DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: “116” [Fig. 1A]; “124” [Fig. 1A]; “126” [Fig. 1A].
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
The Examiner notes that ¶0027 of the Applicant’s Specification uses reference character “140” to refer to a paperfluidic layer and paperfluidics of paperfluidic layer 106
Appropriate correction is required.
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the abstract is less than 50 words in length. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim(s) 2-3 is/are objected to because of the following informalities:
Claim 2 should read “laser-induced graphene (LIG) electrodes” [line 2].
Claim 3 should read “The wearable biosensor” [line 1].
Appropriate correction is required.
Claim Interpretation
Examiner Notes: currently, NO limitation invokes interpretation under § 112(f).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim(s) 3 and those dependent therefrom is/are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitation “wherein the two LIG electrodes are an anode and a cathode” [lines 1-2], wherein the recited “two LIG electrodes” are considered to lack antecedent basis, as claims 1 [from which claim 3 depends] and 3 fail to previously define two LIG electrodes; and wherein the recited limitation is further considered to render claim 3 indefinite, as it is not clear whether claim 3 is meant to be dependent from claim 2 or not, wherein claim 2 is noted as defining two LIG electrodes [line 2], or whether claim 3 is meant to define two LIG electrodes. For examination purposes, the Examiner has interpreted either identified interpretation to be applicable in light of any prior art applied under § 102 or § 103.
Claim Rejections - 35 USC § 103
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 14, and 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Begtrup (US-20190254641-A1).
Regarding claim 1, Begtrup teaches
A wearable biosensor for real-time quantification of a biomarker in a biofluid, the wearable biosensor comprising:
at least one functional module [see device of Begtrup Fig. 2] wherein the at least one functional module comprises:
a microfluidic layer [The device is attached to skin by an adhesive (not shown), which may be a pressure sensitive, liquid, tacky hydrogel, which promotes robust electrical, fluidic, and iontophoretic contact with skin (Begtrup ¶0058, Fig. 2), wherein the adhesive being configured to allow for fluidic coupling between skin and the microfluidic component is considered to read on the claimed microfluidic layer],
a plurality of multimodal biosensors [The primary sensor 220 measures the presence, concentration, or other property of one or more solutes in sweat. For example, sensor 220 can be an impedance sensor for a cytokine biomarker, an ion-selective electrode to measure sodium, or an electrochemical aptamer-based (EAB) sensor to measure cortisol. One or more secondary sensors 222, such as a drift-free reference electrode, or a sensor to detect the presence of sweat, such as a galvanic skin response sensor, or a sensor to measure the flow rate of sweat, such as a micro-thermal flow rate sensor, or a temperature sensor, or other sensor may also be included (Begtrup ¶0058, Fig. 2)], and
a paperfluidic layer [The microfluidic component 230 could be, for example, paper,… or other means to transport sweat from skin to the sensors (Begtrup ¶0058, Fig. 2)].
However, while Begtrup discloses the use of iontophoresis in the embodiment as depicted by Fig. 2 [The device is attached to skin by an adhesive (not shown), which may be a pressure sensitive, liquid, tacky hydrogel, which promotes robust electrical, fluidic, and iontophoretic contact with skin (Begtrup ¶0058)] and further discloses an iontophoresis induction module in separate embodiments [Sweat stimulation, or sweat activation, can be achieved by known methods. For example, sweat stimulation can be achieved by simple thermal stimulation, chemical heating pad, infrared light, by orally administering a drug, by intradermal injection of drugs such as methylcholine or pilocarpine, and by dermal introduction of such drugs using iontophoresis. A device for iontophoresis may, for example, provide direct current and use large lead electrodes lined with porous material, where the positive pole is dampened with 2% pilocarpine hydrochloride and the negative one with 0.9% NaCl solution (Begtrup ¶0056); A sweat stimulating agent, e.g., carbachol, indicated at 940, is provided on one or both of the electrodes 960, 964 for delivery into the skin through iontophoresis. The electrodes 960, 964 may be activated periodically to deliver multiple, short doses of a sweat stimulant directly to the skin. Alternatively, the electrodes may be activated to deliver an initial, short dose of stimulant to the skin, followed by a delay to allow sweating to begin before subsequent doses of stimulant are administered, or any other stimulation protocol that provides sweat stimulation while minimizing irritation or discomfort at the skin surface (Begtrup ¶0077); The biofluid sensing device 10 can also provide sweat stimulation via iontophoresis using a pair of electrodes, or through sweat stimulating components in the second membrane, as described in the previous embodiments (Begtrup ¶0078)], Begtrup fails to explicitly disclose an iontophoresis induction module in the same embodiment applied to teach claim 1.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup to employ an iontophoresis induction module, so as to facilitate collection of sweat to perform measurements on, and would further amount to mere application of a known technique to a known device (method, or product) ready for improvement to yield predictable results [enable sweat stimulation] [MPEP § 2143(I)(D)].
