Advanced Tuneable Micronanoplatforms for Sensitive and Selective Multiplexed Spectroscopic Sensing via Electro-Hydrodynamic Surface Molecular Lithography.

Micro- and nanopatterning of materials, one of the cornerstones of emerging technologies, has transformed research capabilities in lab-on-a-chip diagnostics. Herein, a micro- and nanolithographic method is developed, enabling structuring materials at the submicron scale, which can, in turn, accelerate the development of miniaturized platform technologies and biomedical sensors. Underpinning it is the advanced electro-hydrodynamic surface molecular lithography, via inducing interfacial instabilities produces micro- and nanostructured substrates, uniquely integrated with synthetic surface recognition. This approach enables the manufacture of design patterns with tuneable feature sizes, which are functionalized via synthetic nanochemistry for highly sensitive, selective, rapid molecular sensing. The development of a high-precision piezoelectric lithographic rig enables reproducible substrate fabrication with optimum signal enhancement optimized for functionalization with capture molecules on each micro- and nanostructured array. This facilitates spatial separation, which during the spectroscopic sensing, enables multiplexed measurement of target molecules, establishing the detection at minute concentrations. Subsequently, this nano-plasmonic lab-on-a-chip combined with the unconventional computational classification algorithm and surface enhanced Raman spectroscopy, aimed to address the challenges associated with timely point-of-care detection of disease-indicative biomarkers, is utilized in validation assay for multiplex detection of traumatic brain injury indicative glycan biomarkers, demonstrating straightforward and cost-effective micro- and nanoplatforms for accurate detection.

Hybrid use of Raman spectroscopy and artificial neural networks to discriminate Mycobacterium bovis BCG and other Mycobacteriales.

Even in the face of the COVID-19 pandemic, Tuberculosis (TB) continues to be a major public health problem and the 2nd biggest infectious cause of death worldwide. There is, therefore, an urgent need to develop effective TB diagnostic methods, which are cheap, portable, sensitive and specific. Raman spectroscopy is a potential spectroscopic technique for this purpose, however, so far, research efforts have focused primarily on the characterisation of Mycobacterium tuberculosis and other Mycobacteria, neglecting bacteria within the microbiome and thus, failing to consider the bigger picture. It is paramount to characterise relevant Mycobacteriales and develop suitable analytical tools to discriminate them from each other. Herein, through the combined use of Raman spectroscopy and the self-optimising Kohonen index network and further multivariate tools, we have successfully undertaken the spectral analysis of Mycobacterium bovis BCG, Corynebacterium glutamicum and Rhodoccocus erythropolis. This has led to development of a useful tool set, which can readily discern spectral differences between these three closely related bacteria as well as generate a unique spectral barcode for each species. Further optimisation and refinement of the developed method will enable its application to other bacteria inhabiting the microbiome and ultimately lead to advanced diagnostic technologies, which can save many lives.

Window into the mind: Advanced handheld spectroscopic eye-safe technology for point-of-care neurodiagnostic.

Traumatic brain injury (TBI), a major cause of morbidity and mortality worldwide, is hard to diagnose at the point of care with patients often exhibiting no clinical symptoms. There is an urgent need for rapid point-of-care diagnostics to enable timely intervention. We have developed a technology for rapid acquisition of molecular fingerprints of TBI biochemistry to safely measure proxies for cerebral injury through the eye, providing a path toward noninvasive point-of-care neurodiagnostics using simultaneous Raman spectroscopy and fundus imaging of the neuroretina. Detection of endogenous neuromarkers in porcine eyes' posterior revealed enhancement of high-wave number bands, clearly distinguishing TBI and healthy cohorts, classified via artificial neural network algorithm for automated data interpretation. Clinically, translating into reduced specialist support, this markedly improves the speed of diagnosis. Designed as a hand-held cost-effective technology, it can allow clinicians to rapidly assess TBI at the point of care and identify long-term changes in brain biochemistry in acute or chronic neurodiseases.

Review: Emerging Eye-Based Diagnostic Technologies for Traumatic Brain Injury.

