Nedosekin Dmitry A, Sarimollaoglu Mustafa, Shashkov Evgeny V, Galanzha Ekaterina I, Zharov Vladimir P
Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR, 72205, USA.
Opt Express. 2010 Apr 12;18(8):8605-20. doi: 10.1364/OE.18.008605.
In vivo photoacoustic (PA) flow cytometry (PAFC) has great potential for detecting disease-associated biomarkers in blood and lymph flow, as well as real-time control of the efficacy of photothermal (PT) and other therapies through the counting of circulating abnormal objects. We report on a high speed PAFC with a Yb-doped fiber laser having a 0.5-MHz pulse repetition rate at a wavelength of 1064 nm, pulse width of 10 ns, and energy up to 100 microJ. This is the first biomedical application of PA and PT techniques operating at the highest pulse repetition rate of nanosecond lasers that provide 100-fold enhancement in detection speed of carbon nanotube clusters, as well as real-time monitoring of the flow velocity of individual targets through the width of PA signals. The laser pulse rate limits for PT and PA techniques depending on the sizes of laser beam and targets and flow velocity are discussed. We propose time-overlapping mode and generation of periodic nano- and microbubbles as PA-signal and PT-therapy amplifiers, including discrimination of small absorbing targets among large ones. Taking into account the relatively low level of background signals from most biotissues at 1064 nm, our data suggest that a nanosecond Yb-doped fiber laser operating at high pulse repetition rate could be a promising optical source for time-resolved PA and PT cytometry, imaging, microscopy, and therapy, including detection of nanoparticles and cells flowing at velocities up to 2.5 m/s.
体内光声（PA）流式细胞术（PAFC）在检测血液和淋巴流动中与疾病相关的生物标志物，以及通过计数循环异常物体对光热（PT）和其他疗法的疗效进行实时控制方面具有巨大潜力。我们报道了一种高速PAFC，它采用了掺镱光纤激光器，该激光器在波长1064nm处的脉冲重复频率为0.5MHz，脉冲宽度为10ns，能量高达100微焦。这是PA和PT技术在生物医学领域的首次应用，该技术以纳秒激光器的最高脉冲重复频率运行，能使碳纳米管簇的检测速度提高100倍，还能通过PA信号的宽度对单个目标的流速进行实时监测。讨论了PT和PA技术的激光脉冲速率限制，这取决于激光束和目标的尺寸以及流速。我们提出了时间重叠模式以及生成周期性纳米和微气泡作为PA信号和PT治疗放大器，包括在大的吸收目标中区分小的吸收目标。考虑到大多数生物组织在1064nm处的背景信号相对较低，我们的数据表明，以高脉冲重复频率运行的纳秒掺镱光纤激光器可能是用于时间分辨PA和PT细胞术、成像、显微镜检查和治疗的有前途的光源，包括检测流速高达2.5m/s的纳米颗粒和细胞。