Regarding claim 14, Begtrup teaches
The wearable biosensor of claim 1, wherein the measured biomarker is one of cortisol [Begtrup ¶0058], a hormone, a drug, a metabolite, a protein, or a pathogen.
Regarding claim 19, Begtrup teaches
The wearable biosensor of claim 1, wherein the biofluid is sweat [Begtrup ¶0058].
Regarding claim 20, Begtrup teaches
The wearable biosensor of claim 1, wherein the biofluid is interstitial fluid [As used herein, “sweat” means a biofluid that is primarily sweat, such as eccrine or apocrine sweat, and may also include mixtures of biofluids such as sweat and blood, or sweat and interstitial fluid, so long as advective transport of the biofluid mixtures (e.g., flow) is primarily driven by sweat. As used herein, “biofluid” may mean any human biofluid, including, without limitation, sweat, interstitial fluid, blood, plasma, serum, tears, and saliva (Begtrup ¶¶0026-0027)].
Claim(s) 2-6, 8, 13, and 15-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Begtrup, as applied to claim 1 above, in further view of Wang et al. (“A wearable electrochemical biosensor for the monitoring of metabolites and nutrients”, NPL attached), hereinafter Wang.
Regarding claim 2, Begtrup teaches
The wearable biosensor of claim 1.
However, Begtrup fails to explicitly disclose wherein the iontophoresis induction module comprises two LIG electrodes coated with hydrogels.
Wang discloses a wearable biosensor for measuring analytes in sweat, wherein Wang discloses an iontophoresis induction module comprising two LIG electrodes coated with hydrogels [The flexible and disposable sensor patch consists of two carbachol-loaded iontophoresis electrodes, a multi-inlet microfluidic module, a multiplexed MIP nutrient sensor array, a temperature sensor and an electrolyte sensor (Fig. 1c–f and Supplementary Fig. 1). All flexible electrode and sensor designs are based on the LEG, which has large surface area, has excellent electrochemical properties and can be produced at a large scale directly on a polyimide (PI) substrate via CO2 laser engraving (Supplementary Fig. 2) (Wang p. 1227), wherein the process of engraving polyimide using a CO2 laser to produce a graphene electrode is considered to read on “laser-induced graphene” (LIG); To make this wearable technology broadly applicable, particularly for sedentary individuals, we utilize here a custom-designed iontophoresis module consisting of the LEG anode and cathode coupled with hydrogels containing muscarinic agent carbachol (carbagel) for sustainable sweat extraction (Wang p. 1229); Hydrogels containing muscarinic agent carbachol was prepared as follows. Briefly, for anode gel, agarose (3% w/w) was added into de-ionized water and then heated to 250 °C under constant stirring. After the mixture was fully boiled and became homogeneous without agarose grains, the mixture was cooled down to 165 °C and 1% carbachol was added to the above mixture. Subsequently, the cooled mixture was slowly poured into pre-made cylindrical moulds or into assembled microfluidic patch and solidified for 10 min at 4 °C. The cathode gel was prepared similarly except that NaCl (1% w/w) was used instead of carbachol (Wang p. 1233)].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup to employ wherein the iontophoresis induction module comprises two LIG electrodes coated with hydrogels, as this modification would amount to mere simple substitution of one known element for another with similar expected results [an iontophoresis module configured to promote sweat stimulation/production to allow for sweat collection] [MPEP § 2143(I)(B)].
Regarding claim 3, Begtrup in view of Wang teaches
The wearable sensor of claim 1, wherein the two LIG electrodes are an anode and a cathode [See corresponding § 112(b) rejection and interpretation of claim 3 above, wherein claim 3 is presently interpreted as being dependent from claim 2; See § 103 modification of claim 2 above; Wang p. 1229].
Regarding claim 4, Begtrup in view of Wang teaches
The wearable biosensor of claim 3, wherein the anode electrode comprises a carbachol-loaded hydrogel coating and is positioned to capture the biofluid [See § 103 modification of claim 3 above; Begtrup ¶0077, Wang p. 1233].
Regarding claim 5, Begtrup in view of Wang teaches
The wearable biosensor of claim 3, wherein the cathode electrode comprises a sodium chloride hydrogel coating [See § 103 modification of claim 3 above; Wang p. 1233] and is configured to complete an electrical circuit [Wang p. 1229, wherein the electrodes being defined as a cathode and a corresponding anode is considered to read on the claimed limitation of completing an electrical circuit].
Regarding claim 6, Begtrup in view of Wang teaches
The wearable biosensor of claim 2, wherein the microfluidic layer comprises an inlet layer [Begtrup ¶0058, Fig. 2, wherein the adhesive being configured to allow for fluidic coupling between skin and the microfluidic component is considered to read on the microfluidic layer comprising an inlet layer].
Regarding claim 8, Begtrup in view of Wang teaches
The wearable biosensor of claim 6.
However, Begtrup in view of Wang as presently applied fails to explicitly disclose wherein the inlet layer comprise two arc shaped openings to allow direct contact between the hydrogel and the skin of a user.
Wang depicts sweat stimulation electrodes coated with carbachol gel, wherein Wang further depicts an inlet layer comprises two arc shaped openings to allow direct contact between the carbachol gel and skin of a user [Schematic (c) and layer assembly (d) of the microfluidic ‘NutriTrek’ patch for sweat induction, sampling and biosensing. T, temperature (Wang p. 1226, Fig. 1c-d); The flexible and disposable sensor patch consists of two carbachol-loaded iontophoresis electrodes, a multi-inlet microfluidic module, a multiplexed MIP nutrient sensor array, a temperature sensor and an electrolyte sensor (Fig. 1c–f and Supplementary Fig. 1). All flexible electrode and sensor designs are based on the LEG, which has large surface area, has excellent electrochemical properties and can be produced at a large scale directly on a polyimide (PI) substrate via CO2 laser engraving (Supplementary Fig. 2). The sensor patch can be easily attached to skin with conformal contact and interfaces with a miniaturized electronic module for on-demand iontophoresis control, in situ signal processing and wireless communication with the user interfaces through Bluetooth (Fig. 1g and Supplementary Figs. 3 and 4) (Wang p. 1227); Schematic of localized sweat sampling based on iontophoretic sweat extraction with muscarinic agents: pilocarpine and carbachol (Wang p. 1229, Fig. 3a, f)].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup in view of Wang to employ wherein the inlet layer comprise two arc shaped openings to allow direct contact between the hydrogel and the skin of a user so as to enable control of iontophoresis.
Regarding claim 13, Begtrup in view of Wang teaches
The wearable biosensor of claim 2, wherein LIG electrodes are fabricated on polyimide sheet [See § 103 modification of claim 2 above; Wang p. 1227].
Regarding claim 15, Begtrup teaches
The wearable biosensor of claim 1.
However, while Begtrup discloses electrodes for sensing particular analytes [Begtrup ¶0058], Begtrup fails to explicitly disclose comprising a first LIG electrode configured as a counter electrode, a second LIG electrode comprising an Ag/AgCl coating, and a pair of working electrodes.
Wang discloses Wang discloses a wearable biosensor for measuring analytes in sweat, wherein Wang discloses a first LIG electrode configured as a counter electrode, a second LIG electrode comprising an Ag/AgCl coating, and a pair of working electrodes [Schematic (c) and layer assembly (d) of the microfluidic ‘NutriTrek’ patch for sweat induction, sampling and biosensing. T, temperature (Wang p. 1226, Fig. 1c-d); The flexible and disposable sensor patch consists of two carbachol-loaded iontophoresis electrodes, a multi-inlet microfluidic module, a multiplexed MIP nutrient sensor array, a temperature sensor and an electrolyte sensor (Fig. 1c–f and Supplementary Fig. 1). All flexible electrode and sensor designs are based on the LEG, which has large surface area, has excellent electrochemical properties and can be produced at a large scale directly on a polyimide (PI) substrate via CO2 laser engraving (Supplementary Fig. 2). The sensor patch can be easily attached to skin with conformal contact and interfaces with a miniaturized electronic module for on-demand iontophoresis control, in situ signal processing and wireless communication with the user interfaces through Bluetooth (Fig. 1g and Supplementary Figs. 3 and 4) (Wang p. 1227), wherein the process of engraving polyimide using a CO2 laser to produce a graphene electrode is considered to read on “laser-induced graphene” (LIG); To prepare the reference electrode, Ag was first modified on the corresponding graphene electrode by multi-current electrodeposition with electrochemical workstation (CHI 832D) at −0.01 mA for 150 s, −0.02 mA for 50 s, −0.05 mA for 50 s, −0.08 mA for 50 s and −0.1 mA for 350 s using a plating solution containing 0.25 M silver nitrate, 0.75 M sodium thiosulfate and 0.5 M sodium bisulfite. To obtain the Ag/AgCl electrode, 0.1 M FeCl3 solution was further dropped on the Ag surface for 30 s, and then 3 µl polyvinyl butyral (PVB) reference cocktail prepared by dissolving 79.1 mg of PVB and 50 mg of NaCl in 1 ml of methanol was dropped on the Ag/AgCl electrode and dried overnight (Wang p. 1232); For example, using Prussian Blue nanoparticles (PBNPs) as the RAR (Supplementary Fig. 11), we developed an MIP–LEG Leu sensor with a log-linear relationship between the peak height decrease and Leu concentration and a sensitivity of 702 nA mm−2 per decade of concentration (Fig. 2f). We established this approach to quantify the physiologically relevant range of all nine essential AAs (that is, Leu, Ile, Val, Trp, Phe, histidine (His), lysine (Lys), methionine (Met) and threonine (Thr)) (Fig. 2g and Supplementary Fig. 16) as well as a number of vitamins, metabolites and lipids (vitamins B6, C, D3 and E, glucose, uric acid, creatine, creatinine and cholesterol) (Fig. 2h and Supplementary Fig. 17). In addition to these nutrients and metabolites, this approach can be easily reconfigured to enable the monitoring of a broad spectrum of biomarkers ranging from hormones (for example, cortisol) to drugs (for example, immunosuppressive drug mycophenolic acid) (Supplementary Fig. 18 and Supplementary Tables 2 and 3). Most of these targets are undetectable continuously by any existing wearable technology. Considering that a total level of multiple nutrients (for example, total BCAAs) is often an important health indicator, a multi-template MIP approach can be used to enable accurate and sensitive detection of the total concentration of multiple targets with a single sensor (Fig. 2i,j). These indirect LEG–RAR–MIP sensors can be regenerated in situ by applying constant potential to the working electrode, which repels the bound target molecules from the MIP layer, achieving prolonged re-usability (Fig. 2k) (Wang p. 1227)].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup to employ a first LIG electrode configured as a counter electrode, a second LIG electrode comprising an Ag/AgCl coating, and a pair of working electrodes, as this modification would amount to mere simple substitution of one known element for another with similar expected results [sensor arrangement of Begtrup for the sensor arrangement of Wang, with similar expected results of providing measurements of concentrations of analytes] [MPEP § 2143(I)(B)].
Regarding claim 16, Begtrup in view of Wang teaches
The wearable biosensor of claim 15, wherein a working electrode of the pair of working electrodes is an LIG electrode comprising an electrochemically synthesized cortisol-specific Molecularly Imprinted Polymer coating for cortisol detection and quantification [As the majority of metabolites and nutrients (for example, BCAAs) are non-electroactive and cannot easily be oxidized under operational conditions, we herein utilize an indirect detection approach involving an RAR layer sandwiched between the LEG and MIP layers to enable rapid quantitation (Fig. 2e)… In addition to these nutrients and metabolites, this approach can be easily reconfigured to enable the monitoring of a broad spectrum of biomarkers ranging from hormones (for example, cortisol) (Wang p. 1227)].
Claim(s) 7 and 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Begtrup in view of Wang, as applied to claim 6 above, in further view of Heikenfeld (US-9867539-B2).
Regarding claim 7, Begtrup in view of Wang teaches
The wearable biosensor of claim 6.
However, while Begtrup does disclose that the inlet layer is made of skin adhesive that is configured to form a mechanically robust interface between the skin of a user and the wearable biosensor [Begtrup ¶0058], Begtrup in view of Wang fails to explicitly disclose wherein the inlet layer is made of double-sided skin adhesive that is configured to form a mechanically robust interface between the skin of a user and the wearable biosensor.
Heikenfeld discloses a wearable biosensor, wherein Heikenfeld discloses a microfluidic inlet layer made of skin adhesive that is configured to form a mechanically robust interface between the skin of a user and the wearable biosensor [Some embodiments of the present invention utilize adhesives to hold the device near the skin (Heikenfeld Col 4:62-64); As shown in FIG. 8, the final device (800) integration involves from the bottom up: skin adhesives 808, electronics 812, 816, and 820, paper microfluidics 832, and a vapor porous top adhesive textile 824. All of these layers are laser cut. The bottom, double-sided adhesive layer is 3M™ Double Coated Polyester Tape (P/N: 1567) and cut to a 1 mm offset larger than the trimmed flex circuit layer. An array of circular pores is also laser cut in the bottom adhesive layer to facilitate sweat 828 transmission to the sensor. Extensive wearability studies have not been performed with the patch in this initial demonstration, and in the event that further breathability is needed by skin areas covered by flexible circuit substrate, then the paper-microfluidics layer can simply be integrated beneath the electronics layer to provide horizontal transport of vapor or fluid (Heikenfeld Col 20:5-23, Fig. 8(a))].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup in view of Wang to employ wherein the inlet layer is made of double-sided skin adhesive that is configured to form a mechanically robust interface between the skin of a user and the wearable biosensor, so as to enable coupling between the biosensor and skin, and as this modification would amount to mere simple substitution of one known element for another with similar expected results [enable coupling between the biosensor and skin] [MPEP § 2143(I)(B)].
Regarding claim 9, Begtrup in view of Wang teaches
The wearable biosensor of claim 6, wherein the inlet layer comprises openings fluidly coupled to the paperfluidic layer for biofluid volume and rate quantification [Begtrup ¶0058, Fig. 2, wherein the adhesive being configured to allow for fluidic coupling between skin and the microfluidic component is considered to read on openings fluidly coupled to the paperfluidic layer].
However, Begtrup in view of Wang fails to explicitly disclose wherein the inlet layer comprises one circular opening fluidly coupled to the paperfluidic layer.
Heikenfeld discloses a wearable biosensor, wherein Heikenfeld discloses a microfluidic inlet layer comprising one circular opening fluidly coupled to a paperfluidic layer [Heikenfeld Col 20:5-23, Fig. 8(a), see circular pores 828].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup in view of Wang to employ wherein the inlet layer comprises one circular opening fluidly coupled to the paperfluidic layer, as this modification would amount to mere application of a known technique to a known device (method, or product) ready for improvement to yield predictable results [enable fluid coupling via a circular opening] [MPEP § 2143(I)(D)].
Regarding claim 10, Begtrup in view of Wang teaches
The wearable biosensor of claim 6, wherein the inlet layer has openings to collect the biofluid for quantifying sodium ion (Na+) and cortisol concentrations [Begtrup ¶0058, Fig. 2, wherein the adhesive being configured to allow for fluidic coupling between skin and the microfluidic component is considered to read on openings fluidly coupled to the paperfluidic layer].
However, Begtrup in view of Wang as presently modified fails to explicitly disclose wherein the inlet layer has three circular openings to collect the biofluid; and wherein biofluid is also collected for quantifying pH.
Heikenfeld discloses a wearable biosensor, wherein Heikenfeld discloses a microfluidic inlet layer comprising three circular openings for collecting biofluid [Heikenfeld Col 20:5-23, Fig. 8(a), see circular pores 828].
