Combined biological sampling and injection assembly and related devices, systems, and methods

Abstract

A sampling device includes a container having a body defining a chamber and an opening leading to the chamber. A diaphragm is engaged with the container to cover the opening and hermetically seal the chamber. The diaphragm has an adhesive layer having a first thickness and including material for adhering to the edge of the container to hermetically seal the container. A metal foil layer having a second thickness is attached to the adhesive layer. A resilient layer having a third thickness is attached to the metal foil layer to position the metal foil layer between the adhesive layer and the resilient layer. The third thickness is greater than the sum of the first and second thicknesses.

Description

[0001] Cross-referencing

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 192,480, filed May 24, 2021, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The subject matter described in this application relates to apparatus, systems, and methods for injecting substances into the aqueous humor and vitreous humor of the eye, and for sampling the aqueous humor and vitreous humor of the eye. The intravitreal injection and sampling apparatus of this application has specific, but not exclusive, uses for the diagnosis and treatment of human ophthalmic diseases. Background Technology

[0004] Vitreous fluid is a colorless, gel-like liquid within the eye or eyeball of humans or other vertebrates. It consists of approximately 98-99% water and trace amounts of hyaluronic acid, glucose, anions, cations, ions, and a fine network of collagen. Vitreous fluid provides support to the structures surrounding the eye, absorbs mechanical trauma, and facilitates the circulation and regulation of oxygen, metabolites, and nutrients. It is primarily produced by ciliary body cells. Age-related structural changes in the vitreous humor are crucial in the pathogenesis of many vitreoretinal diseases.

[0005] Intraocular pressure (IOP) quantifies the pressure of the vitreous fluid inside the eye. Many people suffer from conditions associated with chronically elevated IOP, such as glaucoma. Over time, elevated IOP can damage the optic nerve, leading to vision loss.

[0006] Currently, the treatment of eye diseases primarily involves the regular administration of medications to the eyes. These medications can be delivered via, for example, intravitreal injections. Intravitreal injections are one of the most common surgical procedures in ophthalmology today. Various medications are delivered directly into the clear vitreous gel that supports the eyeball. These medications act directly on the vitreous body or surrounding retinal tissue for the next few months. For example, intravitreal injections are a common route for the delivery of vascular endothelial growth factor inhibitors (anti-VEGF) proteins, which are highly potent compounds that are tolerated at high doses and have an intravitreal half-life of approximately one week. Anti-VEGF biologics and steroids are the most commonly used medications via this route. These medications can be administered long-term.

[0007] A recommended procedure for intravitreal injection includes: preparing the needle, local anesthesia and disinfection of the ocular surface, keeping the eye open using a speculum or other device, selective lateral dislocation of the conjunctiva at the injection site, inserting the needle a few millimeters from the limbus to approximately the full depth of the needle, injecting the medication, withdrawing the needle, and allowing the conjunctiva to cover the injection site. Post-injection care typically includes basic verification of functional vision, such as asking the patient to count the number of fingers shown by the doctor. This functional test verifies that the acute increase in intraocular pressure (IOP) induced by the injection has not caused any impact on the optic nerve head that requires immediate relief.

[0008] Another important ophthalmic procedure is vitrectomy. Vitreous sampling can provide information for all aspects of eye care. The cellular contents and extracellular structures of the vitreous sample can be analyzed through histological or immunological analysis. For example, histology can provide a definitive diagnosis of the type of infection causing endophthalmitis.

[0009] Current identification of immune cell types and the characterization of expressed immune mediator proteins can inform the treatment of uveitis. The determination of the amount of VEGF present in the vitreous can indicate the likelihood of impending angiogenesis or the likelihood that VEGF compounds are causing observed angiogenesis. Unresponsiveness to anti-VEGF therapy remains one of the most troublesome aspects of treating angiogenesis in exudative, age-related vascular degeneration (also known as wet AMD), and diabetic retinopathy.

[0010] Two common methods of vitreous sampling—using a cutter or needle aspiration—serve largely the same purpose for protein analysis. State-of-the-art microcutting tools can be delivered using a 23-gauge cannula. Needle aspiration can be performed using needles as small as 30 gauge (approximately half the diameter of a 23-gauge needle). Fine gauges can increase the possibility of dry aspiration and / or modify the properties of the aspirated material by acting as a filter. The advantage of small gauges is that no traction is introduced on the gel matrix, as the gel matrix cannot be pulled into the small needle hole. Vitreous samples are often frozen or otherwise stabilized so that they can be handled in a laboratory setting outside of the operating room or ophthalmology office environment.

[0011] Injecting therapeutic doses of medication into the aqueous humor or vitreous fluid inside the eye can increase intraocular pressure (IOP) by up to 25 mmHg, significantly exceeding the threshold level considered potentially harmful. There is evidence that, although such increases in IOP are temporary, they are actually associated with iatrogenic glaucoma, causing significant loss of nerve fiber layers and visual function in patients with "normal" resting IOP after only a few treatments. See “Anterior chamber paracentesis during intravitreal injections in observational trials: effectiveness, safety and effects,” International Journal of Retina and Vitreous, 5, 8 (2019) (Saxena, S., Lai, TY, Koizumi, H., et al.). Therefore, it is sometimes necessary to remove small amounts of fluid (whether aqueous humor, vitreous fluid, or both) from the eye before injecting a substantial amount of medication. However, removing a certain amount of bodily fluids may lead to insufficient pressure, which can also be harmful to the eyes.

[0012] Therefore, in cases of diagnostic sampling of body fluids, it may be necessary or beneficial to inject a certain volume of fluid (whether drug-containing or otherwise) to replace the aspirated fluid. In any case, care must be taken to ensure that the volume removed and the volume injected are comparable; and, in any case, two separate procedures (sampling and injection) are usually required.

