Near-infrared Optical Window Research Articles

Investigation of a highly-sensitive aluminum-based plasmonic device using antimonene for sensing applications

Aluminum (Al) has gained popularity for surface plasmon resonance-based applications due to its affordability and compatibility with CMOS technology at the nanoscale. Over angle-interrogation mode, plasmonic interactions occurring at the metal-dielectric junction, are the outcomes of the attenuated total internal reflection phenomenon. Modified Al-based Kretschmann configuration results in phase-matching conditions that are seen as resonant points in the reflection characteristics. In our work, we have engineered an Al-based plasmonic device utilizing Antimonene as a 2D nanomaterial for bio-sensing purposes in the Near-Infrared (NIR) spectral domain. The study investigates the performance of Surface Plasmon Resonance (SPR) based refractive index sensor using different 2D nanomaterials with an optimized Al thickness of 30 nm. A comparative analysis of Al-based Kretschmann configurations in the presence of Graphene, Black Phosphorus, MXene, and Antimonene is presented using engineered intermediate layers. It is observed that the Al-antimonene-based plasmonic device exhibits improved sensing parameters in the NIR optical window.

Laser tissue welding by using collagen excitation at a 1,720 nm near-infrared optical window III.

Laser tissue welding (LTW) is a method of fusing incised tissues together. LTW has the potential to revolutionize plastic surgery and wound healing techniques by its ability to produce watertight, scarless seals with minimal foreign body reaction. While using thermal mechanisms to achieve LTW, energy from the incident laser is absorbed by water in the tissue. As the water temperature increases, partial denaturing of the collagen triple helix briefly occurs, which is quickly followed by renaturation of collagen as the tissue cools, thus providing a watertight seal. This research study investigates the efficacy of direct collagen excitation at 1,720nm to accomplish LTW. This wavelength falls within the near-infrared (NIR) optical window III. The tensile strengths of pig skin that have been welded with NIR continuous-wave (CW) diode lasers at 1,455nm, which promote thermal mechanisms of tissue welding, and 1,720nm wavelengths, are compared. Near-infrared lasers tuned to 1,455 and 1,720nm were used to weld incised pieces of porcine skin together without extrinsic solders or dyes. The tensile force of the welded tissues was measured using a digital force gauge. The average tensile force of the welded pig skin using the 1,720nm laser was approximately four times greater than that using the CW 1,455nm laser, suggesting that LTW accomplished through direct collagen excitation in the NIR optical window III provides greater tensile strengths.

Activatable photoacoustic bioprobe for visual detection of aging in vivo

Aging is a natural physiological process with various challenges, related to the loss of homeostasis within the organism, which is not a disease, but a significantly strong risk factor for multiple diseases, including myocardial infarction, stroke, some age-related cancers, macular degeneration, osteoarthritis, neurodegeneration, and many others. In the body, the main manifestation of aging is cellular aging, which exists within tissues and has a local or global impact on tissue function. However, the lack of effective aging detection tools has always been an issue that cannot be ignored in the field of aging research. Therefore, it is necessary to construct a non-invasive tool for in vivo detection of aging. Here, we show that the photoacoustic probe (LGAL), which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to the hallmark of aging, and allows for the microscopic imaging of aging through the intact mice. Firstly, this tool LGAL has been successfully applied to detect senescence in cells, displaying stronger photoacoustic signals than normal cells. Then, by using the photoacoustic probe, the blood vessels and tissues inside the mice can be visualized. Young and elderly mice exhibit varying intensities of photoacoustic signals, marking the first time a probe has been used to explore the aging of blood vessels and tissues inside the mice. Finally, we monitored the changes in the degree of aging during tumor treatment under photoacoustic (PA) imaging for the first time. As the treatment time increased, the degree of aging of the tumor gradually deepened. We expect the powerful tool could be a noninvasive and powerful tool for the study of aging biology.

Hyper-Branched Gold Nanoconstructs for Photoacoustic Imaging in the Near-Infrared Optical Window.

