Arbitrary Construction of Versatile NIR-Driven Microrobots.

Emerging light-driven micro/nanorobots (LMNRs) showcase profound potential for sophisticated manipulation and various applications. However, the realization of a versatile and straightforward fabrication technique remains a challenging pursuit. This study introduces an innovative bulk heterojunction organic semiconductor solar cell (OSC)-based spin-coating approach, aiming to facilitate the arbitrary construction of LMNRs. Leveraging the distinctive properties of a near-infrared (NIR)-responsive organic semiconductor heterojunction solution, this technique enables uniform coating across various dimensional structures (0D, 1D, 2D, 3D) to be LMNRs, denoted as "motorization." The film, with a slender profile measuring ≈140 nm in thickness, effectively preserves the original morphology of objects while imparting actuation capabilities exceeding hundreds of times their own weight. The propelled motion of these microrobots is realized through NIR-driven photoelectrochemical reaction-induced self-diffusiophoresis, showcasing a versatile array of controllable motion profiles. The strategic customization of arbitrary microrobot construction addresses specific applications, ranging from 0D microrobots inducing living crystal formation to intricate, multidimensional structures designed for tasks such as microplastic extraction, cargo delivery, and phototactic precise maneuvers. This study advances user-friendly and versatile LMNR technologies, unlocking new possibilities for various applications, signaling a transformative era in multifunctional micro/nanorobot technologies.

LncRNA SATB2-AS1 promotes tumor growth and metastasis and affects the tumor immune microenvironment in osteosarcoma by regulating SATB2.

Our previous report has identified a lncRNA SATB2-AS1, which was significantly up-regulated in osteosarcoma tissue and promotes the proliferation of osteosarcoma cells in vitro. However, the mechanisms of SATB2-AS1 regulating the growth and metastasis of osteosarcoma cells in vivo and its role in the prognosis of osteosarcoma patients are still unclear. In this study, the transcriptome sequencing data of 87 patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and 7 patients from our clinical center (GZFPH) was used to evaluate the importance of SATB2-AS1 and SATB2 on the prognosis. The effect of SATB2-AS1 on the growth and metastasis of osteosarcoma cells in vivo was verified by a mouse tumor model. The potential mechanisms of SATB2-AS1 regulating SATB2 were further explored by dual-luciferase reporter gene assay, RNA pull-down assay, and bioinformatics analysis. The results suggested that increased co-expression of SATB2-AS1 and SATB2 was significantly associated with poor overall survival (OS) and relapse-free survival (RFS), and was a biomarker for risk stratification in patients with osteosarcoma. Mechanistically, SATB2-AS1 promotes tumor growth and lung metastasis by regulating SATB2 in vivo. SATB2-AS1 directly binds to POU3F1 for mediating SATB2 expression in MNNG/HOS cells. In addition, SATB2-AS1 and SATB2 might be potential immunomodulators for negatively affecting immune cell infiltration by the IL-17 signaling pathway. In summary, SATB2-AS1 promoted tumor cell growth and lung metastasis by activating SATB2, thereby associated with poor prognosis in patients with osteosarcoma, which indicated that SATB2-AS1 and SATB2 might be novel biomarkers for risk stratification and promising therapeutic targets for osteosarcoma.

Capacitive-piezoresistive hybrid flexible pressure sensor based on conductive micropillar arrays with high sensitivity over a wide dynamic range.

