Polymer waveguide backplanes for optical sensor interfaces in microfluidics

A polymer optical backplane capable of generic luminescence detection within microfluidic chips is demonstrated using large core polymer waveguides and vertical couplers. The waveguides are fabricated through a new process combining mechanical machining and vapor polishing with elastomer microtransfer molding. A backplane approach enables general optical integration with planar array microfluidics since optical backplanes can be independently designed but still integrated with planar fluidic circuits. Fabricated large core waveguides exhibit a loss of 0.1 dB cm(-1) at 626 nm, a measured numerical aperture of 0.50, and a collection efficiency of 2.86% in an n = 1.459 medium, comparable to a 0.50 NA microscope objective. In addition to vertical couplers for out-of-plane collection and excitation, polymer waveguides are doped with organic dyes to provide wavelength selective filtering within waveguides, further improving optical device integration. With large core low loss waveguides, luminescence collection is improved and measurements can be performed with simple LEDs and photodetectors. Fluorescein detection via fluorescence intensity with a limit of detection (3sigma) of 200 nM in a 1 microL volume is demonstrated. Phosphorescence lifetime based oxygen detection in water in an oxygen controllable microbial cell culture chip with a limit of detection (3sigma) of 0.08% or 35 ppb is also demonstrated utilizing the waveguide backplane. Single waveguide luminescence collection performance is equivalent to a back collection geometry fiber bundle consisting of nine 500 microm diameter collection fibers.     

Integrated wavelength-selective optical waveguides for microfluidic-based laser-induced fluorescence detection

We demonstrate the fabrication and characterization of a novel, inexpensive microchip capable of laser induced fluorescence (LIF) detection using integrated waveguides with built-in optical filters. Integrated wavelength-selective optical waveguides are fabricated by doping poly(dimethysiloxane) (PDMS) with dye molecules. Liquid-core waveguides are created within dye-doped PDMS microfluidic chips by filling channels with high refractive index liquids. Dye molecules are allowed to diffuse into the liquid core from the surrounding dye-doped PDMS. The amount of diffusion is controlled by choosing either polar (low diffusion) or apolar (high diffusion) liquid waveguide cores. The doping dye is chosen to absorb excitation light and to transmit fluorescence emitted by the sample under test. After 24 h, apolar waveguides demonstrate propagation losses of 120 dB cm(-1) (532 nm) and 4.4 dB cm(-1) (633 nm) while polar waveguides experience losses of 8.2 dB cm(-1) (532 nm) and 1.1 dB cm(-1) (633 nm) where 532 and 633 nm light represent the excitation and fluorescence wavelengths, respectively. We demonstrate the separation and detection of end-labelled DNA fragments using polar waveguides for excitation light delivery and apolar waveguides for fluorescence collection. We demonstrate that the dye-doped waveguides can provide performance comparable to a commercial dielectric filter; however, for the present choice of dye, their ultimate performance is limited by autofluorescence from the dye. Through the detection of a BK virus polymerase chain reaction (PCR) product, we demonstrate that the dye-doped PDMS system is an order of magnitude more sensitive than a similar undoped system (SNR: 138 vs. 9) without the use of any external optical filters at the detector.     

Rapid fabrication of a microfluidic device with integrated optical waveguides for DNA fragment analysis

The fabrication and performance of a microfluidic device with integrated liquid-core optical waveguides for laser induced fluorescence DNA fragment analysis is presented. The device was fabricated through poly(dimethylsiloxane) (PDMS) soft lithography and waveguides are formed in dedicated channels through the addition of a liquid PDMS pre-polymer of higher refractive index. Once a master has been fabricated, microfluidic chips can be produced in less than 3 h without the requirement for a cleanroom, yet this method provides an optical system that has higher performance than a conventional confocal optical assembly. Optical coupling was achieved through the insertion of optical fibers into fiber-to-waveguide couplers at the edge of the chip and the liquid-fiber interface results in low reflection and scattering losses. Waveguide propagation losses are measured to be 1.8 dB cm(-1) (532 nm) and 1.0 dB cm(-1) (633 nm). The chip displays an average total coupling loss of 7.6 dB due to losses at the optical fiber interfaces. In the electrophoretic separation and detection of a BK virus PCR product, the waveguide system achieves an average signal-to-noise ratio of 570 +/- 30 whereas a commercial confocal benchtop electrophoresis system achieves an average SNR of 330 +/- 30. To our knowledge, this is the first time that a waveguide-based system has been demonstrated to have a SNR comparable to a commercially available confocal-based system for microchip capillary electrophoresis.     

