Precise Deciphering of Brain Vasculatures and Microscopic Tumors with Dual NIR‐II Fluorescence and Photoacoustic Imaging

Diagnostics of cerebrovascular structures and microscopic tumors with intact blood–brain barrier (BBB) significantly contributes to timely treatment of patients bearing neurological diseases. Dual NIR‐II fluorescence and photoacoustic imaging (PAI) is expected to offer powerful strength, including good spatiotemporal resolution, deep penetration, and large signal‐to‐background ratio (SBR) for precise brain diagnostics. Herein, biocompatible and photostable conjugated polymer nanoparticles (CP NPs) are reported for dual‐modality brain imaging in the NIR‐II window. Uniform CP NPs with a size of 50 nm are fabricated from microfluidics devices, which show an emission peak at 1156 nm with a large absorptivity of 35.2 L g^?1 cm^?1 at 1000 nm. The NIR‐II fluorescence imaging resolves hemodynamics and cerebral vasculatures with a spatial resolution of 23 µm at a depth of 600 µm. The NIR‐II PAI enables successful noninvasive mapping of deep microscopic brain tumors (<2 mm at a depth of 2.4 mm beneath dense skull and scalp) with an SBR of 7.2 after focused ultrasound‐induced BBB opening. This study demonstrates that CP NPs are promising contrast agents for brain diagnostics.     

NIR‐II‐Excited Intravital Two‐Photon Microscopy Distinguishes Deep Cerebral and Tumor Vasculatures with an Ultrabright NIR‐I AIE Luminogen

Intravital fluorescence imaging of vasculature morphology and dynamics in the brain and in tumors with large penetration depth and high signal‐to‐background ratio (SBR) is highly desirable for the study and theranostics of vascular‐related diseases and cancers. Herein, a highly bright fluorophore (BTPETQ) with long‐wavelength absorption and aggregation‐induced near‐infrared (NIR) emission (maximum at ≈700 nm) is designed for intravital two‐photon fluorescence (2PF) imaging of a mouse brain and tumor vasculatures under NIR‐II light (1200 nm) excitation. BTPETQ dots fabricated via nanoprecipitation show uniform size of around 42 nm and a high quantum yield of 19 ± 1% in aqueous media. The 2PF imaging of the mouse brain vasculatures labeled by BTPETQ dots reveals a 3D blood vessel network with an ultradeep depth of 924 µm. In addition, BTPETQ dots show enhanced 2PF in tumor vasculatures due to their unique leaky structures, which facilitates the differentiation of normal blood vessels from tumor vessels with high SBR in deep tumor tissues. Moreover, the extravasation and accumulation of BTPETQ dots in deep tumor (more than 900 µm) is visualized under NIR‐II excitation. This study highlights the importance of developing NIR‐II light excitable efficient NIR fluorophores for in vivo deep tissue and high contrast tumor imaging.     

Bright Aggregation‐Induced‐Emission Dots for Targeted Synergetic NIR‐II Fluorescence and NIR‐I Photoacoustic Imaging of Orthotopic Brain Tumors

Precise diagnostics are of significant importance to the optimal treatment outcomes of patients bearing brain tumors. NIR‐II fluorescence imaging holds great promise for brain‐tumor diagnostics with deep penetration and high sensitivity. This requires the development of organic NIR‐II fluorescent agents with high quantum yield (QY), which is difficult to achieve. Herein, the design and synthesis of a new NIR‐II fluorescent molecule with aggregation‐induced‐emission (AIE) characteristics is reported for orthotopic brain‐tumor imaging. Encapsulation of the molecule in a polymer matrix yields AIE dots showing a very high QY of 6.2% with a large absorptivity of 10.2 L g^?1 cm^?1 at 740 nm and an emission maximum near 1000 nm. Further decoration of the AIE dots with c‐RGD yields targeted AIE dots, which afford specific and selective tumor uptake, with a high signal/background ratio of 4.4 and resolution up to 38 µm. The large NIR absorptivity of the AIE dots facilitates NIR‐I photoacoustic imaging with intrinsically deeper penetration than NIR‐II fluorescence imaging and, more importantly, precise tumor‐depth detection through intact scalp and skull. This research demonstrates the promise of NIR‐II AIE molecules and their dots in dual NIR‐II fluorescence and NIR‐I photoacoustic imaging for precise brain cancer diagnostics.     

