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Aptamer-Embedded Zirconium-Based Metal–Organic Framework Composites Prepared by de novo Bio-Inspired Approach with Enhanced Biosensing for Detecting Trace Analytes Zhihong Zhang, Feng-He Duan, Jia-Yue Tian, Jun-Ying He, Long-Yu Yang, Hui Zhao, Shuai Zhang, Chun-Sen Liu, Ling-Hao He, Min Chen, Di-Ming Chen, and Miao Du ACS Sens., Just Accepted Manuscript • DOI: 10.1021/acssensors.7b00236 • Publication Date (Web): 29 Jun 2017 Downloaded from http://pubs.acs.org on June 29, 2017

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Aptamer-Embedded Zirconium-Based Metal–

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Organic Framework Composites Prepared by de

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novo Bio-Inspired Approach with Enhanced Bio-

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sensing for Detecting Trace Analytes

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Zhi-Hong Zhang, Feng-He Duan, Jia-Yue Tian, Jun-Ying He, Long-Yu Yang, Hui Zhao, Shuai

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Zhang, Chun-Sen Liu,* Ling-Hao He, Min Chen, Di-Ming Chen, and Miao Du*

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Henan Provincial Key Laboratory of Surface & Interface Science, Zhengzhou University of

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Light Industry, Zhengzhou 450002, China

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ABSTRACT: A series of Zr-based metal–organic framework (MOF) composites embedded with

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three kinds of aptamer strands (509-MOF@Apt) were achieved by a one-step de novo synthetic

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approach. A platform for ultrasensitive detection of analytes, namely, thrombin, kanamycin, and

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carcinoembryonic antigen (CEA), was also established. Considering the conformational changes

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caused by the binding interactions between aptamer strands and targeted molecules, the label-

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free electrochemical aptasensors based on 509-MOF@Apt composites could be developed to de-

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tect various target molecules. By comparing the common fabrication approaches of aptasensors,

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a distinct determination mechanism was presented through analysis of the electrochemical meas-

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urements on different interaction behaviors between probe aptamer strands and 509-MOF mate-

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rials. The optimized aptasensors based on 509-MOFs@Apt demonstrated excellent sensitivity

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(with the detection limit of 0.40, 0.37, and 0.21 pg mL 1 for CEA, thrombin, and kanamycin, re-

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ACS Paragon Plus Environment

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spectively), stability, repeatability, and applicability. This work will provide a new platform for

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direct and feasible detection in biosensing related to clinical diagnostics and therapeutics, and

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further, extend the scope of potential applications for MOF materials.

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KEYWORDS: one-step de novo synthesis, metal–organic frameworks (MOFs), Zr-based MOF

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composites, MOF-based aptasensors, ultrasensitive detection

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Metal–organic frameworks (MOFs) have attracted considerable interest as platforms used to an-

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chor or encapsulate functional components suchlike nanoparticles, organometallic catalysts, and

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organic molecules (e.g. proteins, enzymes, and drugs) for biomedical application.1 As a flourish-

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ing type of porous crystalline materials, MOFs have been well applied in fluorescent or chemical

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sensing. The host frameworks of MOFs can facilitate various interactions with analytes via the

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functional groups in organic ligands for highly sensitive and selective recognition.2 However, the

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encapsulation of targeted molecules into MOFs is costly and will produce large amounts of waste.

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The encapsulation process generally includes three steps: synthesis of MOFs, removal of guests

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from the pores, and incorporation of targeted molecules.3 The encapsulation of biomacromole-

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cules is difficult for the smaller pore sizes of MOFs, resulting in lower current loading capacity

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than that of other carriers (e.g. mesoporous carbon, silica, or polymeric vesicles).4 To overcome

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these drawbacks, the combination of MOFs synthesis and controllable encapsulation with target-

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ed molecules, such as nanoparticles,5 biomacromolecules,6 and anticancer drugs,7 into a one-step

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de novo process has been developed.

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Various organic molecules, including antibiotics, drugs, toxins, and pollutants, are required to

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be detected for environmental protection or medical treatment.8 In this context, thrombin is cru-

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cial in physiological and pathological coagulation, which regulates many processes in inflamma-

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tion and tissue repair at the vessel wall. The concentration of thrombin in the blood during coag-

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ulation varies from nM to M levels, and the detection at high pM range is important for related

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diagnoses.9 In addition, kanamycin has been broadly used in human and veterinary medicine for

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treatment of Gram-negative and Gram-positive infectious diseases. Uncontrolled and incorrect

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applications of kanamycin can lead to overaccumulation of this drug in animal-derived foods.10

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Carcinoembryonic antigen (CEA) has been proven to be the most reliable and specific marker for

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diagnoses of liver, colon, breast, and colorectal cancers,11 and the CEA levels are extremely low

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in adult colon tissues by ca. 2.5 g L 1.12 However, the conventional chromatographic and spec-

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troscopic analytical methods are time consuming and laborious, which require expensive equip-

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ments, trained operators, and tedious pretreatments.13 Thus, the simple, highly efficient, ultrasen-

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sitive, and field-portable screening methods should be developed.

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Among numerous biosensors, aptasensor is a new recognition biosensor with many advantages

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including chemical as-synthesis, high stability, and nontoxicity. Aptamers can bind with the tar-

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gets ranging from small substances to cells with high affinity and specificity.14 Compared with

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the traditional antibodies, aptamers demonstrate the advantages of high thermal stability, ease of

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production and modification, low cost, and lack of toxicity and immunogenicity.15 In comparison

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with other detection methods such as chemiluminescence assay,16 enzyme-linked immunosorbent

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assay,17 mass spectrometric immunoassay,18 radio-immunoassay,19 and fluorescence immunoas-

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say,20 electrochemical immunoassay contributes to optimal technology because of its intrinsic

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advantages including high sensitivity, easy miniaturization, low cost, rapid analysis, and implicit

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instruments.21 However, modification of DNA strands is tedious and expensive.22 Therefore, fast

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and cheap methods related to DNA biosensors fabrication are necessary. In this context, molecu-

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lar recognition of biosensor materials can be used for sensor fabrications23 through incorporation

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of metals or metal-binding units with desired electrical, magnetic, optical, and catalytic proper-

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ties.