Fabrication of ordered mesoporous thin films for optical waveguiding and interferometric chemical sensing

Planar optical waveguides with a propagation loss of 2.9 dB/cm at 633 nm were fabricated using ordered mesoporous thin films of TiO2-P2O5 nanocomposite deposited on the tin-rich surfaces of float glass slides. The resulting waveguides show substantial sensitivity to parts-per-million-level ammonia gas at room temperature on the basis of single-beam polarimetric interferometry.     

集成高分子光子学器件平台

在高分子基板上制作成的单膜全氟高分子波导结构,具有非热敏感性、偏振无关的工作特点,同时,在1310nm、1550nm工作波长分别有<0.04和<0.05dB/cm的超低光损耗.本文研究了在器件制作过程中所产生的孔状结构对传输损耗的直接影响.实验证明,超低的传输损耗可以通过降低孔状结构的尺度至纳米范围来实现.这些波导结构可以成为新一代高性能集成高分子光子器件的技术平台.     

Performance of an in-plane detection cell with integrated waveguides for UV/Vis absorbance measurements on microfluidic separation devices

A microfluidic device with integrated waveguides and a long path length detection cell for UV/Vis absorbance detection is presented. The 750 microm U-cell detection geometry was evaluated in terms of its optical performance as well as its influence on efficiency for electrophoretic separations in the microdevice. Stray light was found to have a strong effect on both, the sensitivity of the detection and the available linear range. The long path length U-cell showed a 9 times higher sensitivity when compared to a conventional capillary electrophoresis (CE) system with a 75 microm inner diameter (ID) capillary, and a 22 times higher sensitivity than with a 50 microm ID capillary. The linear range was comparable to that achieved in a 75 microm ID capillary and more than twice as large as in a 50 microm ID capillary. The use of the 750 microm U-cell did not contribute significantly to band broadening; however, a clear quantification was made difficult by the convolution of several other band broadening sources.     

A multireflection cell for enhanced absorbance detection in microchip-based capillary electrophoresis devices

The design, fabrication and testing of a photolithographically fabricated, glass-based multireflection absorbance cell for microfluidic devices, in particular microchip-based capillary electrophoresis (CE) systems is described. A multireflection cell was fabricated lithographically using a three-mask process to pattern aluminum mirrors above and below a flow channel in a chip, with 30 microm diameter optical entrance or exit apertures (one in each mirror) positioned 200 microm apart. Source and detector were positioned on opposite sides, and the metal mirrors were made 1 cm square, to reduce stray light effects. Calibration curves using bromothymol blue (BTB) with a 633 nm source (He:Ne laser) were linear to at least 0.5 absorbance units, with typical r2 values of 0.9997, relative standard deviations in the slopes of +/- 1.3%, and intercepts of zero within experimental error. Effective optical pathlengths of 50-272 microm were achieved, compared to single-pass pathlengths of 10-30 microm, corresponding to sensitivity enhancements (i.e., optical path length increase) of 5 to 10-fold over single-pass devices. Baseline absorbance noise varied within a factor of two in almost all devices, depending only weakly on path length. This device can give much higher absorbance sensitivity, and should be much easier to manufacture than planar, glass-based devices previously reported.     

高效液相色谱法同时测定制药废水中的交沙霉素、茶碱及扑热息痛

建立了同时测定制药废水中残留的交沙霉素、茶碱、扑热息痛等3种药物的高效液相色谱方法。样品经固相萃取处 理后进行色谱分析。采用的色谱条件:色谱柱为Hypersil ODS柱（4.6 mm i.d.×200 mm）;流动相A液为0.025 mol/L KH2PO4-H3PO4 缓冲液(pH 2.75),流动相B液为甲醇;梯度洗脱;紫外检测波长为230 nm(交沙霉素)、272 nm(茶碱)、243 nm(扑热息痛)。制药废水中3种药物的加标回收率均高于93%,相对标准偏差(n=6)小于2.1%,检测下限(S/N=3)不高于1.0 μg/L。该方法已应用于制药废水的生物强化降解研究。     

Monolithic integration of optical waveguides for absorbance detection in microfabricated electrophoresis devices.

The fabrication and performance of an electrophoretic separation chip with integrated optical waveguides for absorption detection is presented. The device was fabricated on a silicon substrate by standard microfabrication techniques with the use of two photolithographic mask steps. The waveguides on the device were connected to optical fibers, which enabled alignment free operation due to the absence of free-space optics. A 750 microm long U-shaped detection cell was used to facilitate longitudinal absorption detection. To minimize geometrically induced band broadening at the turn in the U-cell, tapering of the separation channel from a width of 120 down to 30 microm was employed. Electrical insulation was achieved by a 13 microm thermally grown silicon dioxide between the silicon substrate and the channels. The breakdown voltage during operation of the chip was measured to 10.6 kV. A separation of 3.2 microM rhodamine 110, 8 microM 2,7-dichlorofluorescein, 10 microM fluorescein and 18 microM 5-carboxyfluorescein was demonstrated on the device using the detection cell for absorption measurements at 488 nm.     

