Drug transport device

Abstract

According to an aspect of the present disclosure, a drug delivery device is presented, the device comprising: a laser-driven photoacoustic microfluidic pump (LDMP); an open-tubular capillary having a first end and a second end, the first end disposed in the LDMP, the open-tubular capillary configured to store a drug; and the LDMP configured to generate a fluid jet from the drug to transport the drug.

Description

Technical Field

[0001] This application relates to an apparatus and method for medical applications of laser-driven microfluidic pumps, particularly to medical applications of laser-driven photoacoustic microfluidic pumps.

[0002] [Cross-Reference to Related Applications] This application claims the benefit and priority of U.S. Provisional Patent Application No. 62 / 852,485, filed on May 24, 2019, the entire content of which is incorporated herein by reference.

Summary of the Invention

Means for Solving the Problems

[0003] This disclosure relates to an apparatus and method for medical applications of laser-driven photoacoustic microfluidic pumps. A drug delivery device according to an aspect of the disclosure is presented. The device includes a laser-driven photoacoustic microfluidic pump (LDMP), an optical fiber element having a first end and a second end, the first end being the optical fiber element disposed on the LDMP, and an open capillary having a first end and a second end, the first end being disposed on the optical fiber element, the open capillary being configured to store a drug. The LDMP is configured to generate a directional fluid jet from the drug and transport the drug.

[0004] In one aspect of the disclosure, the LDMP may include a substrate having a first side and a second side, and a layer of photoacoustic material disposed on the first side of the substrate. The layer of photoacoustic material may be configured to generate directional ultrasonic waves in response to a laser beam incident on the layer. The photoacoustic layer may include nanoparticles.

[0005] A tissue cutting device relating to the aspects of this disclosure is presented. The device comprises a LDMP, an optical fiber element having a first end and a second end, the first end of which is located in the LDMP, and a fluid comprising water, blood, plasma and / or body fluid. The fiber may be located in the fluid. The LDMP may be configured to generate a fluid jet from the fluid and cut the tissue.

[0006] In a certain aspect of this disclosure, the LDMP may comprise a substrate having a first side and a second side, and a layer of photoacoustic material disposed on the first side of the substrate. The layer of photoacoustic material may be configured to generate directional ultrasonic waves in response to a laser beam incident on the layer. The photoacoustic layer may comprise nanoparticles.

[0007] An apparatus for power washing sediment in an artery, comprising a LDMP and an optical fiber element having a first end and a second end, relating to the aspects of this disclosure. The first end is located in the LDMP. The second end is configured to be located in an artery. The artery contains a fluid. The fluid includes water, blood, plasma and / or body fluids. The LDMP is configured to generate a fluid jet from the fluid and remove sediment from the artery.

[0008] In view of this disclosure, the LDMP may comprise a substrate having a first side and a second side, and a layer of photoacoustic material disposed on the first side of the substrate. The layer of photoacoustic material may be configured to generate directional ultrasonic waves in response to a laser beam incident on the layer. The photoacoustic layer may comprise nanoparticles.

[0009] A method for transporting a drug to a tissue, relating to the aspects of this disclosure, is presented. The method comprises generating directional ultrasound based on a laser beam striking a LDMP, thermally expanding and contracting the photoacoustic layer in response to the laser beam striking the photoacoustic layer, and generating a directional fluid jet in a fluid medium. The LDMP comprises a substrate having a first side and a second side, and a layer of photoacoustic material disposed on the first side of the substrate. The layer of photoacoustic material is configured to generate directional ultrasound in response to a laser beam incident on the layer. The photoacoustic layer comprises nanoparticles. The medium comprises a drug stored in an open capillary having a first end and a second end. The first end is disposed in the LDMP. The open capillary is configured to store the drug.

[0010] Apparatus for increasing the flow rate from an LDMP is presented in relation to the aspects of this disclosure. The apparatus comprises an LDMP, an optical fiber element having a first end and a second end, the first end of which is located in the LDMP, a tube into which one end of the optical fiber is inserted, and a fluid comprising water, blood, plasma and / or body fluid. The optical fiber element is located in the fluid. The LDMP is configured to generate a powerful fluid jet that prevents backflow.

[0011] A method for precisely manipulating cells relating to the aspects of this disclosure is presented. The method comprises grasping cells using fluid tweezers, the fluid tweezers comprising a bidirectional LDMP. The method further comprises thermally expanding and contracting a layer of photoacoustic material in response to a laser beam striking the layer of photoacoustic material, and generating two directional fluid jets in a medium. The medium comprises cells manipulated by the fluid tweezers.

