Andres Garcia, Akash Garg, Feimo Yang, O. Burak Ozdoganlar, Philip R. LeDuc
{"title":"Fast Image Segmentation Toward Automation of 3D Ice Printing","authors":"Andres Garcia, Akash Garg, Feimo Yang, O. Burak Ozdoganlar, Philip R. LeDuc","doi":"10.1021/cbmi.5c00064","DOIUrl":"10.1021/cbmi.5c00064","url":null,"abstract":"<p>Freeform 3D ice printing is emerging as a promising additivemanufacturingmethod with potential applications in engineering, medicine, science,and art. Printing ice at the micrometer–millimeter scale isa challenging, high-frequency additive manufacturing process. Freeformice 3D printing though is an early stage manufacturing process wherecomplex geometries require significant time to design manually throughan empirical trial-and-error approach, due to the nonlinear natureof droplet deposition and solidification along with unavoidable uncertaintiesand noise. This process would be tremendously improved with betterunderstanding and harnessing the ability to visualize, analyze andadjust the printing process in real time. For this automation, usingapproaches such as closed loop control that have allowed tremendousadvances in other fields like self-driving cars, plane autopilot,etc. would be very useful. In order to use closed loop control forthis process, ice position and shape must be determined and transformedinto in situ actionable data, which is complicated further by thetransparency of ice and speed required for the phase transition fromwater to ice. We implemented vision techniques to build a data setto train a machine learning algorithm though an ice segmentation approachusing a convolutional filter. We also implemented a hybrid opticalflow algorithm (Farneback-FAST) to create a segmented video framedata set for training a neural network, Icenet. This approach wasfaster than the Farneback-FAST, segmenting frames in 25 ms, whichallows for single and low multi droplet control. Our approaches willenable future closed loop control of the printing process and willbe useful in a variety of areas including additive manufacturing,organ on a chip systems, and biomanufacturing.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"1068–1075"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yidan Rong, Chukai Lin, Min Qi, Wenxuan Fu, Bin Su
{"title":"Recent Advances in Electrochemiluminescence Imaging Applications","authors":"Yidan Rong, Chukai Lin, Min Qi, Wenxuan Fu, Bin Su","doi":"10.1021/cbmi.5c00252","DOIUrl":"10.1021/cbmi.5c00252","url":null,"abstract":"<p>Electrochemiluminescence (ECL) isa special form of chemiluminescence,where light emission results from electrochemically triggered chemicalreactions. By eliminating the requirement for external excitationlight, ECL achieves near-zero background signals, making it a powerfultool for imaging applications. This review provides a comprehensiveoverview of the recent advances in ECL imaging. It begins by elucidatingthe fundamental mechanisms of ECL and emphasizing its inherent advantagesfor imaging applications. The key components of ECL imaging systemsare outlined, with a detailed comparison of three primary microscopeconfigurations, namely, upright, inverted, and side-view. Representativeapplications of ECL imaging are subsequently discussed, includingvisual biochemical detection, imaging of biological entities, single-particleanalysis, and information encryption. Finally, we address currentlimitations of ECL imaging technology and propose potential solutions,highlighting promising directions for future development and broaderapplications.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"984–1003"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yulan Wang, Zhongxiang Cao, Li Shen, Zhihui Dai, Weiliang Guo
{"title":"Bipolar Electrochemiluminescence at Single Gold Microbeads Trapped by Micropipettes","authors":"Yulan Wang, Zhongxiang Cao, Li Shen, Zhihui Dai, Weiliang Guo","doi":"10.1021/cbmi.5c00239","DOIUrl":"10.1021/cbmi.5c00239","url":null,"abstract":"<p>Electrochemiluminescence (ECL) reactionscan take place at singleentities, allowing for the studying of reaction mechanisms at themicro/nanoscale level. However, the ECL generation usually relieson the substrate electrode, where single entities of interest arepositioned, leading to the overlap of ECL-emitting regions. Here,we report the fabrication of an open bipolar electrode (BPE) basedon a single gold-coated microbead (GMB), thus investigating ECL generationmerely from a single bead via a wireless mode. In this configuration,a single GMB was tightly positioned near the tip of a glass micropipetelectrode (MPE) while maintaining the flow of electrolyte solutionthrough the orifice of the micropipette. Thanks to the spatial confinementof the micropipette, ECL generation from