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Notably, Zr-MOFs show excellent stability and potential biomedical applications for low tox-

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icity of Zr.24 Zr-MOFs present high affinity to phosphate groups of biomolecules,25 which have

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been used to selectively enrich phosphopeptides or immobilize DNA probes,26 and to sensitively

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detect phosphates via fluorescence.27 Aromatic electron-rich ligands endow MOFs with the abil-

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ity to absorb single-stranded DNA via

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fluorophores.28 These results inspire us to explore a new route to construct electrochemical ap-

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tasensors based on Zr-MOFs for highly efficient detection of proteins.29 However, Zr-MOFs as

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the sensitive layers of biosensors are not known, although few Zr-MOFs have been selected to

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recognize small molecules (e.g. phosphate).30 Macromolecules with phosphate groups, such as

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DNA or aptamer strands, cannot easily penetrate into the MOF frameworks because of electro-

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static repletion. This feature leads to interaction and coordination difficulty for phosphate groups

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on DNA strand backbone with Zr(IV). As a result, weak interactions of DNA immobilization and

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poor bioaffinity to target molecules will occur.31 As such, a new-style of Zr-MOF-based biosen-

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sors with a feasible and rapid approach should be developed to improve their biosensing ability.

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Therefore, the combination of high stability and biocompatibility of Zr-MOFs with the feasibility

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of one-step de novo process may provide outstanding biosensing performances for applications

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in biomedical and biological fields.

stacking and H-bonding and thus, to quench labeled

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This study reports a series of bioactive Zr-MOF-based composites embedded with aptamer

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strands (509-MOF@Apt) via a simple and straightforward one-step de novo approach, in which

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509-MOF is constructed based on the ligand 4',4''',4'''''-nitrilotris[1,1'-biphenyl]-4-carboxylic acid

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(H3NBB). The initial in situ incorporation of aptamer strands can allow the biomolecules to be

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homogeneously embedded in Zr-MOFs. Thus, the formation of Zr-MOFs and the coordination of aptamer strands with Zr(IV) simultaneously occur. The one-step de novo approach can simplify the synthetic process and facilitate the entry of aptamer strands into MOF frameworks. Once the MOF@Apt composite is coated onto the electrode, the biosensor can be formed and applied to detect the targeted molecules directly. As a result, the designed bioactive Zr-MOF composites show high bioaffinity toward the targeted biomolecules and the finally optimized biosensors represent ideal candidates for highly efficient and ultrasensitive detection of the targets (Scheme 1). This work presents a general, feasible, and time-saving strategy to detect trace analytes by using MOF-based biosensors, which will also provide a universal approach for construction of novel MOFs-based biosensors with desired performances. Scheme 1. Preparation Process of 509-MOF@Apt Composites and Detection Mechanism of 509-MOF@Apt-based Electrochemical Aptasensorsa

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(i) Coordination between Zr(IV) and aptamer strands. (ii) Preparation of 509-MOF@Apt composites. (iii)

Detection of analytes using the developed aptasensors.

EXPERIMENTAL SECTION

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Synthesis of 509-MOF (Powder). ZrOCl2·8H2O (0.5 mmol, 175.0 mg) was dissolved ultrasonically in a mixture of DMF (3 mL) and trifluoroacetic acid (0.5 mL) in a 10 mL screw-capped vial for 10 min. Then, H3NBB (80.0 mg, 0.1 mmol) was dissolved ultrasonically in DMF (3 mL) for 10 min. Finally, the homogeneous mixture was stirred for 2 days under 50 °C. The resulting yellow suspension was isolated by centrifugation at 10,000 r.p.m. for 3 min and then washed for three times with DMF to remove the unreacted precursor and collected by centrifuging at 10,000 r.p.m. for 3 min. As a result, pure 509-MOF powder was obtained and further used in the preparation of two- and three-step fabricated aptasensors. Synthesis of 509-MOF@Apt Composites. The solutions of CEA, thrombin, and kanamycin were separately added into a mixture solution of ZrOCl2·8H2O and H3NBB with sonicating for 30 min, keeping other experimental conditions unchanged with that for 509-MOF (powder). The products were referred to 509-MOF@AptCEA, 509-MOF@Aptthrombin, and 509-MOF@Aptkanamycin, respectively (see Supporting Information for characterization of serials 509-MOFs@Apt), which were applied to detect the individual analyte (called as the one-step fabricated aptasensors). Fabrication of Different Aptasensors. 509-MOF (powder), 509-MOF@Aptthrombin, and 509MOF@Aptkanamycin, and 509-MOF@AptCEA were well grinded, and then dispersed into deionized water (concentration: 1.0 mg mL–1). The homogeneous dispersion (5.0 µL) was dropped onto the surface of a bare Au electrode (AE) for further test. For comparison, three different systems were developed using the one-step de novo as well as two- and three-step methods (Scheme 2). When directly using the 509-MOF@Apt composites for detecting trace analytes, the AE was modified with 509-MOF@Apt composites (509-MOF@Apt/AE), following by detecting the corresponding analyte. When adding the aptamer solution into the dispersion of pure 509-MOF, the aptamer strands can be anchored (509-MOF/Apt). Then, the 509-MOF/Apt composites were coated onto

