Modular Assembled Localized Hybridization Chain Reaction for In Situ mRNA Amplified Imaging.

As a nonenzymatic DNA signal amplification technique, localized hybridization chain reaction (LHCR) was designed to improve the limitations in response speed and low sensitivity of conventional free diffusional HCR (hybridization chain reaction). However, it is still confronted with the challenges of complicated DNA scaffolds with low loading capacity and a time-consuming process of diffusion. Herein, we introduced modular assembly of a DNA minimal scaffold for coassembly of DNA hairpins for amplified fluorescence imaging of mRNA in situ. DNA hairpins were spatially bound to two Y-shaped modules to form H-shaped DNA modules, and then multiple H-shaped DNA modules can further assemble into an H-module-based hairpin scaffold (HHS). Benefiting from highly spatial localization and high loading capacity, the HHS system showed higher sensitivity and faster speed. It has also been proven to work perfectly in vitro and in vivo, which could provide a promising bioanalysis system for low abundance biomolecule detection.

Cell Membrane-Anchored AND Logic Gate Aptasensor for Tumor Cell-Specific Imaging with Improved Accuracy.

Accurate and rapid imaging of tumor cells is of vital importance for early cancer diagnosis and intervention. Aptamer-based fluorescence sensors have become a potent instrument for bioimaging, while false positives and on-target off-tumors linked to single-biomarker aptasensors compromise the specificity and sensitivity of cancer imaging. In this paper, we describe a sequential response aptasensor for precise cancer cell identification that is based on a DNA "AND" logic gate. Specifically, the sensor consists of three single-stranded DNA, including the P-strand that can sensitively respond to an acid environment, the L-strand containing the ATP aptamer sequence, and the R-strand for target cell anchoring. These DNA strands hybridize with one another to create a Y-shaped structure (named Y-ALGN). The aptamer in the R-strand is utilized to anchor the sensor to the target cell membrane primarily. Responding to the extracellular acidic environment of the tumor (input 1), the I-motif sequence forms a tetramer structure so that the P-strand is released from the Y-shaped structure and exposes the ATP binding sites in the L-strand. Extracellular ATP, as input 2, continuously operates the DNA aptasensor to complete the logic computation. Upon the sequential response of both protons and ATP molecules, the aptasensor is activated with restored fluorescence on a particular cancer cell membrane. Benefiting from the precise computation capacity of the "AND" logic gate, the Y-ALGN aptasensor can distinguish between MCF-7 cells and normal cells with high accuracy. As a simple and dual-stimuli-responsive strategy, this nanodevice would offer a fresh approach for accurately diagnosing tumor cells.

A microfluidic chip with integrated plasma separation for sample-to-answer detection of multiple chronic disease biomarkers in whole blood.

Point-of-care testing of multiple chronic disease biomarkers is crucial for timely intervention and management of chronic diseases. Here, a "sample-to-answer" microfluidic chip was developed for simultaneous detection of multiple chronic disease biomarkers in whole blood by integrating a plasma separation module. The whole detection process is very convenient, i.e., just add whole blood and get the results. The chip successfully achieved the simultaneous detection of total cholesterol, triglycerides, uric acid, and glucose in undiluted whole blood within 21 min, including 6 min for plasma separation and 15 min for enzymatic chromogenic reactions. Moreover, the sensitivity levels of on-chip detection of chronic disease biomarkers can also meet clinically relevant thresholds. The chip is easy to use and has significant potential to improve home self-management of chronic diseases and enhance healthcare outcomes.

G-quadruplex-Based Artificial Transmembrane Channels Induce Cancer Cell Apoptosis by Perturbing Potassium Ion Homeostasis.

