Multi-project wafers for flexible thin-film electronics by independent foundries.

Flexible and large-area electronics rely on thin-film transistors (TFTs) to make displays1-3, large-area image sensors4-6, microprocessors7-11, wearable healthcare patches12-15, digital microfluidics16,17 and more. Although silicon-based complementary metal-oxide-semiconductor (CMOS) chips are manufactured using several dies on a single wafer and the multi-project wafer concept enables the aggregation of various CMOS chip designs within the same die, TFT fabrication is currently lacking a fully verified, universal design approach. This increases the cost and complexity of manufacturing TFT-based flexible electronics, slowing down their integration into more mature applications and limiting the design complexity achievable by foundries. Here we show a stable and high-yield TFT platform for the fabless manufacturing of two mainstream TFT technologies, wafer-based amorphous indium-gallium-zinc oxide and panel-based low-temperature polycrystalline silicon, two key TFT technologies applicable to flexible substrates. We have designed the iconic 6502 microprocessor in both technologies as a use case to demonstrate and expand the multi-project wafer approach. Enabling the foundry model for TFTs, as an analogy of silicon CMOS technologies, can accelerate the growth and development of applications and technologies based on these devices.

Combined Photothermal Therapy and Cancer Immunotherapy by Immunogenic Hollow Mesoporous Silicon-Shelled Gold Nanorods.

Hyperthermia can be integrated with tumor-killing chemotherapy, radiotherapy and immunotherapy to give rise to an anti-tumor response. To this end, a nano-delivery system is built, which can connect hyperthermia and immunotherapy. On this basis, the impact of such a combination on the immune function of dendritic cells (DCs) is explored. The core of this system is the photothermal material gold nanorod (GNR), and its surface is covered with a silica shell. Additionally, it also forms a hollow mesoporous structure using the thermal etching approach, followed by modification of targeted molecule folic acid (FA) on its surface, and eventually forms a hollow mesoporous silica gold nanorod (GNR@void@mSiO2) modified by FA. GNR@void@mSiO2-PEG-FA (GVS-FA) performs well in photothermal properties, drug carriage and release and tumor targeting performance. Furthermore, the thermotherapy of tumor cells through in vitro NIR irradiation can directly kill tumor cells by inhibiting proliferation and inducing apoptosis. GVS-FA loaded with imiquimod (R837) can be used as a adjuvant to enhance the immune function of DCs through hyperthermia.

Ultrasensitive 3D Stacked Silicon Nanosheet Field-Effect Transistor Biosensor with Overcoming Debye Shielding Effect for Detection of DNA.

Silicon nanowire field effect (SiNW-FET) biosensors have been successfully used in the detection of nucleic acids, proteins and other molecules owing to their advantages of ultra-high sensitivity, high specificity, and label-free and immediate response. However, the presence of the Debye shielding effect in semiconductor devices severely reduces their detection sensitivity. In this paper, a three-dimensional stacked silicon nanosheet FET (3D-SiNS-FET) biosensor was studied for the high-sensitivity detection of nucleic acids. Based on the mainstream Gate-All-Around (GAA) fenestration process, a three-dimensional stacked structure with an 8 nm cavity spacing was designed and prepared, allowing modification of probe molecules within the stacked cavities. Furthermore, the advantage of the three-dimensional space can realize the upper and lower complementary detection, which can overcome the Debye shielding effect and realize high-sensitivity Point of Care Testing (POCT) at high ionic strength. The experimental results show that the minimum detection limit for 12-base DNA (4 nM) at 1 × PBS is less than 10 zM, and at a high concentration of 1 µM DNA, the sensitivity of the 3D-SiNS-FET is approximately 10 times higher than that of the planar devices. This indicates that our device provides distinct advantages for detection, showing promise for future biosensor applications in clinical settings.

Molecular Dynamics Modeling of Pulsed Laser Fragmentation of Solid and Porous Si Nanoparticles in Liquid Media.