Flexible pressure sensors are the foundation of wearable/implantable biosensing and human-machine interfaces, and mainly comprise piezoresistive-, capacitive-, piezoelectric-, and triboelectric-type sensors. As each type of sensor exhibits different electro-mechanical behaviors, it is challenging to detect various physiological mechanical signals that cover a large pressure range using a given sensor configuration, or even a single type of sensor. Here, we report a capacitive-piezoresistive hybrid flexible pressure sensor based on face-to-face-mounted conductive micropillar arrays as a solution to this challenge. The sensor exhibited high sensitivity over a wide dynamic range of five orders of magnitude, which covers almost the full range of physiological mechanical signals. A process for fabricating large-scale and morphologically homogeneous conductive micropillar arrays was first developed and refined. This track-etched-membrane-based process provides a facile, cost-effective, and highly flexible way to precisely adjust the morphology, modulus, and conductivity of the micropillars according to the application requirements. Subsequently, conductive-micropillar-array-based pressure sensors (MAPS) were developed and optimized to attain all-round sensing performance. The pillar contact behaviors generated significant variations in both the capacitance and resistance of the MAPS in the low-pressure regime (10-4-0.2 kPa), providing high sensitivity in both the capacitive and piezoresistive working modes. The vertical contact, bending and thickening of the pillars under medium pressure (0.2-16 kPa) led to a continuous linear response in both modes. Configuration and optimization enabled the MAPS to detect acoustic pressure (<1 Pa), milligram weights, soft touch (<1 kPa), arterial pulses (1-16 kPa preload), joint motions and plantar pressure (∼100 kPa), and the hybrid sensing mode allowed the MAPS to work in a desirable way. In this work, the piezoresistive mode was mainly employed for a higher accuracy and sampling rate, and can apparently simplify IC design for wearable applications. The circuit converts the resistive variations into electrical signals via the voltage division method and directly reads out the signals after further amplification, filtering and transmission. The improved facile and highly adjustable fabrication process, as well as the flexible hybrid sensing strategy, will benefit the unified design, batch production, quantifiable optimization, and functional diversity of wearable/implantable bioelectronics.

Explainable Deep-Learning-Assisted Sweat Assessment via a Programmable Colorimetric Chip.

Multianalytes and individual differences of biofluids (such as blood, urine, or sweat) pose enormous complexity and challenges to rapid, facile, high-throughput, and accurate clinical analysis or health assessment. Deep-learning (DL)-assisted image analysis has been demonstrated to be an efficient big data process which shows accurate individual identification. However, the data-driven "black boxes" of current DL algorithms are suffering from the nontransparent inner working mechanism. In this work, we designed a programmable colorimetric chip with explainable DL to approach accurate classification and quantification analysis of sweat samples. Gel (sodium alginate) capsules with different indicators were adopted to combinate as designed programmable colorimetric chips. We collected 4600 colorimetric response images as the data set and assessed two DL algorithms and seven machine learning (ML) algorithms. Glucose, pH, and lactate in human sweat could be facilely and 100% accurately classified and quantified by the convolutional neural network (CNN) DL algorithm, and the testing results of actual sweat via the DL-assisted colorimetric approach match 91.0-99.7% with the laboratory measurements. Class activation mapping (CAM) was processed to visualize the inner working mechanism of CNN operation, which could help to verify and explicate the design rationality of colorimetric chips. The explainable DL-assisted programmable colorimetric chip provided an "end-to-end" strategy to ascertain the black box of the DL algorithm, promoted software design or principium optimization, and contributed facile indicators for clinical monitoring, disease prevention, and even new scientific discoveries.

Anticancer mechanism studies of iridium(III) complexes inhibiting osteosarcoma HOS cells proliferation.

Three iridium (III) polypyridine complexes [Ir(bzq)2(maip)](PF6) (Ir1，bzq = benzo[h]quinoline, maip = 3-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(bzq)2(apip)](PF6) (Ir2, apip = 2-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(bzq)2(paip)](PF6) (Ir3, paip = 4-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The cytotoxic activities of the three complexes against human osteosarcoma HOS, U2OS, MG63 and normal LO2 cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The results showed that Ir1-3 exhibited moderate antitumor activity against HOS with IC50 of 21.8 ± 0. 4 µM,10.5 ± 1.8 µM and 7.4 ± 0.4 µM, respectively. We found that Ir1-3 can effectively inhibit HOS cells growth and blocked the cell cycle at the G0/G1 phase. Further studies revealed that complexes can increase intracellular reactive oxygen species (ROS) and Ca2+, which accompanied by mitochondria-mediated intrinsic apoptosis pathway. In addition, autophagy was also investigated. Taken together, the complexes induce HOS apoptosis through a ROS-mediated mitochondrial dysfunction pathway and inhibition of the PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin) signaling pathway. This study provides useful help for understanding the anticancer mechanism of iridium (III) complexes toward osteosarcoma treatment.

Elastic-Electric Coefficient-Sensitive Hydrogel Sensors toward Sweat Detection.

