Author Affiliations
Abstract
1 School of Semiconductor Science and Technology, South China Normal University, Guangzhou 510631, P. R. China
2 Publications Department, Optica, 2010 Massachusetts Avenue NW, Washington, DC 20036, USA, MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, P. R. China
3 The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, P. R. China
4 Tsinghua University, Shenzhen 518055, P. R. China
5 Fujian Normal University, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education of China, Fuzhou 350007, P. R. China
In this paper, optical coherence tomography (OCT) and surface-enhanced Raman spectroscopy (SERS) were used to characterize normal knee joint (NKJ) tissue and knee osteoarthritis (KOA) tissue ex vivo. OCT images show that there is a clear hierarchical structure in NKJ tissue, including surface layer, transitional layer, radiation layer and cartilage matrix calcification layer tissue structure, while the hierarchical structure of KOA tissue is not clear and unevenly distributed, and the pathological tissues at different stages also show significant differences. SERS shows that NKJ tissue and mild osteoarthritic knee cartilage (MiKOA) tissue have strong characteristic Raman peaks at 964, 1073 (1086), 1271, 1305, 1442, 1660 and 1763cm?1. Compared with the Raman spectrum of NKJ tissue, the Raman characteristic peaks of MiKOA tissue have some shifts, moving from 1073cm?1 to 1086cm?1 and from 1542cm?1 to 1442cm?1. There is a characteristic Raman peak of 1271cm?1 in MiKOA tissue, but not in NKJ tissue. Compared with NKJ tissue, severely degenerated cartilage (SdKOA) tissues show some new SERS peaks at 1008, 1245, 1285, 1311 and 1321cm?1, which are not seen in SERS spectra of NKJ tissue. Principal component analysis (PCA) was used to analyze the Raman spectra of 1245–1345cm?1 region. The results show that PCA can distinguish NKJ, MiKOA and SdKOA tissues and the accuracy is about 90%. These results indicate that OCT can clearly distinguish NKJ, MiKOA, moderate osteoarthritic knee cartilage (MoKOA) and SdKOA tissue, while SERS can provide further judgment basis. The results also prove that the contents of protein and polysaccharide in knee tissue are changed during the pathological process of knee tissue, which is the cause of pain caused by poor friction in knee joint during movement.In this paper, optical coherence tomography (OCT) and surface-enhanced Raman spectroscopy (SERS) were used to characterize normal knee joint (NKJ) tissue and knee osteoarthritis (KOA) tissue ex vivo. OCT images show that there is a clear hierarchical structure in NKJ tissue, including surface layer, transitional layer, radiation layer and cartilage matrix calcification layer tissue structure, while the hierarchical structure of KOA tissue is not clear and unevenly distributed, and the pathological tissues at different stages also show significant differences. SERS shows that NKJ tissue and mild osteoarthritic knee cartilage (MiKOA) tissue have strong characteristic Raman peaks at 964, 1073 (1086), 1271, 1305, 1442, 1660 and 1763cm?1. Compared with the Raman spectrum of NKJ tissue, the Raman characteristic peaks of MiKOA tissue have some shifts, moving from 1073cm?1 to 1086cm?1 and from 1542cm?1 to 1442cm?1. There is a characteristic Raman peak of 1271cm?1 in MiKOA tissue, but not in NKJ tissue. Compared with NKJ tissue, severely degenerated cartilage (SdKOA) tissues show some new SERS peaks at 1008, 1245, 1285, 1311 and 1321cm?1, which are not seen in SERS spectra of NKJ tissue. Principal component analysis (PCA) was used to analyze the Raman spectra of 1245–1345cm?1 region. The results show that PCA can distinguish NKJ, MiKOA and SdKOA tissues and the accuracy is about 90%. These results indicate that OCT can clearly distinguish NKJ, MiKOA, moderate osteoarthritic knee cartilage (MoKOA) and SdKOA tissue, while SERS can provide further judgment basis. The results also prove that the contents of protein and polysaccharide in knee tissue are changed during the pathological process of knee tissue, which is the cause of pain caused by poor friction in knee joint during movement.
