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Review article
Aptamers coupled to nanoparticles in the diagnosis and treatment of microbial infections
Aptámeros acoplados a nanopartículas para el diagnóstico y tratamiento de las infecciones microbianas
Juan Carlos Gutiérrez-Santanaa,b,
Corresponding author
biol.jcgutierrez@gmail.com

Corresponding author.
, Julia Dolores Toscano-Garibayc, Marisol López-Lópezd, Victor Rafael Coria-Jiméneza
a Laboratorio de Bacteriología Experimental, Instituto Nacional de Pediatría, Mexico City, Mexico
b Universidad Autónoma Metropolitana, Unidad Xochimilco, Mexico City, Mexico
c Unidad de Investigación en Microbiología y Toxicología, Dirección de Investigación, Hospital Juárez de México, Mexico City, Mexico
d Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Unidad Xochimilco, Mexico City, Mexico
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Morbidity and mortality rates for bacterial infections have increased due to the increased frequency of multidrug-resistant &#40;MDR&#41; bacteria&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> which has reduced the efficacy of available eradication therapies<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and established a major health problem with serious economic and social consequences&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This &#8220;antibiotic resistance crisis&#8221;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> has mainly been generated by the extensive and inappropriate use of antibiotics&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> but also by conventional diagnosis methods involving culture and biochemical tests &#40;standard method&#41;&#44; which take several days to identify infectious agents&#44; allowing the infection to progress&#46; It is therefore necessary to develop rapid methods for bacterial diagnosis&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> to design therapies that evade bacterial resistance mechanisms<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;6</span></a> and&#47;or to improve the action of the existing antibiotics&#44; where nanotechnology appears to be a promising tool&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Aptamers</span><p id="par0015" class="elsevierStylePara elsevierViewall">Aptamers are short&#44; single-stranded nucleic acids&#44; selected <span class="elsevierStyleItalic">in vitro</span> by a process known as systematic evolution of ligands by exponential enrichment &#40;SELEX&#41; to recognise a range of specific targets&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Aptamer-target recognition is achieved through structural compatibility and combining of various non-covalent interactions&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> establishing dissociation constants usually in the picomolar to nanomolar range for targets with high molecular weight&#44; and nanomolar to micromolar range for targets with low molecular weight&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;11</span></a> Aptamers are able to discriminate between enantiomers and molecules that structurally differ in only one functional group&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Their small size and low molecular weight&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleItalic">in vitro</span> synthesis&#44;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;12</span></a> stability under a broad range of conditions<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9&#44;11&#44;12</span></a> and lack of or low toxicity <span class="elsevierStyleItalic">in vivo</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> have also made them attractive molecules for the development of new diagnostic and therapeutic strategies for infectious agents&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9&#44;11&#44;12</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Additionally&#44; these biomolecules can be easily modified to improve their biostability against nucleases&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9&#44;11&#44;12</span></a> increase their bioavailability&#44; pharmacokinetic properties and affinity&#44; evade the immune response&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and even be coupled to reporter molecules&#44; functional groups or nanoparticles &#40;NP&#41; to increase their applicability&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Nanoparticles</span><p id="par0030" class="elsevierStylePara elsevierViewall">NPs are a range of small materials measuring less than 100&#8239;nm&#44; the properties of which depend on their size&#44; shape&#44; distribution and chemical formulation&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;13</span></a> Their high surface area to volume ratio gives them a high degree of reactivity and unique interactions with biological systems&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Moreover&#44; the localised surface plasmon resonance &#40;LSPR&#41; commonly manifested by metal NPs under photonic or electromagnetic stimuli