ce55ea029c16e3d9a9f8c9e7abe9457b biosensors2025.pdf 724a4787e729f9ee5a27262ff8276b0e479a4cce biosensors2025.pdf fda75d9a04ad27483b2f45b21a76fa478d0bcf2ff9ad5a083a244a2d6a40e42a biosensors2025.pdf Title: The Personal Glucose Meter as the Measurement Principle in Point-of-Care Applications Subject: A personal glucose meter (PGM) is a medical device that measures blood glucose levels and can be found worldwide. Owing to their sensitivity, simplicity, portability, and low cost, PGMs stand as one of the most frequently utilized analytical methods. This work reviews the different applied methodologies for detecting analytes other than glucose employing a PGM and how it can be incorporated for point-of-care diagnosis needs. To visualize the variants, first, a classification is made according to the biorecognition elements used (aptamers, antibodies, etc.), and where the determination of different analytes is done through the glucose signal using different glucose-generating enzymes such as invertase or glucosidase. Transduction can also be based on the use of nanocarriers that generally encapsulate glucose, although it is also possible to find a combination of the two aforementioned strategies. The PGM can also be used for the direct detection of interfering substances of the biosensor, such as NADH or paracetamol. Lastly, we discuss how a PGM might have been implemented to detect COVID-19 and how it could be used on a massive scale for the point-of-care diagnosis of a pandemic. Keywords: glucose biosensor; point-of-care; aptamer; antibody; invertase enzyme label Author: Mònica Cano and Manel del Valle Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Feb 21 04:03:46 2025 CET ModDate: Fri Feb 21 04:10:34 2025 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 8400372 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLFTRW+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 MIKRSI+VnURWPalladioL Type 1 Custom yes yes yes 16 0 PZZNLU+URWPalladioL-Roma Type 1 Custom yes yes yes 21 0 JMRUGE+URWPalladioL-Bold Type 1 Custom yes yes yes 27 0 YVAWOB+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 WHVBUY+CMSY10 Type 1 Builtin yes yes yes 58 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 73 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 76 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 82 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 85 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 88 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 102 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 105 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 111 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 114 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 117 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 130 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 133 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 139 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 142 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 145 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 161 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 164 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 167 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 170 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 183 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 186 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 189 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 192 0 LEVXPH+EURM10 Type 1 Builtin yes yes yes 201 0 LHJAKG+Symbol Type 1C Custom yes yes yes 215 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 220 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 223 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 229 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 232 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 235 0 LHJAKG+Symbol Type 