Aiguo Shen

Nuclear targeted nanoprobe for single living cell detection by surface-enhanced Raman scattering.

We present a novel nuclear targeting nanoprobe based on peptide functionalized gold nanoparticles and its surface-enhanced Raman scattering (SERS) in living cells. For the first time, we probe an original SERS signal from the living cell nucleus by using high-selectivity functionalized gold nanoparticles. The gold nanoparticles conjugated with SV-40 large T nuclear localization signal (NLS) peptide successfully enter the cell nucleus after the incubation with Hela cells and deliver the spatially localized chemical information of the nucleus, as well as the signature of chemicals that intruded subsequently. This new targeted nanoprobe is a nontoxic, biocompatible method for biological research, provided with multiple functions comprising subcellular targeting, intracellular imaging, and real-time SERS detection.

A novel biosensor based on single-layer MoS2 nanosheets for detection of Ag+

In this work, we use for the first time single layer MoS2 as the fluorescence quencher to design a detection method for Ag(+) with excellent robustness, selectivity and sensitivity. To maintain the ultrathin MoS2, bulk MoS2 materials have been exfoliated by intercalation with lithium followed by reaction with water. As-prepared two-dimensional MoS2 not only has good water-solubility but also obtains high fluorescence quenching efficiency within 5 min. Importantly, the detection limit of this assay for Ag(+) (1 nM) was lower than the maximum limitation guided by the United States Environmental Protection Agency (EPA) and the World Health Organization (WHO). Further, this new Ag(+) probe was demonstrated in monitoring Ag(+) in lake water samples with satisfactory results.

A longitudinal Raman microspectroscopic study of osteoporosis induced by spinal cord injury

IntroductionA longitudinal study was established to investigate bone compositional information in spinal cord injury (SCI) rat model.MethodsRaman spectroscopy was applied to detect the distal femur and humeri of SCI, sham-operated (SO), and age-matched control (CON) male Sprague-Dawley (SD) rats at first, second, third, and fifth weeks after surgery. One-way ANOVA and Tukey’s HSD post hoc multiple comparison tests were used to analyze the longitudinal data of mineral to matrix ratio and carbonate substitution.ResultsRelative mineral decrease was found in SCI group by more than 20% in femur and approximately 12% in humeri compared with CON group. No significant changes in carbonate substitution were observed.ConclusionsSevere bone loss in the early stage of SCI was confirmed by a continuous decrease of the mineral to collagen matrix ratio. The decrease in the humeri suggested hormone level variations might participate in the etiology of SCI-induced osteoporosis.

Simple, rapid, homogeneous oligonucleotides colorimetric detection based on non-aggregated gold nanoparticles

A simple, rapid colorimetry for DNA detection based on non-aggregated gold nanoparticles and magnetic beads has been developed with high selectivity and sensitivity.

Portable SERS-enabled Micropipettes for Microarea Sampling and Reliably Quantitative Detection of Surface Organic Residues

We report the first microsampling device for reliably quantitative, label-free and separation-free detection of multicomponents of surface organic residues (SORs) by means of a quality controllable surface-enhanced Raman scattering (SERS)-enabled micropipette. The micropipette is comprised of a drawn glass capillary with a tiny orifice (∼50 μm) at the distal tip, where the specially designed nanorattles (NRs) are compactly coated on the inner wall surface. SERS signals of 4-mercapto benzoic acid (MBA) anchored inside the internal gap of NRs could be used to evaluate and control the quality of micropipettes and, therefore, allow us to overcome the limitations of a reliably quantitative SERS assay using traditional substrates without an internal standard. By dropping a trace extraction agent on targeting SORs located on a narrow surface, the capillary and SERS functionalities of these micropipettes allow on-site microsampling via capillary action and subsequent multiplex distinction/detection due to their molecularly narrow Raman peaks. For example, 8 nM thiram (TMTD), 8 nM malachite green (MG), and 1.5 μM (400 ppb) methyl parathion (MPT) on pepper and cucumber peels have been simultaneously detected in a wide detection range. The portable SERS-enabled device could potentially be facilely incorporated with liquid-liquid or solid phase micro-extracting devices for a broader range of applications in rapid and field analysis of food/public/environment security related SORs.

Raman spectral properties of squamous cell carcinoma of oral tissues and cells

Early diagnosis is the key of the improved survival rates of oral cancer. Raman spectroscopy is sensitive to the early changes of molecular composition and structure that occur in benign lesion during carcinogenesis. In this study, in situ Raman analysis provided distinct spectra that can be used to discriminate between normal and malignant tissues, as well as normal and cancer cells. The biochemical variations between different groups were analyzed by the characteristic bands by comparing the normalized mean spectra. Spectral profiles of normal, malignant conditions show pronounced differences between one another, and multiple Raman markers associated with DNA and protein vibrational modes have been identified that exhibit excellent discrimination power for cancer sample identification. Statistical analyses of the Raman data and classification using principal component analysis (PCA) are shown to be effective for the Raman spectral diagnosis of oral mucosal diseases. The results indicate that the biomolecular differences between normal and malignant conditions are more obviously at the cellular level. This technique could provide a research foundation for the Raman spectral diagnosis of oral mucosal diseases.

Bio-Raman spectroscopy: a potential clinical analytical method assisting in disease diagnosis

With the technical progress in lasers, charge coupled device detectors, and fiber-optic probes, Raman spectroscopy (RS) is enjoying a strong resurgence in the field of biomedical science, especially in disease diagnosis. During this time we have witnessed more and more in vitro and in vivo applications of RS, and increasingly frequent reports of its utility. RS enables the extraction of biochemical signatures from biological tissues, and in conjunction with different statistic algorithms, the spectral data with various pathologic attributions can be differentiated and classified depending on their spectral differences, e.g., peak area, peak height or peak shape. This makes RS a potential clinical analytical technique for rapid and non-destructive diagnosis of human diseases. This paper is a review of the biomedical applications of Raman spectroscopic techniques in diagnostics. First, a brief illumination of RS instrumentation and algorithms for data analysis is introduced. Then wide utilization of RS in disease diagnosis is reviewed categorized by different tissues and organs, including brain, eye, body surface organs (breast, skin), abdominal organs (stomach, esophagus, colon, liver), thoracic organs (arteries, lung), reproductive and urinary organs (prostate, cervix, bladder) and hard tissue (bone, teeth). Some other work from our group are also introduced.

Noninvasive Metabolomic Profiling of Human Embryo Culture Media Using a Simple Spectroscopy Adjunct to Morphology for Embryo Assessment in in Vitro Fertilization (IVF)

Embryo quality is crucial to the outcome of in vitro fertilization (IVF); however, the ability to precisely distinguish the embryos with higher reproductive potential from others is poor. Morphologic evaluation used to play an important role in assessing embryo quality, but it is somewhat subjective. The culture medium is the immediate environment of the embryos in vitro, and a change of the substances in the culture medium is possibly related to the embryo quality. Thus, the present study aims to determine whether metabolomic profiling of the culture medium using Raman spectroscopy adjunct to morphology correlates with the reproductive potential of embryos in IVF and, thus, to look for a new method of assessing embryo quality. Fifty seven spent media samples were detected by Raman spectroscopy. Combined with embryo morphology scores, we found that embryos in culture media with less than 0.012 of sodium pyruvate and more than −0.00085 phenylalanine have a high reproductive potential, with up to 85.7% accuracy compared with clinical pregnancy. So, sodium pyruvate and phenylalanine in culture medium play an important role in the development of the embryo. Raman spectroscopy is an important tool that provides a new and accurate assessment of higher quality embryos.

Alkyne-Modulated Surface-Enhanced Raman Scattering-Palette for Optical Interference-Free and Multiplex Cellular Imaging.

The alkyne tags possess unique interference-free Raman emissions but are still hindered for further application in the field of biochemical labels due to its extremely weak spontaneous Raman scattering. With the aid of computational chemistry, herein, an alkyne-modulated surface-enhanced Raman scattering (SERS) palette is constructed based on rationally designed 4-ethynylbenzenethiol derivatives for spectroscopic signature, Au@Ag core for optical enhancement and an encapsulating polyallylamine shell for protection and conjugation. Even for the pigment rich plant cell (e.g., pollen), the alkyne-coded SERS tag can be highly discerned on two-dimension distribution impervious to strong organic interferences originating from resonance-enhanced Raman scattering or autofluorescence. In addition, the alkynyl-containing Raman reporters contribute especially narrow emission, band shift-tunable (2100-2300 cm(-1)) and tremendously enhanced Raman signals when the alkynyl group locates at para position of mercaptobenzene ring. Depending on only single Raman band, the suggested alkyne-modulated SERS-palette potentially provides a more effective solution for multiplex cellular imaging with vibrant colors, when the hyperspectral and fairly intense optical noises originating from lower wavenumber region (<1800 cm(-1)) are inevitable under complex ambient conditions.

Raman scattering properties of human pterygium tissue

Pterygia, caused by fibrovascular growth of conjunctiva, are a common ophthalmic disease. However, the molecular composition of pterygium tissue has not been completely understood, and therefore the aim of this study is to investigate the spectroscopic differences between normal human bulbar conjunctiva and human pterygium tissue using a confocal Raman system. The high signal-to-noise ratio spectra from pterygium and conjunctiva tissue were obtained by this technique without any sample preparation and the time of detection required less than 3 min. Comparing Raman spectra of two types of tissue, there are obvious changes, including intensity decrease at approximately 1585 cm(-1) and intensity increase at approximately 1748, 1156, and 1521 cm(-1) with the lesion of conjunctiva. Additionally, the amide I vibrational mode of proteins in conjunctiva is significantly different than that in pterygium. The use of pathology, immunology, and the peroxidation of the lipids in conjunction with the Raman results indicate that the presence of additional elastic fibers, mast cells, and lymphocytes in pterygium, as compared with normal bulbar conjunctiva, have fewer unsaturated fat acids. The present study demonstrates that Raman spectroscopy can be potentially applied to diagnose pterygia clinically.