3D NIR‐II Molecular Imaging Distinguishes Targeted Organs with High‐Performance NIR‐II Bioconjugates

Greatly reduced scattering in the second near‐infrared (NIR‐II) region (1000–1700 nm) opens up many new exciting avenues of bioimaging research, yet NIR‐II fluorescence imaging is mostly implemented by using nontargeted fluorophores or wide‐field imaging setups, limiting the signal‐to‐background ratio and imaging penetration depth due to poor specific binding and out‐of‐focus signals. A newly developed high‐performance NIR‐II bioconjugate enables targeted imaging of a specific organ in the living body with high quality. Combined with a home‐built NIR‐II confocal set‐up, the enhanced imaging technique allows 900 µm‐deep 3D organ imaging without tissue clearing techniques. Bioconjugation of two hormones to nonoverlapping NIR‐II fluorophores facilitates two‐color imaging of different receptors, demonstrating unprecedented multicolor live molecular imaging across the NIR‐II window. This deep tissue imaging of specific receptors in live animals allows development of noninvasive molecular imaging of multifarious models of normal and neoplastic organs in vivo, beyond the traditional visible to NIR‐I range. The developed NIR‐II fluorescence microscopy will become a powerful imaging technique for deep tissue imaging without any physical sectioning or clearing treatment of the tissue.     

Molecular Cancer Imaging in the Second Near‐Infrared Window Using a Renal‐Excreted NIR‐II Fluorophore‐Peptide Probe

In vivo molecular imaging of tumors targeting a specific cancer cell marker is a promising strategy for cancer diagnosis and imaging guided surgery and therapy. While targeted imaging often relies on antibody‐modified probes, peptides can afford targeting probes with small sizes, high penetrating ability, and rapid excretion. Recently, in vivo fluorescence imaging in the second near‐infrared window (NIR‐II, 1000–1700 nm) shows promise in reaching sub‐centimeter depth with microscale resolution. Here, a novel peptide (named CP) conjugated NIR‐II fluorescent probe is reported for molecular tumor imaging targeting a tumor stem cell biomarker CD133. The click chemistry derived peptide‐dye (CP‐IRT dye) probe afforded efficient in vivo tumor targeting in mice with a high tumor‐to‐normal tissue signal ratio (T/NT > 8). Importantly, the CP‐IRT probes are rapidly renal excreted (≈87% excretion within 6 h), in stark contrast to accumulation in the liver for typical antibody‐dye probes. Further, with NIR‐II emitting CP‐IRT probes, urethra of mice can be imaged fluorescently for the first time noninvasively through intact tissue. The NIR‐II fluorescent, CD133 targeting imaging probes are potentially useful for human use in the clinic for cancer diagnosis and therapy.     

Aggregation‐Induced Nonlinear Optical Effects of AIEgen Nanocrystals for Ultradeep In Vivo Bioimaging

Nonlinear optical microscopy has become a powerful tool in bioimaging research due to its unique capabilities of deep optical sectioning, high‐spatial‐resolution imaging, and 3D reconstruction of biological specimens. Developing organic fluorescent probes with strong nonlinear optical effects, in particular third‐harmonic generation (THG), is promising for exploiting nonlinear microscopic imaging for biomedical applications. Herein, a simple method for preparing organic nanocrystals based on an aggregation‐induced emission (AIE) luminogen (DCCN) with bright near‐infrared emission is successfully demonstrated. Aggregation‐induced nonlinear optical effects, including two‐photon fluorescence (2PF), three‐photon fluorescence (3PF), and THG, of DCCN are observed in nanoparticles, especially for crystalline nanoparticles. The nanocrystals of DCCN are successfully applied for 2PF microscopy at 1040 nm NIR‐II excitation and THG microscopy at 1560 nm NIR‐II excitation, respectively, to reconstruct the 3D vasculature of the mouse cerebral vasculature. Impressively, the THG microscopy provides much higher spatial resolution and brightness than the 2PF microscopy and can visualize small vessels with diameters of ≈2.7 µm at the deepest depth of 800 µm in a mouse brain. Thus, this is expected to inspire new insights into the development of advanced AIE materials with multiple nonlinearity, in particular THG, for multimodal nonlinear optical microscopy.     

