US010201703B2

( 12 ) United States Patent Bogie et al .

( 10 ) Patent No . : US 10 , 201 , 703 B2 ( 45 ) Date of Patent : Feb . 12 , 2019

( 54 ) INTEGRATED SURFACE STIMULATION DEVICE FOR WOUND THERAPY AND INFECTION CONTROL

( 52 ) U . S . CI . CPC . . . . . . . A61N 1 / 36014 ( 2013 . 01 ) ; A61N 1 / 0468

( 2013 . 01 ) ; A61N 1 / 0472 ( 2013 . 01 ) ; ( Continued )

( 58 ) Field of Classification Search CPC . . . . . . . . . . A61B 516833 ; A61B 2560 / 0412 ; A61N

1 / 0472 ; B29K 2079 / 08 ; B29K 2995 / 0005 See application file for complete search history .

( 56 ) References Cited U . S . PATENT DOCUMENTS

7 , 970 , 450 B2 * 6 / 2011 Kroecker . . . . . . . . . . . . . A61B 5 / 0006 600 / 391

2010 / 0241057 A1 * 9 / 2010 Pak . . . . . . . . . . . . . . . . . . . . . . A61N 1 / 044 604 / 20

OTHER PUBLICATIONS Wound EL ( Mölnlycke Health Care ) Non patent literature / product , accessed on May 1 , 2015 : @ http : / / www . molnlycke . com / advanced wound - care - systems / electrical - stimulation / # confirm .

( Continued )

( 71 ) Applicants : The United States of America , as represented by the Department of Veterans Affairs , Washington , DC ( US ) ; Case Western Reserve University , Cleveland , OH ( US )

( 72 ) Inventors : Kath M . Bogie , Shaker Heights , OH ( US ) ; Steven L . Garverick , Cleveland Heights , OH ( US ) ; Christian A . Zorman , Euclid , OH ( US ) ; Daniel S . Howe , San Diego , CA ( US )

( 73 ) Assignees : The United States of America , as represented by the Department of Veterans Affairs , Washington , DC ( US ) ; Case Western Reserve University , Cleveland , OH ( US )

( * ) Notice : Subject to any disclaimer , the term of this patent is extended or adjusted under 35 U . S . C . 154 ( b ) by 0 days .

( 21 ) Appl . No . : 14 / 675 , 270 ( 22 ) Filed : Mar . 31 , 2015 ( 65 ) Prior Publication Data

US 2016 / 0287868 A1 Oct . 6 , 2016 US 2018 / 0369582 A9 Dec . 27 , 2018

Related U . S . Application Data ( 63 ) Continuation of application No . 14 / 363 , 277 , filed as

application No . PCT / US2013 / 022139 on Jan . 18 , 2013 , now Pat . No . 9 , 320 , 907 .

( Continued ) ( 51 ) Int . Cl .

A61B 5 / 0476 ( 2006 . 01 ) AOIN 1 / 36 ( 2006 . 01 ) A6IN 1 / 04 ( 2006 . 01 ) B29K 79 / 00 ( 2006 . 01 ) B29K 105 / 16 ( 2006 . 01 )

( Continued )

Primary Examiner - Michael D Abreu ( 74 ) Attorney , Agent , or Firm — Ballard Spahr LLP ( 57 ) ABSTRACT The present invention provides a thin and flexible device and method of use thereof for wound treatment and infection control . The integrated surface stimulation device may com prise a complete wireless stimulation system in a disposable and / or reusable flexible device for widespread use in mul tiple therapeutic applications . The invention would be situ ated on the skin surface of a patient and would be activated so as to reduce the overall occurrence of infections and / or increase wound healing rates . As provided , the device will comprise an integrated power supply and pre - programmable stimulator / control system on a flexible polymeric substrate layer with areas of stimulating electrodes , applied using techniques such as those found in additive manufacturing processes . The device is especially valuable in treating biofilm - based infections .

12 Claims , 5 Drawing Sheets

30 Adhesive Wireless Communication Module ( s ) Electrodes 10 40

Interconnects 607 - 20 ASIC ( Stimulation Controller )

Substrate 15

US 10 , 201 , 703 B2 Page 2

Related U . S . Application Data ( 60 ) Provisional application No . 61 / 594 , 105 , filed on Feb .

2 , 2012 .

B29K 2995 / 0005 ( 2013 . 01 ) ; B29L 2031 / 753 ( 2013 . 01 ) ; B33Y 10 / 00 ( 2014 . 12 ) ; B33Y 50 / 02

( 2014 . 12 ) ; B33Y 80 / 00 ( 2014 . 12 )

( 56 ) References Cited ( 51 )

OTHER PUBLICATIONS

Int . CI . B29K 505 / 14 ( 2006 . 01 ) B29L 31 / 00 ( 2006 . 01 ) B33Y 10 / 00 ( 2015 . 01 ) B33Y 50 / 02 ( 2015 . 01 ) B33Y 80 / 00 ( 2015 . 01 ) B29C 64 / 135 ( 2017 . 01 ) B29C 64 / 386 ( 2017 . 01 ) U . S . CI . CPC . . . . . . . . . B29C 64 / 135 ( 2017 . 08 ) ; B29C 64 / 386

( 2017 . 08 ) ; B29K 2079 / 08 ( 2013 . 01 ) ; B29K 2105 / 16 ( 2013 . 01 ) ; B29K 2505 / 14 ( 2013 . 01 ) ;

Various Devices , Including GV350 model ( Biomedical Life Sys tems ) Non patent literature / product , accessed on May 1 , 2015 . POS?FECT ( Biofisica ) Non patent literature / product , accessed on May 1 , 2015 : @ http : / / www . wounds - uk . com / journal - articles / bio electrical - stimulation - therapy - using - posifectrd . Procellera Wound Dressing Non patent literature / product , accessed on May 1 , 2015 : @ http : / / procellera . com / procellera / technology .

( 52 )

* cited by examiner

U . S . Patent atent Feb . 12 , 2019 Sheet 1 of 5 US 10 , 201 , 703 B2

FIG . 1

- 30 Adhesive Electrodes 10 L Wireless Communication Module ( s )

40 X

Interconnects 60 - 20 ASIC ( Stimulation Controller )

Substrate 15 -

FIG . 2

Insulating substrate

Platinum

U . S . Patent Feb . 12 , 2019 Sheet 2 of 5 US 10 , 201 , 703 B2

FIG . 3

Microcontroller

Real - time Clock

Custom Integrated Circuit HV Discharge

Switch Electrode

8 - bit PWM HV Boost Converter

Current Sensor Tissue

256B EEPROM Sensor Interface Electrode

10 - bit ADC

UART IrDA Controller IrDA Optical Transceiver

Battery ( power source )

U . S . Patent Feb . 12 , 2019 Sheet 3 of 5 US 10 , 201 , 703 B2

FIG . 4 Fabrication sequence with a polyimide substrate

.

9 .

FATW

12

* * * . . . . . . . . . .

si e polyimide photoresist Pt Cr

U . S . Patent Feb . 12 , 2019 Sheet 4 of 5 US 10 , 201 , 703 B2

Temperature Sensor Accelerometer ilt

non Microcontroller .

FIG . 5

Stimulator HAI - The

was Battery Boost Converter

PIC ICSP Port RS - 232 Port User Interface

U . S . Patent Feb . 12 , 2019 Sheet 5 of 5 US 10 , 201 , 703 B2

FIG . 6 State 1

Low - power Standby ( 610 )

Raw IR signal received

State 2 Parameter

Programming ( 620 )

Treatment Start Command Received

Treatment Period Elapsed

( 0 - 168 hrs )

State 3 Pre - Treatment Measurements

( 630 ) Stimulation Period Not Elapsed

State 4 Analysis Phase ( 32 msec ) ( 640 )

State 5 Boost Phase

( 0 - 64 msec ) ( 650 )

State 6 Discharge Phase ( 0 - 200 usec ) ( 660 )

Stimulation Period Elapsed ( 0 - 60 minutes )

State 7 Post - Treatment

Sleep ( 0 - 60 Minutes ) ( 670 )

US 10 , 201 , 703 B2

INTEGRATED SURFACE STIMULATION through the use of an integrated surface stimulation device DEVICE FOR WOUND THERAPY AND ( ISSD ) . The ISSD for wound management and infection

INFECTION CONTROL control , according to the present invention , is a wearable , flexible adhesive electrical stimulation patch that is wireless ,

