Label-free, single molecule detection of cytokines using optical microcavities

Interleukin-2 (IL2) is a cytokine that regulates T-cell growth and is used in cancer therapies. By sensitizing a microcavity sensor surface with anti-IL2 and monitoring the resonant frequency, single molecules of IL2 can be detected

Electrical thermo-optic tuning of ultrahigh-Q microtoroid resonators

The ability to tune resonant frequency in optical microcavities is an essential feature for many applications. Integration of electrical-based tuning as part of the fabrication process has been a key advantage of planar microresonant devices. Until recently, the combination of these features has not been available in devices that operate in the ultrahigh-Q regime where device quality factors (Q) can exceed 100 million. In this letter, we demonstrate an electrically tunable resonator on a chip with ultrahigh-quality factors. Futhermore, the devices have demonstrated tuning rates in excess of 85 GHz/V2 and are capable of tuning more than 300 GHz

Label-free detection of cytokines using optical microcavities

Ultra-high-Q microresonators have demonstrated sensitive and specific chemical and biological detection. The sensitivity is derived from the long photon lifetime inside the cavity and specificity is achieved through surface functionalization. Here, ultra-high-Q microcavities demonstrate label-free, single molecule detection of Interleukin-2 (IL-2) in fetal bovine serum (FBS). IL-2 is a cytokine released in response to immune system activation. The surface of the microtoroids was sensitized using anti-IL-2. The detection mechanism relies upon a thermo-optic mechanism to enhance resonant wavelength shifts induced through binding of a molecule

Chemical and biological detectors using ultra-high-Q microresonators

Recently, a method for fabricating planar arrays of optical microtoroid resonators with quality factors greater than 500 million was developed. These devices have previously demonstrated Raman and OPO lasing and radiation pressure induced oscillations. When immersed in an aqueous environment, these devices are able to maintain their ultra-high Q factors by operating in the visible wavelength band, enabling very sensitive chemical and biological detection. The fabrication and optical properties of these devices will be described. These devices have performed both chemical and biological detection. Systems which have been detected include D_2O in water and a variety of biological molecules. Sensitivity limits will also be discussed

Portable Polarimetric Fiber Stress Sensor System for Visco-elastic and Biomimetic Material Analysis

Non-destructive materials characterization methods have significantly changed our fundamental understanding of material behavior and have enabled predictive models to be developed. However, the majority of these efforts have focused on crystalline and metallic materials, and transitioning to biomaterials, such as tissue samples, is non-trivial, as there are strict sample handling requirements and environmental controls which prevent the use of conventional equipment. Additionally, the samples are smaller and more complex in composition. Therefore, more advanced sample analysis methods capable of operating in these environments are needed. In the present work, we demonstrate an all-fiber-based material analysis system based on optical polarimetry. Unlike previous polarimetric systems which relied on free-space components, our method combines an in-line polarizer, polarization-maintaining fiber, and a polarimeter to measure the arbitrary polarization state of the output, eliminating all free-space elements. Additionally, we develop a more generalized theoretical analysis which allows more information about the polarization state to be obtained via the polarimeter. We experimentally verify our system using a series of elastomer samples made from polydimethylsiloxane (PDMS), a commonly used biomimetic material. By adjusting the base:curing agent ratio of the PDMS, we controllably tune the Young’s modulus of the samples to span over an order of magnitude. The measured results are in good agreement with those obtained using a conventional load-frame system. Our fiber-based polarimetric stress sensor shows promise for use as a simple research tool that is portable and suitable for a wide variety of applications

Spatiotemporal Fluorescent Detection Measurements Using Embedded Waveguide Sensors

Integrated waveguide biosensors, when combined with fluorescent labeling, have significantly impacted the field of biodetection. While there are numerous types of waveguide sensors, the fundamental excitation method is fairly consistent: the evanescent field of the waveguide excites a fluorophore whose emission is detected, either directly via imaging or indirectly via a decrease in power transfer. Recently, a sensor device was demonstrated which is able to back-couple the emitted light into the waveguide, allowing the signal to be detected directly. However, this previous work focused on the development of an empirical model, leaving many theoretical questions unanswered. Additionally, the results from the novel back-coupling route were not compared with the results from the more conventional imaging technique. In this study, we develop finite difference time domain simulations to predict the sensor\u27s performance both in air and aqueous environments. We also perform complementary experiments to verify the modeling, measuring the fluorescence coupled into the waveguide, and radiated perpendicular to the waveguide. Finally, we performed spatiotemporal measurements of the fluorescence on the waveguide. Utilizing these measurements, we are able to measure the fluorescent decay rate of the fluorescent dye at arbitrary points along the length of the waveguide

Low threshold Er³⁺/Yb³⁺ co-doped microcavity laser

An Erbium:Ytterbium codoped microcavity-based laser which is lithographically fabricated from sol-gel is demonstrated. Both single-mode and multimode lasing is observed in the C band (1550nm). The quality factor and pump threshold are experimentally determined for a series of erbium and ytterbium doping concentrations, verifying the inter-dependent relationship between the two dopants. The lasing threshold of the optimized device is 4.2 μW

Detecting disruption of HER2 membrane protein organization in cell membranes with nanoscale precision

The spatio-temporal organization of proteins within the cell membrane can affect numerous biological functions, including cell signaling, communication, and transportation. Deviations from normal spatial arrangements have been observed in various diseases, and better understanding this process is a key stepping-stone to advancing development of clinical interventions. However, given the nanometer length scales involved, detecting these subtle changes has primarily relied on complex super resolution and single molecule imaging methods. In this work, we demonstrate an alternative fluorescent imaging strategy for detecting protein organization based on a material that exhibits a unique photophysical behavior known as aggregation induced emission (AIE). Organic AIE molecules have an increase in emission signal when they are in close proximity and the molecular motion is restricted. This property simultaneously addresses the high background noise and low detection signal that limit conventional widefield fluorescent imaging. To demonstrate the potential of this approach, the fluorescent molecule sensor is conjugated to a human epidermal growth factor receptor 2 (HER2) specific antibody and used to investigate the spatio-temporal behavior of HER2 clustering in the membrane of HER2-overexpressing breast cancer cells. Notably, the disruption of HER2 clusters in response to an FDA-approved monoclonal antibody therapeutic (Trastuzumab) is successfully detected using a simple widefield fluorescent microscope. While the sensor demonstrated here is optimized for sensing HER2 clustering, it is an easily adaptable platform. Moreover, given the compatibility with widefield imaging, the system has the potential to be used with high-throughput imaging techniques, accelerating investigations into membrane protein spatio-temporal organization

Label-free single-molecule all-optical sensor

Recently, quality factors greater than 100 million were demonstrated using planar arrays of silica microtoroid resonators. These high Q factors allow the toroidal resonators to perform very sensitive detection experiments. By functionalizing the silica surface of the toroid with biotin, the toroidal resonators become both specific and sensitive detectors for Streptavidin. One application of this sensor is performing detection in lysates. To mimic this type of environment, additional solutions of Streptavidin were prepared which also contained high concentrations (nM and μM) of tryptophan