Semiconducting Polymer Nanoparticles for Centimeters‐Deep Photoacoustic Imaging in the Second Near‐Infrared Window

Thienoisoindigo‐based semiconducting polymer with a strong near‐infrared absorbance is synthesized and its water‐dispersed nanoparticles (TSPNs) are investigated as a contrast agent for photoacoustic (PA) imaging in the second near‐infrared (NIR‐II) window (1000–1350 nm). The TSPNs generate a strong PA signal in the NIR‐II optical window, where background signals from endogenous contrast agents, including blood and lipid, are at the local minima. By embedding a TSPN‐containing tube in chicken‐breast tissue, an imaging depth of more than 5 cm at 1064 nm excitation is achieved with a contrast‐agent concentration as low as 40 µg mL^?1. The TSPNs under the skin or in the tumor are clearly visualized at 1100 and 1300 nm, with negligible interference from the tissue background. TSPN as a PA contrast in the NIR‐II window opens new opportunities for biomedical imaging of deep tissues with improved contrast.     

Atomic‐Precision Gold Clusters for NIR‐II Imaging

Near‐infrared II (NIR‐II) imaging at 1100–1700 nm shows great promise for medical diagnosis related to blood vessels because it possesses deep penetration and high resolution in biological tissue. Unfortunately, currently available NIR‐II fluorophores exhibit slow excretion and low brightness, which prevents their potential medical applications. An atomic‐precision gold (Au) cluster with 25 gold atoms and 18 peptide ligands is presented. The Au₂₅ clusters show emission at 1100–1350 nm and the fluorescence quantum yield is significantly increased by metal‐atom doping. Bright gold clusters can penetrate deep tissue and can be applied in in vivo brain vessel imaging and tumor metastasis. Time‐resolved brain blood‐flow imaging shows significant differences between healthy and injured mice with different brain diseases in vivo. High‐resolution imaging of cancer metastasis allows for the identification of the primary tumor, blood vessel, and lymphatic metastasis. In addition, gold clusters with NIR‐II fluorescence are used to monitor high‐resolution imaging of kidney at a depth of 0.61 cm, and the quantitative measurement shows 86% of the gold clusters are cleared from body without any acute or long‐term toxicity at a dose of 100 mg kg^?1.     

Emitting/Sensitizing Ions Spatially Separated Lanthanide Nanocrystals for Visualizing Tumors Simultaneously through Up‐ and Down‐Conversion Near‐Infrared II Luminescence In Vivo

Near‐infrared lights have received increasing attention regarding imaging applications owing to their large tissue penetration depth, high spatial resolution, and outstanding signal‐to‐noise ratio, particularly those falling in the second near‐infrared window (NIR II) of biological tissues. Rare earth nanoparticles containing Er³⁺ ions are promising candidates to show up‐conversion luminescence in the first near‐infrared window (NIR I) and down‐conversion luminescence in NIR II as well. However, synthesizing particles with small size and high NIR II luminescence quantum yield (QY) remains challenging. Er³⁺ ions are herein innovatively combined with Yb³⁺ ions in a NaErF₄@NaYbF₄ core/shell manner instead of being codoped into NaLnF₄ matrices, to maximize the concentration of Er³⁺ in the emitting core. After further surface coating, NaErF₄@NaYbF₄@NaYF₄ core/shell/shell particles are obtained. Spectroscopy studies are carried out to show the synergistic impacts of the intermediate NaYbF₄ layer and the outer NaYF₄ shell. Finally, NaErF₄@NaYbF₄@NaYF₄ nanoparticles of 30 nm with NIR II luminescence QY up to 18.7% at room temperature are obtained. After covalently attaching folic acid on the particle surface, tumor‐specific nanoprobes are obtained for simultaneously visualizing both subcutaneous and intraperitoneal tumor xenografts in vivo. The ultrahigh QY of down‐conversion emission also allows for visualization of the biodistribution of folate receptors.     

Low‐Temperature Heteroepitaxy of 2D PbI2/Graphene for Large‐Area Flexible Photodetectors

Heterostructures based on graphene and other 2D atomic crystals exhibit fascinating properties and intriguing potential in flexible optoelectronics, where graphene films function as transparent electrodes and other building blocks are used as photoactive materials. However, large‐scale production of such heterostructures with superior performance is still in early stages. Herein, for the first time, the preparation of a submeter‐sized, vertically stacked heterojunction of lead iodide (PbI₂)/graphene on a flexible polyethylene terephthalate (PET) film by vapor deposition of PbI₂ on graphene/PET substrate at a temperature lower than 200 °C is demonstrated. This film is subsequently used to fabricate bendable graphene/PbI₂/graphene sandwiched photodetectors, which exhibit high responsivity (45 A W^?1 cm^?2), fast response (35 µs rise, 20 µs decay), and high‐resolution imaging capability (1 µm). This study may pave a facile pathway for scalable production of high‐performance flexible devices.     

