Dr. Anqi Zhang is currently an American Heart Association (AHA) postdoctoral fellow advised by Professor Zhenan Bao in the Department of Chemical Engineering and Professor Karl Deisseroth in the Department of Bioengineering at Stanford University. She received her Ph.D. degree under the supervision of Professor Charles M. Lieber in the Department of Chemistry and Chemical Biology at Harvard University in 2020, and her B.S. degree in Materials Chemistry from Fudan University in 2014. She is interested in combining novel electronic, chemical, and genetic tools to monitor and modulate neural circuits in a minimally invasive manner.
Ph.D., Harvard University, Chemistry (2020)
M.A., Harvard University, Chemistry (2017)
B.S., Fudan University, Materials Science (2014)
Biochemically functionalized probes for cell-type-specific targeting and recording in the brain.
2023; 9 (48): eadk1050
Selective targeting and modulation of distinct cell types and neuron subtypes is central to understanding complex neural circuitry and could enable electronic treatments that target specific circuits while minimizing off-target effects. However, current brain-implantable electronics have not yet achieved cell-type specificity. We address this challenge by functionalizing flexible mesh electronic probes, which elicit minimal immune response, with antibodies or peptides to target specific cell markers. Histology studies reveal selective association of targeted neurons, astrocytes, and microglia with functionalized probe surfaces without accumulating off-target cells. In vivo chronic electrophysiology further yields recordings consistent with selective targeting of these cell types. Last, probes functionalized to target dopamine receptor 2 expressing neurons show the potential for neuron-subtype-specific targeting and electrophysiology.
View details for DOI 10.1126/sciadv.adk1050
View details for PubMedID 38019917
Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation.
bioRxiv : the preprint server for biology
Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, ‶spiral transformation, to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.
View details for DOI 10.1101/2023.10.02.560482
View details for PubMedID 37873341
Genetically targeted chemical assembly of polymers specifically localized extracellularly to surface membranes of living neurons.
2023; 9 (32): eadi1870
Multicellular biological systems, particularly living neural networks, exhibit highly complex organization properties that pose difficulties for building cell-specific biocompatible interfaces. We previously developed an approach to genetically program cells to assemble structures that modify electrical properties of neurons in situ, opening up the possibility of building minimally invasive cell-specific structures and interfaces. However, the efficiency and biocompatibility of this approach were challenged by limited membrane targeting of the constructed materials. Here, we design a method for highly localized expression of enzymes targeted to the plasma membrane of primary neurons, with minimal intracellular retention. Next, we show that polymers synthesized in situ by this approach form dense extracellular clusters selectively on the targeted cell membrane and that neurons remain viable after polymerization. Last, we show generalizability of this method across a range of design strategies. This platform can be readily extended to incorporate a broad diversity of materials onto specific cell membranes within tissues and may further enable next-generation biological interfaces.
View details for DOI 10.1126/sciadv.adi1870
View details for PubMedID 37556541
Ultraflexible endovascular probes for brain recording through micrometer-scale vasculature.
Science (New York, N.Y.)
2023; 381 (6655): 306-312
Implantable neuroelectronic interfaces have enabled advances in both fundamental research and treatment of neurological diseases but traditional intracranial depth electrodes require invasive surgery to place and can disrupt neural networks during implantation. We developed an ultrasmall and flexible endovascular neural probe that can be implanted into sub-100-micrometer-scale blood vessels in the brains of rodents without damaging the brain or vasculature. In vivo electrophysiology recording of local field potentials and single-unit spikes have been selectively achieved in the cortex and olfactory bulb. Histology analysis of the tissue interface showed minimal immune response and long-term stability. This platform technology can be readily extended as both research tools and medical devices for the detection and intervention of neurological diseases.
View details for DOI 10.1126/science.adh3916
View details for PubMedID 37471542
A CMOS-based highly scalable flexible neural electrode interface.
2023; 9 (23): eadf9524
Perception, thoughts, and actions are encoded by the coordinated activity of large neuronal populations spread over large areas. However, existing electrophysiological devices are limited by their scalability in capturing this cortex-wide activity. Here, we developed an electrode connector based on an ultra-conformable thin-film electrode array that self-assembles onto silicon microelectrode arrays enabling multithousand channel counts at a millimeter scale. The interconnects are formed using microfabricated electrode pads suspended by thin support arms, termed Flex2Chip. Capillary-assisted assembly drives the pads to deform toward the chip surface, and van der Waals forces maintain this deformation, establishing Ohmic contact. Flex2Chip arrays successfully measured extracellular action potentials ex vivo and resolved micrometer scale seizure propagation trajectories in epileptic mice. We find that seizure dynamics in absence epilepsy in the Scn8a+/- model do not have constant propagation trajectories.
View details for DOI 10.1126/sciadv.adf9524
View details for PubMedID 37285436
View details for PubMedCentralID PMC10246892
Tissue libraries enable rapid determination of conditions that preserve antibody labeling in cleared mouse and human tissue.
Difficulty achieving complete, specific, and homogenous staining is a major bottleneck preventing the widespread use of tissue clearing techniques to image large volumes of human tissue. In this manuscript, we describe a procedure to rapidly design immunostaining protocols for antibody labeling of cleared brain tissue. We prepared libraries of .5-1.0 mm thick tissue sections that are fixed, pre-treated, and cleared via similar, but different procedures to optimize staining conditions for a panel of antibodies. Results from a library of mouse tissue correlate well with results from a similarly prepared library of human brain tissue, suggesting mouse tissue is an adequate substitute for protocol optimization. These data show that procedural differences do not influence every antibody-antigen pair in the same way, and minor changes can have deleterious effects, therefore, optimization should be conducted for each target. The approach outlined here will help guide researchers to successfully label a variety of targets, thus removing a major hurdle to accessing the rich 3D information available in large, cleared human tissue volumes.
View details for DOI 10.7554/eLife.84112
View details for PubMedID 36656755
- Nanowire-enabled bioelectronics NANO TODAY 2021; 38
- Nanowire probes could drive high-resolution brain-machine interfaces NANO TODAY 2020; 31
Scalable ultrasmall three-dimensional nanowire transistor probes for intracellular recording
2019; 14 (8): 783-+
New tools for intracellular electrophysiology that push the limits of spatiotemporal resolution while reducing invasiveness could provide a deeper understanding of electrogenic cells and their networks in tissues, and push progress towards human-machine interfaces. Although significant advances have been made in developing nanodevices for intracellular probes, current approaches exhibit a trade-off between device scalability and recording amplitude. We address this challenge by combining deterministic shape-controlled nanowire transfer with spatially defined semiconductor-to-metal transformation to realize scalable nanowire field-effect transistor probe arrays with controllable tip geometry and sensor size, which enable recording of up to 100 mV intracellular action potentials from primary neurons. Systematic studies on neurons and cardiomyocytes show that controlling device curvature and sensor size is critical for achieving high-amplitude intracellular recordings. In addition, this device design allows for multiplexed recording from single cells and cell networks and could enable future investigations of dynamics in the brain and other tissues.
View details for DOI 10.1038/s41565-019-0478-y
View details for Web of Science ID 000478794700018
View details for PubMedID 31263191
Specific detection of biomolecules in physiological solutions using graphene transistor biosensors
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2016; 113 (51): 14633–38
Nanomaterial-based field-effect transistor (FET) sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although direct measurements in high-ionic-strength physiological solutions remain challenging due to the Debye screening effect. Recently, we demonstrated a general strategy to overcome this challenge by incorporating a biomolecule-permeable polymer layer on the surface of silicon nanowire FET sensors. The permeable polymer layer can increase the effective screening length immediately adjacent to the device surface and thereby enable real-time detection of biomolecules in high-ionic-strength solutions. Here, we describe studies demonstrating both the generality of this concept and application to specific protein detection using graphene FET sensors. Concentration-dependent measurements made with polyethylene glycol (PEG)-modified graphene devices exhibited real-time reversible detection of prostate specific antigen (PSA) from 1 to 1,000 nM in 100 mM phosphate buffer. In addition, comodification of graphene devices with PEG and DNA aptamers yielded specific irreversible binding and detection of PSA in pH 7.4 1x PBS solutions, whereas control experiments with proteins that do not bind to the aptamer showed smaller reversible signals. In addition, the active aptamer receptor of the modified graphene devices could be regenerated to yield multiuse selective PSA sensing under physiological conditions. The current work presents an important concept toward the application of nanomaterial-based FET sensors for biochemical sensing in physiological environments and thus could lead to powerful tools for basic research and healthcare.
