WO2012149466A2

WO2012149466A2 - Body associated device and method of making same

Info

Publication number: WO2012149466A2
Application number: PCT/US2012/035650
Authority: WO
Inventors: Lawrence Arne; James Hutchison
Original assignee: Proteus Biomedical, Inc.
Priority date: 2011-04-29
Filing date: 2012-04-27
Publication date: 2012-11-01
Also published as: WO2012149466A3

Abstract

Methods of manufacturing a body associated device are disclosed. The methods include providing an inlay substrate comprising a first side, a second side, and at least one conductive trace and providing an interposer substrate comprising a first side, a second side, and at least one conductive trace. An electrically conductive layer is applied to the first side of the inlay substrate. The at least one conductive trace is electrically coupled to the conductive layer. The first side of the interposer substrate is coupled to the first side of the inlay substrate to form a subassembly. The at least one conductive trace on the interposer substrate is electrically coupled to the at least one conductive trace on the inlay substrate through the electrically conductive layer. A body associated device with a wet electrode manufactured in accordance with a first process is disclosed. A body associated device with a dry electrode manufactured in accordance with a second process is disclosed.

Description

BODY ASSOCIATED DEVICE AND METHOD OF MAKING SAME CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Patent Application No.61 /480, 789 entitled "Body Associated Device and Method of Making the Same" and filed on April 29, 201 1 , which is herein entirely incorporated by reference.

INTRODUCTION

[0001] The present disclosure is related generally to various configurations of body associated devices such as a patch and methods for manufacturing such devices. In particular, the present disclosure is related to various physical configurations of wearable body associated devices compatible for a web handling manufacturing process.

[0002] A broad industry with diverse product offerings is developing around body associated devices. Such devices include patches, personal monitors that sense physiologic parameters of a living subject and communicate such information to body-area network devices in

communication with the personal monitor, personal communication devices, and the like. Body associated devices can monitor and record individual physiological parameters, e.g., physical activity, heart rate, respiration, temperature, sleep, pulse oxymetry, etc., of the living subject and communicate these parameters beyond the body of the living subject to other devices, e.g., mobile phones, computers, internet servers, etc. As the functionality of such body associated devices becomes more complex, methods for manufacturing and assembling such body associated devices also become more complex. Therefore, there is room for improvements in manufacturing such body associated devices in high volume manufacturing environments and in particular in a web handling or web processing manufacturing environment to provide for high volume production and lower cost assembled body associated device.

SUMMARY

[0003] In one aspect, a method of manufacturing a body associated device is provided. The method comprises providing an inlay substrate comprising a first side, a second side, and at least one conductive trace and providing an interposer substrate comprising a first side, a second side, and at least one conductive trace. An electrically conductive layer is applied to the first side of the inlay substrate. The at least one conductive trace is electrically coupled to the conductive layer. The first side of the interposer substrate is coupled to the first side of the inlay substrate to form a subassembly. The at least one conductive trace on the interposer substrate is electrically coupled to the at least one conductive trace on the inlay substrate through the electrically conductive layer.

BRIEF DESCRIPTION OF THE DRAWINGS

[0004] FIG. 1 is an exploded view of one aspect of a body associated device.

[0005] FIG. 2 is a perspective view of a body associated device assembly shown in FIG. 1 .

[0006] FIG. 3 is a top view of the body associated device shown in FIG. 1 .

[0007] FIG. 4 is a sectional view of the body associated device shown in FIG. 3 taken along section 4—4.

[0008] FIG. 5 is a bottom view of the body associated device shown in FIG. 1 .

[0009] FIG. 6 is a sectional view of the body associated device shown in FIG. 5 taken along section 6—6.

[0010] FIG. 7 is a side view of the body associated device shown in FIG. 1 .

[0011] FIG. 8 is a side view of the body associated device shown in FIG. 1 .

[0012] FIG. 9 is a top view of a two-layer interposer substrate according to one aspect of the body associated device shown in FIG. 1 .

[0013] FIG. 10 is a bottom view of the two-layer interposer substrate shown in FIG. 9.

[0014] FIG. 1 1 is a top view of an inlay substrate according to one aspect of the body associated device shown in FIG. 1 .

[0015] FIG. 12 is a bottom view of the inlay substrate according to one aspect of the body associated device shown in FIG. 1 1 .

[0016] FIG. 13 is a side view of one aspect of an inlay substrate comprising wet electrodes with a hydrogel interface.

[0017] FIG. 14 is a side view of one aspect of an inlay substrate comprising dry electrodes and guard traces.

[0018] FIG. 15 is a side view of one aspect of an inlay substrate comprising dry electrodes, guard traces, and multiple layers. [0019] FIG. 16 is a schematic diagram of a bio-potential electrode model.

[0020] FIG. 17 is a schematic diagram representing unwanted stray capacitance resulting from coupling dry electrodes to the skin of a living subject.

[0021] FIG. 18 is a schematic diagram representing a guard tracing circuit technique to address unwanted stray capacitance resulting from coupling dry electrodes to the skin of a living subject as shown in FIG. 17.

[0022] FIG. 19 is a plot showing impedance versus frequency of the bio-potential electrode model shown in FIG. 16.

[0023] FIG. 20 is a sectional view of printed circuit board signal traces located between upper and lower guard traces.

