Devices, systems and methods for biological sample collection

Abstract

To provide a small, handheld device for collecting a small amount of a biological sample, such as vitreous humor, from the eye.SOLUTION: A device comprises: a syringe including a plunger and a barrel having a longitudinal axis and a sample collection volume; a needle hub including a mounting device to which the syringe is connected; a syringe support connected to the needle hub; a microcontroller disposed within the syringe support; a needle connected to the needle hub; an inner needle being hollow and partially disposed within a lumen of the needle; and a motor for rotationally moving an inner needle within the needle, disposed inside the needle hub, and including a permanent magnet attached to the inner needle, the motor further including a plurality of coils mounted outside the needle hub. The needle includes a first opening formed on a side surface. The inner needle includes a second opening formed on a side surface. When the second opening is aligned with the first opening, a material can enter. When the second opening rotates and passes through the first opening, the material is cut.SELECTED DRAWING: Figure 1

Description

Detailed Description of the Invention

[0001] [Technical field] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 62 / 850,913, filed May 21, 2019, the entire contents of which are incorporated herein by reference.

[0002] Provided herein are devices, systems, and methods for biological sample collection. In particular, provided herein are devices, systems, and methods that use small, handheld devices to collect small biological samples, such as the vitreous, from the eye for diagnostic, research, and other purposes.

[0003] [Background technology] Liquid biopsies are increasingly being utilized in various medical settings as a minimally invasive approach to providing real-time information about a patient's medical condition. By extracting and analyzing samples of specific biological fluids, clinicians obtain information about the tissues with which the fluid has come into contact. Many collection options exist for primarily liquid samples, such as blood, urine, and saliva. Other sample types, such as the vitreous, a gelatinous fluid that fills the posterior segment of the eye, present more significant challenges. Because the vitreous is juxtaposed to the light-sensing retina, liquid vitreous biopsies can provide information about sight-threatening retinal diseases. However, challenges in collecting vitreous samples limit their potential for diagnostic applications. Furthermore, vitreous biopsies are of great clinical importance because retinal biopsies are not possible in most cases.

[0004] Currently, there are two types of devices for removing vitreous from the eye: one optimized for use in the operating room and the other optimized for use in a clinical setting. Modern operating room devices are based on vitreous injection and aspiration cutters designed for vitrectomy surgery in the 1970s. These operating room units are optimized for removing the entire volume of vitreous and incorporate additional instruments to assist with vitrectomy, such as injection and illumination. Operating room-based vitreous cutting devices are large, difficult to transport, and expensive. Portable vitreous cutters designed for clinical use were developed in the 1990s and partially overcome these drawbacks. These clinical devices are smaller and slightly less expensive than their operating room counterparts, but suffer from the disadvantages of requiring a power cord, two users (operator and assistant), and simultaneous injection (administration of a substance into the eye to replace the removed material). Like operating room vitreous cutters, clinical vitreous cutters are optimized solely for extracting large samples.

[0005] The high cost, large size, and limited capacity of current operating room and clinical vitreous cutter models to minimize sample volume pose a steep barrier to expanding the use of liquid vitreous biopsy in clinical practice. Improved devices, systems, and methods are needed.

[0006] [Summary of the Invention] Provided herein are devices, systems, and methods for biological sample collection. In particular, provided herein are devices, systems, and methods that use small, handheld devices to collect small biological samples, such as the vitreous, from the eye for diagnostic, research, and other purposes.

[0007] The systems, devices, and methods are exemplified by collecting vitreous from an eye. It should be understood that the systems, devices, and methods are particularly effective, but not limited to, collecting vitreous samples. A wide variety of sample types can be collected.

[0008] With respect to vitreous collection, the systems, devices, and methods overcome unresolved barriers left by the prior art. To overcome these barriers, in some embodiments, the devices herein provide low-cost, handheld, disposable devices designed to excise small (e.g., 1 mL or less, 500 μL or less, 250 μL or less, 100 μL or less) samples of vitreous that can be analyzed for diagnostic purposes. In some embodiments, the devices use small-gauge needles with cutting actuation, extract small volumes of fluid, and do not require injection components. Together, these design features simplify the operator's procedure and provide a safe mechanism for liquid vitreous biopsy in a clinical setting.

[0009] For example, in some embodiments, provided herein is a device or system including one or more or each of: a) a syringe including a barrel having a longitudinal axis, the barrel comprising a sample collection volume; b) a needle connected to a distal end of the syringe at a needle hub, the needle having a lumen; c) a cutting tool disposed within the lumen of the needle; and d) an actuator for linearly or rotationally moving the cutting tool within the needle. In some embodiments, the actuator is external to the syringe barrel. In some embodiments, the actuator is disposed at the distal end of the needle hub.

[0010] In some embodiments, provided herein is a device or system including: a) a syringe comprising: i) a cutting accessory disposed within a needle lumen, the cutting accessory having a proximal end including one or more permanent magnets and configured for linear or rotational movement within the needle lumen; and ii) a barrel having a longitudinal axis, the barrel containing a sample collection volume; and b) a motor (e.g., an electromagnetic motor) disposed outside the syringe configured to linearly or rotationally move the cutting accessory under magnetic force. In some embodiments, the motor is external to the syringe barrel. In some embodiments, the motor is disposed at the distal end of the needle hub.

[0011] In some embodiments, provided herein is a device or system comprising: a) a syringe comprising: i) a cutting accessory disposed within a needle lumen, the cutting accessory having a proximal end including one or more metal structures (e.g., a squirrel cage or conductive loop) and configured to move linearly or rotationally within the needle lumen; and ii) a barrel having a longitudinal axis, the barrel containing a sample collection volume; and b) a motor disposed outside the syringe configured to move the cutting accessory linearly or rotationally under magnetic force. In some embodiments, the motor is external to the syringe barrel. In some embodiments, the motor is disposed at the distal end of the needle hub.

[0012] In some embodiments, the needle is a 20 gauge or smaller needle (e.g., 24 gauge, 26 gauge or smaller, etc.) and is hollow with a lumen. The needle can be any standard length (e.g., 3 / 8 inch to 3 1 / 2 inches). In some embodiments, the needle is 1 / 2 inch long. Any desired cutting tool can be used. In some embodiments, the cutting tool comprises a drill bit (e.g., a twist drill bit). In some embodiments, the cutting tool has a distal blade. In some embodiments, the cutting tool is configured as a needle within a needle. In some embodiments, the tip of the needle, and optionally the needle tip of the cutting tool, are closed. In some embodiments, the needle and cutting tool have a side opening that allows material to enter when aligned and provides a cutting mechanism (guillotine) when the opening is closed. In some embodiments, the collection volume is 1 mL or less (e.g., 500 μL or less, 250 μL or less, 100 μL or less).

