Medical device detection system and method

Abstract

A biomarker detection system is disclosed, comprising a target biomarker and a fluid distribution system, the fluid distribution system having a delivery device, the delivery device having a distal end. The fluid distribution system is in contact with the target biomarker. The delivery device comprises a lumen and a fluid channel. The disclosed biomarker detection system further comprises a biomarker luminescent material in contact with the distal end of the delivery device. The system also comprises an optical system in optical communication with the biomarker luminescent material, the optical system comprising an optical receiver and a detector.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 770,676, entitled “DETECTION SYSTEMS AND METHODS FOR MEDICAL DEVICES,” filed on November 21, 2018, and any other U.S., international, or national phase patent applications resulting from the aforementioned application, which are incorporated herein by reference in their entirety, with the limitation that any subject matter contrary to the express disclosure herein is not incorporated. Technical Field

[0003] The present disclosure relates to systems and methods for detecting biological substances and differentiating between bodily media. More specifically, the present disclosure relates to systems and methods for detecting biological substances and differentiating between bodily media in conjunction with a medical device that can be advanced into a patient's body. Background Art

[0004] Efforts to improve surgical outcomes and cost structures, especially for spinal surgery, have led to an increase in the use of minimally invasive surgery. These surgeries typically use image-guided modalities, such as fluoroscopy, CT, neurostimulators, and, in recent years, Doppler ultrasound. Although minimally invasive spinal surgery, pain management surgery, nerve blocks, ultrasound-guided interventions, biopsies, percutaneous placement, or open intraoperative placements are generally less risky than surgical procedures, there is still a risk of ineffective results and iatrogenic injury, such as infection, stroke, paralysis, and death caused by penetration of various structures (including but not limited to organs, soft tissues, vascular structures, and neural tissues such as the spinal cord, which are fatal). Regardless of the experience of the practitioner, injury may occur because surgical instruments must pass through multiple layers of body tissue and fluids to reach the desired cavity in the spinal canal.

[0005] To illustrate this point, the intrathecal (or subarachnoid) cavity in the spinal region where many drugs are used accommodates nerve roots and cerebrospinal fluid (CSF) and is located between two of the three layers of membranes that wrap the central nervous system. The outermost membrane of the central nervous system is the dura mater, the second layer of membrane is the arachnoid membrane, and the third layer, i.e., the innermost membrane, is the pia mater. The intrathecal cavity is located between the arachnoid membrane and the pia mater. In order to reach this region, surgical instruments may need to first pass through the skin layer, fat layer, interspinous ligament, ligamentum flavum, epidural space, dura mater, subdural space and intrathecal cavity. In addition, for the needle used to apply the drug, the entire pinhole must be in the subarachnoid space.

[0006] Due to the complexity involved in inserting surgical instruments into the lumen of the sheath, penetration of the spinal cord and neural tissue is known to be prone to complications in minimally invasive spinal surgery and spinal surgery. In addition, some operations require the use of larger surgical instruments. For example, spinal cord stimulation in the form of minimally invasive spinal surgery, in which a small wire can be inserted into the spinal epidural space, may require the introduction of a 14-gauge needle into the epidural space to pass the stimulator lead. Needles of this size are technically more difficult to control, resulting in a higher risk of morbidity. Complications may include secondary hematomas caused by dural tears, cerebrospinal fluid leakage, epidural vein rupture, and paralysis caused by direct penetration of the spinal cord or nerves. These and other high-risk situations, such as spinal interventions and radiofrequency ablations, may occur when the practitioner is unable to detect the position of the needle or surgical device tip in critical anatomical structures.

[0007] Currently, detection of such structures is operator dependent, with the operator utilizing touch, contrast agents, palpation of anatomical landmarks, and visualization in an image-guided mode. Patient safety may be dependent on the practitioner’s training and experience in touch and image interpretation. Even though additional training and experience may help the practitioner, iatrogenic injury may occur independently of the practitioner’s experience and skill because anatomical variability may occur naturally or as a result of repeated procedures in the form of scar tissue. Specialty training for some procedures, such as radiofrequency ablation, may not be rigorous enough to ensure competence; even with training, surgical outcomes can vary widely. In the case of epidural injections and spinal surgery, variations in ligamentum flavum thickness, epidural space width, dural expansion, epidural lipomatosis, dural septa, and scar tissue can all present challenges to traditional validation methods, even for experienced operators. Additionally, repeat radiofrequency procedures when nerves are regenerating (usually a year or more later) are often less effective and more difficult because of the additional anatomical variability created by the distribution of the regenerated nerves. Summary of the invention

[0008] In view of these considerations, there is a need for systems and methods that can provide real-time feedback to aid in the precise placement of surgical instruments into a patient's anatomy.

[0009] In one aspect, a biomarker detection system is disclosed, which includes a target biomarker in a biological system. The disclosed biomarker detection system includes a fluid distribution system, which includes a delivery device having a distal end. The fluid distribution system contacts the target biomarker and includes a lumen and a fluid channel. The biomarker luminescent material contacts the distal end of the delivery device. The disclosed biomarker detection system also includes an optical system optically connected to the biomarker luminescent material, wherein the optical system includes an optical receiver and an optical detector. In some embodiments, the optical system may include an optical fiber, an optical coupler, or both.

[0010] In another aspect, a biomarker detection system is disclosed, comprising a target biomarker in a biological system and a fluid distribution system. The fluid distribution system comprises a delivery device having a distal end. The fluid distribution system contacts the target biomarker and the delivery device comprises a lumen and a fluid channel. The disclosed biomarker detection system is in communication with the target biomarker. The detection system uses a method that relies on properties of conductivity, refractive index, or sound to detect the presence of the target biomarker.

[0011] In yet another aspect, a method for delivering a medicinal fluid to a patient is disclosed, the method comprising using a biomarker detection system to locate the presence of a target biomarker in the patient. The biomarker detection system comprises a fluid distribution system, the fluid distribution system comprises a delivery device, the delivery device having a distal end. The fluid distribution system contacts the target biomarker, and the delivery device comprises a lumen and a fluid channel, and the biomarker luminescent material contacts the distal end of the delivery device. The biomarker detection system also comprises an optical system optically connected to the biomarker luminescent material. The optical system comprises an optical receiver and an optical detector. The method further comprises delivering the medicinal fluid to the patient and notifying a clinician that the target biomarker has been detected.

