Combining multiple optical trapping with microflow manipulation for the rapid bioanalytics on microparticles in a chip.

An array of four independent laser traps is combined with a polydimethylsiloxane microfluidic chip to form a very compact system allowing parallel processing of biological objects. Strong three dimensional trapping allows holding objects such as functionalized beads in flows at speeds near 1 mm/s, enabling rapid processing. By pressure control of the inlet flows, the trapped objects can be put in contact with different solutions for analysis purpose. This setup, including a fluorescence excitation-detection scheme, offers the potential to perform complex biochemical manipulations on an ensemble of microparticles.

Rapid and precise in vivo measurement of human corneal thickness with optical low-coherence reflectometry in normal human eyes.

An optical low-coherence reflectometer is used for rapid noncontact measurements of the human corneal thickness in vivo. Thickness measurements on ten volunteers show a standard deviation of 3.4 µm. The experiments reveal that the optical reflectometer benefits from a 2.5 fold enhancement of the measurement precision and a 2.8 fold reduction in measurement time compared to a standard clinical ultrasonic pachometer. © 1998 Society of Photo-Optical Instrumentation Engineers.

Precision and Reproducibility of Measurements of Human Corneal Thickness with Rapid Optical Low-Coherence Reflectometry (OLCR).

This study investigates the precision and intraindividual variability of a clinical optical pachometer based on low-coherence reflectometry, which was used to measure the central thickness of a human cornea in vivo. The instrument, attached to a slit lamp, is a single mode fiber optic based Michelson interferometer with a high repetition rate as previously described. The same operator performed ten sets of measurements on the same subject, each consisting of 20 consecutive scans, on each day for three consecutive days. By computing the means from every scan series, the thickness of the central cornea with optical pachometry was found to be 519.6±1.2 (range 518-521) µm on day 1, 519.9±0.9 (range 519-521) µm on day 2, and 523.8±0.6 (range 523-525) µm on day 3. The thickness values on day 3, where the subject suffered from a cold without clinical ocular involvement, were different from the two previous days (p<0.001, one way analysis of variance). Optical low-coherence reflectometry measurements of corneal thickness can be performed with high precision of about 1 µm and a high intra- and intersession reproducibility. © 1999 Society of Photo-Optical Instrumentation Engineers.

Continuous non-contact corneal pachymetry with a high speed reflectometer.

PURPOSE: We developed an instrument that permits non-contact, continuous, high speed and high precision monitoring of corneal thickness and tested the stability and reproducibility of measurements made over extended time periods and under various conditions of low surface reflectivity encountered during protracted exposure of the unmoistened corneal surface to ambient air. METHODS: The optical pachymeter (basic component of a broad-band, all-fiber Michelson interferometer) was used to monitor changes in the central corneal thickness of enucleated porcine eyes. Measurements were performed on three groups of eight eyes, each with different surface characteristics: intact epithelium, mechanically abraded epithelium, and 90 microm excimer laser keratectomy. Corneal thickness was monitored continuously with values recorded every 2 to 3 minutes for periods up to 1 hour in the absence of surface rinsing. RESULTS: The thicknesses of all unmoistened corneas could be monitored with a precision of 1 microm (ascertained using a calibration glass plate and a living human cornea) over the entire observation period. Under ambient air conditions, deturgescence occurred in each case, and ranged from 1 to 5 microm/min. The rate of corneal thinning was fairly constant during the first 15 minutes of monitoring, but was nonlinear thereafter. Corneas with an intact epithelium had the lowest thinning rate with only 10% of the original thickness lost during the course of 1 hour. Deturgescence increased to 25% in corneas that had mechanical removal of the epithelium and to 28.5% in those that had an anterior excimer laser keratectomy, during a similar time-period. CONCLUSION: With this new interferometric method, continuous, non-contact measurement of corneal thickness is possible to within a precision of 1 microm for periods up to 1 hour, even under the modified surface conditions after photoablative keratectomy. This device may be useful for on-line monitoring of ablation depths during such procedures.

Temperature dependence of reflectance and transmittance of the artery exposed to air during laser irradiation.