[0013] The information contained in the background section of this specification, including any references cited herein and any descriptions or discussions thereof, is included for technical reference purposes only and is not considered as subject matter as defined by the scope of this application. Summary of the Invention

[0014] This document discloses apparatus, components, and sub-components for performing biosampling and injection procedures. The components may include: a syringe containing, or configured to contain, a liquid drug or agent; an adapter; a working barrel; and a sample container positioned within the working barrel. The sample container or chamber may include a cylindrical body and at least one multilayer diaphragm providing an airtight seal for at least one opening of the cylindrical body. The multilayer construction of the diaphragm may include a layer of metal foil and an elastic layer to reduce gas permeability and maintain a vacuum inside the sample container. The assembly performs biosampling and drug injection by progressively moving the drug-eluting syringe, such that a biological sample is obtained when the syringe is moved to a first position within the barrel, and a drug is injected when the syringe is moved to a second position within the barrel. In some aspects, the combined biosampling and injection assembly can be controlled by a physician with one hand, thereby improving efficiency and reducing procedural complexity.

[0015] Examples of sampling devices may include a container and an opening, wherein the container has a body defining a chamber. The sampling device also includes a diaphragm that engages with the container at the opening to hermetically seal the chamber. The diaphragm includes an adhesive layer formed of a material configured to adhere to the edge of the container to provide an hermetically tight seal. A metal foil layer is coupled to the adhesive layer. An elastic layer is coupled to the metal foil layer to position the metal foil layer between the adhesive layer and the elastic layer.

[0016] On the other hand, whether considered alone or in combination with any other aspect, the adhesive layer may have a first thickness, the metal foil layer may have a second thickness, and the elastic layer may have a third thickness. The third thickness is greater than the sum of the first and second thicknesses.

[0017] On the other hand, considered alone or in combination with any other aspect, the opening of the container is a distal opening. The container also includes a proximal opening. In some embodiments, the sampling device further includes a proximal diaphragm bonded to the container at the proximal opening. The proximal diaphragm includes an adhesive layer formed of a material configured to adhere to the proximal edge of the container to provide an hermetically tight seal with the container. A metal foil layer is attached to the adhesive layer of the proximal diaphragm. An elastic layer is attached to the metal foil layer of the proximal diaphragm to position the metal foil layer of the proximal diaphragm between the adhesive layer and the elastic layer of the proximal diaphragm. The adhesive layer may include a thermally activated material that, when heat is applied, engages with the edge of the container. The adhesive layer may include an adhesive.

[0018] Another example provides a system for using a syringe to obtain a biological sample and deliver a drug to a patient. The system includes a barrel having a hollow body defining an internal region. An adapter is positioned within the internal region and has a proximal connector configured to engage the adapter with a distal end of the syringe. A first diaphragm is disposed at the distal end of the adapter. An evacuated container is slidably received within the internal region away from the adapter, and the evacuated container includes a body defining a chamber configured to receive a biological sample and an opening extending into the chamber. A second diaphragm covers the opening. Bilateral needles have a proximal end and a distal end, wherein the proximal end is disposed within the barrel away from the evacuated container, while the distal end is positioned for injection into a patient. The evacuated chamber within the barrel is movable to a first position, such that the proximal end of the needle is positioned within the chamber to draw a biological sample from the patient into the chamber, and is also movable to a second position, in which the proximal end of the needle passes completely through the evacuated chamber and through the first diaphragm to deliver a drug from the syringe to the patient.

[0019] On the other hand, whether considered alone or in combination with any other aspect, the evacuated container can move relative to the cylinder in the same direction to reach the first and second positions.

[0020] On the other hand, considered alone or in combination with any other aspect, the container opening is a distal opening, and the second diaphragm includes an adhesive layer having a material configured to adhere to the distal edge of the container to provide an airtight seal. A metal foil layer is attached to the adhesive layer of the second diaphragm. An elastic layer is attached to the metal foil layer of the second diaphragm to position the metal foil layer of the second diaphragm between the adhesive layer and the elastic layer of the second diaphragm.

[0021] On the other hand, considered alone or in combination with any other aspect, the adhesive layer has a first thickness, the metal foil layer has a second thickness, and the elastic layer has a third thickness. The third thickness is greater than the sum of the first and second thicknesses.

[0022] On the other hand, considered alone or in combination with any other aspect, the evacuated container also includes a third diaphragm, which engages with the container at a distal opening opposite and aligned with the proximal port to cover the proximal opening. The third diaphragm includes an adhesive layer having a material configured to adhere to the proximal edge of the container to provide an airtight seal. A metal foil layer is bonded to the adhesive layer of the third diaphragm. An elastic layer is bonded to the metal foil layer of the third diaphragm. The metal foil layer of the third diaphragm is disposed between the adhesive layer and the elastic layer of the third diaphragm.

[0023] On the other hand, considered alone or in combination with any other aspect, the adhesive layer of the third diaphragm has a fourth thickness, the metal foil layer of the third diaphragm has a fifth thickness, and the elastic layer of the third diaphragm has a sixth thickness. The sixth thickness is greater than the sum of the fourth and fifth thicknesses.

[0024] On the other hand, whether considered alone or in combination with any other aspect, the adapter has an O-ring surrounding the periphery of the adapter. The outer diameter of the O-ring corresponds to the inner diameter of the cylinder.

[0025] On the other hand, whether considered alone or in combination with any other aspect, the cylinder also includes a tactile feature in the internal area that mates with an O-ring to indicate that the evacuated container is in the first position.

[0026] On the other hand, whether considered alone or in combination with any other aspect, the proximal end of the double-sided needle has a beveled opening.

[0027] On the other hand, considered alone or in combination with any other aspect, the cylinder defines the longitudinal axis, and at least the proximal ends of the bilateral needles are offset from the longitudinal axis. The beveled opening is configured such that when the second diaphragm of the evacuated container is perforated, the proximal portions of the bilateral needles deflect toward the longitudinal axis.

[0028] In another example, an adapter for connection to a syringe is provided. The adapter includes a receiver configured to receive a portion of the syringe. A proximal connector on the receiver is configured to mate with a corresponding connector feature of the syringe. The proximal connector is a first-type connector. The proximal connector includes a channel extending along the needle axis. A diaphragm disposed at the distal end of the receiver is configured to mate with a needle assembly including a second-type connector. The second-type connector differs from the first-type connector.

[0029] On the other hand, whether considered alone or in combination with any other aspect, the receiver has a columnar body with at least one side window extending through the columnar body.

[0030] On the other hand, whether considered alone or in combination with any other aspect, the proximal connector includes a female luer-lock connector, and the diaphragm includes a multi-puncture septum.

[0031] On the other hand, whether considered alone or in combination with any other aspect, the receiver has a first width, and the adapter also includes a distal neck that is coupled to the diaphragm and has a second width that is smaller than the first width.

[0032] On the other hand, considered alone or in combination with any other aspect, a relief needle assembly is provided, comprising a needle having a proximal portion and a distal portion. A needle cap is positioned around the distal portion. A spacer engages with the needle cap and extends from the needle cap towards the proximal portion. The spacer is arranged to at least partially surround the proximal portion of the needle and is releasably engaged with the distal connector.

[0033] On the other hand, whether considered alone or in combination with any other aspect, the spacer is configured for releasable engagement with the distal connector, thereby allowing the proximal portion of the needle to puncture the diaphragm.

[0034] Other aspects, features, and advantages of this application will become apparent from the following detailed description. Attached Figure Description

[0035] Illustrative embodiments of this application will be described in conjunction with the accompanying drawings, wherein:

[0036] Figure 1 This is a perspective view of the ocular sampling and injection process performed according to the combined biosampling and injection assembly of this application.

[0037] Figure 2 This is a front view of the combined biosampling and injection assembly according to this application.

[0038] Figure 3A This is a front view of the sustained-release needle and adapter sub-assembly of the combined biosampling and injection assembly according to this application.

[0039] Figure 3B yes Figure 3A The exploded perspective view of the sustained-release needle and adapter sub-assembly according to this application is shown.

[0040] Figure 3C yes Figure 3A The diagram shown is a three-dimensional exploded view of the combined biosampling and injection assembly according to this application.

[0041] Figure 3D yes Figure 3C The adapter in the middle is connected to Figure 3A The diagram shows a cross-sectional view of the syringe of the biosampling and injection assembly according to this application.

[0042] Figure 4A This is a front view of the working cylinder of the biosampling and injection assembly according to this application.

[0043] Figure 4B yes Figure 4A The exploded perspective view of the working barrel of the biosampling and injection assembly according to this application is shown.

[0044] Figure 5 This is a cross-sectional view of a evacuated sample container having a multi-layer pierceable septa, according to this application.

[0045] Figure 6This is a flowchart of a method for performing a biosampling and injection process using a combined biosampling and injection assembly, according to this application.

[0046] Figure 7A This is an exploded view of the sustained-release needle and adapter sub-assembly of the combined biosampling and injection assembly according to this application.

[0047] Figure 7B This is a front view of the sustained-release needle and adapter sub-assembly in the first step of the method for performing a biosampling and injection process according to this application.

[0048] Figure 7C This is a front view of the drug injector and adapter sub-assembly in the second step of the method for performing a biological sampling and injection process according to this application.

[0049] Figure 7D This is a front view of the drug injector and adapter subassembly, as well as the working barrel and sampling subassembly, in the third step of the method for performing a biological sampling and injection process according to this application.

[0050] Figure 7E This is a front view of the combined biosampling and injection assembly in the fourth step of the method for performing a biosampling and injection process according to this application.

[0051] Figure 7F This is a front view of the combined biosampling and injection assembly in the fifth step of the method for performing a biosampling and injection process according to this application.

[0052] Figure 8 This is a front view of a multi-perforated pre-filled drug syringe of the combined biosampling and injection assembly according to this application.

[0053] Figure 9A This is a schematic diagram of a working cylinder including an angle deflection needle according to this application.

[0054] Figure 9B This is a schematic diagram of a working cylinder including a lateral deflection needle according to this application. Detailed Implementation

[0055] To facilitate an understanding of the principles of this application, reference will now be made to the embodiments illustrated in the accompanying drawings, and specific language will be used to describe the same embodiments. However, it should be understood that the scope of this application is not intended to be limited. Any changes and further modifications to the described apparatus, systems, and methods that would normally occur to those skilled in the art, as well as any further applications of the principles of this application, are fully considered and included within this application. Specifically, it is entirely contemplated that features, components, and / or steps described with respect to one embodiment can be combined with features, components, and / or steps described with respect to other embodiments of this application. However, for the sake of brevity, these numerous combinations will not be described separately.

[0056] This document discloses apparatus, components, and sub-components for performing biosampling and injection procedures. Components may include a syringe containing a liquid drug or agent, an adapter, a working barrel, and a sample container positioned within the working barrel. The assembly provides biosampling and drug injection through progressive movement of the drug-injected syringe, such that a biological sample is obtained when the syringe is moved distally to a first position within the barrel, and the drug is injected when the syringe is moved to a second position within the barrel. In some aspects, the combined biosampling and injection assembly can be controlled by a physician with one hand, thereby improving efficiency and reducing procedural complexity.

[0057] Figure 1 This is an example of a combined biosampling and injection assembly 100, which is used by a physician's hand 10 to extract a sample from a patient's eye 50 and deliver a drug or agent into the eye 50. In an exemplary embodiment, assembly 100 can be used to obtain a vitreous fluid sample and inject a drug into the vitreous fluid.

[0058] However, replacing or except Figure 1 Beyond the ophthalmic procedures illustrated, component 100 can also be used in other scenarios. This could include, for example, obtaining a blood sample and injecting a drug into a patient's blood vessels. In some aspects, component 100 can be configured to inject a drug volume equal to or approximately equal to the sample volume obtained from the patient's body structure.

[0059] like Figure 2As shown in Figure 3, component 100 includes a drug injector 110 and an adapter 120 connected to the distal end of the drug injector 110. A working barrel 130 slidably receives the drug injector 110, the adapter 120, and an evacuation sampling chamber or device 136. For this purpose, the injector 110 and / or adapter 120 may include one or more features that form an interference fit with the inner surface of the working barrel 130. The friction generated by the interference fit allows the injector 110 and adapter 120 to move longitudinally within the working barrel 130 while providing a certain degree of resistance and stability so that the injector 110 and / or adapter 120 do not move freely within the working barrel 130 without the doctor's hand 10 applying force. In other embodiments, the frictional force associated with the interference fit may be low enough that the injector 110 and / or adapter can move freely within the working barrel 130 even without the doctor's hand 10 applying force. A needle 132 is coupled to the distal end of the working barrel 130.

