Real-time needle tip tissue analysis

Abstract

A real-time needle tip tissue analysis system and methods for detecting biological substances in conjunction with medical devices that can be advanced into a patient, wherein the device includes a needle-mounted detection system. The system can include a needle structured and configured to be inserted into human tissue, where there can be a flex print disposed within the needle's lumen. On the flex print there may be at least one LED die disposed where the LED die can be in communication with the flex print. Also, there may also be at least one detector in communication with the flex print and opposed to the LED die. A test chamber can be formed between the LED and the detector. The system can include an output module configured to generate a variable output based on the location of the needle.

Description

REAL-TIME NEEDLE TIP TISSUE ANALYSISFIELD OF THE INVENTION

[0001] The present disclosure relates to systems and methods for detecting biological substances and the nature of these substances. More particularly, it relates to systems and methods for detecting biological substances in conjunction with medical devices that can be advanced into a patient, wherein the device includes a needle-mounted detection system.BACKGROUND

[0002] Needle tip placement within the body and its internal parts is critical to success in the injection of medications, blood, vaccines, and other substances for improving health. It may also be employed to detect certain materials and extract them from the body. In some cases, it is desired to place the needle tip within a vein or artery. In other cases, it is essential to avoid injection into a vein or an artery. Improper placement of a needle tip can result in severe complications and even death.

[0003] The present technical standard is to use ultrasound or x-ray to guide needle placement. Other methods for needle placement can include syringe plunger retraction or IV fluid flow to verify proper placement. The present technology is compatible with these technologies as an adjunct.

[0004] It is desirable to know the nature of the tissue at the needle’s tip in real-time while the procedure is in process without the added cost, complexity, and time of using ultrasound or x-ray techniques.SUMMARY

[0005] Provided is a real-time needle tip tissue analysis system. The disclosed systems can include an embodiment where A real-time needle tip tissue analysis system may include a needle, with a lumen having proximal and distal ends, where the distal end can be configured to be inserted into human tissue. The lumen can include a flex print disposed thereon, with at least one LED die disposed on the flex print at the distal end of the needle. The LED die can be in communication with the flex print. Further, in such an embodiment, there can also be at least one detector disposed on the flex print, where the at least one detector is also in communication with the flex print and spaced from and opposite to the at least one LED die. A test chamber can be formed between the at least one LED and the at least one detector. Along with the LED and detector, there can be an output module, that can be in communication with the flex print, and the output module isstructured and configured to generate a variable output based on the location of the distal end of the needle.

[0006] A variation of such an embodiment can further include a ramp, where the ramp can be placed on the flex print and bound a side of the test chamber. Additionally, in that embodiment the, at least one LED die may be covered with an encapsulant. Furthermore, the encapsulant can be configured to have a reflective surface, where the reflective surface may direct light from any of the LED dies through the test chamber and toward any one of the detectors, where only light from one LED is directed to a single detector.

[0007] Another variation of such an embodiment can include an output module that may be disposed on the needle. The output module may also include an indication light that is configured to produce the variable output, and where the output module could be a speaker that is configured to produce the variable output.

[0008] Another variation of such an embodiment can include two LED dies, and two detectors, wherein the two LED dies may be configured to produce different wavelengths of light, and wherein each detector can be configured to receive light from one of the LED dies.

[0009] The disclosed systems can also include an embodiment where a real-time needle tip tissue analysis system can include a needle, where the needle can include a lumen that can have proximal and distal ends, and where the distal end can be structured to be inserted into human tissue. In such an embodiment, there may also be a flex print that can be disposed on the lumen, and where there can be at least one LED die disposed on the flex print at the distal end of the needle, where the at least one LED die can be in communication with the flex print. This embodiment can also include at least one detector that can be disposed on the flex print at the distal end of the needle, where the at least one detector can be in communication with the flex print and opposite and spaced from the at least one LED die. Between the at least one LED and the at least one detector, a test chamber can be formed. This embodiment may also include an output module, where the output module can be in communication with the flex print, and structured and configured to transmit a signal via a wireless transmitter to an output device. The output device can be configured to produce a variable output based on the location of the distal end of the needle.

[0010] 1 A variation of such an embodiment can further include a ramp, where the ramp can be disposed on the flex print and bound a side of the test chamber. Such a variation can also have the at least one LED die that may be covered with an encapsulant, and where the encapsulant can be configured to have a reflective surface. Such a reflective surface can be configured to direct light from the LED die through the test chamber and towards the at least one detector.

[0011] A variation of such an embodiment can further have the output module that can be disposed on the needle. Or where the output device is a smartwatch, smartphone, or a dedicated remote receiver.

[0012] The disclosed systems can also include an embodiment where the real-time needle tip tissue analysis system can include a needle, where the needle may have a lumen with proximal and distal ends. The distal end can be structured and configured to be inserted into human tissue. This embodiment can also include a flex print that may be disposed on the lumen, where at least one LED die can be disposed on the flex print at the distal end of the needle, and where the at least one LED die can be in communication with the flex print. Also, in such an embodiment, there may be at least one detector that can be disposed on the flex print at the distal end of the needle, where the at least one detector can be in communication with the flex print and opposite to and spaced from the at least one LED die. There may also be a test chamber that can be formed between the at least one LED and the at least one detector. Such an embodiment can also include an output module that can be in communication with the flex print, and the output module can be structured and configured to generate a variable output based on the location of the distal end of the needle. Furthermore, in such an embodiment, there may be a resistance sensor that can be disposed closer to the distal end of the needle than the test chamber.

