Interferometric Biosensor for High Sensitive Label-Free Recording of HiPS Cardiomyocytes Contraction in Vitro.

Heart disease remains a leading cause of global mortality, underscoring the need for advanced technologies to study cardiovascular diseases and develop effective treatments. We introduce an innovative interferometric biosensor for high-sensitivity and label-free recording of human induced pluripotent stem cell (hiPSC) cardiomyocyte contraction in vitro. Using an optical cavity, our device captures interference patterns caused by the contraction-induced displacement of a thin flexible membrane. First, we demonstrate the capability to quantify spontaneous contractions and discriminate between contraction and relaxation phases. We calculate a contraction-induced vertical membrane displacement close to 40 nm, which implies a traction stress of 34 ± 4 mN/mm2. Finally, we investigate the effects of a drug compound on contractility amplitude, revealing a significant reduction in contractile forces. The label-free and high-throughput nature of our biosensor may enhance drug screening processes and drug development for cardiac treatments. Our interferometric biosensor offers a novel approach for noninvasive and real-time assessment of cardiomyocyte contraction.

Comparison of measurements and calculated lens power using three biometers: a Scheimpflug tomographer with partial coherence interferometry and two swept source optical coherence tomographers.

PURPOSE: To compare the biometric measurements obtained from the Pentacam AXL Wave, IOLMaster 700, and ANTERION and calculate the recommended intraocular lens power using the Barrett Formulae. METHODS: This was a retrospective cross-sectional study of patients who underwent biometry using the Pentacam AXL Wave, IOLMaster 700, and ANTERION. Flat keratometry (K1), steep keratometry (K2), anterior chamber depth (ACD), and axial length (AL) from each device were measured and compared. These parameters were used to calculate the recommended IOL powers using the Barrett formula. RESULTS: The study included 252 eyes of 153 patients. The IOLMaster had the highest acquisition rate among the two biometers. The Pentacam obtained the shortest mean AL, the IOLMaster measured the highest mean keratometry values, and the ANTERION measured the highest mean ACD. In terms of pairwise comparisons, keratometry and axial length were not significantly different between the Pentacam-IOLMaster and ANTERION-IOLMaster groups, while the rest of the pairwise comparisons were statistically significant. In nontoric and toric eyes, 35-45% of patients recommended the same sphere of IOL power. In another 30-40%, the Pentacam and ANTERION recommended an IOL power one step greater than that of the IOLMaster-derived data. 50% of the study population recommended the same toric-cylinder IOL power. CONCLUSIONS: The Pentacam AXL Wave, IOLMaster 700, and ANTERION can reliably provide data for IOL power calculations; however, these data are not interchangeable. In nontoric and toric eyes, 35-45% of cases recommended the same sphere IOL power, and in another 30-40%, the Pentacam and ANTERION recommended one-step higher IOL power than the IOLMaster-derived data. In targeting emmetropia, selecting the first plus IOL power is advisable when using the Pentacam and ANTERION to approximate the IOL power calculations recommended by the IOLMaster 700.

Agreement between a new fully automatic ocular biometer based on optical low-coherence reflectometry and an optical biometer based on Scheimpflug imaging combined with partial coherence interferometry.