The production of non-toxic and homogeneous colloidal solutions of nanoparticles (NPs) for biomedical applications is of extreme importance nowadays. Among the various methods for generation of NPs, pulsed laser ablation in liquids (PLAL) has proven itself as a powerful and efficient tool in biomedical fields, allowing chemically pure silicon nanoparticles to be obtained. For example, laser-synthesized silicon nanoparticles (Si NPs) are widely used as contrast agents for bio visualization, as effective sensitizers of radiofrequency hyperthermia for cancer theranostics, in photodynamic therapy, as carriers of therapeutic radionuclides in nuclear nanomedicine, etc. Due to a number of complex and interrelated processes involved in the laser ablation phenomenon, however, the final characteristics of the resulting particles are difficult to control, and the obtained colloidal solutions frequently have broad and multimodal size distribution. Therefore, the subsequent fragmentation of the obtained NPs in the colloidal solutions due to pulsed laser irradiation can be utilized. The resulting NPs' characteristics, however, depend on the parameters of laser irradiation as well as on the irradiated material and surrounding media properties. Thus, reliable knowledge of the mechanism of NP fragmentation is necessary for generation of a colloidal solution with NPs of predesigned properties. To investigate the mechanism of a laser-assisted NP fragmentation process, in this work, we perform a large-scale molecular dynamics (MD) modeling of FS laser interaction with colloidal solution of Si NPs. The obtained NPs are then characterized by their shape and morphological properties. The corresponding conclusion about the relative input of the properties of different laser-induced processes and materials to the mechanism of NP generation is drawn.

From Self-Assembly of Colloidal Crystals toward Ordered Porous Layer Interferometry.

Interferometry-based, reflectometric, label-free biosensors have made significant progress in the analysis of molecular interactions after years of development. The design of interference substrates is a key research topic for these biosensors, and many studies have focused on porous films prepared by top-down methods such as porous silicon and anodic aluminum oxide. Lately, more research has been conducted on ordered porous layer interferometry (OPLI), which uses ordered porous colloidal crystal films as interference substrates. These films are made using self-assembly techniques, which is the bottom-up approach. They also offer several advantages for biosensing applications, such as budget cost, adjustable porosity, and high structural consistency. This review will briefly explain the fundamental components of self-assembled materials and thoroughly discuss various self-assembly techniques in depth. We will also summarize the latest studies that used the OPLI technique for label-free biosensing applications and divide them into several aspects for further discussion. Then, we will comprehensively evaluate the strengths and weaknesses of self-assembly techniques and discuss possible future research directions. Finally, we will outlook the upcoming challenges and opportunities for label-free biosensing using the OPLI technique.

Manufacture of Mesoporous Silicon Microparticles (MSMPs) as Adjuvants for Vaccine Delivery.

The advent of computational approaches has accelerated the identification of vaccine candidates like epitope peptides. However, epitope peptides are usually very poorly immunogenic and adequate platforms are required with adjuvant capacity to verity immunogenicity and antigenicity of vaccine subunits in vivo. Silicon microparticles are being developed as potential new adjuvants for vaccine delivery due to their physicochemical properties. This chapter explains the methodology to fabricate and functionalize mesoporous silicon microparticles (MSMPs) which can be loaded with antigens of different nature, such as viral peptides, proteins, or carbohydrates, and this strategy is particularly suitable for delivery of epitopes identified by computer.

Luminescent quantum dots: Synthesis, optical properties, bioimaging and toxicity.

Luminescent nanomaterials such as semiconductor nanocrystals (NCs) and quantum dots (QDs) attract much attention to optical detectors, LEDs, photovoltaics, displays, biosensing, and bioimaging. These materials include metal chalcogenide QDs and metal halide perovskite NCs. Since the introduction of cadmium chalcogenide QDs to biolabeling and bioimaging, various metal nanoparticles (NPs), atomically precise metal nanoclusters, carbon QDs, graphene QDs, silicon QDs, and other chalcogenide QDs have been infiltrating the nano-bio interface as imaging and therapeutic agents. Nanobioconjugates prepared from luminescent QDs form a new class of imaging probes for cellular and in vivo imaging with single-molecule, super-resolution, and 3D resolutions. Surface modified and bioconjugated core-only and core-shell QDs of metal chalcogenides (MX; M = Cd/Pb/Hg/Ag, and X = S/Se/Te,), binary metal chalcogenides (MInX2; M = Cu/Ag, and X = S/Se/Te), indium compounds (InAs and InP), metal NPs (Ag, Au, and Pt), pure or mixed precision nanoclusters (Ag, Au, Pt), carbon nanomaterials (graphene QDs, graphene nanosheets, carbon NPs, and nanodiamond), silica NPs, silicon QDs, etc. have become prevalent in biosensing, bioimaging, and phototherapy. While heavy metal-based QDs are limited to in vitro bioanalysis or clinical testing due to their potential metal ion-induced toxicity, carbon (nanodiamond and graphene) and silicon QDs, gold and silica nanoparticles, and metal nanoclusters continue their in vivo voyage towards clinical imaging and therapeutic applications. This review summarizes the synthesis, chemical modifications, optical properties, and bioimaging applications of semiconductor QDs with particular references to metal chalcogenide QDs and bimetallic chalcogenide QDs. Also, this review highlights the toxicity and pharmacokinetics of QD bioconjugates.

Foliar application of silicon, selenium, and zinc nanoparticles can modulate lead and cadmium toxicity in sage (Salvia officinalis L.) plants by optimizing growth and biochemical status.

Different techniques have been used to alleviate metal toxicity in medicinal plants; accordingly, nanoparticles (NPs) have a noticeable interest in modulating oxidative stresses. Therefore, this work aimed to compare the impacts of silicon (Si), selenium (Se), and zinc (Zn) NPs on the growth, physiological status, and essential oil (EO) of sage (Salvia officinalis  L.) treated with foliar application of Si, Se, and Zn NPs upon lead (Pb) and cadmium (Cd) stresses. The results showed that Se, Si, and Zn NPs decreased Pb accumulation by 35, 43, and 40%, and Cd concentration by 29, 39, and 36% in sage leaves. Shoot plant weight showed a noticeable reduction upon Cd (41%) and Pb (35%) stress; however, NPs, particularly Si and Zn improved plant weight under metal toxicity. Metal toxicity diminished relative water content (RWC) and chlorophyll, whereas NPs significantly enhanced these variables. The noticeable raises in malondialdehyde (MDA) and electrolyte leakage (EL) were observed in plants exposed to metal toxicity; however, they were alleviated with foliar application of NPs. The EO content and EO yield of sage plants decreased by the heavy metals but increased by the NPs. Accordingly, Se, Si, and Zn NPS elevated EO yield by 36, 37, and 43%, respectively, compared with non-NPs. The primary EO constituents were 1,8-cineole (9.42-13.41%), α-thujone (27.40-38.73%), ß-thujone (10.11-12.94%), and camphor (11.31-16.45%). This study suggests that NPs, particularly Si and Zn, boosted plant growth by modulating Pb and Cd toxicity, which could be advantageous for cultivating this plant in areas with heavy metal-polluted soils.

Functionalization of a Fully Integrated Electrophotonic Silicon Circuit for Biotin Sensing.

Electrophotonic (EPh) circuits are novel systems where photons and electrons can be controlled simultaneously in the same integrated circuit, attaining the development of innovative sensors for different applications. In this work, we present a complementary metal-oxide-semiconductor (CMOS)-compatible EPh circuit for biotin sensing, in which a silicon-based light source is monolithically integrated. The device is composed of an integrated light source, a waveguide, and a p-n photodiode, which are all fabricated in the same chip. The functionalization of the waveguide's surface was investigated to biotinylate the EPh system for potential biosensing applications. The modified surfaces were characterized by AFM, optical microscopy, and Raman spectroscopy, as well as by photoluminescence measurements. The changes on the waveguide's surface due to functionalization and biotinylation translated into different photocurrent intensities detected in the photodiode, demonstrating the potential uses of the EPh circuit as a biosensor.

Refractive Index Measurement Using SOI Photodiode with SP Antenna toward SOI CMOS-Compatible Integrated Optical Biosensor.