[0012] In this disclosure, the terms:

[0013] "Optical receiver" means a light detection device constructed and arranged to detect light returning along an optical path from a bioluminescent device to an optical detector;

[0014] "Optical detector" means a device that senses and can measure the amount of light in its optical path;

[0015] "Optical coupler" means a device constructed and arranged to couple light between a fluid channel and at least one optical fiber; and

[0016] An "optical filter" refers to a device that receives light and allows only light having specific properties, such as wavelength, polarity, intensity, or other selective properties, to pass therethrough. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The following description should be read with reference to the accompanying drawings. The drawings, which are not necessarily drawn to scale, depict examples and are not intended to limit the scope of the present disclosure. The present disclosure may be more fully understood by considering the following description of various examples in conjunction with the accompanying drawings, in which:

[0018] Figure 1 is a schematic half-section view of an illustrative example of a portion of a biomarker detection system according to the present disclosure;

[0019] Figure 2 is a schematic half-section view of another illustrative example of a portion of a biomarker detection system according to the present disclosure;

[0020] Figure 3A is a schematic cross-sectional view of yet another illustrative example of components that are part of a biomarker detection system according to the present disclosure;

[0021] Figure 3B Is provided to show Figure 3A schematic cross-sectional views of enlarged views of details of some components of the system;

[0022] Figure 4 is a schematic cross-sectional view of yet another illustrative example of components of a portion of a biomarker detection system according to the present disclosure;

[0023] Figure 5A is a schematic cross-sectional view of yet another illustrative example of a portion of a biomarker detection system according to the present disclosure;

[0024] Figure 5B Is provided to show Figure 5A schematic cross-sectional views of enlarged views of details of some components of the system;

[0025] Fig. 6A is a schematic cross-sectional view of yet another illustrative example of a portion of a biomarker detection system depicted in a detection configuration according to the present disclosure;

[0026] Figure 6B Is in a post-test fluid delivery configuration Fig. 6A Schematic cross-sectional view of the system.

[0027] Fig. 7A is a schematic cross-sectional view of an embodiment of a biomarker detection needle according to the present disclosure;

[0028] Figure 7B It is from Fig. 7A When viewed from the left side of the depicted needle Fig. 7A A schematic plan view of a needle;

[0029] Fig. 8A ,8B , 8C and 8D are schematic cross-sectional views down the bore of a needle according to the present disclosure providing an optical fiber and a lumen along its length;

[0030] Fig. 9 is a schematic cross-sectional view of an embodiment of a fiber optic sensor for distinguishing between air and liquid applicable to the provided disclosure;

[0031] Fig.10 is a schematic cross-sectional view down a bore of an illustrative example of a needle system that may incorporate the disclosed fiber optic air sensor;

[0032] Fig.11 is a schematic cross-sectional view of an embodiment of a needle system that may incorporate an acoustic wave air sensor;

[0033] Fig. 12A is a schematic plan view of an illustrative example of an embodiment of a needle system that may incorporate an electrical air sensor;

[0034] Fig. 12B yes Fig. 12A A schematic side cross-sectional view of a needle system;

[0035] Fig. 12C is along Fig. 12A A schematic cross-sectional view of a needle system with the hole pointing downward;

[0036] Fig.13A is a schematic side cross-sectional view of an illustrative example of another embodiment of a needle system that may be incorporated with an electrical air sensor;

[0037] Fig. 13B is along Fig.13A A schematic cross-sectional view of a configuration of a needle system with the hole facing downward; and

[0038] Fig. 13C is along Fig.13A Schematic cross-sectional view of another configuration of the needle system with the hole downward.

[0039] The disclosed biomarker detection system can improve some shortcomings in the field. Its use can improve surgical outcomes and cost structures, especially spinal surgery and other minimally invasive surgical procedures. The disclosed biomarker detection device can eliminate the operator's dependence on finding target biomarker materials, instead of relying on touch, contrast agents, anatomical landmark palpation, and visualization in image-guided mode, thereby improving the safety and effectiveness of surgeries requiring biomarker identification. DETAILED DESCRIPTION

[0040] The present disclosure relates to systems and methods for detecting biological substances (e.g., body fluids and tissues, including blood) and for distinguishing body media (e.g., liquids and air). Various embodiments of the system and method will be described in detail with reference to the accompanying drawings, wherein similar reference numerals may represent similar components and assemblies throughout several views. Reference to various embodiments does not limit the scope of the system and method disclosed herein. In addition, any examples set forth in this specification are not intended to be restrictive, and only set forth some of the many possible embodiments for the system and method. It should be understood that, when circumstances dictate or as the case may be, various omissions and substitutions of equivalents are contemplated, but these omissions and substitutions are intended to include applications or embodiments without departing from the spirit or scope of the present disclosure. In addition, it should be understood that the wording and terminology used herein are for the purpose of description and should not be considered as restrictive.

[0041] The present disclosure provides systems and methods that are constructed, configured and / or capable of detecting one or more biomarkers and optical detection of the interaction via the interaction of the biomarker with one or more detection materials. In some examples, the interaction of the biomarker with the detection material can result in a luminescent emission of light that can be sensed, wherein the sensing of the luminescent light provides proof of the interaction, and thus provides proof of the presence of the biomarker. In some of these examples, the emission of light can be an intrinsic chemiluminescent product of the interaction between the biomarker and the detection material. In other examples of these examples, when the biomarker is present, the illumination of an external light source of the detection material can result in a fluorescent or phosphorescent emission of light that can be sensed. The present disclosure provides systems and methods that can provide detection of biomarkers via sensing chemiluminescence, fluorescence and / or phosphorescence.

[0042] Although multiple examples of biomarker detection systems shown and described in the present disclosure include or can be used in combination with needles and fluid delivery systems, the applications of the disclosed biomarker detection systems and methods are not limited to fluid delivery applications. In the present disclosure, medicinal fluids can be delivered by the disclosed fluid delivery systems. Fluid delivery systems incorporating the detection technology of the present disclosure can be used to deliver wires / leads, nanoparticles, and any suitable pharmacological or other therapeutic agents, including regenerative medicines and chemotherapeutic drugs.

[0043] Figure 1An illustrative example of a biomarker detection system 100 of the present disclosure is schematically depicted. The system 100 can include a needle 102 having a lumen 103 that can deliver fluid from a syringe 104 or other suitable fluid dispensing system to a tip 106 of the needle via a fluid channel 108 (the fluid channel including the lumen 103). A biomarker luminescent material 110 can be placed at or within and adjacent to the tip 106 of the needle 102, for example, via a coating process.

[0044] The system 100 may include an optical coupler 112 that may be constructed and configured to couple light between the fluid channel 108 and the optical fiber 114. The optical coupler 112 of the present disclosure and any other optical coupler may be constructed and configured to be used as a wavelength division multiplexer that may improve the signal-to-noise ratio by, for example, filtering the spectrum of light reaching the detector. The optical fiber 114 having a core material having a refractive index substantially close to or substantially equal to the refractive index of the fluid in the fluid channel 108 may be selected so that light can be easily coupled between the two while minimizing reflection losses and other optical problems that may be caused by optical mismatches. Alternatively or in addition, for example, by selecting the concentration of various components of the fluid (e.g., glucose, alcohol, sugar salts, and / or any other biocompatible fluid), the refractive index of the fluid in the channel 108 may be adjusted to substantially or substantially accurately match the refractive index of the core of the optical fiber 114. The fluid channel 108 may be constructed and configured so that it may be used as an optical waveguide in the presence of a fluid.

