Wireless triggering device

Abstract

Disclosed herein is a wireless trigger device for implantation at a site for monitoring a condition at the site, comprising: a modulator implantable at the site, the modulator comprising: a detector operable to detect a predetermined condition at the site; and a modulation circuit configured to be physically coupled to an antenna implanted at the site, the antenna being operable to receive a wireless trigger signal, and a modulation circuit operable to receive the wireless trigger signal from the antenna and to modulate the wireless trigger signal based on the detected predetermined condition to thereby generate a backscatter response signal having a particular harmonic for wireless transmission by the antenna, wherein the detector comprises a passive component of the modulation circuit.

Description

[0001] This application is a divisional application of the invention patent application with application date of November 9, 2020, application number 202080091928.9, and invention name “Wireless Trigger Device”. Technical Field

[0002] The present invention relates to wireless triggering devices and particularly, but not exclusively, to devices for in situ sensing and transmission at a remote location, particularly within the body. Background Art

[0003] After a physical trauma such as surgery, a cut, infection, or other injury, conditions may develop that may impede healing or require further intervention, etc. For example, wound dehiscence may result in the need to replace sutures.

[0004] When these conditions are internal, they can be particularly difficult to detect. With internal surgical procedures, dehiscence, infection, and other conditions can often only be identified after symptoms indicate the occurrence or presence of the condition. In such cases, the condition may cause patient discomfort or necessitate more drastic surgery.

[0005] Furthermore, even in the absence of adverse events, it may be very difficult to assess the condition of the internal surgical site to determine, for example, the extent to which the site has healed. Furthermore, it may be desirable to provide additional support for the healing process at the site of interest without further surgical intervention.

[0006] It would therefore be desirable to provide a means for earlier identification of the condition that would overcome or ameliorate at least one of the above problems, to enable the surgeon to more confidently identify healing, or at least provide a useful alternative. Summary of the invention

[0007] In a first aspect, a wireless trigger device for in vivo implantation is provided, the device comprising: a conductive suture; an electronic circuit coated with a biocompatible packaging material and communicatively coupled to the conductive suture, the electronic circuit being arranged to convert a received wireless trigger signal into an electrical signal for passing through the conductive suture.

[0008] Wireless triggering means that one or more operations of the device are initiated by the arrival of a wireless signal, such as an electromagnetic signal, for example a radio frequency signal or a magnetic signal.

[0009] The term conductive suture is intended to mean a thread that is both capable of apposing tissue portions and capable of carrying electrical signals.Preferably, the electrical conductivity of the conductive suture is greater than 100 S / m.

[0010] Advantageously, the wireless triggering device of the present invention enables enhancement of surgical sutures via electrical signals, enables providing sensing capabilities directly at the wound site, and / or provides other functions that support wound healing at the site via the suture.

[0011] The conductive suture may include a first conductive portion, a second conductive portion, and an insulating portion between the first conductive portion and the second conductive portion, the electronic circuit being communicatively coupled to the first conductive portion and the second conductive portion and arranged to allow electrical signals to pass through the first conductive portion and the second conductive portion. Preferably, the conductive suture comprises a conductive surgical thread, the conductive surgical thread comprising an inner surgical thread, a conductive coating on the inner surgical thread, the conductive coating comprising a biocompatible conductive polymer, and a biocompatible protective coating on the conductive coating. Such a surgical thread provides good conductivity without compromising strength and flexibility.

[0012] Alternatively, the conductive suture may comprise stainless steel surgical wire.

[0013] The length of the suture may be between 1 mm and 1 m. The length of the suture may be between 1 mm and 50 cm. Preferably, the suture has a length greater than 20 mm. Preferably, the suture has a length less than 30 mm. Preferably, the suture has a length of about 25 mm. Sutures of this length enable maximum power transmission.

[0014] Preferably, the device is a passive electronic device. This allows the device to be used for a long time without having to implant an additional source into the body.

[0015] The biocompatible encapsulation material may be selected from PDMS, silicone, parylene-C and polyurethane.

[0016] The conductive suture may be arranged to receive a wireless trigger signal, and the electronic circuit may include a modulation circuit operable to modulate the received wireless trigger signal to produce a backscatter response signal having specific harmonics as an electrical signal for transmission by the conductive suture. This arrangement advantageously enables wireless sensing at a wound site without the need to implant an additional antenna. The sensing functionality provided by the device may be further enhanced by the device further comprising a detector operable to detect a predetermined condition at the site, and wherein the modulator is operable to modulate the backscatter signal based on the detected predetermined condition. The detector may include passive components of the modulation circuit. Advantageously, such a sensing device enables monitoring of internal or external wounds using only simple low-power or passive devices and the suture as an antenna, thereby minimizing the number of devices to be implanted in the patient's body.

[0017] The predetermined condition may include one or more adverse pathophysiological conditions, such as bleeding, infection (such as bacterial growth), gastric fluid leakage, and anastomotic leakage. The modulation circuit may be an RLC circuit, and the resonant frequency of the RLC circuit may be varied based on the detected predetermined condition, for example, the passive component may be a capacitor or an inductor of the RLC circuit.

[0018] Preferably, the device further comprises a support member for supporting a layer of responsive material susceptible to change under predetermined conditions, the support member being configured to support the responsive material above the passive component. The support member comprises a plurality of relief structures extending from the modulation circuit and defining a cavity for receiving the responsive material, such as pillars and / or walls or any other type of relief structure capable of supporting the responsive material in place. The presence of a coating of responsive material on the passive component enables the modulation circuit to respond to one or more pathophysiological conditions in a controlled and predictable manner. Preferably, the responsive material is a hydrogel, such as a DNA hydrogel susceptible to degradation in the presence of nucleases secreted by bacteria, a peptide hydrogel susceptible to degradation in the presence of pepsin, or a heme hydrogel susceptible to solidification in the presence of blood.

[0019] Alternatively or additionally, the electronic circuit of the device may include a rectifier operable to rectify the wireless trigger signal to produce a current as an electrical signal, which is passed through the conductive suture. In this embodiment, the device may also include an antenna for receiving the wireless trigger signal, and the rectifier is communicatively coupled to the antenna. The antenna may be the conductive suture or another conductive suture. The device according to this embodiment advantageously enables wireless power supply at the wound site. For example, the device can be configured to stimulate nerves by passing current through the conductive suture, or the suture can be electrically connected to the electronic device and configured to supply power to the electronic device.

[0020] In a second aspect, a wireless trigger sensing device for monitoring conditions at a site is provided, the device comprising: a detector operable to detect a predetermined condition at the site; a modulation circuit configured to be communicatively coupled to an antenna, the modulation circuit operable to modulate a wireless trigger signal received at the antenna based on the detected predetermined condition to generate a backscatter response signal having specific harmonics for transmission by the antenna, wherein the detector comprises passive components of the modulation circuit.

[0021] Advantageously, such a sensing device provides a simple low power or passive device for monitoring conditions at a remote location. Components of the modulation circuit itself are used as detectors, so no additional detection components need to be employed, thereby ensuring that the size, complexity and cost of the sensing device are minimized. Preferably, the device is a passive electronic device, thereby enabling long term monitoring without the need for an additional power source.

[0022] The device may further include an antenna, and the modulation circuit and / or the antenna may be printed on a printed circuit board.

[0023] The device may be adapted for implantation in vivo, such as at a wound site, in which case the modulation circuit is coated with a biocompatible packaging material, which may be selected from PDMS, silicone, parylene-C and polyurethane. In this case, the device may also be a connector for connecting the device to a wound closure device so that it can be implanted in vivo, which may be a mechanical connector, such as suture or stapling, or a chemical adhesive, such as glue. The wound closure device may include sutures, staples, surgical zippers, endoscopic clips, etc. Alternatively, the antenna may be a conductive component of a medical device, which may be one or more of a bandage, a valve, a prosthesis and an implant.

[0024] In the case where the device is suitable for implantation in vivo, the predetermined condition may include one or more adverse pathophysiological conditions, such as bleeding, infection (such as bacterial growth), gastric fluid leakage, and anastomotic leakage. The modulation circuit is an RLC circuit, and the resonant frequency of the RLC circuit can be changed based on the detected predetermined condition, for example, the passive component can be a capacitor or an inductor of the RLC circuit.

[0025] In other embodiments, the predetermined condition may include a non-pathological condition, such as a vital sign measurement, such as heart rate monitoring or pulse monitoring, or suture breakage.

[0026] Preferably, the device further comprises a support member for supporting a layer of responsive material susceptible to undergoing a change in the predetermined condition, the support member being configured to support the responsive material above the passive component. The support member comprises a plurality of relief structures protruding from the modulation circuit and defining a cavity, such as a pillar and a wall, for receiving the responsive material. The presence of a coating of responsive material on the passive component enables the modulation circuit to respond to one or more acetone pathological conditions in a controlled and predictable manner. Preferably, the responsive material is a hydrogel, such as a DNA hydrogel susceptible to degradation in the presence of nucleases secreted by bacteria, a peptide hydrogel susceptible to degradation in the presence of pepsin, or a heme hydrogel susceptible to solidification in the presence of blood.

[0027] In an alternative embodiment, the device may be intended to be included in food packaging and the predetermined condition may be bacterial growth in the food. In this embodiment, the device may also include a support member for supporting a layer of responsive material susceptible to undergoing a change in the predetermined condition, the support member being configured to support the responsive material above the passive component. The support member includes a plurality of relief structures protruding from the modulation circuit and defining a cavity for receiving the responsive material, such as pillars and / or walls or any other type of relief structure capable of supporting the responsive material in place. The presence of a coating of responsive material on the passive component enables the modulation circuit to respond to one or more conditions in a controlled and predictable manner. Preferably, the responsive material is a hydrogel, such as a hydrogel susceptible to change in the presence of foodborne bacteria.

[0028] A reader may be provided for use with a wireless trigger device, the wireless trigger device comprising: a conductive suture; an electronic circuit coated with a biocompatible encapsulation material and communicatively coupled to the conductive suture, the electronic circuit being arranged to convert a received wireless trigger signal into an electrical signal for passing through the conductive suture, the conductive suture being arranged to receive the wireless trigger signal, and the electronic circuit comprising a modulation circuit operable to modulate the received wireless trigger signal to produce a backscatter response signal having a specific harmonic as the electrical signal for transmission by the conductive suture. Alternatively, a reader may be provided for use with a wireless trigger device, the wireless trigger device comprising: a detector operable to detect a predetermined condition at a site; a modulation circuit configured to be communicatively coupled to an antenna, the modulation circuit operable to modulate the wireless trigger signal received at the antenna based on the detected predetermined condition to produce a backscatter response signal having a specific harmonic for transmission by the antenna, wherein the detector comprises a passive component of the modulation circuit. In either case, the reader may include: a transmitter configured to transmit a plurality of interrogation signals configured to stimulate backscattered response signals from a device; a receiver configured to receive the backscattered response signals from the device; and a processor configured to determine conditions at a site based on the backscattered response signals. The reader may be provided with a wireless trigger device as a sensing platform.

[0029] In a third aspect, there is provided a conductive surgical thread for use as a suture to appose tissue portions, the surgical thread comprising: an endosurgical thread; a conductive coating on the endosurgical thread, the conductive coating comprising a biocompatible conductive polymer; and a biocompatible protective coating on the coating.

[0030] Advantageously, surgical threads according to embodiments enable electrical conductivity to be incorporated into surgical sutures without compromising the flexibility or strength of the suture.

[0031] The biocompatible conductive polymer may include one or more of the following: PEDOT:PSS, poly(pyrrole); polythiophene; poly(3-alkylthiophene); polyphenylene-vinylene; polyaniline; and poly(p-phenylene sulfide). Preferably, the biocompatible conductive polymer includes PEDOT:PSS, which provides good conductivity while maintaining excellent flexibility. The biocompatible conductive polymer includes three or more layers of PEDOT:PSS to optimize conductivity.

[0032] The biocompatible protective coating may include Parylene-C, and the inner surgical thread may include silk. The inner surgical thread may include any material. However, surgical threads according to embodiments having inner silk threads have been shown to provide sutures with particularly good signal-to-noise ratios when used as antennas. The surgical thread may have any thickness. However, surgical threads according to embodiments having a diameter of USP size 0 have been shown to provide sutures with particularly good signal-to-noise ratios when used as antennas.

