coupled to one of the multiple microfluidic tubes 135.

[0058] The rear connector region 160 may also include one or more connector electrodes 145 (or "multiple connector electrodes 145"). In the illustrated example, the rear connector region 160 includes multiple connector electrodes 145, which are respectively coupled to electrode 140 at or near the second end of the tapered fiber probe structure 110 (e.g., electrical ground, communication ground, operatively ground). Each connector electrode 145 may be coupled to a rear portion (e.g., an exposed rear portion) of electrode 140 at or near the second end of the tapered fiber probe structure 110, such that the tip portion of electrode 140 at the first end of the tapered fiber probe structure 110 can be coupled to an external device (e.g., electrical ground, communication ground, operatively ground). For example, each connector electrode 145 may be coupled to a rear portion of electrode 140 at or near the second end of the tapered fiber probe structure 110, such that the exposed cross-sectional surface of electrode 140 at the angled tip 155 can be coupled to an external device (e.g., electrical ground, communication ground, operatively ground). In the example shown, each connector electrode 145 is directly coupled to one of the plurality of electrodes 140 at or near the second end of the tapered fiber probe structure 110.

[0059] Any or all of the connector electrodes 145 may be embodied as wires, such as, for example, copper wire. In one example, any or all of the connector electrodes 145 may be embodied as insulated copper wire. In one example, any or all of the connector electrodes 145 may be embodied as 42 American Wire Gauge (AWG) copper wire, and may depend on other specifications. In other examples, the rear connector region 160 may also include one or more pin connectors, a printed circuit board (PCB), or any combination thereof. In one example, one end of each connector electrode 145 may be coupled to the rear portion of electrode 140 at or near the second end of the tapered fiber optic probe structure 110, and the other end of connector electrode 145 may be coupled to a pin connector. In another example, one end of each connector electrode 145 may be coupled to the rear portion of electrode 140 at or near the second end of the tapered fiber optic probe structure 110, and the other end of connector electrode 145 may be coupled to a PCB.

[0060] In some cases, the probe device 100 may also include a sealant to seal the microfluidic tube 135 to the microfluidic channel 130. For example, the probe device 100 may include ultraviolet (UV) epoxy resin, which may be coupled to the second end of the tapered fiber probe structure 110 and also to the microfluidic tube 135 and / or the aforementioned fluid connector. The UV epoxy resin may also be coupled to any or all of the optical waveguide 120, the aforementioned fiber connector, the fiber optic cable 125, the electrode 140, the connector electrode 145, the aforementioned pin connector, or the PCB, or any combination thereof, to provide support for these components.

[0061] The probe device 100 can be manufactured in various sizes, geometries, configurations, or any combination thereof. In some cases, the probe device 100 can be manufactured such that the optical waveguide 120, the microfluidic channel 130, and / or the electrode 140 are juxtaposed within the tapered fiber probe structure 110 according to different arrangements. For example, the probe device 100 can be manufactured such that the optical waveguide 120, the microfluidic channel 130, and / or the electrode 140 are arranged according to the description herein and respectively within... Figure 2A , Figure 2B and Figure 2C The probe component arrangement shown is any one of 200a, 200b or 200c or according to another probe component arrangement and is juxtaposed within the tapered fiber probe structure 110.

[0062] Figure 2A , Figure 2B and Figure 2C An example probe component arrangement of a multimode fiber optic probe device according to various aspects and embodiments of the present disclosure is shown. Figure 2A , Figure 2B and Figure 2C This discloses a multimode fiber optic probe device (such as, for example, referenced herein). Figure 1 Different example probe component arrangements formed in the described probe device 100. Figure 2A A cross-sectional view of an example tapered fiber optic probe structure 110 with probe component arrangement 200a is shown. More specifically, Figure 2A A cross-sectional view is shown at the tip region 150 and / or the angled tip 155 of an example tapered fiber optic probe structure 110 having a probe component arrangement 200a.

[0063] In the example shown, the tapered fiber probe structure 110 includes, according to Figure 2A The probe assembly shown 200a comprises an optical waveguide 120, a microfluidic channel 130, and eight electrodes 140 disposed within a tapered fiber optic probe structure 110. For clarity, in... Figure 2A Only a single electrode 140 is indicated. The optical waveguide 120 and the microfluidic channel 130 are coaxially located at... Figure 2A The probe component arrangement shown is in a tapered fiber probe structure 110 in a 200a. An optical waveguide 120 extends along the longitudinal axis of the tapered fiber probe structure 110 from one end to the second end, surrounding a microfluidic channel 130. In this example, the longitudinal axis of the tapered fiber probe structure 110 is located at the center of the microfluidic channel 130, and it extends in and out in a direction parallel to the axis "Z". Figure 2A The page.

[0064] exist Figure 2AIn the probe component arrangement 200a shown, the tapered fiber probe structure 110 includes an annular region 210 with an annular cross-section. In this example, the annular region 210 surrounds the optical waveguide 120 and extends from a first end to a second end of the tapered fiber probe structure 110. The annular region 210 surrounds the optical waveguide 120 and extends in and out of the tapered fiber probe structure 110 from the first end to the second end in a direction parallel to the "Z" axis. Figure 2A The page. Figure 2A In the probe component arrangement 200a shown, each electrode 140 is positioned in an annular region 210 and extends from a first end of the tapered fiber probe structure 110 through the annular region 210 to a second end. For example, each electrode 140 is positioned in the annular region 210 and extends in and out of the tapered fiber probe structure 110 from the first end to the second end in a direction parallel to the "Z" axis. Figure 2A The page.

[0065] Any fiber optic probe structure described herein may include one or more divider regions positioned between various probe components (e.g., optical waveguides, electrodes, microfluidic channels) integrated within and extending through the fiber optic probe structure. The divider regions may extend along the entire length of the fiber optic probe structure and may isolate (e.g., physically) and insulate (e.g., electrically, optically, electromagnetically, chemically) the probe components from each other. For example, the tapered fiber optic probe structure 110 may also include one or more divider regions positioned between at least two of the optical waveguide 120, microfluidic channel 130, or electrode 140. For brevity, only a single divider region of the tapered fiber optic probe structure 110 is described herein, and for clarity... Figure 2A The Chinese side indicated that...

[0066] In the example described, the tapered fiber probe structure 110 includes a partition region 215 positioned within an annular region 210 between the optical waveguide 120 and each electrode 140. The partition region 215 surrounds the optical waveguide 120 and extends from a first end to a second end of the tapered fiber probe structure 110. The partition region 215 surrounds the optical waveguide 120 and extends in and out of the tapered fiber probe structure 110 from the first end to the second end in a direction parallel to the Z-axis. Figure 2AThe page. Separating region 215 insulates and isolates the optical waveguide 120 from the electrode 140, and vice versa. Separating region 215 includes material from one or more portions of at least one of the following: tapered fiber probe structure 110 (e.g., a polymer or polycarbonate used to form the tapered fiber probe structure 110), optical waveguide 120 (e.g., a poly(2-methyl methacrylate) cladding of the optical waveguide 120), or electrode 140 (e.g., an insulating coating, wrapping, sheath, or sleeve of any or all of the electrodes 140). The tapered fiber probe structure 110 in this example also includes an additional separating region positioned in an annular region 210 between the paired electrodes 140. These additional separating regions isolate (e.g., physically) and insulate (e.g., electrically, electromagnetically) the electrodes 140 from each other, and they comprise one or more portions of material from at least one of the tapered fiber probe structure 110 (e.g., the polymer or polycarbonate used to form the tapered fiber probe structure 110) or the electrodes 140 (e.g., the insulating coating, wrapping, sheath, or sleeve of any or all of the electrodes 140).

[0067] Figure 2B Another example probe component arrangement 200b is shown according to various aspects and embodiments of this disclosure. For example, Figure 2B A cross-sectional view of another example tapered fiber probe structure 110 with probe component arrangement 200b is shown. More specifically, Figure 2B A cross-sectional view is shown at the tip region 150 and / or the angled tip 155 of another example tapered fiber probe structure 110 with probe component arrangement 200b.

[0068] according to Figure 2B The probe component arrangement 200b shown includes a tapered fiber probe structure 110 comprising four optical waveguides 120, eight microfluidic channels 130, and eight electrodes 140 arranged juxtaposed within the tapered fiber probe structure 110. For clarity, in... Figure 2B Only a single optical waveguide 120, a single microfluidic channel 130, and a single electrode 140 are indicated. The optical waveguide 120 and electrode 140 are positioned within... Figure 2B The probe component arrangement 200b is located in and around the peripheral region of the tapered fiber probe structure 110, and the microfluidic channel 130 is positioned in the central region of the tapered fiber probe structure 110. In this example, each of the optical waveguide 120, the microfluidic channel 130, and the electrode 140 extends from a first end to a second end of the tapered fiber probe structure 110 along its longitudinal axis. In this example, the longitudinal axis of the tapered fiber probe structure 110 is located at the center of the tapered fiber probe structure 110 and extends in and out in a direction parallel to the axis "Z". Figure 2B The page.

[0069] The tapered fiber probe structure 110 may further include one or more partition regions positioned between at least two of any one of the optical waveguide 120, microfluidic channel 130, or electrode 140. In the example shown, the tapered fiber probe structure 110 includes a partition region 215 positioned between any pair of optical waveguides 120, microfluidic channels 130, and electrodes 140. For clarity, in Figure 2B Only a single dividing region 215 is indicated. In this example, dividing regions 215 are located between these probe components and extend from the first end to the second end of the tapered fiber probe structure 110. For example, dividing regions 215 extend in and out of the tapered fiber probe structure 110 from the first end to the second end in a direction parallel to the "Z" axis. Figure 2B The page. Separating region 215 isolates (e.g., physically) and insulates (e.g., electrically, optically, electromagnetically, chemically) the optical waveguide 120, the microfluidic channel 130, and the electrode 140 from each other. Separating region 215 includes material from one or more portions of at least one of the following: tapered fiber probe structure 110 (e.g., a polymer or polycarbonate for forming tapered fiber probe structure 110), optical waveguide 120 (e.g., a poly(2-methyl methacrylate) cladding of optical waveguide 120), microfluidic channel 130 (e.g., a polymer or polycarbonate tube for at least partially forming microfluidic channel 130), or electrode 140 (e.g., an insulating coating, wrapping, sheath, or sleeve of any one or all of electrode 140).

[0070] Figure 2C Another example probe component arrangement 200c is shown according to various aspects and embodiments of this disclosure. For example, Figure 2C A cross-sectional view of another example tapered fiber probe structure 110 with probe component arrangement 200c is shown. More specifically, Figure 2C A cross-sectional view is shown at the tip region 150 and / or the angled tip 155 of another example tapered fiber probe structure 110 with probe component arrangement 200c.

[0071] In the example shown, the tapered fiber probe structure 110 includes, according to Figure 2C The probe assembly shown is arranged 200c and contains eight optical waveguides 120 and twelve microfluidic channels 130 within a tapered fiber probe structure 110. In this example, electrodes 140 are omitted from the tapered fiber probe structure 110. For clarity, in... Figure 2C Only a single optical waveguide 120 and a single microfluidic channel 130 are indicated. The optical waveguide 120 is positioned within... Figure 2CThe probe component arrangement 200c is positioned around and around the peripheral region of the tapered fiber probe structure 110, and the microfluidic channel 130 is positioned in the central region of the tapered fiber probe structure 110. Each of the optical waveguide 120 and the microfluidic channel 130 extends from a first end to a second end of the tapered fiber probe structure 110 along its longitudinal axis. In this example, the longitudinal axis of the tapered fiber probe structure 110 is located at the center of the tapered fiber probe structure 110 and extends in and out in a direction parallel to the axis "Z". Figure 2C The page.

[0072] The tapered fiber probe structure 110 may further include one or more partition regions positioned between at least two of any one of the optical waveguides 120 and the microfluidic channels 130. The tapered fiber probe structure 110 includes a partition region 215 positioned between the paired optical waveguides 120 and the microfluidic channels 130. For clarity, in Figure 2C Only a single dividing region 215 is indicated. In this example, dividing regions 215 are located between these probe components and extend from the first end to the second end of the tapered fiber probe structure 110. For example, dividing regions 215 extend in and out of the tapered fiber probe structure 110 from the first end to the second end in a direction parallel to the "Z" axis. Figure 2C The page. Separating region 215 isolates (e.g., physically) and insulates (e.g., optically, electromagnetically, chemically) the optical waveguide 120 from the microfluidic channel 130, and vice versa. Separating region 215 includes material from one or more portions of at least one of the following: tapered fiber probe structure 110 (e.g., a polymer or polycarbonate used to form the tapered fiber probe structure 110), optical waveguide 120 (e.g., a poly(2-methyl methacrylate) cladding of the optical waveguide 120), or microfluidic channel 130 (e.g., a polymer or polycarbonate tube used to form the microfluidic channel 130).

[0073] Figure 3A , Figure 3B and Figure 3C Example optical waveguide addressable modes of a multimode fiber optic probe device according to various aspects and embodiments of this disclosure are shown. For example, Figure 3A , Figure 3B and Figure 3C Multimode fiber optic detection devices that can be used with this disclosure (such as, for example, those referenced herein) are shown. Figure 1 The example optical waveguide addressable mode implemented by the described detection device 100.

[0074] Figure 3A , Figure 3B and Figure 3CExample optical waveguide addressable modes 300a, 300b, and 300c according to various aspects and embodiments of this disclosure are shown respectively. For example, Figure 3A , Figure 3B and Figure 3C The following are respectively shown according to the description in this article and Figure 2C The cross-sectional view of the tip region 150 and / or the angled tip 155 of the example tapered fiber optic probe structure 110 formed by the probe component arrangement 200c shown. For example, Figure 3A , Figure 3B and Figure 3C Cross-sectional views of optical waveguide addressable modes 300a, 300b, and 300c are shown, which can be implemented at the tip region 150 and / or the angled tip 155 of the example tapered fiber probe structure 110 formed according to the probe component arrangement 200c. Figure 3A , Figure 3B and Figure 3C In the example shown, in optical waveguide addressable mode 300a, the shaded optical waveguide 120 is used to transmit light of approximately 660 nanometers (nm), and the solid-filled optical waveguide 120 is used to transmit light of approximately 520 nm. For clarity, Figure 3A , Figure 3B and Figure 3C This document only illustrates a single optical waveguide 120 for transmitting light at approximately 520 nm and a single optical waveguide 120 for transmitting light at approximately 660 nm. In various embodiments, each of the optical waveguides 120 and others described herein can transmit light across the entire visible wavelength range. Figure 3A , Figure 3B and Figure 3C As shown in the example optical waveguide addressable modes 300a, 300b, and 300c, any one or all of the optical waveguides 120 of the probe device 100 can be configured and operable such that they are individually and collectively addressable (e.g., operated, controlled).

[0075] The tapered fiber optic probe structure 110 of the probe device 100 can be configured according to any one or the other probe component arrangement of probe component arrangement 200a, 200b or 200c by implementing the description herein and respectively in Figure 4A , 4B The probe device 100 can be manufactured using the preform manufacturing processes 400a, TDP (Thermal Stretching Process), and TTP (Thermal Tapering Process) 400c shown in 4C. The entire probe device 100 can be manufactured by implementing the processes described herein and respectively in… Figure 4A , Figure 4B , Figure 4C and Figure 4D The preform is manufactured using the preform manufacturing process 400a, hot stretching process 400b, hot tapering process 400c, and rear-end connection process 400d shown in the figure.

[0076] Figure 4A , Figure 4B , Figure 4C and Figure 4D Together, an example manufacturing process for the various multimode fiber optic probe devices used in this disclosure is illustrated. Figure 4A An example preform manufacturing process 400a according to various aspects and embodiments of this disclosure is shown. Figure 4A The preform manufacturing process 400a or its variations shown can be used to manufacture various preforms, each of which can then be used to manufacture the fiber probe structure of the multimode fiber probe device described herein. The preform manufacturing process 400a or its variations can be implemented to manufacture preforms that can then be used to manufacture the fiber probe structure of the multimode fiber probe device described herein, according to various sizes, geometries, configurations, or any combination thereof. For example, the preform manufacturing process 400a or its variations can be implemented to manufacture preforms that can then be used to manufacture… Figure 1 The tapered fiber optic probe structure 110 of the probe device 100, as described herein and respectively in Figure 2A , Figure 2B and Figure 2C The probe component arrangement shown in the figure is any one of 200a, 200b, 200c, or according to another probe component arrangement, forming one or more of optical waveguide 120, microfluidic channel 130 and / or electrode 140 in tapered fiber probe structure 110.

[0077] Figure 4A Example manufacturing steps of preform manufacturing process 400a are shown, which can be implemented as described herein to form various preforms, such as, for example, preform 405 shown in this example. In some cases, preform 405 can be used to form micro preform 409, which can then be used to form tapered fiber probe structure 110, as referenced herein. Figure 4B and Figure 4C As stated above.

[0078] At 402a, the preform manufacturing process 400a may include forming one or more channels 430 in and / or through the preform material (such as, for example, preform rod 401). In some examples, one or more channels 430 may be formed in and / or through the preform rod 401 to create the features referenced herein. Figure 1The described tapered fiber probe structure 110 includes any or all of the optical waveguide 120, microfluidic channel 130, or electrode 140. In one example, the preform rod 401 may be embodied as a PC rod. In this example, the PC rod may be processed at 402a of the preform manufacturing process 400a to produce one or more channels 430, which may be used to form one or more of the optical waveguide 120, microfluidic channel 130, or electrode 140 in the tapered fiber probe structure 110. The channels 430 may be formed in and through the preform rod 401 with various cross-sectional geometries, configurations, and dimensions. For example, any or all of the channels 430 may be formed with a circular cross-section, a rectangular cross-section, a triangular cross-section, another cross-sectional geometry, or any combination thereof.

[0079] At 404a, the preform manufacturing process 400a may include inserting or embedding one or more probe components (such as, for example, one or more optical waveguides or electrodes) into one or more channels 430 of the preform rod 401. In the example shown, some channels 430 are formed through the central region of the preform rod 401, and some channels 430 are formed in or near the peripheral region or surface of the preform rod 401. The channels 430 formed through the central region of the preform rod 401 may be used at 404a of the preform manufacturing process 400a for inserting, for example, one or more optical waveguides and / or electrodes, which may be formed as one or more of the optical waveguide 120 and / or electrode 140 as described herein.

[0080] In this example, the channel 430 formed in or near the peripheral region or surface of the preform rod 401 is embodied as a space or recess. Such a space or recess can also be used at 404a of the preform manufacturing process 400a for inserting or embedding, for example, one or more optical waveguides and / or electrodes, which can be formed as one or more of the optical waveguide 120 and / or electrode 140 as described herein. In one example, one or more optical waveguides having a PC core (e.g., having a refractive index n = 1.586) and a poly(2-methyl methacrylate) (PMMA; having a refractive index n = 1.49) cladding, along with one or more bismuth-tin (BiSn) alloy electrodes, can be inserted into the corresponding channel 430 of the preform rod 401 at 404a of the preform manufacturing process 400a.

[0081] At 406a, the preform manufacturing process 400a may include applying or wrapping a preform film 403 around a preform rod 401 and consolidating the wrapped preform rod 401 in a vacuum furnace to produce a preform 405. In some cases, the preform film 403 may be embodied as a PC film. By performing the thermostretching process 400b described herein, in one example, a final preform 405 having a diameter of about 30 mm can be heated and stretched into an optical fiber (e.g., a micro preform 409) having a diameter of about 2 mm, such as... Figure 4B As shown.

[0082] For the preforms described herein (e.g., preform 405), in some examples, consolidation can be performed by heating the wrapped preform rod 401 under vacuum at, for example, about 190 degrees Celsius (°C). In some examples, the polymeric materials used to manufacture the preforms described herein (e.g., PC films, tubes, rods, preforms, and micro-preforms) can be baked under vacuum at, for example, about 80°C to ensure they are free of moisture. In various other examples, the preform manufacturing process 400a may also include one or more additional steps such as machining, insertion and / or embedding, film wrapping and / or consolidation.

[0083] In one example, an example tapered fiber probe structure 110 has eight electrodes 140, a microfluidic channel 130, and an optical waveguide 120 (e.g., Figure 2A An example preform 405 can be manufactured by first winding one or more polyvinylidene fluoride (PVDF) films or multilayer films onto a PC tube (e.g., a tube for microfluidic channels 130) to form an initial preform. One or more PC films can then be wound onto the initial preform and bonded. Next, eight grooves (e.g., eight channels 430) can be machined into the bonded initial preform. The grooves can then be inlaid with a BiSn alloy material to form eight electrodes 140. Additional one or more PC films can then be wrapped around the bonded initial preform with the inlaid BiSn alloy material and bonded to produce a final preform, which can be used as referenced herein. Figure 4B The described hot stretching process 400b.

[0084] In another example, an example tapered fiber probe structure 110 has eight electrodes 140, eight microfluidic channels 130, and four optical waveguides 120 (e.g., Figure 2BExample preform 405 can be manufactured by first milling four channels (e.g., using a computer numerical control (CNC) milling machine) into solid PC bars to form an initial preform. The initial preform can then be wrapped with one or more PC films and bonded. Next, four additional channels can be machined into the bonded initial preform, which can then be wrapped with one or more additional PC films and bonded. Twelve additional channels can then be machined into the double-bonded initial preform. Grooves can then be inlaid with eight BiSn alloy strips and four polymer waveguides (e.g., PC core, poly(2-methyl methacrylate) cladding) to form eight electrodes 140 and four optical waveguides 120, respectively. Finally, the double-bonded initial preform with inlaid BiSn alloy material and polymer waveguides can be wrapped with one or more additional PC films and bonded to produce a final preform, which can be used as referenced herein. Figure 4B The described hot stretching process 400b.