[0024] FIG. 21 is a flow diagram of a method of manufacturing one aspect of a body associated device.

DESCRIPTION

[0025] In one aspect, the present disclosure provides multiple configurations of a body associated device. In various aspects, the body associated device may comprise a patch, a biocollection patch, a patch receiver, a receiver, a wearable personal communication device ("personal communicator"), among others, which may be individually or collectively referred to herein as a "patch," without limitation. In one aspect, a body associated device is attached to the body of a living subject and is electrical communication with the living subject.

[0026] In other aspects, the body associated device may be in vivo, partially insertible, or ex vivo, i.e., present outside of the body of the living subject during use. In certain aspects the body associated device may be configured to be associated with a desirable skin location. Accordingly, the body associated device may be configured to contact a topical skin location of a subject. Configurations of interest include, but are not limited to: patches, wrist bands, belts, jewelry, watch, apparel, among other configurations. For instance, a watch or belt worn externally and equipped with suitable receiving electrodes can be used as receivers in accordance with the disclosed aspects. The body associated device may provide a

communication path via which collected data can be extracted by a patient or health care practitioner. Accordingly, such body associated devices comprise electronic components to provide such communication capabilities. [0027] In various aspects discussed herein, the body associated device comprises miniaturized electronic components integrated with one or more electrodes to form a bandage- style patch where electrodes, when applied, contact the skin of the living subject. The bandage- style patch may be removably attachable to the living subject, e.g., via an adhesive layer or other construction. A battery and electronics also may be included. The bandage-style patch may be configured to be positioned on a desirable target skin site of the subject, e.g., on the wrist, chest, back, side of the torso, etc. In these aspects, the bandage circuitry may be configured to receive signals, communications, data and the like from devices inside of the subject, e.g., Implantable Pulse Generator, cardiac lead, an ingestible device such as an identifier of a pharma-informatics enabled pharmaceutical composition, etc., and may be configured to relay this information to an external processing device, e.g., a PDA, smartphone, mobile phone, handheld device, computer, etc., as described in greater detail elsewhere.

[0028] In various aspects, the disclosed body associated device comprises an interposer substrate (also known as a strap) and an inlay substrate coupled to the interposer substrate. The interposer substrate forms the core of the device assembly and may comprise high density electronics assembled onto a conventional printed circuit board (PCB), for example. In one aspect, the inlay substrate may be a flexible circuit element electrically coupled to electrodes for electrically coupling the body associated device to a living subject. Electrical connections to the interposer substrate couple the electrodes to the electronic components on the inlay substrate.

[0029] The body associated device may be assembled in a two-phase process. In one phase, electronic components are assembled onto the interposer substrate using any suitable conventional robotic pick-and-place process. In a second phase, the inlay substrate may be attached to the populated interposer substrate using various attachment techniques as discussed hereinbelow which are compatible with high volume web handling manufacturing processes. Since the precision robotic pick-and-place phase is separate from the web assembly phase, the two-phase process minimizes the amount of precision required during the web assembly process. In one aspect, the body associated device assembly also may comprise a foam housing laminated over the interposer-inlay assembly and sealed into a bandage-style patch, for example. Prior to describing the various assembly techniques for manufacturing various aspects of the body associated device, the present disclosure first provides a description of the structural and electrical components of the body associated device.

[0030] FIG. 1 is an exploded view of one aspect of a body associated device 100. FIG. 2 is a perspective view of a fully assembled body associated device 100 shown in FIG. 1 . FIG. 3 is a top view of a fully assembled body associated device 100 shown in FIG. 1 . FIG. 4 is a sectional view of the body associated device 100 shown in FIG. 3 taken along section 4— 4. FIG. 5 is a top view of a fully assembled body associated device 100 shown in FIG. 1 . FIG. 6 is a sectional view of the body associated device 100 shown in FIG. 5 taken along section 6— 6. FIGS. 7 and 8 are side views of the fully assembled body associated device 100. The body associated device 100 will now be described in connection with FIGS. 1 -8.

[0031] Accordingly, with reference now to FIGS. 1 -8, in one aspect the body associated device 100 comprises a housing formed of a top portion 102 and a bottom portion 104. In one aspect, the top and bottom housing portions 102, 104 may be made of a closed cell foam material or other suitable resilient material, e.g., injection-moldable or thermo-formable plastic material. The top and bottom housing portions 102, 104 contain the components of the body associated device 100. Once the components are inserted with the top and bottom housing portions 102, 104 the top and bottom housing portions 102, 104 may be coupled (e.g., sealed, fitted together, connected) using any suitable technique including welding, ultrasonic welding, heat welding, adhesively coupling, riveting, screwing, snap fitting, shrink fitting, button snap fitting, to mention but a few suitable techniques. Located between the top and bottom housing portions 102, 104, are an inlay substrate 106 (e.g., flex circuit) and an interposer substrate 1 16 (e.g., PCB).

[0032] The interposer substrate 1 16 comprises one or more electronic components 1 18 assembled thereon forming an electronic circuit configured to perform a variety of functions. The interposer substrate 1 16 is attached to the bottom portion 126 of the inlay substrate 106 using a variety of techniques discussed hereinbelow.