[0013] In some embodiments, the actuator includes one or more magnets, the poles of which may be perpendicular to the longitudinal axis of the needle for rotational movement or parallel to (along) the longitudinal axis of the needle for linear movement.

[0014] In some embodiments, the actuator includes a plurality of electromagnets arranged about the longitudinal axis. In some embodiments, the actuator includes a plurality of electromagnets arranged along the longitudinal axis. In some embodiments, the plurality of electromagnets includes two or more (e.g., three, four, five, six or more, etc.) electromagnets. In some embodiments, the plurality of electromagnets includes four or more electromagnets. In some embodiments, the electromagnets are on the same or different support structures (e.g., stator rings or assemblies). In some embodiments, the electromagnets are on two or more support structures. In some embodiments, the support structure is a slotted stator. In some embodiments, the actuator includes multiple phase coils. In some embodiments, the actuator includes one or more slotless stators. In some embodiments, the device is configured to change the magnetic field by changing the polarity of the electromagnets. In some embodiments, the device is configured to change the magnetic field by changing the physical position of the magnets or electromagnets.

[0015] In some embodiments, the motor includes a plurality of electromagnets arranged about the longitudinal axis. In some embodiments, the motor includes a plurality of electromagnets arranged along the longitudinal axis. In some embodiments, the plurality of electromagnets includes two or more (e.g., three, four, five, six or more, etc.) electromagnets. In some embodiments, the plurality of electromagnets includes four or more electromagnets. In some embodiments, the electromagnets are on the same or different support structures (e.g., stator rings or assemblies). In some embodiments, the electromagnets are on two or more support structures. In some embodiments, the support structure is a slotted stator. In some embodiments, the motor includes multiple phase coils. In some embodiments, the actuator includes one or more slotless stators. In some embodiments, the device is configured to change the magnetic field by changing the polarity of the electromagnets. In some embodiments, the device is configured to change the magnetic field by changing the physical position of the magnets or electromagnets.

[0016] In some embodiments, the device further comprises one or more permanent magnets. In some embodiments, the one or more permanent magnets are disposed inside the barrel (e.g., attached to the proximal end of the cutting accessory). In some embodiments, the one or more permanent magnets are disposed inside the needle hub (e.g., attached to the proximal end of the cutting accessory inside the needle hub). In some embodiments, the one or more permanent magnets are replaced by a metal structure (e.g., a squirrel cage or other conductive loop structure) designed to generate an electromagnetic force (Lorentz force) when a changing magnetic field is applied. In some embodiments, the device further comprises a spring or counter force adjacent to the one or more permanent magnets or metal structure.

[0017] The actuator can be driven by any mechanism. In some embodiments, the actuator or motor is battery powered and the device includes a battery compartment housing one or more batteries. In some embodiments, the device includes a power cord. In some embodiments, the device or system includes a switch or other control mechanism for actuating the actuator.

[0018] Also provided herein are systems (e.g., kits) that include a device and one or more additional components, including, but not limited to, a power system, packaging, instructions, a label, a biological sample contained in (e.g., collected by) the device, a computer control system, diagnostic reagents (e.g., for analyzing a sample collected by the device), etc.

[0019] Also provided herein are methods of collecting a sample (e.g., a biological sample, such as a vitreous sample) using the device. In some embodiments, the method includes: a) positioning the distal end of the needle in a region containing the sample to be collected; b) actuating the actuator to rotate the cutting tool; and c) drawing the sample into a collection volume. In some embodiments, the method further includes at least one or all of: attaching a syringe to the needle hub; detaching the syringe from the needle hub; attaching an injection syringe to the needle hub, the injection syringe containing a fluid to be injected; and injecting a fluid into the region. The injection fluid may include a pharmaceutical agent. In some embodiments, the method is performed without injecting or injecting a material into the sample location (e.g., the eye). definition To facilitate the understanding of this invention, several terms are defined below.

[0020] As used herein, the term "sample" is used in its broadest sense. In one sense, it is intended to include specimens obtained from any source, including biological and environmental samples. Biological samples can be obtained from animals (including humans) and include liquids, solids, tissues, and gases. However, such examples should not be construed as limiting the type of sample.

[0021] As used herein, the term "subject" refers to any animal (e.g., mammal), including, but not limited to, humans, non-human primates, rodents, etc. Typically, the terms "subject" and "patient" are used interchangeably herein in reference to a human subject.

[0022] As used herein, the term "non-human animal" refers to all non-human animals, including, but not limited to, vertebrates such as rodents, non-human primates, sheep, cattle, ruminants, lagomorphs, pigs, goats, horses, dogs, cats, eyes, etc.

[0023] A "syringe" is a device containing a barrel, typically but not necessarily tubular, that injects or withdraws a sample in a thin stream, typically through a hollow needle. The sample is injected or withdrawn via pressure, usually from a reciprocating pump (e.g., using a piston or plunger). The plunger can be pulled or pushed linearly along the inside of the barrel, allowing the syringe to take in and expel liquid or gas through an outlet opening at the front (open) end of the tubing. The open end of the syringe can be fitted with a hypodermic needle, nozzle, or tubing to help direct the flow into and out of the barrel. The open end of the syringe can be fitted with a cutting device, including a needle and a cutting tool, as described herein.

[0024] The "gauge" of a needle refers to the diameter of the needle. Different gauge systems are known in the art. Numerical gauge values presented herein use the Birmingham Gauge (also known as Stubs Iron Wire Gauge or Birmingham Wire Gauge) to refer to specific dimensions. Table 1 below provides values for inner and outer diameters.

[0025] [Table 1]

[0026] [Brief description of the drawing] FIG. 1 illustrates an exemplary device having an electromagnetic motor mounted on the outside of a syringe barrel.

[0027] [FIG. 2] FIGS. 2A-2D show an exemplary device having a stator attached to the outside of a syringe barrel.

[0028] 3A-3D show exemplary magnet mounting components.

[0029] 4A to 4D show an exemplary stator.

[0030] [FIG. 5] FIGS. 5A-5D show an exemplary device including a needle.

