白皮书
医疗器械挑战：
异种金属细丝焊接
综述
不锈钢或镍钛合金是医疗器械中常用的材料。 相干公司的应用专家针对这种难以焊接的细丝材料，开发了一种安全焊接的工艺。 该过程甚至可以在不破坏任何塑料涂层的情况下进行
“在激光器中集成快速功率调制，可缩短实验时间、提高性能并降低使用成本。”
医疗器械的微焊接
激光焊接广泛用于制造医疗器械，如植入物或内窥镜设备，通常用于连接精密部件。 如果所需焊接的部件是由难以焊接的材料制成的非常细的细丝，这会变得非常有挑战性。 典型材料包括不锈钢、镍钛合金或钛，因为它们具有生物相容性、耐腐蚀且易于灭菌。 如果要进行异种材料连接，将变得更加困难。 激光器是此任务的首选工具（如果不是唯一工具）。 此类材料的焊接不得损害其所需的物理特性，例如镍钛合金的记忆特性。
连接细丝时，要求实现零间隙；它们必须精确地相互对接，因为不使用填充金属，即使是很小的间隙也可能太大而无法实现可靠的连接。 因此，激光光束也必须精确聚焦。 虽然第一个问题可以通过夹具得到解决，但后一个任务需要通过自动视觉系统来对齐激光焦点位置。
电光调制
电光调制器 (EOM) 利用普克尔斯效应，通过对光束施加相位延迟来调制激光功率。 在电光调制器中，通过施加电场，在非中心对称的晶体中诱发双折射。 EOM也包括偏振分析仪。
纵向设计的普克尔斯盒，可以在长度较短的晶体中实现大孔径的光束输出。 在这种情况下，典型的 ½ 半波电压（即偏振旋转 90 度所需的电压）约为 6 kV，这在双光子显微镜的速度和占空比下难以实现。 大多数双光子显微镜采用横向电场设计，使用更长的晶体，这会显著降低半波电压。 这种设计里面通常配置两块以上的晶体，位置可以相对旋转，以降低电压并补偿热负载效应。
通过晶体校准和偏移（偏置）电压调整来优化脉冲对比度，以获得优异的图像对比度。
Figure 1: Simplified representation of transverse Pockels cell operation. Transmission through the analyzer is modulated by adjustment of the applied electric field.
普克尔斯盒由于设计比较简单，在双光子显微成像中得到了广泛应用，尤其适用于常见的激光波长，用户自己搭建的双光子系统。
例如，磷酸二氘钾 (KD*P) 普克尔盒可为 1100 nm 的 双光子成像 提供出色的透射率、速度和对比度特性，并提供适中的激光功率。 此外，KD*P 具有很低的群速度色散特性，从而显著减小群延迟色散 (GDD)。 对于没有色散预补偿以及波长调谐范围有限的超快激光器（例如钛宝石激光器），KD*P 普克尔斯盒是一种很好的选择。
Figure 2: Typical Pockels cell deployment on a two-photon microscope. The EOM is just below the user’s right hand. P hotograph courtesy Packer Lab, University of Oxford, UK.
声光调制
声光调制器 (AOM) 包含一个透明晶体或玻璃，里面附有一个压电换能器。 施加到换能器的射频 (RF) 会诱发产生声波，使晶体介质密度呈现周期性变化，折射率也发生相应的周期性变化，这样声光介质在超声场的作用下，就变成了一个等效的相位光栅。 光经过晶体后会产生布拉格衍射。
光学上升/下降时间与声波穿过激光束时间成正比，因此可以通过减小晶体中的光束宽度来获得最快速度。
晶体中的零级和一级衍射间的角度(θS) 以及到工作平面的距离，决定了AOM的分辨率和对比度。
“对于680-1300 nm 波长 2 W以上的一体化可调谐激光器，需要一种新型的激光调制方法。”
The most common AOM material used in two-photon microscopy is tellurium dioxide, (TeO2). This material demonstrates excellent diffraction efficiency and high-power handling over a wide wavelength range. Maximum transmission efficiencies are achieved with modest RF powers in the order of 30 dBm.
TeO2 AOMs are usually configured in the Bragg interaction regime which offers best diffraction efficiency into the first order, with higher orders destructively annihilated. Note that to achieve high efficiency with minimal RF power levels, crystal lengths of >1 cm are needed, resulting in non-negligible group delay dispersion (GDD). Considering also the dispersion of other downstream optics and especially the objective lens, AOM-based microscope systems benefit by being partnered with lasers equipped with dispersion precompensation, in order to maintain the shortest pulses at the sample plane.
Deployment of AOMs for tunable lasers requires both careful optical and control electronics design. Since the separation angle (θS) is dependent on both the RF drive frequency (ie grating period) and the laser wavelength, the RF drive frequency must be carefully calibrated to ensure minimal pointing change when tuning the laser wavelength. Additionally, the maximum diffraction efficiency is achieved at different RF powers for different wavelengths. The more onerous integration effort resulting from the need to carefully control the RF frequency and power, and manage a relatively large GVD in a tunable imaging system has hitherto limited AOM usage in many home-builder and custom settings, despite the excellent performance characteristics.