[0033] A battery 1 12 is located between a space 128 defined by a flange 1 10 and an interposer coupling portion 130 of the inlay substrate 106. In other aspects, the battery 1 12 may be coupled or attached to the interposer substrate 1 16 along with the electronic components 1 18. The battery may achieve electrical contact to contacts on the interposer substrate 1 16 and/or the inlay substrate 106 using a spring clip, conductive adhesive, low temperature solders or high temperature solders.

[0034] A dome switch 108 may be provided for communication with the electronic circuit. An indicator 1 14 may be provided for external communication. In various aspects, the indicator 1 14 may be an optical indicator such as a light emitting diode (LED), as depicted in FIG. 1 , or may be an acoustical, electrical, haptic, indicator, among others. These components may achieve electrical contact to contacts on the interposer substrate 1 16 and/or the inlay substrate 106 using a spring clip, conductive adhesive, low temperature solders or high temperature solders.

[0035] A skin adhesive layer 124 is positioned below the bottom housing portion 104.

[0036] The outer portions of the inlay substrate 106, located laterally from the interposer coupling portion 130, comprise an electrically conductive coating or layer (e.g., usually applied in the form of an ink) formed on a bottom portion thereof to electrically couple the inlay substrate 106 to electrodes 120a, 120b. The electrodes 120a, 120b are positioned through corresponding apertures 132a, 132b formed in the bottom housing portion 104 such that the top portions of the electrodes 120a, 120b make electrical contact with the electrically conductive coating on the bottom portion of the lateral portions of the inlay substrate 106. In one aspect, the electrically conductive coating comprises silver/silver chloride (Ag/AgCI). The electrodes 120a, 120b are received through apertures 134a, 134b defined by corresponding standoffs 122a, 122b, and are received partially through corresponding apertures 136a, 136b defined by a skin adhesive layer 124. In various aspects, the standoffs 122a, 122b may be made of a foam material or other suitable resilient material. In various aspects, the electrodes 120a, 120b may be hydrophilic, hydrophobic, wet, dry, high impedance, low impedance, capacitive, etc. In one aspect, the electrodes 120a, 120b may comprise a hydrogel material (hydrophilic) and in another aspect, the electrodes 120a, 120b may comprise dry electrode material (hydrophobic), as explained in more detail hereinbelow. The standoffs function as a reservoir for hydrogel and to mechanically de-couple the skin adhesive from the electronics housing. In certain applications where a hydrogel is not required, the standoff may be minimized to a simple layer of adhesive.

[0037] FIGS. 9 and 10 illustrate top and bottom views of one aspect of an interposer substrate 1 16, respectively. As shown in FIG. 9, the interposer substrate 1 16 comprises an electrical component side 142 and as shown in FIG. 10, an inlay substrate coupling side 144. The inlay substrate coupling side 144 comprises one or more conductive pads 140, which may be employed to electrically couple the interposer substrate 1 16 to the inlay substrate 106. As shown in FIGS. 9 and 10, the interposer substrate 1 16 comprises a plurality of conductive traces for signal transmission and conductive pads for receiving electrical components thereon. In the illustrated embodiment, the interposer substrate 1 16 comprises wirebond connections and surface mounted technology (SMT) pads.

[0038] FIGS. 1 1 and 12 show top and bottom views of a two-layer inlay substrate 106 according to one aspect of the body associated device shown in FIG. 1 . The top side shown in FIG. 1 1 comprises a plurality of conductive pads 150 for electrically coupling the inlay substrate 106 to the corresponding conductive pads 140 located on the inlay substrate coupling side 144 of the interposer substrate 1 16, as shown in FIG. 10. The bottom portion of the inlay substrate 106 shown in FIG. 12 comprises a layer or coating of electrically conductive ink, typically made with (a) a polymeric binder and (b) conductive particles of one of following: carbon, copper, gold, nickel, silver, or similar conductive material. In one aspect, the electrically conductive ink comprises a Ag/AgCI ink 152a-d for electrically coupling the electrodes 120a, 120b (FIGS. 1 -8) to the interposer substrate 1 16 through electrically conductive vias 154.

[0039] It will be appreciated, that some implementations of the inlay substrate 106 may require three or more (or any suitable number of) electrodes instead of two. Fundamentally, the signal detected from the body of the living subject to be coupled for further processing is a dipole, and usually can be measured using two electrodes. A third electrode may be employed due to the characteristics of the front end amplifier and signal conditioning circuits. Whether or not a particular aspect of the body associated device comprises two or three electrodes is in part a function of the impedance versus frequency characteristics of the front end amplifier and signal conditioning circuits. As shown in FIG. 12, a third electrode may be created on section 209 of the inlay substrate 106, which also comprises electrically conductive (e.g., Ag/AgCI) ink layers 152c, 152d. Where the third discrete electrode is omitted from the design, the reference electrode between the device and body is effectively created by the capacitance between the device ground plane (either on the interposer substrate 1 16 or the inlay substrate 106) and the body.

[0040] When fully assembled, the body associated device 100 may be attached to the skin of a living subject with the pressure sensitive skin base adhesive layer 124. The electrodes 120a, 120b make electrical contact with the skin of the living subject and with the Ag/AgCI layer on the bottom of the lateral portions of the inlay substrate 106. Conductive traces formed on the inlay substrate 106 couple the Ag/AgCI portions to the electronic components 1 18 located on the interposer substrate 1 16. The electronic components 1 18 may be configured into a variety of circuits to perform a variety of functions, including, without limitation, monitoring physiological parameters of the living subject, communicating with other ex-vivo devices or in-vivo devices located on or in the living subject (e.g., receivers, transmitters, and/or transceivers),

communicating with communication nodes external to the living subject, and so on.

