Nghiên cứu và chế tạo cảm biến sinh học điện hóa độ nhạy cao sử dụng điện cực in các bon ứng dụng trong chẩn đoán bệnh sớm

TR B GIÁO D C VẨ ẨO T O NG I H C BÁCH KHOA HÀ N I TH NG C TRÂM NGHIÊN C U VÀ CH T O C M BI N SINH H C I N HÓA NH Y CAO S D NG I N C C IN CÁC BON NG D NG TRONG CH N OỄN B NH S M LU N ÁN TI N S V T LÝ K THU T Hà N i - 2019 TR B GIÁO D C VẨ ẨO T O NG I H C BÁCH KHOA HÀ N I TH NG C TRÂM NGHIÊN C U VÀ CH T O C M BI N SINH H C I N HÓA NH Y CAO S D NG I N C C IN CÁC BON NG D NG TRONG CH N OỄN B NH S M Ngành: V t lý k thu t Mã s : 9520401 LU N ÁN TI N S V T LÝ K THU T NG IH NG D N KHOA H C: PGS.TS Tr ng Th Ng c Liên GS.TS Patrick Wagner Hà N i - 2019 L IC M N L i đ u tiên, tơi xin bày lịng bi t n sơu s c nh t đ n t p th cán b h ng d n PGS.TS Tr ng Th Ng c Liên tr ng i h c Bách khoa Hà N i GS.TS Patrick Wagner tr ng i h c KU Leuven, V ng qu c B đư nhi t tình ch b o, đ nh h ng vƠ giúp đ v m t khoa h c đ tơi có th hồn thành lu n án ti n s Tơi xin chân thành c m n thành viên phịng thí nghi m C m bi n sinh h c thu c B môn V t li u i n t , phịng thí nghi m c a GS Yoshiakia Ukita thu c i h c Yamanashi Nh t B n, phịng thí nghi m tr ng m Qu c gia v V t li u Linh ki n i n t , Phịng thí nghi m Siêu c u trúc Công ngh nano y sinh thu c Vi n V sinh d ch t , Khoa V t lý tr ng i h c Khoa h c T nhiên - i h c Qu c gia Hà N i đư giúp đ t o u ki n thu n l i giúp th c hi n thí nghi m th i gian nghiên c u Tôi xin chân thành c m n s h tr tài c a đ tài NAFOSTED mã s 103.99.2012.12, đ tài VLIR-UOS mã s ZEIN2013RIP022 vƠ đ tài AUN/SEED-Net CRC 2016-2018 Tôi xin c m n t i ban lưnh đ o Vi n V t lý k thu t tr ng i h c Bách khoa Hà N i đư t o u ki n thu n l i h tr th i gian h c t p Tôi c ng xin c m n t p th th y cô, anh ch b n bè đ ng nghi p thu c b môn V t li u n t , Vi n Hóa h c Vi n Công ngh sinh h c ậ Vi n Hàn lâm Khoa h c Công ngh Vi t Nam đư h tr đóng góp nh ng ý ki n q báu v m t chun mơn trình th c hi n đ tài Cu i cùng, tác gi xin dành nh ng tình c m chân thành sâu s c nh t t i gia đình đư ln sát cánh, chia s nh ng khó kh n, thơng c m đ ng viên su t trình h c t p, nghiên c u Tác gi Th Ng c Trâm I L I CAM OAN Tác gi xin cam đoan đơy lƠ cơng trình nghiên c u tác gi th c hi n d i s h ng d n c a PGS.TS Tr ng Th Ng c Liên GS.TS Patrick Wagner Các s li u k t qu lu n án trung th c vƠ ch a đ c tác gi khác công b b t k cơng trình T t c cơng trình đư cơng b chung v