This application claims priority to U . S . non - provisional 5 with the totality of the component electronics and power patent application Ser . No . 14 / 363 , 277 , filed on Jun . 5 , 2014 , which is a U . S . National Stage filing under 35 USC 371 of , source being wholly encapsulated thereon in a thin , flat and in turn claims priority from , PCT Application No . instantiation . In providing the above , the invention utilizes PCT / US13 / 22139 , filed on Jan . 18 , 2013 , which in turn advanced materials and fabrication techniques , and is claims priority from U . S . provisional Patent Application No . - designed so as to have a simple , user - friendly communica 61 / 594 , 105 , filed on Feb . 2 , 2012 , the contents of which are 10 tion interface . More specifically , one embodiment of the each hereby incorporated by reference in the entirety . invention contains all the components of a single - channel ,

current - controlled stimulation system within a lightweight , FIELD OF THE INVENTION flexible , independently - powered portable device utilizing a

The present invention relates to medical devices that 15 5 custom , miniaturized ( approximately 2 - 9 mm² ) Application utilize electrical stimulation for surface - stimulated treatment Specific Integrated Circuit ( ASIC ) , also known as a custom of infections and wounds in the human body . The present IC . The ISSD uses advanced materials and cutting - edge invention is a patch , i . e . a thin , partially or fully flexible fabrication techniques to provide sustained or intermittent covering , which incorporates a stimulation controller , wire - application of Electrical Stimulation ( ES ) combined with less communication device , miniaturized or wireless power , 20 maintenance of a stable wound healing environment . An and a substrate with customizable treatment electrodes . optional software package with a graphical user interface

Open wounds can be difficult to treat . In particular , ( GUI ) may also be provided for use on a partner device chronic wounds , such as ischemic wounds and pressure connected to the invented device , to be employed by a ulcers , are a major clinical challenge in the long - term care medical professional . of people with physical impairment and / or disability . Even 25 The ISSD comprises a complete wireless stimulation in mild cases , special care is required . Scientific studies system in a disposable and / or reusable flexible device for show that electrical stimulation quickens wound healing , widespread use in multiple therapeutic applications . The reduces scar formation , and can reduce discomfort there invented device would be situated on the skin surface of a from . For example , galvanic treatment has been known for patient and would be activated so as to reduce the overall many years as a means to deliver drugs and cosmetic active 30 occurrence of infections and / or increase wound healing agents into the skin for therapeutic purposes . Such rates . As manufactured , the device will comprise an inte approaches are based on mechanisms such as iontophoresis grated power supply and pre - programmable stimulator / con and electro - osmosis . A review of the literature reveals that trol system mounted on the upper face of a flexible poly galvanic treatment is also valuable in the treatment of 5 meric ‘ backbone ' or substrate layer . The lower face of the wounds and scars , via several modes of action including 35 substrate layer will comprise areas of stimulating electrodes , accelerated cell regeneration ; tissue repair ; accelerated cuta applied using thin film deposition techniques such as sput neous barrier recovery ( even with very low current ) ; improved blood circulation ; improved respiration , and scar tering , evaporation , electroplating , and spray coating or foil reduction . However , to date electrotherapy protocol has deposition . Alternatively the substrate layer may be con been quite lacking especially for problematic wounds such 40 structed using additive manufacturing techniques ( one vari as pressure ulcers , and furthermore , its use in corollary ant of which is known as 3D printing in some applications ) , conditions , such as infections is essentially unknown . whereby interconnection means prepared thereon exist for

To this end , there is a recognized need for an improved connection between components of circuitry and include integrated surface stimulation device ( ISSD ) that can be vias that are constructed and filled in a single process . The used in a variety of mobile care settings , from the intensive 45 advantage of additive manufacture of the substrate as dis care unit to the patient ' s home . It would be highly advan - closed herein is that this approach would enable building the tageous for this ISSD to employ electrical stimulation for substrate in a single process using multiple materials , wound treatment and / or infection control , embodied on a thereby eliminating the need for a mask ( hereafter occasion thin and flexible substrate that includes a self - contained ally referred to as a " maskiess fabrication ” of the substrate power source and controller . Preferably , such a system and 50 with electrodes ) , and further to this point , the same may be device should be disposable and customizable for particular customized in a dramatically easier fashion than if produced types of wounds and infection associated therewith , includ according to the other embodiments of manufacturing as ing the treatment protocol itself . Additional benefits may be referenced above . Such maskless fabrication techniques , recognized when such a device may be fabricated according vary , but in one illustrative embodiment , may comprise to novel additive manufacturing techniques , and when pro - 55 additive manufacturing approaches such as selective laser vided with advanced power sources , such as Lithium poly - melting , where successive layers of material powder are mer batteries or the like that provide sufficient power in exposed so as to be melted or heated with a laser or ion order to deliver reliable stimulation to a large wound for an beam , thereby hardening only certain portions in order to extended period of time . Further benefits can be realized produce the desired final structure . Further to this , the when the novel application of the innovative techniques and 60 equipment may be machines such as the Envisiontec Biop apparatus is used in order to effectively treat infected lotterTM , although many other machines may be utilized as wounds , especially those with biofilm colonies . can be readily appreciated . The non - conductive materials

may be polyamide , silicone or other flexible polymeric SUMMARY OF THE INVENTION materials . The conductive materials may by silver particles

65 in a binder material , platinum particles in a binder material , The present invention relates to a novel approach to conductive inks or other conductive polymeric material .

improving the management of infection and wound healing When provided in accordance with the above , the device can

US 10 , 201 , 703 B2

then be applied to the user with a medical grade pressure attached to the substrate layer and in electrical connectivity sensitive adhesive coating provided on the lower face of the with the at least one stimulation controller ; at least one substrate layer . bi - directional wireless communication link , the bi - direc When provided as such , the invented system has features tional wireless communication link or module comprising at

which also make it advantageous for patients when com - 5 least one RF or infrared based interface ; at least one power pared with conventional systems , in that it offers the advan - source electrically coupled to at least one configuration of tage of electrical stimulation for wound management and electrodes and at least one stimulation controller . The ISSD infection control , but does so in a miniaturized , wholly self must also include means for encapsulating the circuitry ; and contained reusable wireless adhesive patch - like device that an adhesive means for attaching the substrate layer to a can be worn on a patient ' s skin . To this end , the present 10 treatment surface . The device is fabricated from thin and invention overcomes the aforementioned and other disad flexible materials to enable at least those surfaces that vantages inherent in the prior art . contact a patient skin to conform to the contour of the

patient , and may be processed with thick or thin film BRIEF DESCRIPTION OF THE DRAWINGS deposition techniques and / or additive manufacturing tech

15 niques for application of the electrodes and other circuitry With reference now to the drawings in detail , it is stressed components , and may also provide for the power source to

that the particulars shown , are by way of example and for the also feature a thin and flexible profile . By way of illustration , purposes of illustrative discussion of embodiments of the one recitation of exemplary additive manufacturing might present invention , and are presented for providing what is include the following steps : 1 ) Load materials into appro believed to be the most useful and readily understood 20 priate low and high temperature cartridges ; 2 ) Adjust tem description of the principles and conceptual aspects of the perature for each dispensing head to deliver appropriate invention . In this regard , no attempt is made to show material flows ; 3 ) Define dispense rate and pressure based structural details in more detail than is necessary for a on materials characteristics ; 4 ) Build up substrate in layers , fundamental understanding of the invention , the description with materials changes in each layer such that the conduc taken with the drawings making apparent to those skilled in 25 tive material is deposited in areas to form electrodes and vias the art how the several forms of the invention may be defined by predetermined geometry and 5 ) Apply hydrogel embodied in practice . Accordingly : over electrode surfaces on lower face of substrate .

FIG . 1 is a photograph showing the physical appearance The principles and operation of powered treatment of an incomplete prototype of a wound treatment device as devices according to the present invention may be better applied to a user , according to one embodiment of the 30 understood with reference to the figures . The figures show invention ; exemplary embodiments of the present invention and are not

FIG . 2 is a schematic representation of an exemplary cross limiting . section of ISSD electrode - supporting substrate in accor - FIG . 1 shows one embodiment of a powered treatment dance with one embodiment of the invention ; device 5 as a patch 5 ' , including only the stimulation

FIG . 3 is an illustrative block diagram of flexible ISSD 35 electrodes and controller components of the ISSD circuitry circuitry 60 and related peripheral electronic components of 60 , where the latter has been fully implemented as an ASIC the device according to one embodiment of the invention ; in order to reduce size and improve flexibility of the device .