[0060] Syringe 110 can be pre-filled with a certain volume of liquid medication, which is typically indicated by graduations on the outside of the syringe body. Syringe 110 can be formed of a transparent material, such as a transparent polymer or plastic. For example, syringe 110 can be formed of transparent polycarbonate, polyester, polypropylene, nylon, cyclic olefin copolymers and / or any other suitable polymer or glass.

[0061] Syringe 110 includes a piston 112 with a push pad 114 at its proximal end. A stop 115 is connected to the distal end of the piston 112 and forms a slidable seal with the inner surface of the syringe body. A first finger grip 116 is disposed at the proximal end of syringe 110. A connector 118 is disposed at the distal end of syringe 110 and defines a fluid passage 111 (see [link to product]). Figure 3D ).

[0062] The adapter 120 includes a connector 125 at its distal end for providing different interfaces to access the drug within the syringe 110. With this in mind, the adapter 120 may be provided with multiple perforated interfaces or diaphragms 124 so that the drug within the syringe 110 can be accessed multiple times.

[0063] like Figure 3B-3DAs shown, an example adapter 120 includes a generally cylindrical receiver 122 and a proximal connector 127. The receiver 122 is for receiving the distal end of a syringe 110, and the proximal connector 127 is for mating with a corresponding distal connector 118 of the syringe 110. For this purpose, the connector 127 of the adapter 120 may include a luer-lock connector, such as a female luer-lock connector or a male luer-lock connector. Similarly, the connector 118 of the syringe 110 may include a luer-lock connector, such as a female luer-lock connector or a male luer-lock connector. However, other connectors are also contemplated, including threaded or non-threaded connectors.

[0064] The remote connector 125 includes a head and a narrow neck. A multi-perforated diaphragm 124 is attached to the head of the connector 125. In the illustrated embodiment, the multi-perforated diaphragm 124 is rolled up around the head and neck. In particular, a roll-up cap 129 can be used to roll the multi-perforated diaphragm 124 around the head and neck of the adapter 120.

[0065] The receiver 122 includes one or more laterally radially extending windows 128 and a proximal ring 121. In some aspects, the receiver 122 of the adapter 120 may be formed of an opaque material. Therefore, the windows 128 allow visualization of the syringe, enabling a physician to monitor the remaining fluid volume in the syringe 110. The proximal ring 121 provides structural integrity and rigidity to the receiver 122. The adapter 120 also includes an O-ring 126. The outer diameter of the O-ring 126 may be selected based on or otherwise set according to the inner diameter of the working barrel 130. Accordingly, the O-ring 126 may provide a sliding interference fit with the inner surface of the working barrel 130.

[0066] like Figure 2 As shown, the working cylinder 130 includes a transparent body, making the components therein (e.g., syringe 110, adapter 120, sampling chamber 136) visible. For example, the working cylinder 130 may be formed of transparent polycarbonate, polyester, polypropylene, nylon, polyvinyl chloride, cyclic olefin copolymers and / or any other suitable polymer.

[0067] The working tube 130 also includes graduated markings to allow the physician to monitor the position and movement of components within the working tube 130. The working tube 130 includes a second finger grip 138, which can be held by the physician (e.g., ...). Figure 1 (As shown). For example, a physician can use the second finger grip 138 to keep the working barrel 130 stationary while pushing the syringe 110, adapter 120, and sampling chamber 136 distally into the working barrel 130 by pushing the push pad 114 of the syringe 110. In some aspects, the finger grips 116, 138 may be referred to as flanges. The finger grips 116, 138 may be integrally formed with the syringe body and the working barrel 130, respectively (e.g., injection molded).

[0068] The working barrel 130 also includes a tactile feature 137 located on the inner surface of the working barrel 130, which is configured to engage and / or connect with one or more surfaces of the adapter 120, the syringe 110, and / or the sampling chamber 136. In the illustrated embodiment, the tactile feature 137 includes annular ridges or protrusions and extends inwardly into the working barrel 130.

[0069] The needle 132 is attached to the distal end of the working barrel 130. A needle cap 134 is attached to the distal end of the working barrel 130 to provide protection for the needle 132 when the working barrel 130 is not in use. The needle 132 may include a dual-sided needle configured to connect to a distal opening or nozzle of the working barrel 130, such that the proximal portion of the needle is positioned within the working barrel 130.

[0070] like Figure 4B As shown, the sampling chamber 136 may include a cylindrical or tubular body or container 131 having openings at both a proximal and distal end. One or both of the proximal and distal openings of the sampling chamber 136 are covered by corresponding diaphragms 133, 135. Diaphragms 133, 135 may be configured to maintain a negative pressure or vacuum inside the sampling chamber 136 relative to the external environment. In some aspects, the sampling chamber 136 is configured to maintain a pressure, for example, lower than the vitreous fluid pressure within a patient's eye 50.

[0071] The cylindrical or tubular body of the sampling chamber 136 may be transparent to allow the physician to observe the material filling the chamber 136. The size, shape, and other structures of the sampling chamber 136 are configured to match within the working barrel 130 and may be constructed to form an interference fit with the inner surface of the working barrel 130. For example, the sampling chamber 136 may be configured to remain stationary within the working barrel 130 until a force (e.g., by syringe 110) is applied relative to the working barrel 130 to the sampling chamber 136.

[0072] Therefore, the width or outer diameter of diaphragms 133, 135 is greater than or equal to the inner width or diameter of the working cylinder 130. Alternatively, the sampling chamber 136 floats freely within the working cylinder, allowing it to slide freely longitudinally relative to the working cylinder 130. Although shown as hexagonal, it is understood that the proximal and distal diaphragms 135, 133 may also be circular, rectangular, octagonal, elliptical, or any other suitable shape.