1C Custom yes yes yes 249 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 254 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 257 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 263 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 266 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 269 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 284 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 287 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 293 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 296 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 299 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 316 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 319 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 322 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 325 0 LHJCKL+PalatinoLinotype,Italic TrueType MacRoman yes yes no 328 0 AMHGJK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 338 0 AMHGJL+PalatinoLinotype CID TrueType Identity-H yes yes yes 341 0 AMHGJM+PalatinoLinotype TrueType WinAnsi yes yes no 347 0 AMHGJO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 350 0 AMHGNN+PalatinoLinotype TrueType MacRoman yes yes no 353 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 364 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 367 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 373 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 376 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 379 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 394 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 397 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 403 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 406 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 409 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 424 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 427 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 430 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 433 0 LHJCKL+PalatinoLinotype,Italic TrueType MacRoman yes yes no 436 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 450 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 453 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 459 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 462 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 465 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 477 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 480 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 486 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 489 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 492 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 507 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 510 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 516 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 519 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 522 0 LHJCKL+PalatinoLinotype,Italic TrueType MacRoman yes yes no 525 0 LHIKKE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 539 0 LHIKLF+PalatinoLinotype CID TrueType Identity-H yes yes yes 542 0 LHIKLG+PalatinoLinotype TrueType WinAnsi yes yes no 548 0 LHIKLI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 551 0 LHIKPH+PalatinoLinotype TrueType MacRoman yes yes no 554 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-04-02 02:07:42 CEST RepresentationInformation: biosensors2025.