BACKGROUND: To analyze the difference and agreement between measurements obtained by a new fully automatic optical biometer, the SW-9000 µm Plus, based on optical low-coherence reflectometry (OLCR) and a commonly used optical biometer (Pentacam AXL) based on Scheimpflug imaging with partial coherence interferometry (PCI). METHODS: The central corneal thickness (CCT), anterior chamber depth (ACD, from epithelium to anterior lens surface), lens thickness (LT), mean keratometry (Km), corneal astigmatism, corneal diameter (CD), pupil diameter (PD), and axial length (AL) of 74 eyes (from 74 healthy subjects) were measured using the SW-9000 µm Plus and the Pentacam AXL to determine the agreement. Double angle plots were used for astigmatism vector analysis. Bland-Altman and 95% limits of agreement (LoA) were calculated. RESULTS: Statistically significant differences were detected for all parameters but J0 vector. The Bland-Altman analysis of AL, CCT, ACD, Km, CD, J0 and J45 indicated a high level of agreement between the two devices. Among AL, CCT, ACD, Km, J0, J45, CD, and PD, the 95% LoA ranged from -0.07 to 0.05 mm, -9.67 to 7.34 mm, -0.11 to 0.04 mm, -0.25 to 0.50 D, -0.22 to 0.20 D, -0.15 to 0.20 D, -0.23 to 0.35 mm and 1.55 to 3.77 mm, respectively. CONCLUSIONS: The measurements of AL, CCT, ACD, Km, corneal astigmatism, and CD showed a narrow LoA and may be used interchangeably in healthy subjects between the new OLCR optical biometer and the Scheimpflug/PCI biometer; however, a poor agreement was noted for PD values.

Fiber Bragg Grating Pulse and Systolic Blood Pressure Measurement System Based on Mach-Zehnder Interferometer.

A fiber Bragg grating (FBG) pulse and systolic blood pressure (SBP) measurement system based on the edge-filtering method is proposed. The edge filter is the Mach-Zehnder interferometer (MZI) fabricated by two fiber couplers with a linear slope of 52.45 dBm/nm. The developed system consists of a broadband light source, an edge filter, fiber Bragg gratings (FBGs), a coarse wavelength-division multiplexer (CWDM), and signal-processing circuits based on a field-programmable gate array (FPGA). It can simultaneously measure pulse pulsations of the radial artery in the wrist at three positions: Cun, Guan and Chi. The SBP can be calculated based on the pulse transit time (PTT) principle. The measurement results compared to a standard blood pressure monitor showed the mean absolute error (MAE) and standard deviation (STD) of the SBP were 0.93 ± 3.13 mmHg. The system meets the requirements of the Association for the Advancement of Medical Instrumentation (AAMI) equipment standards. The proposed system can achieve continuous real-time measurement of pulse and SBP and has the advantages of fast detection speed, stable performance, and no compression sensation for subjects. The system has important application value in the fields of human health monitoring and medical device development.

Balloon-Shaped SMF Blood Glucose Concentration and Temperature Sensor Based on Core-Offset Structure.

A blood glucose concentration and temperature sensor with a balloon-shaped single-mode fiber (SMF) based on a core-offset structure is proposed and experimentally demonstrated. The balloon-shaped SMF is created by offset-fusing a straight-line SMF between two other SMFs, thereby forming a Mach-Zehnder interferometer (MZI). The core-offset structure can effectively excite higher-order cladding modes. The experimental results showed that the maximum sensitivity of blood glucose concentration was 0.331 nm/(mmol/l) and the maximum sensitivity of temperature was 0.216 nm/°C when the offset distance was 10 µm. Dual-parameter measurement was achieved through a dual-parameter matrix. In addition, the sensor has characteristics such as simple structure, low cost, good stability, and electromagnetic interference resistance, making it potentially valuable for diagnosing high blood glucose and related conditions.

Au-NPs signal amplification ultra-sensitivity optical microfiber interferometric biosensor.

An optical microfiber interferometric biosensor for the low concentration detection of sequence-specific deoxyribonucleic acid (DNA) based on signal amplification technology via oligonucleotides linked to gold nanoparticles (Au-NPs) is proposed and experimentally analyzed. The sensor uses a "sandwich" detection strategy, in which capture probe DNA (DNA-c) is immobilized on the surface of the optical microfiber interferometer, the reporter probe DNA (DNA-r) is immobilized on the surface of Au-NPs, and the DNA-c and DNA-r are hybridized to the target probe DNA (DNA-t) in a sandwich arrangement. The dynamic detection of the DNA-t was found to range from 1.0×10-15 M to 1.0×10-8 M, and the limit of detection (LOD) concentration was 1.32 fM. This sensor exhibited not only a low LOD but also excellent selectivity against mismatched DNA-t, and it can be further developed for application in various sensing platforms.