i th y h ng d n khoa h c vƠ đ ng nghi p đ u đ c s đ ng ý c a tác gi tr c đ a vƠo lu n án Hà N i, ngày…… tháng……n m 2019 TM t p th h PGS.TS Tr ng d n Tác gi lu n án ng Th Ng c Liên Th Ng c Trâm II M CL C DANH M C KÝ HI U VÀ CH VI T T T viii DANH M C CÁC B NG x DANH M C CÁC HÌNH NH, M TH xi U CH NG C M BI N SINH H C I N HÓA NG D NG CH N OỄN B NH S M 1.1 C m bi n sinh h c 1.1.1 u thu sinh h c 1.1.2 B ph n chuy n đ i tín hi u 13 1.1.3 Ph ng pháp c đ nh đ u thu sinh h c 15 1.1.4 Các ph ng pháp c đ nh kháng th 17 1.1.4.1 H p ph v t lý 18 1.1.4.2 Liên k t c ng hóa tr 18 1.1.4.3 Ái l c t ng tác sinh h c 20 1.2 C m bi n sinh h c n hóa 21 1.2.1 i n c c n hóa 21 1.2.2 Phân lo i c m bi n sinh h c n hóa 24 1.2.2.1 C m bi n đo dòng 24 1.2.2.2 C m bi n đo n th 26 1.2.2.3 C m bi n đo đ d n 28 1.2.2.4 C m bi n đo ph t ng tr 29 1.3 Ung th vƠ m t s ch t ch d u kh i u 32 1.3.1 Ch d u -hCG vƠ ung th t bào m m tinh 34 1.3.2 Ch d u PSA vƠ ung th ti n li t n 35 1.3.3 Ch d u AFP vƠ ung th gan nguyên phát 36 1.4 Nghiên c u v c m bi n sinh h c n hóa ng d ng phát hi n ch d u kh i u 36 1.4.1 Tình hình nghiên c u ngoƠi n c 36 1.4.2 Tình hình nghiên c u n c 47 1.4.3 nh h ng nghiên c u c a lu n án 47 III CH NG TH C NGHI M VẨ CỄC PH 2.1 Ph NG PHỄP NGHIểN C U 49 ng pháp n hóa 49 2.1.1 Ph ng pháp ph t ng tr n hóa (EIS) 49 2.1.1.1 Mơ hình m ch n t ng đ ng Randles 50 2.1.1.2 Bi u di n ph t ng tr m t ph ng ph c 51 2.1.2 Ph 2.2 Ph ng pháp quét th tu n hoàn (CV) 53 ng pháp kh o sát tính ch t hình thái h c v t li u 54 2.2.1 nh hi n vi n t quét phát x tr 2.2.2 Ph tán x n ng l ng (FE-SEM) 54 ng tia X (EDS) 54 2.2.3 Ph tán x Raman 54 2.3 Công ngh vi l u ly tơm 55 2.3.1 Gi i thi u 55 2.3.2 Thi t k quy trình ch t o chíp vi l u ly tơm 55 2.3.3 V n chuy n dung d ch chíp vi l u ly tơm 57 2.4 Quy trình th c nghi m ch t o c m bi n 58 2.4.1 T ng h p h t nano vƠng n c c làm vi c SPCE 58 2.4.2 MƠng đ n l p t l p ghép (SAM) alkanethiol 58 2.4.3 T ng h p v t li u polyme b ng ph ng pháp trùng h p n hóa 59 2.4.3.1 Polyme đ ng trùng h p PPy-PPa 59 2.4.3.2 V t li u lai c u trúc nano hai chi u gi a polyme đ ng trùng h p PPy-PPa erGO 60 2.4.3.3 V t li u lai poly(p-ATP) h t nano vàng 61 2.4.4 C đ nh đ u thu sinh h c b ng liên k t c ng hóa tr 61 2.4.4.1 Liên k t c ng hóa tr thơng qua nhóm amin c a đ u thu sinh h c 62 2.4.4.2 Liên k t c ng hóa tr thơng qua nhóm cacboxyl c a đ u thu sinh h c 63 2.5 Kh o sát ho t