(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date _ . ... _ . 14 July 2011 (14.07.2011) WO 2011/084768 Al (51) International Patent Classification: Ridge, Loveland, OH 45 140 (US). ARONHALT, Tay¬ A61B 17/00 (2006.01) A61B 19/10 (2006.01) lor, W. [US/US]; 306 Beech Road, Loveland, OH 45140 (US). (21) International Application Number: PCT/US20 10/06 1422 (74) Agents: JOHNSON, Philip, S. et al; Johnson & John son, 1 Johnson & Johnson Plaza, New Brunswick, NJ (22) International Filing Date: 08933 (US). 2 1 December 2010 (21 .12.2010) (81) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of national protection available): AE, AG, AL, AM, (26) Publication Langi English AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (30) Priority Data: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 61/288,375 2 1 December 2009 (21 .12.2009) US HN, HR, HU, ID, JL, IN, IS, JP, KE, KG, KM, KN, KP, 12/971,249 17 December 2010 (17.12.2010) US KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (71) Applicant (for all designated States except US): ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, ETHICON ENDO-SURGERY, INC. [US/US]; 4545 NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, Creek Road, Cincinnati, OH 45242 (US). SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (72) Inventors; and (75) Inventors/ Applicants (for US only): CLYMER, Jeffrey, (84) Designated States (unless otherwise indicated, for every W. [US/US]; 4354 Hyacinth Drive, Mason, OH 45040 kind of regional protection available): ARIPO (BW, GH, (US). MALAVIYA, Prasanna [US/US]; 5840 Maxfli GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, Lane, Mason, OH 45040 (US). KORVICK, Donna, L. ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, [US/US]; 8158 Worcester Drive, Maineville, OH 45309 TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (US). HOUSER, Kevin, L. [US/US]; 570 Foliage Lane, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, Springboro, OH 45066 (US). KIMBALL, Cory, G. [US/ SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, US]; 6136 Lagrange Lane, Cincinnati, OH 45239 (US). GW, ML, MR, NE, SN, TD, TG). STULEN, Foster, B. [US/US]; 6245 Bridgewater Court, Mason, OH 45040 (US). SHELTON, Frederick, E., IV Declarations under Rule 4.17 : [US/US]; 245 E. Main Street, Hillsboro, OH 45 153 (US). — as to the identity of the inventor (Rule 4.17(i)) BAXTER, Chester, O., Ill [US/US]; 6375 Pawnee [Continued on next page] (54) Title: SURGICAL DEVICE USING BIOMARKERS 00 0 o0 (57) Abstract: Biomarkers are collected and used to determine biological propensities of a patient, to determine the efficacy of medical devices, to select and administer therapeutic agents, to select medical devices, to make adjustments to medical devices, and/or to adjust surgical techniques. An apparatus includes a port to draw a biological fluid (e.g., a mist) from a surgical site. The o apparatus includes a sensor having a cantilevered beam. The beam includes substances selected to attract certain biomarkers as the fluid is communicated across the beam. The same apparatus or another apparatus is used to administer a therapeutic agent based at least in part on collected biomarker data. The therapeutic agent delivery apparatus may include a device that is also used to create a wound at a surgical site. For instance, a harmonic surgical instrument may be used to both collect biomarkers and administer a therapeutic agent (e.g., gene therapy using sonoporation). w o 2011/084768 Al III III II II III I I1 1 lll l II llll 11III II I II Published: as to applicant's entitlement to apply for and be granted a patent (Rule 4.1 7( )) — with international search report (Art. 21(3)) as to the applicant's entitlement to claim the priority of — before the expiration of the time limit for amending the the earlier application (Rule 4.17(Hi)) claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) SURGICAL DEVICE USING BIOMARKERS Jeffrey W. Clymer Prasanna Malaviya Donna L. Korvick Kevin L. Houser Cory G. Kimball Foster B. Stulen Frederick E Shelton IV Chester O. Baxter III Taylor W. Aronhalt PRIORITY [0001] This application claims priority to U.S. Provisional Patent Application Serial No. 61/288,375, entitled "Method of Developing Surgical Devices Using Biomarkers," filed December 21, 2009, and to U.S. Nonprovisional Patent Application Serial No. 12/971,249, entitled "Use of Biomarkers and Therapeutic Agents with Surgical Devices," filed December 17, 2010, the disclosures of which are incorporated by reference herein. BACKGROUND [0002] Tissue trauma resulting in a wound may be an unavoidable consequence of accidental or intentional injury (e.g., from surgery, etc.). The process of wound healing is thought by some to take place in four stages. The first stage is hemostasis which may begin immediately after the cutting occurs. In hemostasis, clotting may occur by natural means of platelet degranulation. Hemostasis may also be induced by artificial means to affect protein denaturation. The second stage is inflammation. In this stage, the immune system may provide a response to the threat of possible infection via signaling to defensive immune cells such as neutrophils and macrophages. The third stage is the proliferation stage. In this stage, fibroblasts may enter the wound area and produce large amounts of collagen that result in scar formation. A prolonged hemostatic or inflammatory stage may result in additional scar formation that delays both this third stage and the final stage of wound healing. The final stage of wound healing is remodeling. This may occur once a scar has formed and the breaking strength of the wound begins to increase. In this stage, the temporary collagen may be replaced by permanent tissue and the scar slowly fades. The duration of this final stage may depend upon how much scar tissue was formed in the previous stage. [0003] While a variety of methods for monitoring the progress of wound healing have been made and used, it is believed that no one prior to the inventor(s) has made or used the technology as described herein. BRIEF DESCRIPTION OF THE DRAWINGS [0004] While the specification concludes with claims which particularly point out and distinctly claim this technology, it is believed this technology will be better understood from the following description of certain examples taken in conjunction with the accompanying drawings, in which like reference numerals identify the same elements and in which: [0005] FIG. 1 depicts a flow diagram of an exemplary method of processing biomarkers; [0006] FIG. 2 depicts a side view of an exemplary harmonic surgical instrument having a biomarker collection feature; [0007] FIG. 3 depicts a partial view of the end effector of the harmonic surgical instrument of FIG. 2; [0008] FIG. 4 depicts a schematic view of an exemplary biomarker collection and processing system; [0009] FIG. 5 depicts a schematic view of biomarker processing components of the system of FIG. 4; [00010] FIG. 6 depicts a partial perspective view of a biomarker sensor of the system of FIG. 4, during a biomarker collection phase; [00011] FIG. 7 depicts a partial perspective view of the biomarker sensor of FIG. 6, during a sensor cleansing phase; [00012] FIG. 8 depicts a schematic view of an exemplary surgical instrument system including biomarker sensor feedback, where the biomarker sensor feedback is used to automatically control or adjust a surgical instrument; [00013] FIG. 9 depicts a schematic view of another exemplary surgical instrument system including biomarker sensor feedback, where the biomarker sensor feedback is used to control an agent administration device; [00014] FIG. 10 depicts a schematic view of another exemplary surgical instrument system including biomarker sensor feedback, where biomarker sensor feedback is provided to the user through a user feedback feature of a surgical instrument; [00015] FIG. 11 depicts a schematic view of another exemplary surgical instrument system including biomarker sensor feedback, where biomarker sensor feedback is provided to the user through a dedicated user feedback device; [00016] FIG. 12 depicts a schematic view of an exemplary gastric band system including biomarker sensor feedback, where biomarker sensor feedback is used to automatically adjust a gastric band; [00017] FIG. 13 depicts a schematic view of another exemplary gastric band system including biomarker sensor feedback, where biomarker sensor feedback is used to provide implant-originated feedback to a patient or clinician; [00018] FIG. 14 depicts a schematic view of an exemplary drug infusion system including biomarker sensor feedback, where biomarker sensor feedback is used to provide automatic adjustment of drug delivery by a drug infusion device; [00019] FIG. 15 depicts a partial perspective view of the distal end of an exemplary harmonic surgical instrument with a harmonic blade having a therapeutic agent delivery feature; [00020] FIG. 16 depicts a partial perspective view of the distal end of another exemplary harmonic surgical instrument with a harmonic blade having a therapeutic agent delivery feature; [00021] FIG. 17 depicts a partial perspective view of the distal end of another exemplary harmonic surgical instrument with a harmonic blade having a therapeutic agent delivery feature; [00022] FIG.