Aptamer-functionalized metal-organic frameworks (MOFs) for biosensing

Abstract

As a class of crystalline porous materials, metal-organic frameworks (MOFs) have attracted increasing attention. Due to the nanoscale framework structure, adjustable pore size, large specific surface area, and good chemical stability, MOFs have been applied widely in many fields such as biosensors, biomedicine, electrocatalysis, energy storage and conversions. Especially when they are combined with aptamer functionalization, MOFs can be utilized to construct high-performance biosensors for numerous applications ranging from medical diagnostics and food safety inspection, to environmental surveillance. Herein, this article reviews recent innovations of aptamer-functionalized MOFs-based biosensors and their bio-applications. We first briefly introduce different functionalization methods of MOFs with aptamers, which provide a foundation for the construction of MOFs-based aptasensors. Then, we comprehensively summarize different types of MOFs-based aptasensors and their applications, in which MOFs serve as either signal probes or signal probe carriers for optical, electrochemical, and photoelectrochemical detection, with an emphasis on the former. Given recent substantial research interests in stimuli-responsive materials and the microfluidic lab-on-a-chip technology, we also present the stimuli-responsive aptamer-functionalized MOFs for sensing, followed by a brief overview on the integration of MOFs on microfluidic devices. Current limitations and prospective trends of MOFs-based biosensors are discussed at the end.

Keywords: Aptamer; Aptasensor; Biosensor; Metal-organic frameworks (MOFs); Microfluidic; Stimuli-responsive.

Fig.1.

Schematic of aptamers-functionalized MOFs-based and microchip biosensors. The photograph of the microfluidic device is reproduced with permission from (Dou et al., 2017a).

Fig. 2.

Schematic of covalent binding between DNA and MOFs. (a) Amide bonds forming between amino groups on UIO-66 and carboxyl groups on the end of nucleic acids. Reproduced with permission from (Chang et al., 2019). (b) Covalent immobilization of nucleic acids with the aid of surfactant and crosslinkers. Reproduced with permission from (Tolentino et al., 2020).

Fig. 3.

Schematic of MOFs-based fluorescence and CL aptasensors. (a) A fluorescence aptasensor based on fluorescence quenching on H₂dtoaCu to detect ATP. Reproduced with permission from (Hai et al., 2018). (b) A chemiluminescent sensing platform based on the luminol-H₂O₂-MOF system. Reproduced with permission from (Xie et al., 2019). (c) A preparation process of Cu-TCPP (Co) MOFs based CL aptasensors. Reproduced with permission from (Ma et al., 2020).

Fig. 4.

Schematic illustrations of ratiometric ECL aptasensors and colorimetric aptasensor. (a) Ru-MOFs based ratiometric ECL-RET aptasensor using Ru-MOFs and carbon nitride nanosheet (g-C3N4 NS). Reproduced with permission from (He et al., 2017). (b) Mimicking enzyme-based colorimetric aptasensor composing of Fe-MIL-88NH₂. Reproduced with permission from (Luan et al., 2017).

Fig. 5.

MOFs-based electrochemical aptasensors. (a) Electrochemical aptasensor using Tb-MOF-on-Fe-MOF for the detection of CA125 and living cancer cells. Reproduced with permission from (Wang et al., 2019c). (b) Fe-MOF-derived nanostructures for heavy ions detection. Reproduced with permission from (Zhang et al., 2017a). (c) MOFs-based PEC aptasensors. A label-free PEC biosensor constructed using MIL-68(In)-NH₂/MWCNT/CdS composites. Reproduced with permission from (Zhang et al., 2019a).

Fig. 6.

Aptasensors using MOFs as small signal molecule nanocarriers. (a) A signal-off electrochemical aptasensor based on UIO-66-NH₂ decorated with MB as signal tags and C60NPs N-CNTs/GO nanocomposite. Reproduced with permission from (He and Dong, 2019). (b) A signal-off detection process using an electrochemical strategy based on Zr-MOFs and MB@Phosphate-terminated DNA. Reproduced with permission from (Qiu et al., 2020).

Fig. 7.

Aptasensors using MOF as nanocarrier for loading enzyme. An impedimetric aptasensor based on Cu-MOFs decorated with GOD and hemin as signal probe. Reproduced with permission from (Zhou et al., 2017).

Fig. 8.

Aptasensors using MOFs as nanocarrier to load metal nanoparticles. (a) UIO-66 embedded silver clusters were used as aptasensor for the detection of CEA. Reproduced with permission from (Guo et al., 2017). (b) A sandwich electrochemical aptasensor based on Au-COFs and Au@ZIF-8(NiPd). Reproduced with permission from (Zhang et al., 2019b).

Fig. 9.

(a) Stimuli-responsive sensors using nucleic acid- functionalized MOFs as nanocarrier to encapsulate drug/signal probes. A homogeneous electrochemical biosensor with MB and TMB encapsulated in nucleic acid-functionalized UIO-66 was assembled for simultaneous detection of two tumor biomarkers. Reproduced with permission from (Chang et al., 2019). (b) Integration of MOFs-based sensors in a microfluidic platform for rapid and in situ molecular detection. Ultrasensitive in situ detection of perfluorooctanesulfonate (PFOS) was achieved by a MOF-based (Cr-MIL-101) impedance sensor integrated in a microfluidic platform. Reproduced with permission from (Cheng et al., 2020).