Between 2024 and 2025, Prof. Li actively participated in a series of outreach courses and seminars on optics and semiconductors. These events, hosted by prestigious institutions including the Chinese Academy of Sciences Shanghai Institute of Optics and Fine Mechanics, Suzhou University, Chinese Laser Press, and the High-End Chip Alliance of China, covered topics from system design to materials, processes, construction, and adjustment. While gaining hands-on expertise in establishing advanced research optical systems, Prof. Li identified exciting new research opportunities at the intersection of optics, cell biology, and materials science. This interdisciplinary approach promises synergistic benefits, leveraging the unique strengths of each field. In this post, I'll share key insights from this journey.
1. "Seeing is Believing": The Critical Lens for Evaluating Optical Imaging Systems.
Understanding how to select and evaluate imaging systems from the user perspective is critical. Guided by the principle that "seeing is believing," we rely extensively on optical imaging to capture high-quality 3D dynamics of microscopic structures in living cells and colloidal materials. Through hands-on experience, we've developed key insights for choosing optimal systems tailored to specific research needs. Since no single solution excels universally, we strategically balance core performance trade-offs: achieving clearer views (spatial resolution via confocal microscopy with high NA lenses, STED, SIM, single-molecule imaging, or TIRF), deeper penetration (imaging depth through multi-photon techniques), longer observation (minimizing phototoxicity with spinning disc confocal or lattice light sheet), faster capture (temporal resolution via spinning disc, light field, or parallel scanning), and wider coverage (field of view with light field systems). Each imaging platform serves distinct combinations of these requirements.
Successfully leveraging these technologies demands persistent curiosity about their principles coupled with rigorous evaluation. Never accept vendor-supplied images or videos at face value, regardless of their apparent quality, and reject viewing advanced equipment as a foolproof "paper printer". Maintain critical scrutiny before major decisions: insist on testing demonstration units with your own samples, thoroughly analyze the results, and incorporate all technical specifications, maintenance needs, and operational costs into your comparative assessment.
2. Fueling Optical and Semiconductor Innovation through Fundamental Surface Science.
My research in colloidal science is fundamentally driven by exploring the microscopic properties and mechanisms of materials and processes critical to the optics and semiconductor industries. I firmly believe that deep understanding of underlying principles is essential for optimizing synthesis and fabrication in applied settings. Research questions naturally emerge when oriented toward addressing major national strategic needs. Consider our ongoing systematic investigation of glass surfaces: realizing that manufacturing optical components—like photolithography lenses or microscope objectives—centers on surface processing, underscored the imperative to fundamentally understand glass surface properties. This involves deciphering complex, dynamic physical and chemical processes at the microscopic scale. This philosophy echoes industry leaders; ASML notes in their product introduction, “As lithography experts, we fundamentally understand the processes that influence chip patterning,” while Corning emphasizes, “Corning produces some of the world's purest glass... The equipment's top-notch quality stems directly from Corning's fundamental understanding of the materials and the science – chemistry and physics – that combine to make the process.“
To validate this perspective, we pursue detailed research questions: How do processing strategies (vapor deposition, thermal treatment) influence surface roughness? How are surface dynamics, mechanics, and structure coupled with the bulk to determine optical properties? How do atomic/molecular interactions govern kinetics like stress release, cracking, erosion, abrasion, or surface "healing"? What are the kinetic pathways of surface gelation/crystallization, and how do these phases affect properties? What defines the microscopic kinetics during polishing/grinding, where external perturbations (pressure, friction, hydrodynamics) interact with intrinsic surface properties? How does surface melting facilitate welding/grinding? How do the shape, size, and interactions of particles in colloidal polishing fluids govern atomic-level material removal? Could multi-mode treatments (thermal, ultrasound, EM fields) enhance polishing? How do coating processes alter surface structure/mechanics via atomistic interactions, determining coating efficacy? In nanofabrication, how do laser/electron beams alter glass microstructure during etching/drilling (TGV)? Could high-thermal-conductivity particle coatings aid localized crater formation? How does curvature alter microscopic structure and stress distribution? How do phonon behaviors differ in surface regions versus the bulk?
Addressing these questions requires condensed matter physics experiments—using in situ high-resolution TEM on real materials or fast confocal microscopy on model colloidal systems—coupled with designed processing techniques (e.g., thermal treatment, polishing). Proper exploration along this basic science trajectory will illuminate pathways to manufacture ultra-precision glass lenses with exceptional surface smoothness and tailored optical properties. Leveraging expertise in colloidal chemistry and physics positions us to achieve breakthroughs in surface processing protocols, polishing slurry formulations, multi-model (heat, flow, electromagnetics, mechanics, etc) coupling procedures, and photonic crystal waveguides. This philosophy—fueling high-end technology through rigorous basic science on core material properties and key processes—aligns with perspectives I shared at a recent semiconductor conference (see related news), which similarly emphasized crystalline materials.