Reflectance, transmittance, and temperature of the arterial wall exposed to air are measured during laser irradiation for different heating dynamics. Temperature dependence of the reflectance and transmittance is then deduced. Our results show a competing effect between temperature and dehydration, resulting in a distinct minimum of transmittance and maximum of reflectance. As a consequence, a direct correlation of reflectance and transmittance with temperature is only possible for a specific dynamics.

Video-rate optical low-coherence reflectometry based on a linear smart detector array.

A low-coherence reflectometer based on a conventional Michelson interferometer and a novel silicon detector chip that allows parallel heterodyne detection is presented. Cross-sectional images of 64x256 pixels covering an area of 1.92 mm x 1.3 mm are acquired at video rate and with a sensitivity close to the shot-noise limit. Applications in surface profiling and thickness measurement are demonstrated.

Temperature-related reversible birefringence changes in rat tail tendon.

By use of a highly sensitive method for measuring slight variations in birefringence it is shown here that a strong reversible correlation exists between rat tail tendon birefringence and temperature. This phenomenon is totally different from the loss of birefringence that results from a denaturation process. Below the threshold temperature leading to denaturation, an increase in temperature is systematically accompanied by a reversible increase in birefringence (0.25% degrees C(-1)). This phenomenon is observed at very fast heating rates (250,000 degrees C s(-1)), such as those induced by pulsed infrared lasers, and confirmed by experiments conducted with slow homogeneous heating of the sample medium (0.1 degrees C s(-1)). The good correlation between birefringence and temperature observed during the fast heating suggests that there are only small modifications of the tissue structure at the fibril level.

Local coupling-coefficient characterization in fiber Bragg gratings.

We propose a new method for characterizing the local parameters of fiber Bragg gratings. This method combines measurement of the complex impulse response by optical low-coherence reflectometry and reconstruction of the complex coupling coefficient by layer peeling. Application of the method to a nonhomogeneous grating shows that the local coupling coefficient can be precisely determined with an axial resolution below 20 microm and a maximum error of less than 5% for amplitude and phase, respectively.

High-precision, high-speed measurement of excimer laser keratectomies with a new optical pachymeter.

In excimer-laser photorefractive keratectomy (PRK) the depth of the stromal tissue ablation is calculated from calibration and empirical data but is not actually measured, since a noncontact high-precision instrument for the measurement of the actual ablation has not been available. With a newly developed method for optical pachymetry we studied the depth of corneal ablations performed with an excimer laser. The excimer laser (Schwind Keratom) was calibrated according to the manufacturers' instructions. On freshly enucleated pig eyes, planokeratectomies with a diameter of 5 mm and a planned depth of 20, 40, 80, 160, and 320 microns were performed. With a newly developed high-precision, high-speed reflectometer the corneal thickness was measured immediately before and after the keratectomy. All ablations were deeper than expected. For a planned keratectomy of 20 microns we found a mean ablation depth of 29 microns; for 40 microns, a mean depth of 51 microns; for 80 microns, a mean depth of 100 microns; for 160 microns, a mean depth of 200 microns; and for 320 microns, a mean depth of 396 microns. The differences between mean and maximal ablation values were 58.6% at the 20-micron setting, 40.9% at the 40-micron setting, 20.1% at the 80-micron setting, 11.5% at the 160-micron and 9.8% at the 320-micron setting. Ablation rates showed the highest degree of variation in the 20-micron ablation group. Absolute variations in the ablation depth increased with ablation depth. In photorefractive procedures the volume of the tissue ablated is calculated from the instrument calibration but is not actually measured. Although the greater than expected ablation depths may in part be explained by differences between human and porcine tissue, the high degree of variability in the laser ablations may have other causes. We suggest that variations in the postoperative refractive results of PRK, which are currently attributed to variations in corneal would healing, may in part be due to variations in ablation depth.

Coupled-mode propagation in multicore fibers characterized by optical low-coherence reflectometry.

A fiber-optical low-coherence ref lectometer has been used to probe a multicore fiber locally at a wavelength of 1.3 microm. This technique allows one to determine the group index of refraction of the modes in the multicore fiber with high accuracy. Light propagation that is due to noncoherent coupling of energy from one fiber core to adjacent cores through cladding modes can be distinguished quantitatively from light propagating in coherently coupled modes. Intercore coupling constants in the range of 0.6-2 mm(-1) have been evaluated for the coupled modes.

