Barrow Innovation Center: A 5-Year Update and Future Direction.

OBJECTIVE: The rich history of neurosurgical innovation served as a model for the Barrow Innovation Center's establishment in 2016. The center's accomplishments are summarized in hopes of fostering the development of similar centers and initiatives within the neurosurgical and broader medical community. METHODS: A retrospective review (January 2016-July 2021) of patent filings, project proposals, and funding history was used to generate the data presented in this operational review. RESULTS: Through the 5-year period of analysis, 55 prior art searches were conducted on new patentable ideas. A total of 87 provisional patents, 25 Patent Cooperation Treaty applications, and 48 national stage filings were submitted. In partnership with Arizona State University, the University of Arizona, California Polytechnic State University, and Texas A&M University, a total of 27 multidisciplinary projects were conducted with input from multispecialty engineers and scientists. These efforts translated into 1 startup company and 2 licensed patents to commercial companies, with most remaining ideas and project efforts awaiting interest from industry. CONCLUSIONS: The multidisciplinary collaborative environment embodied by the Barrow Innovation Center has revolutionized the innovative and entrepreneurial environment of its home institution and enabled neurosurgical residents to get a unique educational experience within the realm of innovation. The bottleneck within the workflow of ideas from conception to commercialization appears to be the establishment of commercial partners; therefore, future efforts within the center will be to establish a panel of industry partnerships to enhance the exposure of ideas to interested companies.

Efficacy of standard chest compressions in patients with Nuss bars.

BACKGROUND: The Nuss procedure temporarily places intrathoracic bars for repair of pectus excavatum (PE). The bars may impact excursion and compliance of the anterior chest wall while in place. Effective chest compressions during cardiopulmonary resuscitation (CPR) require depressing the anterior chest wall enough to compress the heart between sternum and spine. We assessed the force required to perform the American Heart Association's recommended chest compression depth after Nuss repair. METHODS: A lumped element elastic model was developed to simulate the relationship between chest compression forces and displacement with focus on the amount of force required to achieve a depth of 5 cm in the presence of 1-3 Nuss bars. Literature review was conducted for evidence supporting potential use of active abdominal compressions and decompression (AACD) as an alternative method of CPR. RESULTS: The presence of bars notably lowered compression depth by a minimum of 69% compared to a chest without bar(s). The model also demonstrated a dramatic increase (minimum of 226%) in compressive forces required to achieve recommended 5 cm depth. Literature review suggests AACD could be an alternative CPR in patients with Nuss bar(s). CONCLUSIONS: In our model, Nuss bars limited the ability to perform chest compressions due to increased force required to achieve a 5 cm compression. The greater the number of Nuss bars present the greater the force required. This may prevent effective CPR. Use of active abdominal compressions and decompressions should be studied further as an alternative resuscitation modality for patients after the Nuss procedure.

Regulatory and reimbursement innovation.

Coverage with evidence development and parallel review for molecular diagnostics aid regulation and reimbursement.

Optoelectronic energy transfer at novel biohybrid interfaces using light harvesting complexes from Chloroflexus aurantiacus.

In nature, nanoscale supramolecular light harvesting complexes initiate the photosynthetic energy collection process at high quantum efficiencies. In this study, the distinctive antenna structure from Chloroflexus aurantiacusthe chlorosomeis assessed for potential exploitation in novel biohybrid optoelectronic devices. Electrochemical characterization of bacterial fragments containing intact chlorosomes with the photosynthetic apparatus show an increase in the charge storage density near the working electrode upon light stimulation and suggest that chlorosomes contribute approximately one-third of the overall photocurrent. Further, isolated chlorosomes (without additional photosynthetic components, e.g., reaction centers, biochemical mediators) produce a photocurrent (approximately 8-10 nA) under light saturation conditions. Correlative experiments indicate that the main chlorosome pigment, bacteriochlorophyll-c, contributes to the photocurrent via an oxidative mechanism. The results reported herein are the first to demonstrate that isolated chlorosomes (lipid-enclosed sacs of pigments) directly transduce light energy in an electrochemical manner, laying an alternative, biomimetic approach for designing photosensitized interfaces in biofuel cells and biomedical devices, such as bioenhanced retinal prosthetics.

Immobilization of functional light antenna structures derived from the filamentous green bacterium Chloroflexus aurantiacus.