The complex and multivariate biological systems and environment are challenging the development of related detection and analysis. It calls for the multiresponsive and facile sensing material and method for multi-analyte identification. In this work, we proposed an elastic-electric coefficient sensitivity strategy with hydrogel [amino trimethylene phosphonic acid-assisted poly(vinyl alcohol)] to achieve discriminative analysis of various chemicals. Elastic sensitivity based on the Hofmeister effect and electric sensitivity based on hydrated ion migration are explored in detail. With a rational design, the elastic-electric coefficient-sensitive hydrogel can qualify and quantify various kinds of chemicals (cations, anions, amino acids, saccharides, and lactate). The facile hydrogel sensor realized complicated sweat recognition and can be used in various applications such as environment monitoring, disease diagnosis, and athletic training optimization.

Antitumor activity studies of iridium (III) polypyridine complexes-loaded liposomes against gastric tumor cell in vitro.

Two iridium (III) polypyridine complexes [Ir(ppy)2(BIP)]PF6 (ppy = 2-phenylpyridine, BIP = 2-biphenyl-1H-imidazo[4,5-f][1,10]phenanthroline, Ir1), [Ir(piq)2(BIP)]PF6 (piq = 1-phenylisoquinoline, Ir2) and their liposomes Ir1lipo and Ir2lipo were synthesized and characterized. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cytotoxic activity against several cancer cells (A549, HepG2, SGC-7901, Bel-7402, HeLa) and non-cancer cell (mouse embryonic fibroblast, NIH3T3). The results showed that Ir1lipo displays the high cytotoxicity toward SGC-7901 with IC50 value of 5.8 ± 0.2 µM, while the complexes have no cytotoxicity toward A549, HepG2, Bel-7402 and HeLa cells. The cell colony demonstrated that the iridium (III) complexes-loaded liposomes can inhibit cell proliferation, induce cell cycle arrest at G0/G1 phase. Moreover, they also cause autophagy, induce a decrease of mitochondrial membrane potential and increase intracellular reactive oxygen species (ROS) content. These results suggest that the complexes encapsulated liposomes Ir1lipo and Ir2lipo inhibit the growth of SGC-7901 cells through a ROS-mediated mitochondrial dysfunction and activating the PI3K (phosphoinositide-3 kinase)/ AKT (protein kinase B) signaling pathways.

Snake Venom Identification via Fluorescent Discrimination.

The identification and discrimination of snake venom are highly desired for timely clinical treatment. However, the complex components in snake venom make it a great challenge to achieve rapid and accurate identification. Inspired by the organism's taste sensing system, a fluorescent sensor array that could differentiate snake venoms was fabricated. The interaction of snake venoms with different fluorescent dyes in the sensor array gave rich information, based on which efficient detection of complex snake venom was achieved. The main six proteins of snake venom in the same concentration, different concentrations, and their mixtures were identified with 100% accuracy. Furthermore, seven snake venoms belonging to different snake families were discriminated in PBS buffer and human plasma. Interferents of bovine serum albumin (BSA), thrombin, and transferrin (TRF) demonstrated the practicability of the fluorescent sensor array. This strategy of a multiresponse sensor array provides an effective method for accurate and rapid venom toxicology analysis, benefiting early and timely clinical diagnosis and treatment.

An Ultra-Stretchable Sensitive Hydrogel Sensor for Human Motion and Pulse Monitoring.

Ionic hydrogels with intrinsic conductivity and stretchability show great potential in flexible electronics. However, it remains a great challenge to achieve hydrogels with mechanical stretchability, ionic conductivity, optical transparency, and a self-healing ability at the same time. In this paper, we developed a hydroxyethylidene diphosphonic acid (HEDP) assisted poly(vinyl alcohol) (PVA) composite hydrogel to achieve high-performance stretch-sensitive sensor. Through a facile freeze-thaw strategy, the hydrogel could achieve large stretchability (up to 950% strain), good conductivity (10.88 S/m), excellent linear sensitivity (GF = 2.72, within 100% strain), high transparency, and significant self-healing ability. The PVA-HEDP hydrogel-based strain sensor is capable of monitoring various human movements from small scale (e.g., laryngeal vibration while speaking) to large scale (e.g., knee joint movement). Moreover, the multisite sensor array is capable of detecting the subtle differences between the pulse wave features from Cun, Guan and Chi positions, mimicking the three-finger palpation in Traditional Chinese Medicine. This work demonstrates that the composite hydrogel-based flexible sensor provides a promising solution for multifunctional human activities and health monitoring.

