Search Results (23)

Imaging methods by the means of optical sensors are applied in diverse scientific areas such as medical research and diagnostics, aerodynamics, environmental analysis, or marine research. After a general introduction to the field, this review is focused on works published between 2012 and 2022. The covered topics include planar sensors (optrodes), nanoprobes, and sensitive coatings. Advanced sensor materials combined with imaging technologies enable the visualization of parameters which exhibit no intrinsic color or fluorescence, such as oxygen, pH, CO₂, H₂O₂, Ca²⁺, or temperature. The progress on the development of multiple sensors and methods for referenced signal read out is also highlighted, as is the recent progress in device design and application formats using model systems in the lab or methods for measurements’ in the field. Full article

We demonstrate a sensing scheme for liquid analytes that integrates multiple optical fiber sensors in a near-infrared spectrometer. With a simple optofluidic method, a broadband radiation is encoded in a time-domain interferogram and distributed to different sensing units that interrogate the sample simultaneously; the spectral readout of each unit is extracted from its output signal by a Fourier transform routine. The proposed method allows performing a multiparametric analysis of liquid samples in a compact setup where the radiation source, measurement units, and spectral readout are all integrated in a robust telecom optical fiber. An experimental validation is provided by combining a plasmonic nanostructured fiber probe and a transmission cuvette in the setup and demonstrating the simultaneous measurement of the absorption spectrum and the refractive index of water–methanol solutions. Full article

Neuromodulation techniques are essential for exploring brain science and supporting treatments for neurological disorders. Compared to electrical neuromodulation, optogenetic neuromodulation offers advantages in cell type specificity and spatial precision. However, existing optogenetic neuromodulation systems have limited functionality (unable to simultaneously possess functions including optogenetic stimulation, recording, and micro-LED (micro-Light-Emitting Diode) status monitoring) and will restrict normal biological activities due to their large size. To this end, this paper presents an optogenetic neuromodulation system, including a specified neuromodulation IC (Integrated Circuit) and a customized optrode. The ASIC (Application Specific Integrated Circuit) includes a 16-channel neural signal recording module, a 4-channel optogenetic neurostimulator module, and a 4-channel micro-LED detection module. The micro-LED detection module monitors the micro-LED’s long-term status in real time and provides the direct output of its working status for convenient user access. The neuromodulation ASIC was fabricated in the TSMC 65 nm process, and an in situ normal saline experiment was conducted to test the neuromodulation system’s function. Full article

Owing to its capacity to eliminate a long-standing methodological limitation, fiber photometry can assist research gaining novel insight into neural systems. Fiber photometry can reveal artifact-free neural activity under deep brain stimulation (DBS). Although evoking neural potential with DBS is an effective method for mediating neural activity and neural function, the relationship between DBS-evoked neural Ca²⁺ change and DBS-evoked neural electrophysiology remains unknown. Therefore, in this study, a self-assembled optrode was demonstrated as a DBS stimulator and an optical biosensor capable of concurrently recording Ca²⁺ fluorescence and electrophysiological signals. Before the in vivo experiment, the volume of tissue activated (VTA) was estimated, and the simulated Ca²⁺ signals were presented using Monte Carlo (MC) simulation to approach the realistic in vivo environment. When VTA and the simulated Ca²⁺ signals were combined, the distribution of simulated Ca²⁺ fluorescence signals matched the VTA region. In addition, the in vivo experiment revealed a correlation between the local field potential (LFP) and the Ca²⁺ fluorescence signal in the evoked region, revealing the relationship between electrophysiology and the performance of neural Ca²⁺ concentration behavior. Concurrent with the VTA volume, simulated Ca²⁺ intensity, and the in vivo experiment, these data suggested that the behavior of neural electrophysiology was consistent with the phenomenon of Ca²⁺ influx to neurons. Full article

Oxygen (O₂) uptake by cells and tissues is a critical indicator of metabolic demand, changes in microenvironment, and pathophysiology. O₂ uptake from the atmosphere accounts for virtually all the O₂ consumption in the avascular cornea; however, a detailed spatiotemporal profile of corneal O₂ uptake (COU) remains undetermined. Here, we used a non-invasive self-referencing optical fiber O₂ sensor—the scanning micro-optrode technique (SMOT)—to report the O₂ partial pressure and flux variations at the ocular surface of rodents and non-human primates. In vivo spatial mapping in mice revealed a distinct COU, characterized by a centripetal gradient with a significantly higher O₂ influx at the limbus and conjunctiva regions than at the center of the cornea. This regional COU profile was reproduced ex vivo in freshly enucleated eyes. The centripetal gradient was conserved across the following species analyzed: mice, rats, and rhesus monkeys. In vivo temporal mapping in mice showed a significant increase in the O₂ flux in the limbus in the evening compared to other times. Altogether, the data unveiled a conserved centripetal COU profile, which may be associated with the limbal epithelial stem cells residing at the intersection of the limbus and conjunctiva. These physiological observations will serve as a useful baseline for comparative studies with contact lens wear, ocular disease, diabetes, etc. Moreover, the sensor may be applied to understand the responses of the cornea and other tissues to various insults, drugs, or changes in the environment. Full article