tris(2,2′-bipyridyl)ruthenium(II)and tri-<em>n</em>-propylamine can be initiated at a drivingpotential as low as 4 V, which is significantly lower than the theoreticalvalue. Furthermore, the variation of ECL patterns with an externalpotential was resolved. In the narrow potential range from 4 to 5V, the ECL-emitting region spatially extends from the anodic poleto the equator of the GMB, while it sharply shrinks at 5.5 V, mostlikely due to the competition reaction of water oxidation. The contractionof the ECL-emitting region is attributed to the suppression of ECLreactions by a decrease in local pH. This work offers a promisingmethod of modulating the thickness of the ECL-emitting layer at awireless BPE and provides informative insight into ECL generationin a confined volume.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"1196–1201"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147891924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bo Xiang, Kui Yan, Ying Zhang, Wenxiao Wu, Zhuo Zeng, Fan Zhang, Shangfeng Wang
{"title":"Antiaromaticity-Based General Molecular Design of Activatable Near-Infrared Photoacoustic Probes with High Acoustic Loudness","authors":"Bo Xiang, Kui Yan, Ying Zhang, Wenxiao Wu, Zhuo Zeng, Fan Zhang, Shangfeng Wang","doi":"10.1021/cbmi.5c00198","DOIUrl":"10.1021/cbmi.5c00198","url":null,"abstract":"<p>Photoacoustic (PA) imaging offershigh spatial resolution and deeptissue penetration, and the development of activatable PA probes hasgreatly expanded its potential for detecting disease-associated molecularbiomarkers. Optimization of the probe performance has long been acentral challenge. Recently, the proposed acoustic loudness factor(ALF = ε × <em>k</em><sub>nr</sub>) establishedthat strong absorption and ultrafast nonradiative decay are key formaximizing PA output, yet a general molecular design strategy underthis framework remains elusive. Here we report PhAF, an antiaromaticfluorene dye platform in which ground-state antiaromaticity and excited-statearomaticity reversal under Baird’s rule induce strong vibroniccoupling and naturally high <em>k</em><sub>nr</sub>. PhAFexhibits maximal absorption at 950 nm, an ultrashort 3.37 ps lifetime,and a high ALF of 7.25 × 10<sup>15</sup> M<sup>–1</sup> cm<sup>–1</sup> s<sup>–1</sup>, while maintainingexcellent stability in aqueous and biological media. Masking the anilinedonor as an amide yielded nitroreductase-responsive PhAF-N and peroxynitrite-responsivePhAF-R, both showing robust in vivo imaging of tumor hypoxia and drug-inducedliver injury. This work establishes a molecular foundation for designinghigh-performance activatable PA probes for future theranostic applications.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"1153–1162"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fluorescent J-Aggregates in the NIR-II Window: Unlocking Frontiers in Biomedical Imaging","authors":"Xing Wei, Wei Chen","doi":"10.1021/cbmi.5c00232","DOIUrl":"10.1021/cbmi.5c00232","url":null,"abstract":"<p>Fluorescent organic dyes have longserved as versatile scaffoldsfor developing multifunctional imaging tools in biomedicine. The pursuitof fluorophores in the second near-infrared window (NIR-II) representsa major Frontier, aiming to deepen our view into living systems. Currentparadigms, predominantly focused on extending π-conjugation,are frequently hampered by synthetic complexity and aggregation-causedquenching (ACQ), creating a barrier to clinical translation. In thisperspective, we contend that J-aggregation offers a promising andalternative strategy: a more facile and spectrally tunable route tohigh-performance NIR-II emission. We analyze the design principlesregulating J-aggregate formation across diverse molecular scaffolds,from cyanines and boron-dipyrromethene (BODIPY) derivatives to emergingfluorophore scaffolds, and synthesize their recent applications inbioimaging, biosensing, and theranostics. We also discuss the keychallenges of current NIR-II emissive J-aggregates (e.g., low fluorescencequantum yield, poor in vivo stability) in biomedical applications,alongside prospects for advancing their development toward routineuse in biomedicine.