[0012] In view of this disclosure, the bidirectional LDMP comprises an optical fiber bending unit having a first end and a second end, and a layer of photoacoustic material disposed at the second end of the optical fiber. The layer of photoacoustic material is configured to generate directional ultrasonic waves in response to a laser beam incident on the layer of photoacoustic material. The layer of photoacoustic material comprises nanoparticles.

[0013] A method for destroying cerebral thrombi in relation to the aspects of this disclosure is presented. The method comprises generating a directional high-speed flow based on irradiating a LDMP with a laser beam. The method further comprises thermally expanding and contracting a layer of photoacoustic material in response to the laser beam striking the layer of photoacoustic material, and generating a directional fluid jet to the cerebral thrombus within a cerebral blood vessel.

[0014] In view of this disclosure, the LDMP comprises an optical fiber having a first end and a second end, and a layer of photoacoustic material disposed at the second end of the optical fiber. The layer of photoacoustic material is configured to generate directional ultrasonic waves in response to a laser beam incident on the layer of photoacoustic material. The layer of photoacoustic material comprises nanoparticles.

[0015] Further details and perspectives of typical embodiments of this disclosure are described below in more detail with reference to the attached figures. [Brief explanation of the drawing]

[0016] A better understanding of the features and advantages of the disclosed technology can be obtained by referring to the following detailed description, which specifies exemplary embodiments in which the principles of the technology are utilized, and the accompanying figures. [Figure 1A] This shows a quartz window into which gold ions have been implanted and a jet emitted from the window, relating to the aspects of this disclosure. [Figure 1B] This shows a quartz window into which gold ions have been implanted and a jet emitted from the window, relating to the aspects of this disclosure. [Figure 1C]Shows a quartz window implanted with gold ions and a jet emitted from the window according to the perspective of the present disclosure. [Figure 1D-G] Shows a quartz window implanted with gold ions and a jet emitted from the window according to the perspective of the present disclosure. [Figure 2A-D] Is a jet stream pattern by a micropump at various laser powers and spot sizes according to the perspective of the present disclosure. [Figure 3A-F] Shows a moving micropump and two micropumps according to the perspective of the present disclosure. [Figure 4A-F] Shows the generation of a jet by a single laser pulse according to the perspective of the present disclosure. [Figure 5A] Shows long-term photoacoustic oscillation excited by a single laser pulse according to the perspective of the present disclosure. [Figure 5B] Shows a schematic diagram of photoacoustic waves and streaming according to the perspective of the present disclosure. [Figure 6] Is a representative embodiment of a drug delivery device to tissue according to the perspective of the present disclosure. [Figure 7] Is a diagram of the optical fiber element of the device in FIG. 6. [Figure 8A] Is a diagram of the tip of the plane of the optical fiber element in FIG. 7. [Figure 8B] Is a diagram of the convex tip of the optical fiber element in FIG. 7. [Figure 8C] Is a diagram of the concave tip of the optical fiber element in FIG. 7. [Figure 9A] Is an image of laser streaming from a glass fiber according to the perspective of the present disclosure. [Figure 9B] Is an image of laser streaming from a glass fiber according to the perspective of the present disclosure. [Figure 9C] Is an image of laser streaming from a glass fiber according to the perspective of the present disclosure. [Figure 10A] Is a diagram of a catheter-based fluid pump according to the perspective of the present disclosure. [Figure 10B] Is a diagram of a catheter-based fluid pump according to the perspective of the present disclosure. [Figure 10C] A diagram of a catheter-based fluid pump according to an aspect of the present disclosure. [Figure 11] A diagram of a graving tool according to an aspect of the present disclosure. [Figure 12] A diagram of a jetting and cutting tool according to an aspect of the present disclosure. [Figure 13] A diagram of a remotely controlled injector according to an aspect of the present disclosure. [Figure 14] A diagram of a microfluidic chip according to an aspect of the present disclosure. [Figure 15] A diagram of a laser-driven optoacoustic microfluidic pump synthetic cell according to an aspect of the present disclosure.

[0017] Further details and aspects of various embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings.

Mode for Carrying Out the Invention

[0018] The present disclosure relates to devices and methods for medical applications of LDMP.

