Single-cell detection by cavity ring-down spectroscopy
Applied Physics Letters
The implementation of cavity ring-down spectroscopy in an optical fiber resonator extends the viability of this highly sensitive technique for label-free detection of biological species. By chemically treating the surface of discrete tapered sensing regions along the length of a physically extended optical fiber resonator, we show single-cell sensitivity arising from optical scattering of the evanescent field surrounding the fiber. The observed detection limits, based on a minimum detectable
... nimum detectable scattering cross section on the order of 10 m 2 , suggest a broad range of new applications in a simple, inexpensive device for real-time cavity ring-down biosensing. Rapid detection of micro-organisms with both high specificity and single-cell sensitivity is of broad interest in a variety of fields, including molecular biology, medicine, national security, and environmental monitoring. 1 Several techniques address this need, including mass-sensitive mechanical metrology 2 and fluorescence spectroscopy, 3 but these involve expensive equipment or time-consuming sample preparation. Cavity ring-down (CRD) spectroscopy, which is most commonly used in the detection of trace concentrations of absorbing molecules, offers a real-time response in a simple, compact, less expensive arrangement that requires negligible sample preparation. 4 In this Letter, we demonstrate that, using a versatile yet practical device, label-free single-cell detection of biological agents is possible by adapting an optical fiber CRD resonator. The CRD technique has been widely adopted for molecular spectroscopy applications ranging from the monitoring of disperse atmospheric species to the spectral resolution of forbidden overtone transitions in small molecules. 5 CRD is typically implemented in an optical resonator formed by two highly reflective mirrors and derives its high characteristic sensitivity from the measurement of the resonator's decay rate. This rate, which is directly proportional to its internal optical losses, including those due to molecular absorption and scattering, is insensitive to common sources of noise, such as laser intensity fluctuations and interference from external absorbers, allowing quantitative detection of trace concentrations. 6 CRD has recently been shown to be an effective method for direct measurement of the loss in an optical fiber resonator, allowing its application in highly scattering matrices that are otherwise difficult to sample. 7 Such a device, which can be constructed from inexpensive telecommunications components, is responsive to observables not accessible in a traditional CRD arrangement, such as bending attenuation, 8 mechanical strain, 9 refractive index changes, 10 and evanescent field loss. 7,8,10 Furthermore, optical fiber CRD eliminates the need for direct line of sight along the resonator, suggesting a range of new applications, including standoff detection or distributed monitoring over a large physical area.