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the electrode surface (509-MOF/Apt/AE). It also can be applied to detect the corresponding analyte, assigned with the two-step fabrication. As for the three-step one, the AE was modified by pure 509-MOF (509-MOF/AE), following by the immobilization of aptamer strands (Apt/509MOF/AE). Finally, all the developed aptasensors were applied to detect the same analyte to optimize the detection strategy. Additionally, to analyze the real applications of the fabricated aptasensors, diverse concentrations of CEA and thrombin were spiked to human serum that was 50fold diluted with PBS, whereas diverse concentrations of kanamycin were spiked to the 50-fold diluted milk in PBS. RESULTS AND DISCUSSION Synthesis and Crystal Structure of 509-MOF. The extended tricarboxylate organic ligands have been shown to be good candidates for the construction of MOFs with larger pores or channels. Thus, the H3NBB ligand was used to react with Zr(IV) to prepare a new material 509-MOF. The powder product can be obtained under mild condition after several hours and the yield will be increased when the reaction time is prolonged to 48 h. Well-shaped single crystals could be achieved via hydrothermal synthesis at a higher temperature of 110 C for 72 h. The structure of 509-MOF was determined by X-ray diffraction (Tables S1 and S2). The result reveals that 509MOF crystallizes in a cubic space group Im-3m, consisting of octahedral Zr6O8(H2O)8 clusters as nodes (Figure 1a) and fully deprotonated NBB

ligands as linkers (Figure 1b). The asymmetry

unit comprises two eight-coordinated Zr ions in a tetragonal anti-dipyramid geometry. Six waterattached Zr atoms are ligated by eight cores are connected by the NBB

3-O

atoms to form a Zr6O8(H2O)8 core. The Zr6O8(H2O)8

ligands to afford a 3D framework with two types of cavities:

one is the octahedral cage with an inner hole of 3 nm in diameter (Figure 1c), which is formed by six Zr6O8(H2O)8 clusters and eight NBB ligands; and the other is a large 3D channel shaped by

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the packing of the octahedral cages with a diameter of 2.7 nm (Figure 1b). The co-existence of cages and channels contributes to a highly porous framework, which is large enough for another identical interpenetration (Figure 1d). Thus, a doubly interpenetrated framework with a solventaccessible volume of 71.5% is formed. From the topological view point, each Zr6O8(H2O)8 cluster can be regarded as an 8-connected node and each NBB ligand as a 3-connected node. Thus, it can be simplified as a (3,8)-connected network with a the-a topology (Figure S1).

Figure 1. Crystal structure of 509-MOF: (a) Zr6O8(H2O)8 core, (b) octahedral cage, (c) a single framework, and (d) doubly interpenetrated framework. Comparison of Electrochemical Aptasensors with 509-MOFs. EIS is a powerful, nondestructive, and informative technique used to examine microscopic interfacial events and serve as a transducer.32 The semicircle diameter of Nyquist plot equals the electron transfer resistance (Rct) (Figure S7).33 In this work, to evaluate the detection efficiency of aptasensors based on one-step de novo 509-MOF@Apt composites, two- and three-step fabricated aptasensors were also proposed for comparison. Here, we only discuss the detection of CEA using the developed one-step

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de novo aptasensors (see Figures S8 and S9 for thrombin- and kanamycin-detecting aptasensors). For one-step fabricated aptasensor, the 509-MOFs@AptCEA composite was employed as the sensitive layer (Figure 2a), whereas the 509-MOFs/AptCEA composite was directly used to determine CEA in the two-step fabrication (Figure 2b). In case of the three-step aptasensor fabrication, the pure 509-MOF was explored as a platform for the immobilization of CEA-targeted aptamer.

Figure 2. EIS of CEA detection (concentration: 0.005 ng mL 1) procedures with the aptasensors based on (a) 509-MOF@AptCEA ((i) Au electrode (AE), (ii) 509-MOF@AptCEA/AE, and (iii) CEA/509-MOF@AptCEA/AE). (b) 509-MOF/AptCEA ((i) AE, (ii) 509-MOF/AptCEA/AE, and (iii) CEA/509-MOF/AptCEA/AE). (c) 509-MOF (i) AE, (ii) 509-MOF/AE, (iii) AptCEA/509-MOF/AE, and (iv) CEA/AptCEA/509-MOF/AE) in 5 mM [Fe(CN)6]

/4

containing 0.14 M NaCl and 0.1 M

KCl. (d) The detection efficiency of the three kinds of aptasensors (509-MOF@AptCEA for onestep de novo method, 509-MOF/AptCEA for two-step method, and 509-MOF for three-step method) by using the variations of Rct values before and after the CEA detection.

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CEA detection was performed, including Au electrode modification with 509-MOF, aptamer immobilization, and CEA detection (Figure 2c). The bare AE exhibits a relatively low interface of electron-transfer resistance (Rct = 51.5 ohm, curve i, Figure 2a). After the modification with 509-MOF@AptCEA, the Rct value increases to 0.42 kohm (curve ii, Figure 2a). The combination effect of repulsion interaction between negatively charged phosphate groups in aptamer strands, as well as the redox of [Fe(CN)6]

/4

and the blocking effect of organic component in 509-MOF

can thus be explained. The 509-MOF@AptCEA significantly decreases the electron-transfer rate and exhibits a high electron-transfer resistance.34 In the presence of CEA (curve iii, Figure 2a), the composite electrode of CEA/509-MOF@AptCEA/AE shows a high Rct value of 1.43 kohm, which is ascribed to the recognized binding interactions between aptamer and CEA, further decreasing the electron transfer.35 Similarly, the gradual increase in Rct value of the bare AE (curve i, Figure 2b), 509-MOF/AptCEA/AE (curve ii, Figure 2b), and CEA/509-MOF/AptCEA/AE (curve iii, Figure 2b) was observed for CEA detection. The two-step aptasensor fabrication was used with different Rct values. For the three-step development of the aptasensor, the electrode of the bare AE (curve i, Figure 2c), 509-MOF/AE (curve ii, Figure 2c), AptCEA/509-MOF/AE (curve iii, Figure 2c), and CEA/AptCEA//509-MOF/AE (curve iv, Figure 2c) exhibit the Rct values of 39.20 ohm as well as 0.25, 0.59, and 0.77 kohm, also demonstrating an increasing trend in the electrontransfer resistance. EIS results for thrombin and kanamycin detection with three aptasensors (Figures S8 and S9) indicate that the similar behaviors for targeted molecules. The aptasensor performance responding to the immobilization of aptamer probe onto a surface represents an alternative method for detection of protein concentration through recognition binding.36 The difference in Rct value ( Rct) of each step can be referred to the binding amount of the additional layers.37 For further comparison of the detection efficiency, the Rct values of three