Transmembrane ion transport modality has received a widespread attention due to its apoptotic activation toward anticancer cell activities. In this study, G-quadruplex-based potassium-specific transmembrane channels have been developed to facilitate the intracellular K+ efflux, which perturbs the cellular ion homeostasis thereby inducing cancer cell apoptosis. Cholesterol-tag, a lipophilic anchor moiety, serves as a rudiment for the G-quadruplex immobilization onto the membrane, while G-quadruplex channel structure as a transport module permits ion binding and migration along the channels. A c-Myc sequence tagged with two-cholesterol is designed as a representative lipophilic G-quadruplex, which forms intramolecular parallel G-quadruplex with three stacks of G-quartets (Ch2-Para3). Fluorescence transport assay demonstrates Ch2-Para3 a high transport activity (EC50 = 10.9 × 10-6 m) and an ion selectivity (K+/Na+ selectivity ratio of 84). Ch2-Para3 mediated K+ efflux in cancer cells is revealed to purge cancer cells through K+ efflux-mediated cell apoptosis, which is confirmed by monitoring the changes in membrane potential of mitochondria, leakage of cytochrome c, reactive oxygen species yield, as well as activation of a family of caspases. The lipophilic G-quadruplex exhibits obvious antitumor activity in vivo without systemic toxicity. This study provides a functional scheme aimed at generating DNA-based selective artificial membrane channels for the purpose of regulating cellular processes and inducing cell apoptosis, which shows a great promising for anticancer therapy in the future.

A glaucoma micro-stent with diverging channel and stepped shaft structure based on microfluidic template processing technology.

BACKGROUND: Minimally invasive glaucoma surgery (MIGS) has experienced a surge in popularity in recent years. Glaucoma micro-stents serve as the foundation for these minimally invasive procedures. Nevertheless, the utilization of these stents still presents certain short-term and long-term complications. This study aims to elucidate the creation of a novel drainage stent implant featuring a diverging channel, produced through microfluidic template processing technology. Additionally, an analysis of the mechanical properties, biocompatibility, and feasibility of implantation is conducted. RESULTS: The stress concentration value of the proposed stent is significantly lower, approximately two to three times smaller, compared to the currently available commercial XEN gel stent. This indicates a stronger resistance to bending in theory. Theoretical calculations further reveal that the initial drainage efficiency of the gradient diverging drainage stent is approximately 5.76 times higher than that of XEN stents. Notably, in vivo experiments conducted at the third month demonstrate a favorable biocompatibility profile without any observed cytotoxicity. Additionally, the drainage stent exhibits excellent material stability in an in vitro simulation environment. CONCLUSIONS: In summary, the diverging drainage stent presents a novel approach to the cost-effective and efficient preparation process of minimally invasive glaucoma surgery (MIGS) devices, offering additional filtering treatment options for glaucoma.

Atomic Force Microscopy Lifetime Analysis: An Intuitive Method for Evaluating Receptor Tyrosine Kinase Dimer-Targeting Inhibitors.

Overexpression of receptor tyrosine kinases (RTKs) or binding to ligands can lead to the formation of specific unliganded and liganded RTK dimers, and these two RTK dimers are potential targets for preventing tumor metastasis. Traditional RTK dimer inhibitor analysis was mostly based on end point assays, which required cumbersome cell handling and behavior monitoring. There are still challenges in developing intuitive process-based analytical methods to study RTK dimer inhibitors, especially those used to visually distinguish between unliganded and liganded RTK dimer inhibitors. Herein, taking the mesenchymal-epithelial transition factor (MET) receptor, an intuitive method for evaluating MET inhibitors has been developed based on atomic force microscopy (AFM) lifetime analysis. The time interval between the start of the force and the bond break point was regarded as the bond lifetime, which could reflect the stability of the MET dimer. The results showed that there was a significant difference in the lifetime (τ) of unliganded MET dimers (τ1 = 207.87 ± 4.69 ms) and liganded MET dimers (τ2 = 330.58 ± 15.60 ms) induced by the hepatocyte growth factor, and aptamer SL1 could decrease τ1 and τ2, suggesting that SL1 could inhibit both unliganded and liganded MET dimers. However, heparin only decreased τ2, suggesting that it could inhibit only the liganded MET dimer. AFM-based lifetime analysis methods could monitor RTK dimer status rather than provide overall average results, allowing for intuitive process-based analysis and evaluation of RTK dimers and related inhibitors at the single-molecule level. This study provides a novel complementary strategy for simple and intuitive RTK inhibitor research.

Synthetic Cells from Droplet-Based Microfluidics for Biosensing and Biomedical Applications.