[0031] [FIG. 6] FIGS. 6A to 6C show exemplary needle and rotary cutting tool configurations.

[0032] [FIG. 7] FIGS. 7A and 7B show exemplary needle and rotary cutting tool configurations.

[0033]

[0023] FIGS. 8A-8C show exemplary needle and rotary cutting tool configurations.

[0034]

[0023] FIG. 9 illustrates an exemplary device having an electromagnetic motor attached to the distal end of a needle hub attached to a syringe.

[0035]

[0023] FIG. 10 shows a cross-sectional view of an exemplary device having a stator and magnet attached to the distal end of a needle hub.

[0036] 11A and 11B show a needle (FIG. 11A) and a cutting tool (FIG. 11B) for an exemplary needle within a needle cutting tool arrangement.

[0037]

[0023] FIG. 12 shows an enlarged cross-sectional view of an exemplary distal end of a needle hub including an adhesive hub and a permanent magnet.

[0038]

[0033] FIG. 13 illustrates an exemplary device having an electromagnetic motor attached to the distal end of a needle hub attached to a syringe.

[0039]

[0033] FIG. 14 shows a cross-sectional view of an exemplary device having two stators attached to the distal end of a needle hub.

[0040] 15A and 15B show an exemplary needle hub with a needle (FIG. 15A) and a cutting tool (FIG. 15B) for an exemplary needle within the needle cutting tool arrangement.

[0041] [FIG. 16] FIGS. 16A and 16B show cross-sectional views of an exemplary actuation mechanism including linear movement of the cutting accessory within the needle lumen during operation.

[0042]

[0033] FIG. 17 shows a cross-sectional view of an exemplary device having a stator and squirrel cage attached to the distal end of a needle hub.

[0043]

[0033] FIG. 18 illustrates an exemplary needle cutter within a squirrel cage integrated needle cutter configuration.

[0044] [FIG. 19] FIGS. 19A-19C show alternative views of an exemplary device including a syringe support with integrated battery and electronics.

[0045] [FIG. 20] FIGS. 20A-20C show alternative views of an exemplary device including a syringe support with integrated battery and electronics.

[0046] [FIG. 21] FIGS. 21A-21C show alternative views of an exemplary device including a syringe support with integrated battery and electronics.

[0047] [FIG. 22] FIGS. 22A-22C show alternative views of an exemplary device including a syringe support with integrated battery and electronics.

[0048] [Mode for Carrying Out the Invention] While exemplary embodiments of the present invention are shown in the drawings, it should be understood that the present invention is not limited to these specific examples.

[0049] The components of the device can be made of any suitable material, including but not limited to metal, plastic, and ceramic. When used in a medical setting, the materials are preferably non-allergenic and sterilizable.

[0050] Although the collection of diagnostic amounts of vitreous humor is used to highlight the features and advantages of the systems, devices, and methods, the invention is not limited to this sample type or diagnostic method. The systems, devices, and methods are used to collect any sample type that can be drawn into a needle, with or without the aid of a cutting tool. The systems, devices, and methods are also used in research and clinical settings.

[0051] There are many scenarios in which small-volume liquid vitreous biopsies using systems, devices, and methods can be used. Currently, obtaining vitreous samples from patients with infectious eye diseases and eye cancer is difficult. For example, endophthalmitis, a painful and sight-threatening infection within the eye (where the vitreous resides), can be caused by a variety of microorganisms. Determining the correct pharmacological intervention in a given case of endophthalmitis requires identification of the causative microorganism, which requires sample extraction and culture of the involved bacteria. Liquid vitreous biopsy can be easily applied to this process. Similarly, viral retinitis can result from infection with many types of viruses, and vitreous liquid biopsy can be used in a similar manner to identify the causative virus and delineate appropriate treatment. This approach can also be applied to uveitis, another infectious eye disease that can be caused by a wide range of viruses, parasites, or fungi. Furthermore, liquid vitreous biopsy is readily applicable to eye cancers such as uveal melanoma and primary intraocular lymphoma.

[0052] In these situations, analysis of vitreous humor allows for earlier detection and more accurate prediction of prognosis. In addition to these applications, the expanding use of liquid vitreous biopsy in clinical practice will enable precision medicine approaches to diagnosing and treating retinal diseases, enabling the identification of biomarkers and the development of new treatments across a wide range of retinal diseases.

[0053] Liquid biopsy therefore offers a useful, minimally invasive approach for gleaning important information from specific biological fluids regarding adjacent tissues and finds application in monitoring the state of retinal diseases. Current devices for vitreous extraction are cumbersome, expensive, and poorly suited for aspirating small samples, making them suboptimal for liquid vitreous biopsy in outpatient settings. These limitations delay definitive diagnosis and treatment. To overcome these barriers, systems, devices, and methods provide, for example, inexpensive, handheld, disposable devices for extracting small vitreous samples, enabling streamlined analysis. The systems, devices, and methods find application in ocular infections and cancers for diagnostic and pharmaceutical purposes, facilitating personalized approaches to the diagnosis, prognosis, and treatment of a more diverse set of retinal diseases.

[0054] To minimize the risk of retinal detachment, the vitreous humor must be cut for extraction. In some embodiments, the device includes a magnet attached to the cutting tool, which is manually actuated linearly and / or rotationally using a second magnet external to the syringe. The design allows for simultaneous fluid cutting and extraction. In some embodiments, a small motor is used to rotate a gear that houses an external magnet to rotate the needle. The design does not vary the rotational speed. In some preferred embodiments, a brushless motor is used to vary the rotational speed, reducing vibration and providing a hands-free cutting action.

[0055] An exemplary device is shown in FIG. 1. Syringe 100 includes a barrel 110. The syringe can use any desired mechanism for extracting and / or injecting material, including, but not limited to, a plunger, piston, and pump (not shown). The extraction / injection mechanism can be actuated mechanically (e.g., manually by the user), electrically, or by any other desired approach. The barrel's exterior and interior dimensions are selected to accommodate the desired volume of collected material and for ease of use and convenience. In some embodiments, the barrel stores a sample of 5 mL or less (e.g., 2 mL or less, 1 mL or less, 500 μL or less, 250 μL or less, 100 μL or less). Existing commercially available syringe barrels can be used (e.g., Luer-lock syringe barrels). A longitudinal axis 120 passes through the center of barrel 110. The barrel includes a distal end 140 (extraction / injection end) and a proximal end 150. In some embodiments, a needle is connected to the distal end (not shown).