[0019] Although the present disclosure is described with respect to specific embodiments, it will be readily apparent to those skilled in the art that various modifications, rearrangements, and substitutions can be made without departing from the spirit of the present disclosure. The scope of the present disclosure is defined by the claims appended hereto.

[0020] To facilitate understanding of the principles of the present disclosure, reference is made to representative embodiments shown in the drawings, and specific terms are used to describe the same. It should be understood, however, that no limitation of the scope of the present disclosure is thereby intended. Any changes and further modifications of the features of the invention illustrated herein, as well as any additional applications of the principles of the present disclosure shown herein, will occur to those skilled in the relevant technical fields and those possessing the present disclosure, and are considered to be within the scope of the present disclosure.

[0021] The process of converting (or transforming) one form of energy into another is often called transduction. A transducer is a device commonly used to perform this function, and a transductor is characterized by the direction through which a physical system (e.g., pressure, temperature, sound waves, etc.) passes. For example, a sensor is a type of transducer that receives signals / stimuli from a physical system (e.g., temperature) and responds by generating an electrical signal that represents information about the physical system. An actuator, on the other hand, is a transducer that controls / generates a physical system (e.g., sound waves) in response to some electrical signal. For example, a speaker transforms an electrical signal of a recording into a mechanical sound wave.

[0022] As mentioned above, one form of energy can be transformed into another. These forms of energy may include, for example, mechanical energy, electrical energy, chemical energy, electromagnetic energy, thermal energy, and acoustic energy. Research is being conducted on transforming other forms of energy, such as transforming light energy (e.g., high-energy photons) into mechanical energy. Transforming light energy into some form of mechanical energy requires efficient momentum transfer, which is difficult to achieve. An efficient system capable of such transformations is desired.

[0023] Micropumps are divided into two groups based on their operating principle: mechanical and non-mechanical. Mechanical micropumps, developed in the 1980s with the advent of micro-electromechanical systems, are miniaturized macroscopic pumps that directly move fluids, consisting of moving parts such as valves and membranes. Non-mechanical micropumps have no moving parts, but require carefully manufactured microstructures and electrical contacts to generate thermal, electrical, magnetic, or acoustic stimuli to move the fluid. While the performance of micropumps has improved with advances in manufacturing technology, the principle and design of micropumps have remained largely the same for the past several decades. In various embodiments, micropumps do not require microfabrication or nanofabrication because they have no moving parts or electrodes. The size, number, position, and timing of micropumps may be remotely controlled, reconfigured, and programmed in real time. Pumps may feature a translucent plasmonic quartz window. Pumps may also be based on the principle of photoacoustic laser streaming, where ultrasonic waves generated by resonant laser pulses move the fluid via acoustic streaming. The entire surface of the quartz window may be covered with a plasmonic layer. Ultrasound can be generated from any position in the window, acting as a launching pad for the micropump.

[0024] Referring to Figures 1A-D, the quartz window 100 into which Au ions are implanted and the jets emitted from the window are shown. Figure 1A shows the ultraviolet-visible absorption spectrum of the quartz window 100 into which Au ions are implanted.

[0025] The photoacoustic launch pad emits Au ions at approximately 60 keV into a 0.5 mm thick quartz window 100, producing approximately 6 x 10⁻¹⁶ ions per square centimeter. 16The Au ions may be formed by implanting a certain amount of Au ions. Based on the selected acceleration voltage, the Au ions will be implanted within approximately 50 nm of the surface. Relatively large amounts may be used to obtain a sufficient concentration of Au nanoparticles and corresponding light absorption. Figure 1A also shows a schematic diagram of a quartz window 100 with the implantation region 102 positioned in the center of the quartz window 100. The absorption spectrum of Figure 1A shows a peak absorption 103 around 530 nm due to surface plasmon resonance of the Au clusters and nanoparticles.

[0026] Figures 1B and 1C show the setup for generating jets at different angles between the excitation laser beam and the quartz window into which the Au ions are implanted.

[0027] A hydrophone is a microphone used to record or listen to underwater acoustics. Most hydrophones are based on piezoelectric transducers, which generate an electrical potential when subjected to pressure changes such as sound waves.

[0028] To use the window as a launching pad for a micropump, for example, cuvette 106 may be filled with deionized water 108 that does not contain Au nanoparticles. Quartz 100 may be placed inside cuvette 106 (e.g., a 1-cm square glass cuvette) having an adjustable tilt angle. A pulsed laser 104 (e.g., a 527-nm pulsed laser with a pulse width of 150-ns) may be focused onto the quartz window 100 instead of the cuvette wall (using a lens with a focal length of 10-cm) to generate photoacoustic waves 107 and photoacoustic jets. Red fluorescent polymer microspheres 109 and a laser (e.g., a 633-nm HeNe laser) may be used to image the movement of the water 108 with a high-speed color camera 150. The photoacoustic waves 107 may be amplified by a preamplifier before being detected by a hydrophone 120 and subsequently recorded by a high-speed oscilloscope. A long-pass filter may be used to block the 527-nm light for flow imaging. The laser repetition frequency can be approximately 1000 Hz. Once a jet is generated by injecting laser pulses from any position on the window, the micropump is ready to operate.

[0029] Figures 1D-G show snapshots of the jet at incidence angles of 0°, 30°, 40°, and 50°. The dashed line indicates the window surface 100a in contact with the water. The transverse ray 170 is laser light from fluorescence from microspheres under excitation with green light of approximately 527 nm. The jet emitted from the quartz window 100 (Figure 1B) by this micropump always flows perpendicular to the window surface, regardless of the direction of the laser beam. From this observation, a simple conclusion is that the jet is not driven by momentum transfer from the incident photon. Since laser-induced heating of the Au-injected quartz layer and subsequent photothermal expansion are independent of the laser incidence angle, the observation of the jet perpendicular to the surface is consistent with the photoacoustic streaming mechanism and is not inconsistent with previous observations. On the other hand, this window-jet relationship allows the micropump to pump the fluid in the same direction without considering the direction of the laser beam. The direction of pumping can be changed by the orientation of window 100 (Figure 1B).

[0030] Referring to Figures 2A-D, the jet stream patterns produced by the micropump under different laser powers and spot sizes are shown. Figures 2A-C show the case where the laser spot size is 50 μm in diameter and the laser power is (A) 6.3 mW, (B) 10 mW, and (C) 40 mW. Figure 2D shows the case where the laser power is 330 mW and the spot size is approximately 300 μm × 50 μm.

[0031] There is a threshold laser power required to generate a jet. This was confirmed by the observations shown in Figures 2A-C. No streaming was observed at a low power of 6.3 mW, but significant streaming was observed at 10 mW, and even stronger at 40 mW. Firstly, from Figures 2B and 2C, it can be seen that jet velocity is a factor. Faster jets start with a smaller initial diameter and diverge less as they advance. Secondly, as shown by the broad yellow fluorescence path in Figure 2D, using a larger laser spot or micropump allows for the creation of a more collimated jet with less divergence at a distance, but the initial jet size remains small as in Figure 2C. These observations can be roughly understood from the jet streamline, as well as the interaction between the conservation of fluid mass, inertia, and acoustic emission forces. When a high-speed jet is fired from a window, water must be supplied from the surrounding area, so the jet originates from the center of the laser spot, and its initial size is much smaller than that of the laser spot. As the jet moves away from the window, its movement is governed by the fluid's inertia and acoustic radiation force. The larger the laser spot, the more parallel the ultrasound waves it generates, resulting in less divergence in the flow.

[0032] Referring to Figures 3A-C, snapshots of the streaming at 0, 1, and 2 seconds when the laser beam is moving downward at a speed of approximately 1 mm / s are shown. Horizontal arrows indicate the position of the laser spot, and vertical arrows indicate the direction of the laser spot's velocity. Figures 3D-F show streaming from two laser beams with different vertical laser powers.

[0033] The instantaneous operation of micropumps without the preparation of photoacoustic cavities allows for unprecedented freedom in creating micropump patterns and various fluid movements. For example, a swept micropump can be created by sweeping a laser beam (Figures 3A-C). Due to fluid inertia, a moving jet will not travel as far as a stable jet. To generate two micropumps / jets simultaneously, the beam can be split into two. Figures 3D-F show that two jets are generated by two beams, and the strength of each jet can be controlled independently by each beam. However, because the two jets are close together, if both are of the same strength, they will either merge into a wider jet (Figure 3E), or the weaker jet will be swallowed up by the stronger jet, as shown in Figures 3D and 3F. If each jet is considered a single fountain, all sorts of dancing fountains can be created simply by playing with a laser beam.