Fragmentation process of current laser lithotriptors.

BACKGROUND AND OBJECTIVE: Flashlamp pumped dye (FPDL), Q-switched Nd:YAG, and alexandrite lasers are the most clinically used laser lithotriptors. Although calculi are fragmented by laser induced mechanical stresses for all lithotriptors, different fragment sizes and fragmentation efficiencies have been reported. In this work the effect of the pulse duration and pulse shape on the fragmentation processes is studied. MATERIAL AND METHODS: Fragmentation processes are characterized on model stones and on sensing target fibers. Stone fragmentation and cavitation bubble generation are observed by video flash photography. Shock wave occurrence and strength are monitored with an hydrophone. RESULTS: For the FPDL, stone fragmentation is induced by the collapse of the large cavitation bubble formed. For the Q-switched Nd:YAG, fragmentation is already observed during the laser pulse, at the plasma onset, although further fragmentation can occur at the bubble collapse. For pulse durations corresponding to the alexandrite, an intermediate fragmentation regime is observed. CONCLUSION: For the first time the physical basis of the observed differences in the fragmentation efficiencies of current laser lithotriptors is described. For nanosecond durations the fragmentation processes are governed by plasma induced shock waves. On the contrary, for microsecond durations fragmentation is governed by cavitation. The high fragmentation efficiency of microsecond lasers is due to a high laser energy transfer into cavitation.

Optical coherence topography based on a two-dimensional smart detector array.

A low-coherence reflectometer based on a conventional Michelson interferometer and a novel silicon detector chip with a two-dimensional array of pixels that allows parallel heterodyne detection is presented. We demonstrate acquisition of three-dimensional images with more than 100,000 voxels per scan at a sensitivity of -58 dB and a rate of 6 Hz.

Self-referenced method for optical path difference calibration in low-coherence interferometry.

A simple method for the calibration of optical path difference modulation in low-coherence interferometry is presented. Spectrally filtering a part of the detected interference signal results in a high-coherence signal that encodes the scan imperfections and permits their correction. The method is self-referenced in the sense that no secondary high-coherence light source is necessary. Using a spectrometer setup for spectral filtering allows for flexibility in both the choice of calibration wavelength and the maximum scan range. To demonstrate the method's usefulness, it is combined with a recently published digital spectral shaping technique to measure the thickness of a pellicle beam splitter with a white-light source.

Rapid and scalable scans at 21 m/s in optical low-coherence reflectometry.

An optical low-coherence reflectometer is presented that uses a fiber Michelson interferometer with a rotating cube to generate rapid depth scans at a high repetition rate. A folded optical path geometry allows the reference arm to scale up the scan range, scan speed, and scan repetitiveness. Thickness measurements with a repetitiveness of 384 Hz and a longitudinal scanning speed of 21 m/s in air over a range of ~3 mm are demonstrated.

High-resolution reflectometry in biological tissues.

Optical low-coherence ref lectometry is applied for the first time to our knowledge to investigate diffusive biological tissues with a single-mode fiber probe. Samples of fresh arteries are studied, using the backscattered light from the tissue. The probed volume in the vicinity of the fiber tip is estimated to be below 6.7 x 10(-10) cm(3). This noninvasive method allows one to determine optical parameters, such as the index of refraction and the transmission properties, and the tissue thickness.

Interstitial diode laser hyperthermia in the treatment of subcutaneous tumor.