[0013] A variation of such an embodiment can further have at least one LED die that may be covered with an encapsulant, and where the encapsulant may be configured to have a reflective surface, that can direct light from the LED die through the test chamber and towards the at least one detector.

[0014] Another variation of such an embodiment can further have an output module that may be disposed on the needle.

[0015] Another variation of such an embodiment can further have two LED dies and two detectors, where the two LED dies can be configured to produce different wavelengths of light, and where each detector can be configured to receive light from only one of the LED dies at a time.

[0016] In a further variation of such an embodiment, a mechanical agitator can disposed within the test chamber to provide enhanced fluid exchange within the test chamber.

[0017] The above summary is not intended to describe each and every example or every implementation of the disclosure. The description that follows more particularly exemplifies various illustrative embodimentsBRIEF DESCRIPTION OF THE DRAWINGS

[0018] The following description should be read with reference to the drawings. The drawings, which are not necessarily to scale, depict examples and are not intended to limit the scope of the disclosure. The disclosure may be more completely understood in consideration of the following description with respect to various examples in connection with the accompanying drawings, in which:

[0019] FIG. 1 is a top view of an illustrative example of a first embodiment of a real-time sensor system;

[0020] FIG. 1 A is a cross-sectional view of FIG. 1 on the A-A axis;

[0021] FIG. IB is a cross-sectional view of FIG. 1 on the B-B axis;

[0022] FIG. 2 is a partial view of a flex print based assembly and test chamber;

[0023] FIG. 2A a partial view of an encapsulated LED die or detector connected to a flex-print board;

[0024] FIG. 3 is a top view of an illustrative example of another embodiment of a real-time sensor system;

[0025] FIG. 4A a partial view of an LED die or detector connected to a flex-print board without an encapsulant;

[0026] FIG. 4B a partial view of an LED die or detector connected to a flex-print board with an encapsulant;

[0027] FIG. 5 is a top view of an illustrative example of another embodiment of a real-time sensor system

[0028] FIG. 5 A is a partial side view of FIG. 5 showing the bifurcation of the needle;

[0029] FIG. 6 is a partial view of a battery-pull tab assembly;

[0030] FIG. 7 is a partial side view of another embodiment of a real-time sensor system having an output system connected via a wire;

[0031] FIG. 8 is a partial side view of another embodiment of a real-time sensor system having an output system connected via a wireless transmitter;

[0032] FIG. 9 is a partial side view of another embodiment of a real-time sensor system having an output system contained on a needle;

[0033] FIG. 9A is an example of an output system of FIG. 9;

[0034] FIG. 10 is a partial side view of another embodiment of a real-time sensor system having an output system mounted on a needle;

[0035] FIG. 11 is a cross-section view of an embodiment of a real-time sensor system having an output system mounted on a needle;

[0036] FIG. 12 is an example of an output system’s architecture for a hardwired system;

[0037] FIG. 13 is an example of an output system’ s architecture for a wireless transceiver system;

[0038] FIG. 14 is an example of an output system’s architecture for a wireless transceiver system that utilizes BLUETOOTH communication;

[0039] FIG. 15 is an example of an output system that utilizes a smart device;

[0040] FIG. 16 is an example of an output system’s architecture for a needle-mounted threshold detection system;

[0041] FIG. 17A is an example of a two-wire resistance sensor;

[0042] FIG. 17B is an example of a four- wire resistance sensor;

[0043] FIG. 18 is an example of a finger-type resistance sensor;

[0044] FIG. 19 is a top view of an illustrative example of another embodiment of a real-time sensor system having a finger-type resistance sensor;

[0045] FIG. 20 is a graph of the absorption spectra of hemoglobin as a function of wavelength;

[0046] FIG. 21 is a plethysmography tracing, a measure of volumetric changes associated with pulsatile arterial blood flow;

[0047] FIG. 22 is a top view of an illustrative example of another embodiment of a real-time sensor system having a finger-type resistance sensor and a mechanical agitator; and

[0048] FIG. 22A depicts a mechanical agitator that may be within the embodiment of FIG. 22.DETAILED DESCRIPTION

[0049] The present disclosure relates to systems and methods for detecting biological substances and the nature of these substances. More particularly, it relates to systems and methods for detecting biological substances in conjunction with medical devices that can be advanced into a patient wherein the entire system can be integrated into a single-use needle. Various embodiments are described in detail with reference to the drawings, in which like reference numerals may be used to represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the systems and methods disclosed herein. Examples of construction, dimensions, and materials may be illustrated for the various elements; those skilled in the art will recognize that many of the examples provided have suitable alternatives that may be utilized. Any examples set forth in this specification are not intended to be limiting and merely set forth some of the many possible embodiments for the systems and methods. It is understood that various omissions and substitutions of equivalents are contemplated as circumstances maysuggest or render expedient, but these are intended to cover applications or embodiments without departing from the spirit or scope of the disclosure. Also, it is to be understood that the phraseology and terminology used herein are for the purpose of description and should not be regarded as limiting.

[0050] The availability of extremely small-size Light Emitting Diodes (LEDs) has expanded in recent years, in part based upon their use as pixel elements for displays. Also, a wide variety of wavelengths are now available. Such LEDs have very low power consumption, low heat production, are inexpensive, and reliable.