[0034] Referring to Figures 4A-F, the generation of a jet by a single laser pulse is shown. The long-pass filter has been removed so that the green light from the laser pulse can also be observed (Figures 4A, 4B, 4E, 4F). Time-series snapshots of fluid movement before and after the laser pulse. For example, the exposure time is approximately 10 mS. Arrow 403 in Figure 4B indicates the focused spot of the laser on the quartz plate. The bright white color of the microspheres is due to strong fluorescence and CC saturation (Figures 4C and 4D). Enlarged images of the regions indicated by frames A and B. Laser pulse energy: 0.5 mJ.

[0035] On-demand jet generation and controlled laser pulse generation further allow us to explore the pumping mechanism by examining the jet of a single laser pulse. Figure 4 shows a sequence of high-speed images of the fluid every 20 ms before and after the laser pulse strikes. From Figure 4A, we can see that the fluid is initially almost stationary. The fact that the fluid only begins to move when the laser pulse arrives is indicated by the green color of some of the tracing particles in Figure 4B. However, unlike the movement near the window in continuous streaming, the water near the window remains motionless. As indicated by the green box in Figure 4B, the region with the highest fluid velocity is about 1 mm away from the window. Figures 4E and 4F further show that after 40 mS, the fluid velocity decreases rapidly and becomes very small.

[0036] In addition to steady-state streamlining and average flow velocity, a detailed examination of the tracer particle trajectory provides more information about the particle's local instantaneous velocity along that trajectory. This is because the camera continuously records the particle's position during the 10ms exposure time for each image. The fluorescence intensity of a pixel is proportional to the time the particle remained in one position. For stationary particles, the fluorescence intensity of the pixel appears as a bright spot in the image. For fast-moving particles, the trace is darker due to the short exposure time. However, for slow-moving particles, the trace appears brighter due to the increasing exposure time for each pixel. In principle, since the total amount of fluorescence or scattered light is the same for the same exposure time, the integrated fluorescence intensity obtained from the particle trajectory is the same regardless of whether the particle is moving or not. This correlation can be seen in the trajectories in Figures 4A, 4E, and 4F. Tracer particles appear bright when stationary. In Figures 4E and 4F, the trajectory is darker on the left (starting point) and brighter on the right (ending point) because the flow is slowing down.

[0037] Refer to Figure 4B, particularly the two trajectories indicated by arrow 402. The trajectory begins as a green spot and a bright red, becoming darker in the first 1 / 5 of its path (indicated by the tip of arrow 402), but then becoming stronger. These color codes and intensity codes provide a clear picture of the jet's dynamics. The fluid begins to accelerate immediately after irradiation with the laser pulse, as revealed by the weak trajectory, and quickly reaches its maximum velocity. Subsequently, the fluid's velocity begins to decrease, as shown by the strong trajectory. An ultrasonic pulse is generated immediately upon the laser striking the quartz window, but it takes approximately 0.5 μS to reach the two tracing particles. This time delay is negligible compared to the total exposure time of 10 ms. According to the principle of acoustic streaming, the volume force acting on the fluid is proportional to the ultrasonic intensity and in the same direction as the ultrasonic propagation. Since the ultrasonic lasts for approximately 0.5 ms, it can be assumed that the fluid is accelerated during this time and reaches its maximum velocity at the end of the ultrasonic pulse. Because fluid decay begins after the ultrasonic pulse has passed, the green laser is seen first, followed by a short acceleration period and then a long deceleration period.

[0038] Referring to Figures 5A and 5B, diagrams illustrating the mechanism of photoacoustic micropumping are shown. A typical long-lasting photoacoustic oscillation is excited by a single laser pulse. The pressure converted from the hydrophone voltage signal is shown on the right axis. The hydrophone signal for the first 30 μS is shown in Figure 5A. Figure 5B shows a schematic diagram of the photoacoustic wave and streaming. The absorption of the incident laser causes the surface layer to thermally expand and mechanically vibrate, resulting in ultrasound. The streamline in Figure 5B is based on Figure 4E, approximately 20 ms after the laser pulse.

[0039] The mechanism is the same photoacoustic streaming as before, except that the Au nanoparticles / clusters are embedded in the surface layer of the quartz this time, rather than being added to the surface of the cuvette cavity. Here again, the key to the success of laser streaming is that a single laser pulse can generate ultrasound that lasts for a long time. Laser-induced heating and photothermal expansion of the embedded Au particles induce stress inside the quartz plate, causing ultrasonic vibrations of the quartz plate. Such localized surface vibrations and heating induce two-directional water vibrations: longitudinal vibrations perpendicular to the quartz surface and shear vibrations parallel to the surface. However, the shear motion of the plate does not propagate effectively through the liquid because it attenuates exponentially in the liquid, and the penetration distance at room temperature is usually less than 1 μm. Only the longitudinal vibrations of the quartz plate propagate effectively through the liquid. These vibrations induce longitudinal ultrasound in the liquid, resulting in a liquid jet perpendicular to the plate surface.