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-04-01 05:05:49 CEST Size: 8400372 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 847 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Type of Assays Based on the Recognition Element Destination: section.2 Children: Item: Title: Aptamers as the Recognition Element Destination: subsection.2.1 Item: Title: Antibodies as the Recognition Element Destination: subsection.2.2 Item: Title: Specific Peptides as Recognition Elements Destination: subsection.2.3 Item: Title: DNA Genes as Recognition Elements Destination: subsection.2.4 Item: Title: Other Bioreceptors Destination: subsection.2.5 Item: Title: Other Detection Strategies: Glucose-Interfering Agents as Detected Species Destination: section.3 Item: Title: COVID Applications Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: The Personal Glucose Meter as the Measurement Principle in Point-of-Care Applications Author: Mònica Cano and Manel del Valle Subject: A personal glucose meter (PGM) is a medical device that measures blood glucose levels and can be found worldwide. Owing to their sensitivity, simplicity, portability, and low cost, PGMs stand as one of the most frequently utilized analytical methods. This work reviews the different applied methodologies for detecting analytes other than glucose employing a PGM and how it can be incorporated for point-of-care diagnosis needs. To visualize the variants, first, a classification is made according to the biorecognition elements used (aptamers, antibodies, etc.), and where the determination of different analytes is done through the glucose signal using different glucose-generating enzymes such as invertase or glucosidase. Transduction can also be based on the use of nanocarriers that generally encapsulate glucose, although it is also possible to find a combination of the two aforementioned strategies. The PGM can also be used for the direct detection of interfering substances of the biosensor, such as NADH or paracetamol. Lastly, we discuss how a PGM might have been implemented to detect COVID-19 and how it could be used on a massive scale for the point-of-care diagnosis of a pandemic. Keywords: glucose biosensor; point-of-care; aptamer; antibody; invertase enzyme label Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Feb 21 04:03:46 CET 2025 ModDate: Fri Feb 21 04:10:34 CET 2025 ID: 0x0bcca9ec223e2ed2a271cb7b32fac961, 0x0bcca9ec223e2ed2a271cb7b32fac961 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: YVAWOB+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: YVAWOB+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: MIKRSI+VnURWPalladioL FontSubset: true FirstChar: 225 LastChar: 225 FontDescriptor: FontName: MIKRSI+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: PZZNLU+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 243 FontDescriptor: FontName: PZZNLU+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: LEVXPH+EURM10 FontSubset: true FirstChar: 11 LastChar: 22 FontDescriptor: FontName: LEVXPH+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true ToUnicode: true Font: BaseFont: WLFTRW+VnURWPalladioL-Bold FontSubset: true FirstChar: 225 LastChar: 225 FontDescriptor: FontName: WLFTRW+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: WHVBUY+CMSY10 FontSubset: true FirstChar: 0 LastChar: 48 FontDescriptor: FontName: WHVBUY+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true ToUnicode: true Font: BaseFont: JMRUGE+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: JMRUGE+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 50, 177, 152, 186 Annotation: Subtype: Link Rect: 34, 167, 77, 174 Annotation: Subtype: Link Rect: 36, 75, 152, 84 Annotation: Subtype: Link Rect: 34, 63, 89, 72 Annotation: Subtype: Link Rect: 34, 773, 152, 809 Annotation: Subtype: Link Rect: 515, 773, 560, 809 Annotation: Subtype: Link Rect: 196, 666, 207, 677 Annotation: Subtype: Link Rect: 349, 295, 356, 303 ActionDest: 561 Annotation: Subtype: Link Rect: 231, 267, 238, 276 ActionDest: 561 Annotation: Subtype: Link Rect: 238, 266, 245, 276 ActionDest: 561 Annotation: Subtype: Link Rect: 406, 253, 413, 262 ActionDest: 561 Annotation: Subtype: Link Rect: 307, 225, 314, 234 ActionDest: 561 Annotation: Subtype: Link Rect: 314, 225, 321, 234 ActionDest: 561 Annotation: Subtype: Link Rect: 213, 169, 220, 178 ActionDest: 561 Annotation: Subtype: Link Rect: 225, 113, 232, 122 ActionDest: 561 Annotation: Subtype: Link Rect: 487, 71, 494, 81 ActionDest: 561 Annotation: Subtype: Link Rect: 421, 27, 560, 37 Annotation: Subtype: Link Rect: 34, 292, 87, 311 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 469, 730, 481, 740 ActionDest: 561 Annotation: Subtype: Link Rect: 484, 731, 496, 740 ActionDest: 561 Annotation: Subtype: Link Rect: 398, 577, 410, 586 ActionDest: 561 Annotation: Subtype: Link Rect: 287, 550, 299, 559 ActionDest: 561 Annotation: Subtype: Link Rect: 263, 522, 275, 531 ActionDest: 561 Annotation: Subtype: Link Rect: 433, 480, 445, 489 ActionDest: 561 Annotation: Subtype: Link Rect: 258, 452, 270, 461 ActionDest: 561 Annotation: Subtype: Link Rect: 329, 424, 341, 433 ActionDest: 561 Annotation: Subtype: Link Rect: 208, 396, 220, 405 ActionDest: 561 Annotation: Subtype: Link Rect: 192, 368, 204, 377 ActionDest: 561 Annotation: Subtype: Link Rect: 519, 341, 531, 350 ActionDest: 561 Annotation: Subtype: Link Rect: 531, 341, 543, 350 ActionDest: 561 Annotation: Subtype: Link Rect: 544, 341, 556, 350 ActionDest: 561 Annotation: Subtype: Link Rect: 333, 129, 345, 138 ActionDest: 561 Annotation: Subtype: Link Rect: 444, 85, 451, 97 ActionDest: 63 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 201, 506, 212, 515 ActionDest: 561 Annotation: Subtype: Link Rect: 277, 335, 289, 344 ActionDest: 561 Annotation: Subtype: Link Rect: 236, 322, 248, 331 ActionDest: 564 Annotation: Subtype: Link Rect: 213, 252, 225, 261 ActionDest: 561 Annotation: Subtype: Link Rect: 551, 221, 558, 233 ActionDest: 92 Annotation: Subtype: Link Rect: 199, 180, 206, 192 ActionDest: 92 Annotation: Subtype: Link Rect: 419, 141, 431, 149 ActionDest: 561 Annotation: Subtype: Link Rect: 377, 112, 389, 122 ActionDest: 564 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 464, 758, 476, 767 ActionDest: 564 Annotation: Subtype: Link Rect: 544, 759, 556, 767 ActionDest: 564 Annotation: Subtype: Link Rect: 336, 717, 348, 726 ActionDest: 564 Annotation: Subtype: Link Rect: 207, 287, 218, 295 ActionDest: 561 Annotation: Subtype: Link Rect: 289, 133, 301, 142 ActionDest: 564 Annotation: Subtype: Link Rect: 412, 75, 419, 87 ActionDest: 151 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 186, 646, 197, 654 ActionDest: 564 Annotation: Subtype: Link Rect: 219, 580, 231, 589 ActionDest: 564 Annotation: Subtype: Link Rect: 212, 552, 224, 561 ActionDest: 564 Annotation: Subtype: Link Rect: 232, 511, 244, 520 ActionDest: 564 Annotation: Subtype: Link Rect: 395, 508, 402, 520 ActionDest: 151 Annotation: Subtype: Link Rect: 433, 410, 440, 422 ActionDest: 198 Annotation: Subtype: Link Rect: 289, 133, 300, 142 ActionDest: 564 Annotation: Subtype: Link Rect: 231, 110, 243, 119 ActionDest: 564 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 212, 567, 219, 579 ActionDest: 198 Annotation: Subtype: Link Rect: 520, 452, 532, 460 ActionDest: 561 Annotation: Subtype: Link Rect: 520, 440, 532, 449 ActionDest: 561 Annotation: Subtype: Link Rect: 520, 428, 532, 437 ActionDest: 561 Annotation: Subtype: Link Rect: 520, 416, 532, 425 ActionDest: 561 Annotation: Subtype: Link Rect: 520, 404, 532, 413 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 385, 532, 394 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 361, 532, 370 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 343, 532, 352 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 330, 532, 339 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 318, 532, 327 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 306, 532, 316 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 294, 532, 304 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 283, 532, 292 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 271, 532, 280 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 259, 532, 268 ActionDest: 