[0033] In a fourth aspect, there is provided a method of producing a conductive surgical wire, comprising an endosurgical wire; a conductive coating on the endosurgical wire, the conductive coating comprising a biocompatible conductive polymer; and providing a biocompatible protective coating on the coating, the method comprising: providing a surgical wire; coating the wire with a conductive coating comprising a biocompatible conductive polymer; and encapsulating the coated wire in a biocompatible material. Advantageously, the method provides a surgical wire having high conductivity. Preferably, an oxygen plasma treatment is applied to the provided wire prior to removing the wax from the wire. Preferably, the conductive coating is vacuum dried.

[0034] The internal surgical thread can be a medical grade suture. In the alternative, the internal surgical thread can be a commercially available thread.

[0035] In a fifth aspect, a method for monitoring a condition at a site in the body is provided, the method comprising: implanting a device into the site, the device comprising a conductive suture; an electronic circuit coated with a biocompatible packaging material and communicatively coupled to the conductive suture, the electronic circuit being arranged to convert a received wireless trigger signal into an electrical signal for passing through the conductive suture, the conductive suture being arranged to receive the wireless trigger signal, and the electronic circuit comprising a modulation circuit, the modulation circuit being operable to modulate the received wireless trigger signal to generate a backscatter response signal having a specific harmonic as the electrical signal for transmission by the conductive suture; transmitting a plurality of interrogation signals, the interrogation signals being configured to stimulate a backscatter response signal from the device; receiving the backscatter response signal from the device; and determining the condition at the site based on the backscatter response signal. The method advantageously provides an accurate non-invasive method for monitoring a condition in the body.

[0036] The conditions may include one or more pathophysiological conditions. The one or more pathophysiological conditions include one or more of healing, bleeding, infection, dehiscence, suture breakage, heart rate, and respiratory rate. The implant device may include at least a portion of the wound being sutured with a conductive surgical suture.

[0037] In an embodiment, a method of monitoring a condition at a site in a body is provided, the method comprising: implanting a device in the site, the device comprising a detector operable to detect a predetermined condition at the site; a modulation circuit configured to be communicatively coupled to an antenna, the modulation circuit operable to modulate a wireless trigger signal received at the antenna based on the detected predetermined condition to produce a backscatter response signal having specific harmonics for transmission by the antenna, wherein the detector comprises a passive component of the modulation circuit. The condition may comprise one or more pathophysiological conditions. The one or more pathophysiological conditions comprise one or more of healing, bleeding, infection, dehiscence, suture breakage, heart rate, and respiratory rate. Implanting the device may comprise connecting the device to a medical device at the site.

[0038] In a fifth aspect, a transmission component is provided, the transmission component comprising: a transmission device, the transmission device comprising: an antenna connector, the antenna connector is used to connect to an antenna, and a signal generator, the signal generator is used to generate a signal for transmission using the antenna when the transmission device is attached to the antenna, wherein the signal generator has an unaffected condition and an affected condition, and a predetermined condition around the transmission device causes the signal generator to switch to the affected condition. The signal generated by the signal generator in the unaffected condition is different from the signal generated by the signal generator in the affected condition; and an antenna connected to the signal generator through the antenna connector, wherein the antenna includes a conductive stitching line.

[0039] Advantageously, certain embodiments of the present invention use a conductive suture as an antenna for transmitting signals. This enables the transmitting device or transmitting assembly to utilize sutures that already need to be inserted into the patient's body.

[0040] Since the device according to the embodiments can be customized to detect a specific condition - such as blood leakage / bleeding / hemorrhage, bacterial infection, wound dehiscence, etc. - for switching the generator device to the affected condition, the device is able to use the suture as an antenna to indicate a specific condition inside the patient's body, or to indicate a specific condition outside the patient's body, where, for example, the antenna forms part of a wound dressing or is sutured into a wound dressing.

[0041] Harmonic backscatter embodiments may eliminate the use of wires, except to the extent that conductive sutures or the like, which would already need to be provided even in the absence of the device, may be considered wires.

[0042] The device according to the embodiment can be a transponder or radio frequency identification tag for long-term battery monitoring. In view of the present teachings, such a device can be easily made biocompatible and cheap and easy to use. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Embodiments of the invention will now be described, by way of non-limiting examples, with reference to the accompanying drawings, in which:

[0044] Figure 1 A system for monitoring conditions in a remote location according to an embodiment is shown;

[0045] Figure 2 A first example of a sensing device including a series RLC circuit according to an embodiment is shown;

[0046] Figure 3 A second example of a sensing device including parallel RLC circuits according to an embodiment is shown;

[0047] Figure 4A third example of a sensing device including an integrated antenna according to an embodiment is shown;

[0048] Figure 5 shows an example of a modulator attached to a surgical suture according to an embodiment;

[0049] Figure 6 A first example of a modulator for attachment to a surgical suture according to an embodiment is shown;

[0050] Figure 7 A second example of a modulator for attachment to a surgical suture according to an embodiment is shown;

[0051] Figure 8 shows a schematic diagram of a sensing device employed in vivo according to an embodiment;

[0052] Fig. 9 A method of monitoring a wound site using a sensing device according to an embodiment is shown;

[0053] Fig.10 A method of measuring vital signs using a sensing device according to an embodiment is shown;

[0054] Fig.11 Shows Figure 7 A device wherein the antenna passes through the device and the hydrogel is coated on the capacitor;

[0055] Fig.12 A method for producing a DNA hydrogel according to an embodiment is shown;

[0056] Fig.13 Shows Fig.12 Degradation of DNA hydrogels in the presence of nucleases;

[0057] Fig.14 A method for producing a peptide hydrogel according to an embodiment is shown;

[0058] Fig.15 Shows Fig.14 Degradation of peptide hydrogels in the presence of pepsin;

[0059] Fig.16 Shows the use of Fig.14 The process of detecting gastric leakage using peptide hydrogel;

[0060] Fig.17 shows a schematic diagram of a reader for use with a sensing device according to an embodiment;

[0061] Fig.18 shows a schematic diagram of a reader for use with a sensing device according to an embodiment;

[0062] Fig.19a and Fig.19b Shown for use with Fig.18 Antennas for use with readers;

[0063] Fig. 20 A system for rectifying power at a remote location according to an embodiment is shown;

[0064] Fig.21 A first example of a rectifying device according to an embodiment is shown;

[0065] Fig. 22 A method of manufacturing a conductive surgical thread according to an embodiment is shown;

[0066] Fig.23 shows the received power of a suture as a function of suture length for three suture patterns according to an embodiment;

[0067] Fig.24 shows received power as a function of conductivity and diameter of a suture according to an embodiment;

[0068] Fig.25 shows the transmission efficiency of the suture as a function of frequency, and the change in resonant frequency for different capacitor capacities, according to an embodiment;

[0069] Fig.26 shows stress as a function of strain for a number of commercially available sutures compared to sutures produced according to an embodiment;

[0070] Fig. 27 shows the tissue pull force of multiple commercially available sutures compared to sutures produced according to an embodiment;

[0071] Fig.28 shows the change in resistance of a WISE suture produced according to an embodiment when the suture is subjected to a mechanical cycle of contraction and extension;

[0072] Fig.29 shows the change in resistance of a suture produced according to an embodiment measured in a physiological buffer 1X phosphate buffer solution (PBS) over three weeks;

[0073] Fig.30 The cell viability of sutures produced according to the embodiments is shown;

[0074] Fig.31a and Fig.31b shows the change in capacitance caused by exposure of a DNA hydrogel layered on a capacitor to an extracellular nuclease secreted by Staphylococcus aureus bacteria compared to a control;

[0075] Fig.32ashows normalized power as a function of frequency for three different bleeding severities using a combination of a WISE suture and a modulator produced according to an embodiment;

[0076] Figure 32b shows power as a function of frequency for different types of suture breaks using a combination of a WISE suture and a modulator produced according to an embodiment;

[0077] Fig.33a shows inflammation scores over time for wounds closed with sutures according to an embodiment;

[0078] Figure 33b shows healing scores over time for wounds closed with sutures according to an embodiment;

[0079] Fig.34 shows the change in resonant frequency over time of a wound closed with sutures having a modulator fixed thereto according to an embodiment;

[0080] Fig.35 The resistance of sutures prepared according to the scheme of Table 1 is shown;

[0081] Fig.36 shows the effect of the amount of PEDOT:PSS coating on the resistance of a suture according to an embodiment;

[0082] Fig.37 shows images of sutures produced according to embodiments having different sizes;

[0083] Fig.38 shows images of sutures produced according to embodiments with different base sutures;

[0084] Fig.39 Shows Fig.37 Signal and noise measurements of sutures;

[0085] Fig.40 Shows Fig.38 Signal and noise measurements of sutures;

[0086] Fig.41 Shown as Fig.19a and Fig.19b The wireless reflection coefficient S11 of the antenna as a function of frequency is shown in;

[0087] Fig.42a , Figure 42b and Fig.42c The simulated harmonic spectra of the blue bead suture, the overlock suture and the Cushing suture using the surgical thread according to the embodiment are respectively shown;

[0088] Fig.43shows simulated capacitance of a modulation circuit loaded with a cylindrical peptide hydrogel according to an embodiment;

[0089] Fig.44 shows simulated capacitance of a modulation circuit in contact with different types of cylindrical dielectrics according to an embodiment;

[0090] Fig.45 shows the effect of adding nuclease on the resonant frequency of an analog modulation circuit coated with a DNA hydrogel layer;

[0091] Fig.46 The effect of adding 10 μL of DI water on the resonant frequency of the simulated modulation circuit coated with a DNA hydrogel layer is shown;

[0092] Fig.47a , Figure 47b and Fig.47c Dynamic vital sign monitoring using a simulated WISE suture according to an embodiment before and after skin closure, gastric solution injection, and suture breakage are respectively demonstrated;

[0093] Fig.48a , Figure 48b and Fig.48c Spectra obtained from a WISE suture according to an embodiment before and after skin closure, exposure to gastric solution, and suture breakage are shown, respectively;

[0094] Fig.49 shows a comparison of the amplitude of a backscattered signal measured using a WISE suture according to an embodiment to an ECG signal; and Fig.50 Shown are changes in the signal-to-noise ratio of skin (upper panel) and muscle (lower panel) obtained from five samples over the same time period (error bars represent standard deviation). DETAILED DESCRIPTION

[0095] For the purpose of brevity and clarity, the description of the embodiments of the present disclosure relates to sensor devices, conductive sutures, and readers according to the accompanying drawings. Although the various aspects of the present disclosure will be described in conjunction with the embodiments provided herein, it should be understood that they are not intended to limit the present disclosure to these embodiments. On the contrary, the present disclosure is intended to cover alternatives, modifications, and equivalents of the embodiments described herein, which are included within the scope of the present disclosure as defined by the appended claims. In addition, in the following specific embodiments, specific details are set forth in order to provide a thorough understanding of the present disclosure. However, a person of ordinary skill in the art (i.e., a technician) will recognize that the present disclosure can be practiced without specific details and / or with multiple details resulting from a combination of various aspects of a particular embodiment. In many cases, well-known systems, methods, processes, and components are not described in detail to avoid unnecessarily obscuring various aspects of the embodiments of the present disclosure.

[0096] In embodiments of the present disclosure, the depiction of a given element in a particular figure or consideration or use of a particular element number or reference thereto in corresponding descriptive material may include the same, equivalent, or similar elements or element numbers identified in another figure or descriptive material associated therewith.

[0097] References to "an embodiment / example", "another embodiment / example", "some embodiments / examples", "some other embodiments / examples", etc. indicate that the embodiment(s) / example(s) described thus may include a particular feature, structure, characteristic, property, element, or limitation, but not every embodiment / example must include the particular feature, structure, characteristic, property, element, or limitation. Furthermore, repeated use of the phrase "in an embodiment / example" or "in another embodiment / example" does not necessarily refer to the same embodiment / example.

[0098] The terms "comprise", "include", "have", etc. do not exclude the presence of other features / elements / steps than those listed in the embodiments. The description of certain features / elements / steps in mutually different embodiments does not indicate that the combination of these features / elements / steps cannot be used in the embodiments.

[0099] As used herein, the terms "a" and "an" are defined as one or more than one. The recitation of particular values ​​or ranges of values ​​herein should be understood to include or be a recitation of approximate values ​​or ranges of values.

[0100] The ability to non-invasively monitor and communicate rounds of events occurring in remote areas such as a surgical site will pave the way for the development of next generation smart sensing technologies. Disclosed herein is a wireless sensing (WISE) technology for wirelessly transmitting information about a remote site (e.g., a surgical site) to an external reader. In some embodiments, this is accomplished through harmonic backscattering, which can eliminate wires by integrating a highly miniaturized transmitting device (such as a transponder). In some embodiments, the technology is instead employed to provide wireless powering designed to support the healing process at the site.