Modulation in Widely Tunable Lasers
The advent of one-box widely tunable lasers, in the order of 680 - 1300 nm and with powers in excess of 2 W, requires a new regime of performance and integration effort for laser modulation.
The typically used KD*P Pockels cells display thermal blooming effects at high power, which is deleterious to beam pointing, beam waist integrity and lifetime. Longer wavelengths further present higher drive voltage and contrast challenges. Lithium Tantalate is a viable EOM material for wider tuning, however the group delay dispersion of commercial units is higher than the correctable range of dispersion-compensated lasers, thus resulting in longer pulses and reduced peak power, detrimental to efficient imaging.
As previously discussed, despite having potential cost and performance benefits, AOM-based solutions require a high degree of optical design and electronics control expertise to deploy, often not readily available in many bioimaging facilities. That said, AOM solutions are commercially available as an integrated solution from some microscope vendors.
In 2017, Coherent recognized that both users and the microscope industry would benefit from a turn-key solution integrating the AOM modulation with the laser sources. Building on the expertise gleaned from integrated AOM solutions in industrial ultrafast machining lasers, Coherent developed Total Power Control (TPC) – as a fully integrated option for the Chameleon Discovery Laser.
Total Power Control, available on Chameleon Discovery NX, provides high contrast (>1000:1) and high speed (<1 μs rise time) modulation across a full octave tuning range of 660 nm to 1320 nm in a hands-free automated package.
Figure 3: Chameleon Discovery NX TPC and Typical Maximum Output Power after modulation.
All the taxing requirements for RF frequency and power calibration and adjustment are programmed internally to the laser, so all the user or microscope integrator need to provide is the set wavelength and power level required.
Since AOMs are very cost effective, the fixed wavelength 1040 nm output of Chameleon Discovery NX TPC is also equipped with its own, dedicated AOM and driver.
Power can be conveniently controlled by either serial/USB command or by fast analog control input.
Figure 4: The supplied GUI can be used to directly change the output power
or the user can supply an additional fast analog input for flyback blanking
and fast dither control.
Future Trends
As the scope of two-photon imaging techniques drives further into OEM and preclinical applications, the demand for single wavelength, cost effective femtosecond sources is growing. The Axon series of compact ultrafast sources addresses perfectly these requirements.
From product concept stage, TPC capability was integrated into the Axon design to simplify deployment into new microscope designs and applications. This brings ultimate integration convenience for applications where the two-photon microscope system is part of a movable diagnostic, clinical or hi gh-throughput screening device rather than a pure research instrument.
In cutting edge neuroscience research, high-power lasers are playing a key role in all-optical in-vivo imaging techniques, using optogenetic stimulation (Yuste, 2012). Multiple tens of Watts of laser power are split with spatial light modulators (SLMs) into individual beamlets able to individually address tens or hundreds of neurons. This method of optical control requires short and tailorable burst of pulses. High-power fiber lasers like the Coherent Monaco provide the flexibility demanded by these applications thanks to the all fiber design format. The resulting high average power, high energy laser requirements and the need to switch the stimulation beam on a s ub millisecond timescale presents a specific challenge for incumbent Pockels cell technology. To this end, AOM technology has been fully integrated into Monaco, for exquisite pulse control, simplified microscope design and increased imaging system reliability.
Figure 5: An example of high contrast, fast frame rate calcium imaging enabled by Discovery TPC. (Overlay of neurons expressing RCaMP1.07 excited at 1100 nm (red) and astrocytes expressing GCaMP6s excited at 940 nm (green), in-vivo, mouse. Excitation source Chameleon Discovery TPC. Figure credit Weber Lab, University of Zurich).
Figure 6: All Axon lasers offer TPC functionality as an option, within a common form factor.
Figure 7: Chameleon Discovery NX TPC partnered with Axon 920 TPC. TPC enables simplified optical layouts and saves valuable table space. Photo courtesy Neil Merovitch, Hospital for Sick Children, Toronto.
Summary
In this technical note, we have discussed the two leading approaches to modulate the laser output power of femtosecond lasers used in two-photon microscopy – Electro-Optic and Acousto-Optic modulation. Most “home-builders” have so far chosen EOMs because of the relative simplicity of deploying this high-voltage powered device in the optical path. Various microscope vendors offer either EOMs or AOMs partially integrated in their laser delivery train, with their software architecture controlling both microscope and laser. Using its manufacturing experience with high power fiber lasers designed for 24/7 manufacturing environments, Coherent recognized that the advantages of the AOM approach in term of size, cost, speed and overall performance would also fulfil two-photon imaging applications. By integrating the sophisticated control of the AOM within the laser software and hardware architecture of Discovery NX, Axon and Monaco, two-photon users – both home builders and scope companies - benefit from a greatly simplified and easier to control optical set-up, for applications ranging from advanced neuroscience to medical diagnostics.