đ ng c a c m bi n ph t ng tr n hóa 63 2.6 Quy ho ch s li u th c nghi m 65 2.6.1 nh y c a c m bi n 65 2.6.2 Kho ng n tính c a c m bi n 66 2.6.3 l p l i c a c m bi n 66 2.6.4 Gi i h n phát hi n c a c m bi n 66 IV 2.6.5 ch n l c c a c m bi n 67 CH NG C M BI N MI N D CH PHÁT HI N CH D U -hCG NG D NG CH N OỄN U T BÀO M M TINH 68 3.1 M đ u 68 3.2 Th c nghi m 69 3.2.1 Hóa ch t 69 3.2.2 i n c c linh ki n 70 3.2.3 Quy trình c đ nh mAb hCG n c c vàng 71 3.2.4 Kh o sát ho t đ ng c a c m bi n mAb hCG/SAM(MHDA)/QCM 72 3.2.4.1 Vi cân tinh th th ch anh 72 3.2.4.2 Kh o sát ho t đ ng c a c m bi n 73 3.2.5 Kh o sát ho t đ ng c a c m bi n mAb hCG/SAM(MHDA)/SPAuE 73 3.3 K t qu th o lu n 74 3.3.1 C m bi n mi n d ch nh y kh i l ng mAb hCG/SAM(MHDA)/QCM 74 3.3.1.1 Hi u su t c đ nh kháng th 74 3.3.1.2 c tr ng chu n c a c m bi n 75 3.3.2 C m bi n mi n d ch ph t ng tr mAb hCG/SAM(MHDA)/SPAuE 77 3.3.2.1 c tính n hóa sau m i b 3.3.2.2 c tr ng chu n c a c m bi n 79 c công ngh 77 3.4 K t lu n 81 CH NG C M BI N APTAMER PHÁT HI N CH D U PSA NG D NG CH N OỄN UNG TH TI N LI T TUY N 82 4.1 M đ u 82 4.2 Th c nghi m 83 4.2.1 Hóa ch t 83 4.2.2 i n c c linh ki n 84 4.2.3 T ng h p h t nano vƠng n c c SPCE 84 4.2.4 C đ nh aptamer 86 4.3 K t qu th o lu n 87 4.3.1 C m bi n aptamer ph t ng tr n hóa 87 4.3.2 C m bi n PSA-aptamer/SAM (MHDA)/SPAuE 88 V 4.3.2.1 c tính n hóa sau m i b 4.3.2.2 nh h c công ngh 88 ng c a n ng đ aptamer lên tín hi u c m bi n 89 4.3.3 C m bi n PSA-aptamer/SAM (MHDA)/AuNPs-SPCE 90 4.3.3.1 Phân tán aptamer 90 4.3.3.2 c tính n hóa sau m i b 4.3.3.3 c tr ng chu n c a c m bi n 95 4.3.3.4 ch n l c c a c m bi n 97 c công ngh 93 4.4 K t lu n 97 CH NG C M BI N MI N D CH PHÁT HI N CH D U AFP NG D NG CH N OỄN UNG TH GAN 98 5.1 M đ u 98 5.2 Th c nghi m 99 5.2.1 Hóa ch t vƠ n c c 99 5.2.2 C đ nh mAb AFP lên n c c PPy-PPa/SPCE PPy-PPa/erGO-SPCE 99 5.2.3 C đ nh mAb AFP lên n c c SPCE bi n tính b i SAM (p-ATP) 100 5.2.4 C đ nh mAb AFP lên n c c SPCE bi n tính b i v t li u lai poly(p-ATP) h t nano vàng 100 5.3 K t qu th o lu n 101 5.3.1 C m bi n mi n d ch n hóa mAb AFP/PPy-PPa/SPCE 101 5.3.1.1 Polyme đ ng trùng h p PPy-PPa n c c SPCE 101 5.3.1.2 T i u hóa t s h p ph n c a monome Pa v i Py 103 5.3.1.3 c tr ng chu n c a c m bi n 104 5.3.2 C m bi n mi n d ch n hóa mAb AFP/PPa-PPy/erGO-SPCE 107 5.3.2.1 Kh n hóa GO SPCE 107 5.3.2.2 Hình thái h c b m t n c c 111 5.3.2.3 c tr ng chu n c a c