High sensitivity X-ray phase contrast imaging by laboratory grating-based interferometry at high Talbot order geometry.

X-ray phase contrast imaging is a powerful analysis technique for materials science and biomedicine. Here, we report on laboratory grating-based X-ray interferometry employing a microfocus X-ray source and a high Talbot order (35th) asymmetric geometry to achieve high angular sensitivity and high spatial resolution X-ray phase contrast imaging in a compact system (total length <1 m). The detection of very small refractive angles (∼50 nrad) at an interferometer design energy of 19 keV was enabled by combining small period X-ray gratings (1.0, 1.5 and 3.0 µm) and a single-photon counting X-ray detector (75 µm pixel size). The performance of the X-ray interferometer was fully characterized in terms of angular sensitivity and spatial resolution. Finally, the potential of laboratory X-ray phase contrast for biomedical imaging is demonstrated by obtaining high resolution X-ray phase tomographies of a mouse embryo embedded in solid paraffin and a formalin-fixed full-thickness sample of human left ventricle in water with a spatial resolution of 21.5 µm.

Quantification of HER2 in COS7 cells using quantum weak measurement.

A Mach-Zehnder interferometer system based on weak measurement was set up to determinate the concentration variation of molecule by measuring the phase difference change between the two optical paths. The spectrum of the light was recorded to monitor the concentration of trastuzumab (Herceptin), which is a humanised monoclonal antibody, targeted to human epidermal growth factor receptor 2 (HER2). The trastuzumab targeting to HER2 was real-time detected and continuously monitored, the HER2 numbers of COS7 cells on a coverslip was determined at pico-molar level. Our weak measurement enabled method proposes an alternative approach for the concentration detection of molecules, providing a promising functional tool for the quantification of HER2 in cancer cells, possibly promoting fields such as the diagnosis and treatment of cancer.

Brillouin Light Scattering: Applications in Biomedical Sciences.

Brillouin spectroscopy and imaging are emerging techniques in analytical science, biophotonics, and biomedicine. They are based on Brillouin light scattering from acoustic waves or phonons in the GHz range, providing a nondestructive contactless probe of the mechanics on a microscale. Novel approaches and applications of these techniques to the field of biomedical sciences are discussed, highlighting the theoretical foundations and experimental methods that have been developed to date. Acknowledging that this is a fast moving field, a comprehensive account of the relevant literature is critically assessed here.

Real-time measurement method for the skin temperature of the human arm via large lateral shearing interferometry.

This paper presents a real-time measurement method for the skin temperature of the human arm. In this method, the air temperature close to the arm skin is measured via large lateral shearing interferometry, thus avoiding the possible influences of the different physical characteristics of different people, while maintaining the advantages of optical measurement, including its noncontact, noninvasive, and rapid features. The method captures the real-time fringe patterns generated using a parallel-sided plate when a collimated laser light beam transfers through the air surrounding the arm to be measured. Additionally, the phase difference distribution caused by the temperature difference is calculated in combination with the background fringe patterns. The phase difference in the light close to the arm skin is then estimated via a linear fitting method. Accordingly, based on the size parameters of the arm cross section and the ambient temperature monitored in real time, the air temperature close to the arm skin, which is considered equal to the arm skin temperature, is determined while considering the heat conduction effect. Experimental measurements of the temperature of human arm skin were conducted using the proposed method, and the axillary temperatures of the same person before and after the experiments were also measured using an electronic thermometer and a mercury thermometer. Good agreements were found, verifying the reliability of the proposed method. Moreover, based on this method, the possibility for the construction of a real-time body temperature measurement system is also discussed.

Tapered Mach-Zehnder interferometer based on PbS quantum dots modified by polymers for copper ion sensing.