[0085] In another example, an example tapered fiber probe structure 110 has twelve microfluidic channels 130 and eight optical waveguides 120 (e.g., Figure 2C The example preform 405 can be manufactured in a similar manner to the example preform 405 of the example tapered fiber probe structure 110 described above, which has eight electrodes 140, eight microfluidic channels 130, and four optical waveguides 120. For example, several differences are: a) eight channels can be fabricated for the second layer of microfluidic channels 130; b) there will be eight optical waveguides 120 instead of four; and c) the BiSn strip will be omitted from the outermost layer of the preform.

[0086] Figure 4B An example hot stretching process 400b is shown according to various aspects and embodiments of this disclosure. Figure 4B The illustrated hot stretching process 400b or its variations can be used to manufacture various micro preforms, each of which can then be used to manufacture the fiber probe structure of the multimode fiber probe device described herein. Hot stretching process 400b or its variations can be implemented to manufacture micro preforms, which can then be used to manufacture the fiber probe structure of the multimode fiber probe device described herein, according to various sizes, geometries, configurations, or any combination thereof. For example, hot stretching process 400b or its variations can be implemented to manufacture micro preforms, which can then be used to manufacture... Figure 1 The tapered fiber optic probe structure 110 of the probe device 100, as described herein and respectively in Figure 2A , Figure 2B and Figure 2CThe probe component arrangements shown in the figure, 200a, 200b, 200c, or according to another probe component arrangement, form one or more of the optical waveguide 120, microfluidic channel 130, and / or electrode 140 in the tapered fiber probe structure 110.

[0087] In various examples, a hot stretching process 400b can be implemented to form micro preforms from preforms that have been used herein and in Figure 4A The preform manufacturing process 400a shown in the figure is used for fabrication. In these or other examples, a hot stretching process 400b can be performed to form a micro preform, such that the optical waveguides, microfluidic channels, and / or electrodes of the preform are formed in the micro preform in the same or similar manner as they are formed in the preform. For example, a hot stretching process 400b can be performed to form a micro preform, such that each of the optical waveguides, microfluidic channels, and electrodes is formed in the micro preform having the same or similar cross-sectional geometry and relative positions as in the preform.

[0088] Figure 4B An example manufacturing step of a hot stretching process 400b is shown, which can be implemented as described herein to form various micro preforms, such as, for example, the micro preform 409 shown in this example. The micro preform 409 in this example can be manufactured by methods described herein and in… Figure 4A The preform 405 shown is formed. A hot stretching process 400b can be performed to form a micro preform 409, such that the optical waveguide 420, channel 430 and electrode 440 are formed in the micro preform 409 in the same or similar manner as they are formed in the preform 405, for example, having the same or similar cross-sectional geometry and relative positions as in the preform 405.

[0089] The hot stretching process 400b may include heating and stretching a preform, such as, for example, preform 405. For example, preform 405 may be heated in a furnace and stretched into fiber 407 (e.g., optical fiber) using, for example, a winch motor. The furnace may be divided into a top section, a middle section, and a bottom section, each individually set to different temperatures. The top section of the furnace may be where preform 405 is preheated. The middle section of the furnace may be where preform 405 is softened and stretched into fiber 407. The bottom section of the furnace may be where the resulting fiber 407 is cooled. In one example, the top, middle, and bottom sections of the furnace may be set to 150°C, 275°C, and 120°C, respectively. In some examples, during the hot stretching process 400b, the temperature of the preform 405 in any given section of the furnace is the same as or approximately the same as the temperature of that section of the furnace. In other examples, during the hot stretching process 400b, the temperature of the preform 405 in any given section of the furnace is different from the temperature of such furnace section.

[0090] In some examples, a laser micrometer can be used to closely monitor the cross-sectional dimensions (e.g., diameter) of the fiber 407 formed during the hot stretching process 400b. The cross-sectional dimensions (e.g., diameter) of the fiber 407 during the hot stretching process 400b can also be controlled by adjusting the stretching speed of the winch motor and / or the temperature of one or more sections of the furnace. In the illustrated example, the hot stretching process 400b may also include cutting the fiber 407 to form one or more micropreforms 409. The hot stretching process 400b may include drawing a preform 405 with a diameter of about 30 mm into the fiber 407, such that both the fiber 407 and the micropreform 409 have a diameter of about 2 mm. The fiber 407 can then be cut into, for example, one or more micropreforms 409 10 cm long, each micropreform 409 which may be used as referenced herein. Figure 4C The described thermal tapering process 400c.

[0091] Figure 4C An example thermal tapering process 400c according to various aspects and embodiments of this disclosure is shown. The thermal tapering process 400c can be implemented and is referred to herein as a convergent tapering process. Figure 4C The thermal tapering process 400c or its variations shown can be used to manufacture various fiber probe structures for the different multimode fiber probe devices described herein. Thermal tapering process 400c or its variations can be implemented to manufacture fiber probe structures for the multimode fiber probe devices described herein according to various sizes, geometries, configurations, or any combination thereof. For example, thermal tapering process 400c or its variations can be implemented to manufacture… Figure 1 The tapered fiber optic probe structure 110 of the probe device 100, as described herein and respectively in Figure 2A , Figure 2B and Figure 2C The probe component arrangements shown in the figure, 200a, 200b, 200c, or according to another probe component arrangement, form one or more of the optical waveguide 120, microfluidic channel 130, and / or electrode 140 in the tapered fiber probe structure 110.

[0092] In various examples, a thermal tapering process 400c can be implemented to form fiber optic probe structures from micro preforms, which have been used herein and respectively in Figure 4A and Figure 4B The preform manufacturing process 400a and hot stretching process 400b shown are fabricated from the preform. In these or other examples, a hot tapering process 400c can be implemented to form a fiber optic probe structure, such that the optical waveguides, microfluidic channels, and / or electrodes of the preform and micropreform are formed in the fiber optic probe structure in the same or similar manner as they are formed in the preform and micropreform. For example, the hot tapering process 400c can be implemented to form a fiber optic probe structure such that each of the optical waveguides, microfluidic channels, and electrodes is formed in the fiber optic probe structure having the same or similar cross-sectional geometry and relative position as each of the preform and micropreform. For example, the hot tapering process 400c can be implemented to form a fiber optic probe structure such that each of the optical waveguides, microfluidic channels, and electrodes is formed in the reduced cross-sectional region produced in the micropreform and / or at the tip region of the fiber optic probe structure, with the same or similar cross-sectional geometry and relative position as each of the preform and micropreform.

[0093] Figure 4C An example fabrication step of the thermal tapering process 400c is shown, which can be implemented as described herein to form various fiber optic probe structures, such as, for example, the tapered fiber optic probe structure 110 shown in this example. The tapered fiber optic probe structure 110 in this example can be fabricated as described herein and... Figure 4BThe micropreform 409 shown is formed. A thermal tapering process 400c can be implemented to form a tapered fiber probe structure 110, such that the optical waveguide 120, microfluidic channel 130, and electrode 140 are formed in the tapered fiber probe structure 110 in the same or similar manner as the optical waveguide 420, channel 430, and electrode 440 formed in the micropreform 409, for example, having the same or similar cross-sectional geometry and relative positions as in the micropreform 409. In this example, the implementation of the thermal tapering process 400c results in the formation of the optical waveguide 120, microfluidic channel 130, and electrode 140 by the optical waveguide 420, channel 430, and electrode 440, respectively. In this example, a thermal tapering process 400c can be implemented to form a tapered fiber probe structure 110, such that each of the optical waveguide 120, microfluidic channel 130, and electrode 140 is formed in a reduced cross-sectional region 450 generated in the micro preform 409 and / or in the tip region 150 of the tapered fiber probe structure 110, with the same or similar cross-sectional geometry and relative position as in the micro preform 409.

[0094] Similar to the glass pipette pulling process, at 402c of the thermal tapering process 400c, the micro preform 409 can be heated until it softens. Then, the micro preform 409 is pulled in the opposite direction to create a reduced cross-sectional area 450 within the micro preform 409, as... Figure 4C As shown. At 402c, the thermal tapering process 400c may include holding the micropreform 409 in place and / or adjusting the alignment of the micropreform 409 using optomechanical components. The thermal tapering process 400c may also include heating and softening the micropreform 409 using a furnace set, for example, to about 230°C. In some examples, the temperature of the micropreform 409 in the furnace during the thermal tapering process 400c is the same as or approximately the same as the furnace temperature. In other examples, the temperature of the micropreform 409 in the furnace during the thermal tapering process 400c is different from the furnace temperature. Once the micropreform 409 has softened to the desired degree, it can be pulled in the opposite direction, for example, by a computer-controlled linear motor, to transform the micropreform 409 into a tapered micropreform structure 410 having a reduced cross-sectional area 450. The speed and / or travel distance of the linear motor may be varied to adjust the resulting geometry or area (e.g., diameter) of the reduced cross-sectional area 450. The resulting geometry or area (e.g., diameter) of the reduced cross-sectional region 450 can be closely monitored during the thermal tapering process 400c using a laser micrometer. The resulting geometry or area (e.g., diameter) of the reduced cross-sectional region 450 can also be controlled during the thermal tapering process 400c by adjusting the stretching speed of the linear motor and / or the furnace temperature.

[0095] At 404c, the process includes cutting a reduced cross-sectional region 450 of the tapered micropreform structure 410 at a desired angle (θ) to produce two separate tapered fiber probe structures 110. For example, after softening and pulling the micropreform 409 at 402c, the resulting tapered micropreform structure 410 can be cut at a desired location along the reduced cross-sectional region 450 to produce two separate tapered fiber probe structures 110. To produce the tapered fiber probe structure 110 having a tip region 150 that minimizes tissue damage when inserted into a subject (e.g., a patient, human, or animal), the reduced cross-sectional region 450 can be cut with a cross-section 411 at a set angle (θ) to produce an angled tip 155 of the tapered fiber probe structure 110. For example, the reduced cross-sectional area 450 may be transversely cut at a set angle (θ) at any location along the reduced cross-sectional area 450 relative to the longitudinal axis or cross-section of at least one of the reduced cross-sectional area 450, the micro preform 409, or the tapered micro preform structure 410 to form the angled tip 155 of the tapered fiber probe structure 110.

[0096] Figure 4D An example back-end connection process 400d is shown according to various aspects and embodiments of this disclosure. Figure 4D The back-end connection process 400d shown herein, or variations thereof, can be used to manufacture various multimode fiber optic probe devices described herein. For example, back-end connection process 400d can be implemented to manufacture the back-end connector region of the multimode fiber optic probe device described herein, such as, for example, the back-end connector region 160 of probe device 100. In some cases, Figure 4D The back-end joining process 400d may include the use of a translation stage and a digital microscope to provide finer positional control during joining. In one example, the back-end joining process 400d may be as referenced herein. Figure 4D Implement it as described.

[0097] At 402d, the back-end connection process 400d may include coupling connector electrode 145 (e.g., electrically grounded, operably grounded) to electrode 140 located at or near the second end of tapered fiber probe structure 110. For example, connector electrode 145 may be coupled to electrode 440 formed in tapered micro preform structure 410, as referenced herein. Figure 4A , Figure 4B and Figure 4CThe preform manufacturing process 400a, the hot stretching process 400b, and the hot tapering process 400c are shown in the diagram. In one example, the electrical connection between the connector electrode 145 and the electrode 140 can be achieved by heating the second end of the tapered fiber probe structure 110 to about 160°C to melt a portion of the electrode 140 located in that region of the tapered fiber probe structure 110 to a desired molten state. This temperature (e.g., 160°C) is high enough to melt the electrode 140, but low enough to avoid damaging the tapered fiber probe structure 110. In one example, each connector electrode 145 can be embodied as a copper wire (e.g., insulated copper wire) that can be inserted into one of the molten electrodes 140 located at its second end of the tapered fiber probe structure 110. In some cases, the connector electrode 145 (e.g., copper wire) can be guided by a hypodermic needle as it descends into the molten electrode 140. The second end of the tapered fiber probe structure 110 can then be cooled to allow the electrode 140 and the connector electrode 145 to solidify.

[0098] At 404d, the back-end connection process 400d may include connecting a microfluidic tube 135 (e.g., fluid ground, communication ground, operable ground) to a microfluidic channel 130 located at or near the second end of the tapered fiber probe structure 110. For example, the microfluidic tube 135 may be connected to a channel 430 formed in the tapered micropreform structure 410, as referenced herein. Figure 4A , Figure 4B and Figure 4C The preform manufacturing process 400a, the hot stretching process 400b, and the hot tapering process 400c are shown in the diagram. In one example, the microfluidic connection between the microfluidic tube 135 and the microfluidic channel 130 can be achieved by inserting a drawn microfluidic tube 135, embodied as a drawn polycarbonate (PC) tube, into each microfluidic channel 130 located at its second end of the tapered fiber probe structure 110. In one example, each microfluidic tube 135 can be embodied as a PC tube having an OD of about 150 μm and an ID of about 75 μm, although in some cases other PC tubes with different ODs and / or IDs can be used.

[0099] At 406d, the back-end connection process 400d may include connecting the optical fiber 125 (e.g., optical ground, communication ground, operable ground) to an optical waveguide 120 located at or near the second end of the tapered fiber probe structure 110. For example, the optical fiber 125 may be connected to an optical waveguide 420 formed in the tapered micro preform structure 410, as referenced herein. Figure 4A , Figure 4B and Figure 4CThe preform manufacturing process 400a, hot stretching process 400b, and hot tapering process 400c are shown in the diagram. In one example, the optical connection between the fiber 125 and the optical waveguide 120 can be achieved by connecting a drawn fiber 125, embodied as a drawn polymer fiber (e.g., a PC core with a poly(2-methyl methacrylate) cladding), to one of the optical waveguides 120 located at the second end of the tapered fiber probe structure 110. In one example, each fiber 125 can be embodied as a polymer fiber with a diameter of approximately 200 μm. In one example, each fiber 125 can be embodied as a polymer fiber, which can be directly connected to one of the optical waveguides 120 via epoxy resin at 406d of the back-end connection process 400d. In some cases, each fiber 125 can be embodied as a polymer fiber, which can be polished using, for example, 30-1 μm coarse sandpaper before being connected to the corresponding optical waveguide 120.

[0100] In some cases, the back-end connection process 400d may also include using UV epoxy resin to seal and secure at least one of the aforementioned electrical, microfluidic, or optical connections in place. By completing... Figure 4D The back-end connection process shown is 400d. The multimode fiber optic probe device described herein can be equipped with an industry-standard adapter compatible with electrophysiological equipment, optical modules, and drug delivery pumps.

[0101] Figure 5A , Figure 5B and Figure 5C Various views of another example multimode fiber optic probe device 500 (or "probe device 500") according to various aspects and embodiments of this disclosure are shown. Figure 5A A perspective view of an example multimode fiber optic probe device 500 according to various aspects and embodiments of the present disclosure is shown. Figure 5B A top view of the tip region 550 of an example multimode fiber optic probe device 500 according to various aspects and embodiments of the present disclosure is shown. Figure 5C An isometric view of the tip region 550 of an example multimodal fiber optic probe device 500 according to various aspects and embodiments of the present disclosure is shown. In the examples herein, the probe device 500 may be designed, embodied, and implemented as a flexible multimodal nerve fiber probe device. For example, the probe device 500 may be designed, embodied, and implemented as a cone-shaped drug delivery, photostimulation, and electrophysiology (T-DOpE) probe device described in the various embodiments herein. Similar to probe device 100, probe device 500 offers relatively higher complexity at the tip region compared to existing devices, while also simplifying the connection between the rear connector region and external electronics that can be coupled to probe device 500.

[0102] The probe device 500 is described herein and Figure 1The example alternative embodiment of probe device 100 shown is illustrated. Probe device 500 may include the same or similar structures, components, features, materials, and functions as probe device 100. The difference between probe device 500 and probe device 100 is that the cross-sectional geometry of probe device 500 is rectangular rather than circular. Another difference between probe device 500 and probe device 100 is the arrangement of the optical waveguides, microfluidic channels, and electrodes relative to each other in each such device. Another difference between probe device 500 and probe device 100 is the number of optical waveguides, microfluidic channels, and electrodes in each such device. Another difference between probe device 500 and probe device 100 is that the electrodes in probe device 500 are bundled in a subset or group referred to as "tetraodes". Another difference between probe device 500 and probe device 100 is that the electrode material of the tetraodes in probe device 100 may be a bismuth-tin (BiSn) alloy in some examples, while the electrode material of the tetraodes in probe device 500 may be a nickel-chromium (NiCr) alloy in some examples.

[0103] Figures 5A to 5C The illustrated probe device 500 includes a tapered fiber optic probe structure 510. The tapered fiber optic probe structure 510 can be embodied and implemented as a flexible tapered fiber optic probe structure as described in the examples herein. The tapered fiber optic probe structure 510 may include one or more optical waveguides 520, one or more microfluidic channels 530, one or more tetraodes 540a, 540b, 540c (or "multiple tetraodes 540"), or any combination thereof. In the illustrated example, the tapered fiber optic probe structure 510 includes a single optical waveguide 520 and a single microfluidic channel 530. In this example, each tetraode 540 is embodied as and therefore includes electrodes 542, 544, 546, 548. For example, tetrode 540a is embodied and includes electrodes 542a, 544a, 546a, and 548a; tetrode 540b is embodied and includes electrodes 542b, 544b, 546b, and 548b; and tetrode 540c is embodied and includes electrodes 542c, 544c, 546c, and 548c. For clarity, in... Figure 5C In this designation, only individual electrodes 542a, 542b, and 542c are designated for tetrodes 540a, 540b, and 540c, respectively. Optical waveguide 520, microfluidic channel 530, and tetrodes 540 (e.g., electrodes 542, 544, 546, 548) can be formed within the tapered fiber probe structure 510 such that they are substantially parallel to the longitudinal axis of the tapered fiber probe structure 510 and extend along the longitudinal axis of the tapered fiber probe structure 510 from a first end (e.g., the first distal end) to a second end (e.g., the second distal end), as shown below. Figure 5A , Figure 5B and Figure 5C As shown. For example, the centerlines of the optical waveguide 520, the microfluidic channel 530, and the tetrode 540 can be parallel to each other and coplanar or approximately coplanar along the longitudinal axis of the tapered fiber probe structure 510 from the first end to the second end of the tapered fiber probe structure 510.

[0104] The first end of the tapered fiber probe structure 510 can be characterized by having a first width ( w 1 The first width is, for example, between about 50 μm and about 750 μm, within a microscale region. In one embodiment, the first end of the tapered fiber probe structure 510 may have a first width of about 300 μm. w 1 The first end of the tapered fiber probe structure 510 may have a first thickness ranging from, for example, about 10 μm to about 250 μm. t 1 In one embodiment, the first end of the tapered fiber probe structure 510 may have a first thickness of approximately 100 μm. t 1 The first end of the tapered fiber optic probe structure 510 may include or be embodied as a microscale tip region, wherein at least one of the optical waveguide 520, microfluidic channel 530, or tetrode 540 (e.g., electrodes 542, 544, 546, 548 of tetrode 540) has one or more exposed portions or surfaces with microscale dimensions. The second end of the tapered fiber optic probe structure 510 may be embodied as having a second width ( w 2 The second width is located in a macroscopic region, ranging from, for example, about 1.5 mm to about 2.5 mm, or in some cases larger. In one embodiment, the second end of the tapered fiber probe structure 510 may have a second width of about 2 mm. w 2 The second end of the tapered fiber probe structure 510 may have a second thickness ranging from, for example, about 0.25 mm to about 1.25 mm. t 2 In one embodiment, the second end of the tapered fiber probe structure 510 may have a second thickness of approximately 0.75 mm. t 2The second end of the tapered fiber probe structure 510 may include or be embodied as a macroscale connector region, wherein at least one of the optical waveguide 520, microfluidic channel 530, or tetrode 540 (e.g., electrodes 542, 544, 546, 548 of tetrode 540) has one or more exposed portions or surfaces whose macroscale dimensions or cross-sectional areas are approximately 10 to 30 times (e.g., 20 times) the corresponding dimensions or cross-sectional areas of the components at the first end of the tapered fiber probe structure 510.

[0105] In the example shown, the tapered fiber optic probe structure 510 is embodied as having a rectangular shape and a rectangular cross-section. In various embodiments, the cross-section of the first end of the tapered fiber optic probe structure 510 and the corresponding cross-section of the second end of the tapered fiber optic probe structure 510 are both embodied as rectangular cross-sections. For example, the cross-section perpendicular to the longitudinal axis of the tapered fiber optic probe structure 510, taken at or near the first end of the tapered fiber optic probe structure 510, and the corresponding cross-section also perpendicular to the longitudinal axis of the tapered fiber optic probe structure 510, taken at or near the second end of the tapered fiber optic probe structure 510, are both rectangular cross-sections in the example shown. Although Figures 5A to 5C The tapered fiber probe structure 510 shown is embodied in having a rectangular shape and a rectangular cross-section, but the scope of this disclosure is not limited thereto. In other examples, the tapered fiber probe structure 510 may be embodied such that it has a circular cross-section, an annular cross-section, a triangular cross-section, a square cross-section, or a cross-section with other geometries. In some embodiments, the cross-section of the first end of the tapered fiber probe structure 510 and the corresponding cross-section of the second end of the tapered fiber probe structure 510 are both embodied in a circular cross-section, an annular cross-section, a triangular cross-section, a square cross-section, or a cross-section with other geometries.

