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Effect of folding on the optical quality of soft acrylic intraocular lenses.

PURPOSE: To assess the effect of folding procedures on modulation transfer function (MTF) and resolving power (RP) in soft acrylic intraocular lenses (IOLs). SETTING: Faculty of Engineering, Chiba University, Chiba, Japan. METHODS: Folding procedures and other manipulations were performed on +18.0 diopter soft acrylic lenses (MA60BM, AcrySof, Alcon Surgical). The IOLs were then immersed in the water chamber of a model eye and MTF and RP under veiling glare light measured. The optical surfaces of the IOLs were examined microscopically. RESULTS: After the IOLs had been folded for 30 seconds, MTF recovered 8 and 6 minutes after unfolding in 20 degrees C 37 degrees C balanced salt solution, respectively. Prolonged folding of 10, 20, and 60 minutes did not affect the final MTF, which was measured 30 minutes after unfolding. However, RP deteriorated after the 60 minute folding. Optic damage was observed after the 20 and 60 minute foldings. Neither parameter changed after the IOLs were tightly folded for 30 seconds; however, both deteriorated slightly after the IOLs were tightly folded for 5 minutes, and minor damage was seen on the optics. With fewer than 10 artificial linear cracks in the central 3 mm of the optic, MTF was not affected; with 20 or fewer, RP was not affected. After forceps pressure on the central optic, MTF recovered within 6 minutes. CONCLUSION: The optical quality of soft acrylic IOLs are not easily affected unless extreme nonphysiological manipulations are applied.

Acrylates↗

Keratometric index, videokeratography, and refractive surgery.

PURPOSE: To clarify the confusion resulting from the use of slightly different refractive indices in calculations related to optical modeling of the cornea for refractive surgery, corneal diagnostics, and cataract surgery. SETTING: Scientific Institute H.S. Raffaele, Milan, Italy. METHODS: The cornea is represented as a centered optical system composed by 1, 2, or 3 spherical interfaces, in progression of modeling accuracy. Optical analysis is performed with the usual formulas of paraxial geometrical optics as well as with ray tracing. Simple models are also provided for corneas having both incisional and photoablative refractive surgery. Values of geometrical parameters are taken from the Gullstrand eye model. RESULTS: Using the keratometric index of refraction of 1.3375 is validated for estimating optical power differences on untreated corneas or after incisional keratotomy. It is not as accurate in assigning absolute values of dioptric power, where the value 1.3315 is more appropriate. For photorefractive keratectomy (PRK), however, the proper stromal index of refraction, 1.376, must be used for ablation calculations and dioptric change estimates. CONCLUSION: Videokeratographic instruments should include three distinct values of refraction index (1.3375, 1.376, and 1.3315) for an accurate and complete characterization of dioptric power maps. In cataract surgery, corrections must be introduced in the calculation of intraocular lens power for patients who have previously had PRK.

Cataract Extraction↗

Cleavage of tertiary amidomethyl ester prodrugs of carboxylic acids by rat liver homogenates.

The hydrolysis of tertiary amidomethyl ester prodrugs of carboxylic acids by rat liver homogenates is reported. Amidomethyl esters are rapidly and quantitatively converted to the corresponding acid and secondary amide. Reactivity is inversely dependent upon the molar refractivity and lipophilicity of the ester, as well as with steric bulk in the carboxylic acid moiety. In contrast to chemical and plasma hydrolyses, no dependence upon the pK(a) of the carboxylate leaving group was observed, nor was there any dependence upon the amide N-substituent. The rate of decomposition was inhibited by the carboxylesterase inhibitor eserine but not by the cytochrome P450 inhibitor SKF-525A, indicating the involvement of esterases in the hydrolysis reaction. These results indicate that amidomethyl esters may be expected to be readily cleaved in vivo.

Amides↗

Effect of incident angle of light on sensitivity and detection limit for layers of antibody with surface plasmon resonance spectroscopy.