[0051] Similarly, in recent years, the variety of photodetectors has increased while their size has been dramatically reduced. Semiconductor photodetectors, commonly referred to as photodiodes, are the predominant types of photodetectors used in optical communication systems because of their small size, fast detection speed, and high detection efficiency. They are low noise and inexpensive. Typically, such semiconductor photodetectors can sense a broad band of light wavelengths. For example, Metal-Semiconductor-Metal Photodetectors (MSM detectors) are available in sizes as small as 10 pm diameters; these are extremely fast. An MSM detector is a micro-device containing two metallic electrodes (Schottky contacts) on a semiconductor material. This kind of Schottky barrier detector functions by applying a voltage to the electrodes; when light impinges on the semiconductor between the electrodes, it generates electric carriers (electrons and holes), which are collected by the electric field and form a photocurrent.

[0052] Together, an LED and photodetector can form a test chamber to measure the nature of the fluid between said elements. LEDs and photodetectors of a size down to 5 microns are available. With the small size, one or more of the detection cells can be placed within the bore of a hypodermic needle near the tip on the surface of the lumen. At a minimum, light absorption can serve to distinguish between vascular blood, tissue, interstitial fluid, and spinal fluid.

[0053] Additionally, owing to the size of the LEDs, conduction detectors, and photodetectors, a needle-mounted threshold and status indication system can potentially be integrated into a single disposable device. For example, a needle may include detectors within the tip of the needle’s lumen. The detectors may then work in conjunction with an indication module that can also integrated with the needle. Other embodiments may include an indication module that can be communicated via wired or wireless methods.

[0054] Several options can be employed to shield the test chamber from interference from room ambient light. Such options can Include filters on the detector to allow only the wavelength of the paired LED to pass. Other options can be light shields that allow fluids to pass but may block room lighting.

[0055] An embodiment of the present invention can involve the use of multiple light wavelengths that can be used to extract more information about the nature of the fluids. For example, in pulse oximetry, oxygenated hemoglobin absorbs less light at 660 nm than reduced hemoglobin, and vice versa at 940 nm. This same technology can be employed to determine the oxygenation of the fluid. Such an embodiment could use two light sources, -660 nm and -940 nm, controlled by a microcontroller to perform pulse oximetry. This approach provides additional information to improve the detection accuracy of the nature of the fluid in the test chamber. Activating both LEDs at the same time can produce a third data point to improve accuracy.

[0056] The LED “on” time can be relatively short duration (for example 10 msec) since the response time of the detector tends to be very fast. This serves to reduce power consumption. The “on” time pulses can be close together as needed to create real-time feedback, for example 40 Hz.

[0057] FIG.l discloses a real-time needle tip tissue analysis system 100 embodiment comprising a needle 110 that depicts a transverse two- wavelength needle geometry with flex print circuit board 130. The needle 110 includes a lumen 120 having the flex print circuit board 130 disposed within the lumen 120. LED dies can be disposed on the flex print 130. For example, LED dies 141 and 142. Across from the LED dies, at least one detector may also be disposed on the flex print 130 that can be structured and configured to receive light emitted from an LED Die. As shown in FIG. 1, there are two detectors, 143 and 144, that are disposed on the flex print 130. The flex print circuit board 130 may accommodate the curvature of the needle bore in the design where necessary. In any embodiment of a real-time needle tip tissue analysis system disclosed herein, besides the flex print circuit, any circuit board known in the art may be adapted for use within the system. For instance, any printed circuit board (PCB) may be used; e.g., single-sided PCB, doublesided PCB, multilayer PCB, rigid PCB, rigid PCB, rigid-flex PCB, and ceramic hybrids.

[0058] Both the LED die and the detector can be electrically isolated from environmental solutions by the use of an encapsulant, which can be placed on any and all of the LED dies or detectors. The encapsulant can electrically isolate any wires bonded to the LED dies or detectors. Additionally, such encapsulants can include a reflective material that can direct light from an LED die to a detector. For example, transparent injection molded mirrors and / or lenses can be included within the encapsulant. As illustrated in FIG. 1A, a first encapsulant 151, may include such a reflective material. Such reflective surfaces may also provide protection from ambient lighting.

[0059] The space bounded by the LED dies, and detectors can form a test chamber similar to the test chamber 140 of FIGs. 1 and 1A. The test chamber 140 can provide an area where the light emitted from an LED die can pass through fluids that arrive within the test chamber 140 and thenonto the detector when the needle 110 is inserted into a patient. For example, the light that is collected by detector 143 from LED die 141 after passing through a fluid from a patient can be analyzed to determine the properties of that fluid. At a minimum, the light absorption can serve to distinguish between vascular blood, tissue, interstitial fluid, and spinal fluid. The position of detectors can avoid air lock and may provide direct access to fluids within the test chamber.

[0060] Other features may be included in the real-time needle tip tissue analysis system 100, such as a ramp 148, wherein the ramp can be useful in preventing the catching of the needle 110 on a patient’s tissues. The ramp 148 can be located on the side of the test chamber 140, where it can bound the test chamber 145. The ramp inclines from the distal end of the needle 110.

[0061] In an embodiment of the real-time needle tip tissue analysis system, an LED die and a detector can be assembled on a Kapton flex print by using an automated pick-and-place and surface mount technologies. The flex print can then be bonded to the bore of the needle. A flex print pigtail lead can then bring the signal in and out of the needle, as shown in FIG. 7. The location of the sensor at the needle tip may provide immediate identification of the fluid within a test chamber in real-time as the needle is inserted.