Design and fabrication of single mode rib waveguides using sol–gel derived organic–inorganic hybrid materials

Multi-layer buried rib waveguides were fabricated using sol–gel derived photopatternable organic–inorganic hybrid materials through multi-step spin coating and photolithography. A single mode circular waveguide at 1,550 nm was designed and fabricated using the equivalent refractive index method. Propagation loss in the order of 1.0 dB/cm was measured by cutback method. Waveguide thermal stability and thermo-optic coefficient were investigated using thermogravimetric analysis (TGA) and spectroscopic ellipsometry, respectively. Results suggest that the single mode waveguide can be used to develop thermal optical devices such as thermo-optic switches.     

Separation and determination of norepinephrine, epinephrine and isoprinaline enantiomers by capillary electrophoresis in pharmaceutical formulation and human serum

A capillary electrophoresis method with ultraviolet (UV) detection was developed and optimized for the enantiomer separation of norepinephrine (NE), epinephrine (EP) and isoprenaline (IP) using dual cyclodextrins (CDs) of 2-hydroxypropyl-beta-CD (HP-beta-CD) and heptakis (2,6-di-o-methyl)-beta-CD (DM-beta-CD) as chiral selectors. Optimal separation was obtained using a running buffer of 50mM phosphate containing 30mM HP-beta-CD and 5mM DM-beta-CD at pH 2.90 and a field strength of 20kV in 45cmx75mum (40cm effective length) uncoated capillary. The UV absorbance detection was set at 205nm. A 0.1% (w/w) polyethylene glycol or 0.1% (v/v) acetonitrile was used to enhance the detection sensitivity. There was a wide and excellent linear calibration graph for each enantiomer in the range 1.0x10(-3) to 1.0x10(-6)M and the detection limit (S/N=3) was found from 8.5x10(-7) to 9.5x10(-7)M. The method has been applied for the determination of isoprenaline in isoprenaline hydrochloride aerosol and to the analysis of serum samples. The recoveries of NE and EP in serum and IP in drug were ranged from 90 to 110%. The relative standard deviations of all the analyte peaks were less than 2.8% for migration time and less than 4.8% for peak area.     

Microstructural and Spectroscopic Studies of Sol-Gel Derived Silica-Titania Waveguides

Silica-titania planar waveguides were prepared via the sol-gel method from acid-catalyzed solutions of firstly, ÿ-Glycidoxypropyltrimethoxysilane mixed with tetrapropylorthotitanate (labeled as GT), and secondly, ÿ-Glycidoxypropyltrimethoxysilane mixed with both tetrapropylorthotitanate and tetraethoxysilane (labeled as GTT). Atomic force microscopy, thermal gravimetric analysis, differential thermal analysis, UV-visible spectroscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy were used to study the structural and optical properties of the waveguide films prepared from the two types of sols. The obtained results showed that in both cases, crack-free and highly transparent silica-titania films with a thickness of more than 0.5 m could be obtained by a single spin-coating process after a heat treatment at 500°C. The GT derived films showed more shrinkage and a higher refractive index after annealing as compared to the GTT derived films. When such films were deposited on a silica-on-silicon substrate to act as a surface planar waveguide, the light propagation loss was measured to be about 0.9 dB/cm and 1.3 dB/cm respectively. Raman spectroscopy results indicated that the GTT derived waveguide films with 0.5 molar titanium content contained amorphous carbon phase after being heated at above 500°C in air directly.     

高效液相色谱法同时测定诺诺感冒片中扑尔敏、扑热息痛、盐酸伪麻黄碱的含量

 采用反相高效液相色谱法 ,在C18柱上以V(甲醇 )∶V(水 ) =2 5∶75的溶液为流动相 (内含 0 .0 5mol/L磷酸二氢钠 ) ,检测波长为 2 0 5nm ,同时分离测定诺诺感冒片中扑尔敏、扑热息痛、盐酸伪麻黄碱的含量。扑尔敏、扑热息痛和盐酸伪麻黄碱的检出限分别为 1.16mg/L ,0 .15mg/L和 1.82mg/L ,其相应的回收率分别为 98.35 % (n =5 ,RSD =1.6 0 % ) ,10 1.16 % (n =5 ,RSD =1.5 0 % )和 98.5 0 % (n =5 ,RSD =1.5 9% )。方法简便、快速 ,重现性好 ,适用于诺诺感冒片的质量检验分析。     