[0056] The device in Figure 1 uses a motor to actuate a cutting device (not shown) located inside the needle. The motor in Figure 1 consists of four electromagnets 300 made of wire wound around wire mounts 310, shown here as a slotted stator. The wire mounts 310 may contain iron, essentially resulting in electromagnets 300 with a ferromagnetic core. Alternatively, the motor or actuator may include multiple phase coils made of wound or coiled wire, such as a slotless stator design. Any number of electromagnets can be used (e.g., 2, 4, 6, 8, etc.). The electromagnets can be directly or indirectly attached to the exterior surface of the barrel. In Figure 1, the inner surface of the stator is in contact with the exterior surface of the barrel. The stator can be secured to the barrel by pressure, adhesive, or any other desired attachment mechanism. For the prototype used to generate the data in Example 1, two lengths of 40-gauge copper wire were wound around the four poles of the wire mount using a Gorman Star Winder D winding machine (Gorman Machine Corporation, Middleborough, Massachusetts). For rotational motion, the wires were wound in the same direction with opposite poles. For example, if one pole was wound counterclockwise, the opposite pole was also wound counterclockwise, so that the opposite magnetic pole would face the syringe when a current was induced. From an electromechanical standpoint, the above design is very similar to a brushless motor. The permanent magnet(s) (not shown) are conveniently located inside the syringe barrel, keeping the electronics outside. In some embodiments, the permanent magnets are housed in a magnet mounting component 500 that fits within the inner diameter of the barrel 110. In some embodiments, the magnet mounting component 500 has an outer diameter similar to the inner diameter of the barrel, allowing for a snug fit within the barrel 110. In some embodiments, the magnet mounting component 500 is fixed (e.g., via adhesive) to the inner surface of the barrel 110 (magnet not shown). In some embodiments, the magnet mounting component 500 is movable within the barrel.In some embodiments, the magnetic mounting component 500 has an open center in which one or more permanent magnets and cutting tools are positioned to facilitate rotation of the cutting tool in the magnetic field generated by activation of the electromagnetic poles 300. The housing 400, shown here as two separate and distinct sub-components, encloses and protects the electronics.

[0057] Figures 2A-D show different views of an exemplary device, here showing the proximal end of needle housing 760 positioned within barrel 110 of syringe 100. Figure 2A shows a view of the distal end looking into the longitudinal axis of the syringe barrel. Figure 2B shows a side view. Figures 2C and 2D show angled side views.

[0058] 3A-D show different views of an exemplary magnet mounting component 500 with exemplary dimensions (in millimeters). In this embodiment, magnet mounting component 500 includes a stabilizing sleeve 510 sized to fit snugly and contactingly within the inner diameter of a syringe barrel. Magnet mounting component 500 further includes a rotating instrument guide 520, here having a diameter sized to fit snugly and contactingly within the inner diameter of the syringe barrel around its entire circumference. A channel 530 is provided in the rotating instrument guide. The channel accommodates a small permanent magnet and a cutting tool (not shown) that rotates within channel 530 in response to activation of an electromagnet located outside the syringe barrel. FIG. 3A shows a bottom view of magnet mounting component 500. FIG. 3B shows an end view of magnet mounting component 500. FIG. 3C shows an angled side view of magnet mounting component 500. FIG. 3D shows a side view of magnet mounting component 500.

[0059] 4A-D show different views of an exemplary stator 600, along with exemplary dimensions (in millimeters). The exemplary stator has four wire mounts 310. Any number of desired wire mounts can be used. For example, in a slotless design, no wire mounts are used. The stator 600 has a central channel 610 sized to fit the outer diameter of a syringe. FIG. 4A shows a side view of the stator 600. FIG. 4B shows an end view of the stator 600. FIG. 4C shows an angled side view of the stator 600. FIG. 4D shows an alternative side view of the stator 600.

[0060] Figures 5A-D show different views of the assembly of stator 600 and housing 400 attached to syringe 100. A needle 700, including a needle shaft 710, is attached to the distal end of syringe 100 via a needle hub 720. Figure 5A shows a top view of the assembly (end view from the proximal end of the syringe). Figure 5B shows a side view of the assembly. Figure 5C shows a bottom view of the assembly (end view from the distal end of the syringe). Figure 5D shows a cross-sectional view of the assembly at section AA, the location identified in Figure 5B. The proximal end of cutting tool 800 is shown attached to permanent magnet 900. During use, permanent magnet 900 is attached to a magnet mounting component (not shown) below the stator to facilitate cutting rotation of cutting tool 800.

[0061] 6A-C show an exemplary needle 700 and cutting tool 800 configuration. The needle 700 is attached to the distal end of the syringe 100 via a needle hub 720. The cutting tool 800 is disposed within the lumen of the needle shaft 710. A close-up of the needle tip is shown with a 15:1 aspect ratio, showing the tip 810 of the cutting tool 800 disposed at the needle point bevel 730. FIG. 6A shows a side view, FIG. 6B shows a top view, and FIG. 6C shows a close-up angled side view. The exemplary cutting tool 800 has a tapered tip 810. The proximal end of the cutting tool 800 extends from the needle lumen into the syringe interior, where it is connected to a magnetic mounting component (not shown) to facilitate rotation of the cutting tool and rotation of the cutting tool tip 810 within the needle lumen. With this design, the cutting action occurs from the side. The side cuts are designed to allow material entry when the tool tips are aligned and create a guillotine effect when closed. Figures 7A and 7B show an alternative cutting tool 800 design, in this case a twist drill bit configuration. Figures 8A-C show yet another alternative cutting tool 800 design, in which the needle 700 does not terminate in a traditional bevel but rather includes an opening 740. The cutting tool 800 includes a hollow section 820 that provides the cutting action when rotated. In some embodiments, the cutting tool tip has a bladed chisel-like design similar to a regular needle, but with a flat, wide tip to cut the vitreous and remove the outer needle end with each cut. The cutting edge can use different designs (e.g., chisel, convex, asymmetrical, hollow) to improve the cutting action. In some embodiments, the cutting tool employs a double-sided razor blade-like design, whereby the cutting edges are positioned along the sides of the inner rotating portion. Combinations of different cutting designs can also be used.