Lab-on-fiber (LoF) optrodes offer several advantages over conventional techniques for point-of-care platforms aimed at real-time and label-free detection of clinically relevant biomarkers. Moreover, the easy integration of LoF platforms in medical needles, catheters, and nano endoscopes offer unique potentials for in vivo biopsies and tumor microenvironment assessment. The main barrier to translating the vision close to reality is the need to further lower the final limit of detection of developed optrodes. For immune-biosensing purposes, the assay sensitivity significantly relies on the capability to correctly immobilize the capture antibody in terms of uniform coverage and correct orientation of the bioreceptor, especially when very low detection limits are requested as in the case of cancer diagnostics. Here, we investigated the possibility to improve the immobilization strategies through the use of hinge carbohydrates by involving homemade antibodies that demonstrated a significantly improved recognition of the antigen with ultra-low detection limits. In order to create an effective pipeline for the improvement of biofunctionalization protocols to be used in connection with LoF platforms, we first optimized the protocol using a microfluidic surface plasmon resonance (mSPR) device and then transferred the optimized strategy onto LoF platforms selected for the final validation. Here, we selected two different LoF platforms: a biolayer interferometry (BLI)-based device (commercially available) and a homemade advanced LoF biosensor based on optical fiber meta-tips (OFMTs). As a clinically relevant scenario, here we focused our attention on a promising serological biomarker, Cripto-1, for its ability to promote tumorigenesis in breast and liver cancer. Currently, Cripto-1 detection relies on laborious and time-consuming immunoassays. The reported results demonstrated that the proposed approach based on oriented antibody immobilization was able to significantly improve Cripto-1 detection with a 10-fold enhancement versus the random approach. More interestingly, by using the oriented antibody immobilization strategy, the OFMTs-based platform was able to reveal Cripto-1 at a concentration of 0.05 nM, exhibiting detection capabilities much higher (by a factor of 250) than those provided by the commercial LoF platform based on BLI and similar to the ones shown by the commercial and well-established bench-top mSPR Biacore 8K system. Therefore, our work opened new avenues into the development of high-sensitivity LoF biosensors for the detection of clinically relevant biomarkers in the sub-ng/mL range. Full article

Optrodes, which are single shaft neural probes integrated with microelectrodes and optical light sources, offer a remarkable opportunity to simultaneously record and modulate neural activities using light within an animal’s brain; however, a common problem with optrodes is that stimulation artifacts can be observed in the neural recordings of microelectrodes when the light source on the optrode is activated. These stimulation artifacts are undesirable contaminants, and they cause interpretation complexity when analyzing the recorded neural activities. In this paper, we tried to mitigate the effects of the stimulation artifacts by developing a low-noise, double-sided optrode integrated with multiple Electromagnetic Shielding (EMS) layers. The LED and microelectrodes were constructed separately on the top epitaxial and bottom substrate layers, and EMS layers were used to separate the microelectrodes and LED to reduce signal cross-talks. Compared with conventional single-sided designs, in which the LED and microelectrodes are constructed on the same side, our results indicate that double-sided optrodes can significantly reduce the presence of stimulation artifacts. In addition, the presence of stimulation artifacts can further be reduced by decreasing the voltage difference and increasing the rise/fall time of the driving LED pulsed voltage. With all these strategies, the presence of stimulation artifacts was significantly reduced by ~76%. As well as stimulation suppression, the sapphire substrate also provided strong mechanical stiffness and support to the optrodes, as well as improved electronic stability, thus making the double-sided sapphire optrodes highly suitable for optogenetic neuroscience research on animal models. Full article

Biocompatibility and potential efficacy in biological applications rely on the bio-interactions of graphene nanoparticles with biological tissues. Analyzing and modulating cellular and device-level activity requires non-invasive electrical stimulation of cells. To address these needs, G-optrodes, bio-interfaces based on graphene, have been developed. These devices use light to stimulate cells without modifying their genetic code. Optoelectronic capabilities, in particular the capacity to transform light energy into electrical energy, will be maintained throughout the procedures of neural stimulation. G-optrodes have also been studied as thin films on a range of substrates, and they have been designed to function at a very small scale. This study examines the impact of G-optrode-based substrate designs on the optical stimulation of pheochromocytoma (PC-12). Graphene electrodes, known as G-optrodes, are responsible for converting light into electrical pulses with stimulating effects. G-optrode bio-interfaces provide a stimulus that is independent of wavelength range but is sensitive to changes in illuminance. The authors have performed a comprehensive investigation based on the correct effects of the medication in vitro, employing substrate-based G-optrode biointerfaces. In substrate-based systems, the authors have proven that graphene is biocompatible. PC-12 cells were cultured on graphene for 7 days. Based on the findings, 20-nm and 50-nm thick G-optrodes are being studied for possible use in biological and artificial retinal applications. The findings of this study highlight the significance of biocompatibility in the selection and use of G-optrodes for biomedical purposes. Full article