Synthetic cells function as biological mimics of natural cells by mimicking salient features of cells such as metabolism, response to stimuli, gene expression, direct metabolism, and high stability. Droplet-based microfluidic technology presents the opportunity for encapsulating biological functional components in uni-lamellar liposome or polymer droplets. Verified by its success in the fabrication of synthetic cells, microfluidic technology is widely replacing conventional labor-intensive, expensive, and sophisticated techniques justified by its ability to miniaturize and perform batch production operations. In this review, an overview of recent research on the preparation of synthetic cells through droplet-based microfluidics is provided. Different synthetic cells including lipid vesicles (liposome), polymer vesicles (polymersome), coacervate microdroplets, and colloidosomes, are systematically discussed. Efforts are then made to discuss the design of a variety of microfluidic chips for synthetic cell preparation since the combination of microfluidics with bottom-up synthetic biology allows for reproductive and tunable construction of batches of synthetic cell models from simple structures to higher hierarchical structures. The recent advances aimed at exploiting them in biosensors and other biomedical applications are then discussed. Finally, some perspectives on the challenges and future developments of synthetic cell research with microfluidics for biomimetic science and biomedical applications are provided.

Development of an aptamer capable of multidrug resistance reversal for tumor combination chemotherapy.

Multidrug resistance (MDR) is a major factor in the failure of many forms of tumor chemotherapy. Development of a specific ligand for MDR-reversal would enhance the intracellular accumulation of therapeutic agents and effectively improve the tumor treatments. Here, an aptamer was screened against a doxorubicin (DOX)-resistant human hepatocellular carcinoma cell line (HepG2/DOX) via cell-based systematic evolution of ligands by exponential enrichment. A 50 nt truncated sequence termed d3 was obtained with high affinity and specificity for HepG2/DOX cells. Multidrug resistance protein 1 (MDR1) is determined to be a possible recognition target of the selected aptamer. Aptamer d3 binding was revealed to block the MDR of the tumor cells and increase the accumulation of intracellular anticancer drugs, including DOX, vincristine, and paclitaxel, which led to a boost to the cell killing of the anticancer drugs and lowering their survival of the tumor cells. The aptamer d3-mediated MDR-reversal for effective chemotherapy was further verified in an in vivo animal model, and combination of aptamer d3 with DOX significantly improved the suppression of tumor growth by treating a xenograft HepG2/DOX tumor in vivo. This work demonstrates the feasibility of a therapeutic DNA aptamer as a tumor MDR-reversal agent, and combination of the selected aptamer with chemotherapeutic drugs shows great potential for liver cancer treatments.

Wearable Sensing Device Integrated with Prestored Reagents for Cortisol Detection in Sweat.

Wearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g., pH level and ionic strength in sweat may decrease the affinity between analytes and recognition elements. Here, we developed a wearable sensing device for cortisol detection in sweat using an aptamer as the recognition element. The device integrated functions of sweat collection, reagent prestorage, and signal conversion. Especially, the components of prestored reagents were optimized according to the inherent characteristics of sweat samples and electrodes, which allowed us to keep optimal conditions for aptamers. The sweat samples were transferred from the inlet of the device to the reagent prestored chamber, and the dry preserved reagents were rehydrated with sweat and then arrived at the aptamer-modified electrodes. Sweat samples of volunteers were analyzed by the wearable sensing device, and the results showed a good correlation with those of the ELISA kit. We believe that this convenient and reliable wearable sensing device has significant potential in self-health monitoring.

"One suction and one extrusion" mode-based wash-free platform for determination of breast cancer cell-derived exosomes.

A simple and wash-free POCT platform based on microcapillary was developed, using breast cancer cell-derived exosomes as a model. This method adopted the "one suction and one extrusion" mode. The hybridized complex of epithelial cell adhesion molecule (EpCAM) aptamer and complementary DNA-horseradish peroxidase conjugate (CDNA-HRP) was pre-modified on the microcapillary's inner surface. "One suction" meant inhaling the sample into the functionalized microcapillary. The exosomes could specifically bind with the EpCAM aptamer on the microcapillary's inner wall, and then the CDNA-HRP complex was released. "One extrusion" referred to squeezing the shedding CDNA-HRP into the 3,3',5,5'-tetramethylbenzidine (TMB)/H2O2 solution, and then the enzyme-catalyzed reaction would occur to make the solution yellow using sulfuric acid as the terminator. Therefore, exosome detection could be realized. The limit of detection was 2.69 × 104 particles mL-1 and the signal value had excellent linearity in the concentration range from 2.75 × 104 to 2.75 × 108 particles⋅mL-1 exosomes. In addition, the wash-free POCT platform also displayed a favorable reproducibility (RSD = 2.9%) in exosome detection. This method could effectively differentiate breast cancer patients from healthy donors. This work provided an easy-to-operate method for detecting cancer-derived exosomes without complex cleaning steps, which is expected to be applied to breast cancer screening.