[0062] FIG. 9 shows an exemplary device having a motor attached to the distal end of a needle hub 720 attached to a syringe 100. The syringe 100 includes a syringe barrel 110 and a plunger 170. A needle 700, including a luminal cutting tool 800, is attached to the distal end of the syringe 100 via the needle hub 720. The device can be used with any of the needle 700 and cutting tool 800 configurations described above. In this design, the stator 600 is either external to or attached to the needle hub 720, with the inner surface of the stator contacting the outer surface of the needle hub. The proximal end of the permanent magnet and cutting tool (not shown) are housed inside the needle hub 720. The proximal end of the needle hub 720 includes an attachment device 750 for secure integration and connection with the syringe 100.

[0063] FIG. 10 shows a cross-sectional view of an exemplary device with a motor attached to the distal end of needle hub 720, a stator 600 attached to the outside of the distal end of needle hub 720, and a permanent magnet 900 inside the distal end of needle hub 720. Magnet 900 has an internal channel used to align and secure cutting accessory 800. In this device, cutting accessory 800 is a needle in a needle configuration such that sample passes through central lumen 840 of cutting accessory 800 and enters the syringe barrel (not shown). A seal or separator 930 separates permanent magnet 900 from syringe tip 160 while allowing cutting accessory 800 to pass through and transfer sample into syringe barrel 110. Pivoting platform 850 reduces contact friction of permanent magnet 900 during rotation by minimizing the contact area between permanent magnet 900 and body 910. Alternatively, or in addition, this may be included at the proximal end of permanent magnet 900. Adhesive hub 920 adhesively bonds needle 700 to needle hub 720. In this device, attachment device 750 is a luer lock connector.

[0064] 11A and 11B show alternative views of the device, including a cutting tool 800 for use with a rotary motor and a needle within the needle configuration of needle 700. FIG. 11A shows one design of needle 700 that includes an opening 740 toward the distal end of the needle and a closed tip. In this embodiment of the needle included in the needle design, cutting tool 800 is an open-tipped needle with a square opening 830, as shown in FIG. 11B. As cutting tool 800 rotates within needle 700, the alignment of opening 740 and opening 830 allows material to enter the central lumen 840 of the cutting tool, and as cutting tool 800 rotates, the sample is severed by a guillotine-like mechanism.

[0065] 12 is a close-up view of the distal end of the needle hub with the needle within the needle cutting accessory arrangement. The needle 700 is secured to the needle hub with adhesive hub 920, providing a central location. The cutting accessory 800 is secured and stabilized in the central internal channel 960 of the permanent magnet. Rotation of the permanent magnet 900 and cutting accessory 800 is driven by the magnetic field generated by the stator (not shown), as described above.

[0066] FIG. 13 shows an exemplary device having a motor attached to the distal end of a needle hub 720 attached to a syringe 100 configured with two or more stators 600. The syringe 100 includes a syringe barrel 110 and a plunger 170. A needle 700 including a luminal cutting tool 800 is attached to the distal end of the syringe 100 via the needle hub 720. The device can be used with any of the needle 700 and cutting tool 800 configurations described above. The distal end of the needle hub 720 contains the motor. In this design, the two stators 600 are either external to or attached to the needle hub 720, with the inner surfaces of the stators contacting the outer surface of the needle hub. Alternative configurations and multiple stator rings are possible for the device. The proximal end of the permanent magnet and cutting tool (not shown) are housed inside the needle hub 720 of the body 910. The proximal end of the needle hub 720 includes an attachment device 750 for secure integration with the syringe 100 .

[0067] FIG. 14 shows a cross-sectional view of an exemplary device with a motor attached to the distal end of the needle hub 720. The polarity of the magnetic field of the stator 600 actuates the permanent magnet 900 and cutting accessory 800 housed in the body 910. In an alternative embodiment (not shown), a single stator and spring or opposing forces can be used to actuate the permanent magnet 900 and cutting accessory 800. A single spring can be adjacent to the permanent magnet 900 at either end of the body 910. In this device, the magnetic field generated by each stator 600 results in linear motion (proximal to distal) of the permanent magnet 900 and cutting accessory 800 within the body 910, causing the cutting accessory 800 to move back and forth within the lumen of the needle 700. Alternatively, a single stator can be used with an opposing force (e.g., a spring) to move the permanent magnet 900 and cutting accessory 800 (proximal to distal) within the body 910.

[0068] Permanent magnet 900 has an internal channel (not shown) that is used to align and secure cutting accessory 800. In this device, cutting accessory 800 is a needle in a needle configuration such that sample passes through central lumen 840 of cutting accessory 800 and into syringe barrel 110. Seal or separator 930 separates the magnet from syringe tip 160 while allowing cutting accessory 800 to pass so that sample can be transferred into syringe barrel 110. Adhesive hub 920 adhesively secures needle 700 to needle hub 720. In this device, attachment device 750 is a luer lock connector.

[0069] Figures 15A and 15B show alternative views of a device including a cutting accessory 800 and a needle within the needle configuration of needle 700. Figure 15A shows an exemplary design of needle 700 with an opening 740 toward the distal end of the needle. In this needle included design, cutting accessory 800 is an open-tipped needle, as shown in Figure 15B.

[0070] 16A and 16B show two cross-sectional views of the device in operation, illustrating an exemplary cutting mechanism of this design. The needle 700 is centrally located and secured to the needle hub 720 with adhesive hub 920. The attraction or repulsion of the magnetic field of each stator 600 causes the permanent magnet 900 and cutting tool 800 to slide within the body 910, with the cutting tool 800 moving within the lumen of the needle 700. Movement within the lumen causes the cutting tool 800 to pass back and forth across the opening 740, thereby acting like a guillotine to cut the sample before it is transferred into the syringe barrel (not shown). Copper wire is wrapped around each stator approximately 200 times in opposite directions to generate a magnetic field that attracts or repels the poles of the permanent magnets. In this respect, the motor design resembles a linear stepper motor.

[0071] 17-20 illustrate an exemplary embodiment of the device including a syringe support 940 connected to the proximal end of the needle hub 720 to connect the syringe tip 160 to the mounting device 750. The syringe support 940 may include an integrated electronics and battery compartment 970, as well as a power button 950 and a power indicator (e.g., an LED) 960. The battery compartment 970 is accessible through a fully or partially removable battery door 980. The syringe support may take any of a variety of configurations to facilitate use by a single operator, either two-handed, as shown in FIGS. 17B, 18B, and 20B, or one-handed, as shown in FIG. 19B. The syringe support may further include a transparent cover 990 (FIG. 20A). The syringe support, needle hub with needle, and cutting tool may be provided as sterile, disposable components for use with a standard sterile syringe supplied separately. Alternatively, the syringe support may be provided with designated syringe(s), needle(s), and cutting tool(s) in a single or multiple package.