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"957–969"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"pH-Responsive Materials for Therapy and Precision Biomedical Imaging","authors":"Qing Wang, Zhibin Guo, Ziqun Chen, Caiyu Wang, Yahui Yang, Qi Shi, Qichao Gao, Hanping Li, Dongdong Zhang, Yi Liu, Yujiao Liu","doi":"10.1021/cbmi.5c00279","DOIUrl":"10.1021/cbmi.5c00279","url":null,"abstract":"<p>The acidic tumor microenvironment (TME) presents a keypathologicalhallmark that can be exploited for targeted therapeutic and diagnosticinterventions. This review systematically outlines the design andapplication of pH-responsive materials in biomedical imaging and therapy,emphasizing their role in achieving spatial and temporal control overdrug delivery and imaging contrast. We first detail the fundamentalchemical mechanisms underpinning pH responsiveness, including dynamiccovalent bonds (e.g., acylhydrazone, imine, orthoester, and borateester), metal–ligand coordination bonds, and pH-dependent noncovalentinteractions. These principles are then translated into a varietyof nanocarrier platforms, such as polymeric micelles, liposomes, hydrogels,metal–organic frameworks (MOFs), PROTAC conjugates, and self-assemblingpeptides, all of which are designed to undergo structural or functionalchanges in response to acidic conditions. The convergence of thesesmart materials with advanced imaging modalities has enabled transformativeapplications, including activatable probes for high-contrast functionalimaging, multistimuli responsive theranostics, organelle-precisiontargeting, and spatiotemporally programmed release systems. Theseinnovations collectively enhance diagnostic accuracy, therapeuticspecificity, and the potential for real-time treatment monitoring.However, clinical translation remains challenged by issues relatedto reproducible synthesis, long-term biocompatibility, and the complexheterogeneity of <em>in vivo</em> environments. Future advancementsare anticipated to focus on the integration of artificial intelligencefor material design, the development of closed-loop feedback systems,and rigorous translational studies to bridge the gap between laboratoryinnovation and clinical application.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"1018–1042"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multiplexed Detection of Reactive Biomolecules via Chemoresponsive DNA Accumulation on Fluorescence-Encoded Beads","authors":"Tatsuya Nishihara, Masato Sugawara, Reoto Mio, Yuto Motohashi, Kazuhito Tanabe","doi":"10.1021/cbmi.5c00226","DOIUrl":"10.1021/cbmi.5c00226","url":null,"abstract":"<p>The multiplex analysis of reactive biomolecules is crucialin diagnosticsand life science research. However, conventional methods using small-molecule-basedfluorescent probes are limited in the number of simultaneously detectabletargets because of the spectral overlap of their fluorescence wavelengths.Herein we present a sequencing-free multiplexed analysis platformusing chemoresponsive DNA-based fluorescent probes. A target-responsivemoiety was installed in the phosphate backbone of the probe to strategicallydestabilize the DNA duplex. Reaction with a target molecule such ashydrogen peroxide or nitroreductase cleaved this moiety, restoringduplex stability and thereby triggering the accumulation of fluorescentproduct DNAs on beads functionalized with a complementary sequence.By encoding beads with distinct fluorescence intensity ratios andsizes, we achieved the simultaneous and specific detection of multipletargets in a single sample. The system performed well even with complexbiological samples. This modular “reaction-to-accumulation”strategy offers a generalizable approach for developing DNA-basedmultiplex detection systems tailored to different target molecules.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"1062–1067"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Scalable Synthesis of Calcium Fluoride Nanoparticles as a Novel Ultrasound Contrast Agent for Imaging Tumor Targeted Delivery of Therapeutics","authors":"Suresh Thangudu, Arutselvan Natarajan, Sourabh Mehta, Kireeti Phani Devarakonda, Tarik F. Massoud, Ramasamy Paulmurugan","doi":"10.1021/cbmi.5c00259","DOIUrl":"10.1021/cbmi.5c00259","url":null,"abstract":"<p>Ultrasound (US) imaging is one of the most widely usednoninvasivediagnostic techniques in clinical practice due to its safety, real-timecapability, and cost-effectiveness. However, traditional B-mode imagingprovides limited information with low sensitivity. Recently microbubble(MB)-based contrast agents have been employed to enhance contrastsignals while also facilitating the imaging of molecular targets intarget tissues or pathological locations. Currently available MBsface several limitations, including large size (typically 1–10μm), limited ability to penetrate beyond blood vessels, poor <em>in vivo</em> stability, susceptibility to gas leakage, and highproduction costs, which collectively hinder their clinical efficiencyand applicability. To address these limitations, we developed calciumfluoride (CaF<sub>2</sub>) nanoparticles (NPs) using a scalable synthesisprocess as a next-generation ultrasound contrast agent via a coprecipitationmethod using citrate as a stabilizing agent. The synthesized NPs exhibiteda uniform size distribution (∼100 nm) with consistent reproducibilityduring scalable production