[0101] Figure 1A schematic diagram of a system 10 for sensing an event occurring in a remote area or location according to an embodiment is shown. The system 10 includes a sensing device 101, which includes an antenna 105 and a modulator 103 in communication connection 107 with the antenna 105. The system 10 also includes a reader 109, which can be remote from the device 101 and communicatively coupled to the device 101. The antenna 105 can be configured to receive a signal 111 transmitted by the reader 109, which is equivalent to an interrogation signal. As will be clear from the embodiments discussed below, the signal can be a radio frequency signal, a magnetic field, or any other signal with known or identifiable characteristics (such as frequency and amplitude). The signal 111 can also be capable of providing power to the modulator 103. This process will be further discussed below in conjunction with specific embodiments. The interrogation signal can stimulate the antenna to send a response signal 113. In specific embodiments, the response signal can be the result of backscatter coupling between the antenna 105 and the reader 109, that is, the response signal 113 can be a backscatter signal. In another embodiment, the response signal 113 may be stimulated by inductive coupling between the reader 109 and the antenna 105, for example, when both the reader and the antenna include inductive coils.

[0102] The connection 107 between the antenna and the modulator may simply comprise an electrical contact, such as a metal to metal contact, or may comprise a weld or solder or any other form of electrical connection.

[0103] In an embodiment, power for the device 101 may be provided by a battery or an energy harvester device. In a particular embodiment, the device 101 is passive, i.e., it does not include a power source, nor any physical connection (e.g., wires) to a power source. In this embodiment, power is instead provided to the device wirelessly, e.g., via a received receive signal 111 (by inductive or backscatter coupling) or via other wireless charging methods.

[0104] In an embodiment, the modulator 103 is configured to modulate (i.e. change) at least one characteristic of the backscattered signal 113. In an embodiment, it may be configured to change the spectrum of the signal. Thus, in an embodiment, the sensing device 101 may be configured to receive a signal 111 of a given characteristic, change one or more characteristics of the signal, and backscatter it with the changed characteristic as a response signal 113. In an embodiment, in addition to the modulation by the modulator 103, further changes in the signal characteristics may also occur at the antenna 105.

[0105] In embodiments, the modulation or change in the characteristics of the response signal applied by the modulator 103 (and antenna 105, where appropriate) depends on the conditions in which the device 101 is located. For example, the modulator 103 may be sensitive to or otherwise affected by liquids, gases, or other substances, sensing device 101, or a particular portion of sensing device 101, that come into contact with it. Similarly, the antenna 105 may be sensitive to or otherwise affected by the conditions in which it is located. In some embodiments, the device may not output a signal at all, depending on the conditions. The sensing device 101, or a portion of the sensing device 101, may be particularly adapted to change its behavior when a particular event occurs.

[0106] Therefore, the sensing device 101 can be used to monitor the occurrence of at least one event, which is associated with a change in the conditions around the device. The reader 109 can receive the response signal 113 and determine that the event has occurred or is occurring based on the characteristics of the response signal.

[0107] Thus, it can be said that the sensing device 101 has an unaffected condition and an affected condition, the unaffected condition being a condition indicating that the condition that the sensing device 101 seeks to monitor does not yet exist. In the affected condition, the event that is sought to be monitored has occurred or is occurring. In the affected condition, the device 101 no longer sends a signal or sends a signal that is different from the signal that it would send in the unaffected condition. This means that a predetermined condition around the device 101 (i.e., the occurrence of an event) causes the sensing device 101 to transition to an affected condition, such that the signal output by the device 101 in the unaffected condition is different from the signal output by the device 101 in the affected condition. Therefore, the absence of a signal or a changed signal indicates that an event has occurred.

[0108] Figure 2 1 shows a circuit diagram of an apparatus 101 according to an embodiment. In this embodiment, the modulator 103 includes a modulation circuit 201, which is an RLC circuit including a capacitor 203, an inductor coil 205 and a diode 207 connected in series. In other embodiments (see, for example, Figure 3 ), they can be connected in parallel.

[0109] exist Figure 2In the embodiment of the invention, the antenna 105 is connected across the modulation circuit 201 for receiving and / or transmitting signals. It should be understood that the antenna includes two separate conductive parts 1051 and 1053, which are connected via the modulation circuit 201 so that the device functions as described. When the antenna 105 receives a signal oscillating at the resonant frequency f0 of the circuit 201, the modulation circuit 201 will cause the antenna 105 to backscatter the signal at the second harmonic of the resonant frequency 2f0, that is, the signal is modulated into a change in the second harmonic resonant frequency. The resonant frequency of the circuit 201 depends on the inductance of the inductor 205, the capacitance of the capacitor 203 and the resistance or impedance in the circuit.

[0110] Thus, a typical sensing measurement performed by a reader 109 used with the device 101 may be performed by sweeping a signal from a first frequency to a second frequency having the same amplitude (e.g., 1 to 2 GHz), while simultaneously recording the second harmonic by a spectrum analyzer. It will be appreciated that the frequency range of the signal may vary, but preferably includes the resonant frequency of the RLC circuit of the device in its unaffected condition.

[0111] In an embodiment, one or more circuit parameters of modulation circuit 201 are configured to change in response to conditions in which circuit 201 is located. In an embodiment, capacitor 203 is configured such that its capacitance changes in response to conditions in which device 101 is located. For example, the capacitance of capacitor 203 may change due to contact of a substance with device 101 or with a portion of the device that includes capacitor 203. The change in capacitance changes the resonant frequency of the circuit, and thus the spectrum of signal 113 backscattered by antenna 105 will shift. This may be achieved by: Figure 3 This is schematically shown in , where the resonant frequency of the spectrum 140 (the minimum in the spectrum) is shifted to a higher frequency in 142 .

[0112] Likewise, in the case of inductive coupling with the reader 109 , changes in the capacitance of the modulation circuit 201 will result in changes in the magnetic field induced by the inductor 205 .

[0113] In other embodiments, sensing device 101 may be configured such that other components, such as inductor 205, change their electrical properties in the presence of one or more external substances. Similarly, sensing device 101 may be configured such that the resistance of a circuit is affected by a particular event.

[0114] The exact values ​​and form of the circuit 201 may vary in a manner that will be apparent from the present teachings while maintaining the functionality described herein. Specifically, a change (whether a step change or a gradual change) in a circuit parameter or characteristic (e.g., resistance or impedance, capacitance, inductance, etc.) will indicate a transition to an affected condition. Notably, the affected condition may constitute a series of signals, such as a gradual condition (such as a bacterial infection), or may be a fixed change, such as a single removal in the case of antenna damage.

[0115] In embodiments, power for the sensing device 101 may be provided by a small battery, an energy harvester device, or specifically, may be generated by current flowing through the antenna 105 when the signal 111 is captured, or by another passive charging mechanism such as an electromagnetic field (EMF) applied by the reader 109 or other remote device simultaneously with or including the signal 111. In other embodiments, the reader 109 generates an EMF that charges the sensing device to cause it (i.e., its modulator) to transmit a signal. The modulator 103 may alternatively be activated by a remote device that activates the modulation circuit 201 included in the modulator 103 by transmitting a signal at a resonant wavelength of the modulation circuit 201 that is captured by the antenna 105. The captured signal may stimulate a response in the device, which is battery driven or passively charged as described above.

[0116] In some embodiments, the sensing device 101 is a highly miniaturized transponder for transmitting information from a remote location, such as deep tissue, to an external wireless reader. The transponder may use harmonic backscattering. The transponder may alternatively transmit a signal of a different frequency or amplitude, or a signal of a mixed frequency, that is not a harmonic of the stimulation signal, i.e., a signal supplied by a remote device or remote system to stimulate a response from the transponder or activate the transponder.

[0117] In other embodiments, the sensing device 101 is an RFID tag that is charged by an applied electromagnetic field to transmit a signal. The present technology can therefore also be used to activate tags / transponders on demand to perform desired monitoring activities in and around the location of the sensing device 101.

[0118] The sensing device 101 according to an embodiment enables efficient and secure wireless signal transmission between a sensing device (e.g., a transponder) (which may be an implant) and an external reader to provide information about a remote area monitored by the sensing device. In the illustrated embodiment, changes in the environment surrounding the sensing device are sensed by changes in the resistance, capacitance, or inductance (RLC) of a modulated circuit, and the properties of the circuit thus change as the modulator transitions to an infected condition. This results in modulation of the signal sent by the sensing device 101 and may manifest as a change in resonant frequency. The sensing device thus enables non-invasive monitoring of remote sites such as surgical sites within the body to provide real-time continuous or on-demand information.

[0119] Figure 3 Another example of a sensing device 101 is shown, which includes an RLC-based modulation circuit 201 as a modulator 103, wherein an inductor and a capacitor are arranged in parallel. Otherwise, the function of the device is similar to Figure 2 The function of the device.

[0120] Figure 4 A design of a sensing device 101 according to an embodiment is shown, wherein all components, antenna 105 and modulator 103 (and connection 107) are incorporated into the same component as a flexible printed circuit board 303. The sensing device 101 comprises an interdigitated capacitor 203, an inductor-Schottky diode 307 and a printed antenna 105. In an embodiment, the printed circuit board 303 may be encapsulated or coated with a material that allows it to be used in a specific environment, for example, a biocompatible silicone polymer, to enable use in the human or animal body. In an embodiment, the thickness or type of the encapsulation material or coating may be selected so that the material in contact with the encapsulation material can change the dielectric constant of the capacitor 203 or the electrical properties of other components, thereby enabling the electrical response of the circuit to conditions external to the device. The exact thickness will vary depending on the application and the specific material employed. However, in general, the thinner the encapsulation material, the greater the responsiveness of the electrical properties of the circuit to any body fluid such as blood, gastric fluid, wound pus, etc. Preferably, the thickness of the encapsulation material is in the range of 1 micron-5 cm. Preferably, its thickness is greater than 400 microns. Preferably, its thickness is less than 600 microns. Preferably, the thickness of the encapsulation material is about 500 microns.

[0121] In an embodiment, the printed circuit board may be further coated or partially coated with a material that is responsive to a particular substance. This will be discussed further below.

[0122] In an embodiment, antenna 105 may not be integrated into the same component as modulator 103, but may comprise a separate component to which modulator 103 is connected or not included at all, as described above. Such an embodiment will be discussed in detail below.

[0123] In certain embodiments, the sensing device 101 or a portion of the sensing device 101 (such as, for example, the modulator 103) is configured for attachment to a wound closure device, including but not limited to surgical staples, sutures, bandages, surgical gauze, zippers, endoscopic clips, etc. The device can be mechanically (e.g., via sutures or stapling) or chemically (e.g., via glue) attached to the wound closure device. The sensing device 101 is compatible with any medical implant, including but not limited to orthopedic, breast, and cardiac implants, to monitor the site of the implant, and is also compatible with devices such as catheters, drainage bags, etc., to monitor the entry and exit sites of complications.

[0124] In certain embodiments, the sensing device 101 as a whole or only the modulator 103 is configured to be attached to a surgical suture. The device can be attached to the suture by passing the suture through a fixing device in the device. Alternatively or additionally, the device can also be attached to the suture by clamping or using a suitable adhesive.

[0125] In such embodiments, the sensing device 101 can be configured to monitor events associated with wounds and / or surgical sutures. For example, the sensing device 101 itself can monitor the occurrence of at least one event, such as bleeding, dehiscence, infection, leakage, or in a more positive aspect, healing.

[0126] The sensing device 101 (or modulator 103, as the case may be) may be attached after the suture is placed, for example by clamping to the suture or with an adhesive (e.g., surgical glue or tape). In other embodiments, the sensing device 101 or modulator 103, as the case may be, may be incorporated into the suture or attached before the suture is placed, for example by sewing the suture through or through a fixture on the device. In addition, more than one device 101 or modulator 103 may be attached to a single suture, so that each sensing device (in the case of multiple devices) or each modulator (in the case of multiple modulators of a sensing device) monitors one of many different conditions.

[0127] Devices according to embodiments may be produced using conventional techniques for producing printed circuit boards (PCBs), such as chemical etching of copper foil laminated to an insulating substrate, with one or more components mounted in electrical connection with the copper on the surface of the PCB. In embodiments, the capacitor is a printed interdigitated capacitor.