The effect of the incident angle of light on sensitivity and the detection limit for surface-plasmon resonance spectroscopy were examined. The sensitivities and the detection limit were experimentally measured using an antibody as a modeled analyte in the incident angles of a light region of 66-76 degrees. The results showed that the sensitivity of a smaller incident angle was higher than that of a larger one. For instance, the sensitivity of a 66 degree incident angle was three times higher than that of a 76 degree incident angle. The detection limit with a 66 degree incident angle was one-tenth of that with a 76 degree incident angle. These sensitivities and detection limits were compared with those of a commercially produced surface-plasmon resonance instrument. This comparison demonstrated that a wavelength resolution of the order of less than 10(-2) nm was necessary to obtain satisfactory sensitivities and detection limits. In addition, the refractive index and thickness of the antibody layer formed on a sensor surface was proposed by experimental results and theoretical calculation.

Adsorption↗

Optical chip immunoassay for hCG in human whole blood.

We report on the development of an integrated optic chip sensor for performing rapid and sensitive immunoassays with human whole blood using human chorionic gonadotropin (hCG) as the model system. The optical chip is based on the Hartman interferometer, which uses a single planar lightbeam to address multiple interferometers, each comprising a signal/reference pair of sensing regions. The binding of antigen to specific capture antibodies on the signal sensing region causes a change in the refractive index of the surface layer, which is detectable by its effect on the evanescent field of the guided lightbeam. The reference-sensing region is coated with an irrelevant antibody, which optically cancels a large fraction of the non-specific adsorption that occurs on the specific-sensing region when the sensor is tested with clinical specimens. This work extends previous experiments with buffer and human serum to measurements in undiluted whole human blood. Optical chips were stored dry after surface functionalization, and rehydrated with blood. Colloidal gold nanoparticles conjugated to a second anti-hCG monoclonal antibody were used to provide signal amplification, thereby enhancing assay sensitivity, in a one-step procedure with the gold conjugate added to the test sample immediately prior to measurement. Background signals due to non-specific binding (NSB) in blood were found to be higher than those previously reported with human serum. In addition, a high level of background signal was found with the gold conjugate, which had not been observed in experiments with either buffer or serum. Nevertheless, hCG could be detected at 0.5 ng/ml within 10 min of sample application. The sensor response was linear over the concentration range 0.5-5 ng/ml hCG, as compared with the clinically-relevant range 0.3-1.5 ng/ml. Detection at higher concentrations was affected by scattering from large amounts of bound gold nanoparticles. However, initial binding rate measurements could be used to maintain assay quantitation.

Chorionic Gonadotropin↗

Detection of progesterone in whole blood samples.

The progesterone concentration in blood samples can be utilised as a marker for the diagnosis of early pregnancy, endocrinopathy and virilism. Here, we describe a method for progesterone detection and measurement in whole blood samples by a surface sensitive biosensor used in conjunction with an integrated optical grating coupler. This device determines refractive index changes near the biosensor's surface. Hence, biological species bound to a surface layer can be measured in real-time without any label. For the measurements, we have modified the indirect competitive immunoassay principle. The concentration of the progesterone antibody was kept at 1 microg/ml. Progesterone concentration was determined in buffer solution and whole blood in a range between 0.005 and 10 ng/ml. The detection limit was determined to be 3 pM. The relative standard deviation was calculated to be 3.5%.

Antigen-Antibody Complex↗

Application of the optical waveguide lightmode spectroscopy to monitor lipid bilayer phase transition.

An instrument for optical waveguide lightmode spectroscopy (OWLS) was designed and developed for measurements at different and controlled temperatures in a range of 15 degrees C around room temperature. The instrument allows to scan the waveguide modes at different wavelengths on the same optical chip using different lasers. This instrument was used to monitor DMPC lipid bilayer main phase transition around the critical temperature. The main problem in these experiments is that the OWLS measurements do not give enough information about an optically anisotropic system like a lipid bilayer. Experimental OWLS data at two different wavelengths can however approximately solve the problem. The temperature dependence of the thickness and the refractive indices (ordinary and extraordinary) for the lipid bilayer around the phase transition is presented. (A theoretical derivation of the extraordinary refractive index is given in.)