[0106] The tapered fiber optic probe structure 510 can be formed using one or more preform materials for manufacturing fiber optic probe structures, and therefore may include one or more preform materials for manufacturing fiber optic probe structures, such as at least one of polymer materials or polycarbonate (PC) materials. In some examples, the tapered fiber optic probe structure 510 can be formed using one or more polymer or PC plates having grooves or channels into which optical waveguides and electrodes can be inserted, and wherein microfluidic channels can be formed as described in the examples herein. In some cases, the tapered fiber optic probe structure 510 can be formed from a rectangular PC preform that can be produced by milling (e.g., using a CNC milling machine) or otherwise forming multiple grooves or channels in a PC plate. In one example, a first portion (e.g., a half) of each such groove or channel can be milled into a first PC plate, and a second portion (e.g., a half) of each such groove or channel can be milled into a second PC plate, such that when the first and second PC plates are positioned (e.g., stacked) to form the rectangular PC preform, the first and second portions of each groove or channel are aligned. In another example, the tapered fiber probe structure 510 can be formed from a rectangular PC preform, which can be produced by milling or otherwise forming multiple grooves or channels in a PC board and stacking one or more additional PC boards on at least one side or surface of the PC board (e.g., the top or bottom side or surface) to form the rectangular PC preform. Any one or two of the aforementioned rectangular preforms can then be processed into micro-preforms, which can be used to produce the tapered fiber probe structure 510, as further described in the examples herein.

[0107] Optical waveguide 520 can be configured and operable to control optogenetics. In some examples, optical waveguide 520 can be embodied in or comprise a polymer material. In other examples, optical waveguide 520 can be embodied in or comprise a polycarbonate material. In some cases, optical waveguide 520 can comprise a polycarbonate (PC) core and a poly(2-methyl methacrylate) cladding. In one example, optical waveguide 520 can comprise a PC core with a refractive index of n=1.586 and a poly(2-methyl methacrylate) cladding with a refractive index of n=1.49. Optical waveguide 520 can have a diameter ranging from, for example, about 5 μm to about 300 μm, but in some cases may depend on a diameter outside this range. In the example shown, the optical waveguide 520 of probe device 500 can have a diameter of about 50 μm.

[0108] The microfluidic channel 530 can be configured and operable to allow local drug infusion. In some cases, the microfluidic channel 530 can be formed as one of the grooves or channels that can be formed in the aforementioned rectangular PC preform, or formed by one of the grooves or channels that can be formed in the aforementioned rectangular PC preform, which can then be used to produce a miniature preform of the tapered fiber probe structure 510, and ultimately produce the tapered fiber probe structure 510. In other examples, the microfluidic channel 530 can be formed as a tube inserted into one of the grooves or channels, or formed by one of the tubes inserted into one of the grooves or channels, which can be formed in the aforementioned rectangular PC preform, which can be used to produce a miniature preform of the tapered fiber probe structure 510, and ultimately produce the tapered fiber probe structure 510 as described herein. For example, the microfluidic channel 530 can be formed as or formed by a PC tube having a 150 μm OD and a 75 μm inner diameter ID, although in some cases other OD and / or ID dimensions may be required. The microfluidic channel 530 may have a diameter ranging from, for example, about 5 μm to about 100 μm, but in some cases may depend on a diameter outside this range. In the example shown, the microfluidic channel 530 of the probe device 500 may have a diameter of about 75 μm.

[0109] The terelectrode 540 and electrodes 542, 544, 546, and 548 may be configured independently or jointly and are operable to record extracellular voltage. In some cases, any one or all of electrodes 542, 544, 546, and 548 may be formed using a bismuth-tin (BiSn) alloy, a nickel-chromium (NiCr) alloy, a stainless steel alloy, gold or a gold alloy, platinum or a platinum alloy, tungsten or a tungsten alloy, another material or alloy, or any combination thereof. In some examples, each of electrodes 542, 544, 546, and 548 of each of the terelectrodes 540 is formed using one or more of the same materials. In other examples, at least one of electrodes 542, 544, 546, and 548 of any terelectrode 540 may be formed using a material different from any material used to form at least one of the other electrodes 542, 544, 546, and 548 of at least one other terelectrode 540. Any or all of electrodes 542, 544, 546, and 548 may have a diameter ranging from, for example, about 5 μm to about 100 μm, but in some cases may depend on another diameter outside this range. In the example shown, each of electrodes 542, 544, 546, and 548 of the probe device 500 may have a diameter of about 25 μm.

[0110] The probe device 500 also includes a tip region 550 positioned at a first end (e.g., a first distal end) of the tapered fiber probe structure 510. The tip region 550 may include or be embodied as a microscale tip region, wherein at least one of the optical waveguide 520, microfluidic channel 530, or tetrode 540 (e.g., electrodes 542, 544, 546, 548 of tetrode 540) has one or more exposed portions or surfaces with microscale dimensions. The tip region 550 may include a tip that can be formed in various geometries (e.g., shape or surface shape), configurations (e.g., arrangement of probe components exposed at the surface of the tip), orientations (e.g., cut angles), and microscale dimensions (e.g., microscale cross-section of the probe components exposed at the surface of the tip), as described in the examples herein. In the illustrated example, the tip of the tip region 550 is embodied as an angled tip 555. Either or both of the tip region 550 and the angled tip 555 may be defined and formed by a cross-section of at least one of the tapered fiber probe structure 510, optical waveguide 520, microfluidic channel 530, tetrode 540, or electrodes 542, 544, 546, 548. For example, the cross-section may be an angled cross-section formed at a set angle (θ) relative to the cross-section of the tip region 550 or the longitudinal axis of the tapered fiber probe structure 510. In the example shown, the angled tip 555 may be formed at such a set angle (θ) relative to the cross-section of the tip region 550 or the longitudinal axis of the tapered fiber probe structure 510.

[0111] In some examples, the tip of the tip region 550 may be a flat tip rather than an angled tip. In these examples, either or both of the tip region 550 and its tip may be defined and formed by a straight cross-section of at least one of the tapered fiber probe structure 510, optical waveguide 520, microfluidic channel 530, or tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c). For example, the tip region 550 may be cross-sectioned at an angle perpendicular to the longitudinal axis of the tapered fiber probe structure 510. In some cases, the tip of the tip region 550 may be a multi-angled tip with multiple outer (e.g., exposed) surfaces that are cross-sectioned at different cutting angles relative to the cross-section of the tip region 150 or the longitudinal axis of the tapered fiber probe structure 110. In these examples, one or more of the exposed surfaces of any one or more of the tapered fiber probe structure 510, optical waveguide 520, microfluidic channel 530, or tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c) can be formed as at least one of these different cut angles at the tip of the tip region 550. The tip region 550, the angled tip 555, or both can be formed as at least one of various defined dimensions, such as, for example, a defined width or a defined thickness. The tip region 550, the angled tip 555, or both can be formed as a first width ( w 1 The thickness ranges from, for example, about 50 μm to about 750 μm. In one embodiment, the tip region 550, the angled tip 555, or both may have a width of about 500 μm. The tip region 550, the angled tip 555, or both may be formed with a first thickness ( t 1 The thickness ranges from, for example, about 10 μm to about 250 μm. In one embodiment, the tip region 550, the angled tip 555, or both may have a thickness of about 100 μm.

[0112] The probe assembly 500 also includes a rear connector region 560 positioned at or near a second end (e.g., a second distal end) of the tapered fiber probe structure 510. The rear connector region 560 may include or be embodied as a macroscale connector region wherein at least one of the optical waveguide 520, microfluidic channel 530, or tetrode 540 (e.g., electrodes 542, 544, 546, 548 of tetrode 540) has one or more exposed portions or surfaces whose macroscale dimensions or cross-sectional areas are approximately 10 to 30 times (e.g., 20 times) larger than the corresponding dimensions or cross-sectional areas of the components at the tip region 550. The rear connector region 560 may be configured and operable to attach one or more probe components of the tapered fiber probe structure 510 to one or more means external to and separate from the probe assembly 500. In the example shown, the back-end connector region 560 can be configured and operable to provide connection of the optical waveguide 520, the microfluidic channel 530, and the tetrodes 540 (e.g., electrodes 542, 544, 546, 548 of each tetrode 540) to one or more devices external to and separate from the probe device 500.

[0113] The rear connector region 560 includes a rear portion (e.g., an exposed rear portion) of an optical waveguide 520 extending from the second end of the tapered fiber probe structure 510. The rear portion of the optical waveguide 520 can be configured and operable (e.g., optically, communicatively, operably) coupled to an external optical component or device, such that the tip portion of the optical waveguide 520 at the first end of the tapered fiber probe structure 510 can be (e.g., optically, communicatively, operably) coupled to such an external optical component or device. For example, the rear portion of the optical waveguide 520 can be configured (e.g., formed) and operable to be coupled to an external optical component or device, such that the exposed cross-sectional surface of the optical waveguide 520 at the angled tip 555 can be (e.g., optically, communicatively, operably) coupled to such an external optical component or device.

[0114] In some examples, the optical fiber may be coupled to the rear end portion (e.g., exposed rear end portion) of the optical waveguide 520 at or near the second end of the tapered optical fiber probe structure 510 (e.g., optically, communicatively, operatively). For example, the optical fiber may be directly coupled to the optical waveguide 520 at or near the second end of the tapered optical fiber probe structure 510. In some examples, the optical fiber may be embodied in or comprise a polymer material. In other examples, the optical fiber may be embodied in or comprise a polycarbonate material. In some cases, the optical fiber may be embodied as an optical fiber or a cable. In one example, the optical fiber may be embodied as a polymer optical waveguide (e.g., a PC core with a poly(2-methyl methacrylate) cladding). In another example, the optical fiber may be embodied as a polymer optical waveguide with a diameter of 200 μm (e.g., a PC core with a poly(2-methyl methacrylate) cladding). In other examples, the rear connector region 560 may also include an optical fiber connector. In one example, the optical fiber connector may be embodied as a stainless steel optical fiber ferrule. For example, the optical fiber connector may be embodied as a stainless steel optical fiber ferrule with an outer diameter of 1.25 mm. In one example, a fiber optic connector can be attached to an optical fiber that can be attached to the back end of the optical waveguide 520.

[0115] The rear connector region 560 also includes a microfluidic tube 535 coupled to the microfluidic channel 530 at or near the second end of the tapered fiber probe structure 510 (e.g., fluidly and operatively). In various examples, the microfluidic tube 535 may be coupled to the rear portion of the microfluidic channel 530 at or near the second end of the tapered fiber probe structure 510, such that the tip portion of the microfluidic channel 530 at the first end of the tapered fiber probe structure 510 can be coupled to an external device (e.g., fluidly and operatively). For example, the microfluidic tube 535 may be coupled to the rear portion of the microfluidic channel 530 at or near the second end of the tapered fiber probe structure 510, such that the open cross-section of the microfluidic channel 530 at the angled tip 555 can be coupled to an external device (e.g., fluidly and operatively). In the illustrated example, the microfluidic tube 535 is at least partially inserted into the microfluidic channel 530 at the second end of the tapered fiber probe structure 510. In one example, the microfluidic tube 535 may be embodied as a polycarbonate (PC) tube. For example, the microfluidic tube 535 can be embodied as a PC tube with a 150 μm OD and a 75 μm ID, although in some cases other OD and / or ID dimensions may be required. In other examples, the rear connector region 560 may also include a fluid connector. In one example, a fluid connector may be coupled to the microfluidic tube 535.

[0116] The rear connector region 560 also includes a rear-end portion (e.g., an exposed rear-end portion) of a tetrode 540 extending from the second end of the tapered fiber probe structure 510 (e.g., the exposed rear-end portion of electrodes 542, 544, 546, 548 of each tetrode 540). The rear-end portions of the tetrodes 540 (e.g., the rear-end portions of electrodes 542, 544, 546, 548 of each tetrode 540) can be configured and operable for (e.g., electrical ground, communication ground, operably) coupling to an external electrical component or device, such that the tip portions of the tetrodes 540 at the first end of the tapered fiber probe structure 510 (e.g., the tip portions of electrodes 542, 544, 546, 548 of each tetrode 540) can (e.g., electrical ground, communication ground, operably) coupling to such an external electrical component or device. For example, the rear end portion of the tetrode 540 can be configured and operable for connection to an external electrical component or device, such that the exposed cross-sectional surface of each tetrode 540 (e.g., the exposed cross-sectional surface of each electrode 542, 544, 546, 548 of each tetrode 540) can be connected to such an external electrical component or device at the angled tip 555.

[0117] In some examples, the rear connector region 560 may also include one or more electrical connectors, which are respectively (e.g., electrical ground, communication ground, operatively ground) connected to one or more tetrodes 540 extending from the second end of the tapered fiber probe structure 510 (e.g., electrodes 542, 544, 546, 548 connected to one or more tetrodes 540). In these examples, each such electrical connector may be connected at or near the second end of the tapered fiber probe structure 510 to a rear portion (e.g., an exposed rear portion) of the tetrode 540 (e.g., the exposed rear portion connected to electrodes 542, 544, 546, 548 of the tetrode 540), such that the tip portion of the tetrode 540 at the first end of the tapered fiber probe structure 510 (e.g., the tip portions of electrodes 542, 544, 546, 548 of the tetrode 540) can be (e.g., electrical ground, communication ground, operatively ground) connected to an external device. For example, each electrical connector may be coupled at or near the second end of the tapered fiber optic probe structure 510 to the rear end portion of each electrode 542, 544, 546, 548 of the tetrode 540, such that the exposed cross-sectional surface of the tetrode 540 at the angled tip 555 (e.g., the exposed cross-sectional surface of each electrode 542, 544, 546, 548 of the tetrode 540) can be coupled (e.g., electrically, communicatively, operatively) to an external device. In these examples, each such electrical connector may be directly coupled at or near the second end of the tapered fiber optic probe structure 510 to one of the tetrodes 540 (e.g., coupled to electrodes 542, 544, 546, 548 of the tetrode 540).

[0118] Any or all of the above-described electrical connectors, which may be used in some examples, may be embodied as wires, such as, for example, copper wire. In one example, any or all of the electrical connectors may be embodied as insulated copper wire. In one example, any or all of the electrical connectors may be embodied as 42AWG copper wire. In other examples, the rear connector region 560 may also include one or more pin connectors, a PCB, or any combination thereof. In one example, one end of each of the above-described electrical connectors may be coupled to the rear portion of the tetrode 540 (e.g., coupled to the exposed rear portion of each electrode 542, 544, 546, 548 of the tetrode 540) at or near the second end of the tapered fiber optic probe structure 110, and the other end of the electrical connector may be coupled to a pin connector. In another example, one end of each electrical connector may be coupled to the rear portion of the tetrode 540 (e.g., coupled to the exposed rear portion of each electrode 542, 544, 546, 548 of the tetrode 540) at or near the second end of the tapered fiber optic probe structure 110, and the other end of the electrical connector may be coupled to a PCB.

[0119] In some cases, the probe device 500 may also include a sealant to seal the microfluidic tube 535 to the microfluidic channel 530. For example, the probe device 500 may include UV epoxy resin, which may be coupled to a second end of the tapered fiber probe structure 510 and also to the microfluidic tube 535 and / or the aforementioned fluid connector. In some cases, the UV epoxy resin may also be coupled to any one or all of, or any combination thereof, of the optical waveguide 520, the aforementioned fiber or fiber connector, the aforementioned electrical connector, pin connector, or PCB to provide support for these components.

[0120] The probe device 500 can be manufactured in various sizes, geometries, configurations, or any combination thereof. In some cases, the probe device 500 can be manufactured such that the optical waveguide 520, the microfluidic channel 530, and / or the tetrode 540 (e.g., electrodes 542, 544, 546, 548) are juxtaposed within the tapered fiber probe structure 510 according to different arrangements. For example, the probe device 500 can be manufactured such that the optical waveguide 520, the microfluidic channel 530, and / or the tetrode 540 (e.g., electrodes 542, 544, 546, 548) are arranged according to the description herein and respectively within... Figure 6A and Figure 6B The probe component arrangement shown is either 600a or 600b or according to another probe component arrangement and is juxtaposed within the tapered fiber probe structure 510.

[0121] Figure 6A and Figure 6BAn additional example probe component arrangement of another example multimode fiber optic probe device according to various aspects and embodiments of this disclosure is shown. Figure 6A and Figure 6B Different example probe component arrangements that can be formed in the multimode fiber optic probe apparatus of this disclosure are shown, for example, those referenced herein. Figures 5A to 5C The probe device 500 is described. Figure 6A An example probe component arrangement 600a according to various aspects and embodiments of the present disclosure is shown. For example, Figure 6A A cross-sectional view of an example tapered fiber optic probe structure 510 formed according to probe component arrangement 600a is shown. For example, Figure 6A A cross-sectional view is shown at the tip region 550 and / or the angled tip 555 of an example tapered fiber optic probe structure 510 formed according to the probe component arrangement 600a.

[0122] In the example shown, the tapered fiber probe structure 510 includes, according to Figure 6A The probe components shown are arranged 600a and disposed within a tapered fiber optic probe structure 510, including an optical waveguide 520, a microfluidic channel 530, and tetrodes 540a, 540b, and 540c (e.g., electrodes 542, 544, 546, and 548 for each tetrode 540a, 540b, and 540c). For clarity, in Figure 6A In this context, for each of the tetrodes 540a, 540b, and 540c, only a single electrode 542a, 542b, or 542c is designated. In the probe assembly arrangement 600a, the optical waveguide 520, microfluidic channel 530, and tetrodes 540 (e.g., electrodes 542, 544, 546, 548) are parallel and coplanar to each other along the longitudinal axis of the tapered fiber probe structure 510 from a first end (e.g., a first distal end) to a second end (e.g., a second distal end). For example, in... Figure 6A In the probe component arrangement 600a shown, the centerlines of the optical waveguide 520, microfluidic channel 530, and tetrodes 540 (e.g., the collective centerline of electrodes 542, 544, 546, and 548 of each tetrode 540a, 540b, and 540c) are parallel or substantially parallel and / or coplanar or substantially coplanar with each other along the longitudinal axis of the tapered fiber probe structure 510 from the first end to the second end of the tapered fiber probe structure 510. In this example, the longitudinal axis of the tapered fiber probe structure 510 is located at the center of the tapered fiber probe structure 510 and extends in and out in a direction parallel to the axis "Z". Figure 6A The page.

[0123] The tapered fiber probe structure 510 may further include one or more partition regions positioned between at least two of any one of the optical waveguide 520, the microfluidic channel 530, or the tetrapod 540 (e.g., electrodes 542, 544, 546, 548 of tetrapods 540a, 540b, 540c). In the illustrated example, the tapered fiber probe structure 510 includes partition regions 615a and 615b. In this example, partition region 615a is positioned between the optical waveguide 520 and the microfluidic channel 530. In this example, partition region 615a is located between these probe components and extends from a first end to a second end of the tapered fiber probe structure 510. For example, partition region 615a extends from the first end to the second end of the tapered fiber probe structure 510 in a direction parallel to the "Z" axis. Figure 6A The page. Separating region 615a isolates (e.g., physically) and insulates (e.g., electrically, optically, electromagnetically, chemically) the optical waveguide 520 from at least one of the microfluidic channel 530 or any one or all of the electrodes 542, 544, 546, 548 of the tetrodes 540a, 540b, 540c. Separating region 615a includes material from one or more portions of at least one of the tapered fiber probe structure 510 (e.g., a polymer or polycarbonate used to form the tapered fiber probe structure 510), the optical waveguide 520 (e.g., a cladding, sheath, enclosure, or coating of the optical waveguide 520), or the microfluidic channel 530 (e.g., a polymer or polycarbonate tube used to form the microfluidic channel 530).

[0124] In the example shown, the separation region 615b is positioned between the microfluidic channel 530 and the tetrode 540c (e.g., electrodes 544c, 546c of the tetrode 540c). In this example, the separation region 615b is located between these probe components and extends from a first end to a second end of the tapered fiber probe structure 510. For example, the separation region 615b extends from the first end to the second end of the tapered fiber probe structure 510 in a direction parallel to the "Z" axis. Figure 6AThe page. Separating region 615b isolates (e.g., physically) and insulates (e.g., electrically, optically, electromagnetically, chemically) any one or all of the electrodes 542, 544, 546, 548 of the tetrodes 540a, 540b, 540c from at least one of the optical waveguides 520 or microfluidic channels 530. Separating region 615b includes material from one or more portions of at least one of the tapered fiber probe structure 510 (e.g., a polymer or polycarbonate used to form the tapered fiber probe structure 510), the microfluidic channel 530 (e.g., a polymer or polycarbonate tube used to at least partially form the microfluidic channel 530), or electrodes 542, 544, 546, 548 (e.g., an insulating coating, wrapping, sheath, or sleeve of one or both of electrodes 544c, 546c).

[0125] The tapered fiber optic probe structure 510 in this example also includes additional separating regions positioned between pairs of tetrodes 540 (e.g., between electrodes 542, 544, 546, and 548 of tetrodes 540a, 540b, and 540c). These additional separating regions isolate (e.g., physically) and insulate (e.g., electrically and electromagnetically) the tetrodes 540 (e.g., electrodes 542, 544, 546, and 548 of tetrodes 540a, 540b, and 540c) from each other. The additional separating regions include material from one or more portions of at least one of the tapered fiber optic probe structure 510 (e.g., the polymer or polycarbonate used to form the tapered fiber optic probe structure 510) or the tetrodes 540 (e.g., the insulating coating, wrapping, sheath, or sleeve of any one or all of electrodes 542, 544, 546, and 548).

[0126] Figure 6B Another example probe component arrangement 600b is shown according to various aspects and embodiments of this disclosure. For example, Figure 6B A cross-sectional view of an example tapered fiber optic probe structure 510 formed according to probe component arrangement 600b is shown. For example, Figure 6B A cross-sectional view is shown at the tip region 550 and / or the angled tip 555 of an example tapered fiber optic probe structure 510 formed according to probe component arrangement 600b. Probe component arrangement 600b is described herein and... Figure 6A The example alternative embodiment of probe component arrangement 600a shown is illustrated below. The difference between probe component arrangement 600b and probe component arrangement 600a is that probe component arrangement 600b includes an additional tetrode 540d replacing the microfluidic channel 530. Tetrode 540d includes additional electrodes 542d, 544d, 546d, and 548d. For clarity, in... Figure 6BThe designation only specifies a single electrode 542d of tetrode 540d. Tetrode 540d may include structures, components, features, materials, and functions that are identical or similar to any one or all of tetrodes 540a, 540b, and 540c. Electrodes 542d, 544d, 546d, and 548d may include structures, components, features, materials, and functions that are identical or similar to any one or all of electrodes 542, 544, 546, and 548 of tetrodes 540a, 540b, and 540c.