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kinds of aptasensors for CEA detection are shown in Figure 2d. The largest Rct value ( Rct = Rct,CEA/509-MOF@AptCEA/AE

Rct,509-MOF@AptCEA/AE, 1.00 kohm) was calculated before and after de-

tecting CEA through one-step fabrication, whereas the lowest detected amount was obtained for the three-step one. To verify the generality of the one-step 509-MOFs@Apt preparation for the detection of target proteins, the 509-MOFs@Aptthrombin and 509-MOFs@Aptkanamycin composites were synthesized and applied to the trace detection of the corresponding analytes. Their Nyquist diagrams for the same procedures and comparison systems are presented in Figures S8d and S9d. The same results indicate the optimal detection efficiency of the one-step fabricated aptasensors. Scheme 2 illustrates the interactions between targeted molecules and the probes for the diverse sensing systems to differentiate the detection mechanisms for three aptasensors. Figures 2d, S8d, and S9d present no significant difference in the analyte detection between the two- and three-step developed aptasensors. To probe the changes of chemical environments or components of different proposed strategies, XPS measurements were taken on the two- and three-step fabricated aptasensors. The main elements for three kinds of two-step fabricated 509-MOF/Apt composites and three kinds of 509-MOF immobilized with aptamer for three-step fabrication are listed in Tables S5 and S6, respectively. The intensities of Zr 2d are lower (from 1.19 to 1.78%; Table S5) than the Zr 3d atomic% of the films spin-coated onto the silicon wafers with one-step developed 509-MOF@Apt composites (ca. 3.45 to 4.08%; Table S3). The lowest values (from 0.46 to 0.92%; Table S6) were detected from the 509-MOF/Apt composites prepared via two-step method and those of three-step prepared 509-MOF immobilized with aptamer strands. Given the stacking interactions and formation of Zr O P groups, the aptamer strands can be absorbed onto the 509-MOF framework.38 However, when the aptamer strands approached the surface of 509MOFs, most of the oligonucleotide molecules would anchor and lie down onto the framework

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surface rather than penetrate into the framework interior because of the repulsion interactions of the negatively charged phosphate groups in the immobilized aptamer strands39 (Parts i and ii in Scheme 2). Therefore, the Zr 3d contents of the two- and three-step fabricated aptasensors decrease because of the coverage of the immobilized aptamer strands. The thickness limitation (< 8 10 nm) makes the chemical components of material surface determined by XPS.40 For the three-step samples, less amounts of Zr 3d can be observed because the 509-MOF surface was immobilized with the oligonucleotide strands. This assumption can be proven by the relative intensities of each oxygen-related group in the two- and three-step fabricated sensing layers. Figure S10 shows the O 1s core-level XPS spectra of the 509-MOF/Apt composites, where the relative intensity of combined peak is higher than those of the two other kinds of fabricated films. This finding can be attributed to the Zr O P, P=O, C O C, C O H, or P OH groups for one-step fabricated 509-MOF@Apt composites. The result reveals that large amounts of aptamer strands anchor within the bulk of the composites. Given the coverage of the immobilized aptamer strands, the relative intensities of the Zr O group of the three-step fabricated films are apparently lower than those of the one- and two-step 509-MOF/Apt composites (Figure S10). When the targeted molecules are present, the aptamer strands cannot easily transform their conformation to bind with them, even if a part of the aptamer strands can permeate into the interior of 509-MOF pores. As a result, although a certain amount of aptamer strands were observed and referred as the variation of the Rct values before and after the aptamer immobilization on the composite electrode, a relatively lower Rct value was obtained after detecting targeted molecules. For the onestep fabricated aptasensor, a significant change of Rct value for three kinds of aptasensors was obtained (Figures 2d, S8d, and S9d). In the preparation procedure of 509-MOF@Apt composites, the aptamer strands were first contacted with free Zr(IV) ions, resulting in the formation of large

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amounts of Zr O P through the covalent bonds between Zr(IV) and the aptamer backbone (Part iii in Scheme 2).41 Once the ligands were introduced into the container, a part of Zr atoms in Zr O P groups will be replaced by the coordination of Zr(IV) with ligands. With the construction of the three-dimensional 509-MOF framework, the aptamer strands were embedded within the crystal lattice. The specific surface areas of the one-step fabricated samples (1511 m2 g 1 for 509-MOFs@AptCEA, 1525 m2 g

1

for 509-MOFs@Aptkanamycin, and 1504 m2 g

1

for 509-

MOFs@Aptthrombin) are lower than those of the pure 509-MOF (2192 m2 g 1, Figure S11). This finding illustrates that the aptamer strands embedded into the 509-MOF composites occupy the porous space in the framework interior. When detecting the targeted molecules, they can feasibly penetrate into the interior of the 509-MOFs@Apt composites and bind with the aptamer sequences.42 As expected, the proposed aptasensor based on the 509-MOF@Apt composites prepared via one-step de novo method has a higher detection amount of targeted molecules than those obtained by the other strategies.

Scheme 2. Detection Mechanism for the Targeted Molecules with the Proposed Aptasensors Fabricated via (i) Three-, (ii) Two-, and (iii) One-step de novo Approaches.

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As shown in Table S7, the atomic% of F 1s in fully clean (FC) samples is lower than those in the related films. To evaluate the effect of the C F2 group reservation on the detection of targeted molecules, the same procedure for each detected system was performed again by using the FC pure 509-MOF and 509-MOFs@Apt composites as sensitive layers. Figure S12 shows the Rct values of each step during the period of the aptasensor fabrications in detecting the targeted molecules. The results show that the three kinds of FC 509-MOF materials and modified electrodes exhibit high Rct values. This finding indicates relatively poor electrochemical activity than that demonstrated by C F2-rich 509-MOFs.43 However, after detecting the analytes, the resultant Rct changes are substantially lower than those of the same aptasensors with 509-MOF@Apt composites with high intensity of C F2 groups. All these findings prove that the reservation of C F2 in 509-MOF is favorable for improving the electrochemical activity of the composite electrode and enhancing the detection efficiency, probably because of the high van der Waals interaction related to the C F2. Consequently, smaller analyte molecules are absorbed. Here, for the two- or three-step fabricated aptasensors based on 509-MOF, the aptamer strands will not only immobilize onto the surface of MOF but also penetrate into the framework interior via physical interactions or hydrophobicity due to the high porosity and bioaffinity of Zr-MOFs. After rinsing with PBS solution, most of the adsorbed molecules could be removed from the bulk material of Zr-MOFs with only a small amount residues. This will account for the fact that other non-targeted molecules can still be adsorbed and determined by EIS as revealed in the selectivity experiments. In the presence of aptamer strands, the targets can bind with them and lead to conformation changes as determined by EIS. Once the first layer of aptamer strands was anchored, it is hard for the next layer of strands to be adsorbed on due to the repulsion interactions between the negative-charged phosphate groups on strands. The less binding amounts of aptamer strands

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would limit the detection efficiency of targeted molecules. As for the one-step fabricated 509MOF@Apt composite, since large amounts of aptamer strands will be embedded within the interior of 509-MOF, more binding sites inside the 509-MOF composite lead to the combination of large amounts of targeted molecules. Therefore, the one-step fabricated aptasensor exhibits higher detection efficiency towards the targets. Sensitivity of the Developed Aptasensors Based on One-Step-Synthesized 509-MOFs. The analytical performance of the aptasensor based on 509-MOF@AptCEA was evaluated by the calibration curves in EIS measurements. For this goal, 509-MOF@AptCEA/AE was exposed to various concentrations for 1 h. The corresponding Nyquist plots of impedance spectra are presented in Figure 3a, in which the diameter of the Nyquist circle increased with increasing concentration of CEA. Notably, the high aptamer concentration can increase the number of CEA bound to the modified AE, which subsequently hinders the definite kinetics for electron transfer. The change in Rct was used to evaluate the response to different concentrations of CEA.44 The sensitivity of the developed aptasensor for detecting CEA was determined based on the values obtained for detecting and quantification limits. The limit of detection (LOD) was defined as the lowest target molecule concentration that can be detected with an acceptable accuracy. As shown in Figure 3b, the Rct values obtained with [Fe(CN)6]

/4

establish a good linear correlation with logarithm of

CEA concentration from 0.001 to 0.50 ng mL 1. The linear regression equation can be expressed as Rct = 1.96 + 0.57 logCCEA (ng mL 1) with a correlation coefficient of 0.991 (n = 3). As such, LOD can be calculated using the parameters obtained from the regression curve. The LOD value was estimated to be approximately 0.40 pg mL

1

at the signal to noise ratio (S/N, defined as the

CEA concentration corresponding to the signal which equals to the zero signal minus three times the standard deviation) of 3 ( is the standard deviation of signal in a blank solution). Further,

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the analytical performance of aptasensor with 509-MOF@Aptkanamycin or 509-MOF@Aptthrombin composites was investigated to detect thrombin and kanamycin (Figures S13 and 14). The linear equation between the kanamycin concentration was observed to be Rct = 4.58 + 1.28 logCkanamycin

(ng mL 1), with LOD of 0.21 pg mL 1 at the S/N of 3 and a correlation coefficient of 0.990

(n = 3); for the detection of thrombin, the equation was Rct = 4.78 + 1.39 logCthrombin (ng mL 1), with LOD of 0.37 pg mL 1 at the S/N of 3 and a correlation coefficient of 0.992 (n = 3). Clearly, the EIS aptasensors herein exhibit better sensitivity than the reported examples (Table S8). These results indicate that the proposed assays are efficient for sensitive detection of the targeted molecules with the one-step fabricated aptasensors.

Figure 3. (a) EIS response of 509-MOF@AptCEA/AE with different concentrations of CEA (0, 0.001, 0.005, 0.01, 0.05, 0.10, and 0.50 ng mL 1). (b) Dependence of Rct values of the modified electrode on concentration of CEA (inset: the linear part of the calibration curve). Selectivity, Stability and Reproducibility of Aptasensors. The selectivity of three kinds of aptasensors was estimated by comparing the electrochemical signals of targets (0.001 ng mL 1) to other possible interferences. The interfering effect is defined as the concentration of interfering species that can change the electrode response toward analyte. For the developed aptasensor

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in CEA detection, the results show that the Rct caused by the addition of interfering components is not significantly affected (Figure 4a).45 Similar results of the selectivity toward thrombin (Figure S15a) and kanamycin detection (Figure S16a) are also observed, even in the presence of different interfering components. The good selectivity of the aptasensors based on 509-MOF@Apt composites is attributed to the high specificity between aptamer strands and targeted molecules.

0.35

(b)

(a)

0.3

0.30 0.25

Rct/kohm

R ct/kohm

1 2 3 4 5 6 327 7 8 9 328 10 11329 12 13330 14 15 331 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30332 31 32 33333 34 35 36334 37 38 39335 40 41336 42 43 337 44 45 46338 47 48339 49 50340 51 52 53341 54 55342 56 57 58 59 60

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0.20 0.15

0.2

0.1

0.10 0.05 0.00

b in -B B M U C 1 o g lo P D G F h em

0.0

H S A p ro tein -f eto

CE A

Different electrodes

Figure 4. (a) Selectivity and (b) reproducibility of the 509-MOF@AptCEA-based aptasensor for detection of CEA with a concentration of 0.001 ng mL 1. To determine the detection of intra-assay stability for each aptasensor, five electrodes were independently fabricated under the same conditions and stored at 4 °C when not in use.44 The variation of Rct values for aptasensors remains stable for different electrodes. The result also reveals the relative standard deviation (RSD) values of fabricated aptasensors for CEA detection (Figure 4b), thrombin (Figure S15b), and kanamycin (Figure S16b) at 3.86, 6.50, and 4.85%, respectively. The stability of inter-assay for each aptasensor was further investigated (Figure S17). After 15 days, the variations of Rct values of the aptasensors show no significant change, revealing a sufficient stability of analyte detection for the proposed aptasensors based on one-step prepared 509-

