My research goal is to develop a multidisciplinary research program that focuses on advancing nanomanufacturing technologies to address the grand challenges in biomedical, communication and energy applications. The three main research areas are novel nanomanufacturing, nanophotonics and quantum optics, and biosensing and liquid biopsy.
1 Novel manufacturing methods
Next-generation manufacturing technologies need new inventions converging materials, processes, systems, and designs. Focusing on micrometer- and nanometer-scale manufacturing, I have built up a 1,500-sqft lab space with photolithography, nanoimprint lithography (NIL) and 3D printing (aka. additive manufacturing) capabilities that actively support a wide range of ongoing research activities.
1.1 3D Printing
Recent development demonstrated the feasibility of printing three-dimensional and complex structures for commercial applications. However, the current demonstrations are limited to macroscale components with dimensions in the millimeter scale or above, and typically require extreme processing conditions (for example laser melting or heating) for metal and dielectric processing. Our group is currently seeking to address this fundamental need of designing multifunctional and multimaterial printing systems at micrometer- and nanometer-scale resolution using a new solution-based scalable additive manufacturing approach.
The long-term objective of our research is to develop a versatile technique that is capable of printing metallic structures at micrometer- and nanometer-scale resolution feasible for electronic and photonic applications. In this project, our research goal is to explore a new solution-based photochemically induced deposition (PIPAD) process to scalably produce thickness- and dimension-controlled, highly reflective and highly conductive metal microstructures. We will explore the fundamental limits in both the lateral and vertical dimensions of the printed structures by combining theoretical and experimental studies. Additionally, we will also apply the technique to non-flat and flexible surfaces, and prove its feasibility in printing different noble metals on a variety of substrate materials.
This project is currently funded by NSF under grant no. 1947753.
Zhi Zhao †*, Jing Bai, Yu Yao, and Chao Wang*, “Printing Continuous Metal Structures via Polymer-Assisted Photochemical Deposition,” Materials Today, doi.org/10.1016/j.mattod.2020.03.001.
1.2 DNA Origami Based Assembly
In this direction, our group, in collaboration with Dr. Yan Liu, is using programmed DNA origami (DO) and single stranded DNA linkers to deterministically assemble anisotropic metallic nanoparticles (MNPs) and emitters with precisely determined geometries and locations, forming plasmonic metamaterial with critical dimensions down to single-digit nanometer scale and achieving strong electromagnetic field interaction with a single emitter at the cavities. We aim to study the fundamental emitter-cavity interactions at nanometer scale assisted by biomolecular assembly, which is a part of the PI’s long-term career goal to bridge quantum optics with biotechnology. Specifically, we will innovative three-dimensional DO designs to assemble anisotropic nanoparticle dimer cavities. Further, we will attach single QD and organic dye emitters to each DO template and the MNP cavity in a deterministic strategy, and use the DO assembled system as a metamaterial platform to experimentally quantify the emission decay rates, Purcell factor, coupling strength, Rabi vacuum energy splitting, and quantum auto-correlation measurements.
Zhi Zhao †, Xiahui Chen, Jiawei Zuo, Ali Basiri, Shinhyuk Choi, Yu Yao, Yan Liu *, and Chao Wang *, “Deterministic Assembly of Single Emitters in Sub-5 Nanometer Optical Cavity Formed by Gold Nanorod Dimers on Three-Dimensional DNA Origami ” Nano Research, 2021, https://doi.org/10.1007/s12274-021-3661-z. (arXiv:2104.02916 ; Springer Nature Content Sharing Initiative)
2．Nanophotonics and Quantum Optics
2.1 Metasurface nanostructures for polarization control and sensing
Circularly polarized light (CPL) has been widely utilized in quantum communication, quantum computing, circular dichroism (CD) spectroscopy and polarimetric imaging and sensing. Traditionally, CP light detection requires multiple bulky optical elements such as polarizers, waveplates and mechanically rotating components, which pose fundamental limitations for device miniaturization, robust system integration and high-speed operation. Recent developments in nanotechnology and nanophotonics have enabled ultra-compact solid-state CPL detection that generally exhibit superior stability in ambient conditions, fast response time and high fidelity. For example, artificial three-dimensional (3D) metamaterials have been demonstrated based on chiral nanostructures to differentiate opposite handedness of CPL. However, fabrication of such complex 3D structures requires stringent process control and its scalability is challenging. More recently, planar (or 2D) chiral plasmonic metasurface structures have also been reported with chiro-optical responses. Compared with 3D chiral metamaterials, the metasurface structures are easier to fabricate and more compatible with on-chip manufacturing technologies; yet, the chiral plasmonic metasurfaces experimentally demonstrated so far usually suffer from low Circular Polarization Extinction Ratios (CPERs) (less than ~5) and limited optical efficiency in experiment (20-50 %). To improve the optical efficiency, chiral dielectric metasurface structures have been achieved in experiment, with optical efficiency up to 90 %. However, their CPERs are still limited (up to 8). To date, it is still challenging to realize ultra-compact CPL detection devices with simultaneously high extinction ratio and optical efficiency.