DNA-Encoded Bidirectional Regulation of the Peroxidase Activity of Pt Nanozymes for Bioanalysis.

Rational regulation of nanozyme activity can promote biochemical sensing by expanding sensing strategies and improving sensing performance, but the design of effective regulatory strategies remains a challenge. Herein, a rapid DNA-encoded strategy was developed for the efficient regulation of Pt nanozyme activity. Interestingly, we found that the catalytic activity of Pt nanozymes was sequence-dependent, and its peroxidase activity was significantly enhanced only in the presence of T-rich sequences. Thus, different DNA sequences realized bidirectional regulation of Pt nanozyme peroxidase activity. Furthermore, the DNA-encoded strategy can effectively enhance the stability of Pt nanozymes at high temperatures, freezing, and long-term storage. Meanwhile, a series of studies demonstrated that the presence of DNA influenced the reduction degree of H2PtCl6 precursors, which in turn affected the peroxidase activity of Pt nanozymes. As a proof of application, the sensor array based on the Pt nanozyme system showed superior performance in the accurate discrimination of antioxidants. This study obtained the regulation rules of DNA on Pt nanozymes, which provided theoretical guidance for the development of new sensing platforms and new ideas for the regulation of other nanozyme activities.

Self-assembled super-small AIEgen nanoprobe for highly sensitive and selective detection of protamine and trypsin.

Amphiphilic aggregation-induced emission (AIE) molecules show superior potential for fabricating novel ultrasmall nanoprobes. Here, an anionic dipyridyl tetraphenylethene (TPE) derivative is rationally designed and a super-small self-assembled AIEgen nanoprobe (TPE-2Py-SO3NaNPs, ca. 2.48 nm) is thus conveniently constructed for the supersensitive detection of protamine and trypsin. In HEPES/DMSO solution (8 : 2, v/v, pH = 7.4), negatively charged TPE-2Py-SO3NaNPs exhibited an AIE effect in the presence of positively charged protamine, presenting a fluorescence enhancement at 498 nm together with a large Stokes shift of 150 nm and a low detection limit of 8.0 ng mL-1. In addition, the in situ formed TPE-2Py-SO3Na/protamine nanocomposite can be dissociated by trypsin due to the highly selective degradation of protamine via enzymatic hydrolysis, achieving a detection limit for trypsin as low as 5.0 ng mL-1.

A Versatile Integrated Microfluidic Chip Based on Sonic Toothbrush-Assisted Mixing for Analyses of Diverse Biomolecules.

Usually, different assays and instrumentation are required for different types of targets, e.g., nucleic acids, proteins, small molecules, etc., because of significant differences in their structures and sizes. To increase efficiency and reduce costs, a desirable solution is to develop a versatile platform suitable for diverse objectives. Here, we established a versatile detection technique: first, target separation and enrichment were carried out using magnetic beads (MBs); then, different targets were converted to same barcoded DNA strands (BDs) released from gold nanoparticles; finally, sensitive detection of three different targets (miRNA-21, digoxigenin antibody, and aflatoxin B1) was achieved through exonuclease III (Exo III) cyclic cleavage-assisted signal amplification. To simplify the operation, we integrated this technique into a microfluidic chip with multiple chambers in which the requisite reagents were prestored. Just by moving the MBs through different chambers with a magnet, multiple steps can be completed. Due to the limited space in microfluidic chips, the full mixing of MBs and solution is a key point to improve reaction efficiency. The mixing can be achieved by acoustic vibration generated by a small, portable sonic toothbrush. Based on the microfluidic chip, the detection limits of the above three targets were 0.76 pM, 0.16 ng/mL, and 0.56 nM, respectively. Furthermore, miRNA-21 and Digoxigenin antibody (Dig-Ab) in serum and AFB1 in corn powder were also used to demonstrate the performance of this chip. Our versatile platform is easy to operate and is expected to develop into an automatic "sample-to-answer" device.

Carbon Nanotube Field-Effect Transistor Biosensor with an Enlarged Gate Area for Ultra-Sensitive Detection of a Lung Cancer Biomarker.