564 Annotation: Subtype: Link Rect: 194, 169, 206, 178 ActionDest: 564 Annotation: Subtype: Link Rect: 351, 169, 363, 178 ActionDest: 564 Annotation: Subtype: Link Rect: 353, 111, 360, 123 ActionDest: 198 Annotation: Subtype: Link Rect: 362, 99, 374, 108 ActionDest: 564 Annotation: Subtype: Link Rect: 200, 69, 207, 81 ActionDest: 239 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 225, 703, 237, 712 ActionDest: 564 Annotation: Subtype: Link Rect: 381, 686, 388, 698 ActionDest: 239 Annotation: Subtype: Link Rect: 249, 486, 260, 494 ActionDest: 564 Annotation: Subtype: Link Rect: 509, 398, 521, 407 ActionDest: 564 Annotation: Subtype: Link Rect: 509, 386, 521, 395 ActionDest: 564 Annotation: Subtype: Link Rect: 509, 374, 521, 383 ActionDest: 564 Annotation: Subtype: Link Rect: 509, 362, 521, 371 ActionDest: 564 Annotation: Subtype: Link Rect: 509, 350, 521, 359 ActionDest: 564 Annotation: Subtype: Link Rect: 509, 338, 521, 347 ActionDest: 564 Annotation: Subtype: Link Rect: 378, 247, 390, 257 ActionDest: 564 Annotation: Subtype: Link Rect: 295, 192, 307, 201 ActionDest: 564 Annotation: Subtype: Link Rect: 307, 175, 314, 187 ActionDest: 274 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 349, 613, 360, 621 ActionDest: 564 Annotation: Subtype: Link Rect: 372, 589, 383, 598 ActionDest: 564 Annotation: Subtype: Link Rect: 473, 436, 485, 445 ActionDest: 564 Annotation: Subtype: Link Rect: 268, 408, 280, 417 ActionDest: 564 Annotation: Subtype: Link Rect: 544, 297, 556, 306 ActionDest: 564 Annotation: Subtype: Link Rect: 260, 280, 267, 292 ActionDest: 274 Annotation: Subtype: Link Rect: 520, 165, 532, 174 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 153, 532, 162 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 141, 532, 150 ActionDest: 564 Annotation: Subtype: Link Rect: 520, 123, 532, 132 ActionDest: 564 Annotation: Subtype: Link Rect: 310, 69, 322, 78 ActionDest: 564 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 501, 717, 513, 726 ActionDest: 564 Annotation: Subtype: Link Rect: 362, 675, 374, 684 ActionDest: 564 Annotation: Subtype: Link Rect: 553, 630, 560, 642 ActionDest: 303 Annotation: Subtype: Link Rect: 516, 473, 528, 482 ActionDest: 564 Annotation: Subtype: Link Rect: 516, 461, 528, 470 ActionDest: 564 Annotation: Subtype: Link Rect: 516, 450, 528, 459 ActionDest: 564 Annotation: Subtype: Link Rect: 460, 345, 472, 354 ActionDest: 564 Annotation: Subtype: Link Rect: 288, 331, 300, 340 ActionDest: 564 Annotation: Subtype: Link Rect: 334, 301, 341, 313 ActionDest: 306 Annotation: Subtype: Link Rect: 193, 81, 205, 90 ActionDest: 564 Annotation: Subtype: Link Rect: 237, 78, 244, 90 ActionDest: 306 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 545, 554, 556, 563 ActionDest: 564 Annotation: Subtype: Link Rect: 516, 453, 528, 462 ActionDest: 564 Annotation: Subtype: Link Rect: 516, 442, 528, 451 ActionDest: 564 Annotation: Subtype: Link Rect: 255, 365, 267, 374 ActionDest: 564 Annotation: Subtype: Link Rect: 434, 309, 446, 318 ActionDest: 567 Annotation: Subtype: Link Rect: 417, 265, 429, 277 ActionDest: 332 Annotation: Subtype: Link Rect: 417, 198, 429, 207 ActionDest: 567 Annotation: Subtype: Link Rect: 430, 128, 442, 137 ActionDest: 567 Annotation: Subtype: Link Rect: 348, 114, 360, 123 ActionDest: 567 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 282, 672, 294, 684 ActionDest: 332 Annotation: Subtype: Link Rect: 207, 471, 218, 479 ActionDest: 567 Annotation: Subtype: Link Rect: 186, 85, 197, 93 ActionDest: 567 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 298, 744, 310, 754 ActionDest: 567 Annotation: Subtype: Link Rect: 366, 714, 379, 726 ActionDest: 384 Annotation: Subtype: Link Rect: 209, 605, 221, 614 ActionDest: 567 Annotation: Subtype: Link Rect: 253, 603, 260, 615 ActionDest: 384 Annotation: Subtype: Link Rect: 186, 386, 197, 395 ActionDest: 567 Annotation: Subtype: Link Rect: 