[0127] In the example shown, according to Figure 6B The probe component arrangement 600b shown includes a tapered fiber optic probe structure 510 comprising an optical waveguide 520 and tetrodes 540a, 540b, 540c, and 540d (e.g., electrodes 542, 544, 546, and 548 for each of the tetrodes 540a, 540b, 540c, and 540d) . For clarity, in Figure 6B In this context, for each of the tetrodes 540a, 540b, 540c, and 540d, only a single electrode 542a, 542b, 542c, or 542d is designated. In the probe assembly arrangement 600b, the optical waveguide 520 and the tetrodes 540 (e.g., electrodes 542, 544, 546, 548) are parallel and coplanar to each other along the longitudinal axis of the tapered fiber probe structure 510 from a first end (e.g., a first distal end) to a second end (e.g., a second distal end). For example, in... Figure 6B In the probe component arrangement 600b shown, the centerlines of the optical waveguide 520 and the tetrodes 540 (e.g., the collective centerline of electrodes 542, 544, 546, 548 of each tetrode 540a, 540b, 540c, 540d) are parallel or substantially parallel and / or coplanar or substantially coplanar with each other along the longitudinal axis of the tapered fiber probe structure 510 from the first end to the second end of the tapered fiber probe structure 510. In this example, the longitudinal axis of the tapered fiber probe structure 510 is located at the center of the tapered fiber probe structure 510 and extends in and out in a direction parallel to the axis "Z". Figure 6B The page.

[0128] The tapered fiber probe structure 510 may further include one or more partition regions positioned between at least two of any one of the optical waveguide 520 or the tetrode 540 (e.g., electrodes 542, 544, 546, 548 of tetrodes 540a, 540b, 540c). In the illustrated example, the tapered fiber probe structure 110 also includes a partition region 615 positioned between the optical waveguide 520 and the tetrode 540d (e.g., electrodes 544d, 546d of tetrode 540d). In this example, the partition region 615 is located between these probe components and extends from a first end to a second end of the tapered fiber probe structure 510. For example, the partition region 615 extends from the first end to the second end of the tapered fiber probe structure 510 in a direction parallel to the "Z" axis. Figure 6B The page. Separating region 615 isolates (e.g., physically) and insulates (e.g., electrically, optically, electromagnetically, chemically) from any one or all of the electrodes 542, 544, 546, 548 of the tetrodes 540a, 540b, 540c, 540d, and vice versa. Separating region 615 includes material from one or more portions of at least one of the following: tapered fiber probe structure 510 (e.g., polymer or polycarbonate used to form tapered fiber probe structure 510), optical waveguide 520 (e.g., cladding, sheath, enclosure, or coating of optical waveguide 520), or electrodes 542, 544, 546, 548 (e.g., insulating coating, enclosure, sheath, or sleeve of one or both of electrodes 544d, 546d).

[0129] The tapered fiber optic probe structure 510 in this example also includes additional separating regions positioned between pairs of tetrodes 540 (e.g., between electrodes 542, 544, 546, and 548 of tetrodes 540a, 540b, 540c, and 540d). These additional separating regions isolate (e.g., physically) and insulate (e.g., electrically or electromagnetically) the tetrodes 540 (e.g., electrodes 542, 544, 546, and 548 of tetrodes 540a, 540b, 540c, and 540d) from each other. The additional separating regions include material from one or more portions of at least one of the tapered fiber optic probe structure 510 (e.g., the polymer or polycarbonate used to form the tapered fiber optic probe structure 510) or the tetrodes 540 (e.g., the insulating coating, wrapping, sheath, or sleeve of any one or all of electrodes 542, 544, 546, and 548).

[0130] Figure 7A , Figure 7B , Figure 7C and Figure 7D Together, another example manufacturing process for fabricating the various multimode fiber optic probe devices disclosed herein is illustrated. Figure 7A Another example preform manufacturing process 700a according to various aspects and embodiments of this disclosure is shown. Figure 7A The preform manufacturing process 700a or its variations shown can be used to manufacture various preforms, each of which can then be used to manufacture the fiber probe structure of the multimode fiber probe device described herein. The preform manufacturing process 700a or its variations can be implemented to manufacture preforms that can then be used to manufacture the fiber probe structure of the multimode fiber probe device described herein, according to various sizes, geometries, configurations, or any combination thereof. For example, the preform manufacturing process 700a or its variations can be implemented to manufacture preforms that can then be used to manufacture… Figures 5A to 5C The tapered fiber optic probe structure 510 of the probe device 500, as described herein and respectively in Figure 6A and Figure 6B The probe component arrangement shown in the figure is either 600a, 600b or according to another probe component arrangement, forming an optical waveguide 520, a microfluidic channel 530 and / or a tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c).

[0131] Figure 7A Example manufacturing steps of preform manufacturing process 700a are shown, which can be implemented as described herein to form various preforms, such as preform 705 as shown in this embodiment, for example. In some cases, preform 705 can be used to form micro preform 709a, and then micro preform 709b, which can then be used to form tapered fiber probe structure 510, as referenced herein. Figure 7B and Figure 7C As stated above.

[0132] The preform manufacturing process 700a may include forming one or more channels 730 in and / or through the preform material (such as, for example, a rectangular preform or one or more preform plates). The preform 705 may be produced by milling (e.g., using a CNC milling machine) or otherwise forming multiple grooves or channels in one or more PC plates (e.g., rectangular PC plates). In one example, a first portion (e.g., a half) of each such groove or channel may be milled into a first PC plate (e.g., a first rectangular PC plate). In this example, a second portion (e.g., a half) of each such groove or channel may be milled into a second PC plate (e.g., a second rectangular PC plate) such that the first and second portions of each groove or channel are aligned when the first and second PC plates are positioned (e.g., stacked) to form the preform 705. In another example, a preform 705 can be produced by milling or otherwise forming multiple grooves or channels in a first rectangular PC board and stacking one or more additional rectangular PC boards on at least one side or surface (e.g., top or bottom side or surface) of the first PC board. Either or both of the aforementioned rectangular preforms can then be machined into micro-preforms 709a and 709b, which can then be used to form a tapered fiber optic probe structure 510, as referenced herein. Figure 7B and Figure 7C The channels 730 can be formed in and through the preform 705 in various cross-sectional geometries, configurations, and dimensions. For example, any or all of the channels 730 can be formed with a circular cross-section, a rectangular cross-section, a triangular cross-section, another cross-sectional geometry, or any combination thereof.

[0133] In some examples, the aforementioned preform material (e.g., a PC sheet with grooves or channels) can be solidified to form preform 705 by heating it under vacuum at, for example, about 190°C. In some examples, the polymer material used to manufacture preform 705 (e.g., PC film, tube, rod, preform, and micropreform) can be baked under vacuum at, for example, about 80°C to ensure it is free of moisture. In one example, the final preform 705 may have a width of about 30 mm. w In another example, preform 705 can be heated and stretched as described herein. Figure 7B The width shown ( w (e.g., micro preform 709a) is an optical fiber of about 2 mm.

[0134] Figure 7B Another example of a hot stretching process 700b according to various aspects and embodiments of this disclosure is shown. Figure 7BThe hot stretching process 700b or its variations shown can be used to manufacture various micro preforms, each of which can then be used to manufacture the fiber probe structure of the multimode fiber probe device described herein. The hot stretching process 700b or its variations can be implemented to manufacture micro preforms, which can then be used to manufacture the fiber probe structure of the multimode fiber probe device described herein, according to various sizes, geometries, configurations, or any combination thereof. For example, the hot stretching process 700b or its variations can be implemented to manufacture micro preforms, which can then be used to manufacture... Figures 5A to 5C The tapered fiber optic probe structure 510 of the probe device 500, as described herein and respectively in Figure 6A and Figure 6B The probe component arrangements 600a, 600b shown, or according to another probe component arrangement, form an optical waveguide 520, a microfluidic channel 530, and / or a tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c) in the tapered fiber probe structure 510.

[0135] In various examples, a hot stretching process 700b can be performed to form a micro preform 709a from a preform 705, which has been used in accordance with the methods described herein and Figure 7A The preform manufacturing process 700a shown in the figure is used for fabrication. In these or other examples, a hot stretching process 700b may be performed to form a micro preform 709a, such that the channels 730 of the preform 705 are formed in the micro preform 709a in the same or similar manner as they are formed in the preform 705. For example, a hot stretching process 700b may be performed to form the micro preform 709a, such that each channel 730 is formed in the micro preform 709a having the same or similar cross-sectional geometry and relative position as in the preform 705.

[0136] The hot stretching process 700b may include heating and stretching a preform 705. For example, the preform 705 may be heated in a furnace and stretched into a fiber 707 (e.g., optical fiber) using, for example, a winch motor. The furnace may be divided into a top section, a middle section, and a bottom section, each individually set to different temperatures. The top section of the furnace may be where the preform 705 is preheated. The middle section of the furnace may be where the preform 705 is softened and stretched into the fiber 707. The bottom section of the furnace may be where the resulting fiber 707 is cooled. In one example, the top, middle, and bottom sections of the furnace may be set to 150°C, 275°C, and 120°C, respectively. In some examples, during the hot stretching process 700b, the temperature of the preform 705 in any given section of the furnace is the same as or approximately the same as the temperature of that section of the furnace. In other examples, during the hot stretching process 700b, the temperature of the preform 705 in any given section of the furnace differs from the temperature of that section of the furnace.

[0137] In some examples, a laser micrometer can be used to closely monitor the cross-sectional dimensions (e.g., width, height, or thickness) of the fiber 707 formed during the hot stretching process 700b. The cross-sectional dimensions (e.g., width, height, or thickness) of the fiber 707 during the hot stretching process 700b can also be controlled by adjusting the stretching speed of the winch motor and / or the temperature of one or more sections of the furnace. In the illustrated example, the hot stretching process 700b may also include cutting the fiber 707 to form one or more micropreforms 709a. In one example, the hot stretching process 700b may include fibers with a width of approximately 30 mm (… w The preform 705 is drawn into fiber 707, such that both fiber 707 and micro preform 709a have a width of approximately 2 mm. w The fiber 707 can then be cut into, for example, one or more 10cm long micro preforms 709a, each of which can be used as referenced herein. Figure 7C The described thermal tapering process 700c.

[0138] Figure 7C Another example thermal tapering process 700c according to various aspects and embodiments of this disclosure is shown. The thermal tapering process 700c can be implemented and is referred to herein as a convergent tapering process. Figure 7C The thermal tapering process 700c or its variations shown can be used to manufacture various fiber probe structures for the different multimode fiber probe devices described herein. Thermal tapering process 700c or its variations can be implemented to manufacture fiber probe structures for the multimode fiber probe devices described herein, according to various sizes, geometries, configurations, or any combination thereof. For example, thermal tapering process 700c or its variations can be implemented to manufacture… Figures 5A to 5CThe tapered fiber optic probe structure 510 of the probe device 500, as described herein and respectively in Figure 6A and Figure 6B The probe component arrangements shown in the figure, 600a, 600b, or according to another probe component arrangement, form an optical waveguide 520, a microfluidic channel 530, and / or a tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c).

[0139] In various examples, a thermal tapering process 700c can be implemented to form fiber optic probe structures from micro preforms, which have been used herein and respectively in Figure 7A and Figure 7B The preform manufacturing process 700a and hot stretching process 700b shown are fabricated from the preform. In these or other examples, a hot tapering process 700c may be implemented to form a fiber optic probe structure such that the optical waveguides, microfluidic channels, and / or tetrodes (e.g., electrodes of each tetrode) of the preform and micropreform are formed in the fiber optic probe structure in the same or similar manner as they are formed in the preform and micropreform. For example, a hot tapering process 700c may be implemented to form a fiber optic probe structure such that each of the optical waveguides, microfluidic channels, and tetrodes (e.g., electrodes of each tetrode) is formed in the fiber optic probe structure having the same or similar cross-sectional geometry and relative position as each of the preform and micropreform. For example, a thermal tapering process 700c can be implemented to form an optical fiber probe structure such that each of the optical waveguide, microfluidic channel, and tetrode (e.g., the electrode of each tetrode) is formed in the reduced cross-sectional region generated in the micro preform and / or at the tip region of the optical fiber probe structure, with the same or similar cross-sectional geometry and relative position as each of the preform and the micro preform.

[0140] Figure 7C An example fabrication step of the thermal tapering process 700c is shown, which can be implemented as described herein to form various fiber optic probe structures, such as, for example, the tapered fiber optic probe structure 510 shown in this example. The tapered fiber optic probe structure 510 in this example can be fabricated as described herein and... Figure 7BThe micro preform 709b shown is formed. A thermal tapering process 700c can be performed to form a tapered fiber probe structure 510, such that the optical waveguide 520, microfluidic channel 530, and tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c) are formed in the tapered fiber probe structure 510 in the same or similar manner as the formation of the optical waveguide 720, channel 730, and tetrode 740 (e.g., electrodes 742, 744, 746, 748 of each of tetrodes 740a, 740b, 740c) in the micro preform 709b, for example, having the same or similar cross-sectional geometry and relative positions as in the micro preform 709b. In this example, the implementation of the thermal taper process 700c results in the formation of optical waveguide 520, microfluidic channel 530, and tetrodes 540 (e.g., electrodes 742, 744, 746, 748 of each of tetrodes 740a, 740b, 740c) by optical waveguide 720, channel 730, and tetrodes 740 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c), respectively. In this example, a thermal tapering process 700c can be implemented to form a tapered fiber probe structure 510, such that each of the optical waveguide 520, the microfluidic channel 530, and the tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of the tetrodes 540a, 540b, 540c) is formed in the reduced cross-sectional region 750 generated in the micro preform 709b and / or at the tip region 550 of the tapered fiber probe structure 510, with the same or similar cross-sectional geometry and relative position as in the micro preform 709b.

[0141] At 702c, the thermal taper process 700c may include inserting one or more probe components (such as, for example, one or more optical waveguides 720 and / or one or more tetrodes 740a, 740b, 740c (or “multiple tetrodes 740”)) into and through one or more channels 730 of the micropreform 709a to produce the micropreform 709b, as... Figure 7CAs shown. In the example shown, each tetrode 740 includes electrodes 742, 744, 746, and 748. In this example, the optical waveguide 720 may be embodied and include structures, components, materials, and functions that are the same as or similar to those of the optical waveguide 520. In this example, tetrodes 740a, 740b, and 740c may be embodied and include structures, components, materials, and functions that are the same as or similar to those of tetrodes 540a, 540b, and 540c, respectively. In this example, electrodes 742, 744, 746, and 748 may be embodied and include structures, components, materials, and functions that are the same as or similar to those of electrodes 542, 544, 546, and 548. As described herein, the optical waveguide 720 and the tetrode 740 (e.g., electrodes 742, 744, 746, 748 of each of tetrodes 740a, 740b, 740c) can be respectively formed as the optical waveguide 520 and the tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c).

[0142] In one example, an optical waveguide 720 having a PC core (e.g., having a refractive index n = 1.586) and a poly(2-methyl methacrylate) (PMMA; having a refractive index n = 1.49) cladding can be inserted into a channel 730 of a preform 705 at 702c of a thermal tapering process 700c. In another example, electrodes 742, 744, 746, 748, embodied in at least one of bismuth-tin (BiSn) alloy, nickel-chromium (NiCr) alloy, stainless steel alloy, gold or gold alloy, platinum or platinum alloy, tungsten or tungsten alloy, or another material or alloy, are configured as tetrodes 740a, 740b, 740c and inserted into corresponding channels 730 of the preform 705 at 702c of a thermal tapering process 700c. In some cases, a PC microfluidic tube can be inserted into one of the channels 730 at 702c of a thermal tapering process 700c. In these cases, the PC microfluidic tube can be formed as a microfluidic channel 530 of the tapered fiber probe structure 510 as described herein. In other examples, one of the channels 730 can remain empty in each of the micropreforms 709a, 709b. In these examples, the empty channel 730 can be formed into the microfluidic channel 530 of the tapered fiber probe structure 510 as described herein.

[0143] Similar to the glass pipette pulling process, at 704c of the thermal tapering process 700c, the micro preform 709b can be heated until it softens, and then pulled in the opposite direction to create a reduced cross-sectional area 750 in the micro preform 709b, as... Figure 7CAs shown. At 704c, the thermal tapering process 700c may include holding the micro preform 709b in place and / or adjusting the alignment of the micro preform 709b using optomechanical components. The thermal tapering process 700c may also include heating and softening the micro preform 709b using a furnace set to, for example, about 230°C. In some examples, the temperature of the micro preform 709b in the furnace during the thermal tapering process 700c is the same as or approximately the same as the furnace temperature. In other examples, the temperature of the micro preform 709b in the furnace during the thermal tapering process 700c is different from the furnace temperature.

[0144] Once the micropreform 709b has softened to the desired degree, it can be pulled in the opposite direction, for example, by a computer-controlled linear motor, to transform it into a tapered micropreform structure 710 with a reduced cross-sectional area 750. The speed and / or travel distance of the linear motor can be varied to adjust the resulting geometry or area (e.g., width, height, or thickness) of the reduced cross-sectional area 750. The resulting geometry or area (e.g., width, height, or thickness) of the reduced cross-sectional area 750 can be closely monitored during the thermal tapering process 700c using a laser micrometer. The resulting geometry or area (e.g., width, height, or thickness) of the reduced cross-sectional area 750 can also be controlled during the thermal tapering process 700c by adjusting the stretching speed of the linear motor and / or the temperature of the furnace.

[0145] At 704c, the thermal tapering process 700c may further include cutting a reduced cross-sectional area 750 of the tapered micropreform structure 710 at a desired angle (θ) to produce two separate tapered fiber probe structures 510. For example, after softening and pulling the micropreform 709b, the resulting tapered micropreform structure 710 may be cut along the reduced cross-sectional area 750 at a desired location to produce two separate tapered fiber probe structures 510. To produce the tapered fiber probe structure 510 having a tip region 550 that minimizes tissue damage when inserted into a subject (e.g., a patient, human, or animal), the reduced cross-sectional area 750 may be cut with a cross-section 711 at a set angle (θ) to produce an angled tip 555 of the tapered fiber probe structure 510. For example, the reduced cross-sectional area 750 may be transversely cut at a set angle (θ) at any position along the reduced cross-sectional area 750 relative to the longitudinal axis or cross-section of at least one of the reduced cross-sectional area 750, the micro preform 709b, or the tapered micro preform structure 710 to form the angled tip 555 of the tapered fiber probe structure 510.

[0146] Figure 7DAnother example back-end connection process 700d according to various aspects and embodiments of this disclosure is shown. Figure 7D The back-end connection process 700d shown herein, or variations thereof, can be used to manufacture various multimode fiber probe devices described herein. For example, back-end connection process 700d can be implemented to manufacture the back-end connector region of the multimode fiber probe device described herein, such as, for example, the back-end connector region 560 of probe device 500. In some cases, Figure 7D The back-end joining process 700d may include the use of a translation stage and a digital microscope to provide finer positional control during joining. In one example, the back-end joining process 700d may be as referenced herein. Figure 7D Implement it as described.

[0147] The back-end connection process 700d may include connecting a microfluidic tube 535 (e.g., fluid ground, communication ground, operable ground) to a microfluidic channel 530 located at or near the second end of the tapered fiber probe structure 510. For example, the microfluidic tube 535 may be connected to a channel 730 formed in the tapered micropreform structure 710, as referenced herein. Figure 7A , Figure 7B and Figure 7C The preform manufacturing process 700a, hot stretching process 700b, and hot tapering process 700c are shown in the diagram. In one example, the microfluidic connection between the microfluidic tube 535 and the microfluidic channel 530 can be achieved by inserting a drawn microfluidic tube 535, embodied as a drawn PC tube, into a microfluidic channel 530 located at its second end of the tapered fiber probe structure 510. In one example, the microfluidic tube 535 can be embodied as a PC tube with an OD of approximately 150 μm and an ID of approximately 75 μm, although in some cases other PC tubes with different ODs and / or IDs can be used.

[0148] In some cases, the back-end connection process 700d may also include connecting the optical fiber (e.g., optically, communicatively, operably) to a back-end portion (e.g., an exposed back-end portion) of the optical waveguide 520 at or near the second end of the tapered optical fiber probe structure 510. For example, the optical fiber may be connected to a back-end portion (e.g., an exposed back-end portion) of the optical waveguide 720 formed in the tapered micro preform structure 710, as referenced herein respectively in Figure 7A , Figure 7B and Figure 7CThe preform manufacturing process 700a, hot stretching process 700b, and hot tapering process 700c are shown in the diagram. In one example, the optical connection between the fiber and the optical waveguide 520 can be achieved by connecting a drawn fiber, embodied as a drawn polymer fiber (e.g., a PC core with a poly(2-methyl methacrylate) cladding), to an optical waveguide 520 located at the second end of the tapered fiber probe structure 510. In one example, the fiber may be embodied as a polymer fiber with a diameter of approximately 200 μm. In one example, the fiber may be embodied as a polymer fiber, which can be connected to the optical waveguide 520 via a stainless steel fiber ferrule during the back-end connection process 700d. In some cases, the fiber may be embodied as a polymer fiber, which can be polished using, for example, 30-1 μm coarse sandpaper before being connected to the optical waveguide 520.