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MOF@Apt composites. Overall, the results demonstrate that the proposed aptasensors have necessary selectivity, stability, and reproducibility. Real Samples. Since CEA or thrombin does not exist in healthy human serum sample, different concentrations of CEA and thrombin are separately spiked into 50-fold-diluted serum samples (obtained from the People’s Hospital of Henan Province, China) to verify the wider applicability of the integrated sensing platform. Notably, the dilution treatment is required since some components contained in human serum sample (e.g. proteins, glucose, and inorganic salts) can interfere the electrochemical measurement result.46,47 As shown in Table S9, the recoveries vary from 99.74 to 103.39% for CEA detection, whereas they change from 98.0 to 110% for thrombin detection. The feasibility of aptasensor based on 509-MOF@Aptkanamycin was used to detect the recoveries of different concentrations of kanamycin in animal-derived food by standard addition methods. Samples were deproteinated and extracted from healthy pork meat, and then the extract was diluted with PBS (pH = 7.4). The recoveries vary from 99.12 to 100.9% for kanamycin detection. CONCLUSIONS In summary, a series of Zr-MOF-based composites embedded with diverse aptamer strands (509MOF@Apt) have been successfully prepared by using a one-step de novo approach, which can be further applied as a platform to ultra-sensitively detect targets, such as thrombin, kanamycin, and CEA. Compared with conventional inorganic or inorganic-organic composite, the optimized aptasensors with 509-MOFs@Apt composites show excellent biosensing capacity, stability, reproducibility, and applicability. The detection mechanism of the one-step de novo approach was presented based on the analysis of different interaction behaviors between probe aptamer strands

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and 509-MOF. Considering the great diversity and tunability for MOF materials, the established one-step de novo strategy may provide important prospects for rational fabrication of multifarious MOF-based aptamer biosensors for specifically targeted analytes, which is essential for timely clinical diagnoses and treatments of diseases. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssensors.xxxxxx Experimental section, crystallographic information, characterization of 509-MOF@Apt, EIS of the thrombin/kanamycin detection procedures, N2 sorption curves, detection efficiency comparison of aptasensors, sensitivity/selectivity/reproducibility of aptasensors for detecting thrombin/kanamycin; the inter-assay stability of aptasensors for detecting CEA/thrombin/kanamycin; detection in the real samples (PDF) Accession Codes CCDC 1508925 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033. AUTHOR INFORMATION Corresponding Author

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* E-mail: [email protected]; [email protected] Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (21471134 and 21571158), Innovation Scientists and Technicians Troop Construction Projects of Henan Province (152101510003), Plan for Scientific Innovation Talent of Henan Province (154200510011), and Program for Science & Technology Innovative Research Team in University of Henan Province (15IRTSTHN-002). REFERENCES (1) Nath, I.; Chakraborty, J.; Verpoort, F. Metal organic frameworks mimicking natural enzymes: a structural and functional analogy. Chem. Soc. Rev. 2016, 45, 4127–4170. (2) Hu, Z.; Deibert, B. J.; Li, J. Luminescent metal–organic frameworks for chemical sensing and explosive detection. Chem. Soc. Rev. 2014, 43, 5815–5840. (3) Liu, R.; Yu, T.; Shi, Z.; Wang, Z. The preparation of metal–organic frameworks and their biomedical application. Int. J. Nanomed. 2016, 11, 1187–1200. (4) Shekhah, O.; Liu, J.; Fischer, R. A.; Wöll, C. MOF thin films: existing and future applications. Chem. Soc. Rev. 2011, 40, 1081–1106. (5) Lu, G.; Li, S.; Guo, Z.; Farha, O. K.; Hauser, B. G.; Qi, X.; Wang, Y.; Wang, X.; Han, S.; Liu, X.; DuChene, J. S.; Zhang, H.; Zhang, Q.; Chen, X.; Ma, J.; Loo, S. C. J.; Wei, W. D.; Yang,

20


Page 21 of 27

1 2 3 4 5 6 405 7 8 9 406 10 11407 12 13 408 14 15 16409 17 18410 19 20 21411 22 23412 24 25 413 26 27 28414 29 30415 31 32 33416 34 35417 36 37 418 38 39 40419 41 42420 43 44 45421 46 47422 48 49 423 50 51 52424 53 54425 55 56 57426 58 59427 60

ACS Sensors

Y.; Hupp, J. T.; Huo, F. Imparting functionality to a metal–organic framework material by controlled nanoparticle encapsulation. Nat. Chem. 2012, 4, 310–316. (6) Liang, K.; Ricco, R.; Doherty, C. M.; Styles, M. J.; Bell, S.; Kirby, N.; Mudie, S.; Haylock, D.; Hill, A. J.; Doonan, C. J.; Falcaro, P. Biomimetic mineralization of metal–organic frameworks as protective coatings for biomacromolecules. Nat. Commun. 2015, 6, 1–8. (7) Zheng, H.; Zhang, Y.; Liu, L.; Wan, W.; Guo, P.; Nyström, A. M.; Zou, X. One-pot synthesis of metal–organic frameworks with encapsulated target molecules and their applications for controlled drug delivery. J. Am. Chem. Soc. 2016, 138, 962–968. (8) Duan, R.; Lou, X.; Xia, F. The development of nanostructure assisted isothermal amplification in biosensors. Chem. Soc. Rev. 2016, 45, 1738–1749. (9) Xiao, Y.; Lubin, A. A.; Heeger, A. J.; Plaxco, K. W. Label-free electronic detection of thrombin in blood serum by using an aptamer-based sensor. Angew. Chem. Int. Ed. 2005, 44, 5456–5459. (10) Bai, X.; Hou, H.; Zhang, B.; Tang, J. Label-free detection of kanamycin using aptamerbased cantilever array sensor. Biosens. Bioelectron. 2014, 56, 112–116. (11) Limbut, W.; Kanatharana, P.; Mattiasson, B.; Asawatreratanakul, P.; Thavarungkul, P. A reusable capacitive immunosensor for carcinoembryonic antigen (CEA) detection using thiourea modified gold electrode. Anal. Chim. Acta 2006, 561, 55–61. (12) Yang, X.; Zhuo, Y.; Zhu, S.; Luo, Y.; Feng, Y.; Xu, Y. Selectively assaying CEA based on a creative strategy of gold nanoparticles enhancing silver nanoclusters’ fluorescence. Biosens. Bioelectron. 2015, 64, 345–351. (13) Chauhan, R.; Singh, J.; Sachdev, T.; Basu, T.; Malhotra, B. D. Recent advances in mycotoxins detection. Biosens. Bioelectron. 2016, 81, 532–545.

