Programmable materials integrated with intelligent signal processing are essential for developing adaptive and autonomous environmental sensing systems. Here, we present a biohybrid material platform in which environmental DNA is captured by streptavidin (SA)-functionalized microparticles and delivered to a cell-free transcription-translation system for intelligent information processing. The microparticles selectively capture biotinylated DNA from their surroundings, which serve as molecular algorithm inputs for downstream biological computation. DNA immobilized on the particle surface remains transcriptionally active, enabling cell-free systems to produce tunable outputs, including (1) linear responses proportional to DNA input concentration and (2) threshold-dependent switching behaviors achieved through competitive binding. By offloading computation to a cell-free biochemical processor, this approach enables scalable, biocompatible sensing without the need for onboard electronics. This biohybrid design provides a versatile framework for engineering intelligent materials with applications in developing smart tools for healthcare and environmental monitoring.
First-generation LUNAR constructs can detect both oligonucleotides and plasmid double-stranded DNA with nanomolar sensitivity in mammalian cells and future work will focus on improving sensitivity, fold-change, and multiplexing capabilities for sequence-specific DNA detection.
Boao Xia, Nicholas A. Kalogriopoulos, Ruoxin Wen et al.· bioRxiv· 0 citations
Data-driven protein engineering has enabled biosensors that directly couple molecular recognition with measurable signal outputs, providing a powerful strategy for rapid protein analysis. However, their integration into automated and portable analytical systems remains limited. Here, we developed an integrated photoelectrochemical and fluorescence digital microfluidic (PF-DMF) platform for automated biomarker detection by combining a programmable "lock-and-cage" protein sensor (LucCage/LucKey) with precise digital microfluidic manipulation. The platform enabled automated detection of human tumor necrosis factor-α (hTNF-α) with a detection limit of 0.1 μM over a linear range of 0.1-10 μM, while exhibiting high specificity, good reproducibility, and minimal sample consumption. Direct analysis of hTNF-α in simulated body fluids was achieved without complex sample pretreatment. The platform was further extended with a CRISPR-based nucleic acid sensing module, enabling nucleic acid detection of Salmonella typhimurium (S. typhimurium) within the same automated workflow. In addition, a standardized reagent kit maintained stable analytical performance for at least 30 days under appropriate storage conditions. Overall, the proposed PF-DMF platform provides a versatile and scalable strategy for automated multimodal biomarker analysis, offering significant potential for portable diagnostics in healthcare and food safety.
The cell membrane plays a central role in signal transduction and material exchange between cells and their surrounding microenvironment. Engineering functional molecules onto the cell surface offers a powerful strategy to regulate cell behavior for biomedical applications. DNA nanotechnology has become a highly promising platform for this purpose owing to its programmable assembly, nanoscale addressability, and excellent biocompatibility. This review first discusses the anchoring strategies of DNA-based cell surface modification, covering noncovalent and covalent approaches. Then the recent progress is highlighted in biological applications of DNA-based cell surface engineering, including programming cell-cell interactions, biosensing of cellular microenvironment, regulation of signal transduction, and disease surveillance and treatment. Finally, the remaining challenges and the prospects of DNA-based cell surface engineering regarding the future development of this technology into biomedical research and therapeutic applications are also discussed.
Min Xiong, Yiming Xie, Na Li et al.· Journal of Physical Chemistr...· 0 citations
A DNA nanodevice that anchors to cell membranes and releases chemotherapy only when three specific cancer markers are detected simultaneously is developed, establishing a versatile platform for logic‑controlled, multimarker‑guided cancer theranostics.
Meiqin Zhang, Ying-Sheng Cheng, Nan Chen et al.· Nature Communications· 0 citations
Modern chemical and biological systems demand sensing platforms capable of recognizing diverse analytes with high stability, tunability, and real time responsiveness, capabilities that conventional biological receptors often fail to provide due to limited operating windows, structural fragility, and narrow design spaces. Corona phase molecular recognition (CoPhMoRe) offers a synthetic alternative, in which polymeric ligands adsorb onto single walled carbon nanotubes (SWCNTs) to form adaptive three dimensional recognition pockets without the need for traditional lock-and-key binding motifs. These corona structures function as artificial molecular interfaces that transduce chemical interactions through the exceptionally stable and tissue penetrative near infrared fluorescence of SWCNTs. In this work, we establish a design-driven framework for constructing, screening, and optimizing corona phases for broad chemical recognition. By integrating high throughput nanosensor fabrication with automated optical screening, molecular dynamics simulations, and docking based interaction analysis, we map design rules across a vast and continuously expandable library of corona structures. This combined experimental–computational strategy accelerates the discovery of selective and robust artificial receptors tailored to chemically diverse targets. These advances have produced nanosensor constructs capable of detecting biomarkers for early diagnosis, resolving molecular efflux signatures from single cells in a label free manner for the precision therapy, and enabling online chemical monitoring in complex industrial and biological reactors. CoPhMoRe thereby supports multidimensional chemical information transfer by embedding specificity, stability, and scalability into a single sensing architecture. Collectively, these results demonstrate how corona phase engineering can create a new class of programmable molecular recognition interfaces, offering a universal and durable sensing paradigm that extends far beyond the constraints of conventional diagnostic and analytical technologies.