[0149] In some cases, the back-end connection process 700d may also include connecting an electrical connector (e.g., electrically grounded, operably grounded) to a tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c) located at or near the second end of the tapered fiber probe structure 510. For example, the electrical connector may be connected to a tetrode 740 (e.g., electrodes 742, 744, 746, 748 of each of tetrodes 740a, 740b, 740c) formed in the tapered micro preform structure 710, as referenced herein respectively in Figure 7A , Figure 7B and Figure 7CThe preform manufacturing process 700a, hot stretching process 700b, and hot tapering process 700c are shown in the diagram. In one example, the electrical connector can be electrically connected to the tetrode 540 (e.g., electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c) by heating the second end of the tapered fiber probe structure 510 to about 160°C, so as to melt a portion of the tetrode 540 (e.g., portions of electrodes 542, 544, 546, 548 of each of tetrodes 540a, 540b, 540c) in that region of the tapered fiber probe structure 510 to a desired molten state. The temperature (e.g., 160°C) is high enough to melt the electrodes 542, 544, 546, and 548 of each of the tetrodes 540 (e.g., electrodes 542, 544, 546, and 548 of each of the tetrodes 540a, 540b, and 540c), but low enough to avoid damaging the tapered fiber probe structure 510. In one example, each such electrical connector may be embodied as a copper wire (e.g., insulated copper wire) that can be inserted into one of the melting electrodes 542, 544, 546, and 548 of the tetrode 540 located at its second end of the tapered fiber probe structure 510. In some cases, the electrical connector (e.g., the copper wire) may be guided by a hypodermic needle as it descends into the melting electrodes 542, 544, 546, and 548. The second end of the tapered fiber probe structure 510 can then be cooled to allow the electrodes 542, 544, 546, and 548 and the electrical connector to solidify.

[0150] In some cases, the back-end connection process 700d may also include using UV epoxy resin to seal and secure at least one of the aforementioned electrical, microfluidic, or optical connections in place. By completing... Figure 7D The back-end connection process 700d shown herein, the multimode fiber optic probe device described herein can be equipped with an industry-standard adapter compatible with electrophysiological equipment, optical modules and drug delivery pumps.

[0151] Figure 8A and Figure 8B A view of another example multimode fiber optic probe device 800 (or "probe device 800") according to various aspects and embodiments of this disclosure is shown. Figure 8A A top view of an exemplary multimode fiber optic probe device 800 according to various aspects and embodiments of the present disclosure is shown. Figure 8B An isometric view of the tip region 850 of an example multimode fiber optic probe device 800 according to various aspects and embodiments of the present disclosure is shown. In the examples herein, the probe device 800 may be designed, embodied, and implemented as a flexible multimode nerve fiber probe device. For example, the probe device 800 may be designed, embodied, and implemented as a fiber optic photometry, drug delivery, photostimulation, and electrophysiology (P-DOpE) probe device described in the various embodiments herein.

[0152] Similar to probe devices 100 and 500, probe device 800 offers relatively higher complexity at the tip region compared to existing devices, while simplifying the connection between the rear connector region and external electronics that can be coupled to probe device 800. Furthermore, probe device 800 can be implemented to concurrently (e.g., simultaneously) perform various electrophysiological and fiber optic photometric measurements in a subject (e.g., a patient, human, or animal). For example, probe device 800 can be implemented to simultaneously perform electrophysiological and fiber optic photometric measurements in such a subject, thereby allowing cross-referencing of electrical and optical signals in the subject. Probe device 800 can be designed and embodied as the fiber optic P-DOpE probe device described herein, which has relatively high spatial and temporal resolution and is capable of detecting both electrical and chemical signals.

[0153] The probe device 800 is described herein and Figures 5A to 5C The example alternative embodiment of probe device 500 shown is illustrated below. Probe device 800 may include the same or similar structures, components, features, materials, and functions as probe device 500. The difference between probe device 800 and probe device 500 lies in the cross-sectional geometry of the fiber optic probe structure of probe device 800 (e.g., width (...)). w ) and thickness ( t The fiber optic probe structure is uniform from one end to the other, rather than tapered. Another difference between probe device 800 and probe device 500 is that probe device 800 includes a silica-based optical waveguide, rather than a polymer- or polycarbonate-based optical waveguide. Another difference between probe device 800 and probe device 500 is that the silica-based optical waveguide and tetrodes (e.g., electrodes of each tetrode) of probe device 800 have a relatively higher melting temperature compared to the polymer-based fiber optic probe structure of probe device 800, which integrates waveguides and tetrodes. This difference in melting temperature between the fiber optic probe structure and the probe components integrated therein allows probe device 800 to be manufactured in a different manner than probe device 500. This difference in melting temperature and manufacturing method allows the fiber optic probe structure of probe device 800 to have a uniform cross-section (e.g., width and thickness) extending from the first end to the second end of probe device 800.

[0154] Figure 8A and Figure 8BThe illustrated probe device 800 includes an optical fiber probe structure 810. The optical fiber probe structure 810 can be embodied and implemented as a flexible optical fiber probe structure as described in the examples herein. The optical fiber probe structure 810 may include one or more optical waveguides 820, one or more microfluidic channels 830, one or more tetrodes 840a, 840b, 840c (or "multiple tetrodes 840"), or any combination thereof. In the illustrated example, the optical fiber probe structure 810 includes a single silicon dioxide optical waveguide 820 and a single microfluidic channel 830. In this example, each tetrode 840 is embodied as and therefore includes electrodes 842, 844, 846, 848. For example, tetrode 840a is embodied and includes electrodes 842a, 844a, 846a, and 848a; tetrode 840b is embodied and includes electrodes 842b, 844b, 846b, and 848b; and tetrode 840c is embodied and includes electrodes 842c, 844c, 846c, and 848c. For clarity, in... Figure 8A and Figure 8B In this document, only individual electrodes 842a, 842b, and 842c are designated for tetrodes 840a, 840b, and 840c, respectively. The silicon dioxide optical waveguide 820, microfluidic channel 830, and tetrodes 840 (e.g., electrodes 842, 844, 846, 848) can be formed in the fiber optic probe structure 810 such that they are substantially parallel to the longitudinal axis of the fiber optic probe structure 810 and extend along the longitudinal axis of the fiber optic probe structure 810 from a first end (e.g., the first distal end) to a second end (e.g., the second distal end), as shown below. Figure 8A and Figure 8B As shown in the diagram. For example, the centerlines of the silicon dioxide optical waveguide 820, the microfluidic channel 830, and the tetrode 840 can be parallel to each other and coplanar or approximately coplanar along the longitudinal axis of the fiber optic probe structure 810 from the first end to the second end of the fiber optic probe structure 810.

[0155] The first and second ends of the fiber optic probe structure 810 can both be formed with a width ranging from, for example, about 70 μm to about 750 μm. w In one embodiment, both the first and second ends of the fiber optic probe structure 810 may have a width of approximately 500 μm. w The first and second ends of the fiber optic probe structure 810 can have a thickness ranging from, for example, about 70 μm to about 250 μm. t In one embodiment, the first and second ends of the fiber optic probe structure 810 may have a thickness of approximately 100 μm. t ).

[0156] In the example shown, the fiber optic probe structure 810 is embodied as having a rectangular shape and a rectangular cross-section. In various embodiments, the cross-section of the first end of the fiber optic probe structure 810 and the corresponding cross-section of the second end of the fiber optic probe structure 810 are both rectangular cross-sections. For example, the cross-section perpendicular to the longitudinal axis of the fiber optic probe structure 810, taken at or near the first end of the fiber optic probe structure 810, and the corresponding cross-section perpendicular to the longitudinal axis of the fiber optic probe structure 810, taken at or near the second end of the fiber optic probe structure 810, are both rectangular cross-sections in the example shown.

[0157] although Figure 8A and Figure 8B The fiber optic probe structure 810 shown is embodied in a rectangular shape and rectangular cross-section, but the scope of this disclosure is not limited thereto. In other examples, the fiber optic probe structure 810 may be embodied such that it has a circular cross-section, an annular cross-section, a triangular cross-section, a square cross-section, or a cross-section with other geometries. In some embodiments, the cross-section of the first end of the fiber optic probe structure 810 and the corresponding cross-section of the second end of the fiber optic probe structure 810 are both embodied in a circular cross-section, an annular cross-section, a triangular cross-section, a square cross-section, or a cross-section with other geometries.

[0158] The fiber optic probe structure 810 can be formed using one or more preform materials for manufacturing fiber optic probe structures, and therefore may include one or more preform materials for manufacturing fiber optic probe structures, such as at least one of polymer materials or polycarbonate (PC) materials. In some examples, the fiber optic probe structure 810 can be formed using one or more polymer or PC plates having grooves or channels into which optical waveguides and electrodes can be inserted, and wherein microfluidic channels can be formed as described in the examples herein. In some cases, the fiber optic probe structure 810 can be formed from a rectangular PC preform, which can be produced by milling or otherwise forming a plurality of grooves or channels in a PC plate. In one example, a first portion (e.g., a half) of each such groove or channel can be milled into a first PC plate, and a second portion (e.g., a half) of each such groove or channel can be milled into a second PC plate, such that when the first and second PC plates are positioned (e.g., stacked) to form the rectangular PC preform, the first and second portions of each groove or channel are aligned. In another example, the fiber optic probe structure 810 can be formed from a rectangular PC preform, which can be produced by milling or otherwise forming multiple grooves or channels in a PC board and stacking one or more additional PC boards on at least one side or surface of the PC board (e.g., the top or bottom side or surface) to form the rectangular PC preform. Any one or two of the aforementioned rectangular preforms can then be processed into micro-preforms, which can be used to produce the fiber optic probe structure 810, as further described in the examples herein.

[0159] The silica optical waveguide 820 can be configured and operable for controlling optogenetics. In some examples, the silica optical waveguide 820 can be embodied in or comprise at least one of silicon or silica materials. In some cases, the silica optical waveguide 820 can be embodied in at least one of silica fiber waveguide, silica fiber, silica-silica fiber, or another silica-based fiber. For example, the silica optical waveguide 820 can be embodied in or comprise a silica fiber having a silica glass core and a silica glass cladding with a refractive index lower than that of the silica glass core. In the illustrated example, the cross-sectional area of ​​the silica optical waveguide 820 at the first end of the fiber probe structure 810 is equal to the corresponding cross-sectional area of ​​the optical waveguide 820 at or near the second end of the fiber probe structure 810. For example, the size of the cross-sectional area of ​​the silica optical waveguide 820 at the first end of the fiber probe structure 810 is the same as or approximately the same as the size of the corresponding cross-sectional area of ​​the optical waveguide 820 at or near the second end of the fiber probe structure 810. For example, the cross-sectional area of ​​the silicon dioxide optical waveguide 820 is uniform or substantially uniform along its entire length. The silicon dioxide optical waveguide 820 may have a diameter ranging from, for example, about 5 μm to about 300 μm, but in some cases may depend on a diameter outside this range. In the example shown, the silicon dioxide optical waveguide 820 of the probe device 800 may have a diameter of about 50 μm.

[0160] The microfluidic channel 830 can be configured and operable to allow local drug infusion. In some cases, the microfluidic channel 830 can be formed as one of the grooves or channels that can be formed in the aforementioned rectangular PC preform, or formed by one of the grooves or channels that can be formed in the aforementioned rectangular PC preform, which can then be used to produce a miniature preform of the fiber optic probe structure 810, and ultimately produce the fiber optic probe structure 810. In other examples, the microfluidic channel 830 can be formed as a tube inserted into one of the grooves or channels, or formed by one of the tubes inserted into one of the grooves or channels, which can be formed in the aforementioned rectangular PC preform, which can be used to produce a miniature preform of the fiber optic probe structure 810, and ultimately produce the fiber optic probe structure 810 as described herein. For example, the microfluidic channel 830 can be formed as or formed by a PC tube having a 50 μm OD and a 25 μm inner diameter ID, although in some cases other OD and / or ID dimensions may be required. In one example, the cross-sectional area of ​​the microfluidic channel 830 is uniform or substantially uniform along its entire length. The microfluidic channel 830 may have a diameter ranging from, for example, about 5 μm to about 100 μm, but in some cases may depend on a diameter outside this range. In the example shown, the microfluidic channel 830 of the probe device 800 may have a diameter of about 75 μm.

[0161] The terelectrode 840 and electrodes 842, 844, 846, 848 can be configured independently or jointly and are operable to record extracellular voltage. In some cases, any one or all of electrodes 842, 844, 846, 848 may be formed using a bismuth-tin (BiSn) alloy, a nickel-chromium (NiCr) alloy, a stainless steel alloy, gold or a gold alloy, platinum or a platinum alloy, tungsten or a tungsten alloy, another material or alloy, or any combination thereof. In some examples, each of electrodes 842, 844, 846, 848 of each of the terelectrodes 840 is formed using one or more of the same materials. In other examples, at least one of electrodes 842, 844, 846, 848 of any terelectrode 840 may be formed using a material different from any material used to form at least one of the other electrodes 842, 844, 846, 848 of at least one of the other terelectrodes 840. In the example shown, the cross-sectional area of ​​each tetrode 840 at the first end of the fiber optic probe structure 810 is equal to the corresponding cross-sectional area of ​​the tetrode 840 at or near the second end of the fiber optic probe structure 810. For example, the size of the cross-sectional area of ​​each electrode 842, 844, 846, 848 of each tetrode 840a, 840b, 840c at the first end of the fiber optic probe structure 810 is the same as or approximately the same as the size of the corresponding cross-sectional area of ​​each electrode 842, 844, 846, 848 of each tetrode 840a, 840b, 840c at or near the second end of the fiber optic probe structure 810. For example, the cross-sectional area of ​​each of the tetrodes 840 (e.g., the cross-sectional area of ​​each electrode 842, 844, 846, 848 of each of the tetrodes 840a, 840b, 840c) is uniform or approximately uniform along its entire length. Any or all of electrodes 842, 844, 846, and 848 may have a diameter ranging from, for example, about 5 μm to about 100 μm, but in some cases may depend on another diameter outside this range. In the example shown, each of electrodes 842, 844, 846, and 848 of the probe device 800 may have a diameter of about 25 μm.

[0162] The probe device 800 also includes a tip region 850 positioned at a first end (e.g., a first distal end) of the fiber optic probe structure 810. The tip region 850 may include a tip that can be formed in various geometries (e.g., shape or surface shape), configurations (e.g., arrangement of probe components exposed at the surface of the tip), orientations (e.g., cut angles), and microscale dimensions (e.g., microscale cross-sections of the probe components exposed at the surface of the tip), as described in the examples herein. In the illustrated example, the tip of the tip region 850 is embodied as an angled tip 855. Either or both of the tip region 850 and the angled tip 855 may be defined and formed by a cross-section of at least one of the fiber optic probe structure 810, a silica optical waveguide 820, a microfluidic channel 830, a tetraode 840, or electrodes 842, 844, 846, 848. For example, the cross-section can be an angled cross-section, which can be formed at a set angle (θ) relative to the cross-section of the tip region 850 or the longitudinal axis of the fiber optic probe structure 810. In the example shown, the angled tip 855 can be formed at such a set angle (θ) relative to the cross-section of the tip region 850 or the longitudinal axis of the fiber optic probe structure 810.

[0163] In some examples, the tip of the tip region 850 may be a flat tip rather than an angled tip. In these examples, either or both of the tip region 850 and its tip may be defined and formed by a straight cross-section of at least one of the fiber optic probe structure 810, optical waveguide 820, microfluidic channel 830, or tetrode 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c). For example, the tip region 850 may be cross-sectioned at an angle perpendicular to the longitudinal axis of the fiber optic probe structure 810. In some cases, the tip of the tip region 850 may be a multi-angled tip with multiple outer (e.g., exposed) surfaces that have been cross-sectioned at different cutting angles relative to the cross-section of the tip region 850 or the longitudinal axis of the fiber optic probe structure 810. In these examples, one or more of the exposed surfaces of any one or all of the fiber optic probe structure 810, optical waveguide 820, microfluidic channel 830, or tetrode 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c) can be formed as at least one of these different cut angles at the tip of the tip region 850. The tip region 850, the angled tip 855, or both can be formed as at least one of various defined dimensions, such as, for example, a defined width or a defined thickness. In the example shown, the tip region 850 and the angled tip 855 are formed as the width of the fiber optic probe structure 810 (… wThe thickness is in the range of approximately 50 μm to approximately 750 μm. In one embodiment, the tip region 850, the angled tip 855, or both may have a width of approximately 500 μm. In the example shown, the tip region 850 and the angled tip 855 are formed to account for the thickness of the fiber optic probe structure 810. t The thickness is in the range of about 10 μm to about 250 μm. In one embodiment, the tip region 850, the angled tip 855, or both may have a thickness of about 100 μm.

[0164] The probe assembly 800 also includes a rear-end connector region 860 located at or near a second end (e.g., a second distal end) of the fiber optic probe structure 810. The rear-end connector region 860 can be configured and operable to connect one or more probe components of the fiber optic probe structure 810 to one or more devices external to and separate from the probe assembly 800. In the example shown, the rear-end connector region 860 can be configured and operable to provide connection between the silica optical waveguide 820, the microfluidic channel 830, and the tetrodes 840 (e.g., electrodes 842, 844, 846, 848 of each tetrode 840) and one or more devices external to and separate from the probe assembly 800.

[0165] The rear connector region 860 includes a rear portion (e.g., an exposed rear portion) of a silica waveguide 820 extending from the second end of the fiber optic probe structure 810. The rear portion of the silica waveguide 820 can be configured and operable (e.g., optically, communicatively, operably) coupled to an external optical component or device, such that the tip portion of the silica waveguide 820 at the first end of the fiber optic probe structure 810 can be (e.g., optically, communicatively, operably) coupled to such an external optical component or device. For example, the rear portion of the silica waveguide 820 can be configured and operable to be coupled to an external optical component or device, such that the exposed cross-sectional surface of the silica waveguide 820 at the angled tip 855 can be coupled to such an external optical component or device.

[0166] In some examples, the rear connector region 860 may also include an optical fiber coupled to the rear portion of the silica waveguide 820 at or near the second end of the optical fiber probe structure 810 (e.g., optically, communicatively, operably). In these examples, the optical fiber may be coupled to the rear portion of the silica waveguide 820 at or near the second end of the optical fiber probe structure 810, such that the tip portion of the silica waveguide 820 at the first end of the optical fiber probe structure 810 can be coupled to an external device (e.g., optically, communicatively, operably). For example, the optical fiber may be coupled to the rear portion of the silica waveguide 820 at or near the second end of the optical fiber probe structure 810, such that the exposed cross-sectional surface of the silica waveguide 820 at the angled tip 855 can be coupled to an external device (e.g., optically, communicatively, operably). For example, the optical fiber may be directly coupled to the rear portion of the silica waveguide 820 at or near the second end of the optical fiber probe structure 810. In some examples, the optical fiber may be embodied in or comprise at least one of silicon or silica materials. In some cases, the optical fiber may be embodied in at least one of silica optical fiber or cable or silica-silica optical fiber or cable, having a silica glass core and a silica glass cladding with a refractive index lower than that of the silica glass core. In one example, the optical fiber may have a diameter of 200 μm. In other examples, the back-end connector region 860 may also include an optical fiber connector. In one example, the optical fiber connector may be embodied in a stainless steel optical fiber ferrule. For example, the optical fiber connector may be embodied in a stainless steel optical fiber ferrule with an outer diameter of 1.25 mm. In one example, the optical fiber connector may be coupled to the back-end portion of the silica optical waveguide 820 at or near the second end of the optical fiber probe structure 810.

[0167] The rear connector region 860 also includes a microfluidic tube 835 coupled to the microfluidic channel 830 at or near the second end of the fiber optic probe structure 810 (e.g., fluidly and operatively). In various examples, the microfluidic tube 835 may be coupled to the rear portion of the microfluidic channel 830 at or near the second end of the fiber optic probe structure 810, such that the tip portion of the microfluidic channel 830 at the first end of the fiber optic probe structure 810 can be coupled to an external device (e.g., fluidly and operatively). For example, the microfluidic tube 835 may be coupled to the rear portion of the microfluidic channel 830 at or near the second end of the fiber optic probe structure 810, such that the open cross-section of the microfluidic channel 830 at the angled tip 855 can be coupled to an external device (e.g., fluidly and operatively). In the illustrated example, the microfluidic tube 835 is at least partially inserted into the microfluidic channel 830 at the second end of the fiber optic probe structure 810. In one example, the microfluidic tube 835 may be embodied as a polycarbonate (PC) tube. For example, the microfluidic tube 835 can be embodied as a PC tube with a 150 μm OD and a 75 μm ID, although in some cases other OD and / or ID dimensions may be required. In other examples, the rear connector region 860 may also include a fluid connector. In one example, a fluid connector may be coupled to the microfluidic tube 835.

[0168] The rear connector region 860 also includes a rear-end portion (e.g., an exposed rear-end portion) of a tetrode 840 extending from the second end of the fiber optic probe structure 810 (e.g., the exposed rear-end portions of electrodes 842, 844, 846, 848 of each of the tetrodes 840a, 840b, 840c). The rear-end portion of the tetrode 840 (e.g., the rear-end portions of electrodes 842, 844, 846, 848 of each of the tetrodes 840a, 840b, 840c) can be configured and operable for (e.g., electrical ground, communication ground, operably) to be coupled to an external electrical component or device, such that the tip portion of the tetrode 840 at the first end of the fiber optic probe structure 810 (e.g., the tip portions of electrodes 842, 844, 846, 848 of each of the tetrodes 840a, 840b, 840c) can (e.g., electrical ground, communication ground, operably) be coupled to such an external electrical component or device. For example, the rear end portion of the tetrode 840 can be configured and operable for connection to an external electrical component or device, such that the exposed cross-sectional surface of each tetrode 840 (e.g., the exposed cross-sectional surface of each electrode 842, 844, 846, 848 of each tetrode 840a, 840b, 840c) can be connected to such an external electrical component or device at the angled tip 855.