“Dual Lock‐and‐Key”‐Controlled Nanoprobes for Ultrahigh Specific Fluorescence Imaging in the Second Near‐Infrared Window

Fluorescence imaging in the second near‐infrared window (NIR‐II) is a new technique that permits visualization of deep anatomical features with unprecedented spatial resolution. Although attractive, effectively suppressing the interference signal of the background is still an enormous challenge for obtaining target‐specific NIR‐II imaging in the complex and dynamic physiological environment. Herein, dual‐pathological‐parameter cooperatively activatable NIR‐II fluorescence nanoprobes (HISSNPs) are developed whereby hyaluronic acid chains and disulfide bonds act as the “double locks” to lock the fluorescence‐quenched aggregation state of the NIR‐II fluorescence dyes for performing ultrahigh specific imaging of tumors in vivo. The fluorescence can be lit up only when the “double locks” are opened by reacting with the “dual smart keys” (overexpressed hyaluronidase and thiols in tumor) simultaneously. In vivo NIR‐II imaging shows that they reduce nonspecific activitation and achieve ultralow background fluorescence, which is 10.6‐fold lower than single‐parameter activatable probes (HINPs) in the liver at 15 h postinjection. Consequently, these “dual lock‐and‐key”‐controlled HISSNPs exhibit fivefold higher tumor‐to‐normal tissue ratio than “single lock‐and‐key”‐controlled HINPs at 24 h postinjection, attractively realizing ultrahigh specificity of tumor imaging. This is thought to be the first attempt at implementing ultralow background interference with the participation of multiple pathological parameters in NIR‐II fluorescence imaging.     

Real‐Time and High‐Resolution Bioimaging with Bright Aggregation‐Induced Emission Dots in Short‐Wave Infrared Region

Fluorescence imaging in the spectral region beyond the conventional near‐infrared biological window (700–900 nm) can theoretically afford high resolution and deep tissue penetration. Although some efforts have been devoted to developing a short‐wave infrared (SWIR; 900–1700 nm) imaging modality in the past decade, long‐wavelength biomedical imaging is still suboptimal owing to the unsatisfactory materials properties of SWIR fluorophores. Taking advantage of organic dots based on an aggregation‐induced emission luminogen (AIEgen), herein microscopic vasculature imaging of brain and tumor is reported in living mice in the SWIR spectral region. The long‐wavelength emission of AIE dots with certain brightness facilitates resolving brain capillaries with high spatial resolution (≈3 µm) and deep penetration (800 µm). Owning to the deep penetration depth and real‐time imaging capability, in vivo SWIR microscopic angiography exhibits superior resolution in monitoring blood–brain barrier damage in mouse brain, and visualizing enhanced permeability and retention effect in tumor sites. Furthermore, the AIE dots show good biocompatibility, and no noticeable abnormalities, inflammations or lesions are observed in the main organs of the mice. This work will inspire new insights on development of advanced SWIR techniques for biomedical imaging.     

High‐Resolution SPECT Imaging of Stimuli‐Responsive Soft Microrobots

Untethered small‐scale robots have great potential for biomedical applications. However, critical barriers to effective translation of these miniaturized machines into clinical practice exist. High resolution tracking and imaging in vivo is one of the barriers that limit the use of micro‐ and nanorobots in clinical applications. Here, the inclusion of radioactive compounds in soft thermoresponsive magnetic microrobots is investigated to enable their single‐photon emission computed tomography imaging. Four microrobotic platforms differing in hydrogel structure and four ^99mTc[Tc]‐based radioactive compounds are investigated in order to achieve optimal contrast agent retention and optimal imaging. Single microrobot imaging of structures as low as 100 µm in diameter, as well as tracking of shape switching from tubular to planar configurations by inclusion of ^99mTc[Tc] colloid in the hydrogel structure, is reported.     