Shake flasks remain one of the most widely used cultivation systems in biotechnology, especially for process development (cell line and parameter screening). This can be justified by their ease of use as well as their low investment and running costs. A disadvantage, however, is that cultivations in shake flasks are black box processes with reduced possibilities for recording online data, resulting in a lack of control and time-consuming, manual data analysis. Although different measurement methods have been developed for shake flasks, they lack comparability, especially when changing production organisms. In this study, the use of online backscattered light, dissolved oxygen, and pH data for characterization of animal, plant, and microbial cell culture processes in shake flasks are evaluated and compared. The application of these different online measurement techniques allows key performance indicators (KPIs) to be determined based on online data. This paper evaluates a novel data science workflow to automatically determine KPIs using online data from early development stages without human bias. This enables standardized and cost-effective process-oriented cell line characterization of shake flask cultivations to be performed in accordance with the process analytical technology (PAT) initiative. The comparison showed very good agreement between KPIs determined using offline data, manual techniques, and automatic calculations based on multiple signals of varying strengths with respect to the selected measurement signal. Full article

This paper presents a tetherless and miniaturized closed-loop optogenetic brain stimulation device, designed as a back mountable device for laboratory mice. The device has the ability to sense the biomarkers corresponding to major depressive disorder (MDD) from local field potential (LFP), and produces a feedback signal to control the closed-loop operation after on-device processing of the sensed signals. MDD is a chronic neurological disorder and there are still many unanswered questions about the underlying neurological mechanisms behind its occurrence. Along with other brain stimulation paradigms, optogenetics has recently proved effective in the study of MDD. Most of these experiments have used tethered and connected devices. However, the use of tethered devices in optogenetic brain stimulation experiments has the drawback of hindering the free movement of the laboratory animal subjects undergoing stimulation. To address this issue, the proposed device is small, light-weight, untethered, and back-mountable. The device consists of: (i) an optrode which houses an electrode for collecting neural signals, an optical source for delivering light stimulations, and a temperature sensor for monitoring the temperature increase at the stimulation site, (ii) a neural sensor for acquisition and pre-processing of the neural signals to obtain LFP signals in the frequency range of 4 to 200 Hz, as electrophysiological biomarkers of MDD (iii) a classifier for classification of the signal into four classes: normal, abnormal alpha, abnormal theta, and abnormal gamma oscillations, (iv) a control algorithm to select stimulation parameters based on the input class, and (v) a stimulator for generating light stimulations. The design, implementation, and evaluation of the device are presented, and the results are discussed. The neural sensor and the stimulator are circular in shape with a radius of 8 mm. Pre-recorded neural signals from the mouse hippocampus are used for the evaluation of the device. Full article

The need for miniaturized biological sensors which can be easily integrated into medical needles and catheters for in vivo liquid biopsies with ever-increasing performances has stimulated the interest of researchers in lab-on-fiber (LOF) technology. LOF devices arise from the integration of functional materials at the nanoscale on the tip of optical fibers, thus endowing a simple optical fiber with advanced functionalities and enabling the realization of high-performance LOF biological sensors. Consequently, in 2017, we demonstrated the first optical fiber meta-tip (OFMT), consisting of the integration of plasmonic metasurfaces (MSs) on the optical fiber end-face which represented a major breakthrough along the LOF technology roadmap. Successively, we demonstrated that label-free biological sensors based on the plasmonic OFMT are able to largely overwhelm the performance of a standard plasmonic LOF sensor, in view of the extraordinary light manipulation capabilities of plasmonic array exploiting phase gradients. To further improve the overall sensitivity, a labelled sensing strategy is here suggested. To this end, we envision the possibility to realize a novel class of labelled LOF optrodes based on OFMT, where an all-dielectric MS, designed to enhance the fluorescence emission by a labelled target molecule, is integrated on the end-face of a multimode fiber (MMF). We present a numerical environment to compute the fluorescence enhancement factor collected by the MMF, when on its tip a Silicon MS is laid, consisting of an array of cylindrical nanoantennas, or of dimers or trimers of cylindrical nanoantennas. According to the numerical results, a suitable design of the dielectric MS allows for a fluorescence enhancement up to three orders of magnitudes. Moreover, a feasibility study is carried out to verify the possibility to fabricate the designed MSs on the termination of multimode optical fibers using electron beam lithography followed by reactive ion etching. Finally, we analyze a real application scenario in the field of biosensing and evaluate the degradation in the fluorescence enhancement performances, taking into account the experimental conditions. The present work, thus, provides the main guidelines for the design and development of advanced LOF devices based on the fluorescence enhancement for labelled biosensing applications. Full article