[0169] In some examples, the rear connector region 860 may further include one or more electrical connectors that are respectively coupled to one or more tetrodes 840 (e.g., electrodes 842, 844, 846, 848 coupled to one or more tetrodes 840) at or near the second end of the fiber optic probe structure 810. In these examples, each such electrical connector may be coupled (e.g., electrically, communicatively, operatively) to the rear portion of the tetrode 840 (e.g., to the rear portion of electrodes 842, 844, 846, 848 of the tetrode 840) such that the tip portion of the tetrode 840 at the first end of the fiber optic probe structure 810 (e.g., the tip portion of electrodes 842, 844, 846, 848 of the tetrode 840) may be coupled (e.g., electrically, communicatively, operatively) to an external device. For example, each electrical connector may be coupled at or near the second end of the fiber optic probe structure 810 to the rear end portion of each electrode 842, 844, 846, 848 of the tetrode 840, such that the exposed cross-sectional surface of the tetrode 840 at the angled tip 855 (e.g., the exposed cross-sectional surface of each electrode 842, 844, 846, 848 of the tetrode 840) can be coupled to an external device. In these examples, each such electrical connector may be directly coupled to one of the tetrodes 840 (e.g., coupled to electrodes 842, 844, 846, 848 of the tetrode 840). Any or all of such electrical connectors in these examples may be embodied as wires, such as, for example, copper wire. In one example, any or all of the electrical connectors may be embodied as insulated copper wire. In one example, any or all of the electrical connectors may be embodied as 42AWG copper wire. In other examples, the rear connector region 860 may also include one or more pin connectors, a PCB, or any combination thereof. In one example, one end of each of the above electrical connectors may be coupled to the rear end portion of the tetrode 840 (e.g., to the exposed rear end portion of each electrode 842, 844, 846, 848 of the tetrode 840) at or near the second end of the tapered fiber optic probe structure 810, and the other end of the electrical connector may be coupled to a pin connector. In another example, one end of each electrical connector may be coupled to the rear end portion of the tetrode 840 (e.g., to the exposed rear end portion of each electrode 842, 844, 846, 848 of the tetrode 840) at or near the second end of the tapered fiber optic probe structure 810, and the other end of the electrical connector may be coupled to a PCB.

[0170] In some cases, the probe device 800 may also include a sealant to seal the microfluidic tube 835 to the microfluidic channel 830. For example, the probe device 800 may include UV epoxy resin, which may be coupled to the second end of the fiber optic probe structure 810 and also to the microfluidic tube 835 and / or the aforementioned fluid connector. In some cases, the UV epoxy resin may also be coupled to any one or all of the aforementioned silicon dioxide optical waveguide 820, the aforementioned fiber optic connector or optical fiber, the rear end of the tetrode 840 (e.g., the rear end of electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c), the aforementioned electrical connector, pin connector, or PCB, or any combination thereof, to provide support for these components.

[0171] The probe device 800 can be manufactured in various sizes, geometries, configurations, or any combination thereof. In some cases, the probe device 800 can be manufactured such that the silica optical waveguide 820, the microfluidic channel 830, and / or the tetrode 840 (e.g., electrodes 842, 844, 846, 848) are juxtaposed within the fiber optic probe structure 810 according to different arrangements. For example, the probe device 800 can be manufactured such that the silica optical waveguide 820, the microfluidic channel 830, and / or the tetrode 840 (e.g., electrodes 842, 844, 846, 848) are arranged according to the description herein and respectively within... Figure 6A and Figure 6B The probe component arrangements 600a or 600b shown are juxtaposed within the fiber optic probe structure 810, or according to another probe component arrangement. In an example of manufacturing the probe device 800 according to either probe component arrangement 600a or 600b, a silicon dioxide optical waveguide 820 may be used in place of optical waveguide 520, and electrodes 842, 844, 846, and 848 may be used in place of electrodes 542, 544, 546, and 548.

[0172] The fiber optic probe structure 810 of the probe device 800 can be arranged according to any one or the other probe component arrangement 600a, 600b, by implementing the description herein and respectively in Figure 7A , Figure 7B and Figure 7C The preform manufacturing process 700a, hot stretching process 700b, and hot tapering process 700c shown herein are used to manufacture the preform. The probe device 800 as a whole can be manufactured by implementing the processes described herein and respectively in... Figure 7A , Figure 7B , Figure 7C and Figure 7D The preform is manufactured using the preform manufacturing process 700a, hot stretching process 700b, hot tapering process 700c, and rear-end connection process 700d shown in the figure.

[0173] In an example of implementing a thermal tapering process 700c to ultimately form an optical fiber probe structure 810, at 702c of the thermal tapering process 700c, a silicon dioxide optical waveguide 820 and a tetrode 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c) can respectively replace the optical waveguide 720 and the tetrode 740 (e.g., electrodes 742, 744, 746, 748 of each of tetrodes 740a, 740b, 740c) inserted into the corresponding channel 730 of the micro preform 709a. In these examples, at 704c of the thermal taper process 700c, a micro preform 709b having an inserted silicon dioxide optical waveguide 820 and tetrodes 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c) can be heated and pulled in the opposite direction as described herein. In these examples, the micro preform 709b can be heated and pulled until the material of the micro preform 709b (e.g., polymer or polycarbonate material) breaks in the reduced cross-sectional area 750 due to this heating and pulling. In these examples, the melting temperature of the silicon dioxide optical waveguide 820 and the tetrodes 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c) can be significantly higher than the melting temperature of the material of the micro preform 709b. Therefore, during 704c of the thermal tapering process 700c, when the material of the micropreform 709b fractures in the reduced cross-sectional region 750, portions of the silicon dioxide optical waveguide 820 and tetrodes 840 (e.g., electrodes 842, 844, 846, 848 of each tetrode 840a, 840b, 840c) located at or near the fracture point of the micropreform 709b can be exposed and extend from the fractured end of the micropreform 709b. In these examples, another location along the reduced cross-sectional region 750 generated in the micropreform 709b can be cut at 704c of the thermal tapering process 700c as described herein to produce an optical fiber probe structure 810. For example, one end of the reduced cross-sectional region 750 opposite the fractured end can be cut to form the tip region 850 of the optical fiber probe structure 810. For example, one end of the reduced cross-sectional region 750 opposite the fracture end can be cut with a cross-section 711 at a set angle (θ) to form an angled tip 855 of the fiber optic probe structure 810. In this example, portions of the silicon dioxide waveguide 820 and tetrode 840 (e.g., electrodes 842, 844, 846, 848 of tetrodes 840a, 840b, 840c) located at or near the fracture point of the micro preform 709b can also be cut to at least partially create the back-end connector region 860.

[0174] Figure 9A and Figure 9B A view of another example multimode fiber optic probe device 900 (or "probe device 900") according to various aspects and embodiments of this disclosure is shown. Figure 9A A top view of an exemplary multimode fiber optic probe device 900 according to various aspects and embodiments of the present disclosure is shown. Figure 9B A front view of the tip region 950 of an exemplary multimodal fiber optic probe device 900 according to various aspects and embodiments of the present disclosure is shown. In the examples herein, the probe device 900 can be designed, embodied, and implemented as a multimodal neural fiber probe device. For example, the probe device 900 can be designed, embodied, and implemented as a fiber optic photometry, drug delivery, photostimulation, and electrophysiology (P-DOpE) probe device described in the various embodiments herein. Similar to probe devices 100, 500, and 800, the probe device 900 provides relatively higher complexity at the tip region compared to existing devices, while also simplifying the connection between the rear connector region and external electronics that can be coupled to the probe device 900. Furthermore, the probe device 900 can be implemented to concurrently (e.g., simultaneously) perform various electrophysiological and fiber optic photometry operations in a subject (e.g., a patient, a person, an animal). For example, the probe device 900 can be implemented to simultaneously perform electrophysiological and fiber optic photometry in such a subject, thereby allowing cross-referencing of electrical and optical signals in the subject. The probe device 900 can be designed and embodied as the fiber optic P-DOpE probe device described herein, which has relatively high spatial and temporal resolution and is capable of detecting electrical and chemical signals.

[0175] The probe device 900 is described herein and Figure 8A The example alternative embodiment of probe device 800 shown in Figure 8C. Probe device 900 may include the same or similar structures, components, features, materials, and functions as probe device 800. The difference between probe device 900 and probe device 800 is that the cross-sectional geometry of probe device 900 is circular rather than rectangular. Another difference between probe device 900 and probe device 800 is that the tip region 950 of probe device 900 includes a flat tip rather than an angled tip. Another difference between probe device 900 and probe device 800 is the arrangement of the optical waveguide, microfluidic channel, and tetrode relative to each other in each such device. Another difference between probe device 900 and probe device 100 is the number of tetrodes in each such device.

[0176] Figure 9A and Figure 9BThe illustrated probe device 900 includes an optical fiber probe structure 910. The optical fiber probe structure 910 may include one or more optical waveguides 820, one or more microfluidic channels 830, one or more tetrodes 840, or any combination thereof. In the illustrated example, the optical fiber probe structure 910 includes a single silicon dioxide optical waveguide 820, a single microfluidic channel 830, and seven tetrodes 840a, 840b, 840c, 840d, 840e, 840f, and 840g. In this example, each tetrode 840 is embodied as and therefore includes electrodes 842, 844, 846, and 848. For example, tetrode 840a is represented and includes electrodes 842a, 844a, 846a, and 848a; tetrode 840b is represented and includes electrodes 842b, 844b, 846b, and 848b; tetrode 840c is represented and includes electrodes 842c, 844c, 846c, and 848c; tetrode 840d is represented and includes electrodes 842d, 844d, 846d, and 848d; tetrode 840e is represented and includes electrodes 842e, 844e, 846e, and 848e; tetrode 840f is represented and includes electrodes 842f, 844f, 846f, and 848f; and tetrode 840g is represented and includes electrodes 842g, 844g, 846g, and 848g. For clarity, in... Figure 9A Only tetrodes 840c and 840f and their corresponding electrodes 846 and 848 are shown. For clarity, [the remaining text is missing]. Figure 9B Only certain tetrodes 840 and their corresponding electrodes 842, 844, 846, and 848 are shown. The silicon dioxide optical waveguide 820, microfluidic channel 830, and tetrodes 840 (e.g., electrodes 842, 844, 846, and 848) can be formed in the fiber optic probe structure 910 such that they are juxtaposed around the longitudinal axis of the fiber optic probe structure 910 and extend along the longitudinal axis of the fiber optic probe structure 910 from a first end (e.g., the first distal end) to a second end (e.g., the second distal end), as shown. Figure 9A and Figure 9B As shown in the diagram, for example, a silica optical waveguide 820, a microfluidic channel 830, and a tetrode 840 (e.g., electrodes 842, 844, 846, and 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, and 840g) can be formed in the fiber optic probe structure 910 such that they are positioned at the same or different radial distances from the longitudinal axis (e.g., the center) of the fiber optic probe structure 910. In this example, the longitudinal axis of the fiber optic probe structure 910 is located at the center of the silica optical waveguide 820, and it extends in and out in a direction parallel to the axis "Z". Figure 9B The page.

[0177] In the example shown, the fiber optic probe structure 910 is embodied as having a cylindrical shape and a circular cross-section. In various embodiments, the cross-section of the first end of the fiber optic probe structure 910 and the corresponding cross-section of the second end of the fiber optic probe structure 910 are both embodied as circular cross-sections. For example, the cross-section perpendicular to the longitudinal axis of the fiber optic probe structure 910, taken at or near the first end of the fiber optic probe structure 910, and the corresponding cross-section also perpendicular to the longitudinal axis of the fiber optic probe structure 910, taken at or near the second end of the fiber optic probe structure 910, are both circular cross-sections in the example shown. Although Figure 9A and Figure 9B The fiber optic probe structure 910 shown is embodied in a cylindrical and circular cross-section, but the scope of this disclosure is not limited thereto. In other examples, the fiber optic probe structure 910 may be embodied such that it has a rectangular cross-section, an annular cross-section, a triangular cross-section, a square cross-section, or a cross-section with other geometries. In some embodiments, the cross-section of the first end of the fiber optic probe structure 910 and the corresponding cross-section of the second end of the fiber optic probe structure 910 are both embodied in a rectangular cross-section, a square cross-section, a triangular cross-section, or a cross-section with other geometries.

[0178] The fiber optic probe structure 910 includes an annular region 911 with an annular cross-section. In this example, the annular region 911 surrounds the silica optical waveguide 820 and extends from a first end to a second end of the fiber optic probe structure 910. For example, the annular region 911 surrounds the silica optical waveguide 820 and extends in and out of the fiber optic probe structure 910 from the first end to the second end in a direction parallel to the "Z" axis. Figure 9B The page. Figure 9A and Figure 9B In the illustrated probe component arrangement, the microfluidic channel 830 and each tetrode 840 (e.g., each electrode 842, 844, 846, 848 of each tetrode 840a, 840b, 840c, 840d, 840e, 840f, 840g) are positioned within an annular region 911 and extend from the first end of the fiber optic probe structure 910 through the annular region 911 to the second end. For example, the microfluidic channel 830 and each tetrode 840 (e.g., each electrode 842, 844, 846, 848 of each tetrode 840a, 840b, 840c, 840d, 840e, 840f, 840g) are positioned within the annular region 911 and extend in and out of the fiber optic probe structure 910 from the first end to the second end in a direction parallel to the "Z" axis. Figure 9B The page.

[0179] The fiber optic probe structure 910 may further include one or more partitioned regions positioned between at least two of any one of the following: a silicon dioxide optical waveguide 820, a microfluidic channel 830, or a tetrahedron 840 (e.g., electrodes 842, 844, 846, 848 in tetrahedrons 840a, 840b, 840c, 840d, 840e, 840f, 840g). For brevity, only certain partitioned regions of the fiber optic probe structure 910 are described herein, and for clarity, [the remaining text is incomplete and cannot be translated]. Figure 9A and Figure 9B The separation regions can extend along the entire length of the fiber optic probe structure 910, and they can isolate (e.g., physically) and insulate (e.g., electrically, optically, electromagnetically, chemically) these probe components from each other.

[0180] In the example shown, the fiber optic probe structure 910 includes a partition region 915a positioned within an annular region 911 between a silicon dioxide optical waveguide 820 and electrodes 842, 844, 846, and 848 of each tetrode 840 (e.g., electrodes 842, 844, 846, and 848 of each tetrode 840a, 840b, 840c, 840d, 840e, 840f, and 840g). In this example, the partition region 915a surrounds the silicon dioxide optical waveguide 820 and extends from a first end to a second end of the fiber optic probe structure 910. For example, the partition region 915a surrounds the silicon dioxide optical waveguide 820 and extends in and out of the fiber optic probe structure 910 from the first end to the second end in a direction parallel to the "Z" axis. Figure 9B The page. Separating region 915a isolates (e.g., physically) and insulates (e.g., electrically, optically, electromagnetically, chemically) the silicon dioxide optical waveguide 820 from the tetrode 840 (e.g., from the electrodes 842, 844, 846, 848 of each of the tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g), and vice versa. The partition region 915a includes material from one or more portions of at least one of the following: fiber optic probe structure 910 (e.g., a polymer or polycarbonate for forming the fiber optic probe structure 910), silica optical waveguide 820 (e.g., a cladding around the silica optical waveguide 820 and / or a coating, wrapping, sheath, or sleeve around the cladding), microfluidic channel 830 (e.g., a polymer or polycarbonate tube for forming the microfluidic channel 830), or tetrode 840 (e.g., an insulating coating, wrapping, sheath, or sleeve of one or more of the electrodes 842, 844, 846, 848 of any one or all of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g).

[0181] In the example shown, the fiber optic probe structure 910 also includes a partition region located in an annular region 911 between the microfluidic channel 830 and the tetrodes 840d, 840e (e.g., electrodes 842, 844, 846, 848 of each tetrode 840d, 840e). For example, the fiber optic probe structure 910 includes a partition region 915b located in the annular region 911 between the microfluidic channel 830 and the tetrode 840e (e.g., electrodes 842e, 848e of the tetrode 840e). In this example, the partition region 915b is located between these probe components and extends from a first end to a second end of the fiber optic probe structure 910. For example, the partition region 915b extends from the first end to the second end of the fiber optic probe structure 910 in a direction parallel to the "Z" axis. Figure 9B The page. Separating region 915b isolates (e.g., physically) and insulates (e.g., electrically, optically, electromagnetically, chemically) the electrodes 842, 844, 846, 848 of the tetrode 840e from the microfluidic channel 830. Separating region 915b includes material from one or more portions of at least one of the following: fiber optic probe structure 910 (e.g., a polymer or polycarbonate used to form the fiber optic probe structure 910), microfluidic channel 830 (e.g., a polymer or polycarbonate tube used to at least partially form the microfluidic channel 830), or tetrode 840e (e.g., an insulating coating, wrapping, sheath, or sleeve of one or both of the electrodes 842e, 848e). The fiber optic probe structure 910 in this example also includes additional separating regions located in annular regions 911 between pairs of tetrodes 840 (e.g., between electrodes 842, 844, 846, and 848 of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, and 840g). These additional separating regions isolate (e.g., physically) and insulate (e.g., electrically and electromagnetically) the pairs of tetrodes 840 (e.g., electrodes 842, 844, 846, and 848 of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, and 840g) from each other. The additional separation region includes material from one or more portions of at least one of the fiber optic probe structure 910 (e.g., a polymer or polycarbonate used to form the fiber optic probe structure 910) or tetrode 840 (e.g., an insulating coating, wrapping, sheath, or sleeve of any one or all of the electrodes 842, 844, 846, 848 of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g).

[0182] The fiber optic probe structure 910 can be formed using one or more preform materials for fabricating fiber optic probe structures, and therefore may include one or more preform materials for fabricating fiber optic probe structures, such as at least one of polymer materials or polycarbonate (PC) materials. In some examples, the fiber optic probe structure 910 can be formed using a polymer or polycarbonate rod having grooves or channels into which optical waveguides and tetrodes (e.g., electrodes of each tetrode) can be inserted, and where microfluidic channels can be formed as described in the examples herein. In some cases, one or more polymer or polycarbonate films can be wrapped around such polymer or polycarbonate rods and around optical waveguides, microfluidic channels, and tetrodes (e.g., electrodes of each tetrode) positioned within the rods to form a preform of the fiber optic probe structure 910. This preform can then be fabricated into a micropreform that can be used to produce a tapered fiber optic probe structure 110, as further described in the examples herein.

[0183] The silica optical waveguide 820 can be configured and operable to control optogenetics in the same or similar manner in each of the probe devices 800, 900. The silica optical waveguide 820 can also be embodied in each of the probe devices 800, 900 in the same or similar manner. In some cases, the silica optical waveguide 820 can be embodied in each of the probe devices 800, 900, comprising the same material and having the same dimensions. In other examples, the silica optical waveguide 820 can be embodied in each of the probe devices 800, 900, using one or more different materials or dimensions. In some examples, the silica optical waveguide 820 can be embodied in or comprise at least one of silicon or silica materials. In some cases, the silica optical waveguide 820 can be embodied in at least one of silica fiber waveguides, silica optical fibers, silica-silica optical fibers, or other silica-based optical fibers. For example, the silica optical waveguide 820 may be embodied in or comprise a silica optical fiber having a silica glass core and a silica glass cladding with a refractive index lower than that of the silica glass core. In the example shown, the cross-sectional area of ​​the silica optical waveguide 820 at the first end of the fiber optic probe structure 910 is equal to the corresponding cross-sectional area of ​​the optical waveguide 820 at or near the second end of the fiber optic probe structure 910. For example, the size of the cross-sectional area of ​​the silica optical waveguide 820 at the first end of the fiber optic probe structure 910 is the same as or substantially the same as the size of the corresponding cross-sectional area of ​​the optical waveguide 820 at or near the second end of the fiber optic probe structure 910. For example, the cross-sectional area of ​​the silica optical waveguide 820 is uniform or substantially uniform along its entire length. The silica optical waveguide 820 may have a diameter ranging, for example, from about 70 μm to about 300 μm, but in some cases, it may depend on another diameter outside this range. In the example shown, the silicon dioxide optical waveguide 820 of the probe device 900 can have a diameter of about 200 μm.

[0184] Microfluidic channels 830 can be configured and operable to allow local drug infusion in the same or similar manner in each of probe devices 800, 900. Microfluidic channels 830 can also be embodied in each of probe devices 800, 900 in the same or similar manner. In some cases, microfluidic channels 830 can be embodied in each of probe devices 800, 900 comprising the same material (e.g., PC tubing) and having the same dimensions. In other examples, microfluidic channels 830 can be embodied in having one or more different materials or dimensions in each of probe devices 800, 900. In some cases, microfluidic channels 830 can be formed as one of the grooves or channels that can be formed in the aforementioned PC rod, or formed by one of the grooves or channels that can be formed in the aforementioned PC rod, which can then be used to produce a miniature preform of fiber optic probe structure 910, and ultimately produce fiber optic probe structure 910. In other examples, the microfluidic channel 830 may be formed as a tube inserted into one of the grooves or channels formed in the aforementioned PC rod, or formed by a tube inserted into one of the grooves or channels formed in the aforementioned PC rod, which can be used to produce a miniature preform of the fiber optic probe structure 910 and ultimately produce the fiber optic probe structure 910 as described herein. For example, the microfluidic channel 830 may be formed as or from a PC tube having a 50 μm OD and a 25 μm inner diameter ID, although in some cases other OD and / or ID dimensions may be required. In one example, the cross-sectional area of ​​the microfluidic channel 830 is uniform or substantially uniform along its entire length. The microfluidic channel 830 may have a diameter ranging from, for example, about 5 μm to about 100 μm, but in some cases another diameter outside this range may be required. In the example shown, the microfluidic channel 830 of the probe device 900 may have a diameter of about 75 μm.

