Cellular dye lasers: lasing thresholds and sensing in a planar resonator

Abstract

Biological cell lasers are promising novel building blocks of future biocompatible optical systems and offer new approaches to cellular sensing and cytometry in a microfluidic setting. Here, we demonstrate a simple method for providing optical gain by using a variety of standard fluorescent dyes. The dye gain medium can be located inside or outside a cell, or in both, which gives flexibility in experimental design and makes the method applicable to all cell types. Due to the higher refractive index of the cytoplasm compared to the surrounding medium, a cell acts as a convex lens in a planar Fabry-Perot cavity. Its effect on the stability of the laser cavity is analyzed and utilized to suppress lasing outside cells. The resonance modes depend on the shape and internal structure of the cell. As proof of concept, we show how the laser output modes are affected by the osmotic pressure. 5647-5652 (2015). 17. R. C. Polson and Z. V. Vardeny, "Random lasing in human tissues," Appl. Phys. Lett. 85(7), 1289-1291 (2004). 18. P. L. Gourley, "Semiconductor microlasers: A new approach to cell-structure analysis," Nat. Med. 2(8), 942-944 (1996). 19. P. Gourley, "Biocavity laser for high-speed cell and tumour biology," J. Phys. D Appl. Phys. 36(14), R228-R239 (2003). 20. P. L. Gourley and R. K. Naviaux, "Optical phenotyping of human mitochondria in a biocavity laser," IEEE J. #247953Sel. Top. Quantum Electron. 11(4), 818-826 (2005). 21. H. Shao, D. Kumar, and K. L. Lear, "Single-cell detection using optofluidic intracavity spectroscopy," IEEE Sens. J. 6(6), 1543-1550 (2006). 22. A. E. Siegman, Lasers (Mill Valley, 1986 3(4), 177-184 (1971). 25. P. Decherchi, P. Cochard, and P. Gauthier, "Dual staining assessment of Schwann cell viability within whole peripheral nerves using calcein-AM and ethidium homodimer," J. Neurosci. Methods 71(2), 205-213 (1997). 26. C. L. Bashford and J. C. Smith, "The use of optical probes to monitor membrane potential," Methods Enzymol.55, 569-586 (1979) Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, "Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence," Biophys. J. 88(5), 3689-3698 (2005).

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

“…The biological cells here provide a crucial role to facilitate lasing, which would otherwise be difficult to attain due to misalignment of the cavity mirrors. As shown in Figure d,e, the cells act as a microlens, and so can stabilize the laser resonator by redirecting the diffracted rays toward the optical axis . To test the effectiveness of the cells in stabilizing the laser resonator, the experiment was repeated with the cells and supernatant sandwiched between two glass slides with one of the slides tilted at an angle.…”

“…Reflectance at the walls is indeed very poor and external agents such as microbeads or scattering nanoparticles/nanocrystals are not introduced in the system. Humar and Yun reported that cell lasers consisting of dye‐doped cells embedded between two high reflective distributed Bragg reflector (DBR) mirrors, in an all‐similar experimental setup with ns pulsed pump laser, display a laser threshold of ≈45 nJ per pulse . In such a case DBR mirrors provided the light confinement required for amplification, and the cells play only a minor role in reducing the laser thresholds owing to a thoroughly described “lens effect” .…”

“…So far it has been achieved as a result of the amplification provided by laser cavities or microresonators while lasing from an isolated individual cell has proven to be elusive, and only observed in isolated adipocytes featuring very large oil droplets (45 µm). 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 …”

Versatile tissue lasers based on high-Q Fabry–Pérot microcavities

“…2e. Such Q-factor degradation is less significant in the case of single-cell lasers due to the lensing effect of the cell 14 . Unfortunately, this lensing effect may not exist for tissue lasers when cells are embedded in the extracellular matrix.…”

Biomaterial microlasers implantable in the cornea, skin, and blood

“…These properties have been harnessed for ultrasensitive sensing [3], spectral multiplexing [4] and sub-diffraction microscopy [5]. Examples of biological lasers include hybrid lasers containing cells [6,7] and tissues [8] inside Fabry-Pérot cavities, microlasers inside cells [4,9] and random lasers [10] in tissues [11]. Lasers made entirely from biomaterials were also demonstrated.…”