[0062] FIG. 2 is an exploded view of a test chamber 240 of an embodiment of a real-time needle tip tissue analysis system. Here, the encapsulants covering LED die 241 and detector 243 contain a reflective surface 245 that guides light from the LED die 241 to the detector 243 along a light path 260. In FIG. 2A, an exploded view of FIG. 2 shows the LED die 241 covered in an encapsulant 251, where the LED die 241 can be bound to the substrate of a flex print board 230 with an adhesive 254. Additionally, in FIG. 2A, there is a wire 270 that is fully enclosed by the encapsulant 251, which can thereby electrically isolate the wire 270 from a fluid contained within a test chamber.

[0063] FIG. 3 is an illustration of another embodiment of a real-time needle tip tissue analysis system 300, having a needle body 310 and lumen 320. This is an example of a transverse two- wavelength needle geometry with a flex print board. In system 300, there is a slightly different arrangement than the system 100 of FIG. 1. Here, the separation of a first LED die 341 and a second LED die 342 is more pronounced. However, both dies are still aligned with a first detector 343 and a second detector 344. Test chamber 340 is formed between the LED dies and detectors that are disposed on a flex print board 330. There is no ramp element in the embodiment of FIG. 3.

[0064] FIGs. 4A-B illustrates an example of the construction of a real-time needle tip tissue analysis system 400. Here, flex print board 430 can be placed on the lumen of a needles bore (not shown), and an LED die 441 or detector 443 can be placed thereon flex print board 430 eitherwith a wire bond bare die operation or with the use of a pick and place die with solder paste and cure solder. For example, in FIG 4A, the solder paste 436 is disposed between the LED die 441 / detector 443 and the flex print board 430. A wire 470 can then be bound to the LED die 441 / detector 443 and the flex print board 430 using different bonding techniques, e.g., a ball bond or a wedge bond. Once the LED die 441 / detector 443 are bound to the flex print board 430, an encapsulant may then be added to encapsulate the bound LED die 441 / detector 443 and wire 470. In some embodiments, a hydrophobic coating may be added for the purpose of minimizing any surface fouling effect that may be caused by blood, which can have a tendency to coat the optical surfaces over time and affect the sensitivity of the real-time needle tip tissue analysis system.

[0065] In another embodiment of a real-time needle tip tissue analysis system 500, as illustrated in FIGs. 5 and 5A, a rigid board 530 may be used, where the rigid board 530 is disposed on a lumen 520 of needle 510. The rigid board 530 can have an LED die 541 and a detector 543 bound to its surface. The space between the LED die 541 and detector 543 can form a test chamber 540. Conductive traces 580 can connect the LED die 541 and detector 543 to a power source (not shown) and a microprocessor (not shown). For construction purposes of the real-time needle tip tissue analysis system 500, the needle 510 may be bisected along the path 512, thereby allowing placement of the rigid board 530 and conductive traces 580. Cross-section A, as illustrated in FIG. 5A illustrates the bisected needle 510. FIG. 6 is an example of a power source 600 that can be connected to the conductive traces 580, further illustrations of that arrangement will be discussed supra. Within FIG. 6, battery 630 can be disposed between an upper contact 640 and a lower contact 650. To prevent drainage of the battery 630 prior to the use by any real-time needle tip tissue analysis system connected thereto, a pull tab 610 can be disposed between a contact and the battery 630. Here, the pull tab 610 is disposed between the battery 630 and the Upper Contact 640; a user needs only to remove the pull tab 610 to initiate a real-time needle tip tissue analysis system connecter to the power source 600.

[0066] FIGs. 7 and 8 are examples of a real-time needle tip tissue analysis system that are disposed within a needle and transmit any acquired information via a wire or wireless transmitter. The systems in FIG. 7 can be configured to communicate with a hardwired control module that’s system architecture is illustrated in FIG. 12. The system architecture for the wired control module 1200 can include a microprocessor 1210, which can be configured to receive power from power source 1220. The microprocessor 1210 may be capable of electronic communication with an A- to-D converter 1230, a first LED driver 1231, a second LED driver 1232, and a status indicator 1240. The a-to-d converter 1230 can be configured to receive a signal from a detector in a realtime needle tip tissue analysis system that is hardwired to the control module 1200. The first LEDdriver 1231, and the second LED driver 1232 can be configured to transmit different wavelengths of light as described earlier, where there is a first LED output 1251, and a second LED output 1252. The microprocessor 1210 can receive inputs from microprocessor input 1270, and it can transmit signals via the microprocessor input 1280 to the status indicator 1240. In some embodiments, the status indicator 1240 can produce variable sounds or light to indicate the type of fluid encountered in a test chamber of a real-time needle tip tissue analysis system.

[0067] FIG. 9 is an example of a real-time needle tip tissue analysis system 900 where the system is entirely disposed on a disposable needle 910. In such a system, the output module 930 may comprise both a visual and an audible output, as illustrated in FIG. 9A, an enlarged view of the output module 930. In FIG. 9A, there can be multiple indications lights 932, where each light can produce a different color to correspond to the needle’s 910 placement within a patient’s tissue. Additionally, or in place of an audible output 934 can be included on the output module 930; here, the audible output 934 can produce different tonal patterns or tones that represent the needle’s 910 placement within a patient’s tissue.

[0068] Similar to the real-time needle tip tissue analysis system 900, is the real-time needle tip tissue analysis system 1000 in FIG. 10. In this embodiment, the multiple indications lights can be replaced with a single indication light 1032 that is disposed within the output module 1030 on a disposable needle 1010.