[0073] In any case, the distal end of the adapter 120 is configured to push the sampling chamber 136 distally within the working barrel 130. For this purpose, the sampling chamber 136 may not be attached or connected to the adapter 120, but is instead configured to be pushed toward the needle 132 into the working barrel 130 by moving the syringe 110 and the adapter 120 distally within the working barrel 130. In other embodiments, the sampling chamber 136 may be attached to, adhered to, welded to, or otherwise connected to the adapter 120 and / or the syringe 110. Propelling the syringe 110, adapter 120, and sampling chamber 136 distally toward the needle 132 causes the proximal end of the needle 132 to sequentially pierce the sampling chamber 136 of the syringe 110 and the drug reservoir.

[0074] Figures 3A-3B Also shown is a sustained-release needle and adapter subassembly 140 that can be used in conjunction with the biosampling and injection assembly 100. The sustained-release needle subassembly 140 includes a needle tip 142, a needle cap 144, and a spacer 146. The sustained-release needle assembly 140 is configured such that the proximal end or opening of the needle tip 142 perforates a multi-perforated diaphragm 124 on the adapter 120. Because the edges of the multi-perforated diaphragm 124 can be crimped onto the distal connector 125, the proximal end of the needle tip 142 can be positioned in fluid or drug fluid communication within the syringe 110. The spacer 146 is releasably coupled to the distal end of the adapter 120. In some aspects, the sustained-release needle assembly 140 and the adapter 120 can be connected to the syringe 110 in a single step. For example, the sustained-release needle assembly 140 and the adapter 120 can be initially connected or coupled to the proximal end of the needle tip 142 that has perforated the multi-perforated diaphragm 124 of the adapter 120. In other embodiments, the sustained-release needle assembly 140 and the adapter 120 may be connected or coupled to the syringe 110 in separate steps.

[0075] In the illustrated embodiment, spacer 146 and needle cap 144 comprise separate components that are joined, attached, or otherwise coupled together using adhesives, mechanical attachments, thermal welding, or any other suitable joining method. In other embodiments, needle cap 144 may be integrally formed with spacer 146, for example, by injection molding. Spacer 146 includes two spacer arms 148a, 148b configured to bend outward away from adapter 120 to disengage the spacer arms 148a, 148b from the head of connector 125 on adapter 120. Recesses 149 may be formed in each spacer arm 148a, 148b to receive the head of connector 125. In some embodiments, an annular sleeve (not shown) may be wrapped around the interface between the release needle assembly 140 and adapter 120 to prevent any fluid leakage from the inside of needle cap 144.

[0076] Figure 5 This is a more detailed cross-sectional view of the evacuated sampling chamber 136. Diaphragms 133 and 135 each comprise multiple layers joined together or otherwise attached to each other. Container 131 comprises a hollow cylindrical or tubular body having sidewalls 151. Container 131 defines a chamber 155 configured to contain a volume of biological fluid. The sidewalls 151 have a thickness 153. In some respects, the thickness 153 may be sufficient to maintain a vacuum or negative pressure within the chamber 155 relative to the external environment.

[0077] In some aspects, container 131 may be formed of a polymeric material, glass, ceramic, metal, or any other suitable material. For example, container 131 may be formed of polyester, polyethylene, polycarbonate, polypropylene, nylon, or any other suitable material or combination of materials. In some aspects, container 131 includes a polymeric body and a glass or ceramic coating on at least one of its inner or outer surfaces. In other embodiments, container 131 includes a polymeric body, such as polyester, wherein a thickness 153 is sufficient to prevent sampling chamber 136 from losing vacuum in chamber 155 over a period of time. In some embodiments, thickness 153 may be between 0.5 mm and 4 mm. In some embodiments, sampling chamber 136 is used to hold fluid in the range of 25 μL to 500 μL.

[0078] In the illustrated embodiment, the first diaphragm 133 and the second diaphragm 135 have similar or identical constructions. However, it should be understood that in other embodiments, the first diaphragm 133 may have a different construction than the second diaphragm 135. The first diaphragm 133 includes an adhesive layer 152, a metal foil layer 154, and an elastic layer 156. The adhesive layer 152 may include a polymeric material configured to bond and / or adhere to a material of the container 131.

[0079] In some embodiments, adhesive layer 152 includes an adhesive or glue configured to provide pressure-activated and / or heat-activated attachment to container 131. In some embodiments, adhesive layer 152 includes a heat-activated material that engages with the edge of container 131 in response to applied heat to provide an airtight seal with container 131. In some embodiments, the heat-activated material may include polyolefins, polyamides, polyester fibers, polyurethanes, and styrene-butadiene copolymers. In some embodiments, the thickness of adhesive layer 152 may be in the range of 0.005 mm to 0.1 mm.

[0080] The metal foil layer 154 includes a metal foil bonded to the adhesive layer 152. In some aspects, the metal foil layer 154 may be adhered to the adhesive layer 152 by an adhesive or other interface layer. The metal foil layer 154 may include a metal having a thickness sufficient to maintain a vacuum or negative pressure within the chamber 155. For this purpose, the metallic material of the foil layer 154 may have lower gas permeability than some polymeric materials. Therefore, the metal foil layer 154 improves the sealing function to better maintain the pressure differential within the chamber 155. The metal foil layer 154 may include, for example, aluminum, gold, silver, copper, and / or alloys thereof. In some embodiments, the thickness of the metal foil layer 154 may be in the range of 0.01 mm to 0.2 mm.

[0081] The elastic layer 156 comprises an elastomeric material, the thickness of which is greater than the thickness of the adhesive layer 152 and / or the metal foil layer 154. In some embodiments, the thickness of the elastic layer 156 is greater than the sum of the thicknesses of the adhesive layer 152 and the metal foil layer 154. For this purpose, the thickness of the elastic layer 156 may be greater than the length of the beveled opening of the needle tip 132. Therefore, the proximal end of the needle tip 132 may include a beveled or angled opening to facilitate perforation of the diaphragms 133, 135 and prevent coring of the diaphragms 133, 135.

