In-vitro sensing of biomechanical forces in live cells by a whispering gallery mode biosensor

Himmelhaus, Michael; François, Alexandre

doi:10.1016/j.bios.2009.07.021

Cited by 56 publications

(51 citation statements)

References 44 publications

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“…Furthermore, the position of the resonances is also dependent on the geometry of the resonator, and this aspect has been used to measure e.g. resonator deformation induced by mechanical stress in various contexts [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…This is a consequence of WGMs having spectral positions that are highly dependent on the resonator's morphology as stated above, and the fact that a microsphere is never perfect, always having a certain degree of asphericity. The asphericity essentially lifts the degeneracy between modes of different polar number resulting in 'mode-splitting,' in which the modes have unique resonance frequencies [6,13,14]. The split in modes is unique to different planes, all of which are excited in the case of an active microsphere.…”

Section: Introductionmentioning

confidence: 99%

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Q-factor limits for far-field detection of whispering gallery modes in active microspheres

et al. 2015

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This paper investigates the Q-factor limits imposed on the farfield detection of the whispering gallery modes of active microspherical resonators. It is shown that the Q-factor measured for a given active microsphere in the far-field using a microscope is significantly lower than that measured using evanescent field collection through a taper. The discrepancy is attributed to the inevitable small asphericity of microspheres that results in mode-splitting which becomes unresolvable in the far-field. Analytic expressions quantifying the Q-factor limits due to small levels of asphericity are subsequently derived.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Q-factor limits for far-field detection of whispering gallery modes in active microspheres

et al. 2015

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“…3 Bovine serum albumin (BSA) coated microresonator endocytosed by a life cell (HUVEC: human umbilical vein endothelial cell); the two subfigures (a) and (b) are orga nized as follows: (top) optical microscopy transmission image; (center) sketch of the microresonator under the corresponding condition; (bottom) measured WGM mode (TE) with ideal WGM peaks added for illustration; then, the two subfigures show: (a) the situa tion when the (freely floating) bead just had come into contact with the cell, thereby sens ing a change in the environmental refractive index by some of the WGMs (with distinct polar direction), thus causing a mode broadening; (b) the bead has now been partially incorporated by the cell and the WGM exhibits a clear mode splitting due to deformation of the bead, so that WGMs travelling in different polar planes can be distinguished. Data taken from [4]. …”

Section: The Lasing Regimementioning

confidence: 99%

“…3, which briefly summarizes a study on the endocytosis of BSA coated microresonators by endothelial cells, which proceeded while the resonators were operated [4]. In Fig.…”

Section: Microresonators Inside Of Life Cellsmentioning

confidence: 99%

“…3b. As detailed elsewhere [4], this deformation can be used for the determination of the forces, by which the cell is acting on the particle. The active component of this force could not been determined before due to lack of suitable measurement techniques, thus underlining novelty and value of freely floating microresonators.…”

Section: Microresonators Inside Of Life Cellsmentioning

confidence: 99%

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Microsensors on the Fly

Himmelhaus¹

2016

Optik & Photonik

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Optically driven microresonators freely floating in liquids, embedded into transparent solid media, or even taken up by life cells, can be exploited as optical microsensors, which yield precise information on the immediate local condition of their respective environment. Besides plain physical information, such as on local refractive indices, mechanical stress, and mixture ratios in composite materials, the sensors may be applied as chemical and even bio-sensors for the specific targeting of biochemical binding reactions if accordingly functionalized. Sensitivity can be further improved by driving the sensors above the lasing threshold, thereby increasing signal intensity and optical resolution at the same time. In this article, we introduce the optical principles, present useful implementations, and illustrate feasibility of this still novel approach to optical sensing by a number of diverse examples.With the advent of the laser diode, microresonators capable of confining light to microscopic volumes have entered everyday's life with applications as laser pointers, light sources in CD, DVD and Blu-ray disk drives, and do-it-yourself metrology tools, to name just the most common examples. Intrinsically shaped into their gain medium, these semiconductor devices can achieve extremely small sizes in the micrometer regime, however, since they are electrically powered, they require a fixed connection to the macroscopic world in the form of some electrical driver, which still renders the entire device macroscopic.Here, we report about optically driven microresonators that overcome the need for fixation to a macroscopic power supply and thus turn into microsensors of 3D quantum system characterized by quantum numbers q, n, m for radial, azimuthal, and polar quantization and polarizations TE, TM (transverse electric / transverse magnetic modes, respectively). Fig. 1 (a) Illustration of a whispering gallery mode with quantum numbers q = 3 (three radial maxima), n = 44 (no. of wavelengths along circumference), and m = n (1 polar maximum); (b) Cross section in radial direction showing the field distribution of the WGM of (a); please note the exponential decay outside of the microresonator, which is a peculiarity of WGM resonators; (c) Fluorescence emission spectra of 10 µm coumarin 6G doped polystyrene microbeads as recorded with a set up as sketched in Fig. 2c; the spectrum plotted in blue origi nates from a spherical bead and exhibits several WGMs with q = 1 and several quantum numbers n (distinguished by a different number of wavelengths fitting into the circumference of the bead). For each quantum number n, there is a pair of modes with differing polariza tion (TE, TM) as indicated in the spectrum. The spectrum plotted in red stems from a particle stained with the same fluorophore, but with an odd shape, so that WGMs are not supported. By subtraction of the two spectra, the non resonant fluorescence background can be removed and the pure WGM spectrum is obtained (spectrum in green, Data of (c) taken from [6]).

