The use of hydrogel microparticles to sequester and concentrate bacterial antigens in a urine test for Lyme disease

被引:40
作者
Douglas, Temple A. [1 ]
Tamburro, Davide [1 ]
Fredolini, Claudia [1 ,2 ,3 ]
Espina, Benjamin H. [4 ]
Lepene, Benjamin S. [4 ]
Ilag, Leopold [5 ]
Espina, Virginia [1 ]
Petricoin, Emanuel F., III [1 ]
Liotta, Lance A. [1 ]
Luchini, Alessandra [1 ]
机构
[1] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA
[2] S Giovanni Bosco Hosp, Dept Urol, I-10154 Turin, Italy
[3] Univ Turin, Dept Med & Expt Oncol, I-10126 Turin, Italy
[4] Ceres Nanosci LLLP, Manassas, VA 20110 USA
[5] Stockholm Univ, Dept Analyt Chem, S-10691 Stockholm, Sweden
关键词
Hydrogel; Microparticle; Affinity; Bacteria; Protein; ALLERGIC CONTACT-DERMATITIS; BORRELIA-BURGDORFERI; DIAGNOSIS; BLOOD; GROWTH; TICKS; ACID; MICE;
D O I
10.1016/j.biomaterials.2010.10.004
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Hydrogel biomarker capturing microparticles were evaluated as a biomaterial to amplify the sensitivity of urine testing for infectious disease proteins. Lyme disease is a bacterial infection transmitted by ticks. Early diagnosis and prompt treatment of Lyme disease reduces complications including arthritis and cardiac involvement. While a urine test is highly desirable for Lyme disease screening, this has been difficult to accomplish because the antigen is present at extremely low concentrations, below the detection limit of clinical immunoassays. N-isopropylacrylamide (NIPAm) - acrylic acid (AAc) microparticles were covalently functionalized with amine containing dyes via arnidation of carboxylic groups present in the microparticles. The dyes act as affinity baits towards protein analytes in solution. NIPAm/AAc microparticles functionalized with acid black 48 (AB48) mixed with human urine, achieved close to one hundred percent capture and 100 percent extraction yield of the target antigen. In urine, microparticles sequestered and concentrated Lyme disease antigens 100 fold, compared to the absence of microparticles, achieving an immunoassay detection sensitivity of 700 pg/mL in 10 mL urine. Antigen present in a single infected tick could be readily detected following microparticle sequestration. Hydrogel microparticles functionalized with high affinity baits can dramatically increase the sensitivity of urinary antigen tests for infectious diseases such as Lyme disease. These findings justify controlled clinical studies evaluating the sensitivity and precision of Lyme antigen testing in urine. (c) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1157 / 1166
页数:10
相关论文
共 36 条
[1]  
Barr W B, 1999, Appl Neuropsychol, V6, P12, DOI 10.1207/s15324826an0601_2
[2]  
Cameron DJ, 2008, NEW ENGL J MED, V358, P429
[3]   Two-year evaluation of Borrelia burgdorferi culture and supplemental tests for definitive diagnosis of Lyme disease [J].
Coulter, P ;
Lema, C ;
Flayhart, D ;
Linhardt, AS ;
Aucott, JN ;
Auwaerter, PG ;
Dumler, JS .
JOURNAL OF CLINICAL MICROBIOLOGY, 2005, 43 (10) :5080-5084
[4]   GROWTH AND MIGRATION OF BORRELIA-BURGDORFERI IN IXODES TICKS DURING BLOOD-FEEDING [J].
DESILVA, AM ;
FIKRIG, E .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1995, 53 (04) :397-404
[5]   IMMUNE CAPTURE AND DETECTION OF BORRELIA-BURGDORFERI ANTIGENS IN URINE, BLOOD, OR TISSUES FROM INFECTED TICKS, MICE, DOGS, AND HUMANS [J].
DORWARD, DW ;
SCHWAN, TG ;
GARON, CF .
JOURNAL OF CLINICAL MICROBIOLOGY, 1991, 29 (06) :1162-1170
[6]   A Portrait of Tissue Phosphoprotein Stability in the Clinical Tissue Procurement Process [J].
Espina, Virginia ;
Edmiston, Kirsten H. ;
Heiby, Michael ;
Pierobon, Mariaelena ;
Sciro, Manuela ;
Merritt, Barbara ;
Banks, Stacey ;
Deng, Jianghong ;
VanMeter, Amy J. ;
Geho, David H. ;
Pastore, Lucia ;
Sennesh, Joel ;
Petricoin, Emanuel F., III ;
Liotta, Lance A. .
MOLECULAR & CELLULAR PROTEOMICS, 2008, 7 (10) :1998-2018
[7]   Regional Cerebral Blood Flow and Metabolic Rate in Persistent Lyme Encephalopathy [J].
Fallon, Brian A. ;
Lipkin, Richard B. ;
Corbera, Kathy M. ;
Yu, Shan ;
Nobler, Mitchell S. ;
Keilp, John G. ;
Petkova, Eva ;
Lisanby, Sarah H. ;
Moeller, James R. ;
Slavov, Iordan ;
Van Heertum, Ronald ;
Mensh, Brett D. ;
Sackeim, Harold A. .
ARCHIVES OF GENERAL PSYCHIATRY, 2009, 66 (05) :554-563
[8]   Concentration and Preservation of Very Low Abundance Biomarkers in Urine, such as Human Growth Hormone (hGH), by Cibacron Blue F3G-A Loaded Hydrogel Particles [J].
Fredolini, Claudia ;
Meani, Francesco ;
Reeder, K. Alex ;
Rucker, Sally ;
Patanarut, Alexis ;
Botterell, Palma J. ;
Bishop, Barney ;
Longo, Caterina ;
Espina, Virginia ;
Petricoin, Emanuel F., III ;
Liotta, Lance A. ;
Luchini, Alessandra .
NANO RESEARCH, 2008, 1 (06) :502-518
[9]  
Harris N., 1995, Journal of Spirochetal and Tick-borne Diseases, V2, P37
[10]  
Hatch KL, 1998, QUANT STRUCT-ACT REL, V17, P20, DOI 10.1002/(SICI)1521-3838(199801)17:01<20::AID-QSAR20>3.3.CO