The prevalence of breast cancer in women underscores the urgent need for innovative and efficient detection methods. This study addresses this imperative by harnessing salivary biomarkers, offering a noninvasive and accessible means of identifying breast cancer. In this study, commercially available disposable based strips similar to the commonly used glucose detection strips were utilized and functionalized to detect breast cancer with biomarkers of HER2 and CA15-3. The results demonstrated limits of detection for these two biomarkers reached as low as 1 fg/ml much lower than those of conventional enzyme-linked immunosorbent assay in the range of 1∼4 ng/ml. By employing a synchronized double-pulse method to apply 10 of 1.2 ms voltage pulses to the electrode of sensing strip and drain electrode of the transistor for amplifying the detected signal, and the detected signal was the average of 10 digital output readings corresponding to those 10 voltage pulses. The sensor sensitivities were achieved approximately 70/dec and 30/dec for HER2 and CA15-3, respectively. Moreover, the efficiency of this novel technique is underscored by its swift testing time of less than 15 ms and its minimal sample requirement of only 3 l of saliva. The simplicity of operation and the potential for widespread public use in the future position this approach as a transformative tool in the early detection of breast cancer. This research not only provides a crucial advancement in diagnostic methodologies but also holds the promise of revolutionizing public health practices.

High-temperature annealing is a promising but still mainly unexplored method for enhancing spin properties of negatively charged nitrogen-vacancy (NV) centers in diamond particles. After high-energy irradiation, the formation of NV centers in diamond particles is typically accomplished via annealing at temperatures in the range of 800-900 °C for 1-2 h to promote vacancy diffusion. Here, we investigate the effects of conventional annealing (900 °C for 2 h) against annealing at a much higher temperature of 1600 °C for the same annealing duration for particles ranging in size from 100 nm to 15 m using electron paramagnetic resonance and optical characterization. At this high temperature, the vacancy-assisted diffusion of nitrogen can occur. Previously, the annealing of diamond particles at this temperature was performed over short time scales because of concerns of particle graphitization. Our results demonstrate that particles that survive this prolonged 1600 °C annealing show increased NV and electron spin relaxation times in 1 and 15 m particles, due to the removal of fast relaxing spins. Additionally, this high-temperature annealing also boosts magnetically induced fluorescence contrast of NV centers for particle sizes ranging from 100 nm to 15 m. At the same time, the content of NV centers is decreased fewfold and reaches a level of <0.5 ppm. The results provide guidance for future studies and the optimization of high-temperature annealing of fluorescent diamond particles for applications relying on the spin properties of NV centers in the host crystals.

Oral squamous cell carcinoma (OSCC) is one of the most common lip and oral cavity cancer types. It requires early detection via various medical technologies to improve the survival rate. While most detection techniques for OSCC require testing in a centralized lab to confirm cancer type, a point of care detection technique is preferred for on-site use and quick result readout. The modular biological sensor utilizing transistor-based technology has been leveraged for testing CIP2A, and optimal transistor gate voltage and load resistance for sensing setup was investigated. Sensitivities of 1 × 10 g/ml have been obtained for both detections of pure CIP2A protein and HeLa cell lysate using identical test conditions via serial dilution. The superior time-saving and high accuracy testing provides opportunities for rapid clinical diagnosis in the medical space.

Leakage of human cerebrospinal fluid (CSF) caused by trauma or other reasons presents exceptional challenges in clinical analysis and can have severe medical repercussions. Conventional test methods, including enzyme-linked immunosorbent assay and immunofixation electrophoresis testing, typically are performed at a few clinical reference laboratories, which may potentially delay proper diagnosis and treatment. At the same time, medical imaging can serve as a secondary diagnosis tool. This work presented here reports the use of a point-of-care electrochemical sensor for detection of beta-2-transferrin (B2T), a unique isomer of transferrin that is present exclusively in human CSF but is absent in other bodily fluids. Limits of detection were examined via serial dilution of human samples with known B2T concentrations down to 7 × 10 g B2T/ml while maintaining excellent sensitivity. Nine human samples with varying levels of B2T were compared using up to 100 times dilution to confirm the validity of sensor output across different patient samples.