21


ACS Sensors

1 2 3 4 5 6 428 7 8 9 429 10 11430 12 13 431 14 15 16432 17 18433 19 20 21434 22 23435 24 25 436 26 27 28437 29 30438 31 32 33439 34 35440 36 37441 38 39 40442 41 42443 43 44 444 45 46 47445 48 49446 50 51 52447 53 54448 55 56 449 57 58 59450 60

Page 22 of 27

(14) Meng, H. M.; Liu, H.; Kuai, H.; Peng, R.; Mo, L.; Zhang, X.-B. Aptamer-integrated DNA nanostructures for biosensing, bioimaging and cancer therapy. Chem. Soc. Rev. 2016, 45, 2583– 2602. (15) Iliuk, A. B.; Hu, L.; Tao, W. A. Aptamer in bioanalytical applications. Anal. Chem. 2011, 83, 4440–4452. (16) Luo, M.; Chen, X.; Zhou, G.; Xiang, X.; Chen, L.; Ji, X.; He, Z. Chemiluminescence biosensors for DNA detection using graphene oxide and a horseradish peroxidase-mimicking DNAzyme. Chem. Commun. 2012, 48, 1126–1128. (17) Sun, W.; Jiao, K.; Zhang, S.; Zhang, C.; Zhang, Z. Electrochemical detection for horseradish peroxidase-based enzyme immunoassay using p-aminophenol as substrate and its application in detection of plant virus. Anal. Chem. Acta 2001, 434, 43–50. (18) Hu, S.; Zhang, S.; Hu, Z.; Xing, Z.; Zhang, X. Detection of multiple proteins on one spot by laser ablation inductively coupled plasma mass spectrometry and application to immunomicroarray with element-tagged antibodies. Anal. Chem. 2007, 79, 923–929. (19) Liu, R.; Zhang, S.; Wei, C.; Xing, Z.; Zhang, S.; Zhang, X. Metal stable isotope tagging: renaissance of radioimmunoassay for multiplex and absolute quantification of biomolecules. Acc. Chem. Res. 2016, 49, 755–783. (20) Zhang, W. H.; Ma, W.; Long, Y. T. Redox-mediated indirect fluorescence immunoassay for the detection of disease biomarkers using dopamine-functionalized quantum dots. Anal. Chem. 2016, 88, 5131–5136. (21) Deng, H.; Li, J.; Zhang, Y.; Pan, H.; Xu, G. A new strategy for label-free electrochemical immunoassay based on “gate-effect” of -cyclodextrin modified electrode. Anal. Chim. Acta 2016, 926, 48–54.

22


Page 23 of 27

1 2 3 4 5 6 451 7 8 9 452 10 11453 12 13 454 14 15 16455 17 18456 19 20 21457 22 23458 24 25 459 26 27 28460 29 30461 31 32 33462 34 35463 36 37 464 38 39 40465 41 42466 43 44 45467 46 47468 48 49469 50 51 52470 53 54471 55 56 57472 58 59473 60

ACS Sensors

(22) Sina, A. A. I.; Carrascosa, L. G.; Palanisamy, R.; Rauf, S.; Shiddiky, M. J. A.; Trau, M. Methylsorb: a simple method for quantifying DNA methylation using DNA-gold affinity interactions. Anal. Chem. 2014, 86, 10179–10185. (23) Waldron, K. J.; Rutherford, J. C.; Ford, D.; Robinson, N. J. Metalloproteins and metal sensing. Nature 2009, 460, 823–830. (24) Bai, Y.; Dou, Y.; Xie, L.-H.; Rutledge, W.; Li, J.-R.; Zhou, H.-C. Zr-based metal–organic frameworks: design, synthesis, structure, and applications. Chem. Soc. Rev. 2016, 45, 2327–2367. (25) Zhang, G.-Y.; Deng, S.-Y.; Cai, W.-R.; Cosnier, S.; Zhang, X.-J.; Shan, D. Magnetic zirconium hexacyanoferrate(II) nanoparticle as tracing tag for electrochemical DNA assay. Anal. Chem. 2015, 87, 9093–9100. (26) Giustina, G. D.; Zambon, A.; Lamberti, F.; Elvassore, N.; Brusatin, G. Straightforward micropatterning of oligonucleotides in microfluidics by novel spin-on ZrO2 surfaces. ACS Appl. Mater. Interfaces 2015, 7, 13280–13288. (27) Yang, J.; Dai, Y.; Zhu, X.; Wang, Z.; Li, Y.; Zhuang, Q.; Shi, J.; Gu, J. Metal–organic frameworks with inherent recognition sites for selective phosphate sensing through their coordination-induced fluorescence enhancement effect. J. Mater. Chem. A 2015, 3, 7445–7452. (28) He, C.; Lu, K.; Liu, D.; Lin, W. Nanoscale metal–organic frameworks for the Co-delivery of cisplatin and pooled siRNAs to enhance therapeutic efficacy in drug-resistant ovarian cancer cells. J. Am. Chem. Soc. 2014, 136, 5181–5184. (29) Bell, J. Predicting disease using genomics. Nature 2004, 429, 453–456. (30) Yang, D.; Ge, F.; Tian, M.; Ning, N.; Zhang, L.; Zhao, C.; Ito, K.; Nishi, T.; Wang, H.; Luan, Y. Dielectric elastomer actuator with excellent electromechanical performance using slidering materials/barium titanate composites. J. Mater. Chem. A 2015, 3, 9468–9479.