[0041] In various aspects, the inlay substrate 106 may be made of any of a variety of suitable materials. Examples of suitable materials for the inlay substrate 106 include, but are not limited to, high Tg polycarbonate, polyethylene terephthalate (PET), polyarylate, polysulfone, a norbornene copolymer, poly phenylsulfone, polyetherimide, polyethylenenaphthalate (PEN), polyethersulfone (PES), polycarbonate (PC), a phenolic resin, polyester, polyimide,

polyetherester, polyetheramide, cellulose acetate, aliphatic polyurethanes, polyacrylonitrile, polytrifluoroethylenes, polyvinylidene fluorides, HDPEs, poly(methyl methacrylates), a cyclic or acyclic polyolefin, or paper. In one aspect, the inlay substrate 106 may comprise conductive on PET. In other aspects, the inlay substrate 106 may comprise copper (Cu) laminated on PET with Ag/AgCI ink for electrode interface. In other aspects, the inlay substrate 106 may comprise Cu laminated on a flex circuit material known under the trade designation KAPTON with Ag/AgCI ink for electrode interface. The inlay substrate 106 may be flexible, rigid, or semi-rigid.

[0042] In various aspects, the interposer substrate 1 16 may be made of any of a variety of suitable materials, for example, suitable flexible polymeric materials, such as PET,

polypropylene or other polyolefins, polycarbonate, or polysulfone. In other aspects, the interposer substrate 1 16 may be made of glass reinforced epoxy laminate sheets, tubes, or rods made of woven fiberglass cloth with an epoxy resin binder that is flame resistant (self- extinguishing) as designated under the FR-4 specification. The inlay substrate 106 may be flexible, rigid, or semi-rigid. The interposer substrate 1 16 also may comprise electrically conductive connections. In one aspect, the conductive connections may include electrically conductive traces or conductive bumps formed on a layer of the interposer substrate.

Alternatively, or in addition, the conductive connections may include conductive ink traces. The conductive bumps may facilitate operative connection of the interposer substrate 1 16 to the inlay substrate 106. The conductive bumps may be any of a variety of electrically conductive materials, such as suitable metals. Examples of metals used in making conductive bumps are gold, aluminum, copper, nickel, and palladium. In addition, the conductive bumps may include a multitude of small, hard particles, providing a multitude of sharp points for penetrating the mating contact surface of the inlay substrate 106, for example. An example of suitable small, hard particles are diamond particles, such as in diamond dust.

[0043] The inlay substrate 106 may be attached to the interposer substrate 1 16 using any suitable attachment technique. For example, the inlay substrate 106 may be attached to the interposer substrate 1 16 via an adhesive. The adhesive may be a conductive adhesive or may be a non-conductive adhesive, such as pressure-sensitive adhesives or epoxy adhesives. A conductive adhesive may comprise, for example, an anisotropic conductive polymer (ACP), an epoxy filled with conductive particles such as, for example, gold, silver, carbon particles. A nonconductive adhesive may comprise, for example, epoxy, including, polyurethane, acrylic, cyanoacrylate, among other chemistries. The non-conductive adhesive acts as a staple, relieving strain from the conductive adhesive which might not have adequate resistance to strain to function in the application by itself. The epoxy may be a thermosetting or ultraviolet curable epoxy. In an alternative aspect, the adhesive may be omitted and the inlay substrate 106 may be welded to the interposer substrate 1 16 such as by laser welding or ultrasonic welding. In one aspect, the connection may be made using an elastomeric connector, a heat seal connector, or a hot bar bond. In the case where an elastomeric connector is used, a spring clip may be employed to apply a suitable force to the elastomeric connector to promote a suitable electrical contact. In one aspect, the adhesive may be in the form of a pressure sensitive adhesive (PSA), which is particularly suitable for high speed web manufacturing on web processing equipment made by Muhlbauer High Tech International with offices in Newport News, VA or web converting equipment made by Delta Industrial of Minneapolis, MN. It will be appreciated that any suitable attachment technique that provides an electrically conductive attachment between the inlay substrate 106 and the interposer substrate 1 16 may be employed to connect the substrates.

[0044] The assembly or sub-assembly formed by the attached the inlay substrate 106 and interposer substrate 106 may be delivered in a variety of suitable forms. Examples of suitable delivery forms include on a roll, in a Z-fold box, trays, or SMT carrier tape.