Reversed-phase capillary electrochromatography for the simultaneous determination of acetylsalicylic acid, paracetamol, and caffeine in analgesic tablets

The separation and simultaneous determination of caffeine, paracetamol, and acetylsalicylic acid in two analgesic tablet formulations was investigated by capillary electrochromatography (CEC). The effect of mobile phase composition on the separation and peak efficiency of the three analytes was studied and evaluated; in particular, the influence of buffer type, buffer pH, and acetonitrile content of the mobile phase was investigated. The analyses were carried out under optimized separation conditions, using a full-packed silica capillary (75 microm ID; 30.0 cm and 21.5 cm total and effective lengths, respectively) with a 5 microm C8 stationary phase. A mixture of 25 mM ammonium formate at pH 3.0 and acetonitrile (30:70 v/v) was used as the mobile phase. UV detection was at 210 nm. Good linearity was found in the range of 50-200, 20-160, and 4-20 microg/mL for acetylsalicylic acid (r2=0.9988), paracetamol (r2=0.9990) and caffeine (r2=0.9990), respectively. Intermediate precision (RSD interday) as low as 0.1-0.8% was found for retention times, while the RSD values for the peak area ratios (Aanalyte/AIS) were in the range of 1.9-2.9%. The optimized CEC method was applied to the analysis of the studied compounds present in commercial tablets.     

A compact optofluidic cytometer with integrated liquid-core/PDMS-cladding waveguides

We developed a simple method to construct liquid-core/PDMS-cladding optical waveguides through pressurized filling of dead-ended micro-channels with optical fluids. The waveguides are in the same layer as microfluidic channels which greatly simplifies device fabrication. With proper contrast between the refractive index of the core and cladding, the transmission loss of the waveguides is less than 5 dB cm(-1). We also developed a method to create flat and optically clear surfaces on the sides of PDMS devices in order to couple light between free-space and the waveguides embedded inside the chip. With these newly developed techniques, we make a compact flow cytometer and demonstrate the fluorescence counting of single cells at a rate of up to ～50 cell s(-1) and total sample requirement of a few microlitres. This method of making liquid-core optical waveguides and flat surfaces has great potential to be integrated into many PDMS-based microsystems.     

Analysis of benzyldimethyldodecylammonium bromide in chemical disinfectants by liquid chromatography and capillary electrophoresis

Two novel analytical methodologies using capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC) were developed and compared for the determination of benzyldimethyldodecylammonium bromide (BAB) in commercial compound chemical disinfectants. The LC analysis was performed with a Kromasil C18 (200 mm x 4.6 mm, 5 microm) column and a mobile phase of A:B = 80:20 (A: acetonitrile, B: 4 mmol/L octanesulfonic sodium--0.02 mol/L acetic sodium, adjusted with acetic acid to pH 5.2) at a flow rate of 1.0 mL/min. Detection was by ultraviolet absorption at 262 nm. The CE analysis was performed in a bare fused-silica capillary with 75 microm i.d. and total length of 46.4 cm with a buffer solution of 50% acetonitrile -50 mmol/L NaH2PO4, pH 2.24. The applied voltage was 20 kV. Detection was by ultraviolet absorption at 214 nm. Under optimized conditions, the HPLC retention time and CE migration time for BAB was 9.18 and 5.08 min, respectively. Calibration curves of peak area versus concentration gave correlation coefficients of 0.9996 for HPLC and 0.9994 for CE. The detection limits for HPLC and CE were 1.6 mg/L and 0.2 mg/L, respectively. Average recoveries at three concentration levels (50, 100, 200 mg/L for HPLC: 20, 40, 100 mg/L for CE) were 99.94 +/- 1.5, 99.64 +/- 1.3 and 99.61 +/- 0.4% for HPLC and 120.47 +/- 2.6, 102.06 +/- 8.7 and 103.05 +/- 3.0% for CE, respectively. Although both methods were shown to be suitable for the determination of BAB in commercial disinfectant compounds, CE provided analysis with less solvent purchase/disposal and better column efficiency, whereas HPLC provided superior precision.     

On-chip absorption measurements using an integrated waveguide

Square hollow waveguides are used to integrate measurement of absorption with chip-based electrophoresis. The 50x50 microm liquid channel and 50x50 microm waveguide are etched as a negative pattern into a silicon master and replicated as a positive in poly-dimethylsiloxane (PDMS). The uniform refractive index of the chip prevents guiding by total internal reflection. Instead, light at 488 nm is guided by reflection at the air-PDMS interface. The waveguide has a 60% efficiency over a distance of 3.2 cm. Separation of fluorescein and the dye BODIPY is demonstrated. A detection limit (S/N=3) of 200 microM fluorescein is obtained using a 50 microm pathlength and a simple photocell detector.     