[0185] The tetrode 840 and electrodes 842, 844, 846, 848 may be configured independently or jointly and are operable to record extracellular voltages in the same or similar manner in each of the probe devices 800, 900. The tetrode 840 may also be embodied in each of the probe devices 800, 900 in the same or similar manner. In some cases, each of electrodes 842, 844, 846, 848 of each of the tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g may be embodied in each of the probe devices 800, 900, comprising the same material and the same dimensions. In other examples, at least one of the electrodes 842, 844, 846, 848 of one or more of the tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g may be embodied as having a material or size different from at least one of the other electrodes 842, 844, 846, 848 of the other tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g. In some cases, any or all of the electrodes 842, 844, 846, 848 may be formed using bismuth-tin (BiSn) alloy, nickel-chromium (NiCr) alloy, stainless steel alloy, gold or gold alloy, platinum or platinum alloy, tungsten or tungsten alloy, another material or alloy, or any combination thereof. In some examples, the electrodes 842, 844, 846, and 848 of each of the tetrodes 840a, 840b, 840c, 840d, 840e, 840f, and 840g are formed using the same one or more materials. In other examples, at least one of the electrodes 842, 844, 846, and 848 of any of the tetrodes 840a, 840b, 840c, 840d, 840e, 840f, and 840g can be formed using a material different from any material used to form at least one of the other electrodes 842, 844, 846, and 848 of at least one of the other tetrodes 840a, 840b, 840c, 840d, 840e, 840f, and 840g. In the example shown, the cross-sectional area of ​​each tetrode 840a, 840b, 840c, 840d, 840e, 840f, 840g at the first end of the fiber optic probe structure 910 is equal to the corresponding cross-sectional area of ​​the tetrode 840a, 840b, 840c, 840d, 840e, 840f, 840g at or near the second end of the fiber optic probe structure 910.For example, the cross-sectional area of ​​each electrode 842, 844, 846, 848 of each tetrode 840a, 840b, 840c, 840d, 840e, 840f, 840g at the first end of the fiber optic probe structure 910 is the same or approximately the same as the corresponding cross-sectional area of ​​each electrode 842, 844, 846, 848 of each tetrode 840a, 840b, 840c, 840d, 840e, 840f, 840g at or near the second end of the fiber optic probe structure 910. For example, the cross-sectional area of ​​each of the tetrodes 840 (e.g., the cross-sectional area of ​​each electrode 842, 844, 846, 848 of each of the tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g) is uniform or approximately uniform along its entire length. Any or all of electrodes 842, 844, 846, and 848 may have a diameter ranging from, for example, about 5 μm to about 100 μm, but in some cases may depend on another diameter outside this range. In the example shown, each of electrodes 842, 844, 846, and 848 of the probe device 900 may have a diameter of about 25 μm.

[0186] The probe device 900 also includes a tip region 950 positioned at a first end (e.g., a first distal end) of the fiber optic probe structure 910. The tip region 950 may include a tip that can be formed in various geometries (e.g., shape or surface shape), configurations (e.g., arrangement of probe components exposed at the surface of the tip), orientations (e.g., cleavage angles), and microscale dimensions (e.g., microscale cross-section of the probe components exposed at the surface of the tip), as described in the examples herein. In the illustrated example, the tip of the tip region 950 is embodied as a flat tip 955. Either or both of the tip region 950 and the flat tip 955 may be defined and formed by a cross-section of at least one of the fiber optic probe structure 910, a silica optical waveguide 820, a microfluidic channel 830, a tetrapter 840a, 840b, 840c, 840d, 840e, 840f, 840g, or electrodes 842, 844, 846, 848. For example, either or both of the tip region 950 and the flat tip region 955 can be defined and formed by a straight cross-section of at least one of the fiber optic probe structure 910, the optical waveguide 820, the microfluidic channel 830, or the tetrode 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g). For example, the tip region 950 can be cross-sectioned at an angle perpendicular to the longitudinal axis of the fiber optic probe structure 910 to form the flat tip 955.

[0187] In some examples, the tip of the tip region 950 may be embodied as an angled tip rather than a flat tip. In these examples, either or both of the tip region 950 and the angled tip may be defined and formed by an angled cross-section, which may be formed at a set angle (θ) relative to the cross-section of the tip region 950 or the longitudinal axis of the fiber optic probe structure 910. In some cases, the tip of the tip region 950 may be embodied as a multi-angled tip having multiple outer (e.g., exposed) surfaces that have been cross-cut at different angles relative to the cross-section of the tip region 950 or the longitudinal axis of the fiber optic probe structure 910. In these examples, one or more of the exposed surfaces of any one or more of the fiber optic probe structure 910, optical waveguide 820, microfluidic channel 830, or tetrode 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g) can be formed at at least one of these different cut angles at the tip of the tip region 950. The tip region 950, the flat tip 955, or both can be formed in various predetermined dimensions, such as, for example, a predetermined diameter ( D In one example, the tip region 950, the flat tip 955, or both may be formed with a diameter of approximately 50 μm. In another example, the tip region 950, the flat tip 955, or both may be formed with a diameter ranging from 50 μm to 750 μm. In yet another example, the tip region 950, the flat tip 955, or both may be formed with a diameter of approximately 750 μm. In some cases, the tip region 950, the flat tip 955, or both may be formed with a diameter less than 50 μm or greater than 750 μm.

[0188] The probe assembly 900 also includes a rear-end connector region 960 located at or near a second end (e.g., a second distal end) of the fiber optic probe structure 910. The rear-end connector region 960 can be configured and operable to connect one or more probe components of the fiber optic probe structure 910 to one or more devices external to and separate from the probe assembly 900. In the example shown, the rear-end connector region 960 can be configured and operable to provide connection between the silica optical waveguide 820, the microfluidic channel 830, and the tetraodes 840 (e.g., electrodes 842, 844, 846, 848 of each tetraode 840) and one or more devices external to and separate from the probe assembly 900.

[0189] The rear connector region 960 includes a rear portion (e.g., an exposed rear portion) of a silica waveguide 820 extending from the second end of the fiber optic probe structure 910. The rear portion of the silica waveguide 820 can be configured and operable (e.g., optically, communicatively, operably) coupled to an external optical component or device, such that the tip portion of the silica waveguide 820 at the first end of the fiber optic probe structure 910 can be (e.g., optically, communicatively, operably) coupled to such an external optical component or device. For example, the rear portion of the silica waveguide 820 can be configured and operable to be coupled to an external optical component or device, such that the exposed cross-sectional surface of the silica waveguide 820 at the flat tip 955 can be coupled to such an external optical component or device.

[0190] In some examples, the rear connector region 960 may also include an optical fiber coupled to the rear portion of the silica waveguide 820 at or near the second end of the optical fiber probe structure 910 (e.g., optically, communicatively, operably). In these examples, the optical fiber may be coupled to the rear portion of the silica waveguide 820 at or near the second end of the optical fiber probe structure 910, such that the tip portion of the silica waveguide 820 at the first end of the optical fiber probe structure 910 can be coupled to an external device (e.g., optically, communicatively, operably). For example, the optical fiber may be coupled to the rear portion of the silica waveguide 820 at or near the second end of the optical fiber probe structure 910, such that the exposed cross-sectional surface of the silica waveguide 820 at the flat tip 955 can be coupled to an external device (e.g., optically, communicatively, operably). For example, the optical fiber may be directly coupled to the rear portion of the silica waveguide 820 at or near the second end of the optical fiber probe structure 910. In some examples, the optical fiber may be embodied in or comprise at least one of silicon or silica materials. In some cases, the optical fiber may be embodied in at least one of silica optical fiber or cable or silica-silica optical fiber or cable, having a silica glass core and a silica glass cladding with a refractive index lower than that of the silica glass core. In one example, the optical fiber may have a diameter of 200 μm. In other examples, the back-end connector region 960 may also include an optical fiber connector. In one example, the optical fiber connector may be embodied in a stainless steel optical fiber ferrule. For example, the optical fiber connector may be embodied in a stainless steel optical fiber ferrule with an outer diameter of 1.25 mm. In one example, the optical fiber connector may be coupled to the back-end portion of the silica optical waveguide 820 at or near the second end of the optical fiber probe structure 910.

[0191] The rear connector region 960 also includes a microfluidic tube 835 coupled to the microfluidic channel 830 at or near the second end of the fiber optic probe structure 910 (e.g., fluidly and operatively). In various examples, the microfluidic tube 835 may be coupled to the rear portion of the microfluidic channel 830 at or near the second end of the fiber optic probe structure 910, such that the tip portion of the microfluidic channel 830 at the first end of the fiber optic probe structure 910 can be coupled to an external device (e.g., fluidly and operatively). For example, the microfluidic tube 835 may be coupled to the rear portion of the microfluidic channel 830 at or near the second end of the fiber optic probe structure 910, such that the open cross-section of the microfluidic channel 830 at the flat tip 955 can be coupled to an external device (e.g., fluidly and operatively). In the illustrated example, the microfluidic tube 835 is at least partially inserted into the microfluidic channel 830 at the second end of the fiber optic probe structure 910. In one example, the microfluidic tube 835 may be embodied as a PC tube with a 50 μm OD and a 25 μm ID, although in some cases other OD and / or ID dimensions may be required. In other examples, the rear connector region 960 may also include a fluid connector. In one example, a fluid connector may be coupled to the microfluidic tube 835.

[0192] The rear connector region 960 also includes a rear portion (e.g., an exposed rear portion) of a tetrode 840 extending from the second end of the fiber optic probe structure 910 (e.g., the exposed rear portion of electrodes 842, 844, 846, 848 of each tetrode 840a, 840b, 840c, 840d, 840e, 840f, 840g). The rear portion of the tetrode 840 (e.g., the rear portion of electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g) can be configured and operable for (e.g., electrical ground, communication ground, operably) to be connected to an external electrical component or device, such that the tip portion of the tetrode 840 at the first end of the fiber optic probe structure 910 (e.g., the tip portion of electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g) can (e.g., electrical ground, communication ground, operably) be connected to such an external electrical component or device. For example, the rear end portion of the tetrode 840 can be configured and operable for connection to an external electrical component or device, such that the exposed cross-sectional surface of each tetrode 840 (e.g., the exposed cross-sectional surface of each electrode 842, 844, 846, 848 of each tetrode 840a, 840b, 840c, 840d, 840e, 840f, 840g) can be connected to such an external electrical component or device at the flat tip 955.

[0193] In some examples, the rear connector region 960 may further include one or more electrical connectors that are respectively coupled to one or more tetrodes 840 (e.g., electrodes 842, 844, 846, 848 coupled to one or more tetrodes 840) at or near the second end of the fiber optic probe structure 910. In these examples, each such electrical connector may be coupled (e.g., electrically, communicatively, operatively) to the rear portion of the tetrode 840 (e.g., to the rear portion of electrodes 842, 844, 846, 848 of the tetrode 840) such that the tip portion of the tetrode 840 at the first end of the fiber optic probe structure 910 (e.g., the tip portion of electrodes 842, 844, 846, 848 of the tetrode 840) may be coupled (e.g., electrically, communicatively, operatively) to an external device. For example, each electrical connector may be coupled at or near the second end of the fiber optic probe structure 910 to the rear end portion of each electrode 842, 844, 846, 848 of the tetrode 840, such that the exposed cross-sectional surface of the tetrode 840 at the flat tip 955 (e.g., the exposed cross-sectional surface of each electrode 842, 844, 846, 848 of the tetrode 840) can be coupled to an external device. In these examples, each such electrical connector may be directly coupled to one of the tetrodes 840 (e.g., coupled to electrodes 842, 844, 846, 848 of the tetrode 840). Any or all of such electrical connectors in these examples may be embodied as wires, such as, for example, copper wire. In one example, any or all of the electrical connectors may be embodied as insulated copper wire. In one example, any or all of the electrical connectors may be embodied as 42AWG copper wire. In other examples, the rear connector region 960 may also include one or more pin connectors, a PCB, or any combination thereof. In one example, one end of each of the above electrical connectors may be coupled to the rear end portion of the tetrode 840 (e.g., to the exposed rear end portion of each electrode 842, 844, 846, 848 of the tetrode 840) at or near the second end of the tapered fiber optic probe structure 910, and the other end of the electrical connector may be coupled to a pin connector. In another example, one end of each electrical connector may be coupled to the rear end portion of the tetrode 840 (e.g., to the exposed rear end portion of each electrode 842, 844, 846, 848 of the tetrode 840) at or near the second end of the tapered fiber optic probe structure 910, and the other end of the electrical connector may be coupled to a PCB.

[0194] In some cases, the probe device 900 may also include a sealant to seal the microfluidic tube 835 to the microfluidic channel 830. For example, the probe device 900 may include UV epoxy resin, which may be coupled to the second end of the fiber optic probe structure 910 and also to the microfluidic tube 835 and / or the aforementioned fluid connector. In some cases, the UV epoxy resin may also be coupled to any or all of the following: the rear end portion of the silicon dioxide optical waveguide 820; the aforementioned fiber optic connector or optical fiber; the rear end portion of the tetrode 840 (e.g., the rear end portions of electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g); the aforementioned electrical connector; the pin connector; or any combination thereof of PCB, to provide support for these components.

[0195] The probe device 900 can be manufactured in various sizes, geometries, configurations, or any combination thereof. In some cases, the probe device 900 can be manufactured such that the silica optical waveguide 820, the microfluidic channel 830, and / or the tetrode 840 (e.g., electrodes 842, 844, 846, 848) are juxtaposed within the fiber optic probe structure 910 according to different arrangements. For example, the probe device 900 can be manufactured such that the silica optical waveguide 820, the microfluidic channel 830, and / or the tetrode 840 (e.g., electrodes 842, 844, 846, 848) are arranged according to... Figure 9B The probe components shown are arranged or, according to another probe component arrangement, are juxtaposed within the fiber optic probe structure 910.

[0196] Both the fiber optic probe structure 910 of probe device 900 and the fiber optic probe structure 810 of probe device 800 can be manufactured in the same or similar manner according to various probe component arrangements. For example, the fiber optic probe structure 910 of probe device 900 can be manufactured according to... Figure 9B The probe component arrangement shown or another probe component arrangement is described in accordance with the reference herein. Figure 8A and Figure 8B The fiber optic probe structure 810 is manufactured by implementing the preform manufacturing process 700a, the hot stretching process 700b, and the hot tapering process 700c in the same or similar manner as described herein. In another example, the probe device 900 as a whole can be manufactured by implementing the methods described herein. Figure 8A and Figure 8B The fiber optic probe structure 810 is manufactured using the preform manufacturing process 700a, the hot stretching process 700b, the hot tapering process 700c, and the back-end connection process 700d described herein.

[0197] In the example of implementing preform manufacturing process 700a to ultimately form fiber optic probe structure 910, according to Figure 9A and Figure 9BThe probe component arrangement of the probe device 900 shown can be formed by creating multiple channels 730 using polymer or PC rods (e.g., instead of plates) to form a cylindrical preform. In an example where a hot stretching process 700b is performed to ultimately form the fiber optic probe structure 910, the cylindrical preform produced by the preform manufacturing process 700a can be stretched into a cylindrical micro-preform with channels 730 corresponding to the probe component arrangement of the probe device 900.

[0198] In an example of implementing the thermal tapering process 700c to ultimately form the fiber optic probe structure 910, at 702c of the thermal tapering process 700c, the silicon dioxide optical waveguide 820 and the tetrode 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g) can be inserted into the corresponding channels 730 of the aforementioned cylindrical micro preform produced by the thermal stretching process 700b. In these examples, silicon dioxide optical waveguide 820 and tetrode 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g) can respectively replace optical waveguide 720 and tetrode 740 (e.g., electrodes 742, 744, 746, 748 of each of tetrodes 740a, 740b, 740c) inserted into the corresponding channel 730 of the cylindrical micro preform. In these examples, at 704c of the thermal taper process 700c, a cylindrical micropreform having an inserted silicon dioxide optical waveguide 820 and tetrodes 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g) can be heated and pulled in opposite directions as described herein. In these embodiments, the cylindrical micropreform can be heated and pulled until the material of the cylindrical micropreform (e.g., polymer or polycarbonate material) breaks in the reduced cross-sectional area 750 due to this heating and pulling. In these examples, the melting temperatures of the silicon dioxide optical waveguide 820 and the tetrode 840 (e.g., electrodes 842, 844, 846, and 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, and 840g) can be significantly higher than the melting temperatures of the material for the cylindrical micro preform. Therefore, during 704c of the thermal tapering process 700c, when the material of the cylindrical micropreform fractures in the reduced cross-sectional area 750, portions of the silicon dioxide optical waveguide 820 and tetrode 840 (e.g., electrodes 842, 844, 846, 848 of each of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g) located at or near the fracture point of the cylindrical micropreform can be exposed and extend from the fractured end of the cylindrical micropreform. In these examples, another location along the reduced cross-sectional area 750 generated in the cylindrical micropreform can be cut at 704c of the thermal tapering process 700c as described herein to produce an optical fiber probe structure 910. For example, one end of the reduced cross-sectional area 750 opposite the fractured end can be cut to form the tip region 950 of the optical fiber probe structure 910.For example, one end of the reduced cross-sectional region 750 opposite the fracture end can be cut with a straight cross-section to form the flat tip 955 of the fiber optic probe structure 910. In this example, portions of the silicon dioxide waveguide 820 and tetrode 840 (e.g., electrodes 842, 844, 846, 848 of tetrodes 840a, 840b, 840c, 840d, 840e, 840f, 840g) located at or near the fracture point of the cylindrical micro preform can also be cut to at least partially create the back-end connector region 960.

[0199] Figure 10 A multimode fiber optic probe device 1000 (or "probe device 1000") manufactured according to exemplary embodiments and aspects of this disclosure is shown. In the illustrated example, the probe device 1000 includes a tapered fiber optic probe structure 1010 having a tip region 1050 having an angled tip 1055. In this example, the probe device 1000 is described herein and Figure 1 The manufacturing embodiment of the probe device 100 shown is illustrated. In this example, the tapered fiber probe structure 1010, the tip region 1050, and the angled tip 1055 are manufacturing embodiments of the tapered fiber probe structure 110, the tip region 150, and the angled tip 155 of the probe device 100, respectively.

[0200] Figure 11A The image shows an image in an upright position according to various aspects and embodiments of this disclosure. Figure 10 An example embodiment of the probe device 1000. For example, Figure 11A An example embodiment of a tapered fiber optic probe structure 1010 of a probe device 1000 in a straight position is shown. Figure 11B The diagram illustrates a bent position according to various aspects and embodiments of this disclosure. Figure 10 An example embodiment of the probe device 1000. For example, Figure 11B An example embodiment of a tapered fiber optic probe structure 1010 of a probe device 1000 in a bent position is shown. Figure 11A and Figure 11B The illustrations depict the flexibility of the probe device 1000, for example, the flexibility of the tapered fiber probe structure 1010. The various multimode fiber probe devices and their corresponding fiber probe structures described herein can achieve [the following is a description of a specific type of fiber probe device / structure]... Figure 11A and Figure 11BThe probe device 1000 shown has the same or similar flexibility. For example, any of the manufacturing embodiments of probe devices 100, 500, or 800 can achieve the same or similar flexibility as probe device 1000. In one example, any of the manufacturing embodiments of probe devices 100, 500, 800, or 1000 can be bent to an angle of approximately 45° without damaging or impairing the function or integrity of such probe device. For example, any of the manufacturing embodiments of tapered fiber optic probe structure 110, tapered fiber optic probe structure 510, fiber optic probe structure 810, or tapered fiber optic probe structure 1010 can be bent to an angle of approximately 45° without damaging or impairing the function or integrity of such fiber optic probe structure.

[0201] Figure 12A Another example implementation of the probe device 1000 according to various aspects and embodiments of this disclosure is shown. For example, Figure 12A An example embodiment of the probe device 1000 is shown, wherein one or more optical fibers 1025, optical fiber connectors 1026, microfluidic tubes 1035, and connector electrodes 1045 (e.g., wires, pin connectors) are at least partially coupled to the rear connector region 1060 of the probe device 1000 via ultraviolet (UV) epoxy resin 1070. In this example, the probe device 1000 is described herein and Figure 1 The following is a manufacturing embodiment of the probe device 100 shown. In this example, the tapered fiber probe structure 1010, the tip region 1050, and the angled tip 1055 are manufacturing embodiments of the tapered fiber probe structure 110, the tip region 150, and the angled tip 155 of the probe device 100, respectively. In this example, the fiber 1025, the microfluidic tube 1035, the connector electrode 1045, and the rear connector region 1060 are embodiments of the fiber 125, the microfluidic tube 135, the connector electrode 145, and the rear connector region 1060 of the probe device 100, respectively. In this example, the fiber optic connector 1026 is an embodiment of the fiber optic connector described herein, such as, for example, a stainless steel fiber optic ferrule. In this example, the UV epoxy resin 1070 is an embodiment of the UV epoxy resin described herein.

[0202] Figure 12A An example of a fully connected multimode fiber optic probe device according to at least one embodiment described herein is shown. Figure 12A The probe device 1000 may include eight electrodes (e.g., electrode 140) respectively connected to eight connector electrodes 1045, eight microfluidic channels (e.g., microfluidic channel 130) respectively connected to eight microfluidic tubes 1035, and four optical waveguides (e.g., optical waveguide 120) respectively connected to four optical fiber connectors 1026 and / or four optical fibers 1025. Figure 12AThe probe device 1000 may include those described herein and Figure 1 The probe device 100 shown has the same properties, structure, components and functions. Figure 12A The probe device 1000 can be implemented by means of the present invention and in each Figure 4A , Figure 4B , Figure 4C and Figure 4A The preform is manufactured using the preform manufacturing process 400a, hot stretching process 400b, hot tapering process 400c, and rear-end connection process 400d shown in the figure.