Besides CPL detection, ultra-compact polarimetric detection and imaging systems are highly desirable for full polarization state measurement in various applications such as communication, remote sensing, polarization imaging and biological diagnostics. Among different polarimeter designs , plasmonics-based polarimetric detecting devices have been reported with unprecedented compactness based on phase-gradient birefringent metagratings, diffracting plasmonic metasurfaces and graphene-integrated anisotropic metasurfaces. However, these devices operate in reflection mode and hence are not compatible for direct on-chip integration with photodetectors or imaging sensors. Polarization-dependent surface plasmon polariton (SPP) structures have also been demonstrated with the feasibility of direct integration on detectors or imaging sensors, however, these devices suffer from low efficiency. Very recently, a highly efficient phase-gradient all-dielectric metasurface polarimeter has been reported with a high efficiency (60-65%). This approach enables splitting and focusing of light in three different polarization bases in transmission mode and provides a feasible method to realize on-chip polarimetric imaging arrays. Yet, the polarization measurement accuracy is fundamentally limited by the cross-talk between different polarization states and degrades noticeably as the super-pixel size becomes smaller than 7.2 µm.
Inspired by the compound eyes of Stomatopods, we have recently demonstrated theoretically and experimentally double-layer chiral metasurface structures for near-infrared wavelength polarimetric detection with a CPER up to 35 and transmission efficiency >80%. The structure consists of a low-loss dielectric metasurface, an oxide spacer layer and a nanowire polarizer, with a total thickness of less than 1 µm. Besides CPL detection units, we have also integrated the chiral metasurface structures on the same chip with linear polarization (LP) filters to perform full-stokes polarimetric detection. Our designs are advantageous for its feasibility of direct and scalable integration onto existing imaging sensors, high extinction ratio, high transmission efficiency, ultra-compact footprint (sub-wavelength thickness, micrometer scale in lateral dimension) and robustness; thus are ideal for ultra-compact imaging, sensing, communication and navigation systems.
Currently we are investigating the design of the metausurface systems as ultracompact on-chip integrated polarimetric imager. One of the applications would be attaching such imagers to drones and deploy them to evaluate the performance of CSP collector systems.
This project is currently funded by NSF under grant no. 1809997. We are working closely with Dr. Yu Yao for this project.
(1) Ali Basiri †, Xiahui Chen, Pouya Amrollahi, Jing Bai, Joe Carpenter, Zachary Holman, Chao Wang *, and Yu Yao *, “Nature-Inspired Chiral Metasurfaces for On-Chip Circularly Polarized Light Detection,” Light: Science & Applications, vol. 8, Article number: 78, 2019.
(2) Jing Bai †, Chu Wang, Xiahui Chen, Ali Basiri, Chao Wang, and Yu Yao *, “On Chip-Integrated Plasmonic Flat Optics for Mid-Infrared Full-Stokes Polarization Detection,” Photonics Research, vol. 7, pp. 1051-1060, 2019.
3．Biosensing and Liquid Biopsy
I am very interested in studying subcellular molecules and their interactions with nanomaterials. I envision a multi-level integrative strategy to explore potentially translational biomedical solutions that are faster, more accurate, less expensive, and more broadly applicable. First, integrated sample handling, detection, and readout all on a compact device is advantageous in minimizing human intervention, pre-analytical errors, sample volume, and sensing time. Further, integrative diagnostics of a panel of biomarkers from genomics and proteomics to epi-genomics and metabolomics can provide valuable systems-biology understandings for complex disease (such as cancer) detection, particularly at an early stage, as well as disease severity analysis and prognostics. Lastly, it is indispensable to integrate multi-disciplinary knowledge from manufacturing, photonics, micro-fluidics, circuits, statistics, machine learning, surface chemistry, and biochemistry for sensing system designs.
3.1 Nano-bioelectronics for Biomolecule Detection
Nanopore sensing is an emerging technology, which has recently been developed towards future precision/personalized medicine applications. A nanopore sensor measures single molecules as they flow through a nanometer hole in a thin membrane separating two fluidic chambers, and collects the electronic signal as a result of modulation of the ion conductivity inside the nanopore, which correlates to the molecular signature of the tested biomolecule. Beyond the DNA primary sequence, nanopore sensors have been used to detect DNA epi-genetic information (such as DNA methylation) as well as other molecules (proteins, extracellular vesicles, etc) related to disease diagnostics. Conventionally, detection of such molecules requires complex procedures for quantification and detection, such as purification, enzymatic amplification, hybridization, etc. Therefore, the detection process is not only costly and time-consuming but also error-prone, due to inevitable bias from sample preparation and human operation errors. In comparison, nanopore sensing is advantageous for its capability of detecting at single-molecule level without complex sample preparation.