[0045] With reference now back to FIGS. 1 -8, in various aspects, the skin adhesive layer 124 may be a pressure sensitive adhesive (PSA) and may be configured to be applied to the skin of the living subject. In various aspects, the adhesive layer 124 provides a strong adhesive connection to the body of a living subject that is suitable for holding the body associated device 100 attached to the living subject during a wear period of, for example, 1 to 3 days, 3 to 7 days, 7 to 14 days, 7 to 21 days, and so on. Such functionality may be achieved, for example, by material selection, design and shape of the adhesion area as well as the location of application to the body of the living subject. In other aspects, the adhesive layer 124 may be selected to provide a non-irritating connection/adhesion to the body of the living subject by selecting suitable biocompatible materials and skin adhesives. Examples of such biologically compatible skin adhesive include, without limitation, any skin adhesive that will successfully maintain the adherence of a dermal dressing to moist (perspiring) skin on a living subject working in hot humid environments, without producing adverse reactions such as rashes and itching. In one aspect, the biologically compatible skin adhesive comprises synthetic emulsions acrylic copolymers which are odorless and pressure sensitive. Such water-insoluble adhesives may comprise hydrophilic units to permit strong bonding to wet human skin and still retain some water resistance to permit durability. The copolymer may be prepared to achieve better wet tack and water resistance and peel adhesion and peel adhesion as a function of rate, and may not contain any residual monomer, which is a potential source of skin irritation. In addition, the adhesive layer 124 comprises rounded edges, which further reduces peeling from the skin as compared to sharp edges.

[0046] Turning now to FIG. 13, a side view of one aspect of the inlay substrate 106 according to one aspect of the body associated device 100 is shown. In the inlay substrate 106 of FIG. 13, the electrodes 120a, 120b comprise a layer of electrically conductive Ag/AgCI ink 152a, 152b deposited on the bottom portions of the corresponding lateral portions 208a, 208b of the inlay substrate 106. A hydrogel 156a, 156b interface forms a wet electrode. The living subject is electrically coupled to the circuit on the interposer substrate by the electrodes 120a, 120b. The hydrogel is hydrophilic and comes in various forms, such as, for example, a low viscosity gel or a substantially thick pre-gelled form which survives long term storage. The hydrogel based electrodes are non-polarizable and behave electrically much like a galvanic battery where ions are exchanged for electrons at various interfaces and thus conducting the signal from the skin of the living subject to the circuit on the interposer substrate.

[0047] FIG. 14 is a side view of one aspect of an inlay substrate 200 comprising dry electrodes 202a, 202b and corresponding electrically conductive guard traces 204a, 204b. In various aspects, dry electrodes provide a suitable stable connection to the body of the living subject and are more compatible with low cost high volume manufacturing such as web processing manufacturing. In contrast to hydrogel (wet) electrodes, dry electrodes are polarizable and behave electrically much like a capacitor. The dry electrodes also have higher impedance relative to the wet (Ag/AgCI-hydrogel) electrode. Accordingly, coupling signals from the skin of the living subject with dry electrodes requires techniques such as guard banding to couple a strong-enough signal.

[0048] To understand the guard banding technique, the description now turns to FIG. 16, which shows a standard bio-potential electrode 300 model. From the front end side, the electrode 300 looks like a 1 nf-1 OnF capacitor in parallel with a 200kQ resistor (R^. The parallel combination is then in series with a ~\ 0Q-2kQ resistance (R₂).

[0049] FIG. 17 is a schematic diagram representing unwanted stray capacitance 304 resulting from coupling dry electrodes 300 to the skin of a living subject 302. It is well known that any conductive wire or trace carrying an electrical signal has stray capacitance to conductive elements around it or to free space. The stray capacitance is represented as capacitor 304, which forms the lower leg of a voltage divider with the capacitance of the electrode 300 to the body of the living subject 302, which can be modeled as shown in FIG. 17. The capacitance of the electrode 300 coupled to the body of the living subject 302 and the stray capacitance 304 to some unwanted potential, either free space or nearby conductive elements, form a voltage divider which attenuates the signal picked up by the electrode 300 from the body of the living subject 302. The two impedances reduce the signal from the living subject 302 and act as a conventional voltage divider coupled to an amplifier 306.

[0050] FIG. 18 is a schematic diagram representing a guard tracing circuit technique to address the unwanted stray capacitance 304 resulting from coupling dry electrodes 300 to the skin of the living subject 302 as shown in FIG. 17. As shown in FIG. 18, a conductive guard 308 is placed around the conductive traces of the electrode 300 and the stray capacitance 304. The guard 308 and the lower leg of the stray capacitance 304 are driven at the same potential by the output 310 of the amplifier 306. The guarding technique essentially nullifies the voltage divider formed by the electrode 300 impedance and the stray capacitance 304 impedance.

Accordingly, the guarding techniques enable the use of a higher impedance electrode, such as the dry electrode.

[0051] The nullification can be modeled by the following formula, where Z_cs is the impedance of the stray capacitance 304:

[0053] Because guard 308 and the lower leg of the stray capacitance 304 are driven at the same potential by the output 310 of the amplifier 306, the / component drops to zero, and the impedance |Z_C5| goes to infinity.

[0054] As a point of reference, the impedance versus frequency behavior of the electrode model 300 of FIG. 16 is shown in FIG. 19. The impedance at low frequency is approximately 200kQ. Physiologic signals detected from the living subject range from approximately 0.1 Hz to a few hundreds of Hz, and ingestible event marker (IEM) signals are detected at approximately 20 kHz, where the impedance is approximately 2kQ and guarding may not be necessary here because the impedance of the electrode is low. Guarding is much more effective at the ECG frequency range where the impedance is very high. [0055] FIG. 20 is a sectional view of printed circuit board signal tracing technique. As shown, signal trace 400 is located between upper 402 and lower 404 guard traces. In one aspect, the trace 400 may be located on the inlay substrate and in another aspect the trace 400 may be located on the interposer substrate or both. The upper guard 402 is located above the traces 400 and the lower guard 404 is located below the trace 400. The guards 402, 404 intercept the majority of the electric field generated by the trace 400. Lateral guard traces 403 also may be employed.