Carcinoembryonic antigen (CEA) is a recognized biomarker for lung cancer and can be used for early detection. However, the clinical value of CEA is not fully realized due to the rigorous requirement for high-sensitivity and wide-range detection methods. Field-effect transistor (FET) biosensors, as one of the potentially powerful platforms, may detect CEA with a significantly higher sensitivity than conventional clinical testing equipment, while their sensitivity and detection range for CEA are far below the requirement for early detection. Here, we construct a floating gate FET biosensor to detect CEA based on a semiconducting carbon nanotube (CNT) film combined with an undulating yttrium oxide (Y2O3) dielectric layer as the biosensing interface. Utilizing an undulating biosensing interface, the proposed device showed a wider detection range and optimized sensitivity and detection limit, which benefited from an increase of probe-binding sites on the sensing interface and an increase of electric double-layer capacitance, respectively. The outcomes of analytical studies confirm that the undulating Y2O3 provided the desired biosensing surface for probe immobilization and performance optimization of a CNT-FET biosensor toward CEA including a wide detection range from 1 fg/mL to 1 ng/mL, good linearity, and high sensitivity of 72 ag/mL. More crucially, the sensing platform can function normally in the complicated environment of fetal bovine serum, indicating its great promise for early lung cancer screening.

The Additive Manufacturing Approach to Polydimethylsiloxane (PDMS) Microfluidic Devices: Review and Future Directions.

This paper presents a comprehensive review of the literature for fabricating PDMS microfluidic devices by employing additive manufacturing (AM) processes. AM processes for PDMS microfluidic devices are first classified into (i) the direct printing approach and (ii) the indirect printing approach. The scope of the review covers both approaches, though the focus is on the printed mold approach, which is a kind of the so-called replica mold approach or soft lithography approach. This approach is, in essence, casting PDMS materials with the mold which is printed. The paper also includes our on-going effort on the printed mold approach. The main contribution of this paper is the identification of knowledge gaps and elaboration of future work toward closing the knowledge gaps in fabrication of PDMS microfluidic devices. The second contribution is the development of a novel classification of AM processes from design thinking. There is also a contribution in clarifying confusion in the literature regarding the soft lithography technique; this classification has provided a consistent ontology in the sub-field of the fabrication of microfluidic devices involving AM processes.

Osmotic-Induced Reconfiguration and Activation in Membranized Coacervate-Based Protocells.

The design and construction of synthetic protocells capable of stimuli response and homeostatic regulation is an important challenge for synthetic protobiology. Here, we develop a step toward the construction of model protocells capable of a hypotonic stress-induced volume response that facilitates an increase in membrane permeability and the triggering of endogenous enzyme reactions. We describe a facile self-transformation process for constructing single- or multichambered molecularly crowded protocells based on the osmotic reconfiguration of lipid-coated coacervate droplets into multicompartmentalized coacervate vesicles. Hypotonic swelling broadens membrane permeability and increases transmembrane transport such that protease-based hydrolysis and enzyme cascades can be triggered and enhanced within the protocells by osmotically induced expansion. Specifically, we demonstrate how the enhanced production of nitric oxide (NO) within the swollen coacervate vesicles can be used to induce in vitro blood vessel vasodilation in thoracic artery rings. Our approach provides opportunities for designing reconfigurable model protocells capable of homeostatic volume regulation, dynamic structural reorganization, and adaptive functionality in response to changes in environment osmolarity, and could find applications in biomedicine, cellular diagnostics, and bioengineering.

One-step multiplex analysis of breast cancer exosomes using an electrochemical strategy assisted by gold nanoparticles.

Exosomes, as a non-invasive biomarker, perform an important role in breast cancer screening and prognosis monitoring. However, establishing a simple, sensitive, and reliable exosome analysis technique remains challenging. Herein, a one-step multiplex analysis electrochemical aptasensor based on a multi-probe recognition strategy was constructed to analyze breast cancer exosomes. HER2-positive breast cancer cell (SK-BR-3) exosomes were selected as the model targets and three aptamers including CD63, HER2 and EpCAM aptamers were used as the capture units. Methylene blue (MB) functionalized HER2 aptamer and ferrocene (Fc) functionalized EpCAM aptamer, which were modified on gold nanoparticles (Au NPs), i.e. MB-HER2-Au NPs and Fc-EpCAM-Au NPs, were used as signal units. When the mixture of target exosomes, MB-HER2-Au NPs and Fc-EpCAM-Au NPs were added on the CD63 aptamer modified gold electrode, two Au NPs modified by MB and Fc could be specifically captured on the electrode by the recognition of three aptamers with target exosomes. Then one-step multiplex analysis of exosomes was achieved by detecting two independent electrochemical signals. This strategy can not only distinguish breast cancer exosomes from other exosomes (including normal exosomes and other tumor exosomes) but also HER2-positive breast cancer exosomes and HER2-negative breast cancer exosomes. Besides, it had high sensitivity and can detect SK-BR-3 exosomes with a concentration as low as 3.4 × 103 particles mL-1. Crucially, this method can be applicable to the examination of exosomes in complicated samples, which is anticipated to afford assistance for the screening and prognosis of breast cancer.