Computer Simulation↗

Highly sensitive biosensing using a supercritical angle fluorescence (SAF) instrument.

We present a new optical biosensor for probing molecular binding to a water/glass interface. The system is designed to measure the kinetics of surface reactions down to low analyte concentrations straightforwardly. The selective detection of surface bound fluorescence is achieved by collecting supercritical angle fluorescence (SAF) emission of surface bound molecules into the glass. Thereby the expansion of the detection volume into the aqueous probe is reduced to about one sixth of the fluorescence wavelength, consequently bulk fluorescence from the solution is rejected successfully. The SAF-signal is captured by a parabolic glass lens, which leads to high spatial collection efficiency and detection sensitivity. The sensor has an inverted optical design and is compatible with common glass cover slips, which strongly facilitates operation for the user working in the biological and biochemical fields. The performance of the system is demonstrated by real time measurements of antibody-antigen reactions. Rate constants of the reaction were extracted. Antigen concentrations were detected down to 10(-13) mol/l.

Antigen-Antibody Complex↗

Novel integrated optical sensor based on a grating coupler triplet.

A novel approach for accomplishing robust integrated optical biosensors is presented. The principle is based on a symmetric grating coupler structure with the inherent feature of compensating disturbances originating from different kinds of mechanical instabilities. The complete sensor system has no moving parts and provides the high sensitivities typical for integrated optical sensors based on grating couplers. The feasibility of this approach is demonstrated by determining the refractive index of liquids as well as by measuring the specific binding of biomolecules (anti-chicken IgG) to immobilized chicken IgG on the sensor chip surface.

Biosensing Techniques↗

Immobilized chicken antibodies improve the detection of serum antigens with surface plasmon resonance (SPR).

Surface plasmon resonance (SPR) and other refractive index and mass sensitive methods are, due to complement activation by mouse monoclonal antibodies and with concomitant high background signal, only rarely used for the detection of antibody-antigen interactions in the blood serum milieu. In the present study chicken IgY and mouse IgG were immobilized to a sensor chip CM5 dextran matrix and compared for their background signal and detection of serum antigen. Ellipsometry with antibodies adsorbed to methylated silicon surfaces was used as a complementary detection method. As expected, fundamental differences in binding properties between the two kinds of antibodies were observed. Mouse antibodies bound large quantities of human serum. Human C1q was detected on mouse IgG and the complement system was activated, as seen from the rapid C3 and properdin depositions. Chicken antibodies bound low quantities of human serum and no human C1q. Moreover, C3 and properdin deposited only after prolonged serum incubations. Addition of EDTA to serum reduced the background signal modestly for both IgG and IgY. Serum samples with different concentrations of human C3 were injected over surfaces with immobilized chicken anti-C3, and the response was measured by SPR. Small concentration differences (< 1.25 micrograms/ml) in a physiologically relevant range (1-40 micrograms/ml after 100 times dilution) could then be detected reproducibly. The SPR signal was totally obscured when a mouse monoclonal anti-C3 antibody was used for the detection.

Animals↗

Specific bio-recognition reactions observed with an integrated Mach-Zehnder interferometer.

The combination of an integrated Mach-Zehnder-interferometer (iMZI) at the bottom of a fluidic microchannel system with supramolecular interfacial binding layers optimized for biosensing purposes is described. The model system used is based on the highly specific interaction of streptavidin to its 'ligand' biotin: a single monolayer of a correspondingly derivatized silane-compound is formed by a self-assembly procedure on top of the channel rib guiding the light through the channels. Injection of a streptavidin solution which leads to the formation of a protein monolayer of d = 2.8 nm in effective thickness results in a phase shift of the sample light relative to the reference channel of delta phi = 6 pi, in good agreement with the theoretical sensitivity of delta phi/delta df = 2.9 pi/nm for a protein layer (n = 1.45) calculated for the device.

Biosensing Techniques↗

Characterisation and some possible uses of Plukenetia conophora and Adenopus breviflorus seeds and seed oils.