[0045] A light source 116, such as a diode laser or other suitable light source, can be optically coupled to the optical fiber 114 so that light from the light source can be delivered to the tip 106 of the needle 102, and more specifically, to the biomarker luminescent material 110 at the tip, via the optical fiber and optical waveguide provided by the fluid channel 108. Light emitted or otherwise scattered from the biomarker luminescent material 110 can be returned by the optical path provided by the fluid channel 108 and the optical fiber 114 to an optical receiver 118, which can be a photodetector or any other suitable light detection device constructed and configured to detect light returned along the optical path from the tip 106 of the needle 102. The optical coupler 112 can be constructed, configured, and tuned so that it can effectively couple light between the fluid channel 108 and the optical fiber 114 for any relevant optical frequency, including one or more emission frequencies of the light source 116 and the emission frequency of the biomarker luminescent material 110.

[0046] Through various mechanisms, light from the light source 116 may undesirably reach the optical receiver 118, for example, via back reflection from tissue and other backscattering pathways, thereby increasing the noise read by the receiver 118 when the receiver 118 measures the signal emitted by the luminescence emission of the biomarker luminescent material 110. This source of measurement noise can be offset in a variety of ways. As previously described, the optical coupler 112 can be constructed and configured to act as a wavelength division multiplexer, which can selectively filter the frequency of light incident on the optical receiver 118 to the frequency emitted from the biomarker luminescent material 110. Alternatively or in addition, the optical receiver 118 can include a filter to selectively prevent frequencies other than the luminescence frequency of the biomarker luminescent material 110 from reaching the optical receiver, such as illumination light from the light source 116 and other light that may be present in the environment, such as ambient room lighting. Other measures to improve the signal-to-noise ratio can be taken, such as filtering the room lighting to attenuate the emission at the sensitivity frequency of the optical receiver 118. Such wavelength and frequency filtering / sensitivity considerations can be applied to any relevant system of the present disclosure.

[0047] Another technique that can be used to improve the signal-to-noise ratio for detecting light emitted from the biomarker luminescent material 110 at the optical receiver 118 is time division multiplexing. This source of noise can be avoided by temporally separating the illumination of the biomarker luminescent material 110 by the light source 116 from the detection of the luminescent emission from the material. In an illustrative example, the light source 116 can be driven with a full-on, full-off square wave. With a light source 116 that can be turned off quickly enough (i.e., fast compared to the decay time constant of the luminescent emission from the biomarker luminescent material 110), data collection from the optical receiver 118 can be gated to be performed only when the light source 116 is off, so that no back-reflected / scattered light originating from the light source 116 is recorded at the optical receiver 118. Potentially, other light sources that may undesirably reach the optical receiver 118 (e.g., as may be employed in a surgical operating room) can also be driven with the same waveform as the light source 116 to prevent it from being detected. At sufficiently high frequencies, such pulses are imperceptible to the human eye. These time division multiplexing methods may be advantageously used with any compatible systems and methods of the present disclosure.

[0048] In an example method of use of the system 100, a clinician may advance the needle 102 into a patient, wherein the light source 116 is activated to provide illumination of the biomarker luminescent material 110. A fluid having an optically suitable refractive index may be present in the fluid channel 108 (including the lumen 103). The needle 102 may be advanced until the tip 106 of the needle encounters a target biomaterial (e.g., blood, but other target biomaterials are possible), where the interaction of the target biomaterial (e.g., blood) with the biomarker luminescent material 110 combined with the illumination light from the light source 116 may result in emission of light from the biomarker luminescent material, which may be detected by the optical receiver 118. A notification system (not shown) operably coupled to the optical receiver 118 may notify the clinician that a target biomarker has been detected. The clinician may then position the tip 106 of the needle 102 based on the detection of the target biomaterial and knowledge of the patient's anatomy (e.g., further advancement, stopping advancement, or retracting the needle). With the tip 106 of the needle 102 properly positioned, delivery of a therapeutic fluid from a fluid delivery system through the fluid channel 108 may be performed.

[0049] Figure 2 Another illustrative example of another biomarker detection system 200 of the present disclosure is schematically depicted. The system 200 can include a needle 202 that can deliver fluid from a syringe 204 or other suitable fluid dispensing system to a tip 206 of the needle via a fluid channel 208. The needle 202 and syringe 204 can be fluidically coupled via one or more fluid connectors 209, which can be any suitable connector, such as (but not limited to) a LUER lock fitting. The fluid channel 208 can include a lumen 210 of the needle 202. In Figure 2 In the configuration of the system 200 shown, the lumen 210 of the needle 202 can be at least partially occupied by an optical fiber 212. The optical fiber 212 can contain a biomarker luminescent material 214 attached to its distal tip, for example, via a coating process. Figure 2 As shown, an optical fiber 212 having a biomarker luminescent material 214 attached to its distal tip can be positioned in the lumen 210 of the needle 202 such that the biomarker luminescent material is positioned at or near the tip 206 of the needle 202. In some embodiments of this configuration, the optical fiber 212 can substantially block the passage of fluid through the lumen 210 of the needle 202. In some other embodiments, the optical fiber present in the lumen 210 can allow at least a portion of the fluid to pass through. In the system 200, the optical fiber 212 can be selectively retracted within the lumen 210 such that the distal tip of the optical fiber can be positioned at or near a position such as position 216, where it can substantially not block the flow of fluid from the syringe 204 to the tip 206 of the needle 202 via the lumen 210.

[0050] The system 200 can include a light source 218, such as a diode laser or other suitable light source, which can be optically coupled to the optical fiber 212 so that light from the light source can be delivered to the distal tip of the optical fiber, and more specifically, to the biomarker luminescent material 214 at the tip. Light emitted or otherwise scattered from the biomarker luminescent material 214 can be returned by the optical fiber 212 to an optical receiver 220, which can be a photodetector or any other suitable light detection device constructed and configured to detect light returned by the optical fiber 212 from the distal tip of the optical fiber.

[0051] The system 200 may include an optical coupler 222 that may be constructed and configured to transmit light from the light source 218 to the biomarker luminescent material 214 at the distal tip of the optical fiber 212 and transmit light emitted from the biomarker luminescent material 214 to the optical receiver 220. The optical coupler 222 may be tuned, for example, as a wavelength division multiplexer, to selectively maximize the transmission of light emitted from the biomarker luminescent material 214 to the optical receiver 220 and minimize the transmission of such emitted light back toward the light source 218. The second optical receiver 224 may be a photodetector or any other suitable light detection device that may be coupled to the optical system of the system 200 via the fiber splitter 222. The second optical receiver 224 may be used to sense the level of the emitted drive signal from the light source 218, which, when interpreted at the optical receiver 220, may be used to create a differential signal to compensate for intensity variations (e.g., drift due to temperature variations) of the light source 218. In some cases, this arrangement may also be used to implement phase-sensitive detection of signals received from the biomarker luminescent material 214 at the optical receiver 220 .

[0052] The system 200 can be used similarly in many respects to those described for the system 100. In operation, the needle 202 of the system 200 can be advanced into the patient's body through the optical fiber 212 positioned in the lumen 210, so that the biomarker luminescent material 214 at the distal tip of the optical fiber is disposed at or near the tip 206 of the needle 202. Once the biomarker luminescent material 214 contacts the target biological material (e.g., blood), the light generated by such contact can be transmitted up the optical fiber to the optical receiver 220, and the detection result can be indicated to the user of the system. Once the needle is properly positioned (e.g., in the blood), the optical fiber 212 can be retracted (e.g., to 216), opening the lumen 210 to allow fluid to flow from the syringe 204 for delivery at the tip 206 of the needle 202.

[0053] Figure 3A Another illustrative example of components of another biomarker detection system 300 of the present disclosure is schematically depicted, and Figure 3B Provides a Figure 3A An enlarged view of the details of some of the components shown.The system 300 can be used similarly in many respects as described for the system 100 for biomarker detection and therapeutic delivery. Figure 3A , 3B The system may include a needle 302 that may deliver fluid from a fluid delivery system (not shown in its entirety) via a fluid channel 304 of a fluid line 306 . Figure 3A , 3B The system 300 may include a coupler 308 that can couple the needle 302 to a fluid delivery system and an optical system (not shown in its entirety). Figure 3A , 3B The system 300 may employ any suitable fluid connector (not necessarily shown), such as (but not limited to) a LUER lock fitting. The optical system may include an optical fiber 310 and a coupling optic 312, which may include one or more lenses and be optically aligned by an optical support 314. The optical support 314 may be maintained in a positional relationship relative to the coupler housing 316 by a support web 318. The depicted physical arrangement between the optical support 314, the coupler housing 316, and the support web 318, and the physical arrangement therebetween, is merely an example and should not be considered limiting.

[0054] When properly positioned and aligned relative to the optical fiber 310, the coupling optics 312 can couple or focus the illumination light emitted from the optical fiber into the lumen 320 of the needle 302. The inner walls 322 of the lumen 320 surrounding the needle 302 can be polished or otherwise smoothed, for example, by electrochemical or other suitable processes, so that they can serve as a waveguide for the illumination light so coupled. In some examples, the inner walls 322 of the lumen 320 surrounding the needle 302 can be coated or lined with a thin layer of dielectric material, such as glass or polymer, whose refractive index is lower than the refractive index of the fluid in the lumen, so that a total internal reflection waveguide similar to an optical fiber can be obtained, wherein the higher refractive index fluid in the lumen serves as the "core" and the lower refractive index thin dielectric layer coating the walls of the lumen serves as the "cladding". (This waveguide configuration can potentially be applied to any system of the present disclosure in which light propagates through a fluid channel, including the fluid channels in the needles 102, 402, 502 and 602 of the systems 100, 400, 500 and 600, respectively). Illumination light provided by any suitable light source (not shown) (e.g., a diode laser) can be delivered via downward propagation of the lumen 320 of the needle 302 to its tip 324, where the biomarker luminescent material 326 can be positioned, for example, via a coating process. Light emitted or otherwise scattered from the biomarker luminescent material 326 can be returned via a reverse optical path (waveguide of the needle lumen 320, then coupled to the optical fiber 310 via the optics 312) to an optical receiver (not shown), which can be a photodetector or any other suitable light detection device constructed and configured to detect light returned from the tip 324 of the needle 302 by the optical fiber 310.

[0055] The coupler 308 may include one or more fluid channels 328 that may be in fluid communication between the fluid channel 304 of the fluid line 306 and the lumen 320 of the needle 302. The optical support 314 may define or provide a void 330 that may be fluidically sealed from the fluid path (304, 328, 320) of the fluid delivery system and in which a vacuum or gas atmosphere of a stable refractive index may be maintained, such that the effects of refractive index changes on optical coupling may be reduced or eliminated. For the same reason, the side of the lens 312 that faces the fluid may be a planar surface.

[0056] Figure 4 Another illustrative example of components of another biomarker detection system 400 of the present disclosure is schematically depicted. Figure 4 The system 400 may include a needle 402 that may deliver a fluid from a fluid delivery system (not shown) through a lumen 404 to a tip 406 of the needle 402 . Figure 4The system 400 can include a fluid coupler 408 that can couple the needle 402 to the fluid delivery system via a fluid connector 410, which can be any suitable fluid connector, such as (but not limited to) a LUER lock fitting. The coupler 408 and / or the needle 402 can include or define one or more fluid channels 411, which can be in fluid communication between a connector-side fluid channel 413 and the lumen 404 of the needle 402.

[0057] The biomarker luminescent material 412 can be positioned at the tip 406 of the needle 402, for example, via a coating process. The inner walls of the lumen 404 surrounding the needle 402 can be polished or otherwise smoothed, for example, by electrochemical or other suitable processes, so that they can form a waveguide to effectively transmit light emitted from the biomarker luminescent material 412 to an optical receiver 414, which can be a photodetector or any other suitable light detection device constructed and configured to detect light emitted from the biomarker luminescent material. A wavelength discrimination filter 416 tuned to one or more wavelengths of light emitted by the biomarker luminescent material 412 can help reject stray light and improve the signal-to-noise ratio. The optical receiver 414 can be electrically connected to the detection electronics via connection 418.

[0058] Figure 4 The system 400 can be adapted for use with a biomarker luminescent material 412 that can generate light when in contact with a target biological material (e.g., blood) without the need for illumination from an external light source. Omitting the illumination light source can make the biomarker detection device and system relatively simple. Figure 4 An example of a biomarker luminescent material that does not necessarily require external illumination for use with the system is luminol.

[0059] The system 400 may be used similarly in many respects as described with respect to the system 100 for biomarker detection and therapy delivery, except that illumination of the biomarker luminescent material 412 by an external light source is omitted.