gives them optical properties equivalent to 10 fluorophores&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> so they could be used for the development of diagnostic tools&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">There are also NPs which&#44; at non-toxic doses to human cells&#44; have outstanding antimicrobial qualities against various pathogens and their MDR variants&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;13</span></a> where metal NPs appear to be promising&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> as they produce reactive oxygen species&#44; constantly release metal cations<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3&#44;14</span></a> and are generally positively charged&#44; contributing to their adhesion and accumulation in the bacterial outer membrane&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;14</span></a> dissociating it and causing the elimination of the proton gradient and the subsequent exit of the cytoplasmic content&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3&#44;14</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Furthermore&#44; smaller NPs and metal cations can become internalised inside the bacteria&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> adding far-reaching antimicrobial effects&#44; such as inhibition of enzymes crucial for DNA replication and adenosine triphosphate &#40;ATP&#41; production&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;14</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Non-antimicrobial NPs can be useful for designing diagnostic and therapeutic strategies for bacterial infections&#44; by adapting them for the transport-delivery of antimicrobial compounds to specific sites &#40;nanocarriers&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a> accumulating the compound on the bacterial surface and improving its pharmacokinetics&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4&#44;13&#44;15</span></a> In this review&#44; we discuss some examples of selective aptamers for pathogenic bacterial species which have been used with NPs for the design of novel diagnostic and&#47;or therapeutic strategies against bacterial pathogens &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Aptamers and nanoparticles for the identification of bacterial pathogens</span><p id="par0050" class="elsevierStylePara elsevierViewall">Aptamers targeting various bacterial species have been selected&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7&#44;8&#44;10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> mainly used as stationary phase for molecule capture&#44; and are capable of identifying bacteria in environmental and clinical samples&#44; with sensitivities equivalent to or greater than those of conventional cultures&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;12</span></a> The potential for aptamers and NPs to be used in biomedicine has been demonstrated by the synergy between them<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#59; the affinity of an aptamer for its target is increased by a high density of aptamers on NPs&#44; increasing the number of interactions with the target thanks to a cooperative action &#40;multivalent effect&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;16</span></a> which in turn protects the aptamers from nuclease digestion&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Bacteria detection based on aptamers and <span class="elsevierStyleItalic">quantum dots</span></span><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Quantum dots</span> &#40;QDs&#41; are a type of NP with appreciable fluorescent properties&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;17</span></a> They have been used in pilot tests for the development of a semiquantitative detection system for <span class="elsevierStyleItalic">Escherichia coli</span>&#44; <span class="elsevierStyleItalic">Salmonella typhimurium</span> and <span class="elsevierStyleItalic">Bacillus subtilis</span> by way of conjugating aptamers to QDs&#44; and the system proved to be capable of recognising each microorganism from variations in the fluorescence of the QDs&#46; The initial detection was evaluated with &#8764;2&#46;8&#8239;&#215;&#8239;10<span class="elsevierStyleSup">6</span> bacteria&#47;mL and the fluorescence intensity was modified in proportion to the number of bacteria present&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> showing its potential for bacterial diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> An anti-<span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> aptamer has also been used to develop a method for detecting this bacteria in drinking water&#46; By labelling aptamers with fluorescein isothiocyanate &#40;FITC&#41; and using aptamer-conjugated QDs&#44; these conjugates were found to have decreased affinities for the FITC-labelled aptamer&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> showing that nanotechnology can also produce poor results for promising recognition molecules&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Carbon