[0072] 17-20 further illustrate an exemplary needle within a needle cutting tool configuration in which an inner needle cutting tool 800 rotates within the lumen of needle 700. Needle 700 has an opening 740 along the side (e.g., 1-5 mm from the tip). When aligned with opening 830 in cutting tool 800, sample material enters central lumen 840 of cutting tool 800. As cutting tool 800 rotates, the opening provides a guillotine-like cutting mechanism as it closes across opening 740. The exemplary device can be used with any needle and cutting tool configuration and, as described above, can use an actuator for linear or rotational movement of the cutting tool.

[0073] A variation of the device uses the induction motor principle. This design does not require a magnet as the internal rotor. Instead, a similar effect is achieved through induction. The magnet is replaced with a conductive loop or squirrel cage-like section made of metal (e.g., copper, aluminum), as shown in Figures 17 and 18. The rotating magnetic field induces current in the cage bars inside the cage. This in turn generates an electromagnetic force, causing it to rotate. This induction motor-like design can use any of the internal rotating parts / needles described in the brushless-like design above. Induction motors can also be used for linear motion. Linear motion is achieved by a pulsating electric field rather than a rotating one, as described for rotation, and uses reaction plates instead of permanent magnets.

[0074] FIG. 17 shows a cross-sectional view of an exemplary device with a motor attached to the distal end of the needle hub 720, a stator 600 attached to the outside of the distal end of the needle hub 720, and a squirrel cage 860 inside the distal end of the needle hub 720. The size of the squirrel cage 860 is configured to provide clearance around the edges to ensure smooth rotation. The cutting accessory 800 passes through the center of the squirrel cage 860. The squirrel cage 860 and cutting accessory 800 can rotate from low to high speeds as controlled by the device user. In this device, the cutting accessory 800 is a needle in a needle configuration such that the sample passes through the central lumen 840 of the cutting accessory 800 and enters the syringe barrel 110. A seal or separator 930 separates the squirrel cage 860 from the syringe tip 160 while allowing the sample to pass through the cutting accessory 800 and transfer to the syringe barrel 110. The pivoting platform 850 reduces contact friction of the squirrel cage 860 during rotation by minimizing the contact area between the squirrel cage 860 and the body 910. Alternatively, or in addition, it may be included at the proximal end of the squirrel cage 860. An adhesive hub 920 adhesively secures the needle 700 to the needle hub 720. In this device, the attachment device 750 is a luer lock connector.

[0075] FIG. 18 shows an alternative view of a device including a cutting accessory 800 and a needle within a squirrel cage 860 needle configuration. In this device, the squirrel cage 860 is composed of two shorting disks 870 and a number of metal posts 880 spanning between the shorting disks. When a magnetic field is generated by a stator (not shown), current is induced along the metal posts 880, generating a force that generates sufficient torque to rotate the squirrel cage 860 according to Lorentz's law. Given that the cutting accessory 800 is fixed to the two shorting disks 870 of the squirrel cage 860, the cutting accessory 800 will rotate relative to the squirrel cage 860. In this embodiment, the cutting accessory 800 is a needle within a needle design that includes an open-tipped needle with a square opening 830.

[0076] Another variation of the device uses a mechanical component to actuate the cutting tool. For example, a mechanism such as a spring can be used to store energy and convert it into linear or rotational motion of the cutting tool. The devices described herein can be used in methods for collecting a sample (e.g., a biological sample, such as a vitreous sample). In some embodiments, the method includes: a) positioning the distal end of the needle in a region containing the sample to be collected; b) actuating an actuator to rotate the cutting tool; and c) drawing the sample into a collection volume. In some embodiments, the method further includes attaching a syringe to the needle hub; detaching the syringe from the needle hub; capping a collection volume for transport; and dispensing the sample from the collection volume for analysis. In some embodiments, the method is performed without injecting a material into the sample location (e.g., the eye). In some embodiments, the method is performed after or before injecting a material into the eye. In some embodiments, the method further includes detaching the syringe from the needle hub; attaching an injection syringe to the needle hub, the injection syringe containing the fluid to be injected; and injecting the fluid into the region. The fluid to be injected may include a pharmaceutical agent.

[0077] In some embodiments, the collected sample is tested to identify one or more markers of interest. Identification can occur within the device. Alternatively, the sample is expelled or otherwise removed from the device and tested externally. In some embodiments, the sample is drawn into a test zone within the device. The test zone contains one or more reagents or other components that detect one or more markers of interest. Markers of interest include, but are not limited to, proteins, peptides, nucleic acids (e.g., mRNA, microRNA, DNA, DNA methylation status, cfDNA, etc.), hormones, metabolites, chemokines, cytokines, inflammatory markers, cancer or precancerous biomarkers, infectious disease agents or components or by-products thereof, drugs and other therapeutic or candidate therapeutic agents, etc. The test zone may contain capture particles specific for the marker(s). In some embodiments, a lateral flow strip is provided in the device to detect one or more markers of interest using either a sandwich or competitive immunoassay format. Analysis of biomarkers finds use in detecting, analyzing, and monitoring diseases and conditions, and medical interventions for such diseases and conditions, including, but not limited to, infectious diseases, cancer and other proliferative diseases, diabetes (e.g., diabetic retinopathy), Alzheimer's disease, ischemic retinopathy, glaucoma, endophthalmitis, macular degeneration, vision problems, dry eye, and the like.

[0078] The present invention can also be configured as follows.

[0079] <1> A device, a) a syringe including a barrel having a longitudinal axis, the barrel comprising a sample collection volume; b) a needle connected to the distal end of the syringe at a needle hub, the needle having a lumen; c) a cutting tool disposed within the lumen of the needle; and d) an actuator that moves the cutting tool linearly or rotationally within the needle.

[0080] <2> A device, a) a syringe, i) a cutting tool disposed at least partially within the needle lumen, the cutting tool having a proximal end including one or more permanent magnets or metallic structures, the cutting tool configured for linear or rotational movement within the needle lumen; ii) a barrel having a longitudinal axis, the barrel containing a sample collection volume; and b) a motor disposed outside the syringe configured to linearly or rotationally move the cutting tool under magnetic force.