Repurposing Cyanine NIR‐I Dyes Accelerates Clinical Translation of Near‐Infrared‐II (NIR‐II) Bioimaging

The significantly reduced tissue autofluorescence and scattering in the NIR‐II region (1000–1700 nm) opens many exciting avenues for detailed investigation of biological processes in vivo. However, the existing NIR‐II fluorescent agents, including many molecular dyes and inorganic nanomaterials, are primarily focused on complicated synthesis routes and unknown immunogenic responses with limited potential for clinical translation. Herein, the >1000 nm tail emission of conventional biocompatible NIR cyanine dyes with emission peaks at 700–900 nm is systematically investigated, and a type of bright dye for NIR‐II imaging with high potential for accelerating clinical translation is identified. The asymmetry of the π domain in the S₁ state of NIR cyanine dyes is proven to result in a twisted intramolecular charge‐transfer process and NIR‐II emission, establishing a general rule to guide future NIR‐I/II fluorophore synthesis. The screened NIR dyes are identified to possess a bright emission tail in the NIR‐II region along with high quantum yield, high molar‐extinction coefficient, rapid fecal excretion, and functional groups amenable for bioconjugation. As a result, NIR cyanine dyes can be used for NIR‐II imaging to afford superior contrast and real‐time imaging of several biological models, facilitating the translation of NIR‐II bioimaging to clinical theranostic applications.     

Hierarchically Nanostructured Hybrid Platform for Tumor Delineation and Image‐Guided Surgery via NIR‐II Fluorescence and PET Bimodal Imaging

Bimodal imaging with fluorescence in the second near infrared window (NIR‐II) and positron emission tomography (PET) has important significance for tumor diagnosis and management because of complementary advantages. It remains challenging to develop NIR‐II/PET bimodal probes with high fluorescent brightness. Herein, bioinspired nanomaterials (melanin dot, mesoporous silica nanoparticle, and supported lipid bilayer), NIR‐II dye CH‐4T, and PET radionuclide ⁶⁴Cu are integrated into a hybrid NIR‐II/PET bimodal nanoprobe. The resultant nanoprobe exhibits attractive properties such as highly uniform tunable size, effective payload encapsulation, high stability, dispersibility, and biocompatibility. Interestingly, the incorporation of CH‐4T into the nanoparticle leads to 4.27‐fold fluorescence enhancement, resulting in brighter NIR‐II imaging for phantoms in vitro and in situ. Benefiting from the fluorescence enhancement, NIR‐II imaging with the nanoprobe is carried out to precisely delineate and resect tumors. Additionally, the nanoprobe is successfully applied in tumor PET imaging, showing the accumulation of the nanoprobe in a tumor with a clear contrast from 2 to 24 h postinjection. Overall, this hierarchically nanostructured platform is able to dramatically enhance fluorescent brightness of NIR‐II dye, detect tumors with NIR‐II/PET imaging, and guide intraoperative resection. The NIR‐II/PET bimodal nanoprobe has high potential for sensitive preoperative tumor diagnosis and precise intraoperative image‐guided surgery.     

High‐Speed 3D Printing of Millimeter‐Size Customized Aspheric Imaging Lenses with Sub 7 nm Surface Roughness

Advancements in three‐dimensional (3D) printing technology have the potential to transform the manufacture of customized optical elements, which today relies heavily on time‐consuming and costly polishing and grinding processes. However the inherent speed‐accuracy trade‐off seriously constrains the practical applications of 3D‐printing technology in the optical realm. In addressing this issue, here, a new method featuring a significantly faster fabrication speed, at 24.54 mm³ h^?1, without compromising the fabrication accuracy required to 3D‐print customized optical components is reported. A high‐speed 3D‐printing process with subvoxel‐scale precision (sub 5 µm) and deep subwavelength (sub 7 nm) surface roughness by employing the projection micro‐stereolithography process and the synergistic effects from grayscale photopolymerization and the meniscus equilibrium post‐curing methods is demonstrated. Fabricating a customized aspheric lens 5 mm in height and 3 mm in diameter is accomplished in four hours. The 3D‐printed singlet aspheric lens demonstrates a maximal imaging resolution of 373.2 lp mm^?1 with low field distortion less than 0.13% across a 2 mm field of view. This lens is attached onto a cell phone camera and the colorful fine details of a sunset moth's wing and the spot on a weevil's elytra are captured. This work demonstrates the potential of this method to rapidly prototype optical components or systems based on 3D printing.     