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Label‐Free Bioanalysis Based on Low‐Q Whispering Gallery Modes: Rapid Preparation of Microsensors by Means of Layer‐by‐Layer Technology

Olszyna

Debrassi

Üzüm

et al. 2018

Adv Funct Materials

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Low-Q-whispering gallery modes (low-Q-WGM) can be used for label-free detection of interactions between biomolecules, measuring their binding and release kinetics or for analysis of changes in the medium in real-time. The main advantage of the low-Q-WGM approach over other label-free methods is the possibility of measurements in small cavities as the method uses microparticles down to 6 µm as sensors. Commercially available dye-doped microparticles that are used as low-Q-WGM sensors exhibit several drawbacks. Therefore, alternative particle types are developed and optimized as low-Q-WGM sensors. First, dye-doped particles made of different materials are screened. The most critical parameter for WGM performance is the refractive index (RI) of sensor particles. Furthermore, surface roughness of particles, determined by scanning electron microscopy and atomic force microscopy, affects their performance as WGM microsensors. In the second test, fluorescent dyes immobilized on nonfluorescent particles by means of nanometer thick layer-by-layer (LbL) films are shown to generate a strong WGM signal. The LbL-coated particles show remarkably less background fluorescence than dye-doped particles and are easier to prepare. Finally, this article proposes rapid preparation methods for WGM microparticle sensors based on various parameters such as material type, RI, surface roughness, and number of coated polymer layers.of the studied molecules with markers. However, these markers alter the intrinsic protein properties, which in turn can affect their interactions and bioactivity. [11] Therefore, label-free methods such as surface plasmon resonance (SPR), [12] whispering gallery mode (WGM), [13][14][15] quartz crystal microbalance (QCM), [16] reflectometric interference spectroscopy (RIfS), [17] biolayer interferometry (BLI), [18] or nanowire sensors [19] have gained popularity with the ultimate aim of replacing current diagnostic assays. In particular, WGM-based devices provide an excellent means of inexpensive and label-free biomolecule detection. The basic operating principle of WGM relies upon total internal reflection (TIR) of light trapped inside a circular resonator, e.g., a microparticle. [20][21][22] Since the trapped light circulates along the microparticle surface over a thousand times before escaping, photons associated with certain wavelengths create a constructive interference. This set of constructive interferences at discrete wavelengths is called WGM. [20][21][22][23][24] These modes are detectable by a high resolution spectrograph as narrow peaks in the optical spectrum. Any modification in optical geometry or refractive index (RI) of the particle as well as in the surrounding environment induces a shift in WGM wavelength positions Δλ, which is the basis of WGM-based sensing.Sensing performance of the WGM resonator is described by two factors. The first factor is the resonator's quality factor (Q-factor = full widths at half maximum (FWHM)/resonance wavelength), which is proportional to the number of recirculati...

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In-vitro sensing of biomechanical forces in live cells by a whispering gallery mode biosensor

Cited by 56 publications

References 44 publications

Q-factor limits for far-field detection of whispering gallery modes in active microspheres

Q-factor limits for far-field detection of whispering gallery modes in active microspheres

Microsensors on the Fly

Label‐Free Bioanalysis Based on Low‐Q Whispering Gallery Modes: Rapid Preparation of Microsensors by Means of Layer‐by‐Layer Technology

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