[0128] In an embodiment, the sensing device 101 or a portion of the sensing device (such as the modulator 103 and / or the antenna 105) may be encapsulated by a biocompatible material (such as a biocompatible silicone polymer) to prevent undesirable side effects in the human or animal body. In an embodiment, the PCB is coated with the encapsulation material to a desired thickness. Preferably, the biocompatible material is selected from PDMS, silicone, parylene-C and polyurethane.

[0129] For attachment to a wound closure device, such as a suture, the dimensions of the device are preferably in the range of 0.1 mm to 20 cm, and the weight of the device is preferably in the range of 1 g to 20 g.

[0130] In an embodiment, the sensing device 101 or modulator 103 can be attached to a conventional surgical line (e.g., a commercially available surgical line) or a specially adapted surgical line. In an embodiment, the modulator 103 is attached to the surgical line, and the surgical line or a portion of the surgical line is conductive. In this embodiment, the surgical line itself can act as an antenna of the sensing device 101 or a portion of the antenna 105 (such as component 1051 or 1053 on only one side of the circuit).

[0131] Figure 5 , wherein a modulator 103 comprising an RLC circuit 106 according to an embodiment is connected to a portion of a conductive suture 104 arranged across a wound 505 in order to keep it closed. The modulator 103 comprises antenna connectors 102a and 102b for connecting to the suture 104 at a connection point 509 fixed by adhesive or by mechanical clamping. In this embodiment, the suture forms two parts of the antenna 1051 and 1053, and thus has an insulating part 507 between the connection points 509, the outside of which is conductive. Preferably, the conductivity of the conductive part of the conductive suture is higher than 100 S / m to ensure that the suture can function well as an antenna.

[0132] Thus, in this embodiment, according to the above-described embodiments, the suture 104 itself acts as an antenna 105 (e.g., a dipole antenna) for receiving the signal 111 and backscattering the modulated signal 113, and the circuit 106 of the modulator 103 modulates the signal for transmission using the suture when a transmitting device is attached to the suture.

[0133] Hence, in this embodiment, the modulator 103 and the suture 104 together constitute the sensing device 101 according to an embodiment.

[0134] Advantageously, employing the modulator 103 in a surgical setting using the suture 104 as an antenna results in minimal additional devices being implanted during surgery, since the suture is already required, i.e., the use of an additional antenna is avoided. In addition, damage to the suture, such as breakage, can be monitored via the signal modulated by the modulator 103. This will be discussed in detail below.

[0135] In an embodiment, antenna connectors 102a and 102b may include one or more solder pads for soldering attachment to stitching / antenna 104. Figure 6As shown, the antenna connector 102 may alternatively include one or more metal blades 107a, 107b that together form a loop 108. In the case of a surgical suture antenna, the blades 107a, 107b can penetrate the protective cover of the antenna (the position of the protective cover after penetration is indicated by the dotted line 110) to contact the conductive suture underneath. The blades are mounted to the jaws 107a, 107b, and the jaw 107a has a clip 112 that is received around the other jaw 107b to hold the two together.

[0136] Figure 7 A schematic layout of a modulator 103 according to another embodiment is shown, the modulator 103 being configured for attachment to a conductive stitching line. The layout is suitable for printing on a flexible printed circuit board including the components.

[0137] The modulator 103 includes a circuit having an interdigitated capacitor portion 607, an inductor 603, and a diode 605. The modulator 103 also includes a hollow electrode 609 for contacting the conductive suture 104, which can be encapsulated with medical grade silicone as desired. The suture 104 passes through a hole 6011 in the electrode. This Fig.11 As schematically shown in Fig.11 Shows Figure 7 An alternative view of a device of FIG. 6010. The suture is encapsulated by a biocompatible material such as parylene-C, and the electrodes are secured to the suture by adhesive or mechanical clamping. In this embodiment, the electrodes are pre-patterned. As previously described, the suture includes an insulating portion (not shown) between two conductive portions passing through the hole 6011 to enable its two portions to function as an antenna for the device.

[0138] Used for Figure 7 Suitable components for embodiments of or other embodiments described herein are commercially available, such as from Würth Elektronik (eg, 12nH inductor 74765112A) and SKYWORKS SOLUTIONS (Schottky diode SMS7630-079LF). Figure 7 The size of the modulator can be as small as 6mm(l)×2mm(w).

[0139] Figure 8 A schematic diagram of a sensing device for monitoring events involving or surrounding a sutured wound is shown according to an embodiment of the present invention.

[0140] In this embodiment, a modulator 103 including a modulation circuit 201 according to an embodiment is mounted to a suture 104. In an embodiment, a reader 109 generates a signal 111 having a frequency f0. The signal 111 penetrates the patient's skin 128 and tissue 130 and is captured by the suture 104, which acts as an antenna while also closing the surgical wound 505. The length of the suture 104 can be specifically designed to receive signals of a specific frequency f0 or frequency range. The modulator 103, which is typically attached to the suture 104 near the midpoint of the suture 104, receives the signal and generates a response signal 113, i.e., a signal from the modulator 103 whose frequency is a harmonic of the signal 111, such as 2f0. The reader 109 captures the signal 113 and reads the signal 113 based on the frequency (or other parameters of the signal that may be used as needed to create or modulate it, such as a phase shift indicated between the phase of the original signal 111 and the response signal 113 from the antenna, as Figure 3 ) determines whether an event has occurred, i.e., modulator 103 has transitioned to an affected condition.

[0141] Events that the modulator 103 may be adapted to monitor include, but are not limited to, bleeding involving blood leakage or other fluid saturation of the transmitting device, gastric fluid leakage, antenna damage (such as suture breakage), or bacterial infection or bacterial growth, anastomotic leakage and healing.

[0142] In an embodiment, the modulator 103 itself may or may not be particularly adapted to monitor a particular event as desired. For example, in the case of a bacterial infection, the modulator 103 may have a coating that is easily consumed by bacteria, such as a bacterial-specific deoxyribonucleic acid (DNA) hydrogel. When no bacterial infection occurs, the coating will remain intact. Therefore, the circuit of the modulator 103 (particularly the modulation circuit 201) will remain unaffected. When a bacterial infection occurs, the circuit of the modulator 103 will become gradually more exposed to the bacteria or the surrounding tissue or both. The circuit thus becomes affected, resulting in a change in the output of the modulator 103. The change can be a change in the frequency of the signal caused by, for example, a change in the capacitance or inductance of the modulation circuit 201 included in the modulator 103. This change can be gradual, so that in the case of a coating for bacterial consumption, the signal gradually changes as more of the coating is consumed, and the circuit is increasingly affected.

[0143] In the event of antenna damage - e.g., a break in suture 104 in the presence of a laceration - modulator 103 may simply be unable to transmit a signal, so in this and other cases, the change in signal may be that no signal is transmitted. In other embodiments, similar coatings are provided that are susceptible to being consumed, degraded, removed, or altered by other non-bacterial agents. Exemplary devices according to these embodiments are discussed below.

[0144] Bleeding, infection, and compromise of suture integrity discussed above may be post-operative complications that can be monitored by a sensing device according to an embodiment.

[0145] According to the above embodiments, the conductive sutures may be used to close incision wounds on the skin and deep within the body, wherein the device is attached before or after suturing.

[0146] Fig. 9 A flow chart of a general method for monitoring a surgical wound according to an embodiment is shown. In step S4301, a wound or a portion of a wound is sutured using a conductive suture 104 according to an embodiment to which a modulator 103 according to an embodiment is fixed. Alternatively, in step S4303, the wound or a portion of a wound is sutured using the conductive suture 104, and then in step S4305, the modulator 103 is attached to the suture in the body. Subsequently, in step S4307, the reader sends an interrogation signal to the suture. The interrogation signal may include a resonant frequency of a modulation circuit 201 included in the modulator 103 in one or both of an unaffected condition and an affected condition. The wavelength of the interrogation signal can cause backscattering from the suture 104.

[0147] In step S4309, a response signal (e.g., a backscattered signal) is received from the suture, and the characteristics of the signal are analyzed, for example, the spectrum of the signal can be analyzed. In step S4311, it is determined whether a specific event is occurring or has occurred at the wound site, including but not limited to bleeding, dehiscence, suture breakage, bacterial infection, gastric leakage, or anastomotic leakage.

[0148] Healing of the wound site can be determined by the absence of signal changes, indicating the absence of any complications.

[0149] In an embodiment, a modulator and suture may be employed to monitor a patient's vital signs instead of, in addition to, or even after determining the occurrence of a particular event at the wound site (e.g., after a coating susceptible to consumption by bacteria has been completely consumed). This is possible because physiological processes such as breathing and heart rate will change the distance between the antenna (suture) and the reader. This may be particularly useful for monitoring patients after surgery involving an incision. Alternatively, a conductive suture 104 may be employed to attach a modulator to the patient's body for vital sign monitoring without having to be used to close the wound. A method of measuring vital signs according to an embodiment is described in detail in the accompanying drawings. Fig.10 is shown in and described below.

[0150] In step S4401, a conductive suture according to an embodiment to which the modulator 103 is fixed is implanted into the body. Alternatively, in step S4403, the conductive suture is implanted into the body, and then in step S4405, the modulator 103 is attached to the suture in the body. Subsequently, in step S4407, the reader sends an interrogation signal to the suture. The interrogation signal may include sweeping the signal from a first frequency to a second frequency. The interrogation signal may include a resonant frequency of a modulation circuit 201 included in the modulator 103 in one or both of an unaffected condition and an affected condition. The wavelength of the interrogation signal may be capable of causing backscattering from the suture 104.

[0151] In step S4409, a response signal (e.g., a backscattered signal) is received from suture 104, and the characteristics of the signal are analyzed, for example, the spectrum of the signal can be analyzed. In step S4411, the amplitude of the signal indicating the distance of the suture from the reader is analyzed to determine one or more vital signs of the patient.

[0152] Thus, in some embodiments, the modulator may be connected to a conductive suture configured to act as an antenna for the modulator. In addition to ensuring that the overall size of the device remains as small as possible, since no additional components are required for the antenna, employing the suture as an antenna also enables monitoring of suture breakage, since in the event of a suture breakage the signal generated by the antenna will necessarily change, for example by a change in amplitude or the suture may not transmit any signal at all. Suture transmission may also be affected by bleeding at the wound site.

[0153] In an embodiment, a conductive suture is used with a modulator comprising an RLC circuit which is not specifically adapted to monitor events occurring in the body, i.e. the modulator and suture together are configured to monitor only interruptions in the transmission of the suture or vital signs of the patient. Changes in the transmitted signal will therefore only indicate such events. In other embodiments, the modulator may be adapted to monitor specific events occurring in the body, such as gastric leakage, as described above. In this embodiment, the device is therefore configured to monitor breaks (e.g., cracks) in the suture via the suture itself, and to monitor other events occurring in the body via changes in the electrical properties of the modulation circuit included in the modulator.

[0154] As described above, in some embodiments, a responsive material layer is applied to a sensing device according to an embodiment to change an electrical parameter of a modulator 103 (e.g., a modulation circuit 201 included in the modulator 103) when the material degrades or otherwise changes in response to conditions surrounding the sensing device. In an embodiment, the material layer is disposed on a capacitor of the modulation circuit 201.

[0155] Fig.11 Shows Figure 7Schematic diagram of the device 103 of the embodiment of the invention, with a responsive material layer 705 arranged on top of its capacitor. A circuit diagram corresponding to the arrangement of this embodiment is also shown in the inset for reference. In this embodiment, the responsive material layer 705 is arranged in a cylindrical shape to match the shape of the capacitor 607.

[0156] The responsive material 705 is held in place by two pillars 709 mounted on the surface of the substrate and arranged to hold the responsive material above the capacitor 607, i.e., to provide the necessary mechanical support (as required by the viscosity of the material) to the responsive material in the environment in which the device will be employed (e.g., in vivo). Preferably, the pillars are formed of polydimethylsiloxane (PDMS) due to its biocompatibility, however other biocompatible materials may also be used. The pillars are manufactured by 3D printing or using a laser engraved template. They can be mounted to the substrate 707 prior to packaging.

[0157] It will be appreciated that other relief structures such as walls may be used in place of pillars.

[0158] exist Fig.11 In an embodiment of the present invention, the responsive material is arranged above the capacitor 607, particularly above the spaces between the fingers of the capacitor. This arrangement ensures that degradation or other changes in the responsive material will result in changes in the dielectric constant of the capacitor, thereby changing the capacitance of the circuit and changing the resonance of the RLC circuit of which the capacitor 607 is a component. The capacitance change and sensitivity of a given responsive material can be adjusted by changing the gaps between the interdigitated electrodes and the thickness of the packaging material. Preferably, for packages less than 1 mm, the gaps between the interdigitated electrodes of the capacitor are less than 500 nm.