An optical fiber interferometer coated with PbS quantum dots (QDs) was developed for copper ion (${{\rm{Cu}}^{2 +}}$) detection. The QDs were modified by a multifunctional copolymer that enabled QD surface ligation, dispersion, and coordination with ${{\rm{Cu}}^{2 +}}$. ${{\rm{Cu}}^{2 +}}$ coordination with the polymer induced changes in the surrounding refractive index of the interferometer. The sensor was highly selective for ${{\rm{Cu}}^{2 +}}$ and showed a linear detection range of 0-1000 µM with a limit of detection of 2.20 µM in both aqueous and biological solutions.

Interferometric plasmonic imaging and detection of single exosomes.

Exosomes play an important role in numerous cellular processes. Fundamental study and practical use of exosomes are significantly constrained by the lack of analytical tools capable of physical and biochemical characterization. In this paper, we present an optical approach capable of imaging single exosomes in a label-free manner, using interferometric plasmonic microscopy. We demonstrate monitoring of the real-time adsorption of exosomes onto a chemically modified Au surface, calculating the image intensity, and determining the size distribution. The sizing capability enables us to quantitatively measure the membrane fusion activity between exosomes and liposomes. We also report the recording of the dynamic interaction between exosomes and antibodies at the single-exosome level, and the tracking of hit-stay-run behavior of exosomes on an antibody-coated surface. We anticipate that the proposed method will contribute to clinical exosome analysis and to the exploration of fundamental issues such as the exosome-antibody binding kinetics.

Characterisation of the static offset in the travelling wave in the cochlear basal turn.

In mammals, audition is triggered by travelling waves that are evoked by acoustic stimuli in the cochlear partition, a structure containing sensory hair cells and a basilar membrane. When the cochlea is stimulated by a pure tone of low frequency, a static offset occurs in the vibration in the apical turn. In the high-frequency region at the cochlear base, multi-tone stimuli induce a quadratic distortion product in the vibrations that suggests the presence of an offset. However, vibrations below 100 Hz, including a static offset, have not been directly measured there. We therefore constructed an interferometer for detecting motion at low frequencies including 0 Hz. We applied the interferometer to record vibrations from the cochlear base of guinea pigs in response to pure tones. When the animals were exposed to sound at an intensity of 70 dB or higher, we recorded a static offset of the sinusoidally vibrating cochlear partition by more than 1 nm towards the scala vestibuli. The offset's magnitude grew monotonically as the stimuli intensified. When stimulus frequency was varied, the response peaked around the best frequency, the frequency that maximised the vibration amplitude at threshold sound pressure. These characteristics are consistent with those found in the low-frequency region and are therefore likely common across the cochlea. The offset diminished markedly when the somatic motility of mechanosensitive outer hair cells, the force-generating machinery that amplifies the sinusoidal vibrations, was pharmacologically blocked. Therefore, the partition offset appears to be linked to the electromotile contraction of outer hair cells.

Mid-IR refractive index sensor for detecting proteins employing an external cavity quantum cascade laser-based Mach-Zehnder interferometer.

Novel laser light sources in the mid-infrared region enable new spectroscopy schemes beyond classical absorption spectroscopy. Herein, we introduce a refractive index sensor based on a Mach-Zehnder interferometer and an external-cavity quantum cascade laser that allows rapid acquisition of high-resolution spectra of liquid-phase samples, sensitive to relative refractive index changes down to 10-7. Dispersion spectra of three model proteins in deuterated solution were recorded at concentrations as low as 0.25 mg mL-1. Comparison with Kramers-Kronig-transformed Fourier transform infrared absorbance spectra revealed high conformance, and obtained figures of merit compare well with conventional high-end FTIR spectroscopy. Finally, we performed partial least squares-based multivariate analysis of a complex ternary protein mixture to showcase the potential of dispersion spectroscopy utilizing the developed sensor to tackle complex analytical problems. The results indicate that laser-based dispersion sensing can be successfully used for qualitative and quantitative analysis of proteins.

