This perspective gives an overview of recent developments in surface-enhanced Raman scattering (SERS) for biosensing. We focus this review on SERS papers published in the last 10 years and to specific applications of detecting biological analytes. Both intrinsic and extrinsic SERS biosensing schemes have been employed to detect and identify small molecules, nucleic acids, lipids, peptides, and proteins, as well as for in vivo and cellular sensing. Current SERS substrate technologies along with a series of advancements in surface chemistry, sample preparation, intrinsic/extrinsic signal transduction schemes, and tip-enhanced Raman spectroscopy are discussed. The progress covered herein shows great promise for widespread adoption of SERS biosensing.

Inexpensive, reproducible and high-throughput fabrication of nanometric apertures in metallic films can benefit many applications in plasmonics, sensing, spectroscopy, lithography and imaging. Here we use template stripping to pattern periodic nanohole arrays in optically thick, smooth Ag films with a silicon template made via nanoimprint lithography. Ag is a low-cost material with good optical properties, but it suffers from poor chemical stability and biocompatibility. However, a thin silica shell encapsulating our template-stripped Ag nanoholes facilitates biosensing applications by protecting the Ag from oxidation as well as providing a robust surface that can be readily modified with a variety of biomolecules using well-established silane chemistry. The thickness of the conformal silica shell can be precisely tuned by atomic layer deposition, and a 15-nm-thick silica shell can effectively prevent fluorophore quenching. The Ag nanohole arrays with silica shells can also be bonded to polydimethylsiloxane (PDMS) microfluidic channels for fluorescence imaging, formation of supported lipid bilayers, and real-time, label-free SPR sensing. Additionally, the smooth surfaces of the template-stripped Ag films enhance refractive index sensitivity compared with as-deposited, rough Ag films. Because nearly centimeter-sized nanohole arrays can be produced inexpensively without using any additional lithography, etching or lift-off, this method can facilitate widespread applications of metallic nanohole arrays for plasmonics and biosensing.

Self-assembled plasmonic nanoring cavity arrays are formed alongside the curvature of highly packed metallic nanosphere gratings. The sub-10-nm gap size is precisely tuned via atomic layer deposition and highly ordered arrays are produced over a cm-sized area. The resulting hybrid nanostructure boosts coupling efficiency of light into plasmons, and shows an improved SERS detection limit. These substrates are used for SERS detection of the biological analyte, adenine, followed by concurrent localized surface plasmon resonance sensing.

We present a simple and massively parallel nanofabrication technique to produce self-assembled periodic nanohole arrays over a millimeter-sized area of metallic film, with a tunable hole shape, diameter, and periodicity. Using this method, 30 x 30 microm(2) defect-free areas of 300 nm diameter or smaller holes were obtained in silver; this area threshold is critical because it is larger than the visible wavelength propagation length of surface plasmon waves ( approximately 27 microm) in the silver film. Measured optical transmission spectra show highly homogeneous characteristics across the millimeter-size patterned area, and they are in good agreement with FDTD simulations. The simulations also reveal intense electric fields concentrated near the air/silver interface, which was used for surface-enhanced Raman spectroscopy (SERS). Enhancement factors (EFs) measured with different hole shape and excitation wavelengths on the self-assembled nanohole arrays were 10(4)-10(6). With an additional Ag electroless plating step, the EF was further increased up to 3 x 10(6). The periodic nanohole arrays produced using this tunable self-assembly method show great promise as inexpensive SERS substrates as well as surface plasmon resonance biosensing platforms.

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The experimental observation of unusually sharp plasmon resonance peaks in periodic Ag nanohole arrays made using template stripping is reported. The extraordinary optical transmission (EOT) peak associated with the surface plasmon polaritons at the smooth Ag‐water interface shows a well‐defined Fano‐type profile with a linewidth below 10 nm at a wavelength of around 700 nm. Notably, this sharp and intense radiant peak (Q factor of 71) is obtained at visible frequencies in water and at normally incident illumination. This is accomplished by obtaining high‐quality Ag surfaces with a roughness below 1 nm, which reduces the imaginary component of the Ag dielectric function that is associated with material damping, as well as shrinking the nanohole radius to decrease radiative damping of plasmons. The localized spectral response of the radiant plasmon peak is characterized using the nanohole array in water in a layer‐by‐layer fashion via sequential atomic layer deposition of Al2O3. Because the ultrasharp EOT peak is obtained with excellent uniformity over a centimeter‐sized area from the metallic nanohole array in water, these template‐stripped nanohole arrays will benefit many practical applications based on EOT.

ObjectiveRe-implantation of autologous skull bone has been known to be difficult because of its propensity for resorption. Moreover, the structural characteristics of the area of the defect cannot tolerate physiologic loading, which is an important factor for graft healing. This paper describes our experiences and results with cranioplasty following decompressive craniectomy using autologous bone flaps.MethodsIn an institutional review, the authors identified 18 patients (11 male and 7 female) in whom autologous cranioplasty was performed after decompressive craniectomy from January 2008 to December 2011. We examined the age, reasons for craniectomy, size of the skull defect, presence of bony resorption, and postoperative complications.ResultsPostoperative bone resorption occurred in eight cases (44.4%). Among them, two experienced symptomatic breakdown of the autologous bone graft that required a second operation to reconstruct the skull contour using porous polyethylene implant (Medpor®). The incidence of bone resorption was more common in the pediatric group and in those with large cranial defects (>120 cm2). No significant correlation was found with sex, reasons for craniectomy, and cryopreservation period.ConclusionThe use of autologous bone flap for reconstruction of a skull defect after decompressive craniectomy is a quick and cost-effective method. But, the resorption rate was greater in children and in patients with large skull defects. As a result, we suggest compressive force of the tightened scalp, young age, large skull defect, the gap between bone flap and bone edge and heat sterilization of autologous bone as risk factors for bone resorption.

The ability to precisely control the topography, roughness, and chemical properties of metallic nanostructures is crucial for applications in plasmonics, nanofluidics, electronics, and biosensing. Here a simple method to produce embedded nanoplasmonic devices that can generate tunable plasmonic fields on ultraflat surfaces is demonstrated. Using a template‐stripping technique, isolated metallic nanodisks and wires are embedded in optical epoxy, which is capped with a thin silica overlayer using atomic layer deposition. The top silica surface is topographically flat and laterally homogeneous, providing a uniform, high‐quality biocompatible substrate, while the nanoplasmonic architecture hidden underneath creates a tunable plasmonic landscape for optical imaging and sensing. The localized surface plasmon resonance of gold nanodisks embedded underneath flat silica films is used for real‐time kinetic sensing of the formation of a supported lipid bilayer and subsequent receptor‐ligand binding. Gold nanodisks can also be embedded in elastomeric materials, which can be peeled off the substrate to create flexible plasmonic membranes that conform to non‐planar surfaces.