516, 298, 528, 307 ActionDest: 567 Annotation: Subtype: Link Rect: 516, 286, 528, 295 ActionDest: 567 Annotation: Subtype: Link Rect: 516, 267, 528, 277 ActionDest: 567 Annotation: Subtype: Link Rect: 516, 250, 528, 259 ActionDest: 567 Annotation: Subtype: Link Rect: 317, 159, 329, 168 ActionDest: 567 Annotation: Subtype: Link Rect: 399, 159, 411, 168 ActionDest: 567 Annotation: Subtype: Link Rect: 295, 143, 307, 155 ActionDest: 414 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 186, 448, 197, 456 ActionDest: 567 Annotation: Subtype: Link Rect: 244, 425, 256, 434 ActionDest: 567 Annotation: Subtype: Link Rect: 553, 353, 560, 365 ActionDest: 414 Annotation: Subtype: Link Rect: 509, 239, 521, 248 ActionDest: 567 Annotation: Subtype: Link Rect: 509, 226, 521, 235 ActionDest: 567 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 423, 756, 435, 768 ActionDest: 440 Annotation: Subtype: Link Rect: 487, 758, 499, 767 ActionDest: 567 Annotation: Subtype: Link Rect: 374, 583, 386, 593 ActionDest: 567 Annotation: Subtype: Link Rect: 217, 514, 229, 523 ActionDest: 567 Annotation: Subtype: Link Rect: 383, 500, 394, 509 ActionDest: 567 Annotation: Subtype: Link Rect: 198, 455, 210, 467 ActionDest: 440 Annotation: Subtype: Link Rect: 362, 206, 373, 215 ActionDest: 567 Annotation: Subtype: Link Rect: 250, 68, 262, 80 ActionDest: 497 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 231, 744, 243, 754 ActionDest: 567 Annotation: Subtype: Link Rect: 276, 743, 282, 754 ActionDest: 497 Annotation: Subtype: Link Rect: 480, 589, 491, 598 ActionDest: 567 Annotation: Subtype: Link Rect: 515, 479, 527, 488 ActionDest: 567 Annotation: Subtype: Link Rect: 515, 451, 527, 460 ActionDest: 567 Annotation: Subtype: Link Rect: 515, 422, 527, 431 ActionDest: 567 Annotation: Subtype: Link Rect: 515, 393, 527, 402 ActionDest: 567 Annotation: Subtype: Link Rect: 515, 359, 527, 368 ActionDest: 567 Annotation: Subtype: Link Rect: 515, 318, 527, 327 ActionDest: 567 Annotation: Subtype: Link Rect: 515, 277, 527, 286 ActionDest: 567 Annotation: Subtype: Link Rect: 515, 237, 527, 246 ActionDest: 567 Annotation: Subtype: Link Rect: 429, 132, 441, 141 ActionDest: 567 Annotation: Subtype: Link Rect: 242, 90, 254, 99 ActionDest: 567 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 342, 758, 354, 767 ActionDest: 567 Annotation: Subtype: Link Rect: 454, 728, 466, 740 ActionDest: 529 Annotation: Subtype: Link Rect: 545, 383, 556, 391 ActionDest: 567 Annotation: Subtype: Link Rect: 527, 221, 539, 230 ActionDest: 567 Annotation: Subtype: Link Rect: 364, 123, 376, 132 ActionDest: 567 Annotation: Subtype: Link Rect: 265, 67, 277, 76 ActionDest: 567 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 489, 717, 501, 726 ActionDest: 567 Annotation: Subtype: Link Rect: 543, 633, 555, 642 ActionDest: 567 Annotation: Subtype: Link Rect: 390, 423, 402, 432 ActionDest: 561 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 472, 645, 510, 656 Annotation: Subtype: Link Rect: 86, 619, 220, 630 Annotation: Subtype: Link Rect: 399, 606, 560, 617 Annotation: Subtype: Link Rect: 56, 594, 76, 605 Annotation: Subtype: Link Rect: 159, 555, 197, 566 Annotation: Subtype: Link Rect: 203, 555, 239, 566 Annotation: Subtype: Link Rect: 140, 531, 177, 541 Annotation: Subtype: Link Rect: 184, 531, 220, 541 Annotation: Subtype: Link Rect: 95, 505, 133, 515 Annotation: Subtype: Link Rect: 139, 505, 175, 515 Annotation: Subtype: Link Rect: 59, 467, 96, 477 Annotation: Subtype: Link Rect: 397, 440, 434, 451 Annotation: Subtype: Link Rect: 441, 440, 477, 451 Annotation: Subtype: Link Rect: 253, 416, 291, 426 Annotation: Subtype: Link Rect: 176, 390, 214, 400 Annotation: Subtype: Link Rect: 224, 365, 261, 375 Annotation: Subtype: Link Rect: 267, 365, 304, 375 Annotation: Subtype: Link Rect: 302, 338, 339, 349 Annotation: Subtype: Link Rect: 462, 326, 499, 337 Annotation: Subtype: Link Rect: 505, 