Freddy Nguyen, MD, PhD

There is a pressing need for sensors and assays to monitor chemotherapeutic activity within the human body in real time to optimize drug dosimetry parameters such as timing, quantity, and frequency in an effort to maximize efficacy while minimizing deleterious cytotoxicity. Herein, we develop near-infrared fluorescent nanosensors based on single walled carbon nanotubes for the chemotherapeutic Temozolomide (TMZ) and its metabolite 5-aminoimidazole-4-carboxamide using Corona Phase Molecular… Mehr zeigen

There is a pressing need for sensors and assays to monitor chemotherapeutic activity within the human body in real time to optimize drug dosimetry parameters such as timing, quantity, and frequency in an effort to maximize efficacy while minimizing deleterious cytotoxicity. Herein, we develop near-infrared fluorescent nanosensors based on single walled carbon nanotubes for the chemotherapeutic Temozolomide (TMZ) and its metabolite 5-aminoimidazole-4-carboxamide using Corona Phase Molecular Recognition as a synthetic molecular recognition technique. The resulting nanoparticle sensors are able to monitor drug activity in real-time even under in vivo conditions. Sensors can be engineered to be biocompatible by encapsulation in poly(ethylene glycol) diacrylate hydrogels. Selective detection of TMZ was demonstrated using U-87 MG human glioblastoma cells and SKH-1E mice with detection limits below 30 μM. As sensor implants, we show that such systems can provide spatiotemporal therapeutic information in vivo, as a valuable tool for pharmacokinetic evaluation. Sensor implants are also evaluated using intact porcine brain tissue implanted 2.1 cm below the cranium and monitored using a recently developed Wavelength-Induced Frequency Filtering technique. Additionally, we show that by taking the measurement of spatial and temporal analyte concentrations within each hydrogel implant, the direction of therapeutic flux can be resolved. In all, these types of sensors enable the real time detection of chemotherapeutic concentration, flux, directional transport, and metabolic activity, providing crucial information regarding therapeutic effectiveness. Weniger anzeigen

Analysis of diagnostic information in pathology reports for the purposes of clinical or translational research and quality assessment/control often requires manual data extraction, which can be laborious, time-consuming, and subject to mistakes. Objective We sought to develop, employ, and evaluate a simple, dictionary- and rule-based natural language processing (NLP) algorithm for generating searchable information on various types of parameters from diverse surgical pathology reports. Design… Mehr zeigen

Analysis of diagnostic information in pathology reports for the purposes of clinical or translational research and quality assessment/control often requires manual data extraction, which can be laborious, time-consuming, and subject to mistakes. Objective We sought to develop, employ, and evaluate a simple, dictionary- and rule-based natural language processing (NLP) algorithm for generating searchable information on various types of parameters from diverse surgical pathology reports. Design Data were exported from the pathology laboratory information system (LIS) into extensible markup language (XML) documents, which were parsed by NLP-based Python code into desired data points and delivered to Excel spreadsheets. Accuracy and efficiency were compared to a manual data extraction method with concordance measured by Cohen’s κ coefficient and corresponding P values. Results The automated method was highly concordant (90-100%, P<.001) with excellent inter-observer reliability (Cohen’s κ: 0.86-1.0) compared to the manual method in 3 clinicopathologic research scenarios, including squamous dysplasia presence and grade in anal biopsies, epithelial dysplasia grade and location in colonoscopic surveillance biopsies, and adenocarcinoma grade and amount in prostate core biopsies. Significantly, the automated method was 24-39 times faster and inherently contained links for each diagnosis to additional variables such as patient age, location, etc., which would require additional manual processing time. Conclusions A simple, flexible, and scaleable NLP-based platform can be used to correctly, safely, and quickly extract and deliver linked data from pathology reports into searchable spreadsheets for clinical and research purposes. Weniger anzeigen

Exciting, modern technologies for cancer detection are under development in academic and industrial laboratories worldwide. This chapter provides a synopsis of technologies reaching greater importance as they advance toward clinical practice. These methods include significant advances in current methods as well as fundamentally new platforms. We place a special emphasis on point-of-care technologies for use in clinical settings as well as novel methods for use as at-home measurements and… Mehr zeigen

Exciting, modern technologies for cancer detection are under development in academic and industrial laboratories worldwide. This chapter provides a synopsis of technologies reaching greater importance as they advance toward clinical practice. These methods include significant advances in current methods as well as fundamentally new platforms. We place a special emphasis on point-of-care technologies for use in clinical settings as well as novel methods for use as at-home measurements and wearable devices. We also provide a synopsis on the involvement of artificial intelligence-based data analytics such as machine learning algorithms in both existing and developing assessments. Weniger anzeigen

Fluorescent nanosensors hold the potential to revolutionize life sciences and medicine. However, their adaptation and translation into the in vivo environment is fundamentally hampered by unfavourable tissue scattering and intrinsic autofluorescence. Here we develop wavelength-induced frequency filtering (WIFF) whereby the fluorescence excitation wavelength is modulated across the absorption peak of a nanosensor, allowing the emission signal to be separated from the autofluorescence background,… Mehr zeigen

Fluorescent nanosensors hold the potential to revolutionize life sciences and medicine. However, their adaptation and translation into the in vivo environment is fundamentally hampered by unfavourable tissