De Novo Engineering of Metal–Organic Framework‐Printed In Vitro Diagnostic Devices for Specific Capture and Release of Tumor Cells

Abstract

monitoring of disease progression and treatment efficacy. [1] The efficient enrichment of biomarkers with high sensitivity and specificity is usually required for IVDs; however, the complex nature of body fluids (i.e., cell debris, normal blood cells, etc.) may hinder selective biomarker capture. [2] Moreover, the material capture mechanism may induce unrecoverable changes to biomarkers, affecting its accuracy. [2] Therefore, the choice of materials which enable efficient capture of native biomarkers with good cytocompatibility is critical.Various probes (e.g., aptamers, [3] peptides, [4] antibodies [5] ) have been applied to enhance the specificity of biomarker capture and detection. Additionally, nanomaterials have been integrated with biological probes due to their large surface area-to-volume ratio, such as nanofibers, [6] nanowires, [7] 2D materials, [8] and nanoparticles, [9] to improve the capacity to capture target cells. However, limitations of these biological sensing elements include the propensity to deactivate or degrade, high cost and experimentally time-consuming. [2] Non-biological functional groups with high-affinity to target cells are promising as they are more resistant to chemical or biological degradation and less expensive. [10] Boronic acid and its derivatives are such functional groups which can bind cell surface glycans (i.e., sialic acid) overexpressed on the surface of the tumor cells via reversible covalent bonds, enabling the selective capture and isolation of cancer cells. [10] Effective tumor cell capture can occur when boronic acid is constructed on substrates with nanoscale features [10] and only a few studies have reported the efficient capture of cancer cells by a single chemical group. [11] The development of highly efficient boronic acidrich materials have the potential to enhance the efficiency of specific tumor cell capture.Recently, metal-organic nanocomposite materials (e.g., metal-organic frameworks (MOFs), metal-organic cages (MOCs), metal-phenolic networks)) have attracted increasing attention. [12] In particular, MOFs constructed from organic linkers and metal ions or metal-containing clusters, possess versatile functionality, tailored pore size, and versatile composition and structure. [13] Consequently, MOFs have shown great potential in diverse applications including energy storage, [14] gas separation, [15] biopharmaceutical delivery [16] and heterogeneous Herein, a paper-based in vitro diagnostic device (IVD) is developed via inkjet printing of de novo engineered, boronic acid-rich metal-organic frameworks (BMOFs). The newly developed BMOFs simultaneously possess crystalline and amorphous structure, mesopore size, large surface area, and retain a high level of boronic acid integration. After printing the BMOFs on the filter paper, the BMOF-printed paper IVD shows a rapid response time (40 min) towards cancer cell capture and its maximum cell capture capacity reaches approximately (4.5 ±1.1) ×10 4 cells cm −2 . Furthermore, the BMOF-printed IVD shows nine times h...

Covalent-organic framework nanobionics for robust cytoprotection

“…14 MOFs, constructed from metal ions or metalcontaining clusters and organic linkers, possess versatile functionality, tunable pore size, well-dened pore aperture, tailorable composition, and structure. [15][16][17][18][19] These properties are particularly advantageous for controlling molecular transport through coatings. [20][21][22][23][24] MOF coatings can be formed around living cells through in situ or post-loading strategies.…”

Locking the Ultrasound-Induced Active Conformation of Metalloenzymes in Metal–Organic Frameworks

“…However, the wide industrial utilization of enzymes is hindered by their fragile nature, such as low tolerance to most organic solvents and digestive cocktails, narrow optimum pH ranges, and low thermal stability, which easily leads to a decreased enzymatic activity . In the past few years, metal–organic frameworks (MOFs) have attracted wide interest for enzyme immobilization. − Composed of metal nodes and organic ligands, MOFs and their subclass zeolitic imidazolate frameworks (ZIFs) exhibit diverse chemical and structural features (such as shape, pore size, surface area, and structural flexibility). − These versatile features enable MOFs as an inert host as well as tailor the selectivity, stability, and/or activity of the enzymes while protecting them from unfavorable environments. − However, upon immobilization in MOFs, most enzymes experience a decreased activity due to the restricted enzyme conformation and substrate accessibility. Until now, increasing the pore size − and creating hollow cavities within MOFs have been the most popular strategies to improve the biocatalytic MOF activity.…”

Enzymes-Encapsulated Defective Metal–Organic Framework Hydrogel Coupling with a Smartphone for a Portable Glucose Biosensor

“…To this point, zeolite imidazole frameworks (ZIFs), including ZIF-8, ZIF-90, MAF-7, and so forth, are the favorable MOF matrices for enzyme immobilization due to their biocompatible synthesis conditions. − A pioneering work by Liang, Falcaro, and co-workers has found that ZIF-8 could in situ crystallize around a given enzyme, analogous to the natural biomineralization . Utilizing this method, single or multiple enzymes are readily encapsulated into ZIFs, and the encapsulated enzymes display improved stability yet maintain desirable bioactivity. − However, these ZIFs biohybrids are microcrystalline powders and hence are difficult to be mechanically processed and shaped in a controllable manner. This significantly limits the MOF biohybrid acting as the core element in large-scale industrial applications, such as portable biosensors.…”