Particularly, solid-state nanopores are portable, structurally robust, and manufacturable, making them especially appealing to broad genetics-based diagnostic applications in modern clinical as well as in resource-limited settings. However, despite the efforts to improve the nanopore structure design and data analysis algorithms, it often remains difficult to accurately interpret the molecular structure from the electrical current signals. One key challenge is associated with an insufficient signal-to-noise ratio (SNR) of the existing nanopore devices. Specifically, the silicon (Si) substrate’s inherent large electrical capacitance in conventional Si nanopore devices results in a high electrical noise at high frequencies, and hence limits the data-recording speed and complicates the signal retrieval. Using DNA as an example, the complex DNA conformational changes and dynamic interaction with nanopore surface complicates the electrical signal deconvolution partly due to complex DNA translocation dynamics in small solid-state nanopores. Currently, high-speed and accurate DNA detection at the single-molecule level still lags behind.
To address these challenges, we are developing a novel sapphire based solid-state platform that can minimize the device capacitance by more than 2 orders of magnitude and accordingly significantly improve the signal bandwidth and reduce the noise. Importantly, the fabrication method of our platform is compatible with high-throughput batch processing, thus very desirable for large-scale and low-cost production of future electronic sequencers. Specifically, we propose to use anisotropic wet etching to create novel triangular shaped membranes and nanopores on insulating sapphire crystal over a wafer scale. We are investigating a variety of strategies to precisely define the membrane size and thickness. We expect to fabricate ultrathin (1-10 nm thick) and ultrasmall (<10 µm wide) membranes in a variety of materials (SiN, TiO2, and 2D materials) that will yield a device capacitance <1 pF, which will essentially eliminate the nanopore device impact on the electronic noise. Finally, we will study the high-frequency (up to 1 MHz) current noise response and DNA signal integrity using the sapphire chips. Our approach eliminates high-temperature or wet processes that are ineffective and detrimental to ultrasmall structures, which is critical to high-yield manufacturing.
Currently, we are collaborating with Dr. Amit Meller at Technion for DNA methylation detection under NSF grant no. ECCS-2020464 and Dr. Hao Yan and Dr. Rizal Hariadi on DNA memories under NSF grant no. CCF-2027215.
Pengkun Xia †, Jiawei Zuo, Pravin Paudel, Shinhyuk Choi, Xiahui Chen, Md Ashiqur Rahman Laskar, Jing Bai, Weisi Song, JongOne Im, and Chao Wang *, “Sapphire Nanopores for Low-Noise DNA Sensing,” Biosensors and Bioelectronics, org/10.1016/j.bios.2020.112829, 2020.
3.2 Plasmonic Biosensing
Recently, we reported a plasmonic nanosensor for label-free, sensitive, specific, and quantitative identification of nanometer-sized molecules in the infrared range. The device design is based on vertically coupled complementary antennas with densely patterned hot-spots. The elevated metallic nanobars and complimentary nanoslits in the substrate strongly couple at vertical nano-gaps between them, resulting in dual-mode sensing dependent on the light polarization parallel or perpendicular to the nanobars. We demonstrate experimentally that a monolayer of octadecanethiol (ODT) molecules (thickness 2.5 nm) leads to significant antenna resonance wavelength shift over 136 nm, corresponding to 7.5 nm for each carbon atom in the molecular chain or 54 nm for each nanometer in analyte thickness. Additionally, all the four characteristic vibrational fingerprint signals, including the weak CH3– modes, are clearly delineated experimentally in both sensing modes. Such a dual-mode sensing with a broad wavelength design range (2.5 µm to 4.5 µm) is potentially useful for multi-analyte detection.