[0069] In both the 900 and 1000 systems, an output module can comprise an arrangement for the output module, as illustrated in FIG. 11. For example, in FIG. 11, the output module 1130 can include a needle body 1110, a syringe connector 1112 (e.g., a Luer Lock®), a lumen 1120 where the output module 1130 can communicate with an LED / detector / test chamber arrangement that can be located at the distal end of the needle body 1110 similar to the embodiments in FIGs.1-5. In output module 1130, there can be an output circuit board 1140 that can be in electrical communication with microprocessor 1144, which can be configured to receive the signals from the LED / Detector / Test chamber arrangement and in further electrical communication with a battery 1148 and an indication light / audible output 1142. In the output module 1130, there can be a speaker cover / viewing window 1158 positioned over the output 1142.

[0070] In such an embodiment of output module 1130, the LED / Detector / test chamber arrangement can be configured to communicate with the microprocessor 1144 via a flex print 1151 that can be connected to the output circuit board 1140 at a surface mount connection 1150. A sealant 1152 can be applied to the opening in the needle body 1110 to seal off the lumen 1120 from the exterior of the needle body 1110. The sealant 1152 may also be used to waterproof the output module 1130, where the flex print 1151 enters output module 1130.

[0071] Additionally, in the output module 1130, the battery 1148 can be kept in storage by the inclusion of an activation tab 1154 that can be structured and configured to be removable for activation purposes, as the removal of the activation tab 1154 will connect the battery’s 1148 terminal to the battery clip 1146. There may also be a tab seal 1156 that can retain the activation tab 1154 to prevent accidental activation of the output module 1130.

[0072] In some embodiments, the system architecture can be configured for wireless communication. For example, in FIG. 13, the system architecture 1300 can be a wireless transceiver system architecture with a microprocessor 1310 and a first power source 1320. The microprocessor 1310 can communicate to an LED / detector / test chamber arrangement via an A- to-D converter 1330, a first LED driver 1331, and a second LED driver 1332. The microprocessor 1310 can be configured to then receive a microprocessor input 1370 transmitted by any of the detector signal 1360, and transmit a first LED output 1351, and a second LED output 1352. The microprocessor 1310 can be configured to process the signals from the LED / detector / test chamber arrangement and then transmit a microprocessor output 1380 containing the processed information via a first RF translator 1382 and a first antenna 1384.

[0073] The transmitted signal can then be received by a second antenna 1386 and a second RF translator 1388, where a microprocessor 1310 can be configured to convert the signal into an output via a status indicator 1390. The information may also be stored in a memory 1392. The system may also include an ethemet connection 1394 and a second power source 1396. The system architecture 1300 can be configured to work with any of the LED / detector / test chamber arrangements described within the instant disclosure.

[0074] In some embodiments, the system architecture can be configured for a needle-mounted threshold detection and status indication system for wireless communication. For example, in FIG. 14, the system architecture 1400 includes a microprocessor 1410 in communication with a power source 1420 and a voltage regulator 1422. On the same board as the microprocessor 1410, there can be a first A-to-D converter 1430, a first LED driver 1431, a second LED driver 1432, and a second a-to-d converter 1434. The microprocessor 1410 can communicate to an LED / detector / test chamber arrangement via an A-to-D converter 1430, a first LED driver 1431, and a second LED driver 1432. The microprocessor 1410 can be configured to receive inputs transmitted by any of the detector signal 1460, and transmit a first LED output 1451, and a second LED output 1452. The microprocessor 1410 can be configured to process the signals from the LED / detector / test chamber arrangement and then transmit an output containing the processed information via a Bluetooth transceiver 1482 and a Bluetooth antenna 1484. The Bluetooth communication can thenbe received by any number of devices that can provide real-time feedback regarding the location of a needle using the system architecture 1400.

[0075] For example, FIG. 15 illustrates one such embodiment of a device that can provide realtime feedback where a personal smart device 1500 (here being a smartwatch, but can be any such device known in the art that includes an output capability). Here, the personal smart device 1500 can be configured to provide an audio output 1510, a visual output 1520, a haptic output 1530, and any combination thereof. Other devices have been contemplated as devices that can provide real-time feedback. For example, a device that is a dedicated standalone receiver and transmitter. Such a dedicated standalone receiver can include the system architecture illustrated in FIG. 13. The system architecture 1400 can work with the real-time needle tip tissue analysis system 900 in FIG. 9 and the output module 930 of FIG. 9A. A wristwatch-based RF system 1500, illustrated in this embodiment and, may contain a custom or commercially available wristwatch / smartwatch having an RF Communication system that could be employed to serve as the connection to the needle. Such a system may have the advantage of being close to the needle injection point, thereby allowing it to communicate data, threshold levels, or provide haptic communication. Such a device may also provide audio communication, along with battery levels for both the needle and wristwatch / smartwatch. Such an embodiment may also be able to provide encryption and security for the transmitted and stored data storage.

[0076] In another embodiment of a needle-mounted threshold detection and status device, as illustrated in the block diagram of FIG. 16, the system architecture can be configured to have status indications output on the needle mount, as described in FIG. 10. In FIG. 16, the system architecture 1600 can include a microprocessor 1610, a first power source 1620. The microprocessor 1610 can communicate to an LED / detector / test chamber arrangement via an A- to-D converter 1630, a first LED driver 1631, and a second LED driver 1632. The microprocessor 1610 can be configured to then receive a microprocessor input 1670 transmitted by any of the detector signal 1660, and transmit a first LED output 1651, and a second LED output 1652. The microprocessor 1610 can be configured to process the signals from the LED / detector / test chamber arrangement and communicate them via microprocessor output 1680 to any of a first visual output 1691, a second visual output 1692, a third visual output 1693, or a fourth visual output 1694; where each of the visual outputs can be configured to represent a different location of the needle in the needle mounted system.