m bi n 112 5.3.3 C m bi n mi n d ch n hóa mAb AFP/SAM (p-ATP)/AuNPs-SPCE 115 5.3.3.1 nh h ng c a m t đ h t nano vàng 115 5.3.3.2 nh h ng c a th i gian t o màng SAM 118 5.3.3.3 c tr ng n hóa sau m i b 5.3.3.4 c tr ng chu n c a c m bi n 120 c công ngh 119 VI 5.3.4 C m bi n mi n d ch n hóa mAb AFP/poly(p-ATP)/AuNPs-SPCE 121 5.3.4.1 Poly(p-ATP) k t h p h t nano vàng n c c AuNPs-SPCE 122 5.3.4.2 Ph tán x Raman c a màng poly(p-ATP)/AuNPs-SPCE 124 5.3.4.3 c tr ng n hóa sau b 5.3.4.4 c tr ng chu n c a c m bi n 126 c công ngh 125 5.4 K t lu n 128 CH NG C M BI N I N HÓA GLUCOSE 129 6.1 Glucose vƠ đ ng huy t 129 6.2 C m bi n n hóa enzyme GOx 130 6.3 Polyme ơxy hóa kh Osmium c m bi n GOx 133 6.4 Th c nghi m 133 6.4.1 Hóa ch t thi t b 133 6.4.2 Quy trình ch t o c m bi n (GOx/Osmium)n/AuNPs-SPCE 134 6.5 K t qu th o lu n 135 6.5.1 Kh o sát hình thái b m t c u trúc đa l p (GOx/Osmium) 135 6.5.2 Kh o sát nh h ng c a s l p (GOx/Osmium) 136 6.5.3 áp ng dòng-th c a c m bi n (GOx/Osmium)4/AuNPs-SPCE 137 6.6 K t lu n 138 K T LU N 139 KI N NGH 140 TÀI LI U THAM KH O 141 DANH M C CÁC CƠNG TRÌNH CƠNG B C A LU N ÁN 160 PH L C VII DANH M C Kụ HI U VẨ CH Ký hi u VI T T T Ti ng Anh Ti ng Vi t Ab Antibody Kháng th AFP Alpha-fetoprotein Ag Antigen Kháng nguyên AuNPs Gold nano-particles H t nano vàng BSA Bovine serum albumin Albumin huy t bò CA Chronoamperometry K thu t đo dòng ậ th i gian CV Cyclic voltammetry K thu t quét th tu n hoàn DNA Deoxyribo nucleic acid Axít deoxyribonucleic DPV Different pulse voltammetry K thu t đo dòng-th xung vi phân EDC 1-ethyl-3-(3-dimethylaminopropyl) carbodimide EDS Energy dispertive spectroscopy Ph tán x n ng l EIS Electrochemical impedance spectroscopy Ph t ng tr n hóa ELISA Enzyme linked immuno sorbent assay K thu t mi n d ch g n enzyme FAD Flavin adenine dinucleotide GDH Glucose dehydrogenase Enzyme glucose dehydrogenase GMC Graphitized mesoporous carbon Các bon l x p trung bình GOx Glucose oxidase Enzyme 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đoán b nh s m” (ch p nh n đ n h p l ngày 26/06/2018) 160 PH L C Ph l c Giá tr thành hCG/SAM(MHDA)/SPAuE ph n m ch t ng đ ng Randles c a c m bi n N ng đ kháng nguyên -hCG (ng/mL) Rs (k) Rct (k) Cdl (F) 1,60 ± 0,09 9,35 ± 1,8 3,04 ± 0,01 0,1 1,65 ± 0,10 9,41 ± 1,9 2,79 ± 0,02 1,66 ± 0,10 16,5 ± 2,9 2,46 ± 0,02 10 1,49 ± 0,09 19,8 ± 4,7 2,38 ± 0,01 20 1,69 ± 0,09 21,3 ± 2,4 2,05 ± 0,02 30 