The SARS-CoV-2 pandemic has had a significant impact worldwide. Currently, the most common detection methods for the virus are polymerase chain reaction (PCR) and lateral flow tests. PCR takes more than an hour to obtain the results and lateral flow tests have difficulty with detecting the virus at low concentrations. In this study, 60 clinical human saliva samples, which included 30 positive and 30 negative samples confirmed with RT-PCR, were screened for COVID-19 using disposable glucose biosensor strips and a reusable printed circuit board. The disposable strips were gold plated and functionalized to immobilize antibodies on the gold film. After functionalization, the strips were connected to the gate electrode of a metal-oxide-semiconductor field-effect transistor on the printed circuit board to amplify the test signals. A synchronous double-pulsed bias voltage was applied to the drain of the transistor and strips. The resulting change in drain waveforms was converted to digital readings. The RT-PCR-confirmed saliva samples were tested again using quantitative PCR (RT-qPCR) to determine cycling threshold (Ct) values. Ct values up to 45 refer to the number of amplification cycles needed to detect the presence of the virus. These PCR results were compared with digital readings from the sensor to better evaluate the sensor technology. The results indicate that the samples with a range of Ct values from 17.8 to 35 can be differentiated, which highlights the increased sensitivity of this sensor technology. This research exhibits the potential of this biosensor technology to be further developed into a cost-effective, point-of-care, and portable rapid detection method for SARS-CoV-2.

Recently, white-matter fiber tract pathways carrying neural signals through the brain were shown to follow curved, orthogonal grids. This study focuses on how these white-matter fibers may be selectively excited using micromagnetic stimulation (MS), a new type of neuronal stimulation, which generates microscopic eddy currents capable of directionally activating neurons. One of the most remarkable properties of this novel type of stimulation is that the MS fields provide unique directional activation of neuronal elements not seen with traditional electrical stimulation. An initial prototype built with SU-8 based photolithography technology shows that the structure can be fabricated. The coil design was optimized through electrical resistance calculations and electric field simulations to elicit the brain's maximal focal and directional neural responses.

Detection of the SARS-CoV-2 spike protein and inactivated virus was achieved using disposable and biofunctionalized functional strips, which can be connected externally to a reusable printed circuit board for signal amplification with an embedded metal-oxide-semiconductor field-effect transistor (MOSFET). A series of chemical reactions was performed to immobilize both a monoclonal antibody and a polyclonal antibody onto the Au-plated electrode used as the sensing surface. An important step in the biofunctionalization, namely, the formation of Au-plated clusters on the sensor strips, was verified by scanning electron microscopy, as well as electrical measurements, to confirm successful binding of thiol groups on this Au surface. The functionalized sensor was externally connected to the gate electrode of the MOSFET, and synchronous pulses were applied to both the sensing strip and the drain contact of the MOSFET. The resulting changes in the dynamics of drain waveforms were converted into analog voltages and digital readouts, which correlate with the concentration of proteins and virus present in the tested solution. A broad range of protein concentrations from 1 fg/ml to 10 g/ml and virus concentrations from 100 to 2500 PFU/ml were detectable for the sensor functionalized with both antibodies. The results show the potential of this approach for the development of a portable, low-cost, and disposable cartridge sensor system for point-of-care detection of viral diseases.

The demand for new biomaterials in several biomedical applications, such as regenerative engineering and drug delivery, has increased over the past two decades due to emerging technological advances in biomedicine. Degradable polymeric biomaterials continue to play a significant role as scaffolding materials and drug devices. Polyphosphazene platform is a subject of broad interest, as it presents an avenue for attaining versatile polymeric materials with excellent structure and property tunability, and high functional diversity. Macromolecular substitution enables the facile attachment of different organic groups and drug molecules to the polyphosphazene backbone for the development of a broad class of materials. These materials are more biocompatible than traditional biomaterials, mixable with other clinically relevant polymers to obtain new materials and exhibit unique erosion with near-neutral degradation products. Hence, polyphosphazene represents the next generation of biomaterials. In this review, the authors systematically discuss the synthetic design, structure-property relationships, and the promising potentials of polyphosphazenes in regenerative engineering and drug delivery.

Diamond particles containing color centers-fluorescent crystallographic defects embedded within the diamond lattice-outperform other classes of fluorophores by providing a combination of unmatched photostability, intriguing coupled magneto-optical properties, intrinsic biocompatibility, and outstanding mechanical and chemical robustness. This exceptional combination of properties positions fluorescent diamond particles as unique fluorophores with emerging applications in a variety of fields, including bioimaging, ultrasensitive metrology at the nanoscale, fluorescent tags in industrial applications, and even potentially as magnetic resonance imaging contrast agents. However, production of fluorescent nanodiamond (FND) is nontrivial, since it requires irradiation with high-energy particles to displace carbon atoms and create vacancies-a primary constituent in the majority color centers. In this review, centrally focused on material developments, major steps of FND production are discussed with emphasis on current challenges in the field and possible solutions. The authors demonstrate how the combination of fluorescent spectroscopy and electron paramagnetic resonance provides valuable insight into the types of radiation-induced defects formed and their evolution upon thermal annealing, thereby guiding FND performance optimization. A recent breakthrough process allowing for production of fluorescent diamond particles with vibrant blue, green, and red fluorescence is also discussed. Finally, the authors conclude with demonstrations of a few FND applications in the life science arena and in industry.

Although the mechanisms of deep reactive ion etching (DRIE) of silicon have been reported extensively, very little by comparison has been discussed concerning DRIE of germanium. By directly comparing silicon and germanium etching in a time multiplexed DRIE process, the authors extract significant differences in etch mechanisms from a design of experiment and discuss how these differences are relevant to the design and fabrication of silicon and germanium collimating channel array x-ray optics. The differences are illuminated by characteristics such as reactive ion etching (RIE)-lag, aspect ratio dependent etching, and sidewall passivation. Specifically, the authors demonstrate the more severe nature of RIE-lag in germanium, especially at aspect ratios exceeding 13:1. In addition, the differences in the profile evolution between silicon and germanium are shown to be a result of differences in sidewall passivation. There is also a correlation between the different sidewall passivation and the inherent lack of scalloping in the case of germanium DRIE.

Atomic force microscopes (AFMs) are widely used to study molecular interactions with piconewton force sensitivity. In an AFM, interaction forces are measured by reflecting a laser beam off a cantilever onto a position sensitive detector and monitoring cantilever deflection. Precise measurements of interaction forces rely on accurately determining the optical lever sensitivity, i.e., the relationship between cantilever deflection and changes in detector voltage. The optical lever sensitivity is measured by pressing the cantilever against a hard substrate using a piezoactuator and recording the resulting change in detector voltage. However, nonlinearities in the motion of commonly used open-loop piezo actuators introduce significant errors in measured optical lever sensitivities. Here, the authors systematically characterize the effect of piezo actuator hysteresis and creep on errors in optical lever sensitivity and identify measurement conditions that minimize these errors.

The authors study the composition and abruptness of the interfacial layers that form during deposition and patterning of a ferromagnet, Fe on a topological insulator (TI), BiSe, BiTe, and SiO/BiTe. Such structures are potentially useful for spintronics. Cross-sectional transmission electron microscopy, including interfacial elemental mapping, confirms that Fe reacts with BiSe near room temperature, forming an abrupt 5 nm thick FeSe single crystalline binary phase, predominantly (001) oriented, with lattice fringe spacing of 0.55 nm. In contrast, Fe/BiTe forms a polycrystalline Fe/TI interfacial alloy that can be prevented by the addition of an evaporated SiO separating Fe from the TI.

A detailed procedure is presented for fabrication of free-standing silicon photonic devices that accurately reproduces design dimensions while minimizing surface roughness. By reducing charging effects during inductively coupled-plasma reactive ion etching, undercutting in small, high-aspect ratio openings is reduced. Slot structures with a width as small as 40 nm and an aspect ratio of 5.5:1 can be produced with a nearly straight, vertical sidewall profile. Subsequent removal of an underlying sacrificial silicon dioxide layer by wet-etching to create free-standing devices is performed under conditions which suppress attack of the silicon. Slotted one-dimensional photonic crystal cavities are used as sensitive test structures to demonstrate that performance specifications can be reached without iteratively adapting design dimensions; optical resonance frequencies are within 1% of the simulated values and quality factors on the order of 10 are routinely attained.

Transition metal dichalcogenide (TMDC) semiconductors have attracted significant attention because of their rich electronic/photonic properties and importance for fundamental research and novel device applications. These materials provide a unique opportunity to build up high quality and atomically sharp heterostructures because of the nature of weak van der Waals interlayer interactions. The variable electronic properties of TMDCs (e.g., band gap and their alignment) provide a platform for the design of novel electronic and optoelectronic devices. The integration of TMDC heterostructures into the semiconductor industry is presently hindered by limited options in reliable production methods. Many exciting properties and device architectures which have been studied to date are, in large, based on the exfoliation methods of bulk TMDC crystals. These methods are generally more difficult to consider for large scale integration processes, and hence, continued developments of different fabrication strategies are essential for further advancements in this area. In this review, the authors highlight the recent progress in the fabrication of TMDC heterostructures. The authors will review several methods most commonly used to date for controllable heterostructure formation. One of the focuses will be on TMDC heterostructures fabricated by thermal chemical vapor deposition methods which allow for the control over the resulting materials, individual layers and heterostructures. Another focus would be on the techniques for selective growth of TMDCs. The authors will discuss conventional and unconventional fabrication methods and their advantages and drawbacks and will provide some guidance for future improvements. Mask-assisted and mask-free methods will be presented, which include traditional lithographic techniques (photo- or e-beam lithography) and some unconventional methods such as the focus ion beam and the recently developed direct-write patterning approach, which are shown to be promising for the fabrication of quality TMDC heterostructures.

In the present work, the emission characteristics of lipids as a function of the primary ion cluster size and energy were studied using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Characteristic fragmentation patterns for common lipids are described, and changes in secondary ion (SI) yields using various primary ion beams are reported. In particular, emission characteristics were studied for pairs of small polyatomic and nanoparticle primary ion beams (e.g., Bi versus Ar and Au versus Au) based on the secondary ion yield of characteristic fragment and intact molecular ions as a function of the lipid class. Detailed descriptions of the fragmentation patterns are shown for positive and negative mode TOF-SIMS. Results demonstrate that the lipid structure largely dictates the spectral presence of molecular and/or fragment ions in each ionization mode due to the localization of the charge carrier (head group or fatty acid chain). Our results suggest that the larger the energy per atom for small polyatomic projectiles (Bi and Au), the larger the SI yield; in the case of nanoparticle projectiles, the SI increase with primary ion energy (200-500 keV range) for Au and with the decrease of the energy per atom (10-40 eV/atom range) for Ar clusters. The secondary ion yield of the molecular ion of lipids from a single standard or from a mixture of lipids does not significantly change with the primary ion identity in the positive ion mode TOF-SIMS and slightly decreases in the negative ion mode TOF-SIMS.

New strategies for combining conventional photo- and soft-lithographic techniques with high-resolution patterning and etching strategies are needed in order to produce multiscale fluidic platforms that address the full range of functional scales seen in complex biological and chemical systems. The smallest resolution required for an application often dictates the fabrication method used. Micromachining and micropowder blasting yield higher throughput, but lack the resolution needed to fully address biological and chemical systems at the cellular and molecular scales. In contrast, techniques such as electron beam lithography or nanoimprinting allow nanoscale resolution, but are traditionally considered costly and slow. Other techniques such as photolithography or soft lithography have characteristics between these extremes. Combining these techniques to fabricate multiscale or hybrid fluidics allows fundamental biological and chemical questions to be answered. In this study, a combination of photolithography and electron beam lithography are used to produce two multiscale fluidic devices that incorporate porous membranes into complex fluidic networks in order to control the flow of energy, information, and materials in chemical form. In the first device, materials and energy were used to support chemical reactions. A nanoporous membrane fabricated with e-beam lithography separates two parallel, serpentine channels. Photolithography was used to pattern microfluidic channels around the membrane. The pores were written at 150 nm and reduced in size with silicon dioxide deposition from plasma enhanced chemical vapor deposition and atomic layer deposition. Using this method, the molecular weight cutoff of the membrane can be adapted to the system of interest. In the second approach, photolithography was used to fabricate 200 nm thin pores. The pores confined microbes and allowed energy replenishment from a media perfusion channel. The same device can be used for study of intercellular communication via the secretion and uptake of signal molecules. Pore size was tested with 750 nm fluorescent polystyrene beads and fluorescein dye. The 200 nm polydimethylsiloxane pores were shown to be robust enough to hold 750 nm beads while under pressure, but allow fluorescein to diffuse across the barrier. Further testing showed that extended culture of bacteria within the chambers was possible. These two examples show how lithographically defined porous membranes can be adapted to two unique situations and used to tune the flow of chemical energy, materials, and information within a microfluidic network.

The authors have developed a high-resolution technique for fabricating photomasks at the 10-nm half-pitch logic nodes and beyond. Current mask-manufacturing techniques use a chemically amplified resist (CAR) that has a complex mechanism of acid generation, complicating the criteria for selecting the polymer and the quencher for industrial purposes. Thus, it is important to study fabricating masks with non-CARs. The authors exposed a non-CAR, diluted ZEP520A, to variable-shaped electron-beam lithography and used a postexposure bake (PEB) to modify the resist. Studying how the PEB temperature affected the non-CAR and resultant masks, the authors demonstrate that their technique can produce high-resolution structures. By measuring the critical dimensions (CDs), the authors show that the PEB shrunk, enlarged, and retained the size of 1:1 line-and-space, isolated space, and isolated line patterns, respectively. By optimizing the PEB temperature, the authors improved the line-edge roughness (LER) of the 1:1 line-and-space and isolated space CDs by ∼40%. To understand how the PEB affected the resultant structures, the authors measured the hardness of cured resists with and without a PEB at various temperatures. Optimizing the PEB temperature of the non-CAR increased the resist contrast, annealing the resist and improving the LER. As such, their technique is capable of high resolutions on the order of 20 nm. The insights the authors gained from optimizing the PEB might be useful when fabricating next-generation masks.

Delivery of low-volatility precursors is a continuing challenge for chemical vapor deposition and atomic layer deposition processes used for microelectronics manufacturing. To aid in addressing this problem, we have recently developed an inline measurement capable of monitoring precursor delivery. Motivated by a desire to better understand the origins of what is now observable, this study uses computational fluid dynamics and a relatively simple model to simulate the delivery of pentakis(dimethylamido)tantalum (PDMAT) from a commercial vapor draw ampoule. Parameters used in the model are obtained by fitting the performance of the ampoule to a limited dataset of PDMAT delivery rates obtained experimentally using a non-dispersive infrared sensor. The model shows good agreement with a much larger experimental dataset over a range of conditions in both pulsed and continuously flowing operation. The combined approach of experiment and simulation provides a means to understand the phenomena occurring during precursor delivery both quantitatively and qualitatively.

The design, fabrication and characterization of single metal gate layer, metal-oxide-semiconductor (MOS) quantum dot devices robust against dielectric breakdown are presented as prototypes for future diagnostic qubits. These devices were developed as a preliminary solution to a longer term goal of a qubit platform for intercomparison between materials or for in-line diagnostics, and to provide a testbed for establishing classical measurements predictive of coherence performance. For this stage, we seek a robust MOS design that is compatible with wafer and chip architectures, that has a reduced process overhead and is sufficiently capable of challenging and advancing our measurement capabilities. In this report, we present our initial batch of silicon MOS devices using a single gate layer, which have not exhibited any failures with gate voltage excursions > 10 V, but do exhibit the reduced electrostatic control expected of a single gate layer design. We observe quantum dot formation, capacitive charge sensing between channels, and reasonable effective electron temperatures that enable spin qubit studies. The costs and benefits of the trade-off between device performance and fabrication efficiency will be discussed, as well as opportunities for future improvements.

This paper reports high-throughput, light-based, through-focus scanning optical microscopy (TSOM) for detecting industrially relevant sub-50 nm tall nanoscale contaminants. Measurement parameter optimization to maximize the TSOM signal using optical simulations made it possible to detect the nanoscale contaminants. Atomic force and scanning electron microscopies were used as reference methods for comparison.