[0082] If the thickness of the elastic layer 156 is significantly less than the length of the beveled opening of the needle 132, the beveled opening of the needle 132 may undesirably create a fluid path between the chamber 155 and the external environment. This could eliminate or reduce the negative pressure within the chamber 155 before a biological sample can be drawn into the sampling chamber 136. Correspondingly, the relatively large thickness of the elastic layer 156 maintains an airtight seal when the needle perforates the diaphragm 133. Furthermore, in some aspects, the elastic layer 156 can provide a fluid seal with the outer surface of the needle 132, thereby preventing the biological sample within the chamber 155 from leaking into the external environment after the process. In some embodiments, the thickness of the elastic layer 156 can be between 0.2 mm and 3 mm, including values ​​such as 0.4 mm, 0.5 mm, and 0.6 mm.

[0083] The second diaphragm 135 further includes an adhesive layer 162, a metal foil layer 164, and an elastic layer 166. Layers 162, 164, and 166 may be similar to or identical to layers 152, 154, and 156 of the first diaphragm 133. In other embodiments, one or more of layers 162, 164, and 166 may differ from the corresponding layers 152, 154, and 156 in material, thickness, size, or any other aspect.

[0084] In operation, once the sustained-release needle assembly 140 is connected to the adapter 120 and syringe 110, the physician can first press down the piston 112 using the push pad 114 and the finger grip 116. The syringe 110 can be a pre-filled syringe and may include air bubbles or entrained air that the physician wishes to expel. Furthermore, the syringe 110 may contain a volume of medication exceeding the patient's required dose. Accordingly, the physician can perforate the multi-perforated diaphragm 124 within the syringe 110 to expel air bubbles and excess medication through the sustained-release needle 142 and into the needle cap 144. The cap 144 can form a closed space to contain the excess medication expelled through the sustained-release needle 142. The sustained-release needle 142 and needle cap 144 are then removed, and the syringe 110 and adapter 120 are positioned within the working barrel 130, allowing the multi-perforated diaphragm 124 to be perforated a second time to deliver the medication into the patient's body structures (e.g., the vitreous humor).

[0085] With this in mind, component 100 can be operated with one hand, allowing a physician to use one hand 10 to advance the drug injector 110 and adapter 120 distally within the working barrel 130, and to use the other hand to support or stabilize the target human structure (e.g., eye 50). For this purpose, the physician can perform a combined biosampling and injection procedure by advancing the injector 110, adapter 120, and emptied sampling chamber 136 distally toward the proximal end of the needle 132 into the working barrel 130.

[0086] A physician can advance the syringe 110 distally by pressing the piston 112. An annular protrusion 137 is configured to engage at least a portion of the adapter 120 (e.g., an O-ring 126) to alert the physician that the sampling chamber 136 is located where the proximal end of the needle 132 punctures the first diaphragm 133 of the sampling chamber 136. The O-ring 126 and the proximal annular portion 121 keep the adapter 120 centered in the working barrel 130, such that as the adapter 120 moves distally within the working barrel 130, the proximal portion of the needle 132 strikes and perforates the multi-perforated diaphragm 124.

[0087] In the first advancing position, the proximal end of the needle 132 has pierced the diaphragm 133 of the sampling chamber 136, drawing a certain volume of biological fluid into the chamber. The pressure difference between the internal and external environments of the sampling chamber 136 is sufficient to allow biological samples (e.g., vitreous fluid, blood, etc.) to flow automatically through the needle 132 and into the sampling chamber 136.

[0088] Once the physician determines that the sampling chamber 136 is full, the physician continues to advance the syringe 110, adapter 120, and sampling chamber 136 distally into the working barrel 130 to a second advance position until the distal end of the needle 132 exits the sampling chamber 136 by passing through the second diaphragm 135. The needle 132 then pierces the multi-perforated diaphragm 124 of the adapter 120 to place the distal end of the needle 132 in fluid communication with the medication inside the syringe 110. More specifically, fluid from inside the syringe 110 can now drain through the fluid channel 111 and enter the proximal opening of the needle.

[0089] In the second advance position, the force applied to the piston of syringe 110 causes the piston to force the drug through needle 132 out of syringe 110 and into eye 50. Therefore, the combined biosampling and injection process involves a single puncture through the patient's body structure to perform a multi-stage or stepwise movement in the same (distal) direction, thereby increasing efficiency and reducing process complexity.

[0090] As described above, various components of component 100 can be transparent—including the working tube 130, sampling chamber 136, and syringe 110—to allow physicians to observe the biosampling and injection process. This configuration, coupled with the side window 128 in adapter 120 and the aforementioned haptic feedback features, makes the process easy to observe and repeatable.

[0091] Figure 6 and 7A -7F illustrates a method 600 for performing a combined biosampling and injection procedure. Method 600 can be performed using one or more of the aforementioned apparatus, sub-components, or components, including... Figure 1 and 2 The combined biosampling and injection sub-component 100 shown is illustrated.

[0092] Reference Figure 6 , Figure 7A and Figure 7B In step 602, syringe 110 is connected to adapter 120 and sustained-release needle assembly 140. As described above, the connection of adapter 120 and injection needle assembly 140 to syringe 110 can be performed in a single step. In other embodiments, adapter 120 may be first connected to the distal end of syringe 110, and dispensing needle assembly 140 may subsequently be connected to adapter 120 and syringe 110.

[0093] In any case, in step 604, the physician uses the piston 112 of syringe 110 to expel any air bubbles or entrained air from syringe 110, and accesses the drug from syringe 110 through the sustained-release needle 142 into the drug collection chamber defined by needle cap 144. In this way, the physician prepares the drug injection portion of the combined biosampling and injection procedure.

[0094] Reference Figure 6 and Figure 7C In step 606, the physician detaches the sustained-release needle assembly 140 from the adapter 120. The adapter 120 remains connected to the distal end of the syringe 110. The multi-perforated diaphragm 124 of the adapter 120 automatically reseals the perforations formed by the sustained-release needle 142.