Begtrup discloses in the present embodiment applied that additional sensors may be included [Begtrup ¶0058], wherein Begtrup further discloses in a separate embodiment the use of a sensor for quantifying pH in collected biofluid [One or more sensors (not shown) may be located in the evacuation channel 826 for measuring sweat attributes including, for example, concentrations of solutes, sweat rate, pH or salinity (Begtrup ¶0071)].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup in view of Wang to employ wherein the inlet layer has three circular openings to collect the biofluid, as this modification would amount to mere application of a known technique to a known device (method, or product) ready for improvement to yield predictable results [enable fluid coupling via a circular openings] [MPEP § 2143(I)(D)]; and to further employ wherein biofluid is also collected for quantifying pH, as this modification would amount to mere application of a known technique to a known device (method, or product) ready for improvement to yield predictable results [inclusion of an additional sensor for monitoring physiological parameters] [MPEP § 2143(I)(D)].
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Begtrup, as applied to claim 1 above, in further view of Yang et al. (“Wearable and fully printed microfluidic nanosensor for sweat rate, conductivity, and copper detection with healthcare applications”, NPL attached), hereinafter Yang.
Regarding claim 11, Begtrup teaches
The wearable biosensor of claim 1.
However, while Begtrup discloses that the biosensor may be covered by a material that wicks sweat [For continuous monitoring, the microfluidic component 230 could wick sweat past the sensors 220, 222 to a hydrogel component 232, that continuously absorbs and pumps sweat from skin 12 and across the sensors at the rate at which sweat is generated from the skin. The device may be covered with a protective component (not shown), made of material such as one that is porous to sweat, one that wicks sweat like a hydrogel or textile, or one that is impermeable to sweat (Begtrup ¶0058)], Begtrup fails to explicitly disclose the biosensor comprising a paper wicking layer that connects to the paperfluidic layer of the wearable biosensor to efficiently remove accumulated biofluid after quantification is completed.
Yang discloses a wearable biosensor [In this work, we have proved that a fully-printed wearable biosensor for the detection and quantification of copper excreted in sweat is feasible. Furthermore, we integrated in our wearable system an active perspiration stimulating device based on reverse iontophoresis, a simple sweat rate normalization device, and a flexible miniaturized wireless potentiostat managed by a custom smartphone app (Yang p. 9)], wherein Yang further discloses a paper wicking layer that connects to a microfluidic layer of the wearable biosensor to efficiently remove accumulated biofluid after measurements are completed [At the end of the micro-channel, a hole through layer 4 is allowing the sample to exit and come in contact with a paper-based sponge, granting the sample evaporation and emptying the channel after the measurements. This takes the device to the original state and allows its reuse with a second iontophoretic stimulation for a new sweat sample (Yang p. 2-3), wherein the paper-based sponge is considered to define a paper “wicking” layer based on the plain definition of “wick” referring to absorb or drain (a fluid, moisture, etc.) like a wick (https://www.merriam-webster.com/dictionary/wick)].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup to employ a paper wicking layer that connects to the paperfluidic layer of the wearable biosensor to efficiently remove accumulated biofluid after quantification is completed, so as to allow for drainage of the biosensor and enable subsequent sampling.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Begtrup, as applied to claim 1 above, in view of Heikenfeld.
Regarding claim 12, Begtrup teaches
The wearable biosensor of claim 1, wherein the wearable biosensor is encapsulated to minimize biofluid evaporation and to protect the device from environmental contamination [The device may be covered with a protective component (not shown), made of material such as one that is porous to sweat, one that wicks sweat like a hydrogel or textile, or one that is impermeable to sweat (Begtrup ¶0058)].
However, while Begtrup discloses positioning at least a skin adhesive on one side of the biosensor [Begtrup ¶0058, Fig. 2], Begtrup fails to explicitly disclose wherein the wearable biosensor is encapsulated with a skin adhesive.
Heikenfeld discloses a wearable biosensor, wherein the wearable biosensor is encapsulated with a skin adhesive and a medical textile [For packaging and skin adhesion, a survey of numerous medical-grade textiles from 3M™ was conducted to determine which materials would provide maximum adhesion to the wearer's skin and high durability to protect the patch itself. Double sided medical adhesive tape was used below the patch, whereas above the patch, a medical textile covering was added to protect the patch and improve visual aesthetics (all shown in FIG. 8) (Heikenfeld Col 17:8-15, Fig. 8(a))].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup to employ wherein the wearable biosensor is encapsulated with a skin adhesive, so as to protect the biosensor itself.