FIG . 4 is schematic cross - sectional views illustrating an FIG . 2 shows the schematic cross - section of the supporting exemplary fabrication sequence , reading in order from left to substrate , which is optionally made of flexible materials . right , with polyimide substrate used in the device in accor - 40 FIGS . 3 and 5 show two additional embodiments of stimu dance with one embodiment of the invention ; lation controller 20 , one ( FIG . 3 ) which employs an ASIC

FIG . 5 is an electrical schematic diagram of one embodi - ( custom IC ) to implement only the high - voltage , sensing , ment of the device according to the invention ; and and wireless communication modules 40 of stimulation

FIG . 6 is an operational flow diagram illustrating an controller 20 , and another ( FIG . 5 ) in which off - the - shelf exemplary treatment protocol utilized with one embodiment 45 ( OTS ) components have been used to implement these of the invention . functions . In both embodiments , stimulation controller 20

must be interconnected with the electrodes 10 through DETAILED DESCRIPTION OF THE interconnecting wires 17 ( not specifically depicted ) and PREFERRED EMBODIMENTS electrically connected with power source or supply 50 , all of

50 which are carried by a disposable substrate layer 15 . Power Before explaining at least one embodiment of the inven - supply 50 and stimulation controller 20 components can be

tion in detail , it is to be understood that the invention is not electrically connected or alternatively , bonded to the upper limited in this application to the details of construction and face or side of substrate 15 , or alternatively , power supply 50 the arrangement of the components set forth in the following and stimulation controller 20 components can be reversibly description or illustrated in the drawings . The invention is 55 bonded , that is , they can be removed for reuse with a applicable to other embodiments of being practiced or different substrate , by use of releasable connective elements . carried out in various ways . Also , it is to be understood that Thin metallic conductive electrodes and interconnects that the phraseology and terminology employed herein is for the are fabricated thereon . In certain illustrative embodiments , purpose of description and should not be regarded as lim - three different polymeric materials may be used to construct iting . 60 the flexible structures of the substrate layer 15 , specifically At its broadest level , the present invention relates to a materials such as polyimides , liquid crystal polymers , sili

medical device for treatment of wounds and / or infection ( s ) cones , fabrics and thermoplastic polymers . comprising at least one electrically powered patch compris - Flexible stimulating electrode 10 regions can therefore be ing ISSD circuitry that includes interconnecting wires on a microfabricated onto the lower face or side , which will be substrate layer ; at least one stimulation controller , the stimu - 65 secondarily coated and / or printed with a medical grade lation controller being configured so as to provide variable pressure sensitive adhesive for attachment to the user . stimulation patterns ; at least one configuration of electrodes Because one key design concept underlying inventive device

US 10 , 201 , 703 B2

5 is forward compatible upgradeability , it is provided with a noted that the customizing of flexible substrate layer 15 and flexible or adaptable architecture that allows for the potential the topographical layout or mask - like areas of electrically for functional expansion such as multi - channel stimulation conductive materials ( stimulating electrode 10 regions ) and and biofeedback sensor capability , which is provided as an electrically non - conductive materials is done according to alternate embodiment of the present invention . The device 5 the imaging wherein flexible substrate layer 15 will have a comprises an integrated power supply and pre - program - certain shape and dimensions according to the shape and mable stimulation controller 20 system electrically and size of the wound and in consideration of the natural or mechanically connected or otherwise mounted on the upper inherent shape of the affected body part , while stimulating face of a flexible polymeric backbone ’ or substrate layer 15 . electrode 10 regions may have a certain layout or electrode The lower face of substrate layer 15 comprises areas of 10 density based upon the size and shape of the wound . stimulating electrodes 10 , applied using sputter coating In a different embodiment however , the aforementioned techniques as described hereafter and as illustratively shown overall method may alternatively be partially summarized as in FIG . 4 . The device can be applied to the user with a follows : ( i ) forming a flexible substrate layer 15 from the medical grade pressure sensitive adhesive coating 30 . In group comprising polyimides , liquid crystal polymers , sili most cases , it may be helpful to have device 5 sterilized upon 15 cones , fabrics , and thermoplastic polymers ; ( ii ) using a reuse or where not initially sterilized prior to placement over pattern tool having an embossing surface with embossments an open wound area of a patient . Many approaches may be to present a relief pattern complimentary to at least one used for this , and one illustrative sterilization could involve desired relief pattern for a mask layer ; ( iii ) forming apertures using an ethylene oxide , which is a low - temperature method in the mask layer ; ( iv ) forming a conductive material layer that would allow device 5 to be fully sterilized , but would 20 10 on flexible substrate 15 based on the relief pattern of the not damage the on - board electronics . In one embodiment , at mask layer ; and ( v ) electrically connecting via the conduc least integrated power supply and pre - programmable stimu - tive material layer to output terminals of an ISSD the lation controller 20 system of device 5 is capable of being through apertures . sterilized , and to this end , may be fully encapsulated with a The controller circuitry or stimulation controller 20 pro polymer coating or the like in order to enclose the same from 25 vides functions such as timing , intermittent operation , and moisture , and also , for protecting the electronic components power monitoring , and combines with passive components , therein during sterilization by chemicals , etc . , after use . such as resistors , capacitors , an inductor and connective

Accordingly , the above may be summarized in accor - wiring ( interconnecting wires 17 , not specifically depicted ) , dance with one illustrative embodiment as a method for to produce stimulating waveforms that are transmitted to making electrode patterns in flexible substrates for use with 30 inventive flexible ISSD circuitry 60 which utilizes custom an ISSD for wound therapy and infection control , as follows : ized electrode 10 patterns therein to ultimately deliver ES to ( i ) defining dimensions of a flexible substrate layer 15 using a patient wound . In generating the same , the duty factor of at least one STL ( STereoLithography ) file ; ( ii ) defining the high - voltage discharge pulses produced using stimula topographical areas of electrically conductive materials tion controller 20 will be proportionally related to the ( e . g . , stimulating electrode 10 regions and electrically non - 35 average output power . The aforementioned passive elements conductive materials using at least one STL ; ( iii ) forming , are usually separate components , and may , in one embodi through additive manufacturing techniques , the flexible sub ment , be mounted to a rigid circuit board ( not depicted ) and strate layer 15 having the aforementioned dimensions , can be connected by printed wiring ( also not depicted ) . formed from the group comprising polyimides , liquid crystal However , a traditional rigid circuit board may not always polymers , silicones , fabrics , and thermoplastic polymers ; 40 meet design requirements ( such as specific types of required and ( iv ) forming areas of electrically conductive material flexibility ) that may be required in some embodiments for materials ( stimulating electrode 10 regions ) and areas of stimulation controller 20 . In either case , all electronic com electrically non - conductive materials based upon the defin - ponents herein must be minimized in quantity and size to ing of topographical areas of electrically conductive mate - maximize flexibility , as will be further discussed below . rials ( stimulating electrode 10 regions ) and electrically non - 45 Depending on the desired effect and system requirements , conductive materials , such that the forming areas of one may employ one of three possible illustrative embodi electrically conductive material ( stimulating electrode 10 m ents , wherein the stimulation controller 20 comprises regions ) and areas of electrically non - conductive materials is either : ( i ) two ICs ( an IC microcontroller coupled with an done through the aforementioned additive manufacturing ASIC stimulator ) ; or ( ii ) a single IC ( e . g . , an IC microcon techniques and is executed concurrently with the forming of 50 troller coupled with an OTS discrete stimulator ) ; or ( iii ) a said flexible substrate layer 15 . The above is quite novel on full - function IC , i . e . an ASIC that includes both stimulator various points , not the least of which concerns the advan - and microcontroller functions , each of which is preferably tageous provision of concurrent formation of flexible sub - miniaturized . strate layer 15 with electrically conductive material materi - The ASIC embodiment may be either partially or com als ( stimulating electrode 10 regions ) and areas of 55 pletely based on an ASIC that may include all circuit electrically non - conductive materials , a distinction which functions required for actuation and sensing of the ISSD , as affords savings of time , materials and expense in processing , well as communication to the external computing device , and which affords ease of production through portable such as a laptop computer , smart phone or the like , as additive manufacturing machines such as 3 - D printers and contrasted with the discrete stimulator mentioned above the like . In regards to the use of STL file , the above method 60 which provides for these components separately . In either might further comprise imaging a patient wound , by various case , a high - voltage transistor may be required as part of a visual means such as surface scanners , photographic means , boost converter that provides the approximately 100 - V level and / or visual and manual inspection , so as to ascertain required for electrical stimulation in some circumstances . In various wound indicia , at least wound dimensions and one embodiment , all boost converter circuitry , excluding the shape . Once this resulting imaging has been created , the data 65 aforementioned high - voltage inductor , diode , and storage points therefrom are converted or created by use of image capacitor components , could potentially be integrated onto processing software into at least one STL file . It is further the ASIC . Analog preamplifiers and analog - to - digital con