Nanostructured High-Performance Thin-Film Transistors and Phototransistors Fabricated by a High-Yield and Versatile Near-Field Nanolithography Strategy.

Thin-film transistors (TFTs) and field-effect transistors (FETs) are basic units to build functional electronic circuits and investigate transport physics. In conventional TFTs or FETs, performance in terms of current level, on-off ratio, and the sensitivity of detection is limited by homogeneous semiconducting layers. In this paper, we develop TFTs with submicron heterostructures by using a strategy based on near-field photolithography. We use an array of total-reflective polydimethylsiloxane pyramids or trenches as a soft photomask in photolithography to induce multiple reflections and diffractions to focus the light. The textured feature enables the generation of gaps, dots, and grids at the nanoscale, with dimensions as small as sub-100 nm on substrates at the centimeter scale. We demonstrated the very high performance oxide TFTs on the nanoscale and periodic degenerately doped heterojunctions, and they yielded a nearly 20-fold increase in transconductance and apparent device mobility. The on-off ratio was higher than 109, with notably enhanced output current and clear scaling effect with channel length. We also built nanostructured wide-gap/narrow-gap heterojunctions to balance the high on-off ratio and sensitive photoresponse in a unidirectional phototransistor. This study shows the viability of programming a variety of nanoscale submicron patterns or interfaces in TFTs and FETs to significantly enlarge the scope of research on multifunctional TFTs and FETs.

Upregulation of EID3 sensitizes breast cancer cells to ionizing radiation-induced cellular senescence.

Previous studies have shown that BMS-345541 (BMS, a specific IκB kinase ß inhibitor) sensitized various tumor cells including MCF-7 breast cancer cells to ionizing radiation (IR). However, the mechanisms of BMS action are unknown. Since the expression of E1A-like inhibitor of differentiation 3 (EID3) was highly upregulated in MCF-7 cells after BMS treatment, we investigated the role of EID3 in the response of MCF-7 cells to IR. We found that BMS induced EID3 expression in MCF-7 cells in a time- and dose-dependent manner. Knockdown of EID3 by specific shRNA attenuated BMS-induced radiosensitization in MCF-7 cells. In contrast, induction of EID3 expression in an inducible EID3 expressing MCF-7 cell line with doxycycline sensitized the cells to IR. EID3-mediated sensitization of MCF-7 cells to IR was not attributed to an increase in apoptosis. Instead, EID3-expressing MCF-7 cells exhibited significantly higher levels of senescence associated ß-galactosidase (SA-ß-gal) activity and higher levels of p21 and p57 than EID3-MCF-7 cells without induction of EID3 after exposure to IR. Similar findings were observed when EID3-expressing MCF-7 cells were treated with etoposide, a topoisomerase II inhibitor. Taken together, our findings reveal a novel function of EID3 and suggest that the induction of EID3 by BMS may be exploited as a new strategy to sensitize breast cancer cells to IR and chemotherapy by inducing cancer cell senescence.

Multifunctional Highly Sensitive Multiscale Stretchable Strain Sensor Based on a Graphene/Glycerol-KCl Synergistic Conductive Network.

Stretchable strain sensors have promising applications in health monitoring and human motion detection. However, only a few of the strain sensors reported to date have exhibited a multiscale strain range and a high gauge factor simultaneously. As such, most strain sensors cannot be used in applications that require both high sensitivity and a multiscale strain range. In this work, we develop a wearable multifunctional strain sensor using graphene and a new ionic conductor as the sensing material and Ecoflex as the encapsulant. In the ionic conductor, KCl and glycerol are used as the electrolyte and solvent, respectively. This deformable ionic conductor connects cracked graphene sheets electronically, enabling the strain sensor to be stretched to 300% of its original length with a moderate gauge factor of 25.2. The sensor can respond to various mechanical deformations including stretching, bending, and pressing. When attached to human body, the sensor can monitor large-scale strains (>50%) for joint movement and small-scale strains (<10%) for facial expressions and pulses. When stretched, the sensor also shows good sensitivity in static temperature sensing. Therefore, this multifunctional stretchable sensor has good prospect of applications in human motion detection and health monitoring.

Recent Advances in Biointegrated Optoelectronic Devices.