[0040] LDMPs are produced by ion implantation of gold atoms (or other metal atoms) into quartz, glass, or other transparent solid substrates. The size of the substrate may be small, for example, sub-millimeter size. Gold may be implanted into a large, thin substrate. The thin substrate may then be diced into small-sized LDMPs.

[0041] The size of the system may depend on the application. For example, millimeter-sized systems may be used for endoscopic surgery inside the stomach, while sub-millimeter-sized systems may be used for applications in the arteries of the heart. This small LDMP may be mounted (attached, bonded, or fused) to the optical fiber that carries the laser to the LDMP, generating a fluid jet. Metal atoms can be injected directly into the tip of the optical fiber, so that the tip becomes the head of the fluid jet as the laser travels through the fiber to reach the head.

[0042] The fluid may consist of water, blood, plasma, body fluids, or any other fluid, depending on the medical or surgical application. The jet's cross-section is estimated to be less than 0.1 mm in diameter, and the velocity of the jet fluid can reach several cm / sec, depending on the output of the laser that induces the fluid jet forward.

[0043] Referring to Figure 6, a drug delivery device 600 to tissue is shown. This device may comprise an LDMP 680, an optical fiber element 604, and an open-tube capillary 602 positioned on the optical fiber element 604 or the LDMP 680. The optical fiber element 604 comprises a first end portion 604a and a second end portion 604b. The first end portion 604a may be positioned on the LDMP 680. The open-tube capillary 602 comprises a first end portion 602a and a second end portion 602b. The first end portion 602a may be positioned on the optical fiber element 604. The open-tube capillary may be configured to store the drug 608a in a reservoir 608. The LDMP 680 may be configured to generate a directional fluid jet from the drug 608a and deliver the drug 608a. The fluid jet may comprise a gas and / or liquid, but is preferably intended to be a liquid.

[0044] The fluid drug may be stored in an open-tube capillary 602, one end of which is attached to the LDMP680. The liquid jet containing the drug may be directed towards the target area for transport. Alternatively, a small cavity may be pre-drilled in the target area by a laser beam before the drug is transported by the fluid jet. If the same laser can be used for drilling and jetting, it can help with alignment. For example, the size of the target area may be as small as 0.1 mm to 2 mm. It is also conceivable that the laser may be scanned over a larger area.

[0045] A fluid jet stream can be used as a tool for cutting tissue. The fluid jet stream may puncture thin membranes. A fluid jet stream may be used to peel off thin layers of tissue membranes. The power may be adjusted to make the jet stream stronger or weaker. The optical fiber element 604 with the LDMP680 attached may be combined with an endoscope set. For example, by directing the fluid jet stream towards unwanted tissue, the laser jet may be used to target and cut cancer cells.

[0046] A fluid jet stream may be used to cleanse inflamed tissue before drug delivery. The fluid jet stream may also be used as a small plow to loosen disease-causing deposits in arteries. When the optical fiber element 604 is nearly parallel to the artery, the jet stream direction becomes a glancing angle. A filter may be used to filter out small plagues.

[0047] The laser may have any wavelength in the range of approximately 180 nm to 1 mm. The fiber may have a diameter ranging from about a fraction of a micron to several millimeters or more.

[0048] Fiber-based photoacoustic devices can perform drug delivery or other functions within the human body. For example, ultrasound via a fiber can circulate blood or bodily fluids, or move drugs around tumors in the body. For instance, ultrasound can also directly target tissues such as kidney stones.

[0049] Referring to Figures 8A-C, the end face 605 of the optical fiber element 604 may have a flat surface 605a, a dimpled (concave) surface 605c, or a convex shape 605b. For example, a convex shape 605b can be used for laser defocusing. A concave shape 605c may be used to focus the laser onto a small target area.

