Alternative patterning solutions, such as spacer-based pitch splitting, have been a cornerstone of advanced technology nodes to enable device scaling. The greatest utility comes from the ability to self-align a pitch splitting process; however, traditional spacer-based patterning techniques require the deposition and etch of multiple materials, which reduce throughput and increase manufacturing costs. Anti-spacer technology, on the other hand, enables both self-aligned pitch splitting and high throughput via a single pass track-based process. We will describe the advancement of 193i anti-spacer technology to pattern trench dimensions beyond the critical dimension resolution of single-print extreme ultraviolet lithography and the utility of combining anti-spacer patterning with litho-freeze-litho-etch to enable the formation of sub-20-nm slot contact features for a minimum tip-to-tip (T2T) cut, with a roadmap to achieve sub-12 nm. A through process performance evaluation was conducted to further the understanding of fundamental process parameters and their associated effects on anti-spacer roughness and critical dimension uniformity. Such variables include photoresist, developer optimization, and overcoat dissolution. At pitches varying from 50 to 80 nm, we have demonstrated narrow trench widths down to 11.8 nm, which corresponds to the critical T2T dimension. Through hardmask etch transfer, we observe a 56% improvement in unbiased space width roughness and pitch-walking below 0.3 nm at 60-nm pitch.

Novel tetrafluoro-λ6-sulfanyl-containing oligomers prepared by visible light-promoted addition of 1,4-(bis-chlorotetrafluoro-λ6-sulfanyl) benzene or 1,3-(bis-chlorotetrafluoro-λ6-sulfanyl) benzene to either 1,4-diethynyl benzene or the 1,3-diethynyl isomers form hard, stress resistant thin films on spin casting. The isomeric oligomers were utilized to establish a structure-function relationship for the mechanical properties of films prepared from the oligomers. The Young’s moduli of 145-nm-thick cured films could reach 60 GPa. The measured hardnesses, between 1.57 and 2.77 GPa, were more than double those of polymethyl methacrylate (PMMA) films. Curing of the tetrafluoro-λ6-sulfanyl-containing polymer films by UV irradiation resulted in coatings that exhibited remarkable hardness and modulus with good surface adhesion to silicon.

An athletic man in his 40s was brought in to the emergency department by ambulance following a brief episode of central chest pain and dizziness five miles in to a ten mile stationary bike ride. Observations were normal at the scene and there were no ECG changes but he appeared unwell. Further assessment revealed no palpable right radial or brachial pulses and he complained of a severe right frontal headache. CT of the aorta showed an extensive type A dissection with a significantly dilated aortic root. Following emergency cardiothoracic surgery, he was found to have suffered cerebral hypoxia and died.

While injection molding is becoming the fabrication modality of choice for high-scale production of microfluidic devices, especially those used for in vitro diagnostics, its translation into the growing area of nanofluidics (structures with at least one dimension <100 nm) has not been well established. Another prevailing issue with injection molding is the high startup costs and the relatively long time between device iterations making it in many cases impractical for device prototyping. We report, for the first time, functional nanofluidic devices with dimensions of critical structures below 30 nm fabricated by injection molding for the manipulation, identification, and detection of single molecules. UV-resin molds replicated from Si masters served as mold inserts, negating the need for generating Ni-mold inserts via electroplating. Using assembled devices with a cover plate via hybrid thermal fusion bonding, we demonstrated two functional thermoplastic nanofluidic devices. The first device consisted of dual in-plane nanopores placed at either end of a nanochannel and was used to detect and identify single ribonucleotide monophosphate molecules via resistive pulse sensing and obtain the effective mobility of the molecule through nanoscale electrophoresis to allow its identification. The second device demonstrated selective binding of a single RNA molecule to a solid phase bioreactor decorated with a processive exoribonuclease, XRN1. Our results provide a simple path towards the use of injection molding for device prototyping in the development stage of any nanofluidic or even microfluidic application, through which rapid scale-up is made possible by transitioning from prototyping to high throughput production using conventional Ni mold inserts.

Over the last 30-years, microchip electrophoresis and its applications have expanded due to the benefits it offers. Nanochip electrophoresis, on the other hand, is viewed as an evolving area of electrophoresis be-cause it offers some unique advantages not associated with microchip electrophoresis. These advantages arise from unique phenomena that occur in the nanometer domain not readily apparent in the microscale domain due to scale-dependent effects. Scale-dependent effects associated with nanochip electrophore-sis includes high surface area-to-volume ratio, electrical double layer overlap generating parabolic flow even for electrokinetic pumping, concentration polarization, transverse electromigration, surface charge dominating flow, and surface roughness. Nanochip electrophoresis devices consist of channels with di-mensions ranging from 1 to 10 0 0 nm including classical (1-100 nm) and extended (100 nm - 10 0 0 nm) nanoscale devices. In this review, we highlight scale-dependent phenomena associated with nanochip electrophoresis and the utilization of those phenomena to provide unique biomolecular separations that are not possible with microchip electrophoresis. We will also review the range of materials used for nanoscale separations and the implication of material choice for the top-down fabrication and operation of these devices. We will also provide application examples of nanochip electrophoresis for biomolecule separations with an emphasis on nano-electrophoresis (nEP) and nano-electrochromatography (nEC).(c) 2022 Elsevier B.V. All rights reserved.

The presence of air bubbles boosts the shear resistance and causes pressure fluctuation within fluid-perfused microchannels, resulting in possible cell damage and even malfunction of microfluidic devices. Eliminating air bubbles is especially challenging in microscale where the adhesive surface tension force is often dominant over other forces. Here, we present an air bubble removal strategy from a novel surface engineering perspective. A microfluidic port-to-port interconnect was fabricated by modifying the peripheral of the microfluidic ports superhydrophobic, while maintaining the inner polymer microchannels hydrophilic. Such a sharp wettability contrast enabled a preferential fluidic entrance into the easy-wetting microchannels over the non-wetting boundaries of the microfluidic ports, while simultaneously filtering out any incoming air bubbles owing to the existence of port-to-port gaps. This bubble-eliminating capability was consistently demonstrated at varying flow rates and liquid analytes. Compared to equipment-intensive techniques and porous membrane-venting strategies, our wettability contrast-governed strategy provides a simple yet effective route for eliminating air bubbles and simultaneously sealing microfluidic interconnects.

An innovative method of thermal fusion bonding (TFB) using a pressure assisted boiling point (PABP) control system was characterized to determine the optimum parameters for bonding thermoplastic components containing microchannels and thin cover sheets. The PABP TFB system enables precise control of the temperature and the pressure boundary conditions by immersing a bag containing the components being bonded in boiling water and varying the vapor pressure. The original system used a human operator to manually adjust a pressure relief valve and maintain the system temperature, which introduces time delays. A closed loop control system was developed to automatically control the temperature in the pressure vessel. Test structure geometries containing microchannels of two depths, 5μm and 10μm, and four different aspect ratios were designed: 1:10, 1:50, 1:100, and 1:200. Microchannels were hot embossed in polymethyl methacrylate (PMMA) using micro-milled brass mold inserts. Results of bonding with the closed loop systems were evaluated. Mean rupture pressures decreased with increasing AR and were higher for shallower channels for the automated closed loop system. For a given aspect ratio, the rupture pressures ranged from 5%–19% higher for 5 mm channels and increased by 5%–10% in 10 mm channels with the automated closed loop system.

Liquid biopsies are becoming popular for managing a variety of diseases due to the minimally invasive nature of their acquisition, thus potentially providing better outcomes for patients. Circulating tumor cells (CTCs) are among the many different biomarkers secured from a liquid biopsy, and a number of efficient platforms for their isolation and enrichment from blood have been reported. However, many of these platforms require manual sample handling, which can generate difficulties when translating CTC assays into the clinic due to potential sample loss, contamination, and the need for highly specialized operators. We report a system modularity chip for the analysis of rare targets (SMART-Chip) composed of three task-specific modules that can fully automate processing of CTCs. The modules were used for affinity selection of the CTCs from peripheral blood with subsequent photorelease, simultaneous counting, and viability determinations of the CTCs and staining/imaging of the CTCs for immunophenotyping. The modules were interconnected to a fluidic motherboard populated with valves, interconnects, pneumatic control channels, and a fluidic network. The SMART-Chip components were made from thermoplastics via microreplication, which lowers the cost of production making it amenable to clinical implementation. The utility of the SMART-Chip was demonstrated by processing blood samples secured from colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) patients. We were able to affinity-select EpCAM expressing CTCs with high purity (0-3 white blood cells/mL of blood), enumerate the selected cells, determine their viability, and immunophenotype the cells. The assay could be completed in <4 h, while manual processing required >8 h.

We present a new class of EUV antimony carboxylate photoresists with enhanced reactivity and contrast, through the substitution of heteroatoms into the carboxylate. The lithographic performance of (C6H5)(3)Sb(O2CCH2X)(2) photoresists in which X = methoxy, bromine or iodine is presented. The addition of iodine to the photoresist greatly improves dissolution contrast. Utilizing in-situ mass spectrometry, we show how the identity and degree of volatile photoproducts created during EUV exposure change with the composition of the heteroatom.

Many antimony-carboxylate complexes containing polymerizable olefins are highly sensitive EUV photoresists. Herein we report two approaches by which we explored the reactivity of polymerizable olefin antimony carboxylate photoresists to improve lithographic performance. First, we explored the effect of replacing three phenyl groups with methyl groups in an effort to increase the relative concentration of olefins vs. size of the molecule. Second, we explored the effect of increasing the number of polymerizable olefins from two to five. This approach examines the use of tris(4-vinylphenyl)antimony-dicarboxylate complexes as photoresists and the developer chemistry capable of patterning highly crosslinked substrates.

One of the long-standing problems for the nanoparticle-based liquid-repellent coatings is their poor adhesion to substrates. For polymers of low glass transition temperature, it is highly desirable to have low temperature coating strategy to fabricate robust superhydrophobic films. Here, we report a facile method for fabricating robust, transparent, superhydrophobic films on polymer substrates. A mixture of silica particles and silica-based oligomers was spin coated on polymer substrates, followed by oxygen plasma treatment and vapor deposition of 1H,1H,2H,2H-Perfluorodecyltriethoxysilane (FDTS). The resulting superhydrophobic surface has a static contact angle at 160° and contact angle hysteresis lower than 5°. This study provides a practical solution to improve the adhesion of superhydrophobic films on polymer substrates in ambient conditions.

Hypothesis: The superhydrophobic lotus leaf has dual-scale surface structures, that is, nano-bumps on micro-mountains. Large hydrophilic particles, due to its high surface energy and weight, have high affility to substrates and tend to precipitate at the bottom of coating films. Small hydrophobic particles, due to its low surface energy and weight, tends to sit on the top of coating films and form porous structures. To mimic the lotus leaf surface, it may be possible to develop dual-sized particle films, in which small particles are decorated on large particles. Experiments: A one-step spin coating of a mixture of dual-sized silica particles (55/200 nm) was used. Epoxy resin was added to improve the adhesion of particle films. The single-sized and dual-sized particle films were compared. The mechanical robustness of particle films was tested by tape peeling and droplet impact. Findings: The novel combination of hydrophobic silica (55 nm) and hydrophilic silica (200 nm) is essential in creating the hierarchical structures. By combining the strong adhesion of hydrophilic silica (bottom of coating film) to polymer substrates and porous structures of hydrophobic silica (top of coating film), we first time report a one-step and versatile approach to create uniform, transparent, robust, and superhydrophobic surface. Crown Copyright (C) 2020 Published by Elsevier Inc. All rights reserved.

Antimony(V) carboxylate photoresists incorporating polymerizable olefins have demonstrated high photospeeds. The work of Passarelli et al. reported a sensitivity hypothesis, polymerizable olefin loading (POL), in which an increase in photospeed correlates to an increase in the number of olefins per molecular weight of resist.1 Utilizing this sensitivity trend, a photoresist of higher molecular weight, triphenylantimony(V) bis(4-vinylbenzoate) (JP-30), was developed exhibiting moderate photospeed at the cost of improved pattern fidelity. Herein we report three approaches for improving the lithographic performance of polymerizable olefin antimony carboxylate photoresists. Approach 1 increased the number of olefins per molecule through functionalization of the R-group. Tristyreneantimony(V) dicarboxylate photoresists were lithographically evaluated exhibiting high photospeeds and improved resolution capabilities (Figure 1). Approach 2 examined the benefits of blending two antimony carboxylate photoresists with high and low POL values and observing the changes in photospeed. Approach 3 increased the POL relative to JP-30 through reduction in molecular weight of the R-groups by the synthesis and lithographic evaluation of trimethylantimony(V) bis(4-vinylbenzoate).

An improved, laser-induced fluorescence-based micro-optical biosensor was designed and fabricated, with cyclic olefin copolymer (COC) optical waveguides, a poly(methyl methacrylate) (PMMA) fluidic substrate with an array of microlenses, and a COC coupling prism integrated with the waveguide substrate or cover plate. The double-sided hot embossed fluidic substrate had sampling zone microchannels on the bottom and microlenses on the top. Dissolved COC injected into polydimethylsiloxane (PDMS) lost molds embedded the waveguides in the PMMA cover plate and formed the integrated coupling prism. The embedded COC waveguide was flycut down to 50 μm. The cover plate and shallow, 1:20 aspect ratio, microchannels were thermal fusion bonded using a pressure-assisted boiling point control system, without sagging. The large COC prism coupled better to the waveguide. The highest intensity evanescent excitation of the waveguide was obtained near the critical angle. The maximum signal-to-noise ratio (SNR) was 119 and the lowest detection limit was 7.34 × 11 -20 mol at a SNR of 2 for a 100 μm wide by 50 μm deep waveguide. The microlenses highly focused the fluorescent radiation in the sampling zone.

Photochemical initiation of polymerization by visible or broadband ultraviolet irradiation of a mixture of 1,4-(bis-chlorotetrafluoro-lambda(6)-sulfanyl) benzene and 1,4-diethynyl benzene forms light responsive polymers. The novel polymers have a trans-tetrafluoro-lambda(6)-sulfanyl (tetrafluorosulfanyl, -SF4-) group backbone and are sensitive to electron beam (EB) and extreme ultraviolet (EUV) irradiation. Both EB lithography and EUV contrast experiments demonstrate the sensitivity of the polymer films to short wavelength irradiation.

Existing methods for sealing chip-to-chip (or module-to-motherboard) microfluidic interconnects commonly use additional interconnect components (O-rings, gaskets, and tubing), and manual handling expertise for assembly. Novel gasketless superhydrophobic fluidic interconnects (GSFIs) sealed by transparent superhydrophobic surfaces, forming liquid bridges between the fluidic ports for fluidic passages were demonstrated. Two test platforms were designed, fabricated, and evaluated, a multi-port chip system (ten interconnects) and a modules-on-a-motherboard system (four interconnects). System assembly in less than 3 sec was done by embedded magnets and pin-in-V-groove structures. Flow tests with deionized (DI) water, ethanol/water mixture, and plasma confirmed no leakage through the gasketless interconnects up to a maximum flow rate of $100~\mu \text{L}$ /min for the multi-port chip system. The modules-on-a-motherboard system showed no leakage of water at a flow rate of $20~\mu \text{L}$ /min and a pressure drop of 3.71 psi. Characterization of the leakage pressure as a function of the surface tension of the sample liquid in the multi-port chip system revealed that lower surface tension of the liquid led to lower static water contact angles on the superhydrophobic-coated substrate and lower leakage pressures. The high-density, rapidly assembled, gasketless interconnect technology will open up new avenues for chip-to-chip fluid transport in complex microfluidic modular systems. [2020-0168]

Currently there is no in vitro diagnostic test for acute ischemic stroke (AIS), yet rapid diagnosis is crucial for effective thrombolytic treatment. We previously demonstrated the utility of CD8(+) T-cells’ mRNA expression for AIS detection; however extracellular vesicles (EVs) were not evaluated as a source of mRNA for AIS testing. We now report a microfluidic device for the rapid and efficient affinity-enrichment of CD8(+) EVs and subsequent EV’s mRNA analysis using droplet digital PCR (ddPCR). The microfluidic device contains a dense array of micropillars modified with anti-CD8α monoclonal antibodies that enriched 158 ± 10 nm sized EVs at 4.3 ± 2.1 × 10 9 particles/100 µL of plasma. Analysis of mRNA from CD8(+) EVs and their parental T-cells revealed correlation in the expression for AIS-specific genes in both cell lines and healthy donors. In a blinded study, 80% test positivity for AIS patients and controls was revealed with a total analysis time of 3.7 h.

A multi-scale fluidic motherboard, which can be used in a universal molecular processing system (uMPS) integrated with task-specific processing modules, was designed and fabricated in thermoplastics. The motherboard consists of a coverplate and a substrate. The coverplate included fluidic interconnects and thermal grooves on the top side, and the corresponding interconnects on the bottom side. The substrate was comprised of cell lysis microchannels, micromixers, and flow-connecting microchannels on the top side, and reservoirs for sample inputs and waste output, thermal grooves, and valve seats for flow control on the bottom side. The coverplates and substrates were fabricated with double-sided hot embossing of polycarbonate (PC) using four micromilled brass molds, two for the coverplate and another two for the substrate. Evaluation of the relative front-to-backside alignment for the double-sided hot embossing yielded an accuracy of 25 μm ± 14 μm (average ± standard deviation) for the coverplates and 30 μm ± 20 μm for the substrates. Thermal fusion bonding (TFB) of the coverplate and substrate was done using a spring plunger bonding setup with a range of temperatures and pressures. The motherboard bonded at 154 °C and 12.0 psi for 2 hours in a convection oven produced complete bonding with a little deformation of the valve seats. The complete motherboard will be integrated with the task-specific processing modules in the uMPS for investigating circulating markers from whole blood for precision molecular diagnosis of disease at low cost and with high fidelity.

HYPOTHESIS:Compared to vertical micro-pillars, re-entrant micro-structures exhibited superior omniphobicity for suspending liquids to Cassie-Baxter state. However, the existing re-entrant structures rely on complex multi-step deposition and etching procedures. The conventional, rigid-templated imprinting would instead damage the re-entrant structures. This leads to the question: is it possible to preserve the re-entrant curvatures by a flexible-templated imprinting? EXPERIMENTS:We facilely imprinted the re-entrant structures on a plastic substrate using a flexible nylon-mesh template. The effect of imprinting time (15-35 min), temperature (110-120 °C) and pressure (15-50 Bar) was investigated. To further improve the liquid-repellency and abrasion resistance, the silica nanoparticles (30-650 nm) along with epoxy resin binder (10 mg/mL) were pre-coated. FINDINGS:A one-step imprinting is sufficient to fabricate the re-entrant structures by utilizing flexible nylon-mesh template, without damaging the imprinted structures after the demolding process. The pre-coated silica nanoparticles and epoxy resin (1) improved liquid repellency by introducing hierarchical surface structures (e.g. contact angle hysteresis of olive oil reduced > 10°), and (2) acted as a protective layer against mechanical abrasion (omniphobicity maintained after 25 cycles, ~1.6 kPa sand paper abrasion). Additionally, the fluorine-free post-treatment was sufficient for the omniphobicity on the obtained plastic structures.

Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) is used to evaluate the composition of nonvolatile photoproducts created by EUV photolysis of antimony carboxylate photoresists [R3Sb(O2CR′)2]. Dozens of potential photoproduct ions were identified using exact mass and 121Sb/123Sb isotopic ratios. Several oxygen-rich antimony ions were found to increase in abundance with exposure. Two methods were employed to identify photoproducts which create solubility contrast. First, samples were analyzed pre- and post-development to examine the effects of EUV exposure and developer solvent on secondary ion intensity. Secondly, changes in intensity of select ions were compared to dissolution contrast over a range of doses. Through these studies, ion intensities were found to correlate with dissolution contrast for several fragments, indicating their active role in creating negative-tone response.