US 10 , 201 , 703 B2

verter for sensing of electrode current and other biological microcontrollers can be employed . This embodiment pro signals of interest can also be fully integrated . Wireless vides for the function of the stimulator to be preserved in the communication circuits that comprise the wireless commu case where the microcontroller requires upgrading . The nications module 40 ( discussed hereafter ) can also be fully stimulator may be implemented using any preferred tech integrated , except for the infra - red ( IR ) photo diodes based 5 . nology independent of the microcontroller and furthermore , embodiment required by the illustrative IrDA channel when may include sensory circuits such as for monitoring move

ment or other vital statistics in a user . In any case , the above used in a rigid circuit board - based embodiment . Because ISSD circuitry can be encapsulated via an encapsulation IR - based connectivity approaches require line - of - sight to a given partner device , in one illustrative embodiment , wire means that protects the same from moisture and the like , all less communications can employ alternative wireless com of which , when mounted on substrate layer 15 , can be

10 adhered to the skin of a user through the adhesive means munication approaches such as the Bluetooth® Low Energy ( version 4 ) standard , or other RF approaches for wireless described herein . communications module 40 . The inventive flexible ISSD Regardless of the particular embodiment of stimulation circuitry 60 may then comprise at least : ( i ) a stimulation controller 20 , ISSD circuitry 60 may employ an aforemen controller 20 mounted on a circuit board which is in turn tioned high - voltage boost converter circuit with a step - up mounted on substrate layer 15 , wherein the stimulation 15 loop that includes the aforementioned high - voltage transis controller 20 has different embodiments , either two ICs ( an tor , and a storage capacitor that is rated for an illustrative IC microcontroller coupled with an ASIC stimulator ) ; or a maximum 100V , at an illustrative 100 - nF capacity in order single IC ( e . g . , an IC microcontroller coupled with an OTS to maximize the voltage aspects of the overall system , and discrete stimulator ) ; or a full - function ASIC that provides for increasing the ( interchangeable ) battery life of power both microcontroller and stimulator functions , as discussed 20 source 50 . In both the two - IC embodiment and the full herein ) ; ( ii ) a bi - directional wireless communications mod function ASIC embodiment , the step - up capacitor may be ule 40 which includes connectivity to an IR interface ( pho provisioned to be physically separate , off chip , but in elec todiode pair ) or an RF interface required for wireless com trical connectivity therewith . In the particular case of the munication ; ( iii ) a high - voltage boost converter circuit in two - IC embodiment , both ICs can be obtained in die form electrical connectivity with stimulation controller 20 , said high - voltage boost converter circuit comprising an appro - 2 25 and can be 1 ) flip - chip bonded directly to metal traces on the priate high - voltage inductor / diode / storage capacitor as flexible substrate , then sealed with protective coating , or 2 ) required by stimulation controller 20 , said high - voltage wire bonded to the lead frame of a standard surface - mount boost converter circuit being charged to the aforementioned IC package that would then be hermetically sealed . The high - voltage level ; ( iv ) power source 50 connected to the former is potentially smaller and more flexible , while the circuit board upon which stimulation board 20 is mounted ; 30 latter is simpler to manufacture and potentially more robust . ( V ) stimulating electrodes 10 connected an interconnection where an embodiment is desired that includes customized means to the circuit board upon which stimulation board 20 rather than OTS ICs , a custom IC ( ASIC ) could be fabri is mounted ; and ( vi ) the interconnecting means , wherein the cated using an illustrative 0 . 7 - micron high - voltage CMOS interconnection means is provided for electrically connect foundry process provided by ON Semiconductor ( available ing at least stimulating electrodes 10 with stimulation con - 35 mulation con - 35 from ON Semiconductor of Phoenix , Ariz . ) , via the MOSIS troller 20 , the interconnection means illustratively including service of Marina del Rey , Calif . Thereafter , it is noted that at least one or more components chosen from the group in the present invention , variable stimulation patterns are comprising : interconnecting wires 17 ( not specifically provided to accommodate different types of wounds and the depicted ) ; thin film deposited structures ; or thin film plati num interconnect structures in combination with a bonding , changing treatment thereof over time . To this end , software wherein the bonding is chosen from the group comprising 40 can be pre - programmed group comprising 40 can be pre - programmed on the microcontroller of a two - IC wire bonding or flip chip bonding . In contrast to the full embodiment , or on the ASIC of a full - function ASIC function ASIC embodiment , the two - IC embodiment offers embodiment . The various parameters that may be consid a separate high - voltage stimulator ASIC and microcontroller ered when providing such software within device 5 might , in in order to permit straight - forward firmware upgrades and to one embodiment , be effected through usage of the below minimize the cost of the ISSD , given that inexpensive OTS considerations set forth in Table 1 , below .

TABLE 1

Specifications for conformable flexible integrated surface stimulation device ( ISSD )

Variable Relevance Criteria

Safety Substrate materials must be biocompatible & stimulation may be charge - balanced .

Reliability

Prolonged contact with skin requires neither the materials employed nor the stimulation delivered will cause tissue damage In order to be effective , ES must be delivered as programmed . Devices in contact with open wounds must be initially sterile to minimize infection .

Stimulation is ideally delivered consistently over an illustrative 7 day lifetime of the device . May use illustrative ethylene oxide sterilization to achieve sterility while maintaining electrical functionality .

Sterilization

System configuration

Flexible Chronic wounds occur on many Conform to an arc equal in radius to a parts of the body . circumference of any rounded body

parts .

US 10 , 201 , 703 B2

TABLE 1 - continued Specifications for conformable flexible integrated surface stimulation device

( ISSD )

Variable Relevance Criteria

Size Overall footprint will vary to fit target wound .

Device must be suitable for clinical use in a variety of wound locations . Stimulating electrodes deliver therapeutic ES to the wound .

Electrode layout

Low - profile & lightweight

Not interfere with overlying bedclothes or cau pressure if accidentally lain on .

Electrodes to be located at the wound margins and can be patterned based on wound size and shape . Maximum height less than 3 mm in one illustrative embodiment . Maximum weight less than 15 g in one illustrative embodiment .

System function

Wound occlusion A moist microenvironment Maintenance of adherence to skin for up provides optimal wound to 7 days with full wound occlusion . healing

User - friendly interface Clinical acceptance requires Includes a customizable design for an ease - of - use . intuitive GUI for selection and control

of stimulation patterns . Programmable Optimal stimulation variables Stimulation pulse variables making up

for ES therapy can be defined the respective profile ( s ) may be based Stimulation profiles can be on data from prior clinical studies , applied intermittently or illustratively described as : continuous , for duty cycles Range Increment from 5 min / day to 24 h / day . Pulse width 0 - 200 us 5 us

Amplitude 0 - 20 mA 0 . 5 mA Frequency 0 - 20 Hz 1 Hz

Power supply Independent power supply , Battery - powered , capable of up to 7 capable of 7 days use is days continuous use . Battery will last required for un - tethered system . longer with intermittent use .