dots</span> &#40;CDs&#41;&#44; with their promising luminescent&#44; toxic and biocompatibility properties&#44; have also been tested&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;20</span></a> They have been used in conjunction with anti-<span class="elsevierStyleItalic">S&#46; typhimurium</span> aptamers to develop a fluorescence-based detection method&#44; showing limits of detection &#40;LOD&#41; of 50 colony forming units &#40;CFU&#41;&#47;mL in two hours of incubation with liquid bacterial cultures<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;21&#44;22</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; confirmed by the plate count method&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Bacteria detection through aptamers coupled to metal nanoparticles</span><p id="par0065" class="elsevierStylePara elsevierViewall">Currently&#44; gold NPs &#40;AuNPs&#41; are widely used for the generation of bacterial bio-sensors due to the electrochemical&#44; optical and resonance characteristics of plasmons&#44; among other promising properties they possess&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> They have been used in conjunction with aptamers for the detection of <span class="elsevierStyleItalic">Salmonella enteritidis</span>&#44; conjugating aptamers with AuNPs&#44; to later immobilise them on a carbon electrode&#46; This proof of concept demonstrated that when introducing the electrode in solutions with the bacteria&#44; the electrical resistance increased due to the formation of aptamer-bacteria complexes&#44; allowing it to be measured by electrochemical impedance with an LOD of 600&#8239;CFU&#47;mL&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;23</span></a> This has established the bases for using this principle to develop new methods for the detection of different microorganisms&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">A chip has also been developed based on the immobilisation of AuNP coupled to anti-<span class="elsevierStyleItalic">S&#46; typhimurium</span> aptamers&#44; the pilot study for which showed its utility for detecting this pathogen in fluid from rinsing pork&#46; Introducing the chip into the fluid&#44; the aptamer changed structure on binding to the bacteria&#44; modifying the baseline absorbance of the LSPR of the AuNPs which was detected by UV&#47;visible spectrophotometry &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The main limitation of this method and this type of technology is the need to establish different matrices for different foods before it can be marketed&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Another pilot study based on aptamers immobilised on silica-coated gold NPs &#40;Au-silica NPs&#41; enabled the development of a multiplex sensor for <span class="elsevierStyleItalic">Lactobacillus acidophilus</span>&#44; <span class="elsevierStyleItalic">S&#46; typhimurium</span> and <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; which was able to discriminate between each pathogen with an LOD of 3&#8239;CFU per assay&#44; thanks to each aptamer recognising its target&#44; in particular altering the LSPR of the NPs for each bacterial species&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;25&#44;26</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Aptamers and magnetic molecules for bacteria detection</span><p id="par0080" class="elsevierStylePara elsevierViewall">Magnetic NPs &#40;MNPs&#41; can cause a solution to change colour in the presence of a colorimetric substrate such as 3&#44;3&#8242;&#44;5&#44;5&#8242;-tetramethylbenzidine &#40;TMB&#41; and H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span>&#44; in a similar way to peroxidase&#46; This property was used to detect <span class="elsevierStyleItalic">S&#46; typhimurium</span> in a proof-of-concept study&#44; in which anti-<span class="elsevierStyleItalic">S&#46; typhimurium</span> aptamers in solution with MNPs were found to inhibit MNP enzymatic activity&#44; but on addition of 7&#46;5&#8239;&#215;&#8239;10<span class="elsevierStyleSup">5</span>&#8239;CFU&#47;mL of the bacteria&#44; the aptamer became bound to the pathogen&#44; leaving the MNP unprotected and allowing their enzymatic activity&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In addition&#44; magnetic beads &#40;MBs&#41; and the MNPs can be used with the aptamers to develop methods for magnetic capture-separation of pathogens present in a sample&#44; to concentrate them<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;21&#44;25&#44;28&#8211;30</span></a> and subsequently detect them by various strategies&#44; achieving LOD of 1&#8211;682&#8239;CFU&#47;mL validated by the plate count method&#44;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;31&#8211;33</span></a> as follows&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#40;i&#41;</span><p id="par0090" class="elsevierStylePara elsevierViewall">From the variation in the electrical signal caused by the photonic excitation of AuNPs coupled to anti-<span