1,59 ± 0,10 24,7 ± 4,3 1,96 ± 0,02 70 1,55 ± 0,09 32,4 ± 2,5 1,90 ± 0,02 100 1,60 ± 0,09 38,1 ± 5,4 1,75 ± 0,02 mAb Thành ph n m ch Randles Ph l c Giá tr thành ph n m ch t ng đ ng Randles aptamer/SAM(MHDA)/SPAuE v i n ng đ aptamer (5 µg/mL, 50 µg/mL) c m bi n PSA- N ng đ kháng nguyên PSA (ng/mL) µg/mL aptamer /MHDA/ SPAuE 50 µg/mL aptamer /MHDA/ SPAuE Rs (kΩ) Rct (kΩ) Cdl (µF) Rs (kΩ) Rct (kΩ) Cdl (µF) 8,65 9,29 2,44 8,93 20,70 6,46 8,83 8,23 1,85 9,97 19,45 7,35 9,41 6,13 1,13 9,93 18,76 7,03 8,89 7,02 1,23 9,57 18,51 6,91 8,88 7,39 1,30 9,57 18,62 6,95 10 8,67 7,54 1,20 9,17 18,40 6,94 12 8,72 7,67 1,14 9,17 18,23 6,87 14 8,71 7,72 1,15 8,93 20,70 6,46 Giá tr thành ph n c a m ch t -1- ng đ ng Randles Ph l c Giá tr thành ph n m ch t ng đ ng Randles c a c m bi n PSAaptamer/SAM(MHDA)/AuNPs-SPCE v i vòng quét t o h t nano vàng n ng đ aptamer khác (5 µg/mL, 10 µg/mL, 25 µg/mL, 50 µg/mL, 100 µg/mL) PSA/aptamer/MHDA/5 CVs AuNPs-SPCE Giá tr thành ph n m ch t ng đ ng Randles N ng đ Aptamer Aptamer Aptamer Aptamer Aptamer PSA µg/mL 10 µg/mL 25 µg/mL 50 µg/mL 100 µg/mL ng/mL Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) 1,496 3,944 2,691 2,558 1,539 4,173 1,422 4,906 1,650 3,551 1,501 3,806 2,911 2,544 1,743 3,940 1,553 4,683 1,662 3,327 1,623 3,773 2,914 2,501 1,893 3,856 1,613 4,533 1,832 3,042 1,673 3,663 2,958 2,354 1,890 3,776 1,704 4,371 1,837 3,029 1,766 3,577 3,012 2,330 1,921 3,632 1,746 4,107 1,852 3,033 10 1,827 3,580 3,025 2,296 1,946 3,585 1,762 4,114 1,908 3,028 12 1,847 3,493 3,11 2,282 1,966 3,548 1,765 4,095 1,940 2,902 14 1,850 3,495 3,10 2,284 1,967 3,547 1,766 4,097 1,942 2,905 Ph l c Giá tr thành ph n m ch t ng đ ng Randles c a c m bi n PSAaptamer/SAM(MHDA)/AuNPs-SPCE v i 10 vòng quét t o h t nano vàng n ng đ aptamer khác (5 µg/mL, 10 µg/mL, 25 µg/mL, 50 µg/mL, 100 µg/mL) PSA/aptamer/MHDA/10 CVs AuNPs-SPCE Giá tr thành ph n m ch t ng đ ng Randles N ng đ Aptamer Aptamer Aptamer Aptamer Aptamer PSA µg/mL 10 µg/mL 25 µg/mL 50 µg/mL 100 µg/mL ng/mL Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) 1,095 4,172 1,411 3,976 1,488 3,930 1,359 3,878 1,738 3,734 1,358 3,615 1,580 3,992 1,489 3,847 1,472 3,564 1,864 3,555 1,487 3,361 1,582 3,758 1,614 3,666 1,592 3,488 1,934 3,211 1,544 3,329 1,837 3,294 1,655 3,823 1,638 3,432 1,953 3,394 1,584 3,373 1,849 3,284 1,782 3,530 1,638 3,432 1,959 3,260 10 1,720 3,224 1,929 3,301 1,827 3,580 