As mentioned above , the central core of present device 5 be made from liquid crystal polymers , polyimides , vinyl is comprised of a flexible polymeric biomaterial insulating materials or polyester . Optionally , substrate layer 15 can be substrate ( substrate layer 15 ) on which the flexible power of made up of a plurality of materials , which can be stacked or supply 50 and rigid stimulation controller 20 will be connected in a co - planar way by any suitable attachment attached along with the thin metallic electrodes and inter means . In some embodiments , base layer substrate 15 is connects that are fabricated thereon . In certain illustrative made up of one continuous piece of material . Substrate layer embodiments , three different polymeric materials may be 15 may readily facilitate attachment of the overall device 5 used to construct the flexible structures of the substrate layer 10 to a desired body area . Attachment mechanisms may include 15 , specifically materials such as polyimides , liquid crystal but are not limited to medical grade adhesives , adhesive polymers , and thermoplastic polymers . In one particular strips , suction cups and / or any combinations thereof . It has embodiment , a combination of thick polyimide foils and thin also been found that lower cost medical grade pressure film resins may be used for producing substrate layer 15 in sensitive adhesives such as Dermabond® ( 2 - octyl cyano order to meet the requirements for the device to be durable 45 acrylate , marketed under the aforementioned trademark by for longer periods in different environments , such as those Johnson & Johnson of New Brunswick , N . J . ) can be used , in encountered where use is needed for say , one week of one embodiment , to attach substrate layer 15 to intact skin . continuous use in moist environments . One illustrative On removal , this type of medical grade pressure sensitive example of production of this variant of substrate layer 15 adhesive preferentially adheres to the substrate material , within the overall context of the present invention may be 50 thus causing no skin damage , and can remain strongly seen in FIG . 4 , which details an exemplary process sequence adherent after many hours or days . for fabricating a flexible polyimide ISSD substrate . Sub In one embodiment , the present invention provides flex strate layer 15 may optionally be manufactured from any ible ISSD circuitry 60 to be situated on substrate layer 15 polymer material that is suitable for flexible electronics and that is processed from LCP for component side isolation , or biomedical uses according to a process that utilizes pattern - 55 as depicted in FIG . 4 , is alternatively processed from an ing that creates via structures thereon between the afore - illustrative spin - castable polyimide material that utilizes mentioned circuit components through use of a microma - patterning processes in order to create via structures between chining step , or any suitable material which can the circuit components of flexible ISSD circuitry 60 . One accommodate the powered treatment device components . exemplary approach utilizes a micromachining step , such as Suitable materials include , but are not limited to woven 60 a KOH - based wet chemical etching step , in order to create material , non - woven material , polymers , or a combination the via structures depicted in FIGS . 2 and 4 . Such an etchant thereof , and , in the case of woven materials might alterna - is effective in removing polyimide , and the use of etchant tively include the usage of smart fabrics which employ resistant materials such as platinum for electrodes 10 and conductive traces on or within the fabric whether purely illustratively , chromium for the metallic etch mask can offer woven , knitted , sewn , couched , or whether provided as 65 good resistance to the etchant . Alternatively , plasma etching , e - broidery and / or printed structures . Nevertheless , in one laser micromachining or other material removal techniques illustrative embodiment , substrate layer 15 may alternatively can be utilized to realize the same structures , but in either

US 10 , 201 , 703 B2 11 12

case , successful fabrication of the flexible ISSD circuitry 60 cal interconnects . This packaging or encapsulation means is critically dependent on the fabrication of effective inter must not impede the flexibility of the substrate , be imper connect structures that fill the microfabricated vias . Simul - vious to impurity diffusion , be mechanically durable and be taneous electroplating on both the sidewalls and the bottom electrically insulating . Parylene® is one embodiment for surface of the vias enables complete filling within an illus - 5 this application since it meets the design requirements and trative current thickness range of say , 10 microns . Alterna - has been found to be a suitable candidate coating material tive electroplating options may be afforded under ultrasonic for implanted medical devices . The lower side of substrate conditions or with the use of ‘ filler ' materials . Following 15 , which is intended to be applied to the skin of a patient , fabrication of substrate layer 15 and interconnects thereon , is secondarily coated with a medical grade pressure sensitive the discrete components thereof can be mounted at desig - 10 adhesive for attachment to the user , as part of the aforemen nated locations on the ( illustrative polyimide ) substrate layer tioned adhesive means . The metalized surfaces on the com 15 using a conventional electronics packaging adhesive . ponent side are passivated by the application of a vapor Electrical connections that may comprise a part of an deposited Parylene® film and / or spin - castable polymer . interconnection means or in one embodiment , interconnect Windows into the passivation layer can be formed by laser ing wires 17 , between the discrete components and the thin 15 micromachining or plasma etching to facilitate electrical film platinum interconnect structures may , in one illustrative connection with discrete components , and can provide pat embodiment , be made by wire bonding . Flip chip bonding terning in varying layouts as may be required for customized can also be used to make secure electrical connections . The electrode patterns in specific applications involving particu electrical connections can be mechanically secured , electri - lar ( size / type ) wound remediation and the like . In order to cally isolated and environmentally protected by a third 20 meet the need for customization , the above offers an aspect polyimide film of roughly the same thickness as the discrete of provision for modularity wherein the electronic compo components ( 0 . 5 mm ) so as to ensure complete coverage of nents of ISSD circuitry 60 can be mounted on a second LCP the wire bonds . It can be locally applied so as to not interfere sheet that serves as the substrate for the reusable electronic with the global flexibility of the substrate . After localized components . Interconnect structures are fabricated on this polyimide encapsulation , the polyimide substrates can be 25 LCP sheet using the methods described above . Therewith , removed from their silicon wafer pairs by a mild acetone further connections between the electronic components and soak or other appropriate methodology as known in the art . the interconnect structures , including the interconnection

In an additional embodiment ( not specifically depicted ) , means , can also be made by wire bonding or flip chip the present invention provides a method of production of bonding . The reusable component substrate can then device 5 and details of which , in terms of the illustrative 30 mounted on the electrode - supporting substrate using a con materials and fabrication , are discussed henceforth . The ventional packaging adhesive . The reusable component sub central core of the device 5 is a flexible electrode - supporting strate is mechanically secured , electrically isolated and substrate 15 comprised of a Liquid Crystalline Polymer environmentally protected by an encapsulating means of circuit material ( LCP ) sheet with an 18 um copper cladding polymer film of roughly the same thickness as the discrete layer on one of its surfaces , not necessarily depicted in FIG . 35 components ( 0 . 5 mm ) so as to ensure complete coverage of 4 , but which is nevertheless roughly similar to the fabrica - wire bonds . The upper surface of substrate 15 of device 5 is tion sequences of which are illustratively described in one thus composed of a flexible barrier material that provides a embodiment as seen in FIG . 4 . In one embodiment , the safe interface with the patient ' s environment in such a way structures of electrodes 10 are fabricated on the non - copper that protects the electrical components but does not impede clad user - applied side of the insulating substrate 15 by 40 flexibility . Medical grade silicone can also be used to photolithographic patterning , platinum thin film sputtering , encapsulate the electronic components in order to further and lift - off patterning . Electrodes 10 can be made of any ensure biocompatibility , electrical compatibility as an suitable material , such as zinc , copper , manganese dioxide , encapsulating material for microelectronics , and for ease of iron , magnesium , silicon , sodium , silver , silver / silver chlo overall application . ride , carbon , graphite , platinum , nickel , gold , lithium or a 45 In terms of power supply , device 5 provides for varying combination thereof . Optionally , electrodes 10 can be made approaches to power source 50 , which typically requires by any suitable technique . In some embodiments , electrode provision of a requisite voltage that is necessary to generate is made by a suitable printing technique . Electrodes 12 can stimulating waveforms . Power source 50 may comprise be disposed in any suitable way on substrate 15 in spaced single - use batteries , however discharge characteristics must relation to power source 50 and electrically connected to 50 be repeatable to ensure reliable delivery of pre - programmed power source 50 in any suitable way , or as described herein . stimulation patterns . A flat power discharge profile that will Vias for vertical electrical interconnects between the two provide consistent power for longer periods ( e . g . , approxi sides are then formed through the LCP by laser microma - mately 7 days or so ) of stimulation is desirable , although the chining or plasma etching from the copper - clad component inventive electronics design also allows for a somewhat side to the back of the platinum electrodes . Platinum is 55 sloped discharge profile . Therefore , any battery chemistry sputter deposited on the sidewalls of the vias prior to can be used . The battery must be thin , small , durable and electroplating to form a vertical interconnect between the strong . Power supply or source 50 can be modified in 1 . 5 - V bio side electrodes and the stimulation circuitry on the increments as necessary , but generally will be either 1 . 5 V component side , as depicted in FIG . 2 and FIG . 4 . Lateral or 3 . 0 V . To this end , power source 50 is ideally thin and interconnect structures are then fabricated by lithographic 60 flexible as specifically described below in one illustrative patterning and copper etching . The upper surface of the embodiment , but it can nevertheless be of any suitable size substrate 15 can be composed of a flexible or partially and shape that can accommodate the aforementioned flexible barrier material ( optionally part of the aforemen - requirements . In one embodiment , the power source 50 is tioned encapsulation means ) that provides a safe interface depicted as a single electrochemical cell . However , power with the patient ' s environment , yet protects the electrical 65 source 50 need not be limited to one cell , but may include components from direct exposure to moisture , especially for a plurality of connected electrochemical cells , galvanic cells , the sensitive and delicate microprocessor chips and electri batteries , with / without electronics configured to regulate the