[0060] Figure 5A schematically depicts an illustrative example of a "stand-alone" biomarker detection needle system 500 of the present disclosure, and Figure 5B A magnified view is provided showing details of some components of the system 500. The system 500 can include a needle 502 having a lumen 504 and a tip 506, to which a biomarker luminescent material 508 can be positioned, for example, via a coating process. The system 500 can include a support 510 to which the needle 502 can be mounted and connected to a fluid delivery system (not shown) via a fluid connector 512, which can be any suitable fluid connector, such as (but not limited to) a LUER lock fitting.

[0061] The support 510 can house the optics and electronics to enable biodetection using the biomarker luminescent material 508. At the support 510, the system 500 can include a light source 514, such as a diode laser or other suitable light source; and an optical receiver 516, which can be a photodetector or any other suitable light detection device. The optical system of the support 510 can include a beam splitter 518 and a reflector 520. With this optical arrangement, the Figure 5B Illuminating light from the light source 514, represented by the dashed hollow arrow in FIG. 5 , can be directed down the lumen 504 of the needle 502 to the tip 506 of the needle, where it can illuminate the biomarker luminescent material 508. Light emitted or otherwise scattered from the biomarker luminescent material 508 can return to the optical receiver 516 via a reverse light path as indicated by the solid hollow arrow. The inner walls 522 of the lumen 504 surrounding the needle 502 can be polished or otherwise smoothed, for example, by electrochemical or other suitable processes, so that they can serve as waveguides for light propagating in the needle 502. The optical system of the stent 510 can also include an optical window 524, which can provide a barrier for fluid in the lumen 504 of the needle 502 to prevent entry into the optical / electronic space 526 of the stent 510. The optical window 524 can be manufactured to selectively filter wavelengths (e.g., selectively pass illumination light from the light source 514 and light emitted from the biomarker luminescent material 508, while blocking undesirable wavelengths). Selective filtering may also be implemented at one or more surfaces of the beam splitter 518 .

[0062] The support 510 and / or the needle 502 may include or define one or more fluid channels 528 that may fluidly communicate between the connector-side fluid channel 530 and the lumen 504 of the needle 502 , thereby providing a fluid bypass around the reflector 520 .

[0063] The light source 514 and the optical receiver 516 may be electrically coupled to a circuit board 532, which may provide power and control signals to the device and receive and process signals or other information from the device. Figure 5BIn the embodiment, the light source 514 and the optical receiver 516 are both shown as being electrically coupled to the circuit board 532 via wire bonding, but this is not restrictive, and any suitable functional connection (e.g., surface mounting technology) between the device and the circuit board can be adopted. The term "circuit board" used relative to the element 532 of the system 500 is universal and should not be considered restrictive. The circuit board 532 may include a printed circuit board with multiple discrete components, a single-chip processor or a "system on a chip", multiple daughter boards, a hybrid system, or any other suitable device capable of being powered by the elements of the system 500 and performing the functions of the biomarker detection system. The bracket 510 can accommodate or support any suitable user interface element 534, which may include (but is not limited to) buttons, visual indicators (e.g., light emitting diodes) and audio annunciators / speakers. The circuit board 532 may include one or more wireless interfaces, such as a Bluetooth interface, which may be combined with any Bluetooth functions necessary or desired for operation, such as detection signals, self-tests, battery status, etc. The support 510 can house an energy storage device 536, which can be a battery or any other suitable device that can provide operating power for the light source 514, the optical receiver 516, the circuit board 532, and other suitable components carried by the support 510. The system 500 can be used similarly in many aspects to those described for the system 100 for biomarker detection and therapeutic delivery.

[0064] Fig. 6A and 6B Another illustrative example of components of another biomarker detection system 600 of the present disclosure is schematically depicted. Fig. 6A The detection configuration of system 600 is generally depicted, and Figure 6B The post-detection fluid delivery configuration is generally depicted. The system 600 can include a needle 602 having a lumen 604. Fig. 6A In the configuration of FIG. 6 , a semi-permeable barrier 606 disposed at or near the tip 608 of the needle 602 can prevent the biomarker luminescent material fluid present in the lumen 604 from exiting the needle at the tip of the needle and potentially entering the patient. The use of the semi-permeable barrier 606 in the system 600 can enable a large reservoir of biomarker luminescent material fluid to be provided in the lumen 604 of the needle 602, which provides greater illumination and longer duration of sensitivity than other arrangements lacking such a reservoir.

[0065] The semi-permeable barrier 606 can be at least semi-permeable to the target biological material 610, so that the target biological material can contact and react with the biomarker luminescent material fluid present in the lumen 604. In some examples, the semi-permeable barrier 606 can be constructed and configured so that it selectively allows iron ions or iron-containing compounds to pass through, such as those found as components of blood. The biomarker luminescent material fluid present in the lumen 604 can be a material that reacts with such iron ions or iron-containing compounds. In some embodiments, the blood remains active indefinitely. Once any form of iron present in the blood contacts the biomarker luminescent material and emits radiation, the iron is generally not consumed in the reaction.

[0066] In some embodiments, the target biomaterial and the biomarker luminescent material fluid can react such that photons 612 are generated by the reaction. As shown, such photons 612 can be generated in a variety of locations within the lumen 604, depending on the volume of the target biomaterial that penetrates the barrier 606 and enters the lumen. In some embodiments, the semi-permeable barrier 606 can be translucent or at least partially transparent to allow photons 612 generated by the reaction within the barrier to exit the barrier for detection.

[0067] Photons 612 generated due to contact between the target biological material 610 and the biomarker luminescent material fluid can propagate within the lumen 604 of the needle 602 to an optical receiver 614, which can be a photodetector or any other suitable light detection device constructed and configured to detect such light. The inner walls 616 of the lumen 604 surrounding the needle 602 can be polished or otherwise smoothed, for example by electrochemical or other suitable processes, so that they can act as waveguides for light propagating in the needle.

[0068] exist Fig. 6A The biomarker detection system 600 is depicted in a detection configuration, and in Figure 6B After successful detection of the target biomaterial, the system 600 can be moved from Fig. 6A The detection configuration is reconfigured to Figure 6B ed fluid delivery configuration, but this is not limiting and such reconfiguration is not necessarily dependent on successful biomaterial detection.

[0069] refer to Figure 6B, reconfiguration can be achieved by extracting the biomarker luminescent material fluid from the lumen 604 of the needle 602 via the fluid extraction port 618, which can be connected to the lumen fluid of the needle via the extraction hole 620. The extraction hole 620 can be formed by any suitable process (conventional machining, laser drilling, etching, etc.). Arrow 622 indicates the extraction of the biomarker luminescent material fluid, which indicates the flow direction of the biomarker luminescent material fluid during extraction. The semi-permeable barrier 606 can be slidably configured in the lumen 604 of the needle 602. When the biomarker luminescent material fluid is extracted from the lumen 604, it can be extracted from its previous distal position (at the tip 608 of the needle 602) in the proximal direction (towards Fig. 6A and 6B 604 ). After the biomarker luminescent material fluid is substantially completely extracted from the lumen, the semi-permeable barrier 606 is shown at the proximal end of the lumen 604. In some alternative examples, the semi-permeable barrier 606 can take the form of a non-slidable rupture barrier. It is generally desired that such a rupture barrier does not generate any particles when ruptured.