[0159] In an embodiment, the surface of the substrate along with the electrodes may be encapsulated by a biocompatible material, such as medical grade silicone, and the responsive material may be disposed on the surface of the encapsulating material.

[0160] Despite Fig.11 In the figure, according to the preferred embodiment, the responsive material is shown as being arranged above capacitor 607, but the responsive material may alternatively or additionally be arranged above a different component of the RLC circuit (e.g., inductor 605), wherein a change in the responsive material will result in a change in the inductance of inductor 605.

[0161] In an embodiment, the responsive material 705 can be a hydrogel, such as a peptide hydrogel that degrades in the presence of a peptide, a DNA hydrogel that degrades in the presence of a nuclease secreted by bacteria, or a heme hydrogel that solidifies in the presence of blood.

[0162] Fig.12 A method for preparing a sensing device suitable for use with an embodiment of the present invention (e.g., Fig.11The method of using DNA hydrogels together with a sensing device).

[0163] The method includes mixing a DNA gel precursor 801 with 1,4-butanediol diglycidyl ether (BDDE) 803. The presence of N, N, N′, N′-tetramethylethylenediamine (TMEDA) initiates amine-epoxy addition and crosslinks DNA chains with BDDE to form a DNA hydrogel 805.

[0164] Preferably, the DNA precursor can be prepared by dissolving 10wt% sodium deoxyribonucleic acid (smDNA) in 4.0mM NaBr solution and uniformly mixing 2.5wt% crosslinker 1,4-butanediol diglycidyl ether (BDDE) with the precursor and 0.5wt% N, N, N', N'-tetramethylethylenediamine (TMEDA) as a catalyst. This ensures that the appropriate gelation properties are obtained and the viscosity of the hydrogel is obtained to keep the PDMS pillars in place according to the embodiment.

[0165] Those skilled in the art will appreciate that, depending on the embodiments, other DNA hydrogels may be produced according to other methods.

[0166] The DNA hydrogel of this example is easily digested by nucleases. Nucleases are secreted by pathogens and help them escape from neutrophil extracellular traps (NETs). NETs are mainly composed of DNA from neutrophils, and the secreted nucleases cut the backbone of the DNA chain.

[0167] Thus, in the presence of bacteria, the cleavage of the DNA strands in the DNA hydrogel results in the collapse of the DNA gel. Thus, when the DNA gel is arranged above a capacitor, the dissipation of the DNA gel due to this mechanism will result in a change in the capacitance of the capacitor and will therefore be detectable via changes in the electrical properties (particularly the capacitance and hence the resonance) of the device according to the embodiments, as described above. This is Fig.13 As schematically shown in Fig.13 The DNA hydrogel is shown before 805 and after (collapsed state) 807 the introduction of the nuclease.

[0168] Thus, the hydrogel of this embodiment is suitable for use with a device for detecting the occurrence of bacterial infection at a wound site.

[0169] Fig.14 The preparation of a device suitable for use with an embodiment (e.g., including Fig.111 , a method for preparing a peptide hydrogel for use with a sensing device 101 of which a modulation circuit 201 is shown as a portion thereof. Preferably, the peptide precursor 901 has 0.5-1 wt.% glutaraldehyde in DI, 1:1 by volume, resulting in a cross-linking reaction to form the peptide hydrogel 903. This ensures that the appropriate gelation properties are obtained and the viscosity of the hydrogel is obtained to hold the PDMS pillars in place according to the embodiment.

[0170] Crosslinking gives the resulting hydrogel 903 a jelly-like appearance, which advantageously provides mechanical strength for maintaining its structure after coating on a device according to embodiments, e.g. Fig.11 shown.

[0171] Those skilled in the art will appreciate that, according to the embodiments, other peptide hydrogels may be produced according to other methods.

[0172] The peptide hydrogels of this embodiment are easily digested by pepsin. Pepsin may be present, for example, after a leaky stomach, such as after gastric surgery or the like. When the hydrogel is exposed to pepsin, the cross-linked peptides break down into their amino acid components, causing the hydrogel to collapse. As discussed above with respect to the DNA hydrogel, changes in the state of the hydrogel can be detected by a device according to the embodiment due to changes in the ambient dielectric constant of the capacitor. This is particularly useful in Fig.15 As schematically shown in Fig.15 The peptide hydrogel is shown before 903 and after 905 (collapsed state) the introduction of the nuclease.

[0173] Fig.16 A schematic diagram of a method for detecting gastric leakage using a modulator 103 comprising a modulation circuit 201 loaded with a peptide hydrogel 903 is shown. In step S1001, anastomotic leakage occurs from a sutured wound, resulting in leakage of gastric fluid. According to an embodiment, peptides in the gastric fluid cause a reaction of a bio-responsive material (peptide hydrogel) coated on the modulation circuit. This results in a change in the capacitance of the capacitor in step S1003 and a resonant frequency (Δf) of the modulation circuit generated in step S1005. r ) which may be recorded wirelessly by a reader as described above according to an embodiment.

[0174] Fig.17A schematic diagram of a reader 109 according to an embodiment is shown, which is suitable for providing an interrogation signal 111 to a sensing device 101 according to an embodiment and receiving a response signal 113. The reader includes a signal generator 4503, which generates a signal, which may include the resonant frequency of a modulator (in an affected or unaffected condition, or both) to be used by the reader. Typically, the reader scans a range of frequencies, for example by sweeping the signal from a first frequency to a second frequency (e.g., 1 to 2 GHz). The signal passes through a power amplifier 4505, followed by a low-pass filter 4507, and is directed by a directional coupler 4509 to an antenna 4511 for transmission. The signal received by the antenna 4511 is directed by the directional coupler 4509 to a high-pass filter 4513, and then to a spectrum analyzer 4515 for analyzing the signal, enabling the determination of conditions around the device. The output of the spectrum analyzer may be interpreted by a user, or the reader 109 itself may also include a processing circuit configured to determine whether the signal generated by the spectrum analyzer indicates a condition at the sensing device 101. For example, a processing module (not shown) of the reader can be configured to compare the amplitude of the signal to a threshold value stored in memory. If the amplitude of the signal is below the threshold value, the system can determine that there is a suture break and / or split, and provide an output indicating the condition, such as by displaying a warning on a monitor of the system or by outputting an audio signal. The reader can also be configured to record and display changes in the amplitude of the signal over time, such as for vital sign measurements, such as heart rate and respiratory rate measurements.

[0175] In another example, the processor can be configured to compare the spectrum of the received signal with an expected spectrum based on the second harmonic spectrum of the output signal stored in the memory. If the spectrum shift exceeds a threshold, the system can determine that a condition such as gastric leakage, anastomotic leakage, bleeding, or bacterial infection has occurred depending on the configuration of the device employed.

[0176] In an embodiment, the system may be configured to output the characteristics of the signal determined by the spectrum analyzer 4515 to an external device (such as a user device 4517) for processing in order to determine conditions at the site, as described above.

[0177] It should be appreciated that determining conditions at the region of interest from received backscatter signals may be performed in a variety of ways in addition to those described above.

[0178] According to an embodiment, the Fig.17 One or more of the components shown in or adding other components.

[0179] Fig.18A schematic diagram of a reader 109 according to another embodiment is shown, the reader 109 being used to provide an interrogation signal 111 to a sensing device 101 according to an embodiment and to receive a response signal 113. In an embodiment, the reader 109 is a handheld device for ease of application.

[0180] The reader includes a processor 1203 configured to process data related to signals received from a sensing device 101 according to an embodiment and display the data on a display 1231. The device may include a battery 1227 and / or a USB port 1229 for powering the device. The device includes a first signal generator 1205 configured to generate a radio frequency signal at an unaffected resonant frequency of the modulation circuit when the antenna (e.g., suture) is intact, as shown in 1207. The signal generator 1205 is connected to an amplifier 1209 and an antenna 1211 for transmitting the signal generated by the signal generator 1211.

[0181] The reader also comprises a second signal generator 1211 which acts as a reference for receiving power and also for boosting frequency and / or power.

[0182] The reader comprises an antenna 1215 connected to an amplifier 1217 for receiving signals from a sensing device according to an embodiment. The reader may comprise several modules for detecting signals specific to the occurrence of certain events. Fig.18 In an embodiment of the invention, the reader includes filter modules 1231, 1219, and 1221 for filtering signal characteristics indicating a break in a suture stitched on either side of the modulator, on only one side of the modulator, or on a suture to which the modulator is attached, respectively. The filtered signals are then processed by processor 1203 to determine a condition that has occurred.

[0183] The reader also includes an analog-to-digital converter 1225 , a varactor diode 1223 , and a mixer 1233 .

[0184] Fig.19a and Fig.19b The following are respectively shown according to a specific embodiment. Fig.18 Schematic diagram and photograph of antenna 1301 for use with reader 109. The design includes a tilted center-fed planar dipole antenna with an added slot 1303 to improve performance at lower frequencies.

[0185] Those skilled in the art will appreciate that other antennas may be employed depending on the embodiment.

[0186] In the embodiment, according to Fig.18 The reader of the embodiment according to Figure 4 The sensing device 101 of the embodiment is used together as a platform for monitoring the surgical site. Figure 4 The passive sensing device 101 of the embodiment of can be attached to any wound closure device at the surgical site during surgery to sense the physiological functions around the surgical site. Fig.18 The handheld reader 109 of an embodiment of the present invention is used to power the passive sensing device on demand and transmit events occurring at the surgical site.

[0187] Fig. 20 A schematic diagram of a system 54 for providing wireless power to a pair of electrodes 5321, 5323 to provide a function at a remote site is shown according to another embodiment. In an embodiment, the site is within the body.

[0188] The system 54 includes a wirelessly triggered rectifying device 5301, which includes an antenna 105 and a rectifying module 5401 in communication connection 107 with the antenna 105. The system 54 also includes a transmitter 5403, which can be remote and communicatively coupled to the device 54. The antenna 105 can be configured to receive a trigger signal 5405 transmitted by the transmitter 5403. As will be clear from the embodiments discussed below, the signal can be a radio frequency signal, a magnetic field, or any other signal suitable for triggering the device. The trigger signal 5405 can further be capable of providing power to the device 5301. The trigger 5405 can cause a potential difference across the electrodes 5321 and 5323, and thus when the electrodes 5321 and 5323 are placed in electrical connection, a current flows between the electrodes 5321 and 5323.

[0189] The connection 107 between the antenna and the rectifier 5401 may simply comprise an electrical contact - such as a metal-to-metal contact - or may comprise a weld or solder or any other form of electrical connection.

[0190] In an embodiment, power for device 5301 may be provided by a battery or energy harvester device. In a particular embodiment, device 5301 is passive, i.e., it does not include a power source, nor any physical connection (e.g., wires) to a power source. In this embodiment, power is instead provided to the device wirelessly, e.g., via received signal 5405 or via other wireless charging methods.

[0191] Fig.21A circuit diagram of a wireless trigger device 5301 according to an embodiment is shown. The device includes an antenna 105 connected to a Pi matching circuit 5303, which includes a capacitor 203 and an inductor 205. The Pi matching circuit itself is connected to a voltage multiplier circuit 5309, which is configured to rectify the signal received by the antenna and the Pi matching circuit. The Pi matching circuit and the voltage multiplier circuit together constitute a rectifier module 5401. In this example, the voltage multiplier circuit includes capacitors 5311, 5313, 5315 and two diodes 5317, 5319. It should be understood that other designs of rectifier circuits can be used. Electrodes 5321 and 5323 are connected to the rectifier circuit on either side of the capacitor 5315 via connectors 5325 and 5327, respectively. In this embodiment, at least one of the electrodes 5321, 5323, and preferably both electrodes, is formed by a conductive suture.

[0192] As mentioned above Figure 5 As described above, in a preferred embodiment, the suture comprises two conductive portions separated by an insulating portion, thereby enabling it to be used as Fig.21 and 22 The two electrodes in the embodiment.

[0193] As in the case of the above-described embodiments, device 5301 can be produced using conventional techniques for producing printed circuit boards (PCBs), such as chemically etching a copper foil laminated to an insulating substrate, with one or more components mounted in electrical connection with the copper on the surface of the PCB, or by appropriately employing printed components.