conditions. Notably, CaF<sub>2</sub> NPsgenerated substantially better contrast-enhanced ultrasound signalsunder acidic conditions (pH 5.5) than at neutral pH (7.2). The porousstructure of the CaF<sub>2</sub> NPs enabled us to efficiently loaddoxorubicin with the loading efficiency of 29.3 ± 5% and controlledintracellular delivery in MDA-MB-231 breast cancer cells <em>in vitro</em>. <em>In vivo</em> studies using an orthotopicbreast cancer model demonstrated a pronounced pH-responsive ultrasoundcontrast signal following intravenous administration of CaF<sub>2</sub> NPs (15 mg/kg). Tumor signal intensity increased ∼25-foldcompared to controls at 1 h postinjection, with contrast persistingup to 5 h, dramatically outperforming conventional microbubbles thattypically dissipate within 10 min. Biosafety analyses confirmed excellenthemocompatibility and no detectable organ toxicity. To the best ofour knowledge, this is the first report of CaF<sub>2</sub> NPs functioningas a US contrast agent for <em>in vivo</em> tumor imagingand drug delivery. Overall, we identify CaF<sub>2</sub> NPs as safe,long-lasting, and multifunctional US contrast agents with integrateddrug delivery capability, offering a promising platform for advancedultrasound imaging and theranostic applications.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"1202–1213"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enrico Gallo, Antonella Carella, Francesco Gammaraccio, Marco Salvatore, Antonella Accardo, Dario Livio Longo, Silvio Aime
{"title":"Peptide-Based pH-Responsive MRI-CEST Agents: In Vivo Comparison between a Selected Pentapeptide and the Established Iopamidol Reference in Tumor pH Mapping Ability","authors":"Enrico Gallo, Antonella Carella, Francesco Gammaraccio, Marco Salvatore, Antonella Accardo, Dario Livio Longo, Silvio Aime","doi":"10.1021/cbmi.5c00150","DOIUrl":"10.1021/cbmi.5c00150","url":null,"abstract":"<p>Magnetic resonance imaging based on chemical exchangesaturationtransfer (MRI-CEST) has emerged as a powerful imaging technique formapping physiological parameters, such as tissue pH, with high spatialresolution. This study explores the pH-responsive performance of anovel peptide-based CEST agent, selected among several candidates,when compared with the established contrast agent iopamidol. The selectedhLys containing pentapeptide showed enhanced sensitivity and biocompatibilitywhile maintaining an excellent CEST response. In vivo MRI studiesfurther assessed its applicability for tumor pH imaging. The resultsdemonstrate that the selected peptide-based agent displays good CESTcontrast variations in response to pH changes, highlighting its potentialas a pH-responsive CEST agent. The assessed pH values were very similarto those obtained upon the administration of iopamidol, a well-establishedpH-CEST agent. Notably, this result was obtained by administeringa mass dose of contrast agent that is about 8-fold less than thatused in the case of iopamidol. These findings pave the way for thedevelopment of peptide-derived MRI probes for noninvasive tumor microenvironmentassessment.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"1076–1086"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Concurrent Evaluation of Liver and Kidney Function by NIR-II In Vivo Imaging to Assess the Efficacy of Flavonoids in Preventing Their Injuries","authors":"Yuxin Bai, Ruihu Song, Zewei Zhang, Xiangmei Chen, Hao Chen, De-an Guo","doi":"10.1021/cbmi.5c00174","DOIUrl":"10.1021/cbmi.5c00174","url":null,"abstract":"<p>Theliver and kidneys are often synchronously affectedby variousdiseases, posing significant health challenges. Simultaneously monitoringtheir damage would benefit rational drug use. Herein, a new probe,SQE-715-CD, was developed to concurrently assess liver and kidneyinjuries using <em>in vivo</em> NIR-II fluorescence imaging.In addition to diagnostic advancements, this research delves intothe therapeutic potential of flavonoids in protecting against liverand kidney damage caused by cisplatin. Among the seven flavonoidstested, Apigenin stands out for its substantial reduction in cisplatin-inducedtoxicity in both organs. Further experiments reveal that Apigenin’spretreatment lowers kidney inflammation and inhibits the activationof crucial signaling molecules p38, ERK, and JNK. These results suggesta possible mechanism behind Apigenin’s protective effects andunderscore its significance in reducing nephrotoxicity. The capabilityfor <em>in vivo</em> simultaneous monitoring of liver andkidney functions proposed in this study could provide another therapeuticdrug evaluation and screening method.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"4 6","pages":"1116–1127"},"PeriodicalIF":6.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}