[0070] With the biomarker luminescent material fluid extracted from the lumen 604 of the needle 602, the system 600 can be used to deliver fluid from a fluid delivery system (not shown) via a fluid input port 624, which can be in fluid communication with the lumen of the needle via a delivery hole 626. The delivery hole 626 can be formed by any suitable process (conventional machining, laser drilling, etching, etc.). Fluid delivery from the fluid delivery system is indicated by arrow 628.

[0071] Notice, Fig. 6A and 6B The space 630 in the cross-sectional view of can be in fluid communication with the fluid input port 624, for example, via an annular space surrounding the needle 602. Similarly, the space 632 can be in fluid communication with the fluid extraction port 618.

[0072] Other needle configurations for biomarker detection are also possible by sensing the luminescent emission resulting from contact between the biomarker luminescent material and the target biological material. Fig. 7A is a schematic cross-sectional view of a biomarker detection needle 700, and Figure 7B is from Fig. 7ASchematic plan view of needle 700 when viewed from the left side of the needle in FIG. Needle 700 may include biomarker luminescent material 704 at its tip 702. Needle 700 may include one or more optical fibers 706, 708. One of optical fibers 706, 708 may be used to deliver illumination light from a light source (not shown) such as a diode laser or other suitable light source to biomarker luminescent material 704, and the other of the two optical fibers may be used to transmit light emitted from the biomarker luminescent material to an optical receiver (not shown), which may be a photodetector or any other suitable light detection device. Needle 700 may include a lumen 710 suitable for delivering fluid from a syringe or other suitable fluid dispensing system (not shown).

[0073] The configuration of needle 700 employs non-retracting optical fibers 706, 708 for efficient transmission of illumination light and light emitted by the biomarker luminescent material, while providing a lumen that is always open for fluid delivery to the tip 702 of the needle. Figure 2 In the system 200, it may be necessary to retract the optical fiber 212 from the tip 206 to the position 216 to open the lumen 210 for fluid delivery. In some other embodiments of the present disclosure, for example Figure 1 In the system 100, the open lumen of the needle can be used to provide an optical waveguide for light transmission without one or more optical fibers extending to the distal tip of the needle. In many cases, optical fibers can provide higher light transmission efficiency than the lumen of the needle.

[0074] Fig. 8A , 8B , 8C and 8D are schematic cross-sectional views down the bore of a needle providing an optical fiber and lumen to the tip of the needle along its length, similar to Fig. 7A and 7B 700 needles. Fig. 8A The needle 802 can include five optical fibers, wherein the external optical fiber 804 is an illumination optical fiber that delivers illumination light from a light source to a biomarker luminescent material, and the internal optical fiber 806 is a sensing or detection optical fiber for transmitting light emitted from the biomarker luminescent material to an optical receiver. This arrangement of four external illumination optical fibers and one internal detection optical fiber is merely an example and should not be considered restrictive. Other optical fiber arrangements can be considered. The needle 802 can include one or more lumens 808 suitable for fluid delivery. In some examples, multiple lumens can be used to provide higher fluid conductivity for delivering fluids from a common fluid reservoir. In some other examples, multiple lumens can be used to provide independent delivery paths for different fluids.

[0075] Figure 8B The needle 810 may include three optical fibers 812 and three lumens 814 suitable for fluid delivery. Figure 8CThe needle 816 may include two optical fibers 818 and two lumens 820 . Fig.8D The needle 822 can include a single optical fiber 824 and a single lumen 826. These are examples only, and other numbers of optical fibers and lumens can be provided and used with the biomarker detection needles contemplated in the present disclosure. By using, for example, a fiber optic splitter (similar to Figure 2 The optical fiber in the needle with a single optical fiber can be used for both illumination and detection, as shown in the separator 222 of the system 200. Alternatively, the optical fiber in the needle with a single optical fiber can be used only to transmit detection light from the biomarker luminescent material to the optical receiver in a detection arrangement where illumination light is not required.

[0076] In some examples contemplated by the present disclosure, an apparatus having multiple optical fibers, similar to (but not limited to) Fig. 7A , 7B , 8A, 8B and 8C can be used in devices configured to detect multiple biomarkers and / or other detectable substances. Each of the multiple optical fibers can be used for independent detection and / or illumination channels. For example, different biomarker luminescent materials can be coated at the ends of different detection optical fibers at the needle tip, so that different luminescent detection signals can be sensed independently. Different biomarker luminescent materials can have different lighting requirements, which can be provided by multiple illumination optical fibers. As discussed elsewhere herein, separate optical fibers can be used for air / gas detection.

[0077] The biomarker luminescent materials used for biomarker detection in the systems and methods of the present disclosure can utilize a variety of different luminescent phenomena. Some biomarker luminescent materials can rely on chemiluminescence, and the chemical reaction that occurs when the biomarker luminescent material contacts the target biomarker can produce light emission that can be sensed as a detection signal of the biomarker without additional energy input. Systems 400 and 600 (not necessarily including a light source) may be particularly suitable for use with chemiluminescent biomarker luminescent materials because they may be less complex (at least in optical complexity) than systems including light sources. However, potentially any one of systems 100, 200, 300, 400, 500 and 600 and any one of needles 700, 802, 810, 816 and 822 can be used in combination with chemiluminescent detection, although the inclusion of a light source in some of the systems may be irrelevant to the detection of light produced by chemiluminescence.

[0078] Some other biomarker luminescent materials may employ photoluminescence (e.g., fluorescence and / or phosphorescence) activated by contact between the biomarker luminescent material and the target biological material. Illumination light for photoluminescence may be provided by the light source of the illustrative example systems 100, 200, 300, and 500 and may be transmitted through the optical fibers (and / or in some cases, other waveguides) of the systems 100, 200, 300, 500 and at least some of the needles 700, 802, 810, 816, and 822.

[0079] Some biomarker luminescent materials may exhibit photoluminescence in the absence of the target biomarker, and upon exposure to the target biomarker, the photoluminescence may cease or decrease.