14 US 10 , 201 , 703 B2

13 electrical potential ( voltage ) to the level required by the data without a physical connection to device 5 . In such an particular body area of the subject . In some embodiments , illustrative embodiment , the selected communication proto the current and or voltage supplied by the power source is col might allow up to 256 units to be used in the same fixed and cannot be adjusted by a user , although stimulation vicinity . If based on illustrative IrDA - type optical compo controller 20 can provide for any direct stimulation capa - 5 nents , it is noted that the inherently narrow transmission bility . The thickness of the illustrative electrochemical cell focus thereof ( approximately a 30 degree cone ) can mitigate or power supply 50 may be in the range of about 4 - 20 mm potential communications issues emanating from inventive thick . By way of example , a suitable electrochemical cell device 5 , because selection of a given partner device may be a button or watch battery , such as a lithium coin requires pointing the partner device at the inventive device battery providing approximately 40 mA - hr at 3V , may be 10 5 being programmed at any given time . Communication utilized . However , this may in some cases prove too heavy software can further be utilized for modifying stimulation and bulky , and as such in alternative embodiments , power parameters in stimulation controller 20 and for displaying supply 50 may be provided in a 1 . 5 - V cell with step - up stimulation waveform graphs on the partner device . To this circuitry , with total battery current consumption for a nomi end software to allow system control and retrieval of sensor nal stimulation pattern of ~ 1 mA , thereby giving a battery 15 data ( e . g . , outside control adjustment and feedback upload ) life of say , 240 hours with a 15 % stimulation duty cycle , or using the link might be provided in accordance with the may also be provided as a thin cell applied using a suitable illustrative steps 610 - 670 as outlined in FIG . 6 . Sensor data printing technique . Recent developments in battery technol - and other status parameters can be uploaded to the partner ogy have led to the development of very low profile , flexible device and displayed to facilitate any necessary adjustments . “ ribbon ' batteries , such as PowerPaperTM batteries ( available 20 Afterwards , any ( bio ) data provided from the sensors ( elec from Graphic Solutions , Chicago , Ill . ) , which are ultra - trodes 10 ) can be uploaded to the partner device for further thin ( < 1 mm thick ) flexible batteries that can be directly analysis offline , if desired by a given medical professional . printed onto a variety of surfaces . The cathode and anode To this end , the aforementioned optional software package layers of these illustrative batteries are fabricated from may also be provided with a graphical user interface ( GUI ) proprietary ink - like materials , thereby creating a 1 . 5 - V 25 for use on a partner device connected to the inventive battery that is thin and flexible and does not require bulky device , as employed by a medical professional . casing or encapsulation . In addition , the materials used in When provided in accordance with the above , treatment this illustrative battery , zinc and manganese dioxide , are device 5 , including all device components , has an overall classified by the Federal Drug Administration ( FDA ) as thin and flexible profile , which may suit the contour of a environmentally friendly , non - hazardous and may be dis - 30 body area of a subject . Treatment device 5 may therefore be posed of without restriction . These types of batteries are of any size , color and shape suitable for application to a capable of providing up to 1 mA continuous current . How - desired body area . In some embodiments , the thickness of ever , these ribbon type batteries often do not provide device 5 may limited to 10 mm to ensure flexibility , but may adequate power for longer periods , and may be useful for be thicker in other applications . The thickness of device 5 more temporary applications Terminals for connection 35 may also be dependent upon the type of material used and thereto may be located in any desired location to connect to the flexibility of that material . In some embodiments device the specific cell employed and may acquire any suitable 5 may be partially and / or completely disposable . To this end , shape and size , depending on the specific application . in some embodiments substrate layer 15 may be disposable ,

In one alternative embodiment , stimulation controller 20 while the ISSD circuitry 60 may be reusable ( modular , and may include a reusable stimulator PCB ( 35x20 mm ) capable 40 therefore easily switched to anew replacement substrate of producing pulses up 21 mA in amplitude and 250 us in layer 15 ) , or alternatively , the whole device 5 may be duration , powered from a single 450 mAhr rechargeable deemed disposable . Regardless of which embodiment is Lithium Polymer battery such as the PowerStream chosen , device 5 must be stable over a wide range of GM043436 - PCB to power the device . The benefit of such a temperatures and humidity levels , and may be used over all exemplary battery is that it provides sufficient power to 45 body areas of a patient or user , and to this end , may be deliver reliable stimulation to a large wound for an extended designed or customized to fit any area of the body and to period of time ( for example , up to seven days ) and can be have any desirable size , according to the area to be treated . recharged for use with a different substrate on the same By way of further note , electrodes 10 can also be customized patient . As can be appreciated , this represents a significant in terms of overall number , size , and distribution on sub advance in terms of overall performance . 50 strate layer 15 . The customization of electrodes is often less

The invented device may be provisioned as a single - important when the application usage of device 5 is for pain channel , single - pattern stimulator device , which would treatments ( which are better customized through the use of require a system control switch ( not specifically depicted ) to amplitude variations and the like for varied pain states ) . In switch the operating state of device 5 between one of two the ease of wound and / or infection treatment , however , it is states , off and on . However alternative embodiments of the 55 often important to be able to vary the aforementioned design device will also include the potential for multiple stimula parameters in order to adequately treat different types and tion patterns and feedback to the clinician or technician sizes of wounds or states of infection , as well as underlying through stimulation controller 20 , which as discussed above , presenting basis ( e . g . , whether planktonic or biofilm in offers the capability for more sophisticated control , interro - nature ) . gation and feedback options . In providing such features , 60 The device of the present invention can therefore be a bi - directional wireless communication module 40 may fur - fully integrated device or can be part of a kit with removable ther include an RF or an infrared communication link and components so that the covering , battery source , etc . may be protocol ( such as an IrDA - based infrared communication replaced as needed . The device may also be removed from link and protocol ) that allows the ISSD to communicate via the body area at the end of treatment time . Time of treatment multiple channels with outside partner devices ( not 65 can vary , and accordingly , the device in some embodiments depicted ) such as computers , smart phones , tablets , lap tops , can be removed from contact with the body area after a time etc . , so as to allow system control and retrieval of sensor period which can be predetermined , upon expiration of a

US 10 , 201 , 703 B2 15 16

timer , or which can be determined according to the desired planktonic cells of the same species . The electric field from treatment and / or until no more improvement can be seen . the novel ES device and method can aid the disruption or The treatment can optionally be a one - time treatment , or can penetration of the antibacterial agents through the protective be repeated in suitable time intervals any suitable number of polysaccharide and other coatings that shield the biofilm . times . Use of the present invention can facilitate temporary 5 This penetration is , in one illustration , accomplished by a alleviation and elimination of the above conditions . Dura form of electrophoresis that may augment the electrochemi tion of effect can therefore be affected by time and frequency cal generation of resulting surface agents that enhance the of application , stimulation pattern variables , type and efficacy of given antibacterial . amount of current used , and severity of condition . In one In accomplishing the above , the present invention there embodiment , the device is a dermal patch configured for 10 10 fore provides for a method for using an ISSD for wound

therapy as well as for infection control , including for diffi home use . In other embodiments , the device can be applied cult infections like biofilm based infections . To this end , in in a supervised environment . To this point , treatment accord one illustrative embodiment , the method might comprising ing to the present inventions may be beneficial in all body the following steps of : ( i ) assessing a wound and / or infection areas . Being thin , flexible and versatile in shape and form , state ; ( ii ) applying a customized ISSD patch with electrodes the devices of the present invention can be designed to fit 15 10 and a flexible substrate 15 immediate to a wound loca any area of the body and to have any desirable size , tion ; ( iii ) attaching an encapsulated power / control module according to the area having the disorder . 20 to said customized ISSD patch with electrodes and the Novel Electrotherapy for Acute Infected Wounds as a flexible substrate 15 ; ( iv ) setting ISSD controls , including Method for Inhibiting Planktonic and Bacterial Activity . setting at least one of the following of a power profile or at