3. Synergistic Advances: Laser Stimulation and Nanofabrication Empower Cell Biology and Materials Science.
Progress in optical and semiconductor technologies continuously unlocks new frontiers in basic cell research and materials science. Critically, exploring light-matter interactions—between light and cells or materials—reveals profound opportunities. Advanced optical manipulation tools (e.g., optical tweezers, femtosecond laser stimulation) enable in situ, real-time active perturbation of samples. This allows precise dissection of microscopic-level responses within biological or material systems upon external stimuli. For instance, achieving real-time holographic illumination at arbitrary 3D points could drive transformative leaps in optogenetics. These engineered platforms also serve to induce controlled microscopic perturbations within colloidal materials, probing their responses to mechanical, thermal, electromagnetic, or other stimuli with unprecedented precision. Simultaneously, nano/micro-fabrication techniques empower the construction of sophisticated physical environments for multicellular processes, creating biomimetic ex vivo microenvironments.
4. Cultivating Breakthroughs: The Bottom-Up Path to Advanced Optical Imaging.
Achieving transformative breakthroughs in high-end optical imaging systems requires recognizing them as integrated ecosystems where all critical components—from light sources, optical path design, and optomechanics to detectors, lenses, and software—must advance synergistically to optimize performance. This endeavor increasingly demands interdisciplinary collaboration, spanning biochemistry for enhancing sample fluorescence through engineered agents (antibodies, proteins, dyes, nanoparticles) and genetic techniques, to artificial intelligence for sophisticated image processing. Given the escalating complexity of modern systems, reverse engineering alone has become an inadequate strategy. Therefore, alongside conventional top-down design methodologies that begin with comprehensive system blueprints, I advocate for a parallel bottom-up development approach, after considering the underlying logic behind the development of advanced equipment. In this model, imaging systems are constructed organically around specific basic research questions, iteratively refined alongside scientific discoveries, and potentially commercialized through academia-industry partnerships.
This bottom-up strategy ensures continuous user-centric evaluation by researchers who possess intimate operational understanding, guaranteeing clarity of fundamental principles and exceptional extensibility. Crucially, scientists inherently pursue the highest technical specifications—their experimental success depends on equipment capable of revealing novel phenomena. Liberated from predetermined commercial constraints, system designs can evolve dynamically with scientific exploration, embodying an Olympic ethos of "Higher-Faster-Stronger" that fosters genuine innovation beyond imitation. While demanding patience and tolerance for scientific setbacks (distinct from ethical compromises), this process frequently yields conceptually novel architectures or unprecedented performance parameters, creating substantially higher value with higher economic efficiency than derivative products. The inherent trial-and-error of scientific exploration simultaneously cultivates exceptionally creative technical teams. Successful embodiments of this approach—such as compound-eye lenses inspired by Drosophila biology and liquid lenses leveraging soft matter wetting phenomena—demonstrate how interdisciplinary insights fuel revolutionary designs.