In plasmonic nanoconstructs (NCs), fine-tuning interparticle interactions at the subnanoscale offer enhanced electromagnetic and thermal responses in the near-infrared (NIR) wavelength range. Due to tunable electromagnetic and thermal characteristics, NCs can be excellent photoacoustic (PA) imaging contrast agents. However, engineering plasmonic NCs that maximize light absorption efficiency across multiple polarization directions, i.e., exhibiting blackbody absorption behavior, remains challenging. Herein, we present the synthesis, computational simulation, and characterization of hyper-branched gold nanoconstructs (HBGNCs) as a highly efficient PA contrast agent. HBGNCs exhibit remarkable optical properties, including strong NIR absorption, high absorption efficiency across various polarization angles, and superior photostability compared to conventional standard plasmonic NC-based contrast agents such as gold nanorods and gold nanostars. In vitro and in vivo experiments confirm the suitability of HBGNCs for cancer imaging, showcasing their potential as reliable PA contrast agents and addressing the need for enhanced imaging contrast and stability in bioimaging applications.

PHOTOLUMINESCENCE PROPERTIES OF Nd3+, Yb3+ CODOPED Ga2O3 NANOPARTICLES

The availability of sensitive photon detectors and inexpensive lasers allowed us to explore more efficient fluorescent probes that will work in the second near-infrared optical window. In this study, the optical properties of Nd3+ and Yb3+ co-doped Ga2O3 nanoparticles were studied. In order to indicate the correlation between particle size, crystallinity, and optical property of present samples XRD, TEM, and Photoluminescence analyses were performed. Various excitation wavelengths and dopant concentrations were used to understand the energy transfer mechanism in Nd3+ and Yb3+ co-doped Ga2O3 nanoparticles. As the excitation wavelength increased from 325 nm to 477 and 515 nm, Yb3+ emission peak intensity decreased while Nd3+ emission peak intensity increased. This inverse relationship between the emission intensities of Yb3+ and Nd3+ ion showed the presence of energy transfer between them. The resulting emission peaks were broad and weak, indicating the presence of a non-radiative decay channel due to the crystal defects.

Near-infrared fluorescence lifetime imaging of amyloid-β aggregates and tau fibrils through the intact skull of mice.

Non-invasive methods for the in vivo detection of hallmarks of Alzheimer's disease can facilitate the study of the progression of the disease in mouse models and may enable its earlier diagnosis in humans. Here we show that the zwitterionic heptamethine fluorophore ZW800-1C, which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to amyloid-β deposits and to neurofibrillary tangles, and allows for the microscopic imaging of amyloid-β and tau aggregates through the intact skull of mice. In transgenic mouse models of Alzheimer's disease, we compare the performance of ZW800-1C with that of the two spectrally similar heptamethine fluorophores ZW800-1A and indocyanine green, and show that ZW800-1C undergoes a longer fluorescence-lifetime shift when bound to amyloid-β and tau aggregates than when circulating in blood vessels. ZW800-1C may prove advantageous for tracking the proteinic aggregates in rodent models of amyloid-β and tau pathologies.

High Performance Gold Nanorods@DNA Self-Assembled Drug-Loading System for Cancer Thermo-Chemotherapy in the Second Near-Infrared Optical Window.

In terms of synergistic cancer therapy, biological nanomaterials with a second near-infrared (NIR-II) window response can greatly increase photothermal effects and photoacoustic imaging performance. Herein, we report a novel stimuli-responsive multifunctional drug-loading system which was constructed by integrating miniature gold nanorods (GNR) as the NIR-II photothermal nanorods and cyclic ternary aptamer (CTA) composition as a carrier for chemotherapy drugs. In this system, doxorubicin hydrochloride (DOX, a chemotherapy drug) binds to the G-C base pairs of the CTA, which exhibited a controlled release behavior based on the instability of G-C base pairs in the slightly acidic tumor microenvironment. Upon the 1064 nm (NIR-II biowindow) laser irradiation, the strong photothermal and promoted cargo release properties endow gold nanorods@CTA (GNR@CTA) nanoparticles displaying excellent synergistic anti-cancer effect. Moreover, the GNR@CTA of NIR also possesses thermal imaging and photoacoustic (PA) imaging properties due to the strong NIR region absorbance. This work enables to obtaining a stimuli-responsive “all-in-one” nanocarrier, which are promising candidate for bimodal imaging diagnosis and chemo-photothermal synergistic therapy.

Near Infrared Fluorescent Nanostructure Design for Organic/Inorganic Hybrid System.

Near infrared (NIR) light offers high transparency in biological tissue. Recent advances in NIR fluorophores including organic dyes and lanthanide-doped inorganic nanoparticles have realized the effective use of the NIR optical window for in vivo bioimaging and photodynamic therapy. The narrow energy level intervals used for electronic transition that involves NIR light, however, give rise to a need for guidelines for reducing heat emission in luminescence systems, especially in the development of organic/inorganic hybrid structures. This review presents an approach for employing the polarity and vibrational energy of ions and molecules that surround the luminescence centers for the development of such hybrid nanostructures. Multiphonon relaxation theory, formulated for dealing with heat release in ionic solids, is applied to describe the vibrational energy in organic or molecular systems, referred to as phonon in this review, and we conclude that surrounding the luminescence centers either with ions with low vibrational energy or molecules with small chemical polarity is the key to bright luminescence. NIR photoexcited phosphors and nanostructures in organic/inorganic mixed systems, designed based on the guidelines, for photodynamic therapy are reviewed.

Thienothiadiazole-Based NIR-II Dyes with D-A-D Structure for NIR-II Fluorescence Imaging Systems.

Fluorescence imaging (FI) in the second near-infrared optical window (NIR-II, 1000-1700 nm) has received increasing focus due to its capacity of high spatiotemporal resolution, rapid real-time imaging, and deep penetration depth. In addition, D-A-D-based organic small molecules have also attracted wide attention due to their designed chemical structure and rapid renal metabolism. However, most of the fluorescent cores were based on benzobisthiadiazole (BBTD) and 6,7-diphenyl-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TTQ). The design and development of fluorescent core still remain challenging. Therefore, two NIR-II dyes based on the acceptor 4,6-di(2-thienyl)thieno[3,4-c][1,2,5]thiadiazole (TTDT) were designed and developed with donors tributyl(5-(9,9-dioctyl-9H-fluoren-2-yl)thiophen-2-yl)stannane (TF) and (5-(9,9'-spirobi[fluoren]-2-yl)thiophen-2-yl)tributylstannane (TSF) by the Stille coupling reaction, respectively. Subsequently, the corresponding nanoparticles were prepared, and then TTDT-TF-based nanoparticles with superior photostability and strong NIR-II fluorescence signals were chosen for NIR-II FI. More importantly, the in vivo experiments suggested that TTDT-TF NPs exhibited significant accumulation at tumor sites and high signal-to-background ratio (SBR). The above results indicated that the two D-A-D-type fluorophores based on TTDT have potential for NIR-II FI with superior imaging quality and imaging-guided surgery or therapy.

Tunable NIR Absorption Property of a Dithiolene Nickel Complex: A Promising NIR-II Absorption Material for Photothermal Therapy.

Exogenous photothermal agents absorbing in the second near-infrared optical window (NIR-II, 1000-1700 nm) have received much attention due to their use in noninvasive photothermal therapy. A small quantity of organic NIR-II photothermal agents have been exploited, and the development of organic NIR-II photothermal materials is an urgent need for biological applications. In this study, we designed and synthesized three dithiolene nickel(II) complexes with different ligands-bis(phenyl) dithiolene for NiBD-Ph, bis(fluorenyl) dithiolene for NiBD-Fl, and bis(carbazolyl) dithiolene for NiBD-Cz-and investigated their photophysical properties. These complexes exhibited ligand-dependent NIR absorption performance, centered at 854 nm for NiBD-Ph, 942 nm for NiBD-Fl, and 1010 nm for NiBD-Cz, respectively. NiBD-Cz is wrapped in ethylene oxide/propylene oxide block copolymer (F-127) through a hydrophilic-hydrophobic interaction to form water-soluble NiBD-Cz/F-127 nanoparticles (NiBD-Cz NPs), and the absorption peak of NiBD-Cz NPs are red-shifted to 1036 nm. NiBD-Cz NPs exhibit good dispersibility in water, robust photostability, and a high photothermal conversion efficiency (PCE) of 63.6% under 1064 nm laser irradiation, which is the highest PCE among metal bis(dithiolene) complexes up to now. The high PCE makes it possible to achieve better photothermal treatment effects even at low concentrations and under low-power laser irradiation.