It is understood that wound infection delays healing and 20 least one customized stimulation pattern ; ( v ) initiating ES increases mortality . Increasingly , antibiotics are showing power and sequences on a resulting set up ; and ( vi ) moni reduced efficacy in the face of multi - resistant bacteria . The toring wound and at least one of the following of battery increasing prevalence of multi - resistant bacteria indicates power , impedance , and temperature . Additionally , the inven

tive method may further comprise : ( vii ) formulating a cus that novel approaches to infection control are needed as both tomized electrode 10 pattern according to the step of assess alternative and adjunctive therapies to standard antibiotic 25 ing a wound type and infection state ; ( viii ) fabricating said regimes . Such infections are particularly challenging when customized electrode 10 pattern by various techniques , biofilms are involved given that biofilms have protective including foil , additive or 3 - D printing techniques , or alter coatings made up of polysaccharides and other components natively , by traditional deposition techniques ; and ( ix ) com that shield the given bacteria colony in the biofilm from bining said customized electrode 10 pattern with selected treatment . Hence , there is a clinical need for an intervention 30 flexible substrate 15 as a resulting patch 5 ' for patient wound that can reduce incident infection , clear existing infection therapy . Also the method may additionally include : ( x ) and accelerate healing , especially when a patient has an attaching an encapsulated power / control module 20 to cus infection that exhibit biofilm colonies . The novel use of tomized ISSD patch 5 ' with electrodes 10 and a flexible Electrical Stimulation ( ES ) as disclosed herein has the substrate 15 , and additionally ; ( xi ) combining a customized potential to address this clinical challenge by reducing 35 disposable flexible substrate 15 with a re - usable , sterilizable

encapsulated power / control module 20 . What is specifically incident infection , clearing existing infection and accelerat meant by encapsulated power module 20 being sterilizable ing healing or having a sterilizable encapsulation is that it is encapsu Both planktonic and biofilm bacterial wound infections lated in a plastic or other type of complete encapsulation that can be positively impacted by the novel use of ES to can seal off the electronics therein from the harmful effects improve healing rates in both acute and chronic wounds can 40 of water or chemicals that may be used in the course of be effectively treated . The novel system and methods relat sterilization at a level that can kill microorganisms . Sepa ing to ES treatment as disclosed herein increases local rately , it is noted that optional provision is contemplated for metabolic activity of cells and tissue oxygenation ( flesh attaching a power source 50 comprising a rechargeable healing ) , disrupts existing biofilm colonies , and even inhib battery ( power supply 50 ) with capacity of at least 450 its biofilm formation from the outset . Additionally , the novel 45 mA - h . system and methods relating to ES also reduces acute wound In applying the above inventive method in a clinical infection by bactericidal effects on many strains relevant for complications of acute traumatic wounds . These effects may setting , one illustrative approach calls for the novel be due to electrolysis products or to increases in bacterial approach of providing treatment and monitoring of wounds membrane permeability . Sustained ES application in accor and infections concurrently or at same time . Thus , one dance with the present invention is bactericidal when 50 employing this novel approach might be able to simultane applied to infected but unwounded skin , and additionally , ously or concurrently treat and monitor wounds and infec increases blood flow and capillary density in compromised tions through the following steps of : ( i ) applying a custom wounds , thereby speeding up healing rates thereof . The ized ISSD patch 5 ' with electrodes 10 and a flexible substrate resulting efficacy of the present invention appears to vary 15 immediate to a wound of a patient ; ( ii ) electrically with stimulation profile , which in at least one illustrative 55 connecting an encapsulated power and control module 20 to case , is that the primary ES factor being current density , customized ISSD patch 5 ' ; ( iii ) establishing a wireless thereby implying that the bactericidal effect is electrochemi communication connection for remote control between a cally mediated . Low - intensity electric fields ( e . g . , those control module 40 and encapsulated power and control having a field strength of 1 . 5 to 20 V / cm and current module 20 ; ( iv ) monitoring ongoing wound and infection densities of 15 pA / cm2 to 2 . 1 mA / cm2 ) can combat the inherent resistance of biofilm bacteria to biocides and anti 60 indicia over a course of time ; ( v ) establishing , based upon biotics . Biofilm infections are a well known for being the preceding step of monitoring ongoing wound and infec difficult to eradicate , especially when compared with plank tion indicia over a course of time , a dynamic ( e . g . , poten tonic cell of the same species of bacteria . The novel appli tially revisable depending on changes to identified wound cation of electrochemically mediated treatment with the and infection indicia ) wound treatment ES profile for execu inventive device offers a bioelectric effect that reduces the 65 tion over said course of time ; ( vi ) establishing , monitoring concentrations of the antibacterial agents needed to kill ongoing wound and infection indicia over a course of time , biofilm bacteria when compared with those needed to kill a dynamic infection control ES profile for execution over the

17 US 10 , 201 , 703 B2

18 course of time ; and ( vii ) executing , over the course of time , patterns in accordance with the novel approach disclosed said dynamic wound treatment ES profile and the dynamic herein were utilized , which , in this illustration , included infection control ES profile at the control module . Addition stepwise variation , indicating the effects of five ( 5 ) different ally , the method may further include processing steps ( iv ) stimulation paradigms within an appropriate current density ( vi ) through an open loop program option or a closed loop 5 range to be studied . These five ( 5 ) different illustrative option . An open loop program option may be further stimulation paradigms included : Pattern 1 : pulse amplitude described in one embodiment as : In the open - loop embodi - 4 mA , pulse width 100 us , interpulse interval 50 ms ; Pattern ment the medical professional will receive a report of the 2 : pulse amplitude 2 mA , pulse width 100 us , interpulse wound / infection status transmitted from the ISSD . The The interval 50 ms ; Pattern 3 : pulse amplitude 6 mA , pulse width medical professional will be able to alter the ES profile 10 10 100 us , interpulse interval 50 ms ; Pattern 4 : pulse amplitude remotely to maintain optimal treatment . In the closed - loop 4 mA , pulse width 150 us , interpulse interval 50 ms ; and embodiment , the medical professional will receive a report Pattern 5 : pulse amplitude 4 mA , pulse width 100 us , of the wound / infection status transmitted from the ISSD and interpulse interval 40 ms . Within each of the aforementioned the ISSD will adjust the ES profile in real time based on the wound indicia being monitored . 15 five ( 5 ) respective groups , 8 - 10 animals were treated for 28

In the above , it is noted that the wound and infection days or until the ischemic wounds were healed , and addi indicia may include particulars such as wound temperature , tionally , 5 animals were treated for just 12 days . Eight ( 8 ) wound impedance , and wound pH . Monitoring such par rats received sham devices as a control . A quantitative ticulars is advantageous inasmuch as it has now been found multivariable outcomes assessment procedure was used to 1 that impedance decreases over time where a wound is 20 evaluate the effects of ES . healing and / or where infection presence is decreasing , and Results : similarly , temperature exhibits similar paradigms of Ischemic wounds treated with a decreased interpulse decrease . Additionally , the step of monitoring while treating interval ( IPI ) had the highest rate of complete wound closure is further advantageous in that all wound healing ( and at three ( 3 ) weeks . Wounds treated with decreased pulse infection resolution ) goes through different stages over time , 25 amplitude ( PA ) had a lower proportion of closed wounds and consequently , it has now been found that the inventive than sham ( control ) ischemic wounds and showed sustained approach of utilizing treatment factors such as pulse width , inflammation with a lack of wound contraction . pulse interval , and interpulse amplitude variables is to be Results According to Specific Illustrations of Exemplary pursued in a dynamic fashion , whereby the same are Stimulation Variable Settings : increased or decreased over time increments and over the 30 Acute Infected Wounds : overall course of time in response to the respective stage of ES was delivered by the ISSD with a 10 % duty cycle for healing or infection resolution . Similarly , the monitored up to 28 days or until all treatment wounds appeared to be presence of say , just an infection without wound presence fully healed . The median values selected for proof - of con normally entails utilization of different treatment factors , cept testing were pulse amplitude 11 mA , pulse width 110 such as a relatively lower current than that which is normally 35 us , pulse frequency 17 Hz . By 21 days post - injury , ES employed compared to wound healing . Also similarly , moni - treated infected wounds were 84 % smaller than untreated toring for biofilms as opposed to planktonic infections may control wounds . alter the treatment factors , just as monitoring for an acute Chronic Wounds : infection turning into a chronic infection , because a chronic Optimal stimulator parameters will vary depending on infection ( unlike acute ) may normally imply wound treat - 40 wound type and extent , but benefits have been seen for a ment factors in addition to purely infection treatment fac - wide range of parameters . The optimal treatment parameters tors . Hence , the infection state as monitored can drive the for delivery of effective ES for chronic wound therapy are electrical pattern and any accompanying customization therefore guided by the underlying physiological effects . In therewith . pre - clinical testing , ES delivered by the ISSD with a 10 %