[0056] With reference now back to FIG. 14, the inlay substrate 200 comprises first and second dry electrodes 202a, 202b with corresponding top guard bands 204a, 204b and bottom electrically conductive guard bands 206a, 206b to nullify any stray capacitance caused by the high impedance capacitive dry electrodes 202a, 202b. Each of the high impedance capacitive dry electrodes 202a, 202b comprises an electrically conductive layer 210a, 210b (e.g., Ag/AgCI layer) and a nonconductive adhesive 212a, 212b formed over the electrically conductive layer 210a, 210b. The electrically conductive layer 210a, 210b may be printed using silver ink or carbon ink, gold plated copper, platinum plated copper, and the like. The nonconductive adhesive 212a, 212b acts as the dielectric of the capacitive dry electrodes 202a, 202b. The nonconductive adhesive also acts to minimize any motion artifacts that are otherwise typical with dry electrodes. The top guards 204a, 204b are located above the electrodes 202a, 202b whereas the lower guard bands 206a, 206b surround or substantially surround the electrically conductive layer 210a, 210b. The inlay substrate 212 may be formed of PET or any of the inlay substrate materials discussed above.

[0057] FIG. 15 is a side view of one aspect of an inlay substrate 250 comprising dry electrodes 252a, 252b, top electrically conductive guard bands 254a, 254b and bottom electrically conductive guard bands 256a, 256b, and in addition multiple layers 262, 264 of PET materials. The electrodes 252a, 252b each comprise an electrically conductive layer 260a, 260b (e.g., Ag/AgCI layer) printed on the substrate and nonconductive adhesive layers 258a, 258b applied to the electrically conductive layer 260a, 260b. In one aspect, the first layer 262 may be formed by printing a dielectric ink onto a substrate. At least one additional dielectric layer 264 may be stacked on top of each other separated by the electrode guard bands 254a, 254b. One advantage of forming multiple layers by applying inks is in lowering cost and rendering the substrate to remain flexible.

[0058] In one aspect, the electrodes may be made out of conductive fabric for example, any type of fabric (synthetic or natural) that contains conductive fibers or particles made of any of the following: carbon, copper, gold, or similar electrically conductive material. The conductive fabric electrode may be adhered to the body of the living subject with a PSA. Conductive fabric is typically any type of fabric, e.g., commonplace fabrics and those used in the relevant trade that has been loaded with conductive fibers, nickel, carbon, and other suitable conductive materials. In one aspect, the outside layer may be "guarded" by using a second layer of conductive fabric and separating the layers by an insulating layer.

[0059] FIG. 21 is a flow diagram of a method 500 of for manufacturing one aspect of a body associated device 100 as described in connection with FIGS. 1 -8. With reference now also to FIGS. 1 -15, in one aspect, an inlay substrate 106, 200, 250 is provided 502. The inlay substrate 106, 200, 250 comprises a first side, a second side, and at least one conductive trace. An electrically conductive layer is applied 504 to the first side of the inlay substrate 106, 200, 250, wherein the at least one conductive trace is electrically coupled to the conductive layer. An interposer substrate 1 16 is provided 506. The interposer substrate 1 16 comprises a first side, a second side, and at least one conductive trace. The first side of the interposer substrate 1 16 is coupled 508 to the first side of the inlay substrate 1 16, 200, 250 to form a subassembly. The at least one conductive trace on the interposer substrate 1 16 is electrically coupled to the at least one conductive trace on the inlay substrate 106, 200, 250 through the electrically conductive layer. A first and second housing portion is provided. The second housing portion defines at least one aperture configured to receive at least a portion of an electrode therein. The coupled inlay substrate 106, 200, 250 and the interposer substrate 1 16 subassembly is inserted within the first and second housing portions. The first housing portion is coupled to the second housing portion. A skin adhesive layer is applied to a bottom portion of the second housing portion.

[0060] Still with reference to FIGS. 1 -15 and 21 , in one aspect the body associated device 100 may comprise a wet electrode. Accordingly, a hydrogel material may be applied in electrical contact with the electrically conductive layer on the first side of the inlay substrate. At least one standoff defining an aperture may be inserted over the hydrogel material. At least a portion of the hydrogel material is positioned within the aperture.

[0061] Still with reference to FIGS. 1 -15 and 21 , in one aspect the body associated device 100 may comprise a dry electrode. Accordingly, a layer of nonconductive adhesive material is applied over the electrically conductive layer formed on the first side of the inlay substrate. At least one electrically conductive guard band is formed on the second side of the inlay substrate substantially opposite to the electrically conductive layer applied to the first side of the inlay substrate. At least one dielectric layer is applied stacked above the at least one electrically conductive guard band. At least one electrically conductive guard band is formed on the first side of the inlay substrate substantially surrounding the electrically conductive layer applied to the first side of the inlay substrate. In one aspect, at least one lateral electrically conductive guard band is formed on the first side of the inlay substrate.