The integration of highly efficient, natural photosynthetic light antenna structures into engineered systems while their biophotonic capabilities are maintained has been an elusive goal in the design of biohybrid photonic devices. In this study, we report a novel technique to covalently immobilize nanoscaled bacterial light antenna structures known as chlorosomes from Chloroflexus aurantiacus on both conductive and nonconductive glass while their energy transducing functionality was maintained. Chlorosomes without their reaction centers (RCs) were covalently immobilized on 3-aminoproyltriethoxysilane (APTES) treated surfaces using a glutaraldehyde linker. AFM techniques verified that the chlorosomes maintained their native ellipsoidal ultrastructure upon immobilization. Results from absorbance and fluorescence spectral analysis (where the Stokes shift to 808/810 nm was observed upon 470 nm blue light excitation) in conjunction with confocal microscopy confirm that the functional integrity of immobilized chlorosomes was also preserved. In addition, experiments with electrochemical impedance spectroscopy (EIS) suggested that the presence of chlorosomes in the electrical double layer of the electrode enhanced the electron transfer capacity of the electrochemical cell. Further, chronoamperometric studies suggested that the reduced form of the Bchl- c pigments found within the chlorosome modulate the conduction properties of the electrochemical cell, where the oxidized form of Bchl- c pigments impeded any current transduction at a bias of 0.4 V within the electrochemical cell. The results therefore demonstrate that the intact chlorosomes can be successfully immobilized while their biophotonic transduction capabilities are preserved through the immobilization process. These findings indicate that it is feasible to design biophotonic devices incorporating fully functional light antenna structures, which may offer significant performance enhancements to current silicon-based photonic devices for diverse technological applications ranging from CCD devices used in retinal implants to terrestrial and space fuel cell applications.

Multiplexed DNA sequencing-by-synthesis.

We report a new DNA sequencing-by-synthesis method in which the sequences of DNA templates, hybridized to a surface-immobilized array of DNA primers, are determined by sensing the number of nucleotides by which the primers in each array spot are extended in sequential DNA polymerase-catalyzed nucleotide incorporation reactions, each with a single fluorescein-labeled deoxyribonucleoside triphosphate (dNTP) species. The fluorescein label is destroyed after each readout by a photostimulated reaction with diphenyliodonium chloride. A DNA polymerase with enhanced ability to incorporate, and to extend beyond, modified nucleotides is used. Self-quenching of adjacent fluorescein labels, which impedes readout of homopolymeric runs, is avoided by diluting the labeled dNTP with unlabeled reagent. Misincorporation effects have been quantified and are small; however, low-level contamination of dNTPs with other nucleotides mimics misincorporation and can produce significant false-positive signals. These impurities are removed by polymerase-catalyzed incorporation into complementary "cleaning duplexes." Here, we demonstrate the accurate sequence readout for a small array of known DNA templates, the ability to quantify homopolymeric runs, and a short sequencing example of sections of the wild-type and mutant BRCA1 gene. For a 20,000-spot array, readout rates in excess of 6000 bases per minute are projected.

Isolation of plasma from whole blood using planar microfilters for lab-on-a-chip applications.

Researchers are actively developing devices for the microanalysis of complex fluids, such as blood. These devices have the potential to revolutionize biological analysis in a manner parallel to the computer chip by providing very high throughput screening of complex samples and massively parallel bioanalytical capabilities. A necessary step performed in clinical chemistry is the isolation of plasma from whole blood, and effective sample preparation techniques are needed for the development of miniaturized clinical diagnostic devices. This study demonstrates the use of passive, operating entirely on capillary action, transverse-flow microfilter devices for the microfluidic isolation of plasma from whole blood. Using these planar microfilters, blood can be controllably fractionated with minimal cell lysis. A characterization of the device performance reveals that plasma filter flux is dependent upon the wall shear rate of blood in the filtration channel, and this result is consistent with macroscale blood filtration using microporous membranes. Also, an innovative microfluidic layout is demonstrated that extends device operation time via capillary action from seconds to minutes. Efficiency of these microfilters is approximately three times higher than the separation efficiencies predicted for microporous membranes under similar conditions. As such, the application of the microscale blood filtration designs used in this study may have broad implications in the design of lab-on-a-chip devices, as well as the field of separation science.

Characterization of Chlorobium tepidum chlorosomes: a calculation of bacteriochlorophyll c per chlorosome and oligomer modeling.

The bacteriochlorophyll (Bchl) c content and organization was determined for Chlorobium (Cb.) tepidum chlorosomes, the light-harvesting complexes from green photosynthetic bacteria, using fluorescence correlation spectroscopy and atomic force microscopy. Single-chlorosome fluorescence data was analyzed in terms of the correlation of the fluorescence intensity with time. Using this technique, known as fluorescence correlation spectroscopy, chlorosomes were shown to have a hydrodynamic radius (Rh) of 25 +/- 3.2 nm. This technique was also used to determine the concentration of chlorosomes in a sample, and pigment extraction and quantitation was used to determine the molar concentration of Bchl c present. From these data, a number of approximately 215,000 +/- 80,000 Bchl c per chlorosome was determined. Homogeneity of the sample was further characterized by dynamic light scattering, giving a single population of particles with a hydrodynamic radius of 26.8 +/- 3.7 nm in the sample. Tapping-mode atomic force microscopy (TMAFM) was used to determine the x,y,z dimensions of chlorosomes present in the sample. The results of the TMAFM studies indicated that the average chlorosome dimensions for Cb. tepidum was 174 +/- 8.3 x 91.4 +/- 7.7 x 10.9 +/- 2.71 nm and an overall average volume 90,800 nm(3) for the chlorosomes was determined. The data collected from these experiments as well as a model for Bchl c aggregate dimensions was used to determine possible arrangements of Bchl c oligomers in the chlorosomes. The results obtained in this study have significant implications on chlorosome structure and architecture, and will allow a more thorough investigation of the energetics of photosynthetic light harvesting in green bacteria.