23


ACS Sensors

1 2 3 4 5 6 474 7 8 9 475 10 11476 12 13 477 14 15 16478 17 18479 19 20 21480 22 23481 24 25 482 26 27 28483 29 30484 31 32 33485 34 35486 36 37 487 38 39 40488 41 42489 43 44 45490 46 47491 48 49492 50 51 52493 53 54494 55 56 495 57 58 59496 60

Page 24 of 27

(31) Hou, S.; Wang, J.; Martin, C. R. Template-synthesized DNA nanotubes. J. Am. Chem. Soc. 2005, 127, 8586–8587. (32) Shervedani, R. K.; Pourbeyram, S. Zirconium immobilized on gold-mercaptopropionic acid self-assembled monolayer for trace determination of phosphate in blood serum by using CV, EIS, and OSWV. Biosens. Bioelectron. 2009, 24, 2199–2204. (33) Yagati, A. K.; Choi, Y.; Park, J.; Choi, J.-W.; Jun, H.-S.; Cho, S. Silver nanoflower-reduced graphene oxide composite based micro-disk electrode for insulin detection in serum. Biosens. Bioelectron. 2016, 80, 307–314. (34) Furst, A. L.; Hill, M. G.; Barton, J. K. A multiplexed, two-electrode platform for biosensing based on DNA-mediated charge transport. Langmuir 2015, 31, 6554–6562. (35) He, L.; Zhang, S.; Ji, H.; Wang, M.; Peng, D.; Yan, F.; Fang, S.; Zhang, H. Jia, C.; Zhang, Z. Protein-templated cobaltous phosphate nanocomposites for the highly sensitive and selective detection of platelet-derived growth factor-BB. Biosens. Bioelectron. 2016, 79, 553–560. (36) Shin, K.; Cho, J.-H.; Yoon, M.-Y.; Chung, H. Use of multiple peptide-based SERS probes binding to different epitopes on a protein biomarker to improve detection sensitivity. Anal. Chem. 2016, 88, 3465–3470. (37) She, Z.; Topping, K.; Shamsi, M. H.; Wang, N.; Chan, N. W. C.; Kraatz, H.-B. Investigation of the utility of complementary electrochemical detection techniques to examine the in vitro affinity of bacterial flagellins for a toll-like receptor 5 biosensor. Anal. Chem. 2015, 87, 4218– 4224. (38) Zhu, Y.; Cai, Y.; Xu, L.; Zheng, L.; Wang, L.; Qi, B.; Xu, C. Building an aptamer/graphene oxide FRET biosensor for one-step detection of bisphenol A. ACS Appl. Mater. Interfaces 2015, 7, 7492–7496.

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Page 25 of 27

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ACS Sensors

(39) Yiu, H. H. P.; Bouffier, L.; Boldrin, P.; Long, J.; Claridge, J. B.; Rosseinsky, M. J. Comprehensive study of DNA binding on iron(II,III) oxide nanoparticles with a positively charged polyamine three-dimensional coating. Langmuir 2013, 29, 11354–11365. (40) Baena, J. P. C.; Steier, L.; Tress, W.; Saliba, M.; Neutzner, S.; Matsui, T.; Giordano, F.; Jacobsson, T. J.; Kandada, A. R. S.; Zakeeruddin, S. M.; Petrozza, A.; Abate, A.; Nazeeruddin, M. K.; Gr tzel, M.; Hagfeldt, A. Highly efficient planar perovskite solar cells through band alignment engineering. Energy Environ. Sci. 2015, 8, 2928–2934. (41) Liu, H.; Queffelec, C.; Charlier, C.; Defontaine, A.; Fateh, A.; Tellier, C.; Talham, D. R.; Bujoli, B. Design and optimization of a phosphopeptide anchor for specific immobilization of a capture protein on zirconium phosphonate modified supports. Langmuir 2014, 30, 13949–13955. (42) Wang, Y.; Zhu, Y.; Binyam, A.; Liu, M.; Wu, Y.; Li, F. Discovering the enzyme mimetic activity of metal–organic framework (MOF) for label-free and colorimetric sensing of biomolecules. Biosens. Bioelectron. 2016, 86, 432–438. (43) Han, S.-S.; Bae, B.-S. Thermal stability of fluorinated amorphous carbon thin films with low dielectric constant. J. Electrochem. Soc. 2001, 148, 67–72. (44) Xia, W.; Li, Y.; Wan, Y.; Chen, T.; Wei, J.; Lin, Y.; Xu, S. Electrochemical biosensor for estrogenic substance using lipid bilayers modified by Au nanoparticles. Biosens. Bioelectron. 2010, 25, 2253–2258. (45) Kumar, S.; Kumar, S.; Srivastava, S.; Yadav, B. K.; Lee, S. H.; Sharma, J. G.; Doval, D. C.; Malhotra, B. D. Reduced graphene oxide modified smart conducting paper for cancer biosensor. Biosens. Bioelectron. 2015, 73, 114–122.

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(46) Leng, Y.; Wu, W.; Li, L.; Lin, K.; Sun, K.; Chen, X.; Li, W. Magnetic/fluorescent barcodes based on cadmium-free near-infrared-emitting quantum dots for multiplexed detection Adv. Funct. Mater. 2016, 26, 7581–7589. (47) Li, H.; Shi, L.; Sun, D.; Li, P.; Liu, Z. Fluorescence resonance energy transfer biosensor between upconverting nanoparticles and palladium nanoparticles for ultrasensitive CEA detection Biosens. Bioelectron. 2016, 86, 791–798.

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