[0077] In another embodiment of a real-time needle tip tissue analysis system, as illustrated in FIG. 19, where the real-time needle tip tissue analysis system 1900 is similar to the arrangement of the real-time needle tip tissue analysis system 300, having a needle body 1910 and lumen 1920.This is another example of a transverse two-wavelength needle geometry with a flex print board. In this system 1900, there is a slightly different arrangement of than the system 300 of FIG. 3. Not only is there a separation of the first LED die 1941 and the second LED die 1942 that is more pronounced than the real-time needle tip tissue analysis system 100. Both dies are still aligned with a first detector 1943 and a second detector 1944. Test chamber 1940 can still be formed between the LED dies and detectors that are disposed on a flex print board 1930. However, in the real-time needle tip tissue analysis system 1900, there can also be an additional resistance sensor 1950.

[0078] The resistance sensor 1950 can be configured as illustrated in FIGs. 17A or 17B. For example, in FIG. 17A, the resistance sensor 1950 can comprise a two-wire resistance sensor, as this approach may provide a simple means to measure, and may be adequate due to the large variation in tissue conductivity. Another variation of the resistance sensor 1950, the resistance sensor 1950 can be comprised of a four- wire resistance sensor. In a 4-wire mode, the resistance sensor 1950 may require 4-wire switching and more cabling. In such a configuration, the resistance sensor 1950 can be more accurate than the 2-wire mode by achieving more precise measurements with resistances below 100 kQ. When using the 4-wire resistance measurement, current can be forced through the source terminals, making resistance in the drive wires unimportant. The voltmeter can be configured to have a high impedance, which in turn can let the sensor draw almost no current. Such a configuration may make the sense-conductor resistance error extremely small. Voltage levels can be small with this system to avoid any potential negative impacts on the patient.

[0079] The resistance sensor 1950 can be configured to use an interdigitated finger-type resistance sensor, as illustrated in FIG. 18. In such an embodiment, the interdigitated finger type resistance sensor 1800 can be a more efficient way to measure resistance due to a larger contact surface area. It may also provide for a virtually free artifact of the flex print manufacturing process.

[0080] The threshold indication module may include a multi-colored indication light, wherein the indication light uses a spectrum of colors to provide instant feedback to an end user about the location of the tip of the needle within a patient. Such an integrated threshold indication module may provide the end-user total freedom of movement when using the proposed embodiments; the end user may not be encumbered with wires leading from a non-integrated device to an external detection system.

[0081] A key benefit of a wireless configuration can be that the cumbersome nature of the wires is eliminated. There are many protocol options for short-range wireless communication. Some of the most common protocols include Bluetooth®, Bluetooth® LE, Ultra-Wideband (UWB),802.15.4 Based Zigbee, Radio Frequency Identification (RFID), and Wi-Fi, based on 802.11 IEEE standards. In this HIPAA-Compliant World, managing cybersecurity risk is a significant challenge and plays an important role in the selection of a wireless protocol. SOC 2, aka Service Organization Control Type 2, provides a good framework for addressing cybersecurity risk. SOC 2 is a cybersecurity compliance framework developed by the American Institute of Certified Public Accountants (AICPA). The primary purpose of SOC 2 is to ensure that third-party service providers store and process client data in a secure manner.

[0082] Needles can be in dormant storage in a sterile package. During storage, the RF Module battery may need to be disconnected. A well-known way to accomplish activation is the use of a pull tab, a non-conductive strip separating the battery from the mating contact. Said pull tab can be removed prior to use, and the system provides an indication of battery levels necessary for a procedure.

[0083] Oximeters operate based on the principle of different absorption and light emission at different light wavelengths. These oximeters can utilize a microprocessor and a pair of lightemitting diodes (LEDs) connected to fibers passing through a fiber optic splitter and into the test chamber at the needle tip. The light can then be reflected back into the fiber through the splitter and directed to a photodiode. One LED can be red, with a wavelength of 660 nm, and the other can be infrared, with a wavelength of 940 nm. Absorption of light at these wavelengths differs significantly between blood loaded with oxygen and blood lacking oxygen. Oxygenated hemoglobin absorbs more infrared light and allows more red light to pass through. Deoxygenated hemoglobin allows more infrared light to pass through and absorbs more red light.

[0084] In a typical embodiment, the LEDs sequence through their cycle of one on, then the other, and then both off about thirty times per second. The amount of light that can be transmitted (in other words, that is not absorbed) is measured. These signals fluctuate in time because the amount of arterial blood that can be present can increase (literally pulses) with each heartbeat. By subtracting the minimum transmitted light from the peak transmitted light in each wavelength, the effects of other tissues are corrected, allowing for the measurement of only the arterial blood.

[0085] The ratio of the red-light measurement to the infrared light measurement can then be calculated by any of the microprocessors (which represents the ratio of oxygenated hemoglobin to deoxygenated hemoglobin). This ratio can then be converted to SpO2 by any of the microprocessors via a lookup table based on the Beer-Lambert law.

[0086] Another potential aspect of this invention is the use of photoplethysmography. This technology is commonly used in conjunction with blood oxygenation tools to remove errors. With any SpO2 reading is plethysmography tracings or “pleth,” which is a measure of volumetricchanges associated with pulsatile arterial blood flow. Inconsistent or distorted pleth may result in changes to the computer-calculated value, resulting in artificially HIGH or LOW SpO2 readings. Therefore, plethysmography ensures the reliability of the calculated oxygen saturation.