1,670 3,295 2,014 3,246 12 1,759 3,160 1,957 3,203 1,852 3,492 1,716 3,350 2,035 3,095 14 1,760 3,164 1,959 3,200 1,853 3,490 1,718 3,348 2,038 3,093 -2- Ph l c Giá tr thành ph n m ch t ng đ ng Randles c a c m bi n PSAaptamer/SAM(MHDA)/AuNPs-SPCE v i 15 vòng quét t o h t nano vàng n ng đ aptamer khác (5 µg/mL, 10 µg/mL, 25 µg/mL, 50 µg/mL, 100 µg/mL) PSA/aptamer/MHDA/15Cvs AuNPs-SPCE Giá tr thành ph n m ch t N ng đ PSA Aptamer µg/mL Aptamer 10 µg/mL ng đ Aptamer 25 µg/mL ng Randles Aptamer 50 µg/mL Aptamer 100 µg/mL ng/mL Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) 1,561 3,745 1,480 4,173 1,697 3,974 1,379 2,564 1,613 4,533 1,699 3,521 1,598 4,076 1,880 3,849 1,433 2,496 1,684 4,465 1,845 3,422 1,720 3,888 1,890 3,764 1,447 2,439 1,722 4,216 1,901 3,243 1,779 3,737 1,909 3,601 1,506 2,437 1,729 4,153 1,912 3,147 1,840 3,630 1,915 3,471 1,525 2,353 1,744 4,082 10 1,952 3,104 1,852 3,610 1,953 3,465 1,544 2,350 1,747 4,011 12 1,988 3,068 1,888 3,599 1,956 3,390 1,566 2,394 1,758 3,785 14 1,989 3,066 1,890 3,595 1,957 3,387 1,568 2,390 1,759 3,783 Ph l c Giá tr thành ph n m ch t ng đ ng Randles c a c m bi n MHDA/AuNPsmodified SPCE v i 20 vòng quét t o h t nano vàng n ng đ aptamer khác (5 µg/mL, 10 µg/mL, 25 µg/mL, 50 µg/mL, 100 µg/mL) PSA/aptamer/MHDA/20 CVs AuNPs-SPCE Giá tr thành ph n m ch t N ng đ PSA Aptamer µg/mL Aptamer 10 µg/mL ng đ Aptamer 25 µg/mL ng Randles Aptamer 50 µg/mL Aptamer 100 µg/mL ng/mL Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) 1,628 3,932 1,992 3,313 1,918 3,139 1,124 3,415 1,398 2,527 1,680 3,995 2,139 3,261 1,981 3,168 1,168 4,128 1,421 2,377 1,689 4,290 2,137 3,100 2,040 3,024 1,214 4,542 1,429 2,408 1,806 3,731 2,182 2,979 2,094 2,877 1,217 3,663 1,511 2,453 1,861 3,774 2,241 3,134 2,106 2,890 1,221 3,448 1,521 2,334 10 1,876 3,569 2,241 3,134 2,161 2,848 1,243 3,601 1,544 2,394 12 2,091 3,376 2,322 3,076 2,149 2,883 1,336 3,459 1,566 2,439 14 2,093 3,374 2,325 3,073 2,150 2,880 1,339 3,456 1,569 2,433 -3- Ph l c Giá tr thành ph n m ch t ng đ ng Randles c a c m bi n đ c ch t o v i u ki n t i u: h t nano vàng t ng h p SPCE 10 CVs n ng đ aptamer µg/mL N ng đ PSA (ng/mL) Giá tr thành ph n m ch t ng đ ng Randles PSA/aptamer/MHDA/AuNPs-SPCE Rs (kΩ) Rct (kΩ) Cdl (µF) 2,66 1,34 4,58 2,67 1,48 4,17 2,66 1,60 4,08 2,67 1,72 3,90 2,66 1,78 3,74 10 2,66 1,87 3,60 12 2,66 1,88 3,54 14 2,66 1,89 3,61 Ph l c Giá tr