During commercialization, a virtuous cycle emerges: scientists articulate precise user-end requirements while industrial partners refine component quality to meet these challenges. Ultimately, the success of this bottom-up philosophy depends on cultivating a supportive ecosystem—one that deeply values intellectual contributions, actively discourages destructive competition, upholds rigorous collaboration standards, and resists pressures for premature publication. Only within such fertile ground can these user-driven innovations truly flourish and transform optical imaging capabilities.
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2024至2025年间，李教授积极参与了中国科学院上海光机所、苏州大学、中国激光杂志社及中国高端芯片联盟主办的系列光学与半导体前沿课程及研讨会。这些活动涵盖从系统设计到材料工艺、装调测试的全链条主题。在深入掌握先进科研光学系统搭建技术的过程中，李教授通过跨学科视角审视光学与细胞生物学、材料科学的结合点，发现了激动人心的新研究机遇——各领域优势的协同作用将催生突破性进展。本文将分享这一探索历程的核心洞见。
1. "眼见为实"：光学成像系统评估的批判性视角。
秉持"眼见为实"的原则，我们作为光学成像系统的深度用户，致力于捕捉活体细胞与胶体材料微观结构的高质量三维动态。基于终端用户经验，我们总结了选择适配研究需求的成像系统核心方法论：没有任何单一系统能胜任所有任务，关键在于平衡五大性能维度——更清晰（空间分辨率：高数值孔径共聚焦、STED/SIM超分辨、单分子成像与TIRF）、更深入（成像深度：多光子技术）、更长久（光毒性与稳定性：转盘共聚焦、晶格光片）、更快速（时间分辨率：转盘共聚焦、光场成像、并行扫描）及更宽广（视场范围：光场技术）。不同系统针对特定需求组合各具优势。
成功驾驭这些技术既需要保持对成像原理的好奇心，更需秉持批判性评估准则：切勿轻信供应商提供的图像视频，无论其表现多么惊艳；决不可将高端设备视为可盲目输出的"论文打印机"。重大决策前务必坚持严谨验证：要求演示机测试并使用自有样本实操，基于实测结果前瞻性规划，将全部技术细节与维护成本纳入综合对比考量。
2. 基础表面科学：驱动光学与半导体制造的创新引擎。
我结合胶体系统将研究聚焦于光学与半导体产业核心材料及工艺的微观特性与机制。我始终坚信，对基础机制的深刻认知指引着应用端合成与制造的优化。面向国家重大战略需求，科学问题自然涌现。以当前开展的玻璃表面系统性研究为例：当意识到制造光刻镜头或显微物镜等光学器件本质是对玻璃表面的加工时，我立即洞悉了从微观层面理解玻璃表面特性的迫切性——这涉及复杂而动态的物理化学过程。正如ASML在其产品介绍中所强调："作为光刻专家，我们从根本上理解影响芯片图形的工艺"；康宁同样指出："康宁通过一套看似与玻璃无关的工艺制造全球最纯净玻璃，设备的顶尖品质直接源于对材料及制造过程中化学与物理基础科学的深刻认知"。
为验证这一理念，我们提出系列研究命题：加工策略（气相沉积/热处理）如何影响玻璃表面粗糙度？表面动力学、力学与结构（如粗糙度）如何与体相耦合并决定光学特性？原子/分子相互作用如何调控表面残余应力释放、开裂、侵蚀、磨损及自修复的动力学？表面凝胶化/结晶的动力学路径及其对玻璃光学/力学性能的影响机制是什么？抛光/研磨过程中非平衡外扰（压力、摩擦、流体力学等）与玻璃本征属性（原子键合、粗糙度、体相耦合）如何微观互动？表面熔融如何促进焊接与研磨？胶体抛光液中颗粒形状/尺寸/相互作用如何决定原子级材料去除效率？多模式处理（热/超声/电磁场）能否协同提升抛光效果？涂层工艺如何通过表面原子与镀层材料的相互作用改变结构/力学性能并决定镀层效能？激光/电子束在玻璃蚀刻与穿孔（TGV）过程中如何改变表面微观结构？高导热颗粒镀层能否促进局部凹坑形成？曲率如何改变玻璃微观结构与应力分布？表面区域声子行为与体相有何差异？
解答这些问题需依托凝聚态物理实验——通过原位高分辨电镜观测真实材料，或利用快速共聚焦显微镜研究胶体模型体系，并耦合定制化加工工艺（如热处理、抛光）。沿着基础科学指明的方向探索，将助力开发超高表面平整度与定制光学性能的精密玻璃透镜制造方法。融合胶体化学与物理知识，我们有望在表面处理工艺、抛光浆料配方、多模态（热、流、电磁、力等）耦合工艺及光子晶体波导等领域实现突破。此观点与我参与的半导体会议（详见报道）主张高度一致——以深入系统的材料基础研究驱动高端技术革新，在晶体材料领域同样适用。
3. 协同跃迁：激光操控与纳米加工赋能生命与材料研究。
光学与半导体技术的进步持续开拓细胞研究与材料科学的新疆域。探索光与物质（细胞/材料）的相互作用蕴含着巨大机遇：先进光学操控工具（如光镊、飞秒激光刺激）实现对样本的原位实时主动扰动，可精准解析生物或材料系统在外部刺激下的微观响应。例如，实现三维空间任意位点的实时全息光照将推动光遗传学的跨越式发展。这些工程化平台还能诱导胶体材料内部的受控微扰动，以前所未有的精度探测其对机械、热、电磁等刺激的响应，为材料设计提供新范式。同步发展的微纳加工技术赋能复杂多细胞物理环境的构建，创建仿生体外微环境。
4. 培育突破：自下而上构建高端光学成像系统的必由之路。
实现高端光学成像系统的突破性进展需将其视为有机整体——光源、光路设计、光机械、探测器、透镜及软件等核心组件必须协同演进以优化性能。这要求跨学科协作：从生物化学（通过抗体/蛋白/染料/纳米颗粒及基因工程技术优化样本荧光）到人工智能（赋能图像处理与增强）。面对现代系统日益增长的复杂性，单纯逆向工程已难以为继。
在深入思考高端设备设计制造的底层逻辑后，除始于整体蓝图的自上而下经典策略外，我倡导并行的自下而上开发模式：成像系统围绕特定基础研究需求有机构建，随科研进展迭代优化，并通过产学研合作实现潜在商业化。该策略确保研究者基于深度操作认知进行终端用户持续评估，保障原理清晰性、卓越扩展性和经济性。科学家天然追求最高技术参数——其实验成功依赖于能揭示新现象的装备。摆脱预设商业束缚的系统设计可动态适应科学探索（践行"更高-更快-更强"的奥林匹克精神），孕育超越模仿的真正创新。尽管需要科研容错耐心（区别于伦理妥协），该过程常催生概念性新架构或颠覆性性能参数，创造远高于仿制品的价值。科研试错同时锤炼顶尖技术团队。成功案例如受果蝇启发的复眼透镜及基于润湿现象的液体透镜，印证了仿生学与软物质交叉知识如何革新光学设计。
商业化进程中良性循环显现：科学家阐明终端需求，工业界精进组件品质。此自下而上路径的成功亟需培育支持性生态——深度尊重知识产权、抵制破坏性竞争、恪守严谨合作准则、抗拒速成论文压力。唯有如此，用户驱动的创新方能蓬勃生长，重塑光学成像的未来。
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