Optical coherence tomography surface-enhanced Raman spectroscopy knee osteoarthritis 
Journal of Innovative Optical Health Sciences
2022, 15(5): 2250027
许杨 1,2周冲琪 1,3,*何永红 1,2,**
作者单位
摘要
1 清华大学深圳国际研究生院, 光学成像与传感研究所, 深圳市微创医疗技术重点实验室, 广东 深圳 518055
2 清华大学深圳清华国际研究生院, 生物制药与卫生工程研究所, 广东 深圳 518055
3 清华大学物理系, 北京 100084
弱值放大技术由于“异常”的放大效应而被广泛地应用在微小物理效应的测量和高精度计量学中。研究表明,弱值放大能够有效抑制技术噪声和提高系统的分辨率。本文介绍了弱值放大技术的原理和常见的系统构建,简述了弱值放大在生物、材料和化学等领域的应用现状,并对弱值放大技术的发展方向进行了展望。
测量 弱值放大 高精度测量 光束的横向偏移 频移 
中国激光
2021, 48(15): 1504003
Author Affiliations
Abstract
1 Shenzhen Key Laboratory for Minimal Invasive Medical Technologies Graduate School at Shenzhen Tsinghua University, Shenzhen 518055, P. R. China
2 Department of Biomedical Engineering Tsinghua University, Beijing 100084, P. R. China
3 Center of Precision Medicine and Healthcare Tsinghua-Berkeley Shenzhen Institute, Shenzhen 518055, P. R. China
4 Shenzhen Wisonic Medical Technology Co., Ltd. Taoyuan Street, Nanshan District, Shenzhen 518055, P. R. China
We established a photoacoustic imaging (PAI) system that can provide variable gain at different depths. The PAI system consists of a pulsed laser with an optical parametric oscillator working at a 728 nmwavelength and an imaging-acquisition-and-processing unit with an ultrasound transducer. Avoltage-controlled attenuator was used to realize variable gain at different depths when acquiring PAI signals. The proof-of-concept imaging results for variable gain at different depths were achieved using specific phantoms. Both resolution and optical contrast obtained through the results of variable gain for a targeted depth range are better than those of constant gain for all depths. To further testify the function, we imaged the sagittal section of the body of in vivo nude mice. In addition, we imaged an absorption sample embedded in a chicken breast tissue, reaching a maximum imaging depth of ~4.6 cm. The results obtained using the proposed method showed better resolution and contrast than when using 50 dB gain for all depths. The depth range resolution was ~1 mm, and the maximum imaging depth of our system reached ~4.6 cm. Furthermore, blood vessels can be revealed and targeted depth range can be selected in nude mice imaging.
Photoacoustic imaging variable gain imaging depth 
Journal of Innovative Optical Health Sciences
2018, 11(5): 1850022
关添 1,2,*李尧 1,2杨木群 1,2何永红 2
作者单位
摘要
1 清华大学生物医学工程系, 北京 100084
2 清华大学深圳研究生院, 深圳微创医学技术重点实验室, 广东 深圳 518055
目的: 本文设计了一套光声成像(photoacoustic imaging,PAI)系统,由脉冲激光、阵列换能器、临床超声(ultrasound,US)主机、软件平台以及成像样品组成。系统的图像质量、最大成像深度等重要参数需通过实验进行确定。方法: 使用本系统对黑色头发丝横截面进行成像,比较、分析光声(photoacoustic,PA)信号幅值的半极大处全宽度以量化图像分辨率。此外,使用系统对特定的光吸收体和鸡胸肉组织进行成像,确定系统的成像深度。结果: 实验结果证明了PAI系统的实现,其PA图像的平均轴向和横向分辨率分别约为0.18 mm和1.44 mm,系统的最大成像深度达到4.6 cm。结论: 本PAI系统PA图像分辨率优于US主机获得的US图像分辨率,系统最大成像深度与其他国际研究组的系统成像深度的数量级一致。通过进一步优化与活体组织实验的开展,本PAI系统将有望实现临床成像诊断。
光声成像 图像分辨率 成像深度 photoacoustic imaging image resolution imaging depth 
激光生物学报
2018, 27(3): 211
Author Affiliations
Abstract
1 Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P. R. China
2 Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518055, P. R. China
Background: Infrared laser stimulation has been proposed as an innovative method to elicit an auditory nerve response. Most studies have focused on using long-wavelength infrared (> 980 nm) pulsed lasers with high water absorption coe±cients. This paper sought to assess whether a shortwavelength laser (465 nm) with an absorption coe±cient as low as 10-3 cm-1 would activate the auditory nerve and studied its potential mechanism. Method: Optical compound action potentials (OCAPs) were recorded when synchronous trigger laser pulses stimulate the cochlea before and after deafening, varying the pulse durations (from 800 μs to 3600 μs) and the amount of radiant energy (from 18.05 mJ/cm2 to 107.91 mJ/cm2). A thermal infrared imager was applied to monitor the temperature change of the guinea pig cochlea. Results: The results showed that pulsed laser stimulation at 465nm could invoke OCAPs and had a similar waveform compared to the acoustical compound action potentials. The amplitude of OCAPs had a positive correlation with the increasing laser peak power, while the latency of OCAPs showed a negative correlation. The imager data showed that the temperature in the cochlea rose quickly by about 0.3C right after stimulating the cochlea and decreased quickly back to the initial temperature as the stimulation ended. Conclusions: This paper demonstrates that 465-nm laser stimulation can successfully induce OCAPs outside the cochlea, and that the amplitude and latency of the invoked OCAPs are highly affected by laser peak power. This paper proposes that a photothermal effect might be the main mechanism for the auditory nerve response induced by short-wavelength laser stimulation.