View details for DOI 10.1073/pnas.1625010114
View details for Web of Science ID 000390044900045
View details for PubMedID 27930344
View details for PubMedCentralID PMC5187689
Epitaxial Growth of Lattice-Mismatched Core-Shell TiO2@MoS2 for Enhanced Lithium-Ion Storage
2016; 12 (20): 2792-2799
Core-shell structured nanohybrids are currently of significant interest due to their synergetic properties and enhanced performances. However, the restriction of lattice mismatch remains a severe obstacle for heterogrowth of various core-shells with two distinct crystal structures. Herein, a controlled synthesis of lattice-mismatched core-shell TiO2 @MoS2 nano-onion heterostructures is successfully developed, using unilamellar Ti0.87 O2 nanosheets as the starting material and the subsequent epitaxial growth of MoS2 on TiO2 . The formation of these core-shell nano-onions is attributed to an amorphous layer-induced heterogrowth mechanism. The number of MoS2 layers can be well tuned from few to over ten layers, enabling layer-dependent synergistic effects. The core-shell TiO2 @MoS2 nano-onion heterostructures exhibit significantly enhanced energy storage performance as lithium-ion battery anodes. The approach has also been extended to other lattice-mismatched systems such as TiO2 @MoSe2 , thus suggesting a new strategy for the growth of well-designed lattice-mismatched core-shell structures.
View details for DOI 10.1002/smll.201600237
View details for Web of Science ID 000378424400014
View details for PubMedID 27062267
Synthesis, Study, and Discrete Dipole Approximation Simulation of Ag-Au Bimetallic Nanostructures
NANOSCALE RESEARCH LETTERS
2016; 11: 209
Water-soluble Ag-Au bimetallic nanostructures were prepared via co-reduction and seed-mediated growth routes employing poly-(4-styrenesulfonic acid-co-maleic acid) (PSSMA) as both a reductant and a stabilizer. Ag-Au alloy nanoparticles were obtained by the co-reduction of AgNO3 and HAuCl4, while Ag-Au core-shell nanostructures were prepared through seed-mediated growth using PSSMA-Au nanoparticle seeds in a heated AgNO3 solution. The optical properties of the Ag-Au alloy and core-shell nanostructures were studied, and the growth mechanism of the bimetallic nanoparticles was investigated. Plasmon resonance bands in the range 422 to 517 nm were observed for Ag-Au alloy nanoparticles, while two plasmon resonances were found in the Ag-Au core-shell nanostructures. Furthermore, discrete dipole approximation theoretical simulation was used to assess the optical property differences between the Ag-Au alloy and core-shell nanostructures. Composition and morphology studies confirmed that the synthesized materials were Ag-Au bimetallic nanostructures.
View details for DOI 10.1186/s11671-016-1435-4
View details for Web of Science ID 000374678800002
View details for PubMedID 27094823
View details for PubMedCentralID PMC4837194
Spontaneous Internalization of Cell Penetrating Peptide-Modified Nanowires into Primary Neurons
2016; 16 (2): 1509-1513
Semiconductor nanowire (NW) devices that can address intracellular electrophysiological events with high sensitivity and spatial resolution are emerging as key tools in nanobioelectronics. Intracellular delivery of NWs without compromising cellular integrity and metabolic activity has, however, proven difficult without external mechanical forces or electrical pulses. Here, we introduce a biomimetic approach in which a cell penetrating peptide, the trans-activating transcriptional activator (TAT) from human immunodeficiency virus 1, is linked to the surface of Si NWs to facilitate spontaneous internalization of NWs into primary neuronal cells. Confocal microscopy imaging studies at fixed time points demonstrate that TAT-conjugated NWs (TAT-NWs) are fully internalized into mouse hippocampal neurons, and quantitative image analyses reveal an ca. 15% internalization efficiency. In addition, live cell dynamic imaging of NW internalization shows that NW penetration begins within 10-20 min after binding to the membrane and that NWs become fully internalized within 30-40 min. The generality of cell penetrating peptide modification method is further demonstrated by internalization of TAT-NWs into primary dorsal root ganglion (DRG) neurons.