class="elsevierStyleItalic">Staphylococcus aureus</span> &#40;<span class="elsevierStyleItalic">S&#46; aureus</span>&#41; aptamers when bound to said pathogen&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;25&#44;28</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#40;ii&#41;</span><p id="par0095" class="elsevierStylePara elsevierViewall">By the measurement of silver ions &#40;Ag<span class="elsevierStyleSup">&#43;</span>&#41; in solution&#44; produced by silver NPs &#40;AgNPs&#41; coupled to anti-<span class="elsevierStyleItalic">S&#46; aureus</span> aptamers&#44; where the concentration of Ag<span class="elsevierStyleSup">&#43;</span> is directly proportional to the density of the bacteria in a sample&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;29</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#40;iii&#41;</span><p id="par0100" class="elsevierStylePara elsevierViewall">By detection of the specific fluorescence of upconversion NPs &#40;UCNPs&#41; bound to specific anti-<span class="elsevierStyleItalic">S&#46; typhimurium</span>&#44; anti-<span class="elsevierStyleItalic">S&#46; aureus</span> and anti-<span class="elsevierStyleItalic">Vibrio parahaemolyticus</span> aptamers&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;30&#44;31</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#40;iv&#41;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Similarly&#44; from fluorescence detection of carboxyfluorescein &#40;FAM&#41;-modified aptamers selective for <span class="elsevierStyleItalic">S&#46; typhimurium</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;10&#44;34</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#40;v&#41;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Through the identification of specific enzymes produced by a particular pathogen&#44; such as <span class="elsevierStyleItalic">S&#46; aureus</span> micrococcal nucleases &#40;MN&#41; which&#44; by the addition of nano gatekeepers&#44; made up of FAM-labelled oligonucleotides specifically susceptible to MN&#44; are immobilised in the pores of mesoporous silica NP &#40;MSNs&#41; to inhibit FAM fluorescence&#44; but when MN production is stimulated&#44; the oligonucleotides degrade&#44; allowing the fluorescence emission&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#40;vi&#41;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Through the specific interaction of antimicrobials with particular pathogens&#44; such as vancomycin and <span class="elsevierStyleItalic">S&#46; aureus</span>&#44; behaviour which has been useful for the detection of this pathogen through incubation with gold nano-clusters &#40;AuNCs&#41; with fluorescent properties&#44; which are inhibited by vancomycin&#44; but in the presence of <span class="elsevierStyleItalic">S&#46; aureus</span>&#44; vancomycin interacts with the pathogen allowing fluorescence emission from the AuNCs&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p></li></ul></p><p id="par0120" class="elsevierStylePara elsevierViewall">There is also evidence of the combined use of antibodies and aptamers for the fluorometric detection of certain microorganisms&#44; such as methicillin-resistant <span class="elsevierStyleItalic">S&#46; aureus</span> &#40;MRSA&#41; using MBs coated with <span class="elsevierStyleItalic">S&#46; aureus</span> anti-protein A antibodies &#40;SpA&#41; to capture the pathogen&#46; The method involves lysing the bacteria and incubating it in the presence of an FITC-modified anti-PBP2a aptamer &#40;MRSA-specific protein&#41; hybridised to three short DNA molecules to eliminate the fluorescence emission&#46; When the aptamer binds to the PBP2a protein&#44; the fluorescence emission of FITC is rehabilitated&#44; achieving a LOD of 1&#46;38&#8239;&#215;&#8239;10<span class="elsevierStyleSup">3</span>&#8239;CFU&#47;mL&#44; confirmed by conventional microbiological methods&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Bacteria detection based on aptamers coupled to nanostructures</span><p id="par0125" class="elsevierStylePara elsevierViewall">Modified deoxyribozyme &#40;DNAzyme&#41; aptamers immobilised on single-walled carbon nanotubes &#40;SWNTs&#41; have been used for the detection of <span class="elsevierStyleItalic">Salmonella paratyphi A</span>&#44; where the aptamer-<span class="elsevierStyleItalic">S&#46; paratyphi A</span> complex generates a conformational change of the DNAzyme-modified end&#44; enabling it to form complexes with hemins &#40;added to the solution&#41; which&#44; in the presence of luminol &#40;also added to the system&#41;&#44; catalyse the generation of chemiluminescence in the presence of H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span>&#44; with a LOD of 10<span class="elsevierStyleSup">3</span>&#8239;CFU&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">More elaborate systems for the detection of pathogens have also been designed&#44; such as the optofluidic platform built to detect the fluorescent signal of anti-<span class="elsevierStyleItalic">E&#46; coli</span> aptamers coupled to fluorescent NPs &#40;FNPs&#41;&#44; where the microflow of cultures through the system&#39;s microchannel made it possible to identify &#8764;100 <span class="elsevierStyleItalic">E&#46; coli</span> cells per second by means of the fluorescent signal from the FNPs bound to them&#59; these results then being confirmed by plate count&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Multiplex systems have also been designed for the detection of pathogens&#44; such as the immobilisation of anti-<span class="elsevierStyleItalic">S&#46; typhimurium</span>&#44; anti-<span class="elsevierStyleItalic">V&#46; parahaemolyticus</span> and anti-<span class="elsevierStyleItalic">S&#46; aureus</span> aptamers modified with different fluorochromes &#40;FAM&#44; cyanine dye 3 &#40;Cy3&#41; and 6-carboxy-X-rhodamine &#40;ROX&#41;&#41; to detect each pathogen by fluorescence&#46; The aptamers were immobilised on carbon NPs &#40;CNPs&#41;&#44; which enable the assembly of dyes inhibiting their fluorescence&#44; but when the aptamers recognised their target pathogen they dissociated themselves from the CNPs&#44; resulting in the emission and detection of fluorescence&#44;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;38</span></a> with LOD of 50&#44; 25 and 50&#8239;CFU&#47;mL&#44; respectively&#44; validated by plate count&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The relationship between vancomycin and <span class="elsevierStyleItalic">S&#46; aureus</span> has also been used for the pilot study of a detection strategy involving variation in fluorescence resonance energy transfer &#40;FRET&#41;&#44; using AuNCs conjugated to vancomycin as an energy donor element and anti-<span class="elsevierStyleItalic">S&#46; aureus</span> aptamers immobilised on AuNPs as an energy receptor element&#44; which are the FRET-based dual recognition units &#40;DRU-FRET&#41;&#46; Both systems are attracted in the presence of the pathogen&#44; causing the variation of FRET and enabling LOD of 10&#8239;CFU&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">There is other evidence from pilot studies on strategies based on energy donor and acceptor elements&#44; such as the use of anti-<span class="elsevierStyleItalic">E&#46; coli</span> aptamers immobilised on AuNPs &#40;energy acceptor element&#41; and UCNPs coupled to an oligonucleotide of complementary DNA &#40;cDNA&#41; to the aptamer sequence &#40;energy donor element&#41;&#44; which when hybridised inhibit UCNP fluorescence production&#44; but in presence of the pathogen&#44; the aptamer binds it&#44; dissociating its interaction with the UCNPs and causing the emission of fluorescence&#44; with LOD of 3&#8239;CFU&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Strategies for bacteria detection based on aptamers not coupled to nanoparticles</span><p id="par0150" class="elsevierStylePara elsevierViewall">Aptamers and NPs can be used unconjugated for the detection of specific microorganisms&#46; Some properties&#44; such as the natural interaction between aptamers and AuNPs&#44; have been useful in designing detection methods for <span class="elsevierStyleItalic">E&#46; coli</span>&#44; <span class="elsevierStyleItalic">S&#46; typhimurium</span> and <span class="elsevierStyleItalic">S&#46; aureus</span>&#46; Proof-of-concept studies have shown that free aptamers inhibit the aggregation of AuNPs&#44; but in the presence of the target pathogens&#44; the aptamers bind to the bacteria&#44; allowing the aggregation of the AuNPs &#40;causing a change in the colour of the solution&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;10&#44;21&#44;41</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Aptamers can also be used as elements for the recognition and capture of microorganisms&#44; as in the detection methods described for <span class="elsevierStyleItalic">S&#46; aureus</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a><span class="elsevierStyleItalic">Campylobacter jejuni</span> and <span class="elsevierStyleItalic">Campylobacter coli</span><a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> where&#44; when added to bacterial solutions&#44; the aptamers bind specifically to their target pathogen&#44; being eliminated by discarding the cell button and allowing the aggregation of the AuNPs &#40;added to the supernatant&#41;&#44; obtaining LOD of 5&#46;6&#8239;&#215;&#8239;10<span class="elsevierStyleSup">5</span>&#8239;CFU&#47;mL &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#59; sensitivity and specificity were 80&#46;0&#37; and 93&#46;3&#37;&#44; respectively&#44; validated by tazobactam-supplemented cultures &#40;standard method&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> This opens up the opportunity to use similar platforms for other pathogenic bacteria&#44; despite the difficulties in recognising different morphological variants of the same bacterial species&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Treatment based on aptamers and nanoparticles</span><p id="par0160" class="elsevierStylePara elsevierViewall">Despite the promising antimicrobial