[0095] Reference Figure 6 and Figure 7D In step 608, the physician inserts the syringe 110 and adapter 120 into the working barrel assembly, which includes a working barrel 130, an evacuated sampling chamber 136, a needle 132, and a needle cap 134. As noted, the adapter 120 can form a slidable interference fit with the working barrel 130. The resistance between the adapter 120 and the working barrel 130 helps the physician gradually press the syringe 110, adapter 120, and sampling chamber 136 into the working barrel 130 from the proximal end of the needle 132 distally.

[0096] Reference Figure 6 and Figure 7E In step 610, the physician inserts the needle 132 of the working barrel 130 into the patient's eye 50, specifically into the vitreous cavity. In step 612, the physician advances the syringe 110 within and relative to the working barrel 130, causing the proximal end of the needle 132 to pierce the first / distal septum 133 of the sampling chamber 136. To this end, the syringe 110 is advanced distally relative to and into the working barrel 130 by pressing the push pad 114 of the piston 112. Because the multi-perforated septum 124 of the adapter 120 is no longer pierced, pushing the piston 112 causes the entire syringe 110 to be advanced distally into the working barrel 130 without causing additional medication to be expelled from the syringe 110. The physician can use the push pad 114 and the finger grip 138 of the working barrel 130 to advance the syringe 110, adapter 120, and sampling chamber 136 distally within the working barrel 130.

[0097] The proximal end of the needle 132 may include a bevel or angled opening as described above. The length of the beveled opening may be less than the thickness of the first diaphragm 133 of the sampling chamber 136. When the proximal end of the needle 132 enters the evacuated sampling chamber 136, a pressure difference causes vitreous fluid to automatically flow through the needle 132 and into the sampling chamber 136. As noted, the working tube 130 and the sampling chamber 136 are formed of a transparent or translucent material, allowing the physician to observe the flow of vitreous fluid into the sampling chamber 136.

[0098] In addition, the annular protrusion 137 on the working cylinder 130 (see Figure 2 The protrusion 137 provides tactile feedback to the physician when the proximal end of the needle 132 is inserted into the sampling chamber 136. The protrusion 137 may be configured to interact, for example, with the O-ring 126 of the adapter 120 to provide tactile feedback. It should be understood that, in addition to the annular protrusion, the tactile features may also include pawls, ridges, grooves, or any other structural features suitable for providing tactile feedback to the physician regarding the position of the syringe 110, adapter 120, and / or sampling chamber 136 relative to the working barrel 130 and relative to the proximal end of the needle 132.

[0099] like Figure 6 and Figure 7F As shown, in step 614, once the desired volume of vitreous fluid has been collected, the physician advances the syringe 110, adapter 120, and sampling chamber 136 within the working barrel 130 until the proximal end of the needle 132 pierces the multi-perforated diaphragm 124 of the syringe 110. In some aspects, step 614 may include the physician pushing the push pad 114 of the piston 112 until the sampling chamber 136 is stopped by the geometry of the distal end of the working barrel 130. As the sampling chamber 136 is advanced distally into the working barrel 130, the proximal end of the needle 132 perforates the second / proximal diaphragm 135 of the sampling chamber 136, and then perforates the multi-perforated diaphragm 124 of the adapter 120.

[0100] Thus, the proximal end or opening of the needle 132 is placed in fluid communication with the medication within the syringe 110. Accordingly, as the physician continues to push the plunger 114, the force of the piston 112 causes the medication within the syringe 110 to be expelled through the needle 132 and enter the vitreous humor of the patient's eye 50. The volume of medication injected into the patient can be equal to or approximately equal to the volume of the biological sample material aspirated into the sampling chamber 136.

[0101] Figure 8 Another example is shown: a pre-filled syringe 210 has a distal end connector 220, which includes a multi-perforated diaphragm 224 and an O-ring 226. For this, no adapter is used, such as those described above. Figure 2-7FInstead of the adapter 120 shown, a multi-perforated diaphragm 224 is integrated into the syringe 210, enabling the combined biosampling and injection process described above to be performed without an adapter. The multi-perforated diaphragm 224 can be rolled onto the head of the distal connector 220. The syringe 210 can operate with the working barrel 130 and the sustained-release needle assembly 140 in the same manner as described above relative to the syringe 110.

[0102] Figure 9A and Figure 9B The specific construction of the needle 132 of the working barrel 130 is shown. As noted, the needle 132 may include an angled or beveled opening 139 at its proximal end. The angled or beveled opening 139 can facilitate insertion of the needle 132 into the sampling chamber 136. For example, the beveled opening 139 can provide a tip for the needle 132 to perforate the diaphragms 133, 135 of the sampling chamber 136, while reducing or eliminating core removal of the diaphragms 133, 135.

[0103] However, the angled surface of the beveled opening 139 may cause the needle 132 to deflect away from its longitudinal axis 70. Therefore, in Figure 9A In the illustrated embodiment, the needle 132 is initially deflected or pre-deflected to compensate for the deflection caused by the perforation of the diaphragms 133, 135 of the sampling chamber 136 by the beveled opening 139. Specifically, the needle 132 may be deflected or tilted at an angle θ away from the longitudinal axis 70.

[0104] exist Figure 9B In another example shown, the needle 132 may be laterally deflected or moved away from the longitudinal axis 70. In any case, the angle or lateral deflection of the needle 132 may be determined or configured such that the perforation of the beveled opening 139 into the first diaphragm 133 of the evacuated chamber 136 will result in an angled and / or lateral deflection of the proximal portion of the needle 132 toward the longitudinal axis 70.

[0105] It should be understood that the above-described devices, components, and sub-components can be modified according to the specific embodiments shown without departing from the scope of this disclosure. For example, although adapter 120 is described as having a multi-perforated diaphragm 124, other types of connectors and / or interfaces may be used instead of the multi-perforated diaphragm or in addition to it. For example, in some embodiments, adapter 120 may include a single perforated diaphragm. In other embodiments, adapter 120 may include a valve configured to receive a needle or cannula to form a fluid path between syringe 110 and needle 132. Further aspects and / or details of the above-described components and devices can be found in U.S. Patent Application No. 17 / 319,742, filed May 13, 2021, the entire contents of which are incorporated herein by reference.