With recent progress in the design of materials and mechanics, opportunities have arisen to improve optoelectronic devices, circuits, and systems in curved, flexible, stretchable, and biocompatible formats, thereby enabling integration of customized optoelectronic devices and biological systems. Here, the core material technologies of biointegrated optoelectronic platforms are discussed. An overview of the design and fabrication methods to form semiconductor materials and devices in flexible and stretchable formats is presented, strategies incorporating various heterogeneous substrates, interfaces, and encapsulants are discussed, and their applications in biomimetic, wearable, and implantable systems are highlighted.

Liquid-Solid Dual-Gate Organic Transistors with Tunable Threshold Voltage for Cell Sensing.

Liquid electrolyte-gated organic field effect transistors and organic electrochemical transistors have recently emerged as powerful technology platforms for sensing and simulation of living cells and organisms. For such applications, the transistors are operated at a gate voltage around or below 0.3 V because prolonged application of a higher voltage bias can lead to membrane rupturing and cell death. This constraint often prevents the operation of the transistors at their maximum transconductance or most sensitive regime. Here, we exploit a solid-liquid dual-gate organic transistor structure, where the threshold voltage of the liquid-gated conduction channel is controlled by an additional gate that is separated from the channel by a metal-oxide gate dielectric. With this design, the threshold voltage of the "sensing channel" can be linearly tuned in a voltage window exceeding 0.4 V. We have demonstrated that the dual-gate structure enables a much better sensor response to the detachment of human mesenchymal stem cells. In general, the capability of tuning the optimal sensing bias will not only improve the device performance but also broaden the material selection for cell-based organic bioelectronics.

Flexible Organic/Inorganic Hybrid Near-Infrared Photoplethysmogram Sensor for Cardiovascular Monitoring.

Wearable photoplethysmogram (PPG) sensors offer convenient and informative measurements for evaluating daily physiological states of individuals. In this work, epidermal and flexible near-infrared (NIR) PPG sensors integrating a low-power, high-sensitivity organic phototransistor (OPT) with a high-efficiency inorganic light-emitting diode are developed. By exploiting an organic bulk heterojunction active layer and a bilayer gate dielectric design, a low voltage (<3 V) operated OPT with NIR responsivity as high as 3.5 × 105 A W-1 and noise equivalent power of 1.2 × 10-15 W Hz-1/2 is achieved, greatly surpassing commercial available silicon-based photodetectors. In addition, the ultrathin encapsulation structure renders the device highly flexible and allows transfer printing of the device directly onto human skin. It is demonstrated that the epidermal/flexible PPG sensors are capable of continuously monitoring heart rate variability and precisely tracking the changes of pulse pressure at different postures of human subjects with the aid of electrocardiogram monitoring, exhibiting more reliable performance than commercial PPG sensors while consuming less power. The study suggests that the hybrid PPG sensor design may provide a promising solution for low-power, real-time physiological monitoring.

A novel antisense long non-coding RNA SATB2-AS1 overexpresses in osteosarcoma and increases cell proliferation and growth.

The knowledge regarding the importance of long non-coding RNAs (lncRNAs), a new class of genes, is very sparse in osteosarcoma. In the present study, we describe the expression profile of lncRNAs in osteosarcomas compared with paired adjacent non-cancerous tissue (n = 7) using microarray analysis. A total of 25,733 lncRNAs were identified in osteosarcoma; 1995 lncRNAs were consistently upregulated and 2226 lncRNAs were consistently under-regulated in all samples analyzed (≥2.0-fold, p < 0.05). We have validated three over-regulated and three under-regulated lncRNAs in patient samples (n = 7). The antisense transcript of SATB2 protein (SATB2-AS1) was identified as one of the upregulated lncRNAs. The SATB2-AS1 is a 3197-bp lncRNA on chromosome 2. This is the first report, where we have documented the increased expression of SATB2-AS1 in osteosarcoma patients and in human osteosarcoma cancer cell lines (U2OS, HOS, MG63). SATB2-AS1 expression was significantly higher in the metastatic tumors compared to non-metastatic tumors. In vitro gain and loss of function approaches demonstrated that SATB2-AS1 regulates cell cycle, cell proliferation, and cell growth. In addition, SATB2-AS1 affects the translational expression of SATB2 gene. Our data demonstrate that an antisense non-coding RNA regulates the expression of its sense gene, and increases the cell growth, therefore pointing the pivotal functions of SATB2-AS1 in osteosarcoma.