Pulsed laser optical stimulation cochlear implant optical compound action potentials. 
Journal of Innovative Optical Health Sciences
2017, 10(5): 1743004
Author Affiliations
Abstract
1 Department of Ophthalmology, Shanxi Eye Hospital, Taiyuan 030002, P. R. China
2 Department of Ophthalmology, Xin Hua hospital affiliated to Shanghai, JiaoTong University School of Medicine, Shanghai 200092, P. R. China
3 Department of Ophthalmology, MinHang Hospital, Affiliated to Fudan University, Shanghai 201199, P. R. China
4 Shenzhen Key Laboratory for Minimal Invasive Medical Technologies, Institute of optical imaging and sensing, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P. R. China
5 Department of Physics, Tsinghua University, Beijing 100084, P. R. China
Surface functionalization of sensor chip for probe immobilization is crucial for the biosensing applications of surface plasmon resonance (SPR) sensors. In this paper, we report a method circulating the dopamine aqueous solution to coat polydopamine film on sensing surface for surface functionalization of SPR chip. The polydopamine film with available thickness can be easily prepared by controlling the circulation time and the biorecognition elements can be immobilized on the polydopamine film for specific molecular interaction analysis. These opera-tions are all performed under flow condition in the fluidic system, and have the advantages of easy implementation, less time consuming, and low cost, because the reagents and devices used in the operations are routinely applied in most laboratories. In this study, the specific absorption between the protein A probe immobilized on the sensing surface and human immunoglobulin G in the buffer is monitored based on this surface functionalization strategy to demonstrated its feasibility for SPR biosensing applications.
Surface plasmon resonance surface functionalization dopamine molecular interac-tion analysis 
Journal of Innovative Optical Health Sciences
2017, 10(2): 1650040
Author Affiliations
Abstract
1 MOE Key Laboratory of Laser Life Science & SATCM Third Grade Laboratory of Chinese Medicine and Photonics Technology, College of Biophotonics South China Normal University Guangzhou 510631, P. R. China
2 Department of Ophthalmology Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, P. R. China
3 Shenzhen Key Laboratory for Minimal Invasive Medical Technologies Graduate School at Shenzhen, Tsinghua University Shenzhen 518055, P. R. China
4 MOE Key Laboratory of Laser Life Science College of Biophotonics, South China Normal University Guangzhou 510631, P. R. China
We proposed a new saccharides sensor developed by symmetrical optical waveguide (SOW)- based surface plasmon resonance (SPR). This unique MgF2/Au/MgF2/Analyte film structure results in longer surface plasmon wave (SPW) propagation lengths and depths, leading to an increment of resolution. In this paper, we managed to decorate the dielectric interface (MgF2 layer) by depositing a thin polydopamine film as surface-adherent that provides a platform for secondary reactions with the probe molecule. 3-Aminophenylboronic acid (3-PBA) is chosen to be the saccharides sense probe molecule in the present work. The aqueous humor of Diabetes and Cataract patient whose blood glucose level is normal are analyzed and the results demonstrated that this sensor shows great potential in monitoring the blood sugar and can be adapted in the field of biological monitoring in the future.
Saccharides sensor surface plasmon resonance symmetrical optical waveguide 3-Aminophenylboronic acid dopamine 
Journal of Innovative Optical Health Sciences
2015, 8(2): 1550003
Author Affiliations
Abstract
1 Shenzhen Key Laboratory for Minimal Invasive Medical Technologies Graduate School at Shenzhen, Tsinghua University Shenzhen 518055, P. R. China
2 Department of Physics, Tsinghua University Beijing 100084, P. R. China
The contrast mechanism of different polarization imaging techniques for melanoma in mouse skin is studied using both experiments and Monte Carlo simulations. Total intensity, linear polarization difference imaging (DPI), degree of polarization imaging (DOPI) and rotating linear polarization imaging (RLPI) are applied and the relative contrasts of these polarization imaging methods between the normal and cancerous tissues are compared. A two-layer absorption-scattering model is proposed to explain the contrast mechanism of the polarization imaging for melanoma. By taking into account of both scattering of symmetrical and asymmetrical scatterers and absorption of inter-scatterer medium, the two-layer model reproduces the relative contrasts for polarization images observed in experiments. The simulation results also show that, the parameters of polarization imaging change more dramatically with the variation of absorption in the bottom layer than the top layer.
Polarization imaging melanoma two-layer model Monte Carlo simulation 
Journal of Innovative Optical Health Sciences
2014, 7(3): 1450009
CHAN DU 1,2LE LIU 3JUN GUO 1YONGHONG HE 1,*[ ... ]HUI MA 1,2
Author Affiliations
Abstract
1 Shenzhen Key Laboratory for Minimal Invasive Medical Technologies Graduate School at Shenzhen, Tsinghua University Shenzhen 518055, P. R. China
2 Department of Physics, Tsinghua University Beijing 100084, P. R. China
3 Laboratory of Advanced Power Source Graduate School at Shenzhen, Tsinghua University Shenzhen 518055, P. R. China
We developed a biosensor that is capable for simultaneous surface plasmon resonance (SPR) sensing and hyperspectral fluorescence analysis in this paper. A symmetrical metal-dielectric slab scheme is employed for the excitation of coupled plasmon waveguide resonance (CPWR) in the present work. Resonance between surface plasmon mode and the guided waveguide mode generates narrower full width half-maximum of the reflective curves which leads to increased precision for the determination of refractive index over conventional SPR sensors. In addition, CPWR also offers longer surface propagation depths and higher surface electric field strengths that enable the excitation of fluorescence with hyperspectral technique to maintain an appreciable signal-to-noise ratio. The refractive index information obtained from SPR sensing and the chemical properties obtained through hyperspectral fluorescence analysis confirm each other to exclude false-positive or false-negative cases. The sensor provides a comprehensive understanding of the biological events on the sensor chips.
Coupled plasmon waveguide resonance sensing hyperspectral fluorescence 
Journal of Innovative Optical Health Sciences
2014, 7(1): 1450017
E DU 1,2HONGHUI HE 1NAN ZENG 1CELONG LIU 1,2[ ... ]HUI MA 1,2,*
Author Affiliations
Abstract
1 Shenzhen Key Laboratory for Minimal Invasive Medical Technologies, Graduate School at Shenzhen Tsinghua University, Shenzhen 518055, P. R. China
2 Department of Physics, Tsinghua University, Beijing 100084, P. R. China
We developed a model to describe polarized photon scattering in biological tissues. In this model, tissues are simplified to a mixture of scatterers and surrounding medium. There are two types of scatterers in the model: solid spheres and infinitely long solid cylinders. Variables related to the scatterers include: the densities and sizes of the spheres and cylinders, the orientation and angular distribution of cylinders. Variables related to the surrounding medium include: the refractive index, absorption coefficient and birefringence. In this paper, as a development we introduce an optical activity effect to the model. By comparing experiments and Monte Carlo simulations, we analyze the backscattering Mueller matrix patterns of several tissue-like media, and summarize the different effects coming from anisotropic scattering and optical properties. In addition, we propose a possible method to extract the optical activity values for tissues. Both the experimental and simulated results show that, by analyzing the Mueller matrix patterns, the microstructure and optical properties of the medium can be obtained. The characteristic features of Mueller matrix patterns are potentially powerful tools for studying the contrast mechanisms of polarization imaging for medical diagnosis.
Mueller matrix scattering polarization tissue anisotropy 
Journal of Innovative Optical Health Sciences
2014, 7(1): 1350028

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