Development of Position-Dependent Luminescent Sensors: Spectral Rulers and Chemical Sensing Through Tissue

Assessing the performance of medical devices is critical for understanding device function and monitoring pathologies. With the use of a smart device clinically relevant chemical and mechanical information regarding fracture healing may be deduced. For example, strain on the device may be used as a mechanical indicator of weight-bearing capacity. In addition, changes in chemical environment may indicate the development of implant associated infections. Although optical methods are widely used for ex vivostrain/motion analysis and for chemical analyses in cells and histological tissue sections, there utility is limited through thick tissue because light scattering reduces spatial resolution. This dissertation presents four novel luminescent sensors that overcome this limitation. The sensors are capable of detecting chemical and physical changes by measuring position or orientation-dependent color/wavelength changes through tissue. The first three sensors are spectral rulers comprised of two patterned thin films: an encoder strip and an analyzer mask. The encoder strip is either a thin film patterned with stripes of alternating luminescent materials (quantum dots, particles or dyes) or a film containing alternating stripes of a dye that absorbs luminescence from a particle film placed below. The analyzer mask is patterned with a series of alternating transparent windows and opaque stripes equal in width to the encoder lines. The analyzer is overlaid upon the encoder strip such that displacement of the encoder relative to the analyzer modulates the color/spectrum visible through the windows. Relative displacement of the sensor layers is mechanically confined to a single axis. When the substrates are overlaid in the “home position” one line spectrum is observed, and in the “end position,” another line spectrum is observed. At intermediate positions, spectra are a linear combination of the “home” and “end” spectra. The position-modulated signal is collected by a spectrometer and a spectral intensity ratio from closely spaced emission peaks is calculated. By collecting luminescent spectra, rather than imaging the device surface, the sensors eliminate the need to spatially resolve small features through tissue by measuring displacement as a function of color. We measured micron scale displacements through at least 6 mm of tissue using three types of spectral ruler based upon 1) fluorescence, 2) x-ray excited optical luminescence (XEOL), and 3) near infrared upconversion luminescence. The sensors may be used to investigate strain on orthopedic implants, study interfragmentary motion, or assess tendon/ligament tears. In addition to monitoring mechanical strain it is important to investigate clinically relevant implant pathologies such as infection. To address this application, we have developed a fourth type of sensor. The sensor monitors changes in local pH, an indicator of biofilm formation, and uses magnetic fields to modulate position and orientation-dependent luminescence. This modulation allows the sensor signal to be separated from background tissue autofluorescence for spectrochemical sensing. This final sensor variation contains a cylindrical magnet with a fluorescent pH indicating surface on one side and a mask on the other. When the pH indicating surface is oriented towards the collection optics, the spectrum generated contains both the sensor and autofluorescence signals. Conversely, when the pH sensor is oriented away, the collected signal is composed solely of background signals. All four of the sensors described can be used to build smart devices for monitoring pathologies through tissue. Future work will include the application of the strain and chemical sensors in vivo and ex vivo in animal and cadaveric models

On periodic solutions of 2-periodic Lyness difference equations

We study the existence of periodic solutions of the non--autonomous periodic Lyness' recurrence u_{n+2}=(a_n+u_{n+1})/u_n, where {a_n} is a cycle with positive values a,b and with positive initial conditions. It is known that for a=b=1 all the sequences generated by this recurrence are 5-periodic. We prove that for each pair (a,b) different from (1,1) there are infinitely many initial conditions giving rise to periodic sequences, and that the family of recurrences have almost all the even periods. If a is not equal to b, then any odd period, except 1, appears.Comment: 27 pages; 1 figur

Optically-Based Strain Measuring Orthopaedic Screw for Fracture Fixation Implants

Fracture fixation usually involves mechanical fixation with rods, plates and/or screws which repair slowly and are susceptible to infection. Treatment of large defects use allografts which have failure rates of up to 25%, and complication rates as high as 30-60%. Implant infection and loosening are serious concerns, but can currently only be measured through expensive instrumented implants, biopsy culture, or radiographs. None of these directly quantify implant loading and stability however. There is therefore a need for a simple, cost effective way to quantify implant loading and stability in patients. The purpose of our study is to design and evaluate an optically-based strain measuring orthopaedic screw to quantify strain variation in the implant in-vivo after surgery and monitor the load sharing between the bone and the implant. The screw head incorporates a spectral ruler based on Moiré effect which indicates strain. The screw system developed will be able to quantify clinically-relevant bone healing strains in the range of 10-3000μstrains, corresponding to 0.5-150μm change in length for a 5cm gauge. Through this work, we will be able to develop a unique portable tool for physicians to quantify bone healing rather than relying on less quantitative assessments based on pain and radiography