326, 541, 337 Annotation: Subtype: Link Rect: 330, 300, 367, 311 Annotation: Subtype: Link Rect: 374, 300, 410, 311 Annotation: Subtype: Link Rect: 59, 275, 96, 285 Annotation: Subtype: Link Rect: 184, 249, 221, 260 Annotation: Subtype: Link Rect: 227, 249, 263, 260 Annotation: Subtype: Link Rect: 135, 224, 173, 234 Annotation: Subtype: Link Rect: 179, 224, 215, 234 Annotation: Subtype: Link Rect: 287, 185, 324, 196 Annotation: Subtype: Link Rect: 458, 160, 495, 171 Annotation: Subtype: Link Rect: 133, 135, 170, 145 Annotation: Subtype: Link Rect: 261, 108, 299, 119 Annotation: Subtype: Link Rect: 127, 84, 164, 94 Annotation: Subtype: Link Rect: 503, 70, 541, 81 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 322, 743, 360, 754 Annotation: Subtype: Link Rect: 378, 718, 415, 729 Annotation: Subtype: Link Rect: 421, 718, 457, 729 Annotation: Subtype: Link Rect: 224, 693, 261, 703 Annotation: Subtype: Link Rect: 268, 693, 304, 703 Annotation: Subtype: Link Rect: 143, 668, 180, 678 Annotation: Subtype: Link Rect: 345, 641, 383, 652 Annotation: Subtype: Link Rect: 389, 641, 425, 652 Annotation: Subtype: Link Rect: 304, 616, 341, 627 Annotation: Subtype: Link Rect: 427, 590, 465, 601 Annotation: Subtype: Link Rect: 471, 590, 507, 601 Annotation: Subtype: Link Rect: 485, 565, 523, 576 Annotation: Subtype: Link Rect: 173, 526, 210, 537 Annotation: Subtype: Link Rect: 104, 489, 142, 499 Annotation: Subtype: Link Rect: 148, 489, 184, 499 Annotation: Subtype: Link Rect: 292, 462, 329, 473 Annotation: Subtype: Link Rect: 335, 462, 372, 473 Annotation: Subtype: Link Rect: 361, 437, 399, 448 Annotation: Subtype: Link Rect: 288, 411, 325, 422 Annotation: Subtype: Link Rect: 359, 386, 396, 397 Annotation: Subtype: Link Rect: 82, 361, 119, 371 Annotation: Subtype: Link Rect: 301, 335, 339, 346 Annotation: Subtype: Link Rect: 379, 309, 416, 320 Annotation: Subtype: Link Rect: 283, 271, 320, 282 Annotation: Subtype: Link Rect: 325, 246, 362, 256 Annotation: Subtype: Link Rect: 176, 208, 214, 218 Annotation: Subtype: Link Rect: 502, 182, 540, 193 Annotation: Subtype: Link Rect: 205, 156, 242, 167 Annotation: Subtype: Link Rect: 249, 156, 285, 167 Annotation: Subtype: Link Rect: 351, 130, 389, 141 Annotation: Subtype: Link Rect: 299, 105, 337, 116 Annotation: Subtype: Link Rect: 59, 80, 96, 90 Page: Sequence: 20 Annotations: Annotation: Subtype: Link Rect: 355, 743, 392, 754 Annotation: Subtype: Link Rect: 151, 719, 189, 729 Annotation: Subtype: Link Rect: 450, 692, 488, 703 Annotation: Subtype: Link Rect: 494, 692, 530, 703 Annotation: Subtype: Link Rect: 225, 668, 263, 678 Annotation: Subtype: Link Rect: 281, 641, 319, 652 Annotation: Subtype: Link Rect: 520, 616, 557, 627 Annotation: Subtype: Link Rect: 349, 590, 387, 601 Annotation: Subtype: Link Rect: 357, 565, 395, 576 Annotation: Subtype: Link Rect: 401, 565, 437, 576 Annotation: Subtype: Link Rect: 95, 527, 133, 537 Annotation: Subtype: Link Rect: 243, 501, 281, 512 Annotation: Subtype: Link Rect: 520, 475, 557, 486 Annotation: Subtype: Link Rect: 113, 450, 150, 461 Annotation: Subtype: Link Rect: 262, 425, 300, 435 Annotation: Subtype: Link Rect: 391, 399, 429, 410 Annotation: Subtype: Link Rect: 131, 361, 168, 371 Annotation: Subtype: Link Rect: 418, 335, 456, 346 Annotation: Subtype: Link Rect: 182, 310, 219, 320 Annotation: Subtype: Link Rect: 225, 310, 262, 320 Annotation: Subtype: Link Rect: 213, 284, 251, 295 Annotation: Subtype: Link Rect: 257, 284, 293, 295 Annotation: Subtype: Link Rect: 379, 258, 416, 269 Annotation: Subtype: Link Rect: 423, 258, 459, 269 Annotation: Subtype: Link Rect: 380, 233, 418, 244 Annotation: Subtype: Link Rect: 424, 233, 460, 244 Checksum: 603e590e Type: CRC32 Checksum: ce55ea029c16e3d9a9f8c9e7abe9457b Type: MD5 Checksum: 724a4787e729f9ee5a27262ff8276b0e479a4cce Type: SHA-1 Checksum: fda75d9a04ad27483b2f45b21a76fa478d0bcf2ff9ad5a083a244a2d6a40e42a Type: SHA-256