characteristics of NPs and the specificity of aptamers&#44; they have not been widely used to develop therapeutic strategies&#46; However&#44; their use as nanocarriers for drugs is an attractive strategy<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;44&#44;45</span></a> to increase the efficiency of the available antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">NPs can be administered by different routes<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> and at present there are antibacterial treatments such as PolyMemSilver&#174;&#44; Acticoat&#8482;&#44; SilvaSorb&#8482; and Aquacel&#174;Ag<span class="elsevierStyleSup">2</span>&#44; to mention just a few&#44; where AgNPs feature as one of the main elements&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">There have been reports of possible toxicity of certain NPs on the host cells&#44; although they can be modified to reduce this adverse effect&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> One example is conjugation of the NPs with aptamers&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> opening up the possibility of delivering NPs and&#47;or other drugs to the right place at the right concentrations and for the right amount of time&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> which increases their antimicrobial power in the range of 3- to 250-fold&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;14</span></a> and this is why they have been useful for the development of novel therapeutic strategies against different types of cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075"><span class="elsevierStyleItalic">In vitro</span> studies on strategies with therapeutic potential</span><p id="par0175" class="elsevierStylePara elsevierViewall">In terms of treatment against bacterial infections based on aptamers and NPs&#44; the evidence remains scarce but is encouraging&#46; One possibility is the modification of an anti-SpA aptamer with fGmH &#40;2&#8242;-F-dG&#44; 2&#8242;-OMe-dA&#47;dC&#47;dU&#41;&#44; giving it resistance to alkaline hydrolysis and to nucleases present in serum&#46; Additionally&#44; the aptamers conjugate with AgNPs&#44; releasing their specific antimicrobial action against <span class="elsevierStyleItalic">S&#46; aureus</span> in an SpA-dependent manner&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Nano gatekeepers have been found to be effective as nanocarriers for antibiotics&#59; for example&#44; immobilisation of vancomycin in the pores of MSNs and its subsequent conjugation with an anti-<span class="elsevierStyleItalic">S&#46; aureus</span> aptamer&#44; delivering the drug to the exact site and thereby reducing its minimum inhibitory concentration and its toxicity against other related species&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Moreover&#44; the antimicrobial effect of NPs can be improved with the use of different aptamers targeted against the same pathogen&#44; as described for <span class="elsevierStyleItalic">E&#46; coli</span>&#44; where the immobilisation of three aptamers on titanium dioxide NPs &#40;TiO<span class="elsevierStyleInf">2</span>NPs&#41; deactivated 99&#46;9&#37; of bacteria in 30&#8239;min&#44; in contrast to TiO<span class="elsevierStyleInf">2</span>NPs bound to one aptamer and TiO<span class="elsevierStyleInf">2</span>NPs alone&#44; which deactivated the bacteria in 60&#8239;min&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">SWNTs have been shown to possess activity against biofilms<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> &#40;primary strategy used by bacteria to survive in different environments&#41;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> and have been used to develop an anti-biofilm nanocomposite of <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; by using a selective aptamer against this bacteria conjugated to ciprofloxacin &#40;Apt-CPX&#41; and SWNTs &#40;Apt-SWNTs&#41;&#46; Additionally&#44; a molecule was generated made up of the three elements &#40;Apt-CPX-SWNTs&#41; which&#44; <span class="elsevierStyleItalic">in vitro</span>&#44; was able to reduce biofilm formation by 90&#37; and degrade &#8764;75&#37; of established biofilms &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#44; indicating that these tools could be used for the effective treatment of biofilms&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a></p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080"><span class="elsevierStyleItalic">In vivo</span> trials of bacterial eradication therapies</span><p id="par0195" class="elsevierStylePara elsevierViewall">There have been promising results with histidine-labelled anti-<span class="elsevierStyleItalic">S&#46; typhimurium</span> aptamers coupled to AuNPs &#40;AuNP-Apt<span class="elsevierStyleSup">His</span>&#41;&#44; a complex which is in turn conjugated to hexahistidine-labelled antimicrobial peptides &#40;A3-APO<span class="elsevierStyleSup">His</span>&#41;&#44; in eradicating intracellular infections by <span class="elsevierStyleItalic">S&#46; typhimurium</span>&#59; they