[0080] The physical properties of the biomarker luminescent material coating can reflect the balance between competing factors. A thinner coating can be sufficiently translucent to allow illumination light to penetrate and emitted light to escape for detection, while a thicker coating can provide more biomarker detection material and a stronger emission signal. The coating can include a cross-linked hydrophilic coating. The cross-linked hydrophilic coating can include the biomarker luminescent material as part of the coating, or it can be encapsulated or sealed to a delivery device. The porosity of the biomarker luminescent material may be required to facilitate the interaction between the biomarker and the material.

[0081] The present disclosure further contemplates real-time systems and methods for distinguishing between gas (which may be referred to as "air") and liquid within a patient's anatomical structure to aid in the precise placement of surgical instruments therein. Such systems may include optical, acoustic, and / or electrical detection, and may be based on differences in optical, acoustic, and / or electrical impedance.

[0082] Fig. 9 is a schematic cross-sectional view of a fiber optic sensor 900 for distinguishing air from liquid (may be referred to herein as a "fiber optic air sensor"). The sensor 900 may include an optical fiber core 902, which may be surrounded by a cladding 904, which in turn may be surrounded by a buffer zone 906. The buffer zone 906 may include one or more buffer layers, such as a primary buffer layer and a secondary buffer layer. The fiber optic air sensor 900 may include any other suitable layers (not shown) for strength, protection, etc.

[0083] The fiber optic air sensor 900 can be constructed and configured to detect the presence of a signal propagating within the optical fiber toward the detection end (i.e., Fig. 9908) undergoes total internal reflection when incident on the face 909 of the optical fiber core 902 at the detection end to distinguish between liquid and air at the detection end 908. An exemplary light beam is shown as propagating within the core 902 toward (at 910) the detection end 908, and then propagating away from (at 912) the detection end after reflecting from the face 909. In the case of total internal reflection, light incident on the face 909 at an angle shallower than the critical angle of total internal reflection can be substantially completely reflected. If incident at an angle steeper than the critical angle, the light can generally be partially reflected within the core 902 (such as at 912) and partially refracted out of the optical fiber, as schematically shown for light ray 914.

[0084] The surface 909 can be configured to reflect the light propagating in the core 902 back to the detection end 908. They can be oriented at 45 degrees relative to the longitudinal axis of the core 902, for example. In some embodiments, they can be arranged in a solid angle configuration. The surface oriented at 45 degrees relative to the longitudinal axis of the core 902 (basically the light propagation axis) can be appropriately oriented to distinguish between air and liquid. For fused silica optical fiber, the critical angle for total internal reflection relative to the external air medium is about 43 degrees, and the critical angle for total internal reflection relative to the external water medium is about 67 degrees. Therefore, the light propagating along the longitudinal axis of the core 902 and incident on the surface 909 at 45 degrees relative to the longitudinal axis can be incident on the surface in a manner shallower than the critical angle of air and steeper than the critical angle of water.

[0085] In operation, the detection scheme may include an optical receiver (not shown) that may be appropriately configured to detect light from a light source that has been reflected back from the detection end 908. When the face 909 of the detection end 908 is exposed to an external air medium to produce total internal reflection, this reflected signal may generally be brighter than when these faces are exposed to liquid (and therefore do not produce total internal reflection). The face 909 may include a coating to enhance its detection utility. The inner portion 916 of the face 909, including the portion of the face to which the light in the core may be incident, may have a hydrophobic coating to repel residual liquid on the face when the detection end 908 is in air. The outer portion 918 of the face 909 may include a hydrophilic coating to draw liquid away from the inner portion 916.

[0086] Fig.10 is a schematic cross-sectional view down the bore of an illustrative example of a needle system 1000 that may incorporate a fiber optic air sensor 1002 that may be similar to Fig. 9The sensor 1002 of the fiber optic air sensor 900 can be disposed within a hypodermic needle 1004 within a mold 1008. The hypodermic needle 1004 can enclose a fluid channel 1006 for delivering a medicinal fluid, but this is not limiting, and in other embodiments, the needle can deliver or contain other therapeutic payloads and / or devices. It is contemplated that the fiber optic air sensor can be incorporated into other configurations of medical devices, including in conjunction with the biomarker detection systems described herein.

[0087] Fig.11 1 is a schematic cross-sectional view of a needle system 1100 that may incorporate an acoustic probe for distinguishing between air and liquid (which may be referred to herein as an "acoustic air sensor"). A sensing rod 1102 may be mounted within a hypodermic needle 1104 via one or more elastic attachments 1106. The sensing rod 1102 may be driven longitudinally (as indicated by the arrows superimposed thereon) relative to a reaction mass 1110 at an appropriate frequency by a piezoelectric actuator 1108. The tip 1112 of the sensing rod 1102 at the distal end of the needle system 1100 may be in mechanical contact with any medium that may be present at its location, whether the medium is tissue, liquid, or gas. Each of these media may present a different mechanical impedance to the motion of the sensing rod 1102, with the impedance generally decreasing in order (tissue>liquid>gas). The acoustic / mechanical impedance may be measured in a variety of ways, including but not limited to (a) applying a constant driving force and measuring the amplitude; (b) driving to a constant amplitude and measuring the driving force; and / or (c) measuring the phase shift between the driving force and the motion. The needle system 1100 can enclose a fluid channel 1114 for delivering a medicinal fluid, but this is not limiting, and in other embodiments, the needle can deliver or contain other therapeutic payloads and / or devices. It is contemplated that the acoustic air sensor can be incorporated into other configurations of medical devices, including in conjunction with the biomarker detection systems described herein.

[0088] Fig. 12A , 12B12A and 12C are schematic plan views, schematic side cross-sectional views, and schematic cross-sectional views, respectively, along a hole down of an illustrative example of a needle system 1200 that may incorporate an electrical sensor for distinguishing between air and liquid (which may be referred to herein as an "electrical air sensor"). Conductors 1204a, 1204b may be molded into an insulator 1206 located within a hypodermic needle 1202. The hypodermic needle 1202 may be grounded, and the conductors 1204a, 1204b may be connected to an electrical drive and sensing device (not shown). The ends of the conductors 1204a, 1204b may be polished at the distal tip of the needle 1202 so that their faces 1208a, 1208b may be in conductive contact with any medium at the tip of the needle. Typically, the conductivity between the faces 1208a and 1208b of the conductors 1204a, 1204b may depend on the medium. For example, [in (ohm cm) -1 The conductivity of human plasma was measured (13.5×10 -3 ) and the conductivity of gastric fluid (24×10 -3 ) and urine conductivity (40×10 -3 ) is significantly different. The conductivity of air is typically significantly lower. A hydrophobic coating can be placed at the end of the needle to help drain liquid from the faces 1208a and 1208b of the conductors 1204a, 1204b when encountering air space. By monitoring the conductivity between the faces 1208a and 1208b of the conductors 1204a, 1204b, the difference in the medium present at the tip of the needle system 1200 can be detected and in some cases identified. The needle system 1200 can enclose a fluid channel 1210 for delivering a medicinal fluid, but this is not limiting, and in other embodiments, the needle can deliver or accommodate other therapeutic payloads and / or devices. It is contemplated that the electrical air sensor can be incorporated into medical devices of other configurations, including in combination with the biomarker detection system described herein.