[0081] <3> the needle is 20 gauge or smaller; <1> or <2> The device described in

[0082] <4> the needle is 24 gauge or smaller; <3> The device described in

[0083] <5> Equipped with a battery, <1> or <2> The device described in

[0084] <6> Further comprising a power cord; <1> or <2> The device described in

[0085] <7> the cutting tool includes a drill bit; <1> or <2> The device described in

[0086] <8> The drill bit is a twist drill bit. <7> The device described in

[0087] <9> the cutting tool has a distal blade; <1> or <2> The device described in

[0088] <10> The cutting tool is an internal needle. <1> or <2> The device described in

[0089] <11> the cutting tool is hollow; <1> or <2> The device described in

[0090] <12> Both the needle and the cutting tool have openings in their sides that allow material to enter when aligned and provide a guillotine cutting mechanism when closed. <11> The device described in

[0091] <13> The collected volume is 1 mL or less. <1> or <2> The device described in

[0092] <14> The collected volume is 500 μL or less. <13> The device described in

[0093] <15> The collected volume is 250 μL or less. <14> The device described in

[0094] <16> the actuator comprises one or more magnets; <1> The device described in

[0095] <17> the actuator includes a plurality of electromagnets arranged about the longitudinal axis; <16> The device described in

[0096] <18> the plurality of electromagnets includes two or more electromagnets; <17> The device described in

[0097] <19> the plurality of electromagnets includes four or more electromagnets; <17> or <18> The device described in

[0098] <20> the plurality of electromagnets are on the same or different support structures; <17> ~ <19> 1. A device according to any one of the preceding claims.

[0099] <21> the plurality of electromagnets being on two or more support structures; <20> The device described in

[0100] <22> the support structure is a slotted stator; <20> or <21> The device described in

[0101] <23> the actuator includes a plurality of phase coils; <16> The device described in

[0102] <24> the actuator includes one or more slotless stators; <23> The device described in

[0103] <25> the device further comprises one or more permanent magnets or metal structures; <16> ~ <24> 1. A device according to any one of the preceding claims.

[0104] <26> the one or more metallic structures generating an induced current; <25> The device described in

[0105] <27> the one or more metal structures are squirrel cage rotors; <26> The device described in

[0106] <28> the metal structure inside the barrel generates an electromagnetic force; <26> The device described in

[0107] <29> further comprising a spring adjacent to the one or more permanent magnets or metal structures. <25> The device described in

[0108] <30> the actuator is external to the syringe barrel; <25> The device described in

[0109] <31> the one or more permanent magnets or metal structures are disposed inside the barrel; <30> The device described in

[0110] <32> the actuator is disposed at the distal end of the needle hub; <25> The device described in

[0111] <33> the one or more permanent magnets or the one or more metallic structures are disposed inside the distal end of the needle hub; <32> The device described in

[0112] <34> the motor includes a plurality of electromagnets arranged about the longitudinal axis; <2> The device described in

[0113] <35> the plurality of electromagnets includes two or more electromagnets; <34> The device described in

[0114] <36> the plurality of electromagnets includes four or more electromagnets; <34> or <35> The device described in

[0115] <37> the plurality of electromagnets are on the same or different support structures; <34> ~ <36> 1. A device according to any one of the preceding claims.

[0116] <38> the plurality of electromagnets being on two or more support structures; <37> The device described in

[0117] <39> the support structure is a slotted stator; <37> or <38> The device described in

[0118] <40> the motor includes multiple phase coils; <2> The device described in

[0119] <41> the motor includes one or more slotless stators; <40> The device described in

[0120] <42> further comprising a spring adjacent to the one or more permanent magnets or metal structures. <2> The device described in

[0121] <43> the motor is external to the syringe barrel; <2> The device described in

[0122] <44> the one or more permanent magnets or the one or more metal structures are disposed inside the barrel; <43> The device described in

[0123] <45> the motor is disposed at the distal end of the needle hub; <2> The device described in

[0124] <46> the one or more permanent magnets or the one or more metallic structures are disposed inside the distal end of the needle hub; <45> The device described in

[0125] <47> the one or more metallic structures generating an induced current; <2> The device described in

[0126] <48> the one or more metal structures are squirrel cage rotors; <47> The device described in

[0127] <49> the metal structure inside the barrel generates an electromagnetic force; <47> The device described in

[0128] <50> <1> ~ <49> A system comprising the device according to any one of the preceding items and a biological sample.

[0129] <51> the biological sample comprises a vitreous sample; <50> The system described in

[0130] <52> <1> ~ <49> 2. A method comprising collecting a biological sample using the device described in any one of claims 1 to 11.

[0131] <53> a) placing the distal end of the needle in an area containing the biological sample to be collected; b) actuating the actuator to rotate the cutting accessory; and c) drawing a sample into said collection volume; <52> The method described below.

[0132] <54> Attaching the syringe to the needle hub; and further comprising removing the syringe from the needle hub. <52> or <53> The method described below.

[0133] <55> attaching an injection syringe to the needle hub, wherein the injection syringe contains a fluid to be injected; and further comprising injecting a fluid into the region. <54> The method described below.

[0134] <56> the injected fluid comprises a pharmaceutical agent; <55> The method described below.

[0135] <57> further comprising analyzing the biological sample. <52> ~ <56> A method according to any one of the preceding claims.

[0136] <58> the area containing the biological sample to be collected is the eye; <52> ~ <57> A method according to any one of the preceding claims.

[0137] <59> the biological sample is a vitreous sample; <52> ~ <58> A method according to any one of the preceding claims.

[0138] <60> <1> ~ <49> Use of any of the devices.

[0139] <61> for collecting biological samples, <1> ~ <49> Use of a device according to any of the preceding claims.

[0140] <62> the biological sample is a vitreous sample; <61> Use as described in.

[0141] [Example] A prototype device was constructed and tested. A permanent magnet (a 0.125" + 0.004" diameter, 0.250" + 0.004" height, diametrically magnetized, nickel-plated cylinder from K&J Magnetics, Inc. (Item #D24DIA; Pipersville, PA) was used. The cutting tool used was a 0.006" diameter hollow 304 stainless steel hypodermic tubing (Item #304H34RW; MicroGroup; Medway, MA) or a 0.004" diameter 304 stainless steel wire (Item #9882K53; McMaster-Carr; Aurora, OH). Hot glue was used to attach the cutting tool and magnet to a 3D-printed magnet mounting component attached to a syringe. A four-pole electromagnet motor was secured to the outside of the syringe. The motor windings and permanent magnet allowed for variable rotation frequency using a power amplifier and a stepper motor microcontroller. Using a power amplifier and a microcontroller, the internal magnet and needle rotated at a set angular velocity.