[0087] In the present invention, these variations can be used as a secondary indication to confirm that the needle tip is in flowing arterial blood. These signals will be smaller in the needle tip test chamber but are likely to be measurable by the precision optic detection system.

[0088] Photodetectors are commercially available in sizes down to 5 um diameter; note that nanolevel detectors are available with high sensitivity and low noise. There are dozens of detector technologies available with different performance characteristics. Each detector can employ a wavelength notch filter that may be tuned to the wavelength of its companion LED to limit the system's sensitivity to ambient lighting. Additionally, in any embodiment of the real-time needle tip tissue analysis system where there are multiple LEDs, a single broadband detector can be used to detect the light emitted from all of the LEDs. For instance, a real-time needle tip tissue analysis system having two LEDs that emit distinct wavelengths can utilize a single broadband detector.

[0089] FIG. 20 discloses an absorption spectra of hemoglobin as a function of wavelength. This is a descriptive chart showing the value of employing different wavelengths, wherein the response to oxygenation levels has a large and opposite directional effect. This is the most important indication as to the absorption spectra of hemoglobin as a function of wavelength. As is obvious, the two signals are opposite if the correct wavelength of sensing wavelengths are selected. By selecting approximate wavelengths of 700 nm and 900 nm, It is apparent that the signals are opposite in sensitivity direction. This is an ideal scenario for determining oxygenation levels

[0090] FIG. 21 discloses a plethysmography tracing, being a measure of volumetric changes associated with pulsatile arterial blood flow; this can be a great independent secondary indication that the needle is in arterial blood flow, and the pulsatile arterial blood flow can be easily detectable. Plethysmography is defined as the determination of changes in volume, and various plethysmography techniques have been evaluated in the noninvasive examination of the venous system. Photoplethysmography (PPG) utilizes a transducer that emits infrared light from a lightemitting diode into the dermis. The backscattered light is measured by an adjacent photodetector and displayed as a line tracing. The amount of backscattered light varies with the capillary red blood cell volume in the dermis. This can be used as an indicator that the needle tip is in venous blood.

[0091] In a prospective embodiment, a mechanical agitator may be added to the tip of the needle in the sensor system to accomplish enhancements to the operation of the system. The addition of the mechanical agitator may help eliminate trapped air in order to ensure that the LED and sensorare looking through blood and / or bodily fluids. It may also improve the response time of the sensor system due to the agitation of the fluids in the sensor system enabling a faster turnover of the fluids. A preferred embodiment may make use of a piezoelectric actuator which can wave the actuator in a cantilever motion orthogonal to the plane of the piezoelectric actuator. Said actuator is actuated by a square wave or sine wave signal from the control electronics. The impedance from this actuator can also provide a secondary validation that the sensors are in fluid, not air. For example, in FIG. 22, a mechanical agitator 2260 can stir a fluid within the test chamber 2240 so as to prevent vapor lock and to increase the response time of the sensor system by rapidly exchanging any fluid within the test chamber 2240. For example, mechanical agitator 2260 can be a cantilever-type piezoelectric agitator, as illustrated in FIG. 22A, or it may be a serpentine piezoelectric agitator.

[0092] Collected data can be analyzed by an Al system in conjunction with the LED-based sensors. This orthogonal set of data may be able to provide both higher accuracy and greater reliability. Resistive sensing can be a key to the determination of a tissue type. Different tissues in the body have markedly different conductivities. In combination with Al technologies, the resistivity sensed in the system can provide a straightforward indication of the nature of the tissue at the needle tip.

[0093] The combination of LED sensing and resistive sensing as orthogonal inputs to Al may provide a strong and discriminating sensor system embodiment.

[0094] In another embodiment of the threshold indication module, there may also be a system that uses real-time impedance to detect biological substances, such as bodily fluids and tissues, including blood. Various embodiments of real-time impedance measuring needle systems are described in detail with reference to the drawings, wherein like reference numerals may represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the real-time impedance-measuring needle system disclosed herein. Additionally, any examples set forth in this specification are not intended to be limiting and merely set forth some of the many possible embodiments for the real-time impedance measuring needle system. It is understood that various omissions and substitutions of equivalents are contemplated as circumstances may suggest or render expedient, but these are intended to cover applications or embodiments without departing from the spirit or scope of the disclosure. Also, it is to be understood that the phraseology and terminology used herein are for the purpose of description and should not be regarded as limiting.

[0095] When the output indicates that the user is in the wrong tissue or detects certain biological material or tissue that is not desired for delivery of the medical fluid, then the user may repositionthe needle to a different location for further determination of a location for medical fluid delivery. When the user determines that the needle location is suitable for delivery, the user may deliver the medical fluid into the tissue that the needle has entered. In some embodiments, the delivery may be automated or controlled by a computing device when the delivery site is suitable for the medical fluid injection.

[0096] It might be beneficial to have embodiments of a real-time needle tip tissue analysis system to run a self-test upon battery initiation; e.g. when a battery -pull tab assembly is removed from an output module. Part of such self-tests could be a measurement of detector outputs with no fluid in the test chamber, and while still in the in the darkness of the packaging system. This could be useful as a calibration point, identifying changes in the sensitivity of the detector and / or the output of the LEDs.