thành ph n m ch t ng đ ng Randles đ c cho b i kh o sát đ đ c hi u PSA-Aptamer/SAM(MHDA)/AuNPs-SPCE Giá tr thành ph n m ch t N ng đ kháng nguyên hCG ng đ Amylin ng Randles Protein TAU (ng/mL) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) Rct (kΩ) Cdl (µF) 1,090 3,65 1,121 3,71 1,230 2,57 1,097 3,77 1,144 3,68 1,249 2,49 1,149 3,83 1,181 3,50 1,260 2,41 1,179 3,69 1,141 3,42 1,361 2,45 1,178 3,68 1,125 3,45 1,373 2,40 10 1,180 3,73 1,135 3,46 1,370 2,42 12 1,168 3,66 1,125 3,45 1,361 2,42 14 1,170 3,64 1,130 3,46 1,359 2,43 -4- Ph l c Giá tr Rct c a 03 c m bi n mAb AFP/PPy-PPa/SPCE đ c l p ch t o quy trình cơng ngh s d ng xây d ng đ ng đ c tr ng chu n N ng đ kháng nguyên Rct () Rct () AFP (ng/mL) M1 M2 M3 M1 M2 M3 Giá tr trung bình Rct 891,2 945,9 866,2 0,0 0,0 0,0 0,0 1368,0 1308,0 1573,0 476,8 362,1 706,8 484,8 ± 111,0 10 1895,0 1430,0 1880,0 1003,8 484,1 1013,8 859,3 ± 187,6 20 2174,0 1811,0 2032,0 1282,8 865,1 1165,8 1149,1 ± 142,0 30 2443,0 2527,0 2540,0 1551,8 1581,1 1673,8 1679,8 ± 116,4 40 3145,0 3092,0 2800,0 2253,8 2146,1 1933,8 2095,3 ± 104,6 50 3358,0 3377,0 3094,0 2466,8 2431,1 2227,8 2414,6 ± 93,4 60 3820,0 3755,0 3293,0 2928,8 2809,1 2426,8 2831,1 ± 213,1 70 4050,0 3989,0 4024,0 3158,8 3043,1 3157,8 3187,8 ± 101,9 80 4166,0 4270,0 4538,0 3274,8 3324,1 3671,8 3447,1 ± 147,6 90 4072,0 4302,0 4340,0 3180,8 3356,1 3473,8 3465,6 ± 197,1 100 4071,0 4103,0 4242,0 3179,8 3157,1 3375,8 3315,3 ± 146,9 -5- Ph l c 10 Giá tr Rct c a 03 c m bi n mAb AFP/PPy-PPa/erGO-SPCE đ c l p ch t o quy trình cơng ngh s d ng xây d ng đ ng đ c tr ng chu n N ng đ kháng nguyên AFP (ng/mL) Rct () Rct () M1 M2 M3 M1 M2 M3 Giá tr trung bình Rct 286,7 276,4 290,7 0,0 0,0 0,0 0,0 0,1 426,6 465,3 458,4 139,9 188,9 167,7 171,0 ± 17,2 709,9 661,1 751,9 423,2 384,7 461,2 396,5 ± 45,7 1104,0 901,9 1160,0 817,3 625,5 869,3 725,5 ± 117,8 10 1307,0 1491,0 1354,0 1020,3 1214,6 1063,3 1006,4 ± 139,5 20 2088,0 1647,0 1829,0 1801,3 1370,6 1538,3 1630,9 ± 176,4 30 2527,0 2469,0 2408,0 2240,3 2192,6 2117,3 2262,6 ± 118,8 40 2984,0 2649,0 2436,0 2697,3 2372,6 2145,3 2469,4 ± 210,4 50 3633,0 3411,0 3127,0 3346,3 3134,6 2836,3 3199,4 ± 213,9 60 4241,0 4014,0 3894,0 3954,3 3737,6 3603,3 3723,1 ± 122,8 70 4593,0 4525,0 5076,0 4306,3 4248,6 4785,3 4425,6 ± 179,8 80 5173,0 4842,0 5403,0 4886,3 4565,6 5112,3 4780,9 ± 218,4 90 5657,0 6024,0 6089,0 5370,3 5747,6 5798,3 5576,1 ± 196,8 100 