[0142] The device was tested using a water sample to confirm that the fluid was pulled through a small cross-sectional area of the external needle with the internal cutting tool. Experiments were performed to extract milk. The sample fluid was successfully extracted with and without the cutting tool rotating. However, data showed that extraction times were faster (>10% faster) when the motor was running.

[0143] Furthermore, in experiments conducted with egg yolk, this design mechanism prevented the needle from clogging, as observed with standard syringes without a cutting tool. [Brief explanation of the drawings]

[0144] [Figure 1] 1 shows an exemplary device having an electromagnetic motor mounted on the outside of a syringe barrel. [Figure 2] 2A-2D show an exemplary device having a stator attached to the outside of a syringe barrel. [Figure 3] 3A-3D show exemplary magnet mounting components. [Figure 4] 4A-4D show an exemplary stator. [Figure 5] 5A-5D show an exemplary device including a needle. [Figure 6] 6A-6C show exemplary needle and rotary cutting tool configurations. [Figure 7] 7A and 7B show an exemplary needle and rotary cutting tool configuration. [Figure 8] 8A-8C show exemplary needle and rotary cutting tool configurations. [Figure 9] 1 shows an exemplary device having an electromagnetic motor attached to the distal end of a needle hub attached to a syringe. [Figure 10] 1 shows a cross-sectional view of an exemplary device having a stator and magnet attached to the distal end of a needle hub. [Figure 11] 11A and 11B show the needle (FIG. 11A) and cutting tool (FIG. 11B) for an exemplary needle within needle cutting tool configuration. [Figure 12] 1 shows an enlarged cross-sectional view of an exemplary distal end of a needle hub including an adhesive hub and a permanent magnet. [Figure 13] 1 shows an exemplary device having an electromagnetic motor attached to the distal end of a needle hub attached to a syringe. [Figure 14] 1 shows a cross-sectional view of an exemplary device having two stators attached to the distal end of a needle hub. [Figure 15] 15A and 15B show an exemplary needle hub with a needle (FIG. 15A) and a cutting tool (FIG. 15B) for an exemplary needle within the needle cutting tool arrangement. [Figure 16] 16A and 16B show cross-sectional views of an exemplary actuation mechanism involving linear movement of the cutting accessory within the needle lumen during operation. [Figure 17] 1 shows a cross-sectional view of an exemplary device having a stator and squirrel cage attached to the distal end of a needle hub. [Figure 18] 10 shows an exemplary needle cutter within a squirrel cage and integrated needle cutter configuration. [Figure 19A] 19A-19C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 19B] 19A-19C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 19C] 19A-19C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 20A] 20A-20C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 20B] 20A-20C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 20C] 20A-20C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 21A] 21A-21C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 21B] 21A-21C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 21C] 21A-21C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 22A] 22A-22C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 22B] 22A-22C show alternative views of an exemplary device including a syringe support with integrated battery and electronics. [Figure 22C] 22A-22C show alternative views of an exemplary device including a syringe support with integrated battery and electronics.

Claims

1. a syringe comprising a plunger and a barrel having a longitudinal axis and a sample collection volume; a needle hub having an attachment device for connecting to the syringe, the syringe being connected to the needle hub; a syringe support connected to the needle hub, the syringe support including a compartment, a power button, and a power indicator; a microcontroller disposed within the compartment; a needle connected to the needle hub, the needle having a lumen; an inner needle disposed at least partially within the needle lumen, the inner needle being hollow; and a motor for rotationally moving the inner needle within the needle hub, the motor comprising one or more permanent magnets disposed inside the needle hub and attached to the inner needle, the motor further comprising a plurality of coils mounted outside the needle hub; the needle includes a first opening formed in a side of the needle; the inner needle includes a second opening formed in a side of the inner needle; when the second opening is aligned with the first opening, material can enter; The device wherein the material is cut as the second opening rotates past the first opening.

2. The device of claim 1 , wherein the plurality of coils are arranged about the longitudinal axis.

3. The device of claim 1 , wherein the motor is disposed outside the barrel.

4. The device of claim 1 , further comprising a battery disposed within the compartment.

5. The device of claim 1 , wherein the syringe is removably connected to the needle hub.

6. The device of claim 1 , wherein the needle is 20 gauge or smaller.

7. 10. The device of claim 1, further comprising a separator separating the one or more permanent magnets from the syringe for passing a sample through the internal needle and into the barrel.

8. The device of claim 1 , further comprising a pivoting platform in contact with the one or more permanent magnets.

9. The device of claim 1 , wherein the device is provided as a sterile, disposable component.

10. The device of claim 1 , wherein the motor rotationally moves the internal needle at a constant speed.

11. 10. A system comprising the device of claim 1 and a biological sample collected in the barrel.

12. The system of claim 11 , wherein the collected biological sample is 1 mL or less.

13. The system of claim 11 , wherein the collected biological sample is 250 μL or less.

14. The system of claim 11 , wherein the biological sample is a vitreous sample.

15. 10. A method comprising collecting a biological sample with the device of claim 1, comprising: The method comprises: a) positioning the distal end of the needle in an area containing the biological sample to be collected; b) actuating the power button and running the motor to move the internal hand; and c) drawing the biological sample into the sample collection volume; A method comprising:

16. 16. The method of claim 15, further comprising analyzing the biological sample.

17. 17. The method of claim 16, wherein analyzing the biological sample comprises detecting biomarkers for one or more diseases or conditions.

18. The method of claim 15, wherein the biological sample is a vitreous sample.

19. 16. The method of claim 15, further comprising disposing of the device after collecting the biological sample.

20. 16. The method of claim 15, wherein drawing the biological sample into the sample collection volume comprises drawing no more than 1 mL of the biological sample.

21. 16. The method of claim 15, wherein drawing the biological sample into the sample collection volume comprises manually actuating the plunger with one hand while holding the device with the other hand.

22. 16. The method of claim 15, wherein collecting the biological sample is performed by a single operator with two hands.

23. 16. The method of claim 15, wherein collecting the biological sample with the device does not occur in an operating room.

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