Results and Conjectures about Order Lyness' Difference Equation in , with a Particular Study of the Case

We study order q Lyness' difference equation in ℝ∗+:un+qun=a+un+q−1+⋯+un+1, with a>0 and the associated dynamical system Fa in ℝ∗+q. We study its solutions (divergence, permanency, local stability of the equilibrium). We prove some results, about the first three invariant functions and the topological nature of the corresponding invariant sets, about the differential at the equilibrium, about the role of 2-periodic points when q is odd, about the nonexistence of some minimal periods, and so forth and discuss some problems, related to the search of common period to all solutions, or to the second and third invariants. We look at the case q=3 with new methods using new invariants for the map Fa2 and state some conjectures on the associated dynamical system in ℝ∗+q in more general cases

Phylogenetic Analysis of Kindlins Suggests Subfunctionalization of an Ancestral Unduplicated Kindlin into Three Paralogs in Vertebrates

Kindlin proteins represent a newly discovered family of evolutionarily conserved FERM domain-containing proteins. This family includes three highly conserved proteins: Kindlin-1, Kindlin-2 and Kindlin-3. All three Kindlin proteins are associated with focal adhesions and are involved in integrin activation. The FERM domain of each Kindlin is bipartite and plays a key role in integrin activation. We herein explore for the first time the evolutionary history of these proteins. The phylogeny of the Kindlins suggests a single ancestral Kindlin protein present in even the earliest metazoan ie, hydra. This protein then underwent duplication events in insects and also experienced genome duplication in vertebrates, leading to the Kindlin family. A comparative study of the Kindlin paralogs showed that Kindlin-2 is the slowest evolving protein among the three family members. The analysis of synonymous and non-synonymous substitutions in orthologous Kindlin sequences in different species showed that all three Kindlins have been evolving under the influence of purifying selection. The expression pattern of Kindlins along with phylogenetic studies supports the subfunctionalization model of gene duplication

Graphene Bilayer Field-Effect Phototransistor for Terahertz and Infrared Detection

A graphene bilayer phototransistor (GBL-PT) is proposed and analyzed. The GBL-PT under consideration has the structure of a field-effect transistor with a GBL as the channel and the back and top gates. The positive bias of the back gate results in the formation of conducting source and drain sections in the channel, while the negatively biased top gate provides the potential barrier which is controlled by the charge of the photogenerated holes. The features of the GBL-PT operation are associated with the variations of both the potential distribution and the energy gap in different sections of the channel when the gate voltages and the charge in the barrier section change. Using the developed GBL-PT device model, the spectral characteristics, dark current, responsivity and detectivity are calculated as functions of the applied voltages, energy of incident photons, intensity of electron and hole scattering, and geometrical parameters. It is shown that the GBL-PT spectral characteristics are voltage tuned. The GBL-PT performance as photodetector in the terahertz and infrared photodetectors can markedly exceed the performance of other photodetectors.Comment: 7 Pages, 7 figure

Room temperature mid-infrared InAsSbN multi-quantum well photodiodes grown by MBE

Room temperature photoresponse in the mid-infrared spectral region is demonstrated from InAsSbN/InAs multi-quantum well photodiodes grown by nitrogen plasma assisted molecular beam epitaxy. The structural quality of the InAsSbN MQWs was ascertained in situ by reflection high energy electron diffraction and ex situ by high resolution x-ray diffraction and photoluminescence measurements. The extended long wavelength photoresponse is identified to originate from the electron–heavy hole (e1–hh1) and electron–light hole (e1–lh1) transitions in the InAsSbN MQW, with a cut off wavelength ~4.20 µm and peak detectivity D *  =  1.25  ×  109 cm Hz1/2 W−1

Rpl33, a nonessential plastid-encoded ribosomal protein in tobacco, is required under cold stress conditions

Plastid genomes contain a conserved set of genes encoding components of the translational apparatus. While knockout of plastid translation is lethal in tobacco (Nicotiana tabacum), it is not known whether each individual component of the plastid ribosome is essential. Here, we used reverse genetics to test whether several plastid genome-encoded ribosomal proteins are essential. We found that, while ribosomal proteins Rps2, Rps4, and Rpl20 are essential for cell survival, knockout of the gene encoding ribosomal protein Rpl33 did not affect plant viability and growth under standard conditions. However, when plants were exposed to low temperature stress, recovery of Rpl33 knockout plants was severely compromised, indicating that Rpl33 is required for sustaining sufficient plastid translation capacity in the cold. These findings uncover an important role for plastid translation in plant tolerance to chilling stress