[0194] In an embodiment, the device 5301 or a portion of the device may be encapsulated by a biocompatible material, such as a biocompatible silicone polymer, to prevent undesirable side effects in the human or animal body. In an embodiment, the device comprises a PCB coated with the encapsulation material to a desired thickness. Preferably, the biocompatible material is selected from PDMS, silicone, parylene-C and polyurethane. The antenna 105 may comprise a separate component or components, or may be integrated into the same components as those forming the RLC 5303 and / or the voltage multiplier circuit 5309, for example, both the circuit and the antenna may be printed onto a PCB.

[0195] The connections 5325 and 5323 between the electrodes and the rectifying circuit may simply comprise electrical contacts - such as metal to metal contacts - or may comprise welding or solder or any other form of electrical connection. The mechanical connection to the conductive suture may be achieved by threading the suture through a fixture in the device, as described above in conjunction with Fig.11 Alternatively or additionally, the device may also be attached to the suture by clamping or using a suitable adhesive.

[0196] The wireless power received by the antenna 105 of the device 5301 will be modulated by the Pi matching circuit 5305, which acts as an impedance matching circuit. The power is applied to match the voltage multiplier 5309, which rectifies the received modulated RF signal, resulting in a potential difference between the electrodes 5321 and 5323. Therefore, when placed in the body, current will flow between the electrodes due to the inherent conductivity of human or animal tissue.

[0197] Therefore, in this embodiment, in contrast to the above-described embodiment, a conductive suture thread is used as an electrode.

[0198] In an embodiment, the conductive stitching serves as both one or more electrodes and an antenna. This can be accomplished by using two stitchings (one forming the antenna and one forming the electrode) or by using the same method as described above with respect to Figure 5 The two conductive portions described are similarly achieved by dividing a single suture into multiple conductive portions, each conductive portion being separated by an insulating portion.

[0199] Thus, current flow through electrodes can be employed in neurostimulation by delivering neurostimulation pulses by placing electrodes at spaced distances in the body and triggering current flow through them via wireless trigger pulses. For example, the electrodes can be located in the body so as to cause stimulation of the sciatic nerve when current flows between them. The electrical pulses sent by the sutures acting as electrodes can cause a reduction in pain signals sent to the central nervous system, and therefore a reduction in the pain experienced by the patient. They can also stimulate the production of endorphins, which are natural painkillers produced by the body.

[0200] It will be appreciated that the wireless power level and corresponding current used for neural stimulation will depend on the depth at which the device is deployed. However, in an example, they are at least 1 W and 1 microamp, respectively, which is equivalent to a specific absorption rate (SAR value) of 4 W / Kg.

[0201] Thus, device 5301 enables wireless triggering of neural stimulation pulses via radio frequency pulses.

[0202] In other embodiments, electrodes 5321 and 5323 or equivalent portions of conductive suture may be used as leads to power additional devices.

[0203] In an example, the electrodes are used as leads for powering an LED, and the photodetector is used as an optical sensor in the body, for example for detecting bleeding. A change in the transmission quotient between the LED and the photodetector indicates the presence of blood between the two, and thus, for example, bleeding from a sutured wound. Thus, Fig. 20 and 21 Embodiments may form part of a sensing device.

[0204] In another example, electrodes are used for drug elution. In this example, the drug can be placed in a reservoir implanted in the body. The electrodes can then be used to power a heating device that uses the temperature change caused by the device to stimulate the drug to elute from the reservoir. Alternatively, the electrodes can be used to power a light emitting device, such as an LED for stimulating drug elution via light. The electrodes can also be used to electrically stimulate the drug to elute directly from the reservoir.

[0205] Thus, in these examples, device 5301 can be used as a wireless trigger device for stimulating drug elution.

[0206] It will be appreciated that the electrodes may be used as leads for various devices that provide useful functions to the body.

[0207] Therefore, advantageously, according to Fig. 20 and 21 The device of an embodiment of the invention enables wireless powering to monitor, power, stimulate and record events in a remote site, such as neural repair, stimulation and recording. Thus, the device according to this embodiment provides additional support for the healing process directly at the site of interest without further surgical intervention and with minimal additional devices implanted during the initial surgery, as sutures may already be required.

[0208] As described above, according to embodiments, the conductive stitching may be configured to act as an antenna (eg, monopole, dipole, helix, etc.) or an electrode, depending on the application.

[0209] In an embodiment, the conductive surgical suture comprises a suture formed of a conductive material such as stainless steel. In a specific embodiment, the conductive suture comprises a surgical suture for juxtaposing tissue portions, such as a commercially available or otherwise available suture for medical purposes, which is then coated with a conductive coating. The specific suture used as the inner suture (the coating is applied thereto) is not particularly limited. However, suitable examples include sutures made of silk, cotton, or vicryl. Examples of specific commercially available sutures suitable for use include prolene and PDSII sutures, as well as all other commercially available sutures.

[0210] The conductive coating ensures that electrical signals can be carried by the suture, thereby enabling it to act as an antenna and / or electrode. Preferably, the conductive coating is selected to ensure that the conductivity of the suture is greater than 100 S / m.

[0211] The coated surgical suture can then be encapsulated in a protective coating - this can be provided over the length of the suture, or only on the portion to which the modulator is attached. The protective coating can be inert or otherwise non-toxic or non-reactive to the surrounding tissue. For example, the protective coating can be a biocompatible polymer, such as parylene-c. Similarly, the conductive coating can be formed from a non-toxic and non-reactive material, such as a biocompatible conductive polymer. Preferably, the biocompatible conductive polymer is poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS). Advantageously, PEDOT:PSS is a conductive ink that can be adsorbed into the suture material without compromising flexibility while achieving the desired conductivity.

[0212] According to an embodiment, other substances replacing the above-mentioned biocompatible conductive polymers include other conductive polymers such as poly(pyrrole), polythiophene, poly(3-alkylthiophene), poly(p-phenylene vinylene), polyaniline, poly(p-phenylene sulfide); carbon ink, carbon nanotube composites and carbon nanotube nanofibers; metals and liquid metals. Specifically, the protective coating and / or the conductive coating - that is, whichever coating is to contact the tissue - is selected to have appropriate pharmaceutical properties according to the proposed application.

[0213] Once the modulator or rectifier module and antenna are appropriately attached, the components of the modulator or rectifier and stitching may be packaged in silicon, or the associated connections between the modulator or rectifier and antenna may be packaged.

[0214] Thus, sutures can be formed very simply. Using these methods, conductive sutures with medical-grade mechanical properties and biocompatibility can be fabricated. Due to their proximity to the surgical site, surgical sutures are a useful platform for integrating sensing capabilities into medical devices used to monitor surgical sites.

[0215] In a preferred embodiment, the suture is manufactured to have two conductive portions separated by an insulating portion, such as e.g. Figure 5 In this embodiment, the conductive portion of the stitching has the above structure, while the insulating portion includes an inner stitching that is only coated with an encapsulating material. This enables a single stitching to be appropriately used as two parts or two electrodes 5321, 5323 of the antenna 105.

[0216] Due to the potentially fatal consequences of a malfunctioning medical device used during surgery, the key to ensuring the safety of the surgical sutures and other devices described herein is their simplicity and inherent mechanical and functional properties - for example, the sutures described herein can maintain or simulate the inherent mechanical and functional properties of medical-grade sutures as closely as possible.

[0217] As described above, in a specific embodiment, the manufacture of WISE sutures may involve a process of coating a medical-grade surgical suture with a biocompatible conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS) and then encapsulating it with a biocompatible polymer parylene-c. This process ensures the conductivity of the medical-grade suture without compromising the flexible mechanical properties and functionality of the suture. A highly miniaturized tag (modulator or modulator and antenna) with an RLC circuit may then be attached to the suture at the desired location before or after suturing. A sensing device including a modulator and antenna (i.e., a suture) may then be encapsulated with silicone, or a sensing device in which the antenna and modulator are incorporated into the same component.

[0218] Fig. 22 A schematic diagram is shown of a particular method of producing a conductive stitching thread suitable for use as an antenna in accordance with an embodiment.

[0219] In step S1101, a medical grade suture is provided. In an embodiment, the suture is silk. In other embodiments, the suture may include other suitable materials, such as cotton or vicryl.

[0220] In step S1103, the suture is subjected to oxygen plasma treatment. For example, the suture can be placed in an oxygen plasma chamber for at least two minutes. It has been found that oxygen plasma treatment advantageously improves the adsorption of the conductive coating on the suture.

[0221] In step S1105, the suture is chemically treated to remove wax from the suture. Specifically, the suture can be treated with N-methyl-2-pyrrolidone (NMP). For example, the suture can be soaked in NMP for at least two minutes. It has been found that chemical treatment to remove wax advantageously improves adsorption of the conductive coating on the suture. Alternatively, DMSO can be used for the chemical treatment.

[0222] Step S1107, coating the suture with a conductive material. Suitable materials are listed above. In a specific embodiment, it is coated with PEDOT:PSS and then dried under vacuum. In other embodiments, drying can be performed in an oven. Preferably, PEDOT:PSS is mixed with a dopant (such as 5% DMSO) before coating.

[0223] In an embodiment, step S1107 is performed 1 to 5 times. Specifically, it is performed at least 3 times. It has been found that the three-layer coating advantageously reduces the electrical resistance in the suture.

[0224] In step S1109, the suture is encapsulated with a biocompatible encapsulation material. In a particular embodiment, it is encapsulated with parylene-c, however other suitable encapsulation materials may be used. Advantageously, parylene-c ensures that the flexibility of the inner suture is maintained after encapsulation.

[0225] It has been found that the above described method advantageously produces a conductive suture suitable for use as both a suture and an antenna and / or electrode for a device according to the above described embodiments.

[0226] It should be understood that, depending on the embodiment, one or more of the above steps may be omitted, or additional steps may be added. It should also be understood that other conductive sutures having the desired conductivity, strength, and flexibility properties may be used with the device according to the above embodiments.

[0227] Experimental and simulation results

[0228] Certain non-limiting features of the above-described embodiments will now be illustrated using experimental and simulation results.

[0229] Simulations of a modulator according to an embodiment, configured to retransmit the second harmonic of a received signal at a resonant frequency, and stitching produced as described above according to an embodiment were performed to investigate the performance of a WISE suture. Three stitching modes, Cushing stitch 2101, Lock-Stitch 2103, and Lembert stitch 2105, were employed.

[0230] The current distribution measurement indicates that the current is distributed along the entire length of the suture regardless of the type of surgical suturing pattern at both the fundamental frequency and the second harmonic frequency.

[0231] Fig.23 The received power of the suture as a function of suture length for the three suture modes is shown. For all suture modes, the power received by the WISE suture increases as the length of the suture increases to approximately 10 mm, after which there is a slight drop, although the power thereover remains largely constant.

[0232] Fig.24 The received power is shown as a function of the conductivity and diameter of the suture. It can be seen that the power decreases with thickness.

[0233] Fig.25 The transmission efficiency of the WISE suture as a function of frequency is shown, as well as the resonant frequency changes for capacitor capacitances of 2.7 pF (2301), 2.3 pF (2303), 1.9 pF (2305), 1.5 pF (2307), and 1.1 pF (2309).

[0234] Fig.26 The stress (y-axis) as a function of strain (x-axis) is shown for a number of commercially available sutures compared to a WISE suture produced according to an embodiment. Results are shown for monofilament sutures Prolene 5501 and PDSII 5503, as well as braided silk 5505, Vicryl 5507, and WISE 5509 sutures. The figure shows that the stress-strain graph for the WISE suture 5509 according to an embodiment is close to that of a medical grade silk suture, and is within that of a commercially available suture. Specifically, this is aided by starting with the base of a medical grade suture and adding conductive functionality to it, as described above according to an embodiment.

[0235] Fig. 27 The tissue pull forces of multiple commercially available sutures are shown compared to a WISE suture produced according to an embodiment. The graph shows that the tissue pull forces exerted by a WISE suture according to an embodiment are comparable to those of medical grade commercial sutures.

[0236] Fig.28 The change in resistance of a WISE suture produced according to an embodiment is shown when the suture is subjected to a mechanical cycle of contraction and extension. Fig.28 It can be seen that the suture is stable over 2000 mechanical cycles of contraction and extension. Specifically, the change in resistance is not significant over 200 cycles, which means that the electrical characteristics of the signal generator circuit should remain stable over a similar number of contraction and extension cycles.

[0237] The resistance change of the WISE suture produced according to the embodiment was measured in a physiological buffer 1X phosphate buffer solution (PBS) over three weeks, and the results are shown in Fig.29 , where the top 2701 and bottom 2703 figures show PEDOT:PSS coated sutures without and with Parylene-C encapsulation, respectively. The results show that the WISE sutures were found to be stable over a period of 3 weeks with a % change in resistance of less than 10%.