This paper proposes a new optical biosensor composed of a silicon-on-insulator (SOI) p-n junction photodiode (PD) with a surface plasmon (SP) antenna. When the phase-matching condition between two lateral wavelengths of the diffracted light from the SP antenna and the waveguiding mode in the SOI PD is satisfied, we observe sharp peaks in the spectroscopic light sensitivity. Since the peak wavelength depends on the RI change around the SP antenna corresponding to the phase-matching condition, the SOI PDs with an SP antenna can be applied to the optical biosensor. The RI detection limit is evaluated in the measurements with bulk solutions, and 1.11 × 10-5 RIU (refractive index unit) can be obtained, which is comparable to that of a surface plasmon resonance (SPR) sensor, which is well known as a representative optical biosensor. In addition, the response for intermolecular bonds is estimated by the electromagnetic simulations using the finite-difference time-domain (FDTD) method to clarify its ability to detect biomolecular interactions. The results of this paper will provide new ground for high-throughput label-free biosensing, since a large number of SOI PDs with an SP antenna can be easily integrated on a single chip via an SOI complementary metal-oxide-semiconductor (CMOS) fabrication process.

CRISPR Cas12a-Powered Silicon Surface-Enhanced Raman Spectroscopy Ratiometric Chip for Sensitive and Reliable Quantification.

Sensitive and reliable clustered regularly interspaced short palindromic repeats (CRISPR) quantification without preamplification of the sample remains a challenge. Herein, we report a CRISPR Cas12a-powered silicon surface-enhanced Raman spectroscopy (SERS) ratiometric chip for sensitive and reliable quantification. As a proof-of-concept application, we select the platelet-derived growth factor-BB (PDGF-BB) as the target. We first develop a microfluidic synthetic strategy to prepare homogeneous silicon SERS substrates, in which uniform silver nanoparticles (AgNPs) are in situ grown on a silicon wafer (AgNPs@Si) by microfluidic galvanic deposition reactions. Next, one 5'-SH-3'-ROX-labeled single-stranded DNA (ssDNA) is modified on AgNPs via Ag-S bonds. In our design, such ssDNA has two fragments: one fragment hybridizes to its complementary DNA (5'-Cy3-labeled ssDNA) to form double-stranded DNA (dsDNA) and the other fragment labeled with 6'-carboxy-X-rhodmine (ROX) extends out as a substrate for Cas12a. The cleavage of the ROX-tagged fragment by Cas12a is controlled by the presence or not of PDGF-BB. Meanwhile, Cy3 molecules serving as internal standard molecules still stay at the end of the rigid dsDNA, and their signals remain constant. Thereby, the ratio of ROX signal intensity to Cy3 intensity can be employed for the reliable quantification of PDGF-BB concentration. The developed chip features an ultrahigh sensitivity (e.g., the limit of detection is as low as 3.2 pM, approximately 50 times more sensitive than the fluorescence counterpart) and good reproducibility (e.g., the relative standard deviation is less than 5%) in the detection of PDGF-BB.

Two-dimensional devices and integration towards the silicon lines.

Despite technical efforts and upgrades, advances in complementary metal-oxide-semiconductor circuits have become unsustainable in the face of inherent silicon limits. New materials are being sought to compensate for silicon deficiencies, and two-dimensional materials are considered promising candidates due to their atomically thin structures and exotic physical properties. However, a potentially applicable method for incorporating two-dimensional materials into silicon platforms remains to be illustrated. Here we try to bridge two-dimensional materials and silicon technology, from integrated devices to monolithic 'on-silicon' (silicon as the substrate) and 'with-silicon' (silicon as a functional component) circuits, and discuss the corresponding requirements for material synthesis, device design and circuitry integration. Finally, we summarize the role played by two-dimensional materials in the silicon-dominated semiconductor industry and suggest the way forward, as well as the technologies that are expected to become mainstream in the near future.

Probing the Optical Response and Local Dielectric Function of an Unconventional Si@MoS2 Core-Shell Architecture.

Heterostructures of optical cavities and quantum emitters have been highlighted for enhanced light-matter interactions. A silicon nanosphere, core, and MoS2, shell, structure is one such heterostructure referred to as the core@shell architecture. However, the complexity of the synthesis and inherent difficulties to locally probe this architecture have resulted in a lack of information about its localized features limiting its advances. Here, we utilize valence electron energy loss spectroscopy (VEELS) to extract spatially resolved dielectric functions of Si@MoS2 with nanoscale spatial resolution corroborated with simulations. A hybrid electronic critical point is identified ∼3.8 eV for Si@MoS2. The dielectric functions at the Si/MoS2 interface is further probed with a cross-sectioned core-shell to assess the contribution of each component. Various optical parameters can be defined via the dielectric function. Hence, the methodology and evolution of the dielectric function herein reported provide a platform for exploring other complex photonic nanostructures.

"Silicon-On-Insulator"-Based Nanosensor for the Revelation of MicroRNA Markers of Autism.

MicroRNAs (miRNAs), which represent short (20 to 22 nt) non-coding RNAs, were found to play a direct role in the development of autism in children. Herein, a highly sensitive "silicon-on-insulator"-based nanosensor (SOI-NS) has been developed for the revelation of autism-associated miRNAs. This SOI-NS comprises an array of nanowire sensor structures fabricated by complementary metal-oxide-semiconductor (CMOS)-compatible technology, gas-phase etching, and nanolithography. In our experiments described herein, we demonstrate the revelation of ASD-associated miRNAs in human plasma with the SOI-NS, whose sensor elements were sensitized with oligonucleotide probes. In order to determine the concentration sensitivity of the SOI-NS, experiments on the detection of synthetic DNA analogues of autism-associated miRNAs in purified buffer were performed. The lower limit of miRNA detection attained in our experiments amounted to 10-17 M.

[Design Strategy of Biologically Active Compounds Using Various Elements].

Almost all conventional drug discovery research has been based on hydrocarbon-based frameworks and common chemical elements such as nitrogen, oxygen, sulfur, and the halogens. However, triggered by the approval of bortezomib, a boronic acid-containing pharmaceutical agent, the incorporation of functionalities that are not native in biological systems has been intensively investigated. Several other boron-containing pharmaceuticals have also been marketed. Therefore, the inclusion of various elements is one of the most promising strategies for the development of novel and distinctive drug candidates. In this symposium review, the author focused on the 'elements chemistry' approaches for the structural development of biologically active compounds, particularly those involving silicon and phosphorus. The isosteric exchange of Si and C (Si/C-exchange) is one of the most-investigated forms of substituting elements. We revealed the detailed physicochemical impact of Si/C-exchange, and we proposed several applications of silyl functionalities other than the simple Si/C-exchange. Regarding phosphorus, we recently revealed that the P-B substructure can function as the isostere of C-C or Si-C substructures. In addition to these isosteric exchanges, the development of biologically active compounds bearing unique substructures such as carboranes, hydrophobic boron clusters, and ferrocene is introduced. These novel strategies provide several options for structural development, offering great potential for expanding the chemical space of medicinal chemistry.

Protocol for growing silica nanowires on various substrates to enhance superwetting and self-jumping properties.

The protocol outlines the steps for growing silica nanowires on various substrates such as glass and stainless-steel foil. Silica nanowires are grown by thermal chemical vapor deposition via a vapor-liquid-solid mechanism, in which silicon wafers are used as silicon sources and platinum films as catalysts. This protocol can be used to grow silica nanowires on other substrates such as quartz filter, quartz sphere, alumina plate, and silicon wafer, provided the substrate materials can tolerate the temperature during process heating. For complete details on the use and execution of this profile, please refer to Lee et al. (2019), Tsai and Shieh (2019), and Tsai et al. (2021).

Hairpin oligosensor using SiQDs: Förster resonance energy transfer study and application for miRNA-21 detection.

MicroRNAs are known to be tumor suppressors and promoters and can be used as cancer markers. In this work, a novel oligosensor was designed using Si quantum dots (SiQDs) for the detection of miRNAs. Five-nanometer SiQDs were synthesized, with a band gap of 2.8 eV, fluorescence lifetime of 4.56 µs (τ1/2 = 3.26 µs), quantum yield of 25%, fluorescence rate constant of 6.25 × 104, and non-radiative rate constant of 1.60 × 105 s-1. They showed excellent water dispersibility, good stability (with 95% confidence for 6-month storage) without photobleaching, and high biocompatibility, with an IC50 value of 292.2 µg/L. The SiQDs and Black Hole Quencher-1 (BHQ1) were conjugated to the 5' and 3' terminals of an oligomer, respectively. The resulting hairpin molecular beacon showed resonance energy transfer efficiency of 63%. A distance of 0.91 R (Förster distance) between SiQD and BHQ1 was obtained. In the presence of a stoichiometric amount of the complementary oligonucleotide (ΔGhybridization = -35.09 kcal mol-1), 98% of the fluorescence was recovered due to loop opening of the hairpin structure. The probe showed good selectivity toward miRNA-21, with a limit of detection of 14.9 fM. The oligosensor recoveries of miRNA-21 spiked in human serum and urine were 94-98% and 93-108%, respectively.

Nanoplatform to Investigate Tumor-Initiating Cancer Stem Cells: Breaking the Diagnostic Barrier.

Drug-resistant capacity in a small population of tumor-initiating cancer stem cells (tiCSCs) can be due to aberrant epigenetic changes. However, currently available conventional detection methods are inappropriate and cannot be applied to investigate the scarce population (tiCSCs). In addition, selective inhibitor drugs are shown to reverse epigenetic changes; however, each cancer type is discrete. Hence, it is essential to probe the resultant changes in tiCSCs even after therapy. Therefore, we have developed a multimode nanoplatform to investigate tiCSCs, detect epigenetic changes, and subsequently explore their transformation signals following drug therapy. We performed this by developing a surface-enhanced Raman scattering (SERS)-active nanoplatform integrated with n-dopant using an ultrafast laser ionization technique. The dopant functionalization enhances Raman scattering ability and permits label-free analysis of biomarkers in tiCSCs with the resolution down to the cellular level. Here, we investigated epigenetic biomarkers of tiCSCs in pancreatic and lung cancers. An extended study using inhibitor drugs demonstrates an unexpected increase of tiCSCs from lung cancer; this difference can be attributed to transformation changes in lung tiCSC. Thus, our work brings new insight into the differentiation abilities of CSCs upon epigenetic reversal, emphasizing unique perceptions in cancer treatment.

Silicon nanowires decorated with platinum nanoparticles were applied for photothermal-enhanced sonodynamic therapy.

Sonodynamic therapy (SDT) triggered by ultrasound (US) can overcome pivotal limitations of photo-therapy owing to its high depth-penetration and low phototoxicity. However, there is still a need to develop more efficient sonosensitizes to enhance the therapy efficiency. Methods: In this study, Pt nanoparticles (Pt NPs) are reduced on silicon nanowires (SiNWs) by in situ reduction to prepare Si-Pt nanocomposites (Si-Pt NCs). Results: Si-Pt NCs can produce reactive oxygen radicals (ROS) under ultrasound (US) irradiation, which have sonodynamic therapy (SDT) effect. Meanwhile, Si-Pt NCs can convert excess hydrogen peroxide (H2O2) into ROS in the tumor microenvironment, which endow strong chemodynamic therapy (CDT) effect. Taking the advantages of the mesoporous structure of SiNWs, the SDT and CDT effects of Si-Pt NCs are stronger than those of the pure Pt NPs and SiNWs. Besides, the mild photothermal effect of Si-Pt NCs further improves the SDT&CDT activity and realizes the combined cancer therapy. Conclusion: The developed Si-Pt NCs with the ability of photothermal enhanced SDT/CDT combined therapy play a momentous role in the novel cancer treatment.

Nanoarchitectonics: Complexes and Conjugates of Platinum Drugs with Silicon Containing Nanocarriers. An Overview.

The development in the area of novel anticancer prodrugs (conjugates and complexes) has attracted growing attention from many research groups. The dangerous side effects of currently used anticancer drugs, including cisplatin and other platinum based drugs, as well their systemic toxicity is a driving force for intensive search and presents a safer way in delivery platform of active molecules. Silicon based nanocarriers play an important role in achieving the goal of synthesis of the more effective prodrugs. It is worth to underline that silicon based platform including silica and silsesquioxane nanocarriers offers higher stability, biocompatibility of such the materials and pro-longed release of active platinum drugs. Silicon nanomaterials themselves are well-known for improving drug delivery, being themselves non-toxic, and versatile, and tailored surface chemistry. This review summarizes the current state-of-the-art within constructs of silicon-containing nano-carriers conjugated and complexed with platinum based drugs. Contrary to a number of other reviews, it stresses the role of nano-chemistry as a primary tool in the development of novel prodrugs.