[0203] Figure 12B Another example implementation of the probe device 1000 according to various aspects and embodiments of this disclosure is shown. For example, Figure 12B It is shown that, according to the description in this article and Figure 2A An example embodiment of a probe device 1000 manufactured with probe component arrangement 200a shown is illustrated. For example, Figure 12B An example embodiment of the probe device 1000 is shown, wherein an optical fiber connector 1026, a microfluidic tube 1035, and a printed circuit board (PCB) 1046 are at least partially coupled to the rear connector region 1060 of the probe device 1000 via UV epoxy resin 1070. In this example, the probe device 1000 is described herein and Figure 1 The manufacturing embodiment of the probe device 100 shown herein, and in accordance with the description herein and Figure 2A The probe component arrangement 200a shown is used for fabrication. In this example, the tapered fiber probe structure 1010, the tip region 1050, and the angled tip 1055 are respectively embodiments of the tapered fiber probe structure 110, the tip region 150, and the angled tip 155 of the probe device 100 fabricated according to the probe component arrangement 200a. In this example, the microfluidic tube 1035 and the rear connector region 1060 are respectively embodiments of one of the microfluidic tube 135 and the rear connector region 1060 of the probe device 100 fabricated according to the probe component arrangement 200a. In this example, the fiber optic connector 1026 is an embodiment of one of the fiber optic connectors described herein, such as, for example, a stainless steel fiber optic ferrule. In this example, the PCB 1046 is an embodiment of a PCB. In this example, the UV epoxy resin 1070 is an embodiment of the UV epoxy resin described herein.

[0204] Figure 12B Another example of a fully connected multimode fiber optic probe device according to at least one embodiment described herein is shown. Figure 12BThe probe device 1000 may include eight electrodes (e.g., electrode 140) connected to PCB 1046, a microfluidic channel (e.g., microfluidic channel 130) connected to microfluidic tube 1035, and an optical waveguide (e.g., optical waveguide 120) connected to optical fiber connector 1026 and / or optical fiber 1025. Figure 12B The probe device 1000 may include those described herein and Figure 1 The probe device 100 shown has the same properties, structure, components, and functions as described herein, and is consistent with the description and Figure 2A The probe components shown are manufactured in 200a. Figure 12B The probe device 1000 can be implemented by means of the present invention and in each Figure 4A , Figure 4B , Figure 4C and Figure 4D The preform is manufactured using the preform manufacturing process 400a, hot stretching process 400b, hot tapering process 400c, and rear-end connection process 400d shown in the figure.

[0205] Figure 13 A multimode fiber optic probe device 1300 (or "probe device 1300") manufactured according to various aspects and embodiments of the present disclosure is illustrated, along with an example implementation thereof. In the illustrated example, probe device 1300 includes a tapered fiber optic probe structure 1310 having a tip region 1350 with an angled tip 1355. In this example, probe device 1300 also includes a rear connector region 1360. In this example, probe device 1300 is described herein and Figures 5A to 5C The manufacturing embodiment of the probe device 500 shown is illustrated. In this example, the tapered fiber probe structure 1310, the tip region 1350, the angled tip 1355, and the rear connector region 1360 are manufacturing embodiments of the tapered fiber probe structure 510, the tip region 550, the angled tip 555, and the rear connector region 560 of the probe device 500, respectively.

[0206] Figure 13 An example embodiment of probe device 1300 is shown, wherein a fiber optic connector 1026, a microfluidic tube 1035, and a PCB 1046 are at least partially coupled to a rear connector region 1360 of probe device 1300 via UV epoxy resin 1070. In this example, microfluidic tube 1035 is an embodiment of one of the microfluidic tubes 535 of probe device 500. In this example, fiber optic connector 1026 is an embodiment of the fiber optic connector described herein, such as, for example, a stainless steel fiber optic ferrule. In this example, PCB 1046 is an embodiment of a PCB. In this example, UV epoxy resin 1070 is an embodiment of the UV epoxy resin described herein.

[0207] Figure 13 Another example of a fully connected multimode fiber optic probe device according to at least one embodiment described herein is shown. Figure 12B The probe device 1300 may include three tetrodes (e.g., tetrodes 540a, 540b, 540c), each tetrode having four electrodes (e.g., electrodes 542, 544, 546, 548) respectively connected to PCB 1046, a microfluidic channel (e.g., microfluidic channel 530) connected to microfluidic tube 1035, and an optical waveguide (e.g., optical waveguide 520) connected to optical fiber connector 1026 and / or optical fiber 1025. Figure 13 The probe device 1300 may include those described herein and Figures 5A to 5C The probe device 500 shown has the same properties, structure, components and functions. Figure 13 The probe device 1300 can be implemented by means of the present invention and in each Figure 7A , Figure 7B , Figure 7C and Figure 7D The preform is manufactured using the preform manufacturing process 700a, hot stretching process 700b, hot tapering process 700c, and rear-end connection process 700d shown in the figure.

[0208] Unless otherwise specified, disjunctive language such as the phrase “at least one of X, Y or Z” should be understood in context as generally used to refer to items, terms, etc., which may be X, Y or Z, or any combination thereof (e.g., X, Y and / or Z). Therefore, such disjunctive language is generally not intended and should not imply that some embodiments require the presence of at least one of X, at least one of Y, or at least one of Z.

[0209] As referenced herein, the term "user" means at least one of a person, end-user, consumer, computing device and / or program (e.g., processor, computing hardware and / or software, application), agent, machine learning (ML) model and / or artificial intelligence (AI) model, and / or another type of user who can realize and / or facilitate the realization of one or more embodiments of this disclosure as described herein, illustrated in the accompanying drawings, and / or included in the appended claims. As mentioned herein, the terms "includes" and "including" are intended to be inclusive in a manner similar to the term "comprising." As mentioned herein, the terms "or" and "and / or" are generally intended to be inclusive, that is, "A or B" or "A and / or B" are both intended to mean "A or B or both." As mentioned herein, the terms "first," "second," "third," etc., are used interchangeably to distinguish one component or entity from another and are not intended to indicate the location, function, or importance of the respective components or entities. As mentioned herein, the terms “couple,” “couples,” “coupled,” and / or “coupling” refer to chemical coupling (e.g., chemical bonding), communication coupling, electrical and / or electromagnetic coupling (e.g., capacitive coupling, inductive coupling, direct and / or connection coupling), mechanical coupling, operational coupling, optical coupling, and / or physical coupling.

[0210] It should be emphasized that the above embodiments of this disclosure are merely possible examples of implementation methods described for the purpose of clearly understanding the principles of this disclosure. Many variations and modifications can be made to the above embodiments without substantially departing from the spirit and principles of this disclosure. All such modifications and variations are intended to be included within the scope of this disclosure and protected by the following claims.

Claims

1. A multimode fiber optic probe device, comprising: A flexible tapered fiber optic probe structure includes a microscale tip region at a first end and a macroscale connector region at a second end opposite to the first end. An optical waveguide is positioned within the flexible tapered fiber probe structure and extends from the microscale tip region through the flexible tapered fiber probe structure to the macroscale connector region. as well as A microfluidic channel is formed in the flexible tapered fiber probe structure and extends from the microscale tip region through the flexible tapered fiber probe structure to the macroscale connector region.

2. The multimode fiber optic probe device according to claim 1, further comprising: The electrode is positioned in the flexible tapered fiber probe structure and extends from the microscale tip region through the flexible tapered fiber probe structure to the macroscale connector region.

3. The multimode fiber optic probe device according to claim 1, wherein, The microscale tip region is defined at least in part by a cross section of at least one of the flexible tapered fiber probe structure, the optical waveguide, or the microfluidic channel.

4. The multimode fiber optic probe device according to claim 3, wherein, The transverse section includes an angled transverse section formed at a set angle relative to the cross-section or longitudinal axis of the flexible tapered fiber optic probe structure.

5. The multimode fiber optic probe device according to claim 3, wherein, The microscale tip region includes an angled tip positioned at the first end of the flexible tapered fiber optic probe structure, the angled tip being formed at a set angle relative to the cross-section or longitudinal axis of the flexible tapered fiber optic probe structure.

6. The multimode fiber optic probe device according to claim 1, further comprising: The rear connector region is positioned adjacent to the macroscale connector region of the flexible tapered fiber probe structure, the rear connector region including a fiber optic connector connected to the optical waveguide and a microfluidic tube connected to the microfluidic channel.

7. The multimode fiber optic probe device according to claim 6, wherein, The microfluidic tube comprises a polycarbonate tube, and the optical fiber connector comprises a stainless steel optical fiber ferrule.

8. The multimode fiber optic probe device according to claim 2, further comprising: The rear connector region is positioned adjacent to the macroscale connector region of the flexible tapered fiber probe structure, the rear connector region including wires connected to the electrode.

9. The multimode fiber optic probe device according to claim 8, wherein, The rear connector area also includes pin connectors that connect to the wires.

10. The multimode fiber optic probe device according to claim 8, wherein, The rear connector area also includes a printed circuit board connected to the wires.

11. The multimode fiber optic probe device according to claim 2, wherein, The size or cross-sectional area of ​​the exposed portion of each of the optical waveguide, the microfluidic channel, and the electrode in the macroscopic connector region of the flexible tapered fiber probe structure is 10 to 30 times the corresponding size or cross-sectional area of ​​the exposed portion of each of the optical waveguide, the microfluidic channel, and the electrode in the microscopic tip region of the flexible tapered fiber probe structure.

12. The multimode fiber optic probe device according to claim 1, wherein, Each of the cross-sections of the microscale tip region and the corresponding cross-sections of the macroscale connector region of the flexible tapered fiber probe structure includes a rectangular cross-section, an annular cross-section, or a circular cross-section.

13. The multimode fiber optic probe device according to claim 1, wherein: The optical waveguide and the microfluidic channel are coaxially located within the flexible tapered fiber probe structure; as well as The optical waveguide extends from the microscale tip region of the flexible tapered fiber probe structure to the macroscale connector region around the microfluidic channel.

14. The multimode fiber optic probe device according to claim 13, wherein, The flexible tapered fiber probe structure includes an annular region surrounding the optical waveguide and extending from the microscale tip region of the flexible tapered fiber probe structure to the macroscale connector region, the annular region having an annular cross-section.

15. The multimode fiber optic probe device according to claim 14, further comprising: The electrode is positioned in the annular region and extends from the microscale tip region of the flexible tapered fiber probe structure through the annular region to the macroscale connector region.

16. The multimode fiber optic probe device according to claim 1, further comprising: An electrode is positioned within the flexible tapered fiber probe structure and extends from the microscale tip region of the flexible tapered fiber probe structure through the flexible tapered fiber probe structure to the macroscale connector region. The flexible tapered fiber probe structure includes a separation region located between the optical waveguide and the electrode, extending from the microscale tip region of the flexible tapered fiber probe structure to the macroscale connector region.

17. The multimode fiber optic probe device according to claim 1, further comprising: An electrode is positioned within the flexible tapered fiber probe structure and extends from the microscale tip region of the flexible tapered fiber probe structure through the flexible tapered fiber probe structure to the macroscale connector region. in: The flexible tapered fiber optic probe structure includes: a first separating region positioned between the optical waveguide and the microfluidic channel; and a second separating region positioned between the microfluidic channel and the electrode; and Both the first separator and the second separator extend from the microscale tip region of the flexible tapered fiber probe structure to the macroscale connector region.

18. The multimode fiber optic probe device according to claim 1, wherein, The flexible tapered fiber optic probe structure includes at least one of polymer material or polycarbonate material.

19. The multimode fiber optic probe device according to claim 1, wherein, The optical waveguide comprises a polycarbonate core and a poly(2-methyl methacrylate) cladding.

20. The multimode fiber optic probe device according to claim 2, wherein, The electrodes include bismuth-tin alloy electrodes, nickel-chromium alloy electrodes, stainless steel alloy electrodes, gold or gold alloy electrodes, platinum electrodes, or tungsten electrodes.

21. A method for manufacturing a multimode fiber optic probe device, the method comprising: Fluid channels and optical waveguides are formed in the preform material to produce the preform; The preform is subjected to a hot stretching process to produce a micro preform; A thermal tapering process is performed on the micro preform to create a reduced cross-sectional area on the micro preform; as well as The reduced cross-sectional area is transversely cut to produce a flexible tapered fiber probe structure, the flexible tapered fiber probe structure including a fluid channel and an optical waveguide, the fluid channel and the optical waveguide extending from a microscale tip region at a first end of the flexible tapered fiber probe structure through the tapered fiber probe structure to a macroscale connector region at a second end of the flexible tapered fiber probe structure.

22. The method of claim 21, further comprising: The fluid channel, the optical waveguide, and the electrode are formed in the preform.

23. The method according to claim 21, wherein, Transversely slicing the reduced cross-sectional region to create the flexible tapered fiber probe structure includes: The reduced cross-sectional area is transversely cut to create the microscale tip region at the first end of the flexible tapered fiber probe structure, the microscale tip region being at least partially defined by a cross-section of at least one of the flexible tapered fiber probe structure, the optical waveguide, or the fluid channel.

24. The method according to claim 21, wherein, Transversely slicing the reduced cross-sectional region to create the flexible tapered fiber probe structure includes: The reduced cross-sectional area is transversely cut at a set angle relative to the longitudinal axis of the reduced cross-sectional area to form the flexible tapered fiber optic probe structure with an angled tip.

25. The method of claim 21, further comprising: A back-end connector region is formed adjacent to the macroscopic connector region of the flexible tapered fiber probe structure.

26. The method of claim 25, wherein, The region forming the rear connector includes: Insert the polycarbonate tube into the fluid channel.

27. The method according to claim 25, wherein, The region forming the rear connector includes: Connect at least one of the following to the optical waveguide: an optical fiber connector, a stainless steel optical fiber ferrule, or an optical fiber.

28. The method according to claim 25, wherein, The region forming the rear connector includes: A wire is connected to an electrode formed in the flexible tapered fiber probe structure and extends from the microscale tip region of the flexible tapered fiber probe structure through the flexible tapered fiber probe structure to the macroscale connector region of the flexible tapered fiber probe structure; and Connect the pin connector to the wire.

29. The method according to claim 25, wherein, The region forming the rear connector includes: A wire is connected to an electrode formed in the flexible tapered fiber probe structure and extends from the microscale tip region of the flexible tapered fiber probe structure through the flexible tapered fiber probe structure to the macroscale connector region of the flexible tapered fiber probe structure; and Connect the printed circuit board to the wires.

30. The method according to claim 21, wherein, Forming the fluid channel and the optical waveguide in the preform includes: The fluid channel and the optical waveguide are formed in a polymer rod or a polycarbonate rod.

31. The method according to claim 22, wherein, Forming the fluid channel, the optical waveguide, and the electrode in the preform includes: Forming the fluid channel through the preform and along the longitudinal axis of the preform from the first end to the second end of the preform; The optical waveguide is formed coaxially around the fluid channel from the first end to the second end of the preform; and An electrode is formed through an annular region of the preform, the annular region surrounding the optical waveguide and extending from the first end of the preform to the second end.

32. The method according to claim 21, wherein, Performing the thermal tapering process includes: Heat at a set temperature is applied to the micro preform to soften at least a portion of each of the micro preform, the fluid channel, and the optical waveguide; and Pulling the first and second ends of the micro preform in opposite directions creates the reduced cross-sectional area of ​​the micro preform.

33. The method for manufacturing an optical fiber probe device according to claim 21, wherein, Performing the thermal tapering process includes: Adjust at least one of the speed or travel distance of the motors used to pull the first and second ends of the micro preform in opposite directions to produce the reduced cross-sectional area according to the set geometry.

34. The method according to claim 21, wherein, The optical waveguide comprises a polycarbonate core and a poly(2-methyl methacrylate) cladding.

35. The method according to claim 22, wherein, The electrodes include bismuth-tin alloy electrodes, nickel-chromium alloy electrodes, stainless steel alloy electrodes, gold or gold alloy electrodes, platinum electrodes, or tungsten electrodes.

36. A multimode fiber optic probe device, comprising: An optical fiber probe structure includes a first end and a second end opposite to the first end; A silica optical waveguide is positioned in the optical fiber probe structure and extends from the first end of the optical fiber probe structure through the optical fiber probe structure to the second end. as well as A tetrode is positioned within the fiber optic probe structure and extends from the first end of the fiber optic probe structure through the fiber optic probe structure to the second end.

37. The multimode fiber optic probe device according to claim 36, wherein, The tetrode includes: A first electrode, a second electrode, a third electrode, and a fourth electrode, each of which is positioned within the optical fiber probe structure and extends from the first end of the optical fiber probe structure through the structure to the second end.

38. The multimode fiber optic probe device according to claim 36, further comprising: A microfluidic channel is formed in the optical fiber probe structure and extends from the first end of the optical fiber probe structure through the optical fiber probe structure to the second end.

39. The multimode fiber optic probe device according to claim 36, further comprising: A tip region is formed at the first end of the fiber optic probe structure, the tip region being at least partially defined by a cross section of at least one of the fiber optic probe structure, the silicon dioxide waveguide, or the tetrode.

40. The multimode fiber optic probe device according to claim 36, further comprising: The rear connector region is positioned adjacent to the second end of the fiber optic probe structure, and the rear connector region includes: The rear end portion of the silicon dioxide optical waveguide extends from the second end of the optical fiber probe structure; and The rear end portion of the tetrode extends from the second end of the fiber optic probe structure.

41. The multimode fiber optic probe device according to claim 38, further comprising: The rear connector region is positioned adjacent to the second end of the fiber optic probe structure, and the rear connector region includes a microfluidic tube connected to the microfluidic channel.

42. The multimode fiber optic probe device according to claim 36, wherein, The melting temperature of at least one of the silicon dioxide optical waveguide or the tetrode is greater than the melting temperature of the optical fiber probe structure.

43. The multimode fiber optic probe device according to claim 36, wherein: The fiber optic probe structure includes a tapered fiber optic probe structure; as well as The size or cross-sectional area of ​​the second end of the fiber optic probe structure is 10 to 30 times the corresponding size or cross-sectional area of ​​the first end of the fiber optic probe structure.

44. The multimode fiber optic probe device according to claim 36, wherein, The fiber optic probe structure includes a uniform cross-sectional area from the first end to the second end of the fiber optic probe structure.

45. The multimode fiber optic probe device according to claim 36, wherein, Each of the cross-sections of the first end of the optical fiber probe structure and the corresponding cross-sections of the second end of the optical fiber probe structure includes a rectangular cross-section, an annular cross-section, or a circular cross-section.

46. ​​The multimode fiber optic probe device according to claim 36, wherein, The size or cross-sectional area of ​​the exposed portion of each of the silica waveguide and the tetrode at the second end of the fiber optic probe structure is 10 to 30 times that of the corresponding size or cross-sectional area of ​​the exposed portion of each of the silica waveguide and the tetrode at the first end of the fiber optic probe structure.

47. The multimode fiber optic probe device according to claim 36, wherein, The cross-sectional area of ​​the silica optical waveguide at the first end of the optical fiber probe structure is equal to the corresponding cross-sectional area of ​​the silica optical waveguide at the second end of the optical fiber probe structure.

48. The multimode fiber optic probe device according to claim 36, wherein, The cross-sectional area of ​​the tetrode at the first end of the fiber optic probe structure is equal to the corresponding cross-sectional area of ​​the tetrode at the second end of the fiber optic probe structure.

49. The multimode fiber optic probe device according to claim 36, wherein, The fiber optic probe structure includes at least one of a tapered fiber optic probe structure or a flexible fiber optic probe structure.

50. The multimode fiber optic probe device according to claim 36, wherein, The tetrode includes at least one of the following: bismuth-tin alloy electrode, nickel-chromium alloy electrode, stainless steel alloy electrode, gold or gold alloy electrode, platinum electrode, or tungsten electrode.

51. The multimode fiber optic probe device according to claim 36, wherein, The optical fiber probe structure includes at least one of polymer material or polycarbonate material.

52. The multimode fiber optic probe device according to claim 36, wherein, The fiber optic probe structure includes an annular region surrounding the silica optical waveguide and extending from the first end to the second end of the fiber optic probe structure, the annular region having an annular cross-section.

53. The multimode fiber optic probe device according to claim 52, wherein, The tetrode is positioned in the annular region and extends from the first end of the fiber optic probe structure through the annular region to the second end.

54. The multimode fiber optic probe device according to claim 53, further comprising: A microfluidic channel is formed in the annular region and extends from the first end of the fiber optic probe structure through the annular region to the second end.

55. The multimode fiber optic probe device according to claim 36, further comprising: A microfluidic channel is formed in the optical fiber probe structure and extends from the first end of the optical fiber probe structure through the optical fiber probe structure to the second end. The fiber optic probe structure includes a separation region that is positioned between the silicon dioxide waveguide and the tetrode and extends from the first end of the fiber optic probe structure to the second end.

56. The multimode fiber optic probe device according to claim 36, further comprising: A microfluidic channel is formed in the optical fiber probe structure and extends from the first end of the optical fiber probe structure through the optical fiber probe structure to the second end. in: The fiber optic probe structure includes a first partition region positioned between the silicon dioxide optical waveguide and the microfluidic channel, and a second partition region positioned between the microfluidic channel and the tetrode; and Both the first separator and the second separator extend from the first end of the fiber optic probe structure to the second end.

57. The multimode fiber optic probe device according to claim 36, further comprising: One or more additional tetrodes are positioned within the fiber optic probe structure and extend from the first end of the fiber optic probe structure through the fiber optic probe structure to the second end. Wherein, at least one electrode of any one of the one or more additional tetrodes comprises an electrode material different from the electrode material of each electrode of the tetrode.

58. The multimode fiber optic probe device according to claim 39, wherein, The transverse section includes an angled transverse section formed at a set angle relative to the cross-section or longitudinal axis of the fiber optic probe structure.

59. The multimode fiber optic probe device according to claim 39, wherein, The tip region includes an angled tip positioned at the first end of the fiber optic probe structure, the angled tip being formed at a set angle relative to the cross-section or longitudinal axis of the fiber optic probe structure.

60. The multimode fiber optic probe device according to claim 53, further comprising: One or more additional tetrodes are positioned in the annular region and extend from the first end of the fiber optic probe structure through the annular region to the second end.

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