Plasmonic Pt Superstructures with Boosted Near‐Infrared Absorption and Photothermal Conversion Efficiency in the Second Biowindow for Cancer Therapy

Photothermal therapy triggered by near‐infrared light in the second biowindow (NIR‐II) has attracted extensive interest owing to its deeper penetration depth of biological tissue, lower photon scattering, and higher maximum permissible exposure. In spite of noble metals showing great potential as the photothermal agents due to the tunable localized surface plasmon resonance, the biological applications of platinum are rarely explored. Herein, a monocomponent hollow Pt nanoframe (“Pt Spirals”), whose superstructure is assembled with three levels (3D frame, 2D layered shells, and 1D nanowires), is reported. Pt Spirals exhibit outstanding photothermal conversion efficiency (52.5%) and molar extinction coefficients (228.7 m² mol^?1) in NIR‐II, which are much higher than those of solid Pt cubes. Simulations indicate that the unique superstructure can be a significant cause for improving both adsorption and the photothermal effect simultaneously in NIR‐II. The excellent photothermal effect is achieved and subsequently verified in in vitro and in vivo experiments, along with superb heat‐resistance properties, excellent photostability, and a prominent effect on computed tomography (CT) imaging, demonstrating that Pt Spirals are promising as effective theranostic platforms for CT imaging‐guided photothermal therapy.     

Enhanced Controllability of Fries Rearrangements Using High‐Resolution 3D‐Printed Metal Microreactor with Circular Channel

High‐resolution 3D‐printed stainless steel metal microreactors (3D‐PMRs) with different cross‐sectional geometry are fabricated to control ultrafast intramolecular rearrangement reactions in a comparative manner. The 3D‐PMR with circular channel demonstrates the improved controllability in rapid Fries‐type rearrangement reactions, because of the superior mixing efficiency to rectangular cross‐section channels (250 µm × 125 µm) which is confirmed based on the computational flow dynamics simulation. Even in case of very rapid intramolecular rearrangement of sterically small acetyl group occurring in 333 µs of reaction time, the desired intermolecular reaction can outpace to the undesired intramolecular rearrangement using 3D‐PMR to result in high conversion and yield.     

Through Scalp and Skull NIR‐II Photothermal Therapy of Deep Orthotopic Brain Tumors with Precise Photoacoustic Imaging Guidance

Brain tumor is one of the most lethal cancers owing to the existence of blood–brain barrier and blood–brain tumor barrier as well as the lack of highly effective brain tumor treatment paradigms. Herein, cyclo(Arg‐Gly‐Asp‐D‐Phe‐Lys(mpa)) decorated biocompatible and photostable conjugated polymer nanoparticles with strong absorption in the second near‐infrared (NIR‐II) window are developed for precise photoacoustic imaging and spatiotemporal photothermal therapy of brain tumor through scalp and skull. Evidenced by the higher efficiency to penetrate scalp and skull for 1064 nm laser as compared to common 808 nm laser, NIR‐II brain‐tumor photothermal therapy is highly effective. In addition, via a real‐time photoacoustic imaging system, the nanoparticles assist clear pinpointing of glioma at a depth of almost 3 mm through scalp and skull with an ultrahigh signal‐to‐background ratio of 90. After spatiotemporal photothermal treatment, the tumor progression is effectively inhibited and the survival spans of mice are significantly extended. This study demonstrates that NIR‐II conjugated polymer nanoparticles are promising for precise imaging and treatment of brain tumors.     

Flexible Photodetector Arrays Based on Patterned CH3NH3PbI3−xClx Perovskite Film for Real‐Time Photosensing and Imaging

The quest for novel deformable image sensors with outstanding optoelectronic properties and large‐scale integration becomes a great impetus to exploit more advanced flexible photodetector (PD) arrays. Here, 10 × 10 flexible PD arrays with a resolution of 63.5 dpi are demonstrated based on as‐prepared perovskite arrays for photosensing and imaging. Large‐scale growth controllable CH₃NH₃PbI_3?xCl_x arrays are synthesized on a poly(ethylene terephthalate) substrate by using a two‐step sequential deposition method with the developed Al₂O₃‐assisted hydrophilic–hydrophobic surface treatment process. The flexible PD arrays with high detectivity (9.4 × 10¹¹ Jones), large on/off current ratio (up to 1.2 × 10³), and broad spectral response exhibit excellent electrical stability under large bending angle (θ = 150°) and superior folding endurance after hundreds of bending cycles. In addition, the device can execute the functions of capturing a real‐time light trajectory and detecting a multipoint light distribution, indicating that it has widespread potential in photosensing and imaging for optical communication, digital display, and artificial electronic skin applications.