Integrated particle detection chip for environmental monitoring

This paper reports an integrated particle detection chip for low-cost and point-of-interest environmental monitoring; it consists of a micro virtual impactor and a micro corona discharger. With this system, airborne particles are introduced into the micro virtual impactor of the chip where they are classified according to their aerodynamic diameters. The particles are then charged and their number-concentration is detected in the micro corona discharger from the electrical current carried by the charged particles. The characteristics of each component were first analyzed, and the components were then integrated into a single chip. The micro virtual impactor was designed to have a cut-off diameter of 600 nm or 1.0 microm. Its classification characteristics were examined by classifying polydisperse particles-dioctyl sebacate particles ranging in diameter from 100 to 600 nm and carbon particles ranging in diameter from 0.6 to 10 microm. From the classification results, the cut-off diameter of the micro virtual impactor was measured to be either 550 nm or 1.1 microm. The micro corona discharger was fabricated based on a sharp silicon tip and a planar electrode and charged particles at 1.3 kV. Using the integrated particle detection chip comprising the micro virtual impactor and the micro corona discharger, the sensitivity for monodisperse particles-500 nm dioctyl sebacate in diameter-was measured to be 8 x 10(-7) pA/(particle cm(-3)).     

Development and validation of stability-indicating HPLC method for the simultaneous determination of paracetamol, tizanidine, and diclofenac in pharmaceuticals and human serum

A method is described for the simultaneous determination of paracetamol, tizanidine, and diclofenac in mixtures. The method was based on HPLC separation of the three drugs followed by UV detection at 254 nm. The separation was carried out on a Hypersil ODS, C18 (250 x 4.6 mm id, 10 microm particle size) column using the mobile phase aqueous 0.2% ammonium carbonate-methanol (60 + 40, v/v) at a flow rate of 1 mL/min. The linear regression analysis data were used for the regression curve in the range of 170-10 000 ng/mL for paracetamol, 120-10 000 ng/mL for tizanidine, and 20-10 000 ng/mL for diclofenac. No chromatographic interference from tablet excipients was found. In order to check the selectivity of the proposed method, degradation studies were carried out using hydrolysis (acid, basic, and neutral), thermolysis, and oxidation. The developed method, after being validated in terms of precision, robustness, recovery, LOD, and LOQ, was successively applied to the analysis of pharmaceutical formulations and human serum.     

Integrated optical NIR-evanescent wave absorbance sensorfor chemical analysis

A new, long-path integrated optical (IO) sensor for the detection of non-polar organic substances is described. The sensing layer deposited on a planar multimode IO structure is built by a suitable silicone polymer with lower refractive index (RI). It acts as a hydrophobic matrix for the reversible enrichment of non-polar organic contaminants from water or air. Light from the near-infrared (NIR) range is coupled into the planar structure and the evanescent wave part of the light field penetrating into the silicone layer interacts with the enriched organic species. As a result, light is absorbed at the characteristic frequencies of the corresponding C-H, N-H or O-H overtone and combination band vibrations of the analytes. To perform evanescent field absorbance (EFA) measurements, the arc-shaped strip waveguide structure of 172 mm interaction length was adapted to a tungsten-halogen lamp and an InGaAs diode array spectrograph over gradient index fibers. Dimethyl-co-methly(phenyl)polysiloxanes with varying degrees of phenylation were prepared and used as sensitive coating materials for the IO structure. Light attenuation in the arc-shaped waveguides is high and typical insertion losses in the range of 14-18 dB were obtained. When the coated sensors were brought in contact with aqueous samples, the light transmission decreases, which is due to the formation of H(2)O micro-emulsions in the silicone superstrates. Nevertheless, after reaching constant light transmissions, absorbance spectra of aqueous trichloroethene samples were successfully collected. For gas measurements, where water cross sensitivity problems are absent, the sensitivity of the IO device for trichloroethene was tested as a function of the RI of the silicone superstrate. The slope of the TCE calibration function increases by a factor of 10 by using a poly(methylphenylsiloxane) layer with a RI of 1.449 instead of poly(dimethylsiloxane) (RI: 1.41). A comparison of the IO-EFA and an earlier developed fiber-optic EFA sensor for trichloroethene measurements in the gas phase showed an increase in sensitivity per unit length of the waveguide by a factor of up to 120.