The study of ocular manifestations of neurodegenerative disorders, Oculomics, is a growing field of investigation for early diagnostics, enabling structural and chemical biomarkers to be monitored overtime to predict prognosis. Traumatic brain injury (TBI) triggers a cascade of events harmful to the brain, which can lead to neurodegeneration. TBI, termed the "silent epidemic" is becoming a leading cause of death and disability worldwide. There is currently no effective diagnostic tool for TBI, and yet, early-intervention is known to considerably shorten hospital stays, improve outcomes, fasten neurological recovery and lower mortality rates, highlighting the unmet need for techniques capable of rapid and accurate point-of-care diagnostics, implemented in the earliest stages. This review focuses on the latest advances in the main neuropathophysiological responses and the achievements and shortfalls of TBI diagnostic methods. Validated and emerging TBI-indicative biomarkers are outlined and linked to ocular neuro-disorders. Methods detecting structural and chemical ocular responses to TBI are categorised along with prospective chemical and physical sensing techniques. Particular attention is drawn to the potential of Raman spectroscopy as a non-invasive sensing of neurological molecular signatures in the ocular projections of the brain, laying the platform for the first tangible path towards alternative point-of-care diagnostic technologies for TBI.

Optimization of Nanosubstrates toward Molecularly Surface-Functionalized Raman Spectroscopy.

Diagnostic advancements require continuous developments of reliable analytical sensors, which can simultaneously fulfill many criteria, including high sensitivity and specificity for a broad range of target analytes. Incorporating the highly sensitive attributes of surface-enhanced Raman spectroscopy (SERS) combined with highly specific analyte recognition capabilities via molecular surface functionalization could address major challenges in molecular diagnostics and analytical spectroscopy fields. Herein, we have established a controllable molecular surface functionalization process for a series of textured gold surfaces. To create the molecularly surface-functionalized SERS platforms, self-assembled benzyl-terminated and benzoboroxole-terminated monolayers were used to compare which thicknesses and root-mean-square (RMS) roughness of planar gold produced the most sensitive and specific surfaces. Optimal functionalization was identified at 80 ± 8 nm thickness and 7.2 ± 1.0 nm RMS. These exhibited a considerably higher SERS signal (70-fold) and improved sensitivity for polysaccharides when analyzed using principal component analysis (PCA) and self-organizing maps (SOM). These findings lay the procedure for establishing the optimal substrate specifications as an essential prerequisite for future studies aiming at developing the feasibility of molecular imprinting for SERS diagnostic applications and the subsequent delivery of advanced, highly selective, and sensitive sensing devices and analytical platforms.

Electrofluidynamic Patterning of Tailorable Nanostructured Substrates for Surface-Enhanced Raman Scattering.

The unique attributes of surface enhanced Raman spectroscopy (SERS) make it well suited to address the challenges associated with portable diagnostics. However, despite the remarkable progress in this field, where the instrumentation has made great strides forward providing a route to the miniaturization of sensing devices, to date producing three-dimensional low-cost SERS substrates which simultaneously fulfill the multitude of criteria of high sensitivity, reproducibility, tunability, multiplexity, and integratability for rapid sensing has not yet been accomplished. Successful implementation of SERS requires readily fine-tuned nanostructures, which create a high enhancement. Here, an advanced electrofluidynamic patterning (EFDP) technique enables rapid fabrication of SERS active topographic morphologies with high throughput and at a nanoresolution via the spatial and lateral modulation of the dielectric discontinuity due to the high electric field generated across the polymer nanofilm and air gap. The subsequent formation of displacement charges within the nanofilm by coupling to the electric field yield a destabilizing electrostatic pressure and amplification of EFDP instabilities enabling the controllable pattern formation. The top of each gold coated EFDP fabricated pillar generates controllable high SERS enhancement by coupling of surface plasmon modes on top of the pillar, with each nanostructure acting as an individual sensing unit. The absolute enhancement factor depends on the topology as well as the tunable dimensions of the nanostructured units, and these are optimized in the design and engineering of the dedicated EFDP apparatus for reproducible, low-cost fabrication of the three-dimensional nanoarchitectures on macrosurfaces, rendering them for easy integration in further lab-on-a-chip devices. This unique combination of nanomaterials and nanospectroscopic systems lay the platform for a variety of applications in chemical and biological sensing.

Tuneable Metamaterial-like Platforms for Surface-Enhanced Raman Scattering via Three-Dimensional Block Co-polymer-Based Nanoarchitectures.

Surface-enhanced Raman spectroscopy (SERS) pushes past the boundaries and inherent weaknesses of Raman spectroscopy, with a great potential for a broad range of applications particularly, for sensing. Yet, current real world applications are limited due to poor reproducibility, low-throughput, and stability issues. Here, we present the design and fabrication of self-assembly guided structures based on adjustable block co-polymer (BCP) nanomorphologies and demonstrate reproducible SERS enhancement across large areas. Golden three-dimensional (3D) nanostructured morphologies with controllable dimensions and morphologies exhibit high chemical stability, enhanced plasmonic properties and are highly suitable for SERS substrates due to the strong enhancement of the electromagnetic field. Adjustable, free standing porous nanostructures, continuous in 3D space are achieved by removal of selected BCP constituents. Four BCP morphologies and the corresponding achievable enhancement factors are investigated at 633 and 785 nm excitation wavelengths. The choice of excitation laser is shown to greatly affect the observed signal enhancement, highlighting the sensitivity of the technique to the underlying surface architecture and length scales. By using BCP assemblies, it is possible to reliably tune these parameters to match specific applications, thus bridging the gap toward the realization of applied metamaterials. The fabricated SERS platforms via three-dimensional block co-polymer-based nanoarchitectures provide a recipe for intelligent engineering and design of optimized SERS-active substrates for utilization in the Raman spectroscopy-based devices toward enabling the next-generation technologies fulfilling a multitude of criteria.

Fabrication of optimized skin biomimics for improved interfacial retention of cosmetic emulsions.

Retention of hydrophobic active agents on human skin following the use of skin-care formulations is an important indication of the performance of the deposited product. We have developed a novel system which replicates the interaction between human skin and a cosmetic emulsion to systematically establish and characterize the key parameters driving the retention process at the interface. This included a comprehensive study of the skin's biology and physical properties which influenced the process, the fabrication of advanced, improved skin biomimics, the formulation of a cosmetic model-system emulsion, comprising a hydrophobic active agent i.e. petrolatum, commonly used in cosmetic products, the development of a dedicated and highly consistent deposition rig with a corresponding cleaning set-up and the systematic characterization of retention processes on the developed mimics. This study further explores the interplay of petrolatum with skin biomimics and studies the mechanisms that give rise to improved interfacial retention. Petrolatum has been found to create an occlusive layer on the skin mimic, displaying high coverage from emulsion formulations. The large particle size emulsions yielded improved retention on the developed skin biomimics due to the microstructure of the emulsion and the counter effect of the surfactant.

Tunable superapolar Lotus-to-Rose hierarchical nanosurfaces via vertical carbon nanotubes driven electrohydrodynamic lithography.

The development of a robust, cost-effective, scalable and simple technique that enables the design and construction of well-controlled large area superhydrophobic surface structures which can be easily tuned from lotus-leaf to rose-petal state is essential to enable progress in realising the full applied potential of such surfaces. In this study, we introduce the tuneable carbon nanotubes-based electrohydrodynamic lithography (CNT-EHL) to fabricate unique multiscale structured cones and nanohair-like architectures with various periodicities and dimensions, successfully enabling surface energy minimization. The possibility of contact-less lithography via the CNT-EHL morphology replication combined with the electric field coupling to smaller self-assembled patterns within the film, provides a way for hierarchical structure control spanning many length scales along with tuneable wetting capabilities. By controlling the hierarchy of micro- to nano cones and spikes, these morphologies provide a range of architectures with sufficient roughness for very low wettability, with the highest contact angle achieved of 173° and their properties can be easily switched between lotus-leaf to rose-petal behaviour.

Tunable Nanopatterning of Conductive Polymers via Electrohydrodynamic Lithography.

An increasing number of technologies require the fabrication of conductive structures on a broad range of scales and over large areas. Here, we introduce advanced yet simple electrohydrodynamic lithography (EHL) for patterning conductive polymers directly on a substrate with high fidelity. We illustrate the generality of this robust, low-cost method by structuring thin polypyrrole films via electric-field-induced instabilities, yielding well-defined conductive structures with feature sizes ranging from tens of micrometers to hundreds of nanometers. Exploitation of a conductive polymer induces free charge suppression of the field in the polymer film, paving the way for accessing scale sizes in the low submicron range. We show the feasibility of the polypyrrole-based structures for field-effect transistor devices. Controlled EHL pattering of conductive polymer structures at the micro and nano scale demonstrated in this study combined with the possibility of effectively tuning the dimensions of the tailor-made architectures might herald a route toward various submicron device applications in supercapacitors, photovoltaics, sensors, and electronic displays.