ConspectusSurface-enhanced Raman spectroscopy (SERS) fingerprinting is highly promising for identifying disease markers from complex mixtures of clinical sample, which has the capability to take medical diagnoses to the next level. Although vibrational frequency in Raman spectra is unique for each biomolecule, which can be used as fingerprint identification, it has not been considered to be used routinely for biosensing due to the fact that the Raman signal is very weak. Contemporary SERS has been demonstrated to be an excellent analytical tool for practical label-free sensing applications due its ability to enhance Raman signals by factors of up to 108–1014 orders of magnitude. Although SERS was discovered more than 40 years ago, its applications are still rare outside the spectroscopy community and it is mainly due to the fact that how to control, manipulate and amplify light on the “hot spots” near the metal surface is in the infancy stage.In this Account, we describe our contribution to develop nanoachitecture based highly reproducible and ultrasensitive detection capability SERS platform via low-cost synthetic routes. Using one-dimensional (1D) carbon nanotube (CNT), two-dimensional (2D) graphene oxide (GO), and zero-dimensional (0D) plasmonic nanoparticle, 0D to 3D SERS substrates have been designed, which represent highly powerful platform for biological diagnosis. We discuss the major design criteria we have used to develop robust SERS substrate to possess high density “hot spots” with very good reproducibility. SERS enhancement factor for 3D SERS substrate is about 5 orders of magnitude higher than only plasmonic nanoparticle and more than 9 orders of magnitude higher than 2D GO. Theoretical finite-difference time-domain (FDTD) stimulation data show that the electric field enhancement |E|2 can be more than 2 orders of magnitude in “hot spots”, which suggests that SERS enhancement factors can be greater than 104 due to the formation of high density “hot spots” in 3D substrate. Next, we discuss the utilization of nanoachitecture based SERS substrate for ultrasensitive and selective diagnosis of infectious disease organisms such as drug resistance bacteria and mosquito-borne flavi-viruses that cause significant health problems worldwide. SERS based “whole-organism fingerprints” has been used to identify infectious disease organisms even when they are so closely related that they are difficult to distinguish. The detection capability can be as low as 10 CFU/mL for methicillin-resistant Staphylococcus aureus (MRSA) and 10 PFU/mL for Dengue virus (DENV) and West Nile virus (WNV). After that, we introduce exciting research findings by our group on the applications of nanoachitecture based SERS substrate for the capture and fingerprint detection of rotavirus from water and Alzheimer’s disease biomarkers from whole blood sample. The SERS detection limit for β-amyloid (Aβ proteins) and tau protein using 3D SERS platform is several orders of magnitude higher than the currently used technology in clinics. Finally, w...

A combination of silver nanoparticles (AgNPs) and an antibiotic can synergistically inhibit bacterial growth, especially against the drug-resistant bacteria Salmonella typhimurium. However, the mechanism for the synergistic activity is not known. This study chooses four classes of antibiotics, β-lactam (ampicillin and penicillin), quinolone (enoxacin), aminoglycoside (kanamycin and neomycin), and polykeptide (tetracycline) to explore their synergistic mechanism when combined with AgNPs against the multidrug-resistant bacterium Salmonella typhimurium DT 104. Enoxacin, kanamycin, neomycin, and tetracycline show synergistic growth inhibition against the Salmonella bacteria when combined with AgNPs, while ampicillin and penicillin do not. UV–vis and Raman spectroscopy studies reveal that all these four synergistic antibiotics can form complexes with AgNPs, while ampicillin and penicillin do not. The presence of tetracycline enhances the binding of Ag to Salmonella by 21% and Ag+ release by 26% in comparison to that without tetracycline, while the presence of penicillin does not enhance the binding of Ag or Ag+ release. This means that AgNPs first form a complex with tetracycline. The tetracycline–AgNPs complex interacts more strongly with the Salmonella cells and causes more Ag+ release, thus creating a temporal high concentration of Ag+ near the bacteria cell wall that leads to growth inhibition of the bacteria. These findings agree with the recent findings that Ag+ release from AgNPs is the agent causing toxicity.

In the last few decades, Förster resonance energy transfer (FRET) based spectroscopy rulers have served as a key tool for the understanding of chemical and biochemical processes, even at the single molecule level. Since the FRET process originates from dipole-dipole interactions, the length scale of a FRET ruler is limited to a maximum of 10 nm. Recently, scientists have reported a nanomaterial based long-range optical ruler, where one can overcome the FRET optical ruler distance dependence limit, and which can be very useful for monitoring biological processes that occur across a greater distance than the 10 nm scale. Advancement of nanoscopic long range optical rulers in the last ten years indicate that, in addition to their long-range capability, their brightness, long lifetime, lack of blinking, and chemical stability make nanoparticle based rulers a good choice for long range optical probes. The current review discusses the basic concepts and unique light-focusing properties of plasmonic nanoparticles which are useful in the development of long range one dimensional to three dimensional optical rulers. In addition, to provide the readers with an overview of the exciting opportunities within this field, this review discusses the applications of long range rulers for monitoring biological and chemical processes. At the end, we conclude by speculating on the role of long range optical rulers in future scientific research and discuss possible problems, outlooks and future needs in the use of optical rulers for technological applications.

Despite intense efforts, Alzheimer’s disease (AD) is one of the top public health crisis for society even at 21st century. Since presently there is no cure for AD, early diagnosis of possible AD biomarkers is crucial for the society. Driven by the need, the current manuscript reports the development of magnetic core-plasmonic shell nanoparticle attached hybrid graphene oxide based multifunctional nanoplatform which has the capability for highly selective separation of AD biomarkers from whole blood sample, followed by label-free surface enhanced Raman spectroscopy (SERS) identification in femto gram level. Experimental ELISA data show that antibody-conjugated nanoplatform has the capability to capture more than 98% AD biomarkers from the whole blood sample. Reported result shows that nanoplatform can be used for SERS “fingerprint” identification of β-amyloid and tau protein after magnetic separation even at 100 fg/mL level. Experimental results indicate that very high sensitivity achieved is mainly due to the strong plasmon-coupling which generates huge amplified electromagnetic fields at the “hot spot”. Experimental results with nontargeted HSA protein, which is one of the most abundant protein components in cerebrospinal fluid (CSF), show that multifunctional nanoplatform based AD biomarkers separation and identification is highly selective.

Dengue virus (DENV) and West Nile virus (WNV) are two well-documented mosquito-borne flaviviruses that cause significant health problems worldwide. Driven by this need, we have developed a bio-conjugated gold nanoparticle (AuNP)-based surface enhanced Raman spectroscopy (SERS) probe for the detection of both DENV and WNV. Reported data demonstrate anti-flavivirus 4G2 antibody conjugated gold nanoparticle (GNP) SERS probe can be used as a Raman fingerprint for the ultrasensitive detection of DENV and WNV selectively. Experimental data show that due to the plasmon coupling in nano-assembly, antibody conjugated GNP- based SERS is able to detect as low as 10 plaque-forming units (PFU)/ml of DENV-2 and WNV, which is comparable with the sensitivity of quantitative PCR-based assays. Selectivity of our probe was demonstrated using another mosquito-borne chikungunya virus (CHIKV) as a negative control. Experimental data demonstrate a huge enhancement of SERS intensity is mainly due to the strong electric field enhancement, which has been confirmed by the finite-difference time-domain (FDTD) simulation. Reported FDTD simulation data indicate the SERS enhancement factor can be more than 104 times, due to the assembled structure. Reported results suggest that bio-conjugated AuNP-4G2 based SERS probes have great potential to be used to screen viral particles in clinical and research-based laboratories.

In this paper, for the first time, we report a detailed study of the temperature-dependent solvation dynamics of a probe fluorophore, coumarin-500, in AOT/isooctane reverse micelles (RMs) with varying degrees of hydration (w0) of 5, 10, and 20 at four different temperatures, 293, 313, 328, and 343 K. The average solvation time constant becomes faster with the increase in w0 values at a particular temperature. The solvation dynamics of a RM with a fixed w0 value also becomes faster with the increase in temperature. The observed temperature-induced faster solvation dynamics is associated with a transition of bound- to free-type water molecules, and the corresponding activation energy value for the w0 = 5 system has been found to be 3.4 kcal mol-1, whereas for the latter two systems, it is approximately 5 kcal mol-1. Dynamic light scattering measurements indicate an insignificant change in size with temperature for RMs with w0 = 5 and 10, whereas for a w0 = 20 system, the hydrodynamic diameter increases with temperature. Time-resolved fluorescence anisotropy studies reveal a decrease in the rotational restriction on the probe with increasing temperature for all systems. Wobbling-in-cone analysis of the anisotropy data also supports this finding.

Drug resistant superbug infection is one of the foremost threats to human health. Plasmonic nanoparticles can be used for ultrasensitive bio-imaging and photothermal killing by amplification of electromagnetic fields at nanoscale “hot spots”. One of the main challenges to plasmonic imaging and photothermal killing is design of a plasmonic substrate with a large number of “hot spots”. Driven by this need, this article reports design of a three-dimensional (3D) plasmonic “hot spot”-based substrate using gold nanoparticle attached hybrid graphene oxide (GO), free from the traditional 2D limitations. Experimental results show that the 3D substrate has capability for highly sensitive label-free sensing and generates high photothermal heat. Reported data using p-aminothiophenol conjugated 3D substrate show that the surface enhanced Raman spectroscopy (SERS) enhancement factor for the 3D “hot spot”-based substrate is more than two orders of magnitude greater than that for the two-dimensional (2D) substrate and five orders of magnitude greater than that for the zero-dimensional (0D) p-aminothiophenol conjugated gold nanoparticle. 3D-Finite-Difference Time-Domain (3D-FDTD) simulation calculations indicate that the SERS enhancement factor can be greater than 104 because of the bent assembly structure in the 3D substrate. Results demonstrate that the 3D-substrate-based SERS can be used for fingerprint identification of several multi-drug resistant superbugs with detection limits of 5 colony forming units/mL. Experimental data show that 785 nm near infrared (NIR) light generates around two times more photothermal heat for the 3D substrate with respect to the 2D substrate, and allows rapid and effective killing of 100% of the multi-drug resistant superbugs within 5 minutes.

According to the World Health Organization, even in the 21st century, more than one million children die each year due to the rotavirus contamination of drinking water. Therefore, accurate identification and removal of rotavirus are very important to save childrens' lives. Driven by the need, in this Letter, we report for the first time highly selective identification and removal of rotavirus from infected water using a bioconjugated hybrid graphene oxide based three-dimensional (3D) solid architecture. Experimental results show that due to the presence of a high intensity of "hot spots" in the 3D network, an antibody-attached 3D plasmonic-magnetic architecture can be used for accurate identification of rotavirus using surface-enhanced Raman spectroscopy (SERS). Reported data demonstrate that the antibody-attached 3D network binds strongly with rotavirus and is capable of highly efficient removal of rotavirus, which has been confirmed by SERS, fluorescence imaging, and enzyme-linked immunosorbent assay (ELISA) data. We discuss a possible mechanism for accurate identification and efficient removal of rotavirus from infected drinking water.