DNA-Based Artificial Receptors as Transmembrane Signal Transduction Systems for Protocellular Communication.

The ability to reproduce signal transduction and cellular communication in artificial cell systems is significant in synthetic protobiology. Here, we describe an artificial transmembrane signal transduction through low pH-mediated formation of the i-motif and dimerization of DNA-based artificial membrane receptors, which is coupled to the occurrence of fluorescence resonance energy transfer and the activation of G-quadruplex/hemin-mediated fluorescence amplification inside giant unilamellar vesicles. Moreover, an intercellular signal communication model is established when the extravesicular H+ input is replaced by coacervate microdroplets, which activate the dimerization of the artificial receptors, and subsequent fluorescence production or polymerization in giant unilamellar vesicles. This study represents a crucial step towards designing artificial signalling systems with environmental response, and provides an opportunity to establish signalling networks in protocell colonies.

Coacervate Microdroplets as Synthetic Protocells for Cell Mimicking and Signaling Communications.

Synthetic protocells are minimal systems that mimic certain properties of natural cells and are used to research the emergence of life from a nonliving chemical network. Currently, coacervate microdroplets, which are formed via liquid-liquid phase separation, are receiving wide attention in the context of cell biology and protocell research; these microdroplets are notable because they can provide liquid-like compartment structures for biochemical reactions by creating highly macromolecular crowded local environments. In this review, an overview of recent research on the formation of coacervate microdroplets through phase separation; the design of coacervate-based stimuli-responsive protocells, multichamber protocells, and membranized protocells; and their cell mimic behaviors, is provided. The simplified protocell models with precisely defined and tunable compositions advance the understanding of the requirements for cellular structure and function. Efforts are then discussed to establish signal communication systems in protocell and protocell consortia, as communication is a fundamental feature of life that coordinates matter exchanges and energy fluxes dynamically in space and time. Finally, some perspectives on the challenges and future developments of synthetic protocell research in biomimetic science and biomedical applications are provided.

Biocompatible polymers with tunable mechanical properties and conductive functionality on two-photon 3D printing.

Two-photon polymerization (TPP)-based 3D printing technology utilizes the two-photon absorption process of near-infrared radiation, enabling the fabrication of micro- and nano-scale three-dimensional structures with extremely high resolution. It has been widely applied in scientific fields closely related to living organisms, such as tissue engineering, drug delivery, and biosensors. Nevertheless, the existing photoresist materials have poor mechanical tunability and are hardly able to be doped with functional materials, resulting in constraints on the preparation of functional devices with micro-nano structures. In this paper, TPP printable polymer formulas with good mechanical tunability, high resolution, strong functional scalability, and excellent biocompatibility are proposed, by using the synergistic effects of a hydroxyl group-containing photocurable resin prepolymer, UV acrylate monomer, long-chain hydrophilic crosslinking monomer and photo-initiator. This can ensure the printability and help to improve the flexibility of the printed polymer, thereby solving the problem the photosensitive materials suitable for two-photon 3D printing in previous research had in balancing the formability and flexibility. The results of nanoindenter analysis showed that the Young's modulus of the printed structure can be adjusted between 0.3 GPa and 1.43 GPa, realizing mechanical tunability. Also, complex structures, such as micro-scaffold structures and high aspect ratio hollow microneedles were printed to explore the structural stability as well as the feasibility of biodevice application. Meanwhile, the proposed polymer formula can be functionalized to be conductive by doping with functional nanomaterial MXene. Finally, the biocompatibility of the proposed polymer formula was studied by culturing with human normal lung epithelial cells. The results indicated a good potential for biodevice applications.