Two non-conventional seeds, Plukenetia conophora (PKCP) and Adenopus breviflorus (ADB) were analysed for their proximate, fatty acids, sterols composition and physico-chemical characteristics. Crude protein was 25.65% for PKCP and 28.25% for ADB. ADB had lower moisture content (4.5%) than PKCP (8.0%) indicating that the former has better shelf life. Oil yields of the seeds were 49.58% for PKCP and 56.22% for ADB. The major sterols were stigmasterol and beta-sitosterol in PKCP and ADB respectively. PKCP oil had 98.8% unsaturated fatty acids with linolenic acid predominating (70.1%) while ADB had 85.1% unsaturated fatty acids with linoleic acid being most abundant (65.3%). The very high saponification and iodine values of PKCP oil suggest its utilisation in alkyd resin, shoe polish, liquid soap and shampoo production. There is the possibility of using ADB oil in these regards as well as for edible purposes.

Chemical Phenomena↗

Searching for allosteric effects via QSARs.

A study of our database of 7,000 QSARs involving chemical-biological interaction uncovered 11 examples where the QSARs all contain inverted parabolas based on molecular refractivity. That is, biological activity first decreases with increase in MR and then increases. Two of the examples are for enzymes: cyclooxygenase and trypsin. The others are for various receptors. The results seem to be best rationalized by the larger compounds inducing a change in a receptor unit that allows for a new mode of interaction.

Allosteric Regulation↗

Discrimination of glass sources using elemental composition and refractive index: development of predictive models.

Refractive index and metal ion concentrations (Al, Ba, Ca, Fe, Mg, Mn, Sr, Ti and Zr) were determined for four product-use categories: headlamp glass; container glass, non-vehicle window float glass, and vehicle float glass. Linear discriminant modelling using these data allowed differentiation of the four glass types but further discrimination was not possible within a product-use category. For this specific set of glasses, the concentrations of a number of metal ions were found to be correlated in some cases. This precluded the use of traditional probability calculations in using elemental composition data for interpretation of glass evidence. Alternative approaches to glass data interpretation are suggested.

Forensic Medicine↗

Thermal lens spectrometry in aqueous solutions of Brij 35: investigation of micelle effects on the time-resolved and steady-state signals.

This work investigates the effect of micelles on the time-resolved and steady-state thermal lens signals in aqueous solutions. The temperature gradient produced subsequently to non-radiative relaxation of the sample induces migration of micelles towards the colder region of the irradiated area along with an opposite flow of solute molecules. This phenomenon, known as the Soret effect, produces an additional probe beam signal with a rise time that is much longer than the thermal time constant and depends on the surfactant and solute concentrations. Extrapolation of the mass-diffusion constant at zero solute concentration allowed the determination of diffusion coefficients that are close to those derived by other methods for Brij 35 micelles in water. It is also shown that the surfactant has only a small effect on the thermal lens signal and that the enhancement produced by micelles with respect to pure water originates mainly firom the Soret effect. It follows that interpretation of experimental data without discriminating both components of the probe beam signal can lead to erroneous values of dn/dT.

Detergents↗

Investigation of the thermal lens effect in water-ethanol mixtures: composition dependence of the refractive index gradient, the enhancement factor and the Soret effect.

The thermal lens effect produced in binary mixtures of water and ethanol has been investigated. It is shown that the sensitivity of the thermal lens method upon the addition of ethanol in water varies as the temperature-dependent refractive index gradient to thermal conductivity ratio of the mixture. The dependence of k and dn/dT upon the ethanol volume fraction follows a second-order and fourth-order polynomial, respectively, and cannot be precisely predicted using the additive rule. Moreover, depending on the experimental conditions and the mixture composition, the temperature gradient produced subsequently to relaxation of the excited species induces mutual migration of the solvent molecules and the formation of a concentration gradient in the irradiated area. This effect, known as the Soret effect, can locally change the thermo-optical properties of the solution and produce an additional signal, especially when steady-state experiments are done. This may result in errors as large as 20% when quantitative informations have to be derived from experimental data.

Ethanol↗