BACKGROUND AND OBJECTIVE: Interstitial Laser Hyperthermia (ILH) has been investigated since the early 80s in the treatment of deep seated tumors. The purpose of this study was to evaluate the efficiency of diode ILH (830 nm) in a subcutaneous tumor model. STUDY DESIGN/MATERIALS AND METHOD: The antitumoral effect of diode ILH was assessed in a randomized study performed on 80 Swiss nu/nu mice. The tumor model was a subcutaneously implanted HT29 colonic carcinoma. The animals were assigned to four groups of 20 mice: Groups 1 and 3 were treated by ILH, groups 2 and 4 were not treated (control groups). Tumors were removed on day 3 in groups 1 and 2, and on day 30 in groups 3 and 4. The treatment was performed on tumors of 8 mm in diameter and a volume of 140 mm3. A laser irradiation of 360 J (power: 0.2 W; irradiation time: 1800 s) was delivered through a 300 microns optical fiber implanted in the tumor. The laser parameters insured temperatures of 46 degrees C in the central part of the tumor and 42 degrees C at the periphery. Tumor features were evaluated on day 3 and day 30. RESULTS: Untreated tumors grew rapidly up to a mean volume of 241 mm3 on day 3 (group 2) and 2,000 mm3 on day 30 (group 4). Treated tumors regressed to a mean volume of 32 mm3 on day 3 (group 1). On day 30, 40% of the tumors had totally disappeared and 60% showed partial response with small and peripheral residual tumor of 172 mm3 on an average, as to say 11.2 times smaller than in group 4. CONCLUSION: ILH with a low power 830 nm diode laser is an efficient treatment of subcutaneous tumor model. Partial responses are attributed to an insufficient heating at the tumor periphery. More precise control of the peripheral tumor temperature will improve the ILH results.

Postfabrication resonance peak positioning of long-period cladding-mode-coupled gratings.

A simple, flexible method of postfabrication positioning of resonance wavelengths of long-period cladding-modecoupled gratings is proposed. This method is based on changing the outer fiber diameter. Reducing the diameter by etching the fiber in HF acid shifts the loss peaks to higher wavelengths. A shift as large as 130 nm after 5 min of HF etching was observed for our strongest grating peak, corresponding to the cladding mode HE19. The experimental results are in excellent agreement with model calculations.

[Measuring corneal thickness in photo-keratectomy with a reflectometry incorporated into the laser beam of the excimer laser]. / Messung der Hornhautdicke bei der Photo-Keratektomie mit einem in den Strahlengang des Excimer-Lasers integrierten Reflektometer.

PURPOSE: To integrate a newly developed OLCR instrument into the optical system of the excimer laser. The instrument is designed to perform corneal pachymetry before, during, and after corneal photoablation and thus allow for a precise and continuous on-line measurement of the corneal photoablation process. METHODS: The conditions required to integrate the OLCR instrument into the excimer laser optics were investigated. With a technical setting providing on-line data of corneal thickness, three groups of 8-10 corneae received central keratectomies of 27 (group 1), 82 (group 2) and 163 (group 3) microns calculated central depth and 7.38 mm diameter. All measurements were performed with OLCR and ultrasound. RESULTS: The OLCR instrument was coupled into the optical system of the excimer laser and a useful signal obtained at SLD power levels of 40 microW incident on the cornea. Individual corneal thickness measurements were obtained before, during and after the photoablation procedure. In group 1, the ablation was 50.3 (40-68) microns measured with ultrasound and 30.2 (27-38) microns measured with OLCR. In group 2, the ablation was 101.1 (80-113) microns measured with ultrasound and 93.3 (76-109) microns measured with OLCR. In group 3, the ablation was 210.6 (190-227) microns measured with ultrasound and 188.4 (181-197) microns measured with OLCR. The precision (standard deviation) for measurements of individual corneas was 1-2 microns with OLCR and up to 12 mm in Ultrasound measurements. CONCLUSION: With this interferometric method, continuous, non-contact measurement of corneal thickness before, during and after excimer laser photoablation were performed. By establishing a feed-back control between the pachymetric measurements and the photoablation process, the precision of excimer ablation may possibly be further increased.

Spatially incoherent illumination as a mechanism for cross-talk suppression in wide-field optical coherence tomography.

Comparison of two illumination modes for wide-field optical coherence tomography has revealed that spatially coherent illumination generates coherent cross talk, causing significant image degradation, and that spatially incoherent illumination, with an adequate interferometer design, provides an efficient mechanism for suppression of coherent cross talk. This is shown by comparison of a pulsed laser with a thermal light source for a U.S. Air Force resolution target covered with a scattering solution made from microbeads as well as for an ex vivo tooth.