[0089] Fig.13A , 13B and 13C shows a similar Fig. 12A , 12B and 12C system 1200 needle system, Fig.13A , 13B 13A and 13C are schematic side cross-sectional views of an illustrative example of a needle system 1300 that may incorporate an electrical air sensor, and 13C are schematic cross-sectional views down the aperture of two alternative configurations of the needle system 1300, respectively. Fig.13A , 13B In the configuration of 13C, the wire may be engaged within the lumen of the hypodermic needle 1302, as compared to the needle system 1200 in which the conductors 1204a, 1204b are molded within the insulator 1206 within the lumen of the needle 1202. Fig.13A ,13B The leads of the configurations of 1304 and 13C each include a conductor 1304a, 1304b, or 1304c, each of which is surrounded by an insulator 1312. An adhesive 1314 may be used to bond the lead within the needle lumen.

[0090] exist Fig. 13B In a configuration of , a single wire having conductor 1304a can be bonded within needle 1302. In this configuration, conductor 1304a serves as one conductor and needle 1302 serves as the other conductor for electrical air sensing. Fig. 13C In the configuration of , two wires with conductors 1304b, 1304c can be joined within needle 1302 and serve as the two conductors needed to complete the air sensing circuit. A hydrophobic coating can be placed at the end of the needle to help drain liquid from the faces 1308a, 1308b, 1308c of the conductors 1304a, 1304b, 1304c and the end 1316 of the needle 1302 when encountering air space. The needle system 1300 can enclose a fluid channel 1310 for delivering medicinal fluids, but this is not limiting, and in other embodiments, the needle can deliver or contain other therapeutic payloads and / or devices.

[0091] In an example method using a needle system (e.g., one of systems 1000, 1100, 1200, or 1300) with an optical, acoustic, or electrical air detection system, a clinician can push a needle into a patient, with the air detection system activated to provide feedback to the clinician. When the tip of the needle is pushed into a medium of interest, a notification system (not shown) operably coupled to the air detection system can notify the clinician that the target medium has been detected. The clinician can then position the tip of the needle based on detection of the target medium and knowledge of the patient's anatomy (e.g., further advancement, stopping advancement, or retracting the needle). With the tip of the needle properly placed, delivery of a therapeutic fluid (or other therapeutic action) from a fluid delivery system can be performed.

[0092] A person of ordinary skill in the art to which this disclosure and its subject matter relate will recognize that an embodiment may include fewer features than shown in any individual embodiment described by way of example or otherwise contemplated herein. The embodiments described herein are not meant to be an exhaustive presentation of the ways in which various features may be combined and / or arranged. Therefore, the embodiments are not mutually exclusive combinations of features; rather, as understood by a person of ordinary skill in the relevant art, the embodiments may include combinations of different individual features selected from different individual embodiments. Moreover, even if not described in such embodiments, elements described with respect to one embodiment may be implemented in other embodiments, unless otherwise stated. Although a dependent claim may refer to a specific combination with one or more other claims in the claims, other embodiments may also include a combination of a dependent claim with the subject matter of each other dependent claim, or a combination of one or more features with other dependent or independent claims. Unless it is indicated that a specific combination is not intended, such a combination is proposed herein. In addition, it is also intended that the features of a claim be included in any other independent claim, even if the claim is not directly subordinate to the independent claim.

[0093] Any incorporation by reference of the above-mentioned documents is limited so that no subject matter is incorporated contrary to the explicit disclosure herein. Any incorporation by reference of the above-mentioned documents is further limited so that no claims included in the documents are incorporated by reference herein. Any incorporation by reference of the above-mentioned documents is further limited so that any definitions provided in the documents are not incorporated by reference herein unless expressly included herein.

Claims

1. A biomarker detection system, comprising: target biomarkers in biological systems; a needle having a distal end and a proximal end, wherein the distal end is configured to contact the target biomarker and the proximal end is configured to be in fluid communication with a fluid dispensing system, and wherein the needle comprises a lumen having an inner wall; a biomarker luminescent material in contact with the distal end of the needle; and a stent coupled to the needle and comprising an optical system in optical communication with the biomarker luminescent material, in The optical system comprises a light source and an optical detector, The optical system further comprises an optical window, and the optical window is disposed on a wall of the lumen and is a barrier for the fluid in the lumen, In the presence of the biomarker luminescent material, light from the light source can be directed down the lumen to the distal end of the needle and illuminate the biomarker luminescent material at the distal end, causing the biomarker luminescent material to emit light of a different wavelength than the light source, The optical system further comprises a beam splitter disposed between the light source and the optical detector and a reflector disposed within the lumen, and the reflector being configured to reflect light to the biomarker luminescent material and simultaneously reflect the emitted light from the biomarker luminescent material to the optical detector, such that light emitted from the biomarker luminescent material travels from the distal end of the needle upward along the lumen toward the reflector within the lumen and is reflected by the reflector toward the beam splitter, which directs the emitted light toward the optical detector, The lumen further comprises one or more fluid channels, wherein at least one fluid channel is a fluid bypass around the reflector.

2. Use of a biomarker detection system in the preparation of a medicinal fluid product for determining whether to deliver a medicinal fluid product to a patient, comprising: Use biomarker detection systems to locate the presence of target biomarkers in patients, The biomarker detection system comprises: a fluid distribution system having a distal end, wherein the fluid distribution system is connected to the needle at a proximal end of the needle, and wherein the needle comprises a lumen, a distal end, and a stent, wherein the lumen is configured as a waveguide for light propagation and includes one or more fluid channels, and Furthermore, the bracket comprises an optical system having a light source, a beam splitter and an optical detector, wherein the beam splitter is arranged between the light source and the optical detector. The optical system further comprises an optical window, and the optical window is disposed on a wall of the lumen and is a barrier for the fluid in the lumen, a reflector disposed within the lumen and configured to reflect light from the light source down the lumen toward the distal end of the needle, wherein the reflected light illuminates a biomarker luminescent material in contact with the distal end of the needle, wherein light emitted from the biomarker luminescent material returns from the distal end of the needle and travels up the lumen and is reflected by the reflector toward the beam splitter, which directs the emitted light toward the optical detector, and wherein at least one fluid passage of the lumen is a fluid bypass around the reflector, notifying a clinician that the target biomarker has been detected; and The medicinal fluid is delivered to the patient.

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