Rapid detection of infectious diseases, from Ebola virus disease (EVD) to recent coronavirus disease 2019 (COVID-19) and to future disease X, is crucial to isolating infection and disrupting the transmission. Current biomarker-based diagnostics mainly relies on the detection of the genetic (or molecular), antigenic, or serological (antibody) markers. Genetic detection, typically based on polymerase chain reaction (PCR), is the gold standard but more complex, costly, time-consuming and instrument-demanding. My goal is to build a rapid and sensitive point-of-care (POC) tool that can be deployed shortly after pathogen emergence and available in resource-limited settings. In collaboration with Prof. Liangcai Gu at Univ. Washington, we have designed an assay that use nanobody-conjugated nanoparticles for rapid, electronic detection (Nano2RED, bioRxiv 2021.05.09.443341). Using Ebola sGP protein as the target antigen, we synthesized highly specific nanobodies, and demonstrated that sGP-nanobody binding triggers a suspension color change from AuNP aggregation and precipitation. The signals can be read out qualitatively by eyes, or quantitatively using photodetectors with LEDs as a light source. Unlike fluorescence based readout that requires complex optical elements, this electronic readout format can be designed very portable and inexpensive for resource-limited settings. The Nano2RED assay detects sGP proteins in diluted serum down to ~10 pM and 10-100 times better than enzyme-linked immunosorbent assays (ELISA), while specifically distinguishing a membrane-anchored protein isoform (GP1,2). In addition, we have developed a rapid detection scheme to shorten the assay time to a few minutes, by introducing a pre-concentrating step that accelerates antigen-dependent AuNP precipitation. This sensitive, specific, rapid, quantitative, and low-cost platform could be standardized and made available within ~4 weeks for a wide variety of pathogens, potentially well-suited to both clinical and home use for identifying infective individuals, quantifying viral load, and analyzing the immune response. The Nano2RED sensor can be extended to integrate circuit elements to automate data collection, storage, and analysis, further reducing diagnostic workload and speeding up surveillance response. In addition, our sensor has been proven feasible to detect cancer-relevant extracellular vesicles and small molecules (cannabidiol), as well as small non-coding microRNAs.
(1) Xiahui Chen †, Chu Wang, Yu Yao *, and Chao Wang *, “Plasmonic Vertically Coupled Complementary Antennas for Dual-Mode Infrared Molecule Sensing,” ACS Nano, vol. 11, pp. 8034-8046, 2017.
(2) Xiahui Chen †, Shoukai Kang, Md Ashif Ikbal, Zhi Zhaor, Jiawei Zuo, Yu Yao, Liangcai Gu*, and Chao Wang*, “Rapid Electronic Diagnostics of Ebola Virus with Synthetic Nanobody-Conjugated Gold Nanoparticles,” Under review, bioRxiv 2021.05.09.443341.
3.3 Integrated Exosome Molecular Analyzers
Recent studies have revealed the significant clinical potential of extracellular vescicles (e.g. exosome), both as a point of intervention in the treatment of carcinoma and a potential biomarker for disease diagnosis and prognosis. Despite the great promise of exosome-based molecular diagnostics, a number of technological challenges seriously hinders its accuracy and reliability in disease detection. First, the exosome purification process is either too time-consuming (ultracentrifugation) or bias-prone (conventional immunoprecipitation suffers from poor antibody specificity), thus resulting in serious pre-analytical errors and poor statistical stability. Second, concomitant molecular profiling of exosome protein markers and cargo microRNAs promises to significantly improve the diagnostic accuracy, but requires lengthy detection steps, complex sample processing, and frequently introduces biases. The long-term goal of our group to build a fully integrated and multifunctional optofluidic diagnostic technology that seamlessly incorporates exosome purification and exosomal protein and microRNA (miRNA) profiling on a single device to achieve rapid and accurate screening and disease detection at early stage.
Our design will integrate multiple functional modules on the same chip to sequentially achieve label-free exosome purification, surface protein profiling on plasmonic sensors, and multiplexed microRNA detection. Specifically, exosomes will be continuously sorted by size in nanofluidic pillar array, which is based on my previous development at IBM (nnano.2016.134). The purified exosomes will then be captured onto plasmonic sensors labelled with nanometer-sized antibody pairs highly specific to the exosome protein markers for sensitive optical detection.
We are currently supported by NSF under grant no. 1847324 to detect exosomal miRNA molecules.
(1) Benjamin H. Wunsch †, Joshua T. Smith, Stacey M. Gifford, Chao Wang, Markus Brink, Robert Bruce, Robert H. Austin, Gustavo Stolovitzky, and Yann Astier, “Nanoscale Lateral Displacement Arrays for Separation of Exosomes and Colloids Down to 20nm,” Nat. Nanotechnol., vol. 11, pp. 936–940, 2016.
(2) Benjamin H. Wunsch, Sung-Cheol Kim, Stacey M. Gifford, Yann Astier, Chao Wang, Robert L. Bruce, Jyotica V. Patel, Elizabeth A. Duch, Simon Dawes, Gustavo Stolovitzky, and Joshua T. Smith, “Gel-on-a-chip: continuous, velocity-dependent DNA separation using nanoscale lateral displacement”, Lab on a Chip, vol. 19, pp. 1567-1578, 2019.
(3) Lotien Richard Huang, Edward C Cox, Robert H Austin, and James C Sturm, “Continuous particle separation through deterministic lateral displacement,” Science, vol. 304, pp. 987-990, 2004.