have been shown to work <span class="elsevierStyleItalic">in vitro</span> by releasing A3-APO<span class="elsevierStyleSup">His</span> inside HeLa cells infected with the bacteria&#46; In <span class="elsevierStyleItalic">in vivo</span> assays on mice infected with doses that caused the death of the animal in 4&#8211;5 days&#44; the molecule enabled its survival by eradicating the pathogen&#44; verified by a decrease of &#8764;93&#8722;98&#37; in the number of viable bacterial cells in cultures from the infected organs of each mouse&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> suggesting that the combined use of aptamers&#44; NPs and even other antimicrobial compounds may be useful for the development of effective therapies against infections caused by bacteria&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0200" class="elsevierStylePara elsevierViewall">In recent years&#44; nanometric biomedicine has been positioning itself as a promising tool for the diagnosis&#44; prevention and treatment of a number of different diseases&#44; where aptamers and NPs have demonstrated their applicability for diagnosis and treatment&#46; In bacterial infections&#44; proofs of concept of the combined use of both elements have enabled the rapid and specific detection of individual bacterial cells&#46; The future implementation of these methods could therefore enable accurate diagnoses&#44; improving the prognosis of infected patients by allowing them to receive early&#44; specific therapy for the eradication of the infectious agent&#46; Furthermore&#44; <span class="elsevierStyleItalic">in vivo</span> studies of complex nanostructures consisting of NPs&#44; aptamers and even other antimicrobial compounds have shown that they could be a powerful tool in the face of the &#8220;antibiotic resistance crisis&#8221;&#44; allowing eradication of infections with low doses of antimicrobials by delivering them multivalently to the right place and for the precise amount of time&#44; being an ideal therapy which would not affect the organ or tissue microbiota or the host cells&#46; These technological advances suggest that there may soon be rapid and specific tools based on NPs and aptamers for the diagnosis and treatment of infectious diseases&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0205" class="elsevierStylePara elsevierViewall">Juan Carlos Guti&#233;rrez Santana is beneficiary of the <span class="elsevierStyleGrantNumber" refid="gs0005">2018-000068-02NACF-28106</span> grant from the <span class="elsevierStyleGrantSponsor" id="gs0005">Consejo Nacional de Ciencia y Tecnolog&#237;a &#40;CONACyT&#41; &#91;National Council of Science and Technology&#93;&#44; Mexico</span>&#44; and would like to thank this body for its support&#46; This work was financed by federal funds from the <span class="elsevierStyleGrantSponsor" id="gs0010">Instituto Nacional de Pediatr&#237;a &#91;National Institute of Paediatrics&#93; in Mexico</span>&#44; authorisation <span class="elsevierStyleGrantNumber" refid="gs0010">068&#47;2019</span>&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicts of interest</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">There are nanoparticles with remarkable antibacterial characteristics and aptamers able to recognize specific pathogenic bacteria with high affinity and specificity&#46; The combination of both systems has been used to design rapid bacterial detection methods with excellent detection limits&#46; Likewise&#44; the synergism between aptamers and nanoparticles have allowed to optimize the antimicrobial activity of antibiotics and other nanostructures providing them with activity bacterium-specific&#44; turning into attractive and promising tools to fight against bacteria resistant to multiple antimicrobials&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Existen nanopart&#237;culas con caracter&#237;sticas antibacterianas destacables y apt&#225;meros capaces de reconocer con gran afinidad y especificidad a determinadas bacterias pat&#243;genas&#46; La combinaci&#243;n de ambos sistemas se ha utilizado en el dise&#241;o de m&#233;todos r&#225;pidos de detecci&#243;n bacteriana con excelentes l&#237;mites de detecci&#243;n&#46; Asimismo&#44; el sinergismo entre apt&#225;meros y nanopart&#237;culas ha permitido optimizar la actividad antimicrobiana de antibi&#243;ticos y otras nanoestructuras dot&#225;ndolos de actividad bacteria-espec&#237;fica&#44; convirti&#233;ndolas en herramientas atractivas y prometedoras frente a las bacterias resistentes a m&#250;ltiples antimicrobianos&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Guti&#233;rrez-Santana JC&#44; Toscano-Garibay JD&#44; L&#243;pez-L&#243;pez M&#44; Coria-Jim&#233;nez VR&#46; Apt&#225;meros acoplados a nanopart&#237;culas para el diagn&#243;stico y tratamiento de las infecciones microbianas&#46; Enferm Infecc Microbiol Clin&#46; 2020&#59;38&#58;331&#8211;337&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Target bacteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Potential