Integrated optrodes for optogenetics have been becoming a significant tool in neuroscience through the combination of offering accurate stimulation to target cells and recording biological signals simultaneously. This makes it not just be widely used in neuroscience researches, but also have a great potential to be employed in future treatments in clinical neurological diseases. To optimize the integrated optrodes, this paper aimed to investigate the influence of surface material and illumination upon the performance of the microelectrode/electrolyte interface and build a corresponding evaluation system. In this work, an integrated planar optrode with a blue LED and microelectrodes was designed and fabricated. The charge transfer mechanism on the interface was theoretically modeled and experimentally verified. An evaluation system for assessing microelectrodes was also built up. Using this system, the proposed model of various biocompatible surface materials on microelectrodes was further investigated under different illumination conditions. The influence of illumination on the microelectrode/electrolyte interface was the cause of optical artifacts, which interfere the biological signal recording. It was found that surface materials had a great effect on the charge transfer capacity, electrical stability and recoverability, photostability, and especially optical artifacts. The metal with better charge transfer capacity and electrical stability is highly possible to have a better performance on the optical artifacts, regardless of its electrical recoverability and photostability under the illumination conditions of optogenetics. Among the five metals used in our investigation, iridium served as the best surface material for the proposed integrated optrodes. Thus, optimizing the surface material for optrodes could reduce optical interference, enhance the quality of the neural signal recording for optogenetics, and thus help to advance the research in neuroscience. Full article

During the last decade, optogenetics has become an essential tool for neuroscience research due to its unrivaled feature of cell-type-specific neuromodulation. There have been several technological advances in light delivery devices. Among them, the combination of optogenetics and electrophysiology provides an opportunity for facilitating optogenetic approaches. In this study, a novel design of an optrode array was proposed for realizing optical modulation and electrophysiological recording. A 4 × 4 optrode array and five-channel recording electrodes were assembled as a disposable part, while a reusable part comprised an LED (light-emitting diode) source and a power line. After the characterization of the intensity of the light delivered at the fiber tips, in vivo animal experiment was performed with transgenic mice expressing channelrhodopsin, showing the effectiveness of optical activation and neural recording. Full article

Antibiotic resistance is a serious threat to public health. The empiric use of the wrong antibiotic occurs due to urgency in treatment combined with slow, culture-based diagnostic techniques. Inappropriate antibiotic choice can promote the development of antibiotic resistance. We investigated live/dead spectrometry using a fluorimeter (Optrode) as a rapid alternative to culture-based techniques through application of the LIVE/DEAD^® BacLight^TM Bacterial Viability Kit. Killing was detected by the Optrode in near real-time when Escherichia coli was treated with lytic antibiotics—ampicillin and polymyxin B—and stained with SYTO 9 and/or propidium iodide. Antibiotic concentration, bacterial growth phase, and treatment time used affected the efficacy of this detection method. Quantification methods of the lethal action and inhibitory action of the non-lytic antibiotics, ciprofloxacin and chloramphenicol, respectively, remain to be elucidated. Full article

Epilepsy is a chronic, neurological disorder affecting millions of people every year. The current available pharmacological and surgical treatments are lacking in overall efficacy and cause side-effects like cognitive impairment, depression, tremor, abnormal liver and kidney function. In recent years, the application of optogenetic implants have shown promise to target aberrant neuronal circuits in epilepsy with the advantage of both high spatial and temporal resolution and high cell-specificity, a feature that could tackle both the efficacy and side-effect problems in epilepsy treatment. Optrodes consist of electrodes to record local field potentials and an optical component to modulate neurons via activation of opsin expressed by these neurons. The goal of optogenetics in epilepsy is to interrupt seizure activity in its earliest state, providing a so-called closed-loop therapeutic intervention. The chronic implantation in vivo poses specific demands for the engineering of therapeutic optrodes. Enzymatic degradation and glial encapsulation of implants may compromise long-term recording and sufficient illumination of the opsin-expressing neural tissue. Engineering efforts for optimal optrode design have to be directed towards limitation of the foreign body reaction by reducing the implant’s elastic modulus and overall size, while still providing stable long-term recording and large-area illumination, and guaranteeing successful intracerebral implantation. This paper presents an overview of the challenges and recent advances in the field of electrode design, neural-tissue illumination, and neural-probe implantation, with the goal of identifying a suitable candidate to be incorporated in a therapeutic approach for long-term treatment of epilepsy patients. Full article