Coherent silicon photonic interferometric biosensor with an inexpensive laser source for sensitive label-free immunoassays.

Over the past two decades, integrated photonic sensors have been of major interest to the optical biosensor community due to their capability to detect low concentrations of molecules with label-free operation. Among these, interferometric sensors can be read-out with simple, fixed-wavelength laser sources and offer excellent detection limits but can suffer from sensitivity fading when not tuned to their quadrature point. Recently, coherently detected sensors were demonstrated as an attractive alternative to overcome this limitation. Here we show, for the first time, to the best of our knowledge, that this coherent scheme provides sub-nanogram per milliliter limits of detection in C-reactive protein immunoassays and that quasi-balanced optical arm lengths enable operation with inexpensive Fabry-Perot-type lasers sources at telecom wavelengths.

Label-free detection of nosocomial bacteria using a nanophotonic interferometric biosensor.

Nosocomial infections are a major concern at the worldwide level. Early and accurate identification of nosocomial pathogens is crucial to provide timely and adequate treatment. A prompt response also prevents the progression of the infection to life-threatening conditions, such as septicemia or generalized bloodstream infection. We have implemented two highly sensitive methodologies using an ultrasensitive photonic biosensor based on a bimodal waveguide interferometer (BiMW) for the fast detection of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), two of the most prevalent bacteria associated with nosocomial infections. For that, we have developed a biofunctionalization strategy based on the use of a PEGylated silane (silane-PEG-COOH) which provides a highly resistant and bacteria-repelling surface, which is crucial to specifically detect each bacterium. Two different biosensor assays have been set under standard buffer conditions: one based on a specific direct immunoassay employing polyclonal antibodies for the detection of P. aeruginosa and another one employing aptamers for the direct detection of MRSA. The biosensor immunoassay for P. aeruginosa is fast (it only takes 12 min) and specific and has experimentally detected concentrations down to 800 cfu mL-1 (cfu: colony forming unit). The second one relies on the use of an aptamer that specifically detects penicillin-binding protein 2a (PBP2a), a protein only expressed in the MRSA mutant, providing a photonic biosensor with the ability to identify the resistant pathogen MRSA and differentiate it from methicillin-susceptible S. aureus (MSSA). Direct, label-free, and selective detection of whole MRSA bacteria has been achieved, making possible the direct detection of also 800 cfu mL-1. According to the signal-to-noise (S/N) ratio of the device, a theoretical limit of detection (LOD) of around 49 and 29 cfu mL-1 was estimated for P. aeruginosa and MRSA, respectively. Both results obtained under standard conditions reveal the great potential this interferometric biosensor device has as a versatile and specific tool for bacterial detection and quantification, providing a rapid method for the identification of nosocomial pathogens within the clinical requirements of sensitivity for the diagnosis of infections.

Oxidization increases the binding of EGCG to serum albumin revealed by kinetic data from label-free optical biosensor with reference channel.

Epigallocatechin-gallate (EGCG) is the main polyphenol ingredient of green tea. This compound is a strong antioxidant and oxidizes easily. Numerous studies demonstrated its beneficial effects on the human health, for example its anticancer and anti-inflammatory activity. In the body, EGCG is transported by serum albumin. EGCG easily oxidizes and the interactions of the oxidized form presumably present significant differences. However, the presence of oxidized EGCG is usually neglected in the literature and its effects have not been investigated in detail. Here, we applied the label-free grating coupled interferometry method that performs dual-channel measurements. The measured kinetic signal can be compensated with a signal of a reference channel at each measurement time. By testing both hydrophilic and hydrophobic platforms, we found that EGCG can bind to a wide range of surfaces. Exploiting the dual-channel referencing ability as well as the unique sensitivity and throughput of the employed label-free technique, the experiments revealed the specific interactions between bovine serum albumin (BSA) and EGCG and determined the characteristic dissociation constant (Kd) of the binding equilibrium. The obtained binding constants were compared to literature values, showing reasonable agreement with NMR data. Besides the native EGCG, the oxidized form of EGCG was also examined, whose binding behaviors to serum albumins have never been studied. Overstoichiometric binding obtained; BSA has stronger and weaker binding sites, which could be characterized by two separate Kd values. Furthermore, EGCG oxidization increased the bound amount.

