Michael J. McShane

Theoretical justification of wavelength selection in PLS calibration : Development of a new algorithm

The mathematical basis of improved calibration through selection of informative variables for partial least-squares calibration has been identified. A theoretical investigation of calibration slopes indicates that including uninformative wavelengths negatively affect calibrations by producing both large relative bias toward zero and small additive bias away from the origin. These theoretical results are found regardless of the noise distribution in the data. Studies are performed to confirm this result using a previously used selection method compared to a new method, which is designed to perform more appropriately when dealing with data having large outlying points by including estimates of spectral residuals. Three different data sets are tested with varying noise distributions. In the first data set, Gaussian and log-normal noise was added to simulated data which included a single peak. Second, near-infrared spectra of glucose in cell culture media taken with an FT-IR spectrometer were analyzed. Finally, dispersive Raman Stokes spectra of glucose dissolved in water were assessed. In every case considered here, improved prediction is produced through selection, but data with different noise characteristics showed varying degrees of improvement depending on the selection method used. The practical results showed that, indeed, including residuals into ranking criteria improves selection for data with noise distributions resulting in large outliers. It was concluded that careful design of a selection algorithm should include consideration of spectral noise distributions in the input data to increase the likelihood of successful and appropriate selection.

Layer-by-layer assembly for drug delivery and related applications

Introduction: High-performance drug delivery systems are always made through assembly and hybridization of multiple components, each of which possesses its own role within the unified delivery function. The layer-by-layer (LbL) adsorption technique offers huge freedom in material selection and flexibility of structural design, which are fully matched with the fabrication needs of drug delivery materials requiring complicated designs. Areas covered: In this review, film-type LbL assemblies and their drug delivery application are focused on, with selected examples from recent years. In addition to a description of the general progress of this technique in bio-related areas, examples of the delivery of low-molecular-mass drugs, DNA, peptides and proteins are summarized, as well as recent advances in film structures composed of organic/inorganic hybrids. Expert opinion: The authors expect that the highly versatile nature of the LbL assembly can overcome any remaining practical difficulties in delivering therapeutics, because the layer structure, component selection, and the surface nature including biocompatibility, degradability and size/dimension are all adjustable. Furthermore, the simple and inexpensive nature of this technique can also satisfy strict demands from an economic point of view.

Potential for glucose monitoring with nanoengineered fluorescent biosensors.

Possibilities for engineering of fluorescent micro/nanoscale devices for glucose sensing are presented. A description of the potential for clinical use is given in terms of overall concept, current knowledge, advantages of the fabrication approach proposed, and challenges that must be addressed prior to clinical use. Deployment of micro/nanoparticles in the dermis may allow transdermal monitoring of glucose changes in interstitial fluid. Using electrostatic self-assembly, an example of nanotechnology for fabrication, two types of sensors are being studied: (1). solid nanoparticles coated with fluorescent enzyme-containing thin films and (2). hollow micro/nanocapsules containing fluorescent indicators and enzymes or glucose-binding proteins. Nanoengineering of the coated colloids and microcapsules allows precision control over optical, mechanical, and catalytic properties to achieve sensitive response using a combination of polymers, fluorescent indicators, and glucose-specific proteins. Challenges to in vivo use include understanding of material toxicity and failure modes, and determining methods to overcome fouling, protein inactivation, and material degradation.

Microcapsules Ejecting Nanosized Species into the Environment

In this communication we report on microcapsules which eject nanoparticles into the environment. The speed of the nanoparticles ejected in water is approximately 800-fold faster than their Brownian diffusion. Such microcarriers may allow nanosized species to travel long distances, in short times, through highly viscous environments and may find applications in e.g. drug delivery and tissue engineering.

Glucose-sensitive nanoassemblies comprising affinity-binding complexes trapped in fuzzy microshells.

A new design for glucose monitoring with “smart” materials based on self assembly, competitive binding, and resonance energy transfer (RET) is presented. The basic transduction principle is changing RET efficiency from fluorescein isothiocyanate (FITC) to tetramethylrhodamine isothiocyanate (TRITC), as FITC-dextran is displaced from TRITC-Concanavalin A (Con A) with the addition of glucose. Nanoscale fabrication by self-assembly of Con A/dextran into multilayer films, followed by polymer multilayers. The advantages of this approach include physical localization and separation of sensing molecules from the environment via entrapment of the biosensor elements in a semi-permeable polymeric shell, and only functional molecules are included in the sensors. To realize these nanostructures, dissolvable resin microparticles were coated with FITC-dextran+TRITC-Con A multilayers, followed by polyelectrolyte multilayers, and the core particles were then dissolved to yield hollow capsules. The nanoassembly process was studied using microbalance mass measurements, fluorescence spectroscopy, confocal fluorescence microscopy, and zeta-potential measurements. The key findings are that the specific binding between Con A and dextran can be used to deposit ultrathin multilayer films, and these exhibit changing RET in response to glucose. Fluorescence spectra of a microcapsules exhibited a linear, glucose-specific, 27% increase in the relative fluorescence of FITC over the 0–1800 mg/dL range. These findings demonstrate the feasibility of using self-assembled microcapsules as optical glucose sensors, and serve as a basis for work toward better understanding the properties of these novel materials.