utility&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">References&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">QDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; typhimurium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">B&#46; subtilis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">P&#46; aeruginosa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; typhimurium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AuNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; enteritidis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; typhimurium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;10&#44;19&#44;20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;10&#44;19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">C&#46; jejuni</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">C&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">L&#46; acidophilus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Au-silica NPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; typhimurium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;21&#44;22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">P&#46; aeruginosa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; typhimurium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MBs and AuNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;19&#44;21&#44;24&#44;25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; typhimurium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;26&#44;27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MNPs and UCNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;26&#44;27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">V&#46; parahaemolyticus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FAM-labelled aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; typhimurium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;10</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MNPs and <span class="elsevierStyleItalic">nano gatekeepers</span> bound to FAM-labelled oligonucleotides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MBs&#44; AuNCs and vancomycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MBs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FITC-labelled antibody and aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MRSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SWNTs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Modified DNAzyme aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; Paratyphi A</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FAM-labelled aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">V&#46; parahaemolyticus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cy3-labelled aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROX-labelled aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; typhimurium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AuNCs&#44; vancomycin and AuNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AuNPs and UCNPs bound to aptamer cDNA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AgNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">fGmH-modified aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Nano gatekeepers</span> with vancomycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TiO<span class="elsevierStyleInf">2</span>NPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Three aptamers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AuNPs coupled to A3-APO<span class="elsevierStyleSup">His</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Histidine-labelled aptamer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">S&#46; typhimurium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Use of aptamers and nanoparticles used for the design of diagnostic and&#47;or therapeutic strategies against bacterial pathogens&#46;</p>"
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      "titulo" => "References"
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                      "Revista" => array:6 [
                        "tituloSerie" => "Biosens Bioelectron&#46;"
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                          "etal" => false
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                  ]
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                      "titulo" => "Highlight of recent advances in aptamer technology and its application"
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46; Sun"
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                      "doi" => "10.3390/molecules200711959"
                      "Revista" => array:6 [
                        "tituloSerie" => "Molecules&#46;"
                        "fecha" => "2015"
                        "volumen" => "20"
                        "paginaInicial" => "11959"
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                        "link" => array:1 [
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ISSN: 2529993X
Original language: English
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