Engineering vertically interrogated interferometric sensors for optical label-free biosensing.

In this work, we review the technology of vertically interrogated optical biosensors from the point of view of engineering. Vertical sensors present several advantages in the fabrication processes and in the light coupling systems, compared with other interferometric sensors. Four different interrelated aspects of the design are identified and described: sensing cell design, optical techniques used in the interrogation, fabrication processes, fluidics, and biofunctionalization of the sensing surface. The designer of a vertical sensor should decide carefully which solution to adopt on each aspect prior to finally integrating all the components in a single platform. Complexity, cost, and reliability of this platform will be determined by the decisions taken on each of the design process. We focus on the research and experience acquired by our group during last years in the field of optical biosensors.

Critical assessment of relevant methods in the field of biosensors with direct optical detection based on fibers and waveguides using plasmonic, resonance, and interference effects.

Direct optical detection has proven to be a highly interesting tool in biomolecular interaction analysis to be used in drug discovery, ligand/receptor interactions, environmental analysis, clinical diagnostics, screening of large data volumes in immunology, cancer therapy, or personalized medicine. In this review, the fundamental optical principles and applications are reviewed. Devices are based on concepts such as refractometry, evanescent field, waveguides modes, reflectometry, resonance and/or interference. They are realized in ring resonators; prism couplers; surface plasmon resonance; resonant mirror; Bragg grating; grating couplers; photonic crystals, Mach-Zehnder, Young, Hartman interferometers; backscattering; ellipsometry; or reflectance interferometry. The physical theories of various optical principles have already been reviewed in detail elsewhere and are therefore only cited. This review provides an overall survey on the application of these methods in direct optical biosensing. The "historical" development of the main principles is given to understand the various, and sometimes only slightly modified variations published as "new" methods or the use of a new acronym and commercialization by different companies. Improvement of optics is only one way to increase the quality of biosensors. Additional essential aspects are the surface modification of transducers, immobilization strategies, selection of recognition elements, the influence of non-specific interaction, selectivity, and sensitivity. Furthermore, papers use for reporting minimal amounts of detectable analyte terms such as value of mass, moles, grams, or mol/L which are difficult to compare. Both these essential aspects (i.e., biochemistry and the presentation of LOD values) can be discussed only in brief (but references are provided) in order to prevent the paper from becoming too long. The review will concentrate on a comparison of the optical methods, their application, and the resulting bioanalytical quality.

Research on multi-parameter characteristics of a PCF sensor modified by GO composite films.

We propose a photonic crystal fiber (PCF) sensor based on graphene oxide (GO) composite film modification to simultaneously measure the multi-parameter sensing characteristics of humidity, temperature, and glucose concentration. The GO-polyvinyl alcohol (PVA) composite film is used to measure the humidity-sensing characteristics of the sensor, and the glucose oxidase composite film is used to measure the sensing characteristics of the glucose concentration, respectively. Experiment results show that the sensitivities of the temperature of the GO-PVA coating structure are 0.037 nm/°C, 0.047 nm/°C, and 0.031 nm/°C; the sensitivities of humidity are 0.059 nm/%RH, 0.121 nm/%RH, and 0.047 nm/%RH; and the sensitivities of the glucose concentration of the GO-GOD coating structure are 0.028 nm/(g/L), 0.049 nm/(g/L), and 0.010 nm/(g/L) for three interference dips, respectively. The structure is simple to manufacture and can be used as a sensor for detecting multiple parameters. It can be widely used in biomedicine, environmental monitoring, and other fields.