[0106] Those skilled in the art will recognize that the above-described apparatus, systems, and methods can be modified in various ways. Accordingly, those skilled in the art will understand that the embodiments covered by this application are not limited to the specific exemplary embodiments described above. In this regard, although illustrative embodiments have been shown and described, extensive modifications, alterations, and substitutions have been explored in the foregoing disclosure. It should be understood that such changes can be made to the foregoing without departing from the scope of this application.

[0107] Therefore, the appended claims should be interpreted broadly in accordance with this application.

Claims

1. A sampling device, comprising: A cylinder, which includes a hollow body defining the internal region; A container, slidably received within the internal region, and comprising a body defining a chamber, a distal opening leading to the chamber, and a proximal opening opposite to the distal opening. A bilateral needle having a proximal end disposed within the barrel away from the container and a distal end positioned for injection into the patient; A proximal diaphragm, which engages with the container to cover the proximal opening and hermetically seal the chamber; and A distal diaphragm, which engages with the container to cover the distal opening and hermetically seal the chamber, wherein the distal diaphragm comprises: An adhesive layer having a first thickness and comprising a material that adheres to the edge of the container to hermetically seal the container; A metal foil layer having a second thickness and bonded to the adhesive layer; and An elastic layer, having a third thickness, is attached to the metal foil layer to position the metal foil layer between the adhesive layer and the elastic layer, wherein the third thickness is greater than the sum of the first thickness and the second thickness. The chamber is movable within the tube to a first position, thereby placing the proximal ends of the bilateral needles within the chamber to draw biological samples from the patient into the chamber, and is also movable to a second position, in which the proximal ends of the bilateral needles pass through the chamber and through the proximal septum to deliver medication to the patient.

2. The sampling device according to claim 1, in, The proximal opening is aligned with the distal opening; and The proximal diaphragm includes: An adhesive layer comprising a material that adheres to the proximal edge of the container to hermetically seal the container; A metal foil layer, which is bonded to the proximal diaphragm via an adhesive layer; and An elastic layer, which is attached to the metal foil layer of the proximal diaphragm, positions the metal foil layer of the proximal diaphragm between the adhesive layer and the elastic layer of the proximal diaphragm.

3. The sampling device according to claim 2, wherein, The adhesive layer of the proximal diaphragm has a fourth thickness, the metal foil layer of the proximal diaphragm has a fifth thickness, and the elastic layer of the proximal diaphragm has a sixth thickness, wherein the sixth thickness is greater than the sum of the fourth thickness and the fifth thickness.

4. The sampling device according to claim 1, wherein, The adhesive layer comprises a material that engages with the edge of the container in response to the application of heat.

5. The sampling device according to claim 1, wherein, The adhesive layer includes an adhesive.

6. A system for using a syringe to obtain a biological sample and deliver a drug to a patient, the system comprising: A cylinder, which includes a hollow body defining the internal region; An adapter, located within the internal region, has a proximal connector configured to connect the adapter to the distal end of a syringe, the distal end of which has a perforated interface. An evacuated container, slidably received within the internal region away from the adapter, and having a body defining a chamber configured to contain the biological sample and a distal opening extending into the chamber, wherein the distal opening is covered by a distal septum; and A bilateral needle includes a proximal end disposed within the barrel away from the evacuated container and a distal end positioned for injection into a patient, wherein the evacuated chamber within the barrel is movable to a first position, thereby placing the proximal end of the bilateral needle within the chamber to draw a biological sample from the patient into the chamber, and is also movable to a second position, in which the proximal end of the bilateral needle passes completely through the evacuated chamber and through the interface, thereby delivering a drug from the syringe to the patient.

7. The system according to claim 6, wherein, The evacuated container can move in the same direction relative to the cylinder to reach the first position and the second position.

8. The system according to claim 6, wherein, The distal diaphragm includes: An adhesive layer comprising a material that adheres to the distal edge of the container to hermetically seal the container; A metal foil layer, which is bonded to the distal diaphragm via an adhesive layer; and An elastic layer, which is attached to the metal foil layer of the distal diaphragm, positions the metal foil layer of the distal diaphragm between the adhesive layer and the elastic layer of the distal diaphragm.

9. The system according to claim 8, wherein, The adhesive layer has a first thickness, the metal foil layer has a second thickness, and the elastic layer has a third thickness, the third thickness being greater than the sum of the first thickness and the second thickness.

10. The system according to claim 8, wherein, The evacuated container also includes a proximal septum, which engages with the container at a proximal opening opposite and aligned with the distal opening to cover the proximal opening. The proximal septum comprises: An adhesive layer comprising a material that adheres to the proximal edge of the container to hermetically seal the container; A metal foil layer, which is bonded to the proximal diaphragm via an adhesive layer; and An elastic layer, which is connected to the metal foil layer of the proximal diaphragm. The metal foil layer of the proximal diaphragm is disposed between the adhesive layer and the elastic layer of the proximal diaphragm.

11. The system according to claim 10, wherein, The adhesive layer of the proximal diaphragm has a fourth thickness, the metal foil layer of the proximal diaphragm has a fifth thickness, and the elastic layer of the proximal diaphragm has a sixth thickness, wherein the sixth thickness is greater than the sum of the fourth thickness and the fifth thickness.

12. The system according to claim 6, wherein, The adapter includes an O-ring surrounding the periphery of the adapter, wherein the outer diameter of the O-ring corresponds to the inner diameter of the cylinder.

13. The system according to claim 12, wherein, The cylinder also includes a tactile feature within the internal region that engages with the O-ring to indicate that the evacuated container is in the first position.

14. The system according to claim 6, wherein, The proximal end of the double-sided needle has a beveled opening.

15. The system according to claim 14, in, The cylinder defines a longitudinal axis; Wherein, at least the proximal ends of the bilateral needles are offset from the longitudinal axis; and The beveled opening is configured to deflect the proximal portion of the double-sided needle toward the longitudinal axis in response to perforation of the distal diaphragm of the evacuated container.

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