It is further noted that the aforementioned method for 45 duty cycle with pulse amplitude 4 mA , pulse width 100 us , simultaneous treatment and monitoring of wounds and interpulse interval 40 ms had the highest rate of complete infections may provide that the step of monitoring ongoing wound closure at 3 weeks . wound and infection indicia over a course of time , as well Conclusion : as the step of executing the dynamic wound treatment ES The systematic study of innovatively varying ES para profile and the dynamic infection control ES profile may 50 digms using the novel ISSD provides insight into the advan both be effectuated remotely through use of wireless com - tageous use of ES in ischemic wound healing . This conclu munication , such as bi - directional wireless module ( s ) 40 as sion is based upon the following findings . Specifically , depicted in FIG . 1 . In some cases , control module 20 has clinically appropriate ES can more than double the propor wireless communication module 40 encapsulated therewith . tion of ischemic wounds closed by three ( 3 ) weeks in this

Illustratively , the following particulars were observed in 55 model . Ninety percent ( 90 % ) of wounds treated with a one exemplary usage of the inventive system and apparatus decreased IPI healed by twenty - one ( 21 ) days compared for treating wound infections : with only twenty - nine percent ( 29 % ) of ischemic wounds

treated with decreased PA , which appears to inhibit healing . Example 1 – Electrical Stimulation ( ES ) Promotes It is further noted that , in the above example ( as well as

the Healing of Ischemic Wounds 60 for other illustrations of the novel method ) the innovative ISSD undergirded much of the advantageous results . Spe

Approach : cifically , the innovative delivery of power has superior The effects of varying clinically relevant ES variables reliability , and is able to deliver ES over an extended period

were evaluated using a modified version of the Gould F344 of time that heretofore has not been realized . Thus , the rat ischemic wound model . Stimulation was delivered using 65 innovations of : customized electrodes , customized pulse , the novel lightweight integrated , single - channel , current customized width , intermittent v . continuous pulsing , etc as controlled ISSD as further disclosed herein . Customized ES disclosed herein are indeed novel , and furthermore , the

19 US 10 , 201 , 703 B2

20 actual use of ES in both acute and chronic wounds ( espe One skilled in the art can appreciate from the foregoing cially in combating troublesome biofilms ) is heretofore description that the broad techniques of the embodiments of unknown . the present invention can be implemented in a variety of

The above approach can be employed in human ( in vivo ) forms . Therefore , while the embodiments of this invention applications in order to speed up healing of both chronic and 5 have been described in connection with particular examples acute wounds , as well as for reducing infections of both thereof , the true scope of the embodiments of the invention planktonic and biofilm types , especially in topical rather should not be so limited since other modifications will than systemic applications . In doing so , one illustrative become apparent to the skilled practitioner upon a study of method might include some or all of the following exem - the drawings , specification , and following claims . plary steps : 1 ) Assess wound type and / or infection type ; 2 ) 10 Formulate customized electrode pattern by considering , for What is claimed is : example wound size ; 3 ) Fabricate customized electrode 1 . A device for remote monitoring of a wound or wound pattern by various techniques , including additive or 3 - D infection and treatment of the wound , the device compris printing techniques , or alternatively , by traditional deposi - ing : tion techniques , combine with selected flexible substrate as 15 a flexible and customized Integrated Surface Stimulation resulting patch for patient wound ; 4 ) Apply patch immediate Device ( ISSD ) patch with electrodes , at least one to wound location , attach ISSD controls ; 5 ) Set power temperature sensor , and a substrate , wherein at least a profile or customized profile in accordance with particulars portion of the electrodes of said customized ISSD patch described elsewhere herein ; 6 ) Initiate ES power and are configured to measure at least one wound imped sequences on resulting set up ; 7 ) Monitor battery power , 20 ance value associated with said wound or wound infec impedance , and temperature . Thereafter , if the measure tion , wherein the at least one temperature sensor is impedance increases over time from a base impedance as configured to measure at least one wound temperature measured , then that means that the target wound is healing . associated with the wound ; Also , operators should monitor the measured temperature at an encapsulated power and control module electrically the wound site , as this factor is typically related to infection 25 connected to said electrodes and said at least one level , such that elevated temperature indicates infection temperature sensor of said customized ISSD patch , activity overall , although it is to be noted that this normally wherein said encapsulated power and control module is is more indicative of planktonic infections which are often configured to control delivery of electrical stimulation more biologically active , rather than biofilm based infec to said wound or wound infection by said electrodes of tions which tend to be more stable ; 8 ) Retain patch with ES 30 said customized ISSD patch ; and treatment on for a specified period of time . In one exemplary a remote control module having a bidirectional wireless usage where the system is complimentary to antibiotic use , communication module , said remote control module one illustrative period of use is for approximately seven ( 7 ) being in remote communication with said encapsulated days . Note that this treatment period may vary , in accor power and control module wherein : dance with wound type , patient history , electrode customi - 35 said remote control module is configured to receive first zation and ES pattern profiles and current density chosen by and second outputs from said encapsulated power and the medical provider . control module , said first output being indicative of Of additional note , is the understanding that in some said at least one wound impedance value and said

embodiments , one may dispense with steps 2 and 3 in cases second output being indicative of said of said at least where the customized electrode pattern has already been 40 one wound temperature ; fabricated off site and combined with the flexible substrate said remote control module is configured to determine an for use as part of a readily accessible stockpile or pre infection status of the wound and a healing status of the configured customized patches that are suitable for a specific wound based upon said first and second outputs wound types . Such provision would eliminate the need to received from the encapsulated power and control have fabrication equipment on site . In such cases , the stock 45 module ; and customized patches could be respectively produced in mass said remote control module is configured to determine and according to shape and size ( depending on the areas of body execute a variable Electrical Stimulation ( ES ) profile being treated ) and for type of wound ( e . g . , a more electrodes through communication with said encapsulated power or a higher density of electrodes in a given electrode pattern and control module , said electrodes of said customized might be used for wounds such as chronic wounds , or for 50 ISSD patch being configured to deliver electrical stimu acute traumatic or surgical wounds , and the like ) . lation in accordance with the ES profile , said remote

It is noted that the aforementioned can be applied to more control module being further configured to adjust the than just the actual flesh of human patients undergoing the ES profile in real time based upon said first and second innovative ES treatment with the novel apparatus . Specifi outputs received from the encapsulated power and cally , the novel method and apparatus can also be adapted in 55 control module . an alternate embodiment , to medical device surface treat 2 . The device according to claim 1 , wherein said remote ments , such as for oral biofilms , mouth guards , orthodontics , control module is configured to determine the infection tracheostomy tubes , endotracheal tubes , indwelling cath - status of said wound based upon said at least one tempera eters as well as other classes of catheter , and in general other ture value . medical devices that are susceptible to infections , especially 60 3 . The device according to claim 2 , wherein said remote those caused by biofilm buildup . In adapting to the same , an control module is configured to determine changes in said exemplary approach might be as follows : to provide a wound temperature , wherein said changes in wound tem tracheostomy tube with integrated conductive regions which perature are indicative of the healing status of the wound . can be used to deliver bactericidal stimulation , a flexible 4 . The device according to claim 2 , wherein said remote lining for a mouth guard bath with integrated electrodes that 65 control module is configured to determine an increase in said can be activated to deliver bactericidal stimulation while the wound temperature , wherein said increase in wound tem fixture is being cleaned . perature is indicative of infection of said wound .

US 10 , 201 , 703 B2 21

5 . The device according to claim 1 , wherein said elec trodes of said ISSD patch are fabricated on said substrate .

6 . The device according to claim 5 , further comprising electrical interconnects that are fabricated on said substrate to electrically connect said electrodes of said ISSD patch 5 with said encapsulated power and control module .

7 . The device according to claim 1 , wherein said substrate is disposable .

8 . The device according to claim 1 , wherein said encap sulated power and control module is completely encapsu - 10 lated , and wherein said complete encapsulation is configured to seal off electronics of the power and control module .

9 . The device according to claim 1 , further comprising at least one power source electrically connected to said encap sulated power and control module and to said electrodes of 15 said ISSD patch .

10 . The device according to claim 1 , wherein said remote control module is configured to determine the healing status of said wound based upon said at least one impedance value , and wherein an increase in impedance associated with said 20 wound or infection is indicative of progressive said wound .

11 . The device according to claim 1 , wherein said encap sulated power and control module comprises first and sec ond circuits that are configured to respectively determine said infection status and said healing status of said wound . 25

12 . The device according to claim 1 , wherein said remote control module comprises software that , when executed , is configured to determine said infection status and said heal ing status of said wound .

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