[0238] The biocompatibility of the WISE suture according to the embodiment was compared with that of medical grade suture. Human dermal fibroblasts (HDFs) were treated with medical grade silk suture, PEDOT:PSS coated silk suture and WISE suture produced according to the embodiment for 72 hours. Confocal images with live HDFs showed that the WISE suture had no cytotoxicity to HDFs.

[0239] Fig.30The cell viability 162 of the WISE suture is shown to be 100%, which is equal to or exceeds the cell viability of the PEDOT:PSS coating 164 and silk 166, and is therefore generally comparable to the biocompatibility of medical grade sutures.

[0240] Sensing applications using WISE sutures with modulators according to embodiments attached were demonstrated in vivo and in vitro. WISE sutures produced according to embodiments were used to appose incisional wounds on the skin of mice and deep in the body, with the modulators attached before or after suturing. Fig.12 The resulting DNA-hydrogel layers were applied as described above. Fig.11 The described modulator integrates bacterial infection detection into the WISE suture.

[0241] It was found that the DNA hydrogels layered on the capacitors were degraded by extracellular nucleases secreted by Staphylococcus aureus bacteria within 10 hours after treatment with bacteria such as Staphylococcus aureus. The DNA hydrogels attached to the capacitors were degraded by extracellular nucleases secreted by bacteria within 10 hours.

[0242] The progression of S. aureus produces a change in capacitance and, in turn, a change in the resonant frequency of the modulation circuit from 1.18 GHz to almost 1.5 GHz, as Fig.31a Reference numeral 180 is shown for Staphylococcus aureus.

[0243] Control experiments were performed, involving treatment of the hydrogels with healthy human dermal fibroblasts (HDFs). Fig.31a In contrast to the changes seen in Figure 2, the resonant frequency of the control group remained stable at around 1.28 GHz for almost 24 hours. Fig.31b As shown in the figure numeral 182.

[0244] The change of the resonant frequency of the modulation circuit according to the embodiment was explored under the condition of bleeding. Fig.32a , which shows the normalized power as a function of frequency for three different bleeding severities using a WISE suture and modulator combination produced according to an embodiment.

[0245] When bleeding occurs suddenly - 190 - the dielectric constant of the area on the capacitive portion of the modulation circuit changes, resulting in a shift in the resonant frequency. As the sensor is fully saturated, the shift from the unaffected condition 186 becomes more pronounced, as the frequency shifts from 1.6 GHz to 1.45 GHz for the affected condition of mild bleeding - 188, and to 1.3 GHz for the affected condition of severe bleeding - 190. In this embodiment, the affected condition thus constitutes a plurality of conditions that are not the unaffected condition, or indicates a series of events (e.g., mild to severe bleeding), all of which represent affected conditions.

[0246] The effect of suture breakage was also explored. When a WISE suture produced according to an embodiment is combined with a modulator according to an embodiment for apposition to a surgical site, Figure 32b The break of the suture causes the power of the device to be reduced from full power 194, as observed from -85dBm to -95dBm (reference numeral 196) for a break on a single side of the modulator. The suture 198 extends from both sides of the modulator and the break only occurs on one side of the modulator) and reaches -115dBm (reference numeral 200) for a break that passes through both sides of the suture. No power is detected when the suture breaks completely. The resonant frequency remains constant as long as the sensor is intact. The reduction in power is due to the compromise of the suture integrity and indicates that the conductivity of the WISE suture can also be used to sense changes in the event. This communicates or alerts the clinician, patient and / or caregiver that the suture integrity has been compromised.

[0247] In vivo studies were performed using SpragueDawley (SD) male rats according to IACUC standards to demonstrate the wound healing ability and device stability of the WISE sutures produced according to the examples on the skin and in the muscle. Rats were euthanized on days 1, 4, 7, and 14 after surgery to study the histopathological events of the wound healing process. Histopathological staining of the hematoxylin and eosin (H&E) staining process showed that the WISE sutures were similar to medical-grade sutures in that they caused the exact histological events that occurred during the normal, healthy acute wound healing process for 14 days. Observations made on day 1 showed necrosis and inflammatory cells around the incision wound site, days 4 and 7 showed granulation tissue formation and wound healing, and day 14 showed complete re-epithelialization and wound closure.

[0248] Fig.33a and Figure 33b Inflammation (left axis) and healing scores (right axis) of the skin and muscle obtained over 14 days are shown, respectively, with each graph showing the results of inflammation control 4101, inflammation test 4103, healing control 4105, and inflammation test 4107. Inflammation and healing of the skin and muscle increased from day 1 to day 4, and decreased toward day 14.

[0249] The resonant frequency of the device was also measured over a 14-day period and the results were shown in Fig.34 (2401 represents the results for skin and 2403 represents the results for muscle). The results show that the resonant frequency is stable throughout the wound healing period of 14 days. This demonstrates the stability of the WISE suture including the conductive suture and the attached modulator.

[0250] Optimization of WISE suture preparation was explored using 5 different protocols shown in Table 1.

[0251]

[0252] Table 1

[0253] The electrical resistance of the sutures prepared with each protocol was studied and Fig.35 Figure 2 shows the error bars, which represent standard deviation (three sutures were prepared with each protocol).

[0254] Fig.36 The resistance of five sutures prepared using Scheme 5 of Table 1, but with different amounts of PEDOT:PSS coating applied, as shown on the x-axis. The resistance remained roughly constant over the three coatings.

[0255] Three different sizes of PEDOT:PSS-coated silk sutures were successfully prepared using Scheme 5 of Table 1 , such as Fig.37 Similarly, three sutures of the same size (0) were produced using Scheme 5 of Table 1, but different base sutures of silk, cotton, and vicryl were used, as shown in FIG. Fig.38 Thus, the method of producing conductive sutures according to the embodiments is applicable to a range of suture sizes and can be extended to other medical grade sutures besides silk. Note that the suture sizes shown follow the designation of the United States Pharmacopeia (USP).

[0256] The harmonic signal of the prepared suture is measured and the resulting signal 2801 and noise 2803 power are measured at Fig.39 and 40 The results show that all sutures gave a large signal-to-noise ratio, with the best results obtained with size 0 silk suture.

[0257] according to Fig.19a and Fig.19b The performance of the reader antenna of the embodiment was simulated and experimentally tested. The results are Fig.41 The wireless reflection coefficient S11 is shown as a function of frequency in . The results show good performance at all frequencies explored (including lower frequencies).

[0258] The maximum detection depth of WISE sutures with a combination of sutures and modulators produced according to the embodiments was studied for three suture types: Lembert, Lock-stitch, and Cushing. For Lembert suture, the maximum detection depth for 10dB SNR was found to be approximately 5cm, while for Lock-stitch and Cushing suture, the optimal length L was found to be approximately 6cm (i.e., the WISE suture operates as a resonant dipole antenna with maximum power transfer efficiency). It is worth noting that the optimal detection depth can be achieved by selective functionalization of the suture, or adjusted by operating at different frequencies, which is beneficial for monitoring deep surgical sites. In addition, the suture length dependence of the wireless signal observed supports the proposed suture breakage interrogation via a wireless method according to the embodiments.

[0259] Fig.42a , Figure 42b and Fig.42c The simulated harmonic spectra of three different sutures with length L = 20 mm and d = 25 mm, respectively, are shown. The capacitance of the integrated modulation circuit is computationally adjusted to three different values ​​1.0 pF (3101), 0.8 pF (3103), and 0.6 pF (3105) to simulate the changing sensor state. The obtained harmonic spectrum shows a clear shift in the resonant frequency (> 0.32 GHz) with a 0.2 pF change in sensor capacitance, supporting the proposed frequency sensing mode according to the embodiment. The simulation results demonstrate the tunability of the WISE platform and provide guidance for WISE suture design and optimization.

[0260] Basis Fig.11 Schematic diagram of the simulation model to simulate the modulated circuit response with varying hydrogel thickness. The simulation model is based on a 25 μm polyimide substrate, 18 μm copper electrodes (Pyralux® AC), and 0.1 mm medical grade silicone (Kwil-Sil, WPI) as surface encapsulation. Two PDMS pillars provide the necessary mechanical support for the hydrogel in vivo. Fig.43 The simulated capacitance of a modulation circuit loaded with a cylindrical peptide hydrogel of d = 2 mm is shown, showing that the capacitance decreases as the height of the hydrogel decreases.

[0261] Fig.44 The simulated capacitance of the modulated circuit in contact with a cylindrical dielectric (d = 2 mm, h = 1 mm) is shown. These results show that the capacitance change and sensitivity can be tuned by changing the gap between the interdigitated electrodes and the thickness of the silicone coating, thereby changing the relative dielectric constant.

[0262] Fig.45 The effect of adding nucleic acid enzyme on the resonant frequency of the above analog modulation circuit is shown, where there is a capacitor according to Fig.12 The DNA hydrogel layer produced by the method of the present invention is shown before (3403) and after (3401) the addition of 10 μL of nuclease (1000 units / mL) to degrade the DNA hydrogel on the electronic swab within 15 minutes, causing a shift in the resonant frequency of ∼1.2 GHz.

[0263] In contrast, Fig.46 The effect of adding 10 μL of DI water on the resonant frequency of the simulated modulation circuit described above with DNA gel is shown. The spectra are shown before adding 10 μL of DI water (3405) and 15 minutes after adding 10 μL of DI water (3407). No detectable effect was observed, i.e., there was no shift in the resonant frequency.

[0264] Fig.47a , Figure 47b and Fig.47c Dynamic vital sign monitoring using simulated WISE sutures according to an embodiment is shown. The relative distance d between the transmitter and the receiver is encoded by the vibration motion of the physiological process, so vital signs such as breathing rate can be captured by changes in the amplitude of the WISE signal. The figure shows that at 4601 and 4603 ( Fig.47a ) Before skin closure, ( Figure 47b ) before injection of 4701 and 4703 gastric solution and ( Fig.47c ) Received signals before and after suturing of sutures 4801 and 4803 (top). For clarity, the bottom graph shows the normalized signals.

[0265] Continuous wavelet transform (CWT) spectrograms were also obtained, enabling the extraction of the rats’ respiratory rate (RR).

[0266] Fig.48a , Figure 48b and Fig.48c Spectra obtained from WISE suturing according to an embodiment are shown, and before and after skin closure ( Fig.48a ), before and after exposure to gastric solution ( Figure 48b ) and before and after suture rupture ( Fig.48c ), showing that vital sign measurement is possible in all cases except suture rupture.

[0267] Fig.49 Shown is a comparison of the amplitude of the backscatter signal measurements acquired using WISE stitching (top) compared to the ECG signal.

[0268] Harmonic spectra were obtained experimentally on skin and muscle using the WISE suture according to the example over a 14-day period. In both cases, the obtained spectra showed good stability. Fig.50The changes in signal-to-noise ratios for skin (upper panel) and muscle (lower panel) obtained from 5 samples over the same time period are shown (error bars represent standard deviation). Note that for the skin group, only one device was left on days 13 and 14 due to scratching by the rat. Again, the SNR remained relatively consistent over this time period, especially for the muscle.

[0269] As shown, to achieve real-time monitoring of, for example, a surgical site, wireless sensing (WISE) surgical sutures have been developed that can monitor surgical wound dehiscence and subsequent post-operative complications such as compromise of suture integrity, sudden bleeding / hemorrhage, and bacterial infection at the surgical site, and also simultaneously monitor and communicate wound healing status. Some of the sutures disclosed herein overcome challenges through two key advances: (i) medical-grade sutures are functionalized by coating with a biocompatible conductive polymer, poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS), which makes the sutures conductive without compromising the flexible mechanical properties and functionality, and (ii) the sutures wirelessly transmit information to an external device via harmonic backscattering technology, which includes highly miniaturized electronics (less than 1 μm in the smallest version) based on RLC sensors. ) modulates the signal reflected by the conductive stitching.

[0270] Since wireless sensing (WISE) technology sends information about events occurring in remote areas non-invasively to an external device through harmonic backscatter, wires can be eliminated. This involves a highly miniaturized transponder. In addition, the above tests show that the concept is achievable using sutures with medical-grade mechanical properties and biocompatibility. Proof-of-concept experiments demonstrated the ability of WISE sutures to sense bleeding, infection, and compromised suture integrity in real time. The RLC-based sensor used as a modulation circuit attached to the WISE suture can sense and monitor any surgical complications in real time. The WISE suture is also capable of stimulating nerves, eluting drugs, and performing other similar therapeutic diagnostic applications. In vivo studies have shown that the wound healing process is not hindered by the WISE suture and is similar to medical-grade sutures in terms of triggering histopathological events of wound healing. The wireless performance of the WISE suture was stable throughout the 14 days in the animal body.

