Laser-emission imaging of nuclear biomarkers for high-contrast cancer screening and immunodiagnosis

for use in biomedical and biological applications. [1][2][3][4][5] Various types of optical microcavities have been developed, such as Fabry-Perot cavities, [6][7][8] photonic crystals, [9] and whispering-gallery-modes (WGMs), as implemented in ring resonators, [10][11][12] micro-/nanodisks, [13,14] and microspheres. [3][4][5][15][16][17][18][19][20] In particular, microsphere-based WGM lasers are appealing candidates for sensing probes owing to their convenience, extremely high Q factor, and potential for application in intracellular and extracellular probes. [13,15,16,21,22] Moreover, analytes can be positioned outside of the optical cavity, where an evanescent field exists at the external interface between the resonant cavity and surrounding medium. [23][24][25] At present, most microsphere or droplet-based WGM lasers are considered to be passive-detection devices, as they require physical changes (e.g., refractive indexes) to induce a resonance spectral shift, and thus cannot provide detailed biochemical information. [26][27][28] In contrast, active-detection devices, which employ analytes as the gain medium, can provide more selective and sensitive information about the biospecies. [8,29] Therefore, the ability to utilize a biological gain medium on the external surface of a microsphere cavity will allow us to amplify subtle changes in the gain medium and the resultant spectra, threshold, and lasing modes. However, the overlap factor for the optical mode and gain medium is much lower than the value of the gain within the cavity, and the background fluorescence also interferes with the external cavity sensing, making this amplification a difficult task. Thus, to enable amplification of these subtle changes, we have applied the concept of Förster resonance energy transfer (FRET) at the interface of a droplet-based laser to separate the donor and acceptor at the droplet-surface interface (Figure 1a). FRET is an electrodynamic phenomenon that is highly sensitive to distance, spectral overlap, and the orientation between donor and acceptor molecules. In the past decade, FRET has been used as a powerful tool for providing nanoscale information in many biosensing applications. The performance of FRET is mainly dependent on the design of the donor and acceptor pairs. Several groups recently utilized FRET by using donor molecules as exciton funnels, [30,31] or light-harvesting antennas, [31] to realize a wavelength tunable laser, [30] single molecule nanoprobes, [32] or light redirectioning devices [33] that strongly amplify the emission of acceptor molecules when Microlasers are emerging tools for biomedical applications. In particular, whispering-gallery-mode (WGM) microlasers are promising candidates for sensing at the biointerface owing to their high quality-factor and potential in molecular assays, and intracellular and extracellular detection. However, lasing particles with sensing functionality remain challenging since the overlap between the WGM optical mode and external gain medium is much lower compared to ...

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lasing‐Encoded Microsensor Driven by Interfacial Cavity Resonance Energy Transfer

Yuan

Wang

Guan

et al. 2020

“…Biolasers have been employed in the detection of various bioactivities at the molecular, cellular, and tissue levels . Recently, their applications in cell tracking, labeling/probes, implantable devices, cell/tissue imaging start to emerge.…”

Section: Introductionmentioning

confidence: 99%

Biological Lasers for Biomedical Applications

Chen

Fan

2019

Self Cite

120

A biolaser utilizes biological materials as part of its gain medium and/or part of its cavity. It can also be a micro‐ or nanosized laser embedded/integrated within biological materials. The biolaser employs lasing emission rather than regular fluorescence as the sensing signal and therefore has a number of unique advantages that can be explored for broad applications in biosensing, labeling, tracking, contrast agent development, and bioimaging. This article reports on the progress in biolasers with focus on the work done in the past five years. In the end, the possible future directions of the biolaser are discussed.

“…For cells inside a cavity composed of two reflective mirrors, the refractive index contrast between a cell and its surrounding medium has been found to lower the threshold for lasing, due to the so‐called “lens‐effect” . In these conditions, the laser threshold has been reported to carry information on cellular properties (such as the hydration level) and it has been used to discriminate cancer from healthy cells …”

Section: Introductionmentioning

confidence: 99%

Biolasing from Individual Cells in a Low‐Q Resonator Enables Spectral Fingerprinting

Septiadi

Barna

Saxena

et al. 2020

Lasing from cells has recently been subject of thorough investigation because of the potential for sensitive and fast biosensing. Yet, lasing from individual cells has been studied in high‐quality resonators, resulting in limited dependence of the lasing properties on the cellular microenvironment. Here, lasing is triggered by cells floating in a low quality factor resonator composed of a disposable poly(methyl methacrylate) (PMMA) cell counting‐slide, hence in absence of conventional high‐reflectivity optical cavities. The exceptional spectral narrowing and the steep slope increase in the input–output energy diagram prove occurrence of laser action in presence of cells. The observed biolasing is an intrinsically dynamic signal, with large fluctuations in intensity and spectrum determined by the optical properties of the individual cell passing through the pump beam. Numerical simulations of the scattering efficiency rule out the possibility of optical feedback from either WGM (whispering gallery mode) or multiple scattering within the cell, and point to the enhanced directional scattering field as the crucial contribution of cells to the laser action. Finally, principal component analysis of lasing spectra measured from freely diffusing cells yields spectral fingerprints of cell populations, which allows discriminating cancer from healthy Rattus glial cells with high degree of confidence.