Anticancer effect of thalidomide in vitro on human osteosarcoma cells.

Osteosarcoma is a high­grade malignant tumor frequently found in children and adolescents. Thalidomide has been reported for treatment of various malignancies. Thalidomide was added to osteosarcoma cells and studied by cytotoxicity assay, evaluating apoptosis, cell cycle arrest, mitochondrial membrane potential (ΔΨm), and reactive oxygen species (ROS) levels and the expression of Bcl­2, Bax, caspase­3 and NF­κB. The results showed that thalidomide could inhibit the proliferation of MG­63 and U2OS cells in a concentration­ and time­dependent manner. Morphological changes of apoptosis were also observed. Thalidomide increased the apoptosis rate of MG­63 cells and induced cell cycle arrest by increasing the number of cells in the G0/G1 phase and decreasing the percentage of S phase in MG­63 cells. Further investigation showed that a disruption of ΔΨm and upregulation of ROS were induced by thalidomide in high concentration. By western blot analysis, thalidomide resulted in the decreasing expression of Bcl­2 and NF­κB, and the increasing expression of Bcl­2/Bax and caspase­3. Here, we provide evidence that thalidomide could cause apoptosis in osteosarcoma cells. Taken together, these results indicate that thalidomide could be an antitumor drug in the therapy of osteosarcoma.

Anticancer Activity Studies of Ruthenium(II) Complex Toward Human Osteosarcoma HOS Cells.

A new Ru(II) complex [Ru(dmp)2(NMIP)](ClO4)2 (dmp = 2,9-dimethyl-1,10-phenanthroline, NMIP = 2'-(2″-nitro-3″,4″-methylenedioxyphenyl)imidazo[4',5'-f][1,10]-phenanthroline) was synthesized and characterized by elemental analysis, ESI-MS and (1)H NMR. The cytotoxic activity of the complex against MG-63, U2OS, HOS, and MC3T3-e1 cell lines was investigated by MTT method. The complex shows moderate cytotoxicity toward HOS (IC50 = 35.6 ± 2.6 µM) and MC3T3-e1 (IC50 = 41.6 ± 2.8 µM) cell lines. The morphological studies show that the complex can induce apoptosis in HOS cells and cause an increase of reactive oxygen species levels and a decrease in the mitochondrial membrane potential. The cell cycle distribution demonstrates that the complex inhibits the cell growth at S phase. Additionally, the antitumor activity in vivo reveals that the complex can induce a decrease in tumor weight.

Protein-binding, cytotoxicity in vitro and cell cycle arrest of ruthenium(II) polypyridyl complexes.

The cytotoxic activity of two Ru(II) complexes against A549, BEL-7402, HeLa, PC-12, SGC-7901 and SiHa cell lines was investigated by MTT method. Complexes 1 and 2 show moderate cytotoxicity toward BEL-7402 cells with an IC50 value of 53.9 ± 3.4 and 39.3 ± 2.1 µM. The effects of the complexes inducing apoptosis, cellular uptake, reactive oxygen species and mitochondrial membrane potential in BEL-7402 cells have been studied by fluorescence microscopy. The percentages of apoptotic and necrotic cells and cell cycle arrest were studied by flow cytometry. The BSA-binding behaviors were investigated by UV/visible and fluorescent spectra.

Flexure-based Roll-to-roll Platform: A Practical Solution for Realizing Large-area Microcontact Printing.

A continuous roll-to-roll microcontact printing (MCP) platform promises large-area nanoscale patterning with significantly improved throughput and a great variety of applications, e.g. precision patterning of metals, bio-molecules, colloidal nanocrystals, etc. Compared with nanoimprint lithography, MCP does not require a thermal imprinting step (which limits the speed and material choices), but instead, extreme precision with multi-axis positioning and misalignment correction capabilities for large area adaptation. In this work, we exploit a flexure-based mechanism that enables continuous MCP with 500 nm precision and 0.05 N force control. The fully automated roll-to-roll platform is coupled with a new backfilling MCP chemistry optimized for high-speed patterning of gold and silver. Gratings of 300, 400, 600 nm line-width at various locations on a 4-inch plastic substrate are fabricated at a speed of 60 cm/min. Our work represents the first example of roll-to-roll MCP with high reproducibility, wafer scale production capability at nanometer resolution. The precision roll-to-roll platform can be readily applied to other material systems.