[0050] Figures 9A–C illustrate laser streaming from a glass fiber in relation to the aspects of this disclosure. Figure 9A shows an experimental demonstration of laser streaming from a gold-impregnated glass fiber (d=80μm). The surface of one end of the glass fiber is impregnated with approximately 2 × 10¹⁷ / cm² of gold at 60KeV (Figure 9A). When a 10-¹⁵mW pulsed (150nm) laser with a wavelength of 527nm strikes the other end, laser streaming occurs from the gold-impregnated glass fiber (Figure 9B). The laser pushes particles out of the glass tube (Figure 9C). These types of pumps offer many advantages over other mechanical pumps, including, but not limited to, being non-contact flow, thus reducing cell damage and thrombosis caused by conventional mechanically based pumps, being very small, and being able to drive fluids wherever laser energy is available, and / or not requiring electrical or mechanical energy transfer for operation.

[0051] Figures 10A–C illustrate catheter-based fluid pumps in relation to the aspects of this disclosure. The use of laser light as a power source enables very flexible, small profile tools that can establish or enhance fluid flow within the body. These operate similarly to “ramjet” engines, where fluid is delivered to a chamber within a hollow tube and accelerated by an LDMP pump (e.g., single, multiple, and / or positioned in multiple parts of the lumen). This flow may be modified in several ways to enhance the effectiveness of the application. For example, such a flow rate may be adjusted by the amount of light from laser 1002 by providing a constant flow rate (Figure 10A). Pulsating flow may be created to simulate the physiological activity of the heart. This may be achieved by circulating laser 1002 on or off. In addition, ultrasonic or hypersonic fluid circulation may also be created to enhance specific tool activities, such as thrombectomy. For example, multidirectional flow may be created by adjusting the direction of laser 1002. This may include creating vortices 1005 to enhance specific applications (Figure 10B). The design of these pumps is intended to include various fluid inlets and outlets and / or multiple windows 1006 to optimize for various applications (Figure 10C). For example, a method for disrupting cerebral thrombi may comprise generating a directional, high-speed flow based on directing a laser beam to an LDMP. The LDMP comprises an optical fiber having a first end and a second end, and a layer of photoacoustic material positioned at the second end of the optical fiber. The layer of photoacoustic material is configured to generate directional ultrasound in response to a laser beam incident on the layer. The layer of photoacoustic material may comprise nanoparticles. The method may further comprise thermally expanding and contracting the layer of photoacoustic material in response to the laser beam striking the layer of photoacoustic material to generate a directional liquid jet for cerebral thrombosis within the cerebral blood vessels.

[0052] Figure 11 shows a grabbing tool 1100 in relation to the aspects of this disclosure. A flexible catheter 1106 may be used when the flow is reversed within a hollow tube 1004, thereby providing suction capability (e.g., an LDMP suction catheter). For example, the grabbing tool 1100 may be used to grasp cells and / or tissues 1110. The grabbing tool 1100 may be used as a very small and delicate suction tool that can be delivered to multiple parts of the body. Alternatively, the grabbing tool 1100 may be used in research to manipulate cells and / or tissues 1110, and even intracellular elements.

[0053] For example, a grabbing tool can function as a fluid tweezers for manipulating cells. The fluid tweezers may include a LDMP, which comprises an optical fiber bending unit having a first end and a second end, and a layer of photoacoustic material positioned at the second end of the optical fiber. The layer of photoacoustic material may be configured to generate directional ultrasound in response to a laser beam irradiated onto the layer of photoacoustic material. The layer of photoacoustic material comprises nanoparticles. The layer of photoacoustic material may be configured to thermally expand and contract in response to a laser beam striking the layer of photoacoustic material, thereby generating two directional fluid jets in a medium (e.g., a liquid medium) containing cells to be manipulated by the fluid tweezers.

[0054] Figure 12 is a diagram of a jetting and / or cutting tool 1200 relating to the aspects of this disclosure. The jetting and / or cutting tool 1200 generally comprises a flexible hollow tube 1004 configured as a fluid reservoir, an LDMP 1204, one or more fluid windows 1202, and a pressure valve 1206 for generating a high-speed jet flow 1208. A jetting and / or cutting tool 1200 using fluid accelerated by an LDMP pump ("LDMP jet") would be superior to existing "hydrojet" knives because of its very small size and flexibility. The jetting and / or cutting tool 1200 may also be equipped with the use of ambient fluid and / or fluid in a chamber. At very high flow rates, or oscillating flow rates (e.g., high rates and high frequencies), such a tool can cut tissue or small cellular structures.