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Begtrup in view of Wang, as applied to claim 15 above, in further view of Cadogan et al. (“All-solid-state sodium-selective electrode based on a calixarene ionophore in a poly(vinyl chloride) membrane with a polypyrrole solid contact”, NPL attached), hereinafter Cadogan.
Regarding claim 17, Begtrup in view of Wang teaches
The wearable biosensor of claim 15, wherein a working electrode of the pair of working electrodes is an LIG electrode [See § 103 modification of claim 15 above; Wang p. 1227].
However, while Begtrup and Wang each disclose a sensor to quantify sweat Na+ concentration [Begtrup ¶0058; The Na+-selective electrode was prepared as follows: 0.6 µl of Na+-selective membrane cocktail prepared by dissolving 1 mg of Na ionophore X, 0.55 mg sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, 33 mg polyvinyl chloride and 65.45 mg bis(2-ethylhexyl) sebacate into 660 µl of tetrahydrofuran was drop-casted onto the graphene electrode and dried overnight. To obtain the desired stable Na+-sensing performance for long-term continuous measurements, the obtained Na+ sensor was conditioned overnight in 100 mM NaCl (Wang p. 1232)], Begtrup in view of Wang fails to explicitly disclose wherein a working electrode of the pair of working electrodes is an LIG electrode comprising a polypyrrole and sodium ion-selective membrane to quantify sweat Na+ concentration.
Cadogan discloses a sodium-selective electrode, wherein the electrode comprises a polypyrrole and sodium ion-selective membrane to quantify Na+ concentration [As conducting polymers such as PPy also have well-documented electronic conductivity, we propose that PPy could act as a solid contact between a sodium-selective PVC membrane containing an ionophore and a metal contact… Response time measurements involved the injection of 0.450 mL of a 0.1 M solution of NaCl into 50 mL of 10-4 M NaCl, which is close to a 10-fold change in concentration (Cadogan p. 2497); it is clear that the addition of a layer of conducting PPy as a solid contact between Pt and ion selective PVC significantly lowers the charge-transfer resistance and facilitates the transition from ionic to electronic conductivity across the interfaces, i.e. ionic charge transfer at the PVC/solution interface to electronic charge transfer at the Pt/PPy interface (Cadogan p. 2499); The electrode incorporating polypyrrole as a solid contact between platinum and an ion-selective PVC membrane showed improved performance over an electrode without the polypyrrole layer… Analytically the system containing the PPy/PVC solid contact was found to have improved stability characteristics (Cadogan p. 2501), wherein an “ion-selective” electrode is considered to be defined as an electrode for measuring a particular ion concentration, such that the sodium-selective electrode of Cadogan is considered to measure sodium concentration].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup in view of Wang to employ wherein a working electrode of the pair of working electrodes is an LIG electrode comprising a polypyrrole and sodium ion-selective membrane to quantify sweat Na+ concentration, as a polypyrrole and sodium ion-selective membrane is considered to impart improved performance and stability characteristics to the electrode, and as this modification would amount to mere application of a known technique to a known device (method, or product) ready for improvement to yield predictable results [enable electrode measurements of sodium ion concentration] [MPEP § 2143(I)(D)].
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Begtrup in view of Yang, as applied to claim 11 above, in further view of Davis (US-20150087935-A1).
Regarding claim 18, Begtrup in view of Yang teaches
The wearable biosensor of claim 11.
However, Begtrup in view of Yang fails to explicitly disclose wherein the paper wicking layer comprises chromatography paper.
Davis discloses fluid collection and detection systems, wherein Davis discloses known uses of chromatography paper including transportation of fluid across the paper as a microfluidic channel [These sensors exploit microfluidic channels, fabricated from patterned paper (typically, either chromatography paper or a polyester-cellulose blend) with sensing electrodes printed in proximity to these channels. Hydrophobic barriers are created in the paper by wax or polymer patterning on the paper in order to confine liquids in the microchannels. The wicking behavior of these channels can be used to collect and transport the fluid(s) of interest, such as blood, for sensible testing (Davis ¶0112)].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Begtrup in view of Yang to employ wherein the paper wicking layer comprises chromatography paper, as this modification would amount to mere simple substitution of one known element for another with similar expected results [enable transport of fluid across] [MPEP § 2143(I)(B)].
Conclusion
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/SEVERO ANTONIO P LOPEZ/Examiner, Art Unit 3791
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