The polymeric glyco-linker controls the signal outputs for plasmonic gold nanorod biosensors due to biocorona formation.

Gold nanorods (GNRs) are a promising platform for nanoplasmonic biosensing. The localised surface plasmon resonance (LSPR) peak of GNRs is located in the near-infrared optical window and is sensitive to local binding events, enabling label-free detection of biomarkers in complex biological fluids. A key challenge in the development of such sensors is achieving target affinity and selectivity, while both minimizing non-specific binding and maintaining colloidal stability. Herein, we reveal how GNRs decorated with galactosamine-terminated polymer ligands display significantly different binding responses in buffer compared to serum, due to biocorona formation, and how biocorona displacement due to lectin binding plays a key role in their optical responses. GNRs were coated with either poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) or poly(N-hydroxyethyl acrylamide) (PHEA) prepared via reversible addition–fragmentation chain-transfer (RAFT) polymerisation and end-functionalised with galactosamine (Gal) as the lectin-targeting unit. In buffer Gal-PHEA-coated GNRs aggregated upon soybean agglutinin (SBA) addition, whereas Gal-PHPMA-coated GNRs exhibited a red-shift of the LSPR spectrum without aggregation. In contrast, when incubated in serum Gal-PHPMA-coated nanorods showed no binding response, while Gal-PHEA GNRs exhibited a dose-dependent blue-shift of the LSPR peak, which is the opposite direction (red-shift) to what was observed in buffer. This differential behaviour was attributed to biocorona formation onto both polymer-coated GNRs, shown by differential centrifugal sedimentation and nanoparticle tracking analysis. Upon addition of SBA to the Gal-PHEA coated nanorods, signal was generated due to displacement of weakly-bound biocorona components by lectin binding. However, in the case of Gal-PHPMA which had a thicker corona, attributed to lower polymer grafting densities, addition of SBA did not lead to biocorona displacement and there was no signal output. These results show that plasmonic optical responses in complex biological media can be significantly affected by biocorona formation, and that biocorona formation itself does not prevent sensing so long as its exact nature (e.g. ‘hard versus soft’) is tuned.

Short-wave Infrared Neural Stimulation Drives Graded Sciatic Nerve Activation Across A Continuum of Wavelengths.

Infrared neural stimulation (INS) is an optical stimulation technique which uses coherent light to stimulate nerves and neurons and which shows increased spatial selectivity compared to electrical stimulation. This could improve deep brain, high channel count, or vagus nerve stimulation. In this study, we seek to understand the wavelength dependence of INS in the near-infrared optical window. Rat sciatic nerves were excised ex vivo and stimulated with wavelengths between 700 and 900 nm. Recorded compound nerve action potentials (CNAPs) showed that stimulation was maximized in the 700 nm window despite comparable laser power levels across wavelengths. Computational models demonstrated that wavelength-based activation dependencies were not a result of passive optical properties. This data demonstrates that INS is both wavelength and power level dependent, which inform stimulation systems to actively target neural microcircuits in humans.

Research progress of mild photothermal therapy in cancer treatment

Cancer incidence and mortality are rapidly growing around the world. As a noninvasive strategy for cancer treatment, photothermal therapy (PTT) utilizes near-infrared (NIR) light absorbents to produce local hyperpyrexia from light energy, resulting in the thermal elimination of tumors. Different nanostructures that possess strong absorbance of NIR light have been exploited as photothermal agents (PTAs) that need to be biodegradable and have strong optical absorbance in the NIR optical window. However, it remains highly challenging to identify the small molecule-based photothermal agents with a high photothermal conversion efficiency (PCE). Therefore, various types of PTAs have been developed in the last decades. These PTAs usually absorb NIR light where the living cells exhibit no absorption and autofluorescence and are able to transit absorption light to heat energy. Based on previous reports, the synthesized PTAs can be classified into two types: Inorganic nanomaterials and organic small molecular nanomaterials. Recently, for the first time, we demonstrated the synthesis of two dimensional (2D) monoelemental germanene quantum dots (GeQDs) through a facile liquid exfoliation method for photonic cancer nanomedicine. Our research can solve the major problem that 2D materials are difficultly synthetized and traditional materials have low photothermal conversion efficiency. Currently, photothermal therapy is a new type of highly effective, non-invasive and highly targeted therapy for cancer, however, the high temperature induced by PTT may also cause serious damage to healthy tissues. Therefore, mild photothermal therapy (MPTT) with relatively low temperature has attracted more and more attention. Due to the limited antitumor effect of MPTT, it is usually combined with other strategies to synergistically eliminate cancer cells. MPTT nanoplatform with enhanced curative efficacy and lower side effect is promising to apply in the field of drug controlled release, imaging-guided cancer treatment, and integrated therapy with other anticancer approaches. In this review, we briefly introduce the types and characteristics of PTAs, their anticancer function and the combined strategies for cancer therapy. Finally, we discuss the role of MPTT as a promising new therapeutic strategy for cancer therapy.

Engineering Adenylate Cyclase Activated by Near-Infrared Window Light for Mammalian Optogenetic Applications.

Light in the near-infrared optical window (NIRW) penetrates deep through mammalian tissues, including the skull and brain tissue. Here we engineered an adenylate cyclase (AC) activated by NIRW light (NIRW-AC) and suitable for mammalian applications. To accomplish this goal, we constructed fusions of several bacteriophytochrome photosensory and bacterial AC modules using guidelines for designing chimeric homodimeric bacteriophytochromes. One engineered NIRW-AC, designated IlaM5, has significantly higher activity at 37 °C, is better expressed in mammalian cells, and can mediate cAMP-dependent photoactivation of gene expression in mammalian cells, in favorable contrast to the NIRW-ACs engineered earlier. The ilaM5 gene expressed from an AAV vector was delivered into the ventral basal thalamus region of the mouse brain, resulting in the light-controlled suppression of the cAMP-dependent wave pattern of the sleeping brain known as spindle oscillations. Reversible spindle oscillation suppression was observed in sleeping mice exposed to light from an external light source. This study confirms the robustness of principles of homodimeric bacteriophytochrome engineering, describes a NIRW-AC suitable for mammalian optogenetic applications, and demonstrates the feasibility of controlling brain activity via NIRW-ACs using transcranial irradiation.

Spinning-Disc Confocal Microscopy in the Second Near-Infrared Window (NIR-II)

Fluorescence microscopy in the second near-infrared optical window (NIR-II, 1000-1350 nm) has become a technique of choice for non-invasive in vivo imaging. The deep penetration of NIR light in living tissue, as well as minimal or complete absence of tissue autofluorescence within this range, offers increased resolution and contrast with even greater penetration depths. Here, we present a custom-built spinning-disc confocal laser microscope (SDCLM) that is specific to imaging in the NIR-II. The SDCLM achieves a lateral resolution of 0.5±0.1 µm and an axial resolution of 0.6±0.1 µm, showing a ~17% and ~45% enhancement in lateral and axial resolutions, respectively, compared to the corresponding wide-field configuration. We furthermore showcase several applications that demonstrate the use of the SDCLM for in situ, spatiotemporal tracking of NIR particles and bioanalytes within both synthetic and biological systems.

Three‐dimensional cellular imaging in thick biological tissue with confocal detection of one‐photon fluorescence in the near‐infrared II window

Fluorescence imaging in the second near-infrared optical window (NIR-II, 900-1700 nm) has become a technique of choice for noninvasive in vivo imaging in recent years. Greater penetration depths with high spatial resolution and low background can be achieved with this NIR-II window, owing to low autofluorescence within this optical range and reduced scattering of long wavelength photons. Here, we present a novel design of confocal laser scanning microscope tailored for imaging in the NIR-II window. We showcase the outstanding penetration depth of our confocal setup with a series of imaging experiments. HeLa cells labeled with PbS quantum dots with a peak emission wavelength of 1276 nm can be visualized through a 3.5-mm-thick layer of scattering medium, which is a 0.8% Lipofundin solution. A commercially available organic dye IR-1061 (emission peak at 1132 nm), in its native form, is used for the first time, as a NIR-II fluorescence label in cellular imaging. Our confocal setup is capable of capturing optically sectioned images of IR-1061 labeled chondrocytes in fixed animal cartilage at a depth up to 800 μm, with a superb spatial resolution of around 2 μm.

Miniature gold nanorods for photoacoustic molecular imaging in the second near-infrared optical window.

In photoacoustic imaging, the second near infrared (NIR II) window is where tissue generates the least background signal. However, the large size of the few available contrast agents in this spectral range impedes their pharmacokinetics and decreases their thermal stability, leading to unreliable photoacoustic imaging. Here, we synthesize miniaturized gold nanorods absorbing in NIR II that are 5–11 times smaller than regular-sized gold nanorods with a similar aspect ratio. Under nanosecond pulsed laser illumination, small nanorods are about three times more thermally stable and generate 3.5 times stronger photoacoustic signal than absorption-matched large counterparts. These unexpected findings are confirmed using theoretical and numerical analysis, showing that photoacoustic signal is not only proportional to the optical absorption of the nanoparticle solution but also to the surface-to-volume ratio of the nanoparticles. In living tumor bearing mice, these small targeted nanorods display a 30% improvement in efficiency of agent delivery to tumors and generate 4.5 times greater photoacoustic contrast.

Spinning-disc confocal microscopy in the second near-infrared window (NIR-II)

Fluorescence microscopy in the second near-infrared optical window (NIR-II, 1000–1350 nm) has become a technique of choice for non-invasive in vivo imaging. The deep penetration of NIR light in living tissue, as well as negligible tissue autofluorescence within this optical range, offers increased resolution and contrast with even greater penetration depths. Here, we present a custom-built spinning-disc confocal laser microscope (SDCLM) that is specific to imaging in the NIR-II. The SDCLM achieves a lateral resolution of 0.5 ± 0.1 µm and an axial resolution of 0.6 ± 0.1 µm, showing a ~17% and ~45% enhancement in lateral and axial resolution, respectively, compared to the corresponding wide-field configuration. We furthermore showcase several applications that demonstrate the use of the SDCLM for in situ, spatiotemporal tracking of NIR particles and bioanalytes within both synthetic and biological systems.

Theranostic Colloidal Nanoparticles of Pyrrolopyrrole Cyanine Derivatives for Simultaneous Near-Infrared Fluorescence Cancer Imaging and Photothermal Therapy.

Theranostic agents incorporating diagnostic and therapeutic agents together play crucial roles in clinical cancer treatment. On the one hand, near-infrared (NIR) fluorescence imaging strategies are expected to provide high-resolution real-time structural and molecular information with deep penetration to biological tissues in vivo. On the other hand, photothermal therapy (PTT) offers a highly efficient treatment to cancer with negligible safety concerns. To combine the strengths of both NIR fluorescence imaging and PTT for simultaneous cancer imaging and therapy, we report a type of NIR fluorescent nanoparticles (NPs) composed of pyrrolopyrrole cyanines (PPCys) with a strong absorbance in the NIR optical window. These NPs as effective theranostic agents show strong NIR fluorescence and photothermal effect for simultaneous cancer imaging and therapy at both in vitro and in vivo levels. The in vivo imaging and therapy results in nude mice demonstrate the promising potential of these NIR NPs for preclinical and clinical cancer imaging and therapy applications.

Transmittance Characterization of Objective Lenses Covering all Four Near Infrared Optical Windows and its Application to Three-Photon Microscopy Excited at 1820 nm

Near infrared (NIR) excitation or emission is capable of deep-tissue penetration in various modalities of optical microscopy. Based on the transmittance characterization of biological tissue, such as brains, four NIR optical windows have been demonstrated or suggested: The 800-nm, the 1300-nm, the 1700-nm, and the 2200-nm window. High-numerical aperture objective lenses are needed in optical microscopy to both deliver sufficient excitation light and collect efficient signal light to enable deep-tissue imaging. The transmittance performances of objective lenses are of vital importance. However, there is a lack of experimental characterization of the transmittance, especially at long wavelengths, which poses a dramatic obstacle for lens selection in imaging experiments. Here, we demonstrate detailed measurement results of the transmittance performance of air, water-immersion, and oil-immersion objectives available to us, covering all the four NIR optical windows. These results will provide direct guidelines for objective lens selection in terms of transmittance performance. We further demonstrate three-photon microscopy with 1820-nm excitation, close to the edge of the 1700-nm window, using the objective lens based on our transmittance measurement.