Monte Carlo modeling for implantable fluorescent analyte sensors

A Monte Carlo simulation of photon propagation through human skin and interaction with a subcutaneous fluorescent sensing layer is presented. The algorithm will facilitate design of an optical probe for an implantable fluorescent sensor, which holds potential for monitoring many parameters of biomedical interest. Results are analyzed with respect to output light intensity as a function of radial distance from source, angle of exit for escaping photons, and sensor fluorescence (SF) relative to tissue autofluorescence (AF). A sensitivity study was performed to elucidate the effects on the output due to changes in optical properties, thickness of tissue layers, thickness of the sensor layer, and both tissue and sensor quantum yields. The optical properties as well as the thickness of the stratum corneum, epidermis, (tissue layers through which photons must pass to reach the sensor) and the papillary dermis (tissue distal to sensor) are highly influential. The spatial emission profile of the SF is broad compared that of the tissue fluorescence and the ratio of sensor to tissue fluorescence increases with distance from the source. The angular distribution of escaping photons is more concentrated around the normal for SF than for tissue AF. The information gained from these simulations will he helpful in designing appropriate optics for collection of the signal of interest.

Variable Selection in Multivariate Calibration of a Spectroscopic Glucose Sensor

A variable selection method that reduces prediction bias in partial least-squares regression models was developed and applied to near-infrared absorbance spectra of glucose in pH buffer and cell culture medium. Comparisons between calibration and prediction capability for full spectra and reduced sets were completed. Variable selection resulted in statistically equivalent errors while reducing the number of wavelengths needed to fit the calibration data and predict concentrations from new spectra. Fewer than 25 wavelengths were selected to produce errors statistically equivalent to those yielded by the full set containing over 500 wavelengths. The algorithm correctly chose the glucose absorption peak areas as the information-carrying spectral regions.

Application of self-assembled ultra-thin film coatings to stabilize macromolecule encapsulation in alginate microspheres.

Alginate-based hydrogels have several unique properties that have enabled them to be used as a matrix for the entrapment of a variety of enzymes, proteins and cells for applications in bioprocessing, drug delivery and chemical sensing. However, control over release rates or, in some cases, stable encapsulation remains a difficult goal, especially for small particles with high surface-area-to-volume ratios. In this work, the potential to limit diffusion of macromolecules embedded in alginate spheres with nanofilm coatings was assessed. Alginate microspheres were fabricated using an emulsification process with high surfactant concentration to form beads in the size range of 2–10 µm. Using calcium chloride for ionotropic gelation, dextran was encapsulated in the gel phase by mixing with the alginate in solution. The exterior surface was then modified with polyelectrolyte coatings using the layer-by-layer self assembly technique. Leaching studies to assess retention of dextran with varying molecular weights confirmed that the application of multi-layer thin films to the alginate microspheres was effective in reducing leaching rate and total loss of the encapsulated material from the microspheres. For the best case, the rate of release for dextran of 2 000 000 Dalton molecular weight decreased from 1% h−1 in bare microspheres to 0.1% h−1 in polyelectrolyte-coated microspheres. The effectiveness of nanofilms reducing loss of the encapsulated macromolecules was found to vary between different polycation materials used. These studies support the feasibility of using these microsystems for development of long-term stable encapsulated systems, such as implantable biosensors.

A fiber-optic broad-range pH sensor system for gastric measurements

Abstract The construction and performance of a fiber-optic broad-range pH sensor system are described. The general construction of the sensor is similar to the original fiber-optic pH sensor, but two dyes with three p K values have been immobilized to provide resonse over the pH range of 0.5–7 with a precision better than 0.1 pH unit. The range extends to pH9 with less precision. The primary objective of the design is for gastric measurements. The system is based on absorbance dyes bound to polyacrylamide gel containing light-scattering particles. The sensor is constructed on a single 0.25-mm diameter plastic optical fiber. The optical system consists of a tungsten lamp, fiber-optic splitter and CCD/grating detector connected to a computer for spectral analysis, using two wavelength regions. The computer displays the pH graphically over 24 h. The system shows stability within 0.2 pH unit over 24 h, and has been tested with gastric samples in a dog.

Assessment of Partial Least-Squares Calibration and Wavelength Selection for Complex Near-Infrared Spectra

Complex near-infrared (near-IR) spectra of aqueous solutions containing five independently varying absorbing species were collected to assess the ability of partial least-squares (PLS) regression and wavelength selection for calibration and prediction of these species in the presence of each other. It was confirmed that PLS calibration models can successfully predict chemical concentrations of all five chemicals from a single spectrum. It was observed from the PLS spectral loadings that spectral regions containing absorption bands of a single analyte alone were not sufficient for the model to adequately predict the concentration of the analyte because of the high degree of overlap between glucose, lactate, ammonia, glutamate, and glutamine. Three wavelength selection algorithms were applied to the spectra to identify regions containing necessary information, and in each case it was found that nearly the entire spectral range was needed for each determination. The results suggest that wavelength selection does result in a reduction of data points from the full spectrum, but the decrease seen with these near-infrared spectra was less than typically seen in mid-IR or Raman spectra, where peaks are narrower and well separated. As a result of this need for more wavelengths, the engineering of a dedicated system to measure these analytes in complex media such as blood or tissue culture broths by using this near-infrared region (2.0–2.5 μm) is further complicated.