[0055] Figure 13 is a diagram of a remotely controlled injector 1300 relating to the aspects of this disclosure. The remotely controlled injector 1300 generally comprises a catheter 1304, and located within the catheter 1304 are an LDMP 1302, a payload 1306 (e.g., a drug), a pressure valve 1308 configured to regulate pressure, and a payload ejector 1310. The payload 1306 may, after being encapsulated, be activated and actively pumped into a body area or cells. The remotely controlled injector 1300 may be used, for example, in cell therapy where the delivery of a specific drug needs to be carried out in a very small size, or in activities such as in vitro fertilization or gene therapy where small amounts of material can be injected into cells.

[0056] Figure 14 shows a microfluidic chip 1400 relating to the aspects of this disclosure. The microfluidic chip 1400 may comprise a mixing chamber 1402 with an LDMP mixer 1404 for mixing two or more fluids. Microfluidics may be used for scientific research and drug development. The LDMP pump 1406 may generate fluid movement in the microfluidic circuit, for example, through a catheter (a) or directly embedded in the circuit (b). The mixing chamber may be used to facilitate a chemical reaction, and the mixing is induced by the fluid flow induced by the LDMP (c).

[0057] Figure 15 shows LDMP-synthesized cells 1502 as relating to the aspects of this disclosure. By embedding gold particles 1506 into the lipid structure of the cells, an external laser 1504 can be used to move and manipulate these cells 1502.

[0058] The embodiments disclosed herein are examples of the disclosure and may be embodied in various forms. For example, certain embodiments herein are described as separate embodiments, but each embodiment herein may be combined with one or more other embodiments herein. Certain structural and functional details disclosed herein should not be construed as limiting, but rather as representative grounds for the claims and for teaching those skilled in the art to employ various approaches to the disclosure in virtually any appropriately detailed structure. Similar reference numerals may refer to similar or identical elements throughout the description of the figures.

[0059] The phrases “in one embodiment,” “in one embodiment,” “in various embodiments,” “in some embodiments,” or “in other embodiments” may each refer to one or more of the same or different embodiments relating to this disclosure. The phrase A or B means “(A), (B), or (A and B).” The phrase at least one of A, B, or C means “(A); (B); (C); (A and B); (A and C); (B and C); or (A, B, and C).”

[0060] Any method, program, algorithm, or code described herein can be translated or expressed in a programming language or computer program. As used herein, the terms “programming language” and “computer program” include, but are not limited to, any language used to specify instructions to a computer, and encompass the following languages ​​and their derivatives: assembler, BASIC, batch file, BCPL, C, C++, Delphi, Fortran, Java, JavaScript, machine code, operation system command language, Pascal, Perl, PL1, scripting languages, Visual Basic, metalanguages ​​that themselves represent programs, and all computer languages ​​of the first, second, third, fourth, fifth, or later generations. Databases and other data schemas, and any other metalanguages, are also included. There is no distinction between interpreted, compiled, or languages ​​that use both compiled and interpreted approaches. There is no distinction between compiled versions and source versions of programs. Therefore, if a programming language can exist in multiple states (source, compiled, object, link, etc.), a reference to a program refers to any and all of such states. A reference to a program may also include the actual instructions and / or the intent of those instructions.

[0061] It should be understood that the foregoing description is merely illustrative of the present disclosure. Various alternatives and modifications can be devised by those skilled in the art without departing from the present disclosure. Accordingly, the present disclosure is intended to encompass all such alternatives, modifications and differences. The embodiments described with reference to the accompanying drawings are presented solely to illustrate specific examples of the present disclosure. Other elements, steps, methods and techniques substantially different from those described above and / or in the accompanying claims are also intended to be within the scope of the present disclosure.

Claims

1. A drug transport device, Laser-driven photoacoustic microfluidic pump (LDMP), An optical fiber element having a first end and a second end, wherein the first end is arranged in the LDMP, An open capillary having a first end and a second end, wherein the first end is arranged on the optical fiber element, and the open capillary is configured to store a drug, and Equipped with, The optical fiber element is positioned between the LDMP and the drug stored in the open capillary. The aforementioned LDMP is, To generate directional ultrasound based on the laser beam directed towards the LDMP, The directional ultrasonic waves generated by the LDMP are propagated through the optical fiber element to generate a directional fluid jet from the drug. A device configured to transport the aforementioned drug.

2. The aforementioned LDMP is, A substrate having a first side and a second side, A layer of photoacoustic material disposed on the first side of the substrate and Equipped with, The photoacoustic material layer is configured to generate directional ultrasonic waves in response to the laser beam incident on the photoacoustic material layer. The apparatus according to claim 1, wherein the layer of photoacoustic material comprises nanoparticles.

Images