[0097] Persons of ordinary skill in arts relevant to this disclosure and subject matter hereof will recognize that embodiments may comprise fewer features than illustrated in any individual embodiment described by example or otherwise contemplated herein. Embodiments described herein are not meant to be an exhaustive presentation of ways in which various features may be combined and / or arranged. Accordingly, the embodiments are not mutually exclusive combinations of features; rather, embodiments can comprise a combination of different individual features selected from different individual embodiments, as understood by persons of ordinary skill in the relevant arts. Moreover, elements described with respect to one embodiment can be implemented in other embodiments even when not described in such embodiments unless otherwise noted. Although a dependent claim may refer in the claims to a specific combination with one or more other claims, other embodiments can also include a combination of the 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. Such combinations are proposed herein unless it is stated that a specific combination is not intended. Furthermore, it is also intended to include features of a claim in any other independent claim, even if this claim is not directly made dependent to the independent claim.

Claims

CLAIMS1. A real-time needle tip tissue analysis system comprising: a needle, wherein the needle comprises a lumen having a proximal and a distal end, wherein the distal end is structured and configured to be inserted into human tissue; a flex print disposed on the lumen; at least one LED die disposed on the flex print at the distal end of the needle, wherein the at least one LED die is in communication with the flex print; at least one detector disposed on the flex print at the distal end of the needle, wherein the at least one detector is in communication with the flex print and opposed to the at least one LED die; a test chamber, wherein the test chamber is formed between the at least one LED and the at least one detector; and an output module, wherein the output module is in communication with the flex print and the output module is structured and configured to generate a variable output based on the location of the distal end of the needle.

2. The real-time needle tip tissue analysis system of claim 1, further comprising a ramp, wherein the ramp is disposed on the flex print and bounds a side of the test chamber.

3. The real-time needle tip tissue analysis system of claim 2, wherein the at least one LED die is covered with an encapsulant.

4. The real-time needle tip tissue analysis system of claim 3, wherein the encapsulant is configured to have a reflective surface, and wherein the reflective surface directs light from the LED die through the test chamber and towards the at least one detector.

5. The real-time needle tip tissue analysis system of claim 1, wherein the output module is disposed on the needle.

6. The real-time needle tip tissue analysis system of claim 5, wherein the output module comprises an indication light that is configured to produce the variable output.

7. The real-time needle tip tissue analysis system of claim 5, wherein the output module comprises a speaker that is configured to produce the variable output.

8. The real-time needle tip tissue analysis system of claim 1, wherein there are two LED dies and two detectors, wherein the two LED dies are configured to produce differentwavelengths of light, and wherein each detector is configured to receive light from one of the LED dies.

9. A real-time needle tip tissue analysis system comprising: a needle, wherein the needle comprises a lumen having a proximal and a distal end, wherein the distal end is structured and configured to be inserted into human tissue; a flex print disposed on the lumen; at least one LED die disposed on the flex print at the distal end of the needle, wherein the at least one LED die is in communication with the flex print; at least one detector disposed on the flex print at the distal end of the needle, wherein the at least one detector is in communication with the flex print and opposed to the at least one LED die; a test chamber, wherein the test chamber is formed between the at least one LED and the at least one detector; and an output module, wherein the output module is in communication with the flex print and the output module is structured and configured to transmit a signal via a wireless transmitter to an output device, wherein the output device is configured to produce a variable output based on the location of the distal end of the needle.

10. The real-time needle tip tissue analysis system of claim 9, further comprising a ramp, wherein the ramp is disposed on the flex print and bounds a side of the test chamber.

11. The real-time needle tip tissue analysis system of claim 10, wherein the at least one LED die is covered with an encapsulant.

12. The real-time needle tip tissue analysis system of claim 11, wherein the encapsulant is configured to have a reflective surface, and wherein the reflective surface directs light from the LED die through the test chamber and towards the at least one detector.

13. The real-time needle tip tissue analysis system of claim 9, wherein the output module is disposed on the needle.

14. The real-time needle tip tissue analysis system of claim 13, wherein the output device is a smart watch, smart phone, or a dedicated remote receiver.

15. A real-time needle tip tissue analysis system comprising: a needle, wherein the needle comprises a lumen having a proximal and a distal end, wherein the distal end is structured and configured to be inserted into human tissue; a circuit board disposed on the lumen;at least one LED die disposed on the circuit board at the distal end of the needle, wherein the at least one LED die is in communication with the circuit board; at least one detector disposed on the circuit board at the distal end of the needle, wherein the at least one detector is in communication with the circuit board and opposed to the at least one LED die; a test chamber, wherein the test chamber is formed between the at least one LED and the at least one detector; an output module, wherein the output module is in communication with the circuit board and the output module is structured and configured to generate a variable output based on the location of the distal end of the needle; and a resistance sensor, wherein the resistance sensor is disposed closer to the distal end of the needle than the test chamber.

16. The real-time needle tip tissue analysis system of claim 15, wherein the at least one LED die is covered with an encapsulant.

17. The real-time needle tip tissue analysis system of claim 16, wherein the encapsulant is configured to have a reflective surface, and wherein the reflective surface directs light from the LED die through the test chamber and towards the at least one detector.

18. The real-time needle tip tissue analysis system of claim 15, wherein the output module is disposed on the needle.

19. The real-time needle tip tissue analysis system of claim 15, wherein there are two LED dies, and two detectors, wherein the two LED dies are configured to produce different wavelengths of light, and wherein at least one detector is configured to receive light from the LED dies.

20. The real-time needle tip tissue analysis system of claim 15, wherein a mechanical agitator is disposed within the test chamber.

Images