View details for DOI 10.1021/acs.nanolett.6b00020
View details for Web of Science ID 000370215200103
View details for PubMedID 26745653
2016; 116 (1): 215-257
Nano-bioelectronics represents a rapidly expanding interdisciplinary field that combines nanomaterials with biology and electronics and, in so doing, offers the potential to overcome existing challenges in bioelectronics. In particular, shrinking electronic transducer dimensions to the nanoscale and making their properties appear more biological can yield significant improvements in the sensitivity and biocompatibility and thereby open up opportunities in fundamental biology and healthcare. This review emphasizes recent advances in nano-bioelectronics enabled with semiconductor nanostructures, including silicon nanowires, carbon nanotubes, and graphene. First, the synthesis and electrical properties of these nanomaterials are discussed in the context of bioelectronics. Second, affinity-based nano-bioelectronic sensors for highly sensitive analysis of biomolecules are reviewed. In these studies, semiconductor nanostructures as transistor-based biosensors are discussed from fundamental device behavior through sensing applications and future challenges. Third, the complex interface between nanoelectronics and living biological systems, from single cells to live animals, is reviewed. This discussion focuses on representative advances in electrophysiology enabled using semiconductor nanostructures and their nanoelectronic devices for cellular measurements through emerging work where arrays of nanoelectronic devices are incorporated within three-dimensional cell networks that define synthetic and natural tissues. Last, some challenges and exciting future opportunities are discussed.
View details for DOI 10.1021/acs.chemrev.5b00608
View details for Web of Science ID 000368323200006
View details for PubMedID 26691648
View details for PubMedCentralID PMC4867216
- Nanowires: Building Blocks for Nanoscience and Nanotechnology NANOWIRES: BUILDING BLOCKS FOR NANOSCIENCE AND NANOTECHNOLOGY 2016: 1-322
- Hyaluronan/Tween 80-assisted synthesis of silver nanoparticles for biological application JOURNAL OF NANOPARTICLE RESEARCH 2015; 17 (2)
Semiconductor nanowires for biosensors
Semiconductor Nanowires: Materials, Synthesis, Characterization and Applications
Woodhead Publishing. 2015: 471-490
View details for DOI 10.1016/B978-1-78242-253-2.00017-7
Kinetically-controlled template-free synthesis of hollow silica micro-/nanostructures with unusual morphologies
2014; 25 (13): 135608
We report a kinetically-controlled template-free room-temperature production of hollow silica materials with various novel morphologies, including tubes, crutches, ribbons, bundles and bells. The obtained products, which grew in a well-controlled manner, were monodispersed in shape and size. The role of ammonia, sodium citrate, polyvinylpyrrolidone, chloroauric acid and NaCl in shape control is discussed in detail. The oriented growth of these micro-/nanostructures directed by reverse micelles followed a solution-solution-solid (SSS) mechanism, similar to the classic vapor-liquid-solid mechanism. The evolution processes of silica rods, tubes, crutches, bundles and bells were recorded using transmission electron microscopy to prove the SSS mechanism.
View details for DOI 10.1088/0957-4484/25/13/135608
View details for Web of Science ID 000332858700020
View details for PubMedID 24598146
- pH-Dependent shape changes of water-soluble CdS nanoparticles JOURNAL OF NANOPARTICLE RESEARCH 2013; 16 (1)
- Simulated optical properties of noble metallic nanopolyhedra with different shapes and structures EUROPEAN PHYSICAL JOURNAL D 2013; 67 (11)
- Morphology-controllable synthesis of ZnO nano-/microstructures by a solvothermal process in ethanol solution CRYSTAL RESEARCH AND TECHNOLOGY 2013; 48 (11): 947-955
- Reducing Properties of Polymers in the Synthesis of Noble Metal Nanoparticles POLYMER REVIEWS 2013; 53 (2): 240-276
Large-scale synthesis and self-organization of silver nanoparticles with Tween 80 as a reductant and stabilizer
NANOSCALE RESEARCH LETTERS
2012; 7: 612
Tween 80 (polysorbate 80) has been used as a reducing agent and protecting agent to prepare stable water-soluble silver nanoparticles on a large scale through a one-pot process, which is simple and environmentally friendly. Silver ions can accelerate the oxidation of Tween 80 and then get reduced in the reaction process. The well-ordered arrays such as ribbon-like silver nanostructures could be obtained by adjusting the reaction conditions. High-resolution transmission electron microscopy confirms that ribbon-like silver nanostructures (approximately 50 nm in length and approximately 2 μm in width) are composed of a large number of silver nanocrystals with a size range of 2 to 3 nm. In addition, negative absorbance around 320 nm in the UV-visible spectra of silver nanoparticles has been observed, probably owing to the instability of nanosized silver colloids.
View details for DOI 10.1186/1556-276X-7-612
View details for Web of Science ID 000209057000001
View details for PubMedID 23127253
View details for PubMedCentralID PMC3503618