A guidewire (100; 102; 201; 206; 215; 221; 226; 231; 241; 251; 260; 279; 2201; 2215; 2240; 2250; 301; 321; 341; 361; 401; 421; 501; 701; 801; 921; 941; 1101; 1103; 1105) for monitoring electrophysiological activity in the vicinity of an anatomical site of interest within the vicinity of a lumen within a body, the guidewire further comprising: an elongate body dimensioned for insertion into the lumen; and a sensing tip (110; 112; 210; 222; 229; 232; 234; 242; 252; 280; 281; 2205; 2217; 2244; 2252; 303; 323; 343; 363; 403; 423; 507; 601a; 601b; 621; 661; 703; 803; 923; 927; 943; 947; 1001) electrically and mechanically coupled to the elongate body, configured to interface with the wall of the lumen, the sensing tip configured to convey one or more electrophysiological signals associated with the activity; wherein the sensing tip is characterized by: comprises: a flexible substrate (607; 607a; 607b; 652) dimensioned to form a base and two or more tines (603; 603a; 603b; 651) extending from the base; a plurality of electrodes (202; 209; 217; 218; 227; 228; 233; 253; 266; 282; 2256; 605; 605a; 605b; 925; 945; 1003) formed on the two or more tines of the flexible substrate; one or more microcircuits (130; 2223; 611a; 611b; 637; 653) formed on the base of the flexible substrate; one or more conducting traces (609a; 609b) formed on the flexible substrate providing electrical interconnection between the one or more microcircuits and the plurality of electrodes; and one or more interconnects for coupling at least one of the one or more microcircuits formed on the base of the flexible substrate with one or more power and signal lead wires (204; 268; 613a; 613b); wherein the flexible substrate is rolled (615; 5657) to form the sensing tip an elongate body dimensioned for insertion into the lumen; and a sensing tip (110; 112; 210; 222; 229; 232; 234; 242; 252; 280; 281; 2205; 2217; 2244; 2252; 303; 323; 343; 363; 403; 423; 507; 601a; 601b; 621; 661; 703; 803; 923; 927; 943; 947; 1001) electrically and mechanically coupled to the elongate body, configured to interface with the wall of the lumen, the sensing tip configured to convey one or more electrophysiological signals associated with the activity; wherein the sensing tip is characterized by: comprises: a flexible substrate (607; 607a; 607b; 652) dimensioned to form a base and two or more tines (603; 603a; 603b; 651) extending from the base; a plurality of electrodes (202; 209; 217; 218; 227; 228; 233; 253; 266; 282; 2256; 605; 605a; 605b; 925; 945; 1003) formed on the two or more tines of the flexible substrate; one or more microcircuits (130; 2223; 611a; 611b; 637; 653) formed on the base of the flexible substrate; one or more conducting traces (609a; 609b) formed on the flexible substrate providing electrical interconnection between the one or more microcircuits and the plurality of electrodes; and one or more interconnects for coupling at least one of the one or more microcircuits formed on the base of the flexible substrate with one or more power and signal lead wires (204; 268; 613a; 613b); a flexible substrate (607; 607a; 607b; 652) dimensioned to form a base and two or more tines (603; 603a; 603b; 651) extending from the base; a plurality of electrodes (202; 209; 217; 218; 227; 228; 233; 253; 266; 282; 2256; 605; 605a; 605b; 925; 945; 1003) formed on the two or more tines of the flexible substrate; one or more microcircuits (130; 2223; 611a; 611b; 637; 653) formed on the base of the flexible substrate; one or more conducting traces (609a; 609b) formed on the flexible substrate providing electrical interconnection between the one or more microcircuits and the plurality of electrodes; and one or more interconnects for coupling at least one of the one or more microcircuits formed on the base of the flexible substrate with one or more power and signal lead wires (204; 268; 613a; 613b); wherein the flexible substrate is rolled (615; 5657) to form the sensing tip