[0271] The present technology may be part of, incorporated into, or added to a medical device, such as a bandage, stent, valve, prosthesis, or other medical implant or device. For example, a conductive thread may be incorporated into a bandage, and a transmitting device may then be attached to the conductive thread in the same manner as the suture embodiment. In another example, a transponder may be attached to a stent, which itself is typically formed of a conductive material. The technology may also be incorporated into food packaging—e.g., attached to the inner surface of the packaging—to monitor the growth of bacteria that regularly grow in packaged foods.

[0272] As described above, the present transmitting device with or attached to an RF suture can be used to monitor environmental changes at a remote site on demand and continuously. One of the applications of the present invention is to monitor postoperative complications at a surgical site, such as bleeding, infection, damage to suture integrity, etc. It can also be used to monitor food degradation, for example, by incorporation into packaging, etc. The device can be configured so that its capacitance or other electrical properties of the device change in the event of food spoilage, and a handheld reader can be used to power the device and communicate with the device. For example, the device can be coated with a hydrogel or a portion thereof can be coated with a hydrogel that is susceptible to degradation in the presence of foodborne bacteria, in a manner similar to that described above using a combination of Figures 11 to 16 In vivo applications of the described hydrogels.

[0273] Other uses of devices according to embodiments include veterinary surgical site monitoring, crop physiology, and agricultural monitoring, such as soil monitoring.

[0274] Advantageously, where post-operative complications typically materialize very late and require invasive and expensive corrective methods, embodiments of the present invention can eliminate the need for such measures because complications can be wirelessly sensed in real time and thus identified early. Furthermore, the efficiency of the present device is sufficient to safely power devices within the body.

[0275] The use of harmonic backscatter in transponder embodiments means that the signal received by a remote device (such as a portable handheld device) is easily distinguishable from the signal transmitted by the device. By using passive charging, very small batteries or energy harvesting devices, the sensor can be powered with little or no battery power.

[0276] It will be understood that many further modifications and permutations of various aspects of the described embodiments are possible. Accordingly, the described aspects are intended to embrace all such changes, modifications and variations that fall within the spirit and scope of the appended claims.

[0277] Additional embodiments of the present invention are given in the following statements:

[0278] 1. A sending device, comprising:

[0279] an antenna connector for connecting to an antenna; and

[0280] A signal generator for generating a signal for transmission using the antenna when the transmitting device is attached to the antenna, wherein the signal generator has an unaffected condition and an affected condition, and a predetermined condition around the transmitting device causes the signal generator to switch to the affected condition, the signal generated by the signal generator in the unaffected condition being different from the signal generated by the signal generator in the affected condition.

[0281] 2. The transmitting device according to claim 1, which is a transponder.

[0282] 3. The transmitting device according to claim 1 or 2, wherein the predetermined condition includes bacterial growth.

[0283] 4. The transmitting device of claim 3, wherein the signal generator comprises a coating susceptible to being consumed by the bacteria.

[0284] 5. The delivery device of claim 4, wherein the coating comprises a bacteria-specific deoxyribonucleic acid (DNA) hydrogel.

[0285] 6. A delivery device according to claim 1 or 2, wherein the predetermined condition comprises leakage of blood onto the delivery device.

[0286] 7. The transmitting device according to any one of claims 1 to 6, wherein the predetermined condition includes damage to the antenna.

[0287] 8. The transmitting device according to claim 7, wherein the predetermined condition includes a breakage of the antenna, and when the antenna is broken, the signal generator does not transmit the signal.

[0288] 9. The transmitting device according to any one of claims 1 to 8, wherein the signal is generated by harmonic backscattering.

[0289] 10. The transmitting device according to claim 1 or 2, wherein the predetermined condition includes cracking.

[0290] 11. The transmitting device according to any one of claims 1 to 10, wherein the antenna comprises a conductive stitching thread.

[0291] 12. A delivery device according to claim 4 or 5, adapted for placement in a food packaging, wherein the coating is selected for consumption by foodborne bacteria.

[0292] 13. The transmitting device according to any one of claims 1 to 12, further comprising the antenna, wherein the signal generator is activated by a remote device that activates the signal generator by transmitting a signal of a resonant wavelength of the signal generator captured by the antenna.

[0293] 14. The transmitting device according to any one of claims 1 to 12, wherein the signal generator is activated by an electromagnetic field applied by a remote device.

[0294] 15. The transmitting device according to any one of claims 1 to 14, wherein the signal generator is an inductor-capacitor circuit, the inductance and / or capacitance changing as the signal generator transitions to the affected condition.

[0295] 16. A transmitting device according to any one of claims 1 to 15, comprising the antenna, the antenna connector connecting the signal generator about the center of the length of the antenna, the transmitting device being suitable for being located in a surgical site, wherein the signal generator transitions to the affected condition during healing at the surgical site.

[0296] 17. A sending component, comprising:

[0297] A transmitting device according to any one of 1 to 16; and

[0298] The antenna is connected to the signal generator through the antenna connector.

[0299] 18. A conductive suture comprising a surgical suture juxtaposed with tissue portions, the suture being coated in a conductive coating, the coated surgical suture being encapsulated in a protective coating.

[0300] 19. The suture of claim 18, wherein the protective coating is an inert coating.

[0301] 20. The suture of claim 18 or 19, wherein the protective coating is a biocompatible polymer.

[0302] 21. The suture of claim 20, wherein the biocompatible polymer is parylene c.

[0303] 22. The suture of any one of claims 18 to 21, wherein the conductive coating is a biocompatible conductive polymer.

[0304] 23. The suture of claim 22, wherein the biocompatible conductive polymer is poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate).

[0305] 24. A method for forming a conductive stitching thread, comprising:

[0306] Provide medical grade sutures;

[0307] coating the medical grade suture with a conductive coating; and

[0308] Coated medical grade sutures are coated with a protective non-conductive coating.

[0309] 25. A medical device, comprising the transmitting device according to any one of 1 to 16 or the transmitting assembly according to 17.

[0310] 26. The medical device of claim 25, which is one of a suture, a bandage, a stent, a valve, and a prosthesis.

Claims

1. A wireless trigger device for implantation at a site for monitoring a condition at the site, comprising: A modulator capable of being implanted at the site, the modulator comprising: a detector operable to detect a predetermined condition at the site; and a modulation circuit configured to be physically coupled to an antenna implanted at the site, the antenna being operable to receive a wireless trigger signal, the modulation circuit being operable to receive the wireless trigger signal from the antenna and modulate the wireless trigger signal based on the detected predetermined condition to thereby generate a backscatter response signal having specific harmonics, the backscatter response signal being used for wireless transmission by the antenna, Wherein the detector comprises a passive component of the modulation circuit.

2. The wireless triggering device according to claim 1, wherein the wireless triggering device is a passive electronic device. 3 . The wireless triggering device according to claim 1 , further comprising the antenna, wherein the antenna is operable to receive the wireless triggering signal and transmit the backscattered response signal. 4 . The wireless triggering device according to claim 3 , wherein the wireless triggering device comprises a printed circuit board, and wherein the modulation circuit and the antenna are printed on the printed circuit board.

5. The wireless trigger device according to claim 1, wherein the modulation circuit is coated with a biocompatible packaging material.

6. The wireless triggering device according to claim 5, wherein the biocompatible packaging material is selected from PDMS, silicone, parylene-C and polyurethane.

7. The wireless triggering device of claim 5, further comprising a connector for connecting the wireless triggering device to a wound closure device.

8. The wireless triggering device of claim 7, wherein the wound closure device is one of a suture, a staple, a surgical zipper, and an endoscopic clip.

9. The wireless triggering device of claim 7, wherein the connector comprises a mechanical connector or a chemical adhesive.

10. The wireless triggering device of claim 5, wherein the antenna is a conductive component of a medical device.

11. The wireless triggering device of claim 10, wherein the medical device is one or more of a bandage, a valve, a prosthesis, and an implant.

12. The wireless triggering device of claim 5, wherein the predetermined condition comprises one or more adverse pathological physiological conditions.

13. The wireless triggering device according to claim 12, wherein the one or more adverse pathophysiological conditions include one or more of bleeding, bacterial infection, gastric fluid leakage and anastomotic leakage. 14 . The wireless trigger device of claim 5 , wherein the modulation circuit is an RLC circuit, and a resonant frequency of the RLC circuit varies based on the detected predetermined condition.

15. The wireless triggering device according to claim 5, wherein the passive component is a capacitor or an inductor.

16. The wireless trigger device of claim 5, further comprising a support member for supporting a layer of responsive material susceptible to undergoing a change under the predetermined condition, the support member being configured to support the responsive material above the passive component.

17. The wireless trigger device of claim 16, wherein the support member comprises a plurality of relief structures extending from the modulation circuit and defining a cavity for receiving the response material.

18. The wireless trigger device of claim 5, further comprising a responsive material susceptible to undergoing a change under the predetermined condition, the responsive material being coated on the passive component.

19. The wireless triggering device of claim 18, wherein the responsive material is a hydrogel.

20. The wireless triggering device of claim 19, wherein the predetermined condition comprises a bacterial infection, and the responsive material is a DNA hydrogel that is susceptible to degradation in the presence of nucleases secreted by bacteria.

21. The wireless triggering device of claim 19, wherein the predetermined condition comprises leakage of gastric fluid, and the responsive material is a peptide hydrogel that is easily degraded in the presence of pepsin.

22. The wireless triggering device of claim 5, wherein the site is a wound site.

23. A system comprising a reader and the wireless triggering device according to claim 1, wherein the reader comprises: a transmitter configured to transmit a plurality of interrogation signals configured to stimulate backscattered response signals from the wireless trigger device; a receiver configured to receive the backscatter response signal from the wireless trigger device; as well as A processor is configured to determine a condition at a site based on the backscattered response signal.

24. The system of claim 23, wherein the condition at the site comprises one or more of healing, bleeding, infection, bacterial growth, dehiscence, suture breakage, heart rate, and respiratory rate.

25. A conductive surgical thread for use as a suture thread for apposing tissue portions, the surgical thread comprising: a first conductive portion; a second conductive portion; an insulating portion between the first conductive portion and the second conductive portion; forming a first connection point between the first conductive portion and the insulating portion; as well as forming a second connection point between the second conductive portion and the insulating portion, wherein the first connection point and the second connection point are physically connectable to two antenna connectors of a modulator so that the first conductive portion and the second conductive portion can function as two parts of an antenna; wherein each of the first conductive portion and the second conductive portion comprises: internal surgical lines; a conductive coating on the internal surgical wire, the conductive coating comprising a biocompatible conductive polymer; and a biocompatible protective coating on the conductive coating; and The insulating part comprises: Internal surgical lines; and A biocompatible protective coating on the internal surgical thread.

26. The surgical wire of claim 25, wherein the biocompatible conductive polymer comprises one or more of PEDOT:PSS, poly(pyrrole), polythiophene, poly(3-alkylthiophene), polyphenylene-vinylene, polyaniline, and poly(p-phenylene sulfide).

27. The surgical wire of claim 26, wherein the biocompatible conductive polymer comprises PEDOT:PSS.

28. The surgical wire of claim 27, wherein the biocompatible conductive polymer comprises three or more layers of PEDOT:PSS.

29. The surgical wire of claim 25, wherein the biocompatible protective coating comprises parylene-c.

30. The surgical line according to claim 25, wherein the inner surgical line comprises a wire.

31. The surgical thread according to claim 25, having a diameter of USP size 0.

32. A method of producing a conductive surgical thread according to claim 25, the method comprising: providing a surgical wire having a first portion, a second portion, and a third portion between the first portion and the second portion, thereby forming the first conductive portion, the second conductive portion, and the insulating portion, respectively; coating the first portion and the second portion of the surgical wire with a conductive coating comprising a biocompatible conductive polymer; as well as The first coating portion, the second coating portion and the third coating portion of the surgical thread are encapsulated in a biocompatible material to form the first conductive portion, the second conductive portion and the insulating portion of the conductive thread, respectively. The first connection point is formed between the first conductive portion and the insulating portion, and the second connection point is formed between the second conductive portion and the insulating portion.

33. The method of claim 32, further comprising: Oxygen plasma treatment is applied to the surgical thread.

34. The method of claim 32, further comprising: The conductive coating was vacuum dried.

35. The method of claim 32, further comprising: The wax is removed from the surgical threads via a chemical treatment.

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