6207,0 5591,0 6494,0 5920,3 5314,6 6203,3 5804,6 ± 257,2 500 6384,0 6039,0 6839,0 6097,3 5762,6 6548,3 6213,1 ± 283,2 1000 6513,0 5597,0 6053,0 6226,3 5320,6 5756,3 5849,6 ± 311,2 Ph l c 11 Giá tr Rct c a c m bi n mAb AFP/SAM(p-ATP)/AuNPs-SPCE xây d ng đ chu n Rct () Giá tr trung bình N ng đ kháng nguyên AFP (ng/mL) M1 M2 M3 M1 M2 M3 Rct 601,5 627,4 596,8 0,0 0,0 0,0 0,0 819,4 891,2 854,0 217,9 263,8 257,2 246,3 ± 18,9 10 1199,0 1186,0 1344,0 597,5 558,6 747,2 634,4 ± 75,2 20 1553,0 1453,0 1555,0 951,5 825,6 958,2 911,8 ± 57,4 30 2141,0 1853,0 1755,0 1539,5 1225,6 1158,2 1307,8 ± 154,5 40 2460,0 2267,0 2178,0 1858,5 1639,6 1581,2 1693,1 ± 110,3 50 2593,0 2694,0 2442,0 1991,5 2066,6 1845,2 1967,8 ± 81,7 60 2843,0 3094,0 2814,0 2241,5 2466,6 2217,2 2308,4 ± 105,4 70 2983,0 3328,0 3171,0 2381,5 2700,6 2574,2 2552,1 ± 113,7 80 3291,0 3678,0 3661,0 2689,5 3050,6 3064,2 2934,8 ± 163,5 90 3223,0 3273,0 3464,0 2621,5 2645,6 2867,2 2711,4 ± 103,8 100 3151,0 3181,0 3264,0 2549,5 2553,6 2667,2 2590,1 ± 51,4 Rct () -6- ng Ph l c 12 Giá tr Rct c a c m bi n mAb AFP/poly(p-ATP)/AuNPs-SPCE xây d ng đ chu n N ng đ kháng nguyên Rct (k) Rct (k) Giá tr trung bình Rct AFP (ng/mL) M1 M2 M3 M1 M2 M3 5,65 5,59 5,62 0,00 0,00 0,00 0,0 7,81 9,11 9,89 2,16 3,52 4,26 3,31 ± 0,77 10 12,29 13,01 18,43 6,64 7,42 12,81 8,96 ± 2,57 20 24,57 21,98 30,70 18,92 16,39 25,08 20,13 ± 3,29 30 37,27 30,09 34,09 31,62 24,50 28,47 28,19 ± 2,46 40 43,12 37,39 48,49 37,47 31,80 42,87 37,38 ± 3,72 50 50,61 44,31 51,04 44,96 38,72 45,42 43,03 ± 2,873 60 55,04 46,90 55,99 49,39 41,31 50,37 47,02 ± 3,81 70 61,78 54,04 58,99 56,13 48,45 53,37 52,65 ± 2,79 80 65,04 61,78 75,58 59,39 56,19 69,96 61,85 ± 5,41 90 70,76 73,40 81,53 65,11 67,81 75,91 69,61 ± 4,19 100 74,73 75,58 82,51 69,08 69,99 76,89 71,98 ± 3,27 -7- ng ... i n hóa: Ph n ng hóa sinh gi a đ u thu sinh h c ch t c n phân tích s sinh đáp ng tín hi u n hóa nh n áp, c ng đ dòng n hay đ d n Tùy thu c vào tín hi u đ u c a b chuy n đ i mà c m bi n sinh h... Biotin Avidin/Streptavidin có tính đ nh h ng phân b đ ng nh t cao [254] 1.2 C m bi n sinh h c n hóa C m bi n sinh h c n hóa c m bi n ho t đ ng d a nguyên t c chuy n đ i tín hi u t ng tác sinh. .. ơxy hóa- kh t i n c c làm vi c sinh s n ph m ph vƠ n t , (ii) ph n ng ôxy hóa- kh c a m t chu i ch t trung gian có tính ơxy hóa kh sinh n t , (iii) ph n ng ơxy hóa- kh tr c ti p sinh n t không sinh