[0062] Additional disclosure of receivers that may be employed in combination with the biological sample collection devices discussed herein is provided in U.S. Patent Application Serial No. 12/673,326, titled "BODY-ASSOCIATED SIGNAL RECEIVER AND METHOD," filed on February 12, 2010 and published as 2010-0312188 A1 , which is herein entirely incorporated by reference.

[0063] It also can be enabled by employing dry electrodes, which provide a suitable stable connection to the body of the living subject as described in PCT Patent Application No.

PCT/US1 1/23017 dated January 28, 201 1 titled "TWO-WRIST DATA GATHERING SYSTEM" and in PCT Patent Application No. PCT/US1 1/23013 dated January 28, 201 1 titled "DATA GATHERING SYSTEM," in which each of the disclosures is herein entirely incorporated by reference.

[0064] Ingestible event markers (IEM) of interest include those described in PCT Application Serial No. PCT/US2006/016370 published as WO/2006/1 16718; PCT Application Serial No. PCT/US2007/082563 published as WO/2008/052136; PCT Application Serial No.

PCT/US2007/024225 published as WO/2008/063626; PCT Application Serial No.

PCT/US2007/022257 published as WO/2008/066617; PCT Application Serial No.

PCT/US2008/052845 published as WO/2008/095183; PCT Application Serial No.

PCT/US2008/053999 published as WO/2008/101 107; PCT Application Serial No.

PCT/US2008/056296 published as WO/2008/1 12577; PCT Application Serial No.

PCT/US2008/056299 published as WO/2008/1 12578; and PCT Application Serial No.

PCT/US2008/077753 published as WO 2009/042812; each of the foregoing disclosures are herein entirely incorporated by reference.

[0065] Smart parenteral delivery systems are described in PCT Application Serial No.

PCT/US2007/015547 published as WO 2008/008281 ; each of the foregoing disclosures is herein entirely incorporated by reference. Notwithstanding the claims, the invention is also defined by the following clauses:

1 . A method of manufacturing a body associatable device, the method comprising,

in a first step assembling one or more electrical components onto an interposer substrate to form an electronic circuit configured to perform a variety of functions, and in a second step attaching an inlay substrate to the interposer substrate, which inlay substrate is electronically connectable to electrodes for electrically coupling the body associatable device to a living subject.

2. The method according to clause 1 wherein the electrical components are assembled onto the interposer substrate by a robotic pick and place process and the inlay substrate is attached to the interposer substrate using an attachment technique compatible with a high volume web handling manufacturing process.

3. A method of manufacturing a body associatable device according to clauses 1 or 2, wherein the inlay substrate comprises a first side, a second side, and at least one conductive trace;

applying an electrically conductive layer to the first side of the inlay substrate, wherein the at least one conductive trace is electrically coupled to the conductive layer;

wherein the interposer substrate comprises a first side, a second side, and at least one conductive trace; and

the first side of the interposer substrate is coupled to the first side of the inlay substrate to form a subassembly;

wherein the at least one conductive trace on the interposer substrate is electrically coupled to the at least one conductive trace on the inlay substrate through the electrically conductive layer.

4. Method according to any of the preceding clauses further comprising the step of

providing a hydrogel reservoir within the device.

5. The method of any of the preceding clauses further comprising:

applying a hydrogel material in electrical contact with the electrically conductive layer on the first side of the inlay substrate. The method according to any of the preceding clauses further comprising:

inserting at least one standoff defining an aperture over the hydrogel material, wherein at least a portion of the hydrogel material is positioned within the aperture, preferably wherein the standoff functions as the hydrogel reservoir. The method according to any of the preceding clauses further comprising:

applying a layer of nonconductive adhesive material over the electrically conductive layer formed on the first side of the inlay substrate. The method of any of the preceding clauses 3-7 further comprising forming at least one electrically conductive guard band on the second side of the inlay substrate substantially opposite to the electrically conductive layer applied to the first side of the inlay substrate and/or forming at least one electrically conductive guard band on the first side of the inlay substrate substantially surrounding the electrically conductive layer applied to the first side of the inlay substrate, which electrically conductive guard band may be lateral.

The method of clause 8 further comprising:

applying at least one dielectric layer stacked above the at least one electrically conductive guard band. The method according to any of the preceding clauses further comprising arranging an electrode to connect with the inlay substrate. The method according to any of the preceding clauses further comprising:

providing a first housing portion;

providing a second housing portion, the second housing portion defining at least one aperture configured to receive at least a portion of an electrode therein;

inserting the coupled inlay substrate and interposer substrate subassembly within the first and second housing portions; and

coupling the first housing portion to the second housing portion. The method according to any of the preceding clauses, further comprising:

arranging a skin adhesive layer on the device , preferably on the bottom portion of the second housing portion. A body associable device obtainable according to any of the preceding clauses. A wet electrode or dry electrode for a body associatable device made according to the method of any of the preceding clauses 1 -12. A body associatable device which can monitor and record individual physiological parameters, e.g., physical activity, heart rate, respiration, temperature, sleep, pulse oxymetry, of a living subject and communicate these parameters beyond the body of the living subject to other devices, e.g., mobile phones, computers, internet servers, which device comprises:

- an inlay substrate,

-an interposer substrate,

- one or more electrodes, whereby the inlay circuit is flexible circuit element electrically coupled to the electrodes and the interposer substrate comprises high density electronics and electrical connections to the interposer substrate couple the electrodes to flexible circuit element of the inlay circuit. The body associatable device according to clause 15 further comprising a standoff arranged between the electrode and a skin adhesive layer. The body associatable device according to clause 16 wherein the standoff functions as a reservoir for a hydrogel and/or to mechanically de-couple the skin adhesive layer. The body associatable device according to any of the clauses 15-17 wherein the electrode is a wet or dry electrode. The body associatable device according to clause 18 further comprising a guard for guarding against stray capacitance resulting from coupling dry electrodes to a living subject. 20. System comprising a body associatable device according to any of the preceding clauses 15-19 and a receiver for receiving signals from the device.

[0066] It is to be understood that this disclosure is not limited to particular embodiments or aspects described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.

[0067] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the present disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the present disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the present disclosure.

[0068] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, representative illustrative methods and materials are now described.

[0069] All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. [0070] It is noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as solely, only and the like in connection with the recitation of claim elements, or use of a negative limitation.

[0071] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope of the present disclosure. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.

[0072] Although the foregoing disclosure has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this disclosure that certain changes and modifications may be made thereto without departing from the scope of the appended claims.

[0073] Accordingly, it will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the present disclosure and are included within its scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the present disclosure and the concepts contributed by the inventors to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. The scope of the present disclosure, therefore, is not intended to be limited to the exemplary aspects and embodiments shown and described herein. Rather, the scope of present disclosure is embodied by the appended claims.

[0074] It is worthy to note that any reference to "one aspect" or "an aspect" means that a particular feature, structure, or characteristic described in connection with the aspect is included in at least one aspect. Thus, appearances of the phrases "in one aspect" or "in an aspect" in various places throughout the specification are not necessarily all referring to the same aspect. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner in one or more aspects.

[0075] Some aspects may be described using the expression "coupled" and "connected" along with their derivatives. It should be understood that these terms are not intended as synonyms for each other. For example, some aspects may be described using the term

"connected" to indicate that two or more elements are in direct physical or electrical contact with each other. In another example, some aspects may be described using the term "coupled" to indicate that two or more elements are in direct physical or electrical contact. The term

"coupled," however, also may mean that two or more elements are not in direct contact with each other, but yet still co-operate or interact with each other.

[0076] While certain features of the aspects have been illustrated as described herein, many modifications, substitutions, changes and equivalents will now occur to those skilled in the art. It is therefore to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the aspects.

Claims

What is claimed is:

1 . A method of manufacturing a body associated device, the method comprising:

providing an inlay substrate comprising a first side, a second side, and at least one conductive trace;

providing an interposer substrate comprising a first side, a second side, and at least one conductive trace; and

coupling the first side of the interposer substrate to the first side of the inlay substrate to form a subassembly;

2. The method of claim 1 , comprising:

applying a hydrogel material in electrical contact with the electrically conductive layer on the first side of the inlay substrate.

3. The method of claim 2, comprising:

inserting at least one standoff defining an aperture over the hydrogel material, wherein at least a portion of the hydrogel material is positioned within the aperture.

4. The method of claim 1 , comprising:

applying a layer of nonconductive adhesive material over the electrically conductive layer formed on the first side of the inlay substrate.

5. The method of claim 4, comprising:

forming at least one electrically conductive guard band on the second side of the inlay substrate substantially opposite to the electrically conductive layer applied to the first side of the inlay substrate.

6. The method of claim 5, comprising: applying at least one dielectric layer stacked above the at least one electrically conductive guard band.

7. The method of claim 4, comprising:

forming at least one electrically conductive guard band on the first side of the inlay substrate substantially surrounding the electrically conductive layer applied to the first side of the inlay substrate.

8. The method of claim 1 , comprising:

providing a first housing portion;

coupling the first housing portion to the second housing portion.

9. The method of claim 8, comprising:

applying a skin adhesive layer to a bottom portion of the second housing portion.

10. A wet electrode for a body associated device made according to a method, the method comprising:

1 1 . The wet electrode of claim 10, wherein the method comprises: applying a hydrogel material in electrical contact with the electrically conductive layer on the first side of the inlay substrate.

12. The wet electrode of claim 1 1 , wherein the method comprises:

13. The wet electrode of claim 1 1 , wherein the method comprises:

providing a first housing portion;

coupling the first housing portion to the second housing portion.

14. The wet electrode of claim 13, wherein the method comprises:

15. A dry electrode for a body associated device made according to a method, the method comprising:

providing an interposer substrate comprising a first side, a second side, and at least one conductive trace;

wherein the at least one conductive trace on the interposer substrate is electrically coupled to the at least one conductive trace on the inlay substrate through the electrically conductive layer; and

16. The dry electrode of claim 15, wherein the method comprises:

17. The dry electrode of claim 16, wherein the method comprises:

applying at least one dielectric layer stacked above the at least one electrically conductive guard band.

18. The dry electrode of clam 15, wherein the method comprises:

19. The dry electrode of clam 15, wherein the method comprises:

forming at least one lateral electrically conductive guard band on the first side of the inlay substrate.

20. The dry electrode of claim 15, wherein the method comprises: