Label-free surface enhanced Raman spectroscopy analysis of blood serum via coffee ring effect for accurate diagnosis of cancers.

Surface-enhanced Raman spectroscopy (SERS) is considered as an ultrasensitive, non-invasive as well as rapid detection technology for cancer diagnosis. In this study, we developed a novel blood serum analysis strategy using coffee ring effect-assisted label-free SERS for different types of cancer screening. Additionally, the pretreated Ag nanoparticles (Ag NPs) were mixed with the serum from liver cancer patients (n = 40), prostate cancer patients (n = 32) and healthy volunteers (n = 30) for SERS measurement. The droplets of Ag NPs-serum mixture formed the coffee ring on the peripheral after air-drying, and thus extremely enhancing Raman signal and ensuring the stability and reliability of SERS detection. Partial least square (PLS) and support vector machine (SVM) algorithms were utilized to establish the diagnosis model for SERS spectra data classifying, yielding the high diagnostic accuracy of 98.04% for normal group and two types of cancers simultaneously distinguishing. More importantly, for the unknown testing set, an ideal diagnostic accuracy of 100% could be achieved by PLS-SVM algorithm for differentiating cancers from the normal group. The results from this exploratory work demonstrate that serum SERS detection combined with PLS-SVM diagnostic algorithm and coffee ring effect has great potential for the noninvasive and label-free detection of cancer.

Precise closure of single blood vessels via multiphoton absorption-based photothermolysis.

We report a novel approach to selectively close single blood vessels within tissue using multiphoton absorption-based photothermolysis (multiphoton photothermolysis) without the need of exogenous agents. The treatment process is monitored by in vivo reflectance confocal microscopy in real time. Closure of single targeted vessels of varying sizes ranging from capillaries to venules was demonstrated. We also demonstrated that deeply situated blood vessels could be closed precisely while preserving adjacent overlying superficial blood vessels. In vivo confocal Raman spectroscopy of the treatment sites confirmed vessel closure as being mediated by local coagulative damage. Partial vessel occlusion could be achieved, and it is accompanied by increased intravascular blood cell speed. Multiphoton photothermolysis under real-time reflectance confocal imaging guidance provides a novel precision medicine approach for noninvasive, precise microsurgery treatment of vascular diseases on a per-vessel/per-lesion basis. The method could also be used for building ischemic stroke models for basic biology study.

Effects of different-intensity laser acupuncture at two adjacent same-meridian acupoints on nitric oxide and soluble guanylate cyclase releases in human.

OBJECTIVES: The aim of this study was to detect the influences of LA at nonacupoint and two adjacent acupoints of pericardium meridian on the releases of NO and sGC in 20 healthy subjects. METHODS: Different intensities (12, 24, 48 mW) of infrared laser were used for irradiating Jianshi (PC5), Ximen (PC4) acupoints and nonacupoint for 20, 40 minutes, respectively. Semi-circular tubes were taped to the skin surface and filled with NO-scavenging compound for 20 minutes to capture NO and sGC, which were measured using spectrophotometry in a blinded fashion. RESULTS: As the increase in the intensity of LA stimulation, the levels of NO releases over acupoints all were significantly increased, NO releases in nonacupoints following the same treatment only changed slightly, sGC amounts were observably enhanced over acupoints, but did not any change in nonacupoint area. Different intensities of LA treatments can sensitively affect the NO and sGC releases over acupoints. This indicated that LA-induced releases of the NO and sGC were specific to acupoints. CONCLUSIONS: This is the first evidence reporting that LA induced significant elevations of NO-sGC releases over acupoints, and the enhanced signal molecules contribute to local circulation, which improves the beneficial effects of the therapy.

Changes in Nitric Oxide Releases of the Contralateral Acupoint during and after Laser Acupuncture at Bilateral Same-Name Acupoints in Human.

OBJECTIVE: The purpose of the study was to examine the effects of laser acupuncture (LA) at right Neiguan (RPC6)/left Neiguan (LPC6) acupoints on the releases of nitric oxide (NO) in the treated and contralateral/nontreated PC6, compared to the nonacupoint control area. METHODS: 24 mW LA at RPC6, LPC6, and nonacupoint in 22 healthy subjects for 40 min: sterilized dialysis tube was taped to the nontreated PC6/nonacupoint during the treatment and immediately taped to the treated and nontreated PC6/nonacupoint after LA removal. NO-scavenging compound was injected into the tube for 40 min to absorb the molecular which was tested by spectrophotometry in a blinded fashion. RESULTS: LA-induced NO releases over PC6 acupoints for the nontreated and treated sides all significantly increased after LA removal, but for the nontreated acupoints they did not change during LA stimulation. LA at RPC6 induced the more release of the NO at contralateral side than stimulating LPC6, but not on nonacupoints. The results suggest that LA-induced NO release over contralateral acupoint and NO release resulting from the lateralized specificity all are different and specific to the acupoint within different time course. CONCLUSIONS: LA-evoked NO release over acupoints could improve the neurogenic, endothelial activity of the vessel wall to further facilitate microcirculation.

A Correlation Study between Two Adjacent Same-Meridian Acupoints after Laser-Needle Acupuncture with Optical Coherence Tomography and Diffuse Reflectance Spectra.

This study is to investigate the correlations among Sanjian (LI3), Hegu (LI4), and Yangxi (LI5) acupoints and their corresponding nonacupoints on the Yangming Large Intestine Meridian of Hand before and after laser irradiation using optical coherence tomography (OCT) and diffuse reflectance spectra. The experiment was conducted on 10 healthy people. A 658 nm laser with 50 mW output power was used for irradiating LI4, LI5 acupoints and their corresponding nonacupoints. As to LI4 acupoint with laser irradiation for duration of 15 or 45 minutes, the OCT backscattered light intensities of LI4 and LI5 acupoints increased significantly, and the reflectance intensities (RIs) of the LI3, LI4, and LI5 acupoints decreased significantly. As to LI5 acupoint with laser irradiation for duration of 15 or 45 minutes, the changes of OCT backscattered light intensities of the corresponding irradiated acupoint and LI4 acupoint increased significantly, and the RIs decreased significantly. However, the OCT backscattered light intensities and RIs for their nonacupoints were almost not changed. The results show that an association exists between two adjacent same-meridian acupoints on the same meridian after laser-needle acupuncture to some extent.

In vitro investigation on Ho:YAG laser-assisted bone ablation underwater.

Liquid-assisted hard tissue ablation by infrared lasers has extensive clinical application. However, detailed studies are still needed to explore the underlying mechanism. In the present study, the dynamic process of bubble evolution induced by Ho:YAG laser under water without and with bone tissue at different thickness layer were studied, as well as its effects on hard tissue ablation. The results showed that the Ho:YAG laser was capable of ablating hard bone tissue effectively in underwater conditions. The penetration of Ho:YAG laser can be significantly increased up to about 4 mm with the assistance of bubble. The hydrokinetic forces associated with the bubble not only contributed to reducing the thermal injury to peripheral tissue, but also enhanced the ablation efficiency and improve the ablation crater morphology. The data also presented some clues to optimal selection of irradiation parameters and provided additional knowledge of the bubble-assisted hard tissue ablation mechanism.

[Comparative study of time-correlated temperature and back-scattered light intensity for human Hegu acupoint and non-acupoint tissue irradiated by near-infrared laser].

Characteristics and differences of temperature and back-scattered light intensity in different depths of 0.2, 0.4, 0.6, 0.8 and 1 mm for both human Hegu acupoint and non-acupoint tissue irradiated by 808 nm diode laser at the different power of 15, 25 and 35 mW were studied. The temperature and the back-scattered light intensity in different depths of 0.2, 0.4, 0.6, 0.8 and 1 mm for human Hegu acupoint and non-acupoint tissue were measured by using the infrared thermography and optical coherence tomography. The result shows few differences in the temperature and the back-scattered light intensity of human Hegu acupoint and non-acupoint tissue before irradiation. The temperature and back-scattered light intensity of Hegu acupoint and the non-acupoint after irradiation were significantly higher, and the temperature and back-scattered light intensity of Hegu acupoint significantly were higher than the non-acupoint areas. At 0-40 min after the irradiation, the temperature and back-scattered light intensity of Hegu acupoint and the non-acupoint area will fluctuate and gradually decrease with the passage of time. From the results above, it is clearly seen that Hegu acupoint is different from non-acupoint both in the back-scattered light intensity and temperature after irradiation, and Hegu acupoint is more sensitive to laser irradiation than non-acupoint tissue.

[Comparative study of reflectance spectroscopy of human laogong acupoint and non-acupoint tissues irradiated by near-infrared laser].

Characteristics and differences of reflectance spectroscopy of human Laogong acupoint and non-acupoint tissues before and after irradiation by different power of laser were studied in the spectral range from 400 to 1 000 nm. A wavelength 808 nm semiconductor laser was used for irradiation at the power of 20, 50 and 100 mW for ten minutes. Reflectance spectra of human Laogong acupoint and non-acupoint tissues were measured by using an AvaSpec-2048 optical fiber spectroscopy with an integrating sphere attachment. The result shows that before irradiation the shape of the reflectance spectra of Laogong acupoint and non-acupoint is similar, they have the same troughs at 423, 544, 577 and 980 nm, and the reflectance for Laogong acupoint and non-acupoint at these wavelengths is 17.1%, 26.1%, 25.9% and 35.0%, and 17.1%, 27.6%, 28.1% and 36.5% respectively. But from 475 to 1 000 nm, the reflectance of Laogong acupoint is smaller than that of non-acupoint. After being irradiated by semiconductor laser at the power of 20, 50 and 100 mW, there is a very significant decrease in the reflectance of Laogong acupoint compared to that before irradiation, and the higher the power, the lower the reflectance. But there is just a small decrease in the reflectance for non-acupoint compared to that before irradiation. From the above results, it is clearly seen that Laogong acupoint is different from non-acupoint on reflectance spectroscopy, and Laogong acupoint is more sensitive to laser irradiation than non-acupoint tissue.

Differences in optical transport properties between human meridian and non-meridian.

This study is to present a new scheme for the detection of human meridian system non-invasively. The optical transport properties along the pericardium meridian and a non-meridian path about 1 cm away from the meridian were measured non- invasively on 20 healthy people in vivo. 633 nm, 658 nm and 785 nm red lasers were used for irradiation, and the diffuse light emittances at different points on meridian and non-meridian directions were collected respectively and compared. Our study suggested that the light propagation characteristics along both the meridian and non-meridian directions conformed to the Beer's exponential attenuation law. Statistical analysis of the results suggested that the optical properties of human meridian differ from those of the surrounding tissue (p < 0.05), and the light attenuation is less when propagating along the pericardium meridian than along the non-meridian direction. These findings not only confirmed the objective existence of acupuncture meridians, but also shed new light on the understanding of meridians.

Appearance of human meridian-like structure and acupoints and its time correlation by infrared thermal imaging.

The meridians and acupoints of human bodies at natural condition are investigated among 30 healthy volunteers by infrared thermal imaging technique. The results give clear evidence of the existence of infrared radiant tracks along human meridian courses. The time dependent evolution of the infrared radiant track is observed for the first time. The time rhythm of acupoints is also studied. Our findings not only support the view that infrared radiant tracks along human meridian courses is a normal vital and physiological phenomenon appearing in human beings, but also offer a potential method for noninvasive diagnostic by studying the physiological function and pathological change of meridians or acupoints by means of thermography.

Monte Carlo simulation of cutaneous reflectance and fluorescence measurements--the effect of melanin contents and localization.

Melanin content and distribution in skin were studied by examining a patient with white, brown and blue skin tones expressed on skin affected by vitiligo. Both diffuse reflectance and autofluorescence spectra of the three distinction skin sites were measured and compared. Monte Carlo simulations were then performed to help explain the measured spectral differences. The modeling is based on a six-layer skin optical model established from published skin optical parameters and by adding melanin content into different locations in the model skin. Both the reflectance and fluorescence spectra calculated by Monte Carlo (MC) simulation were approximately in agreement with experimental results. The study suggests that: (1) trichrome vitiligo skin may be an ideal in vivo model for studying the effect of skin melanin content and distribution on skin spectroscopy properties. (2) Based on the skin optical model and MC simulation, the content and distribution of melanin in skin, or other component of skin could be simulated and predicted. (3) Both reflectance and fluorescence spectra provided information about superficial skin structures but fluorescence spectra are capable of providing information from deeper cutaneous structures. (4) The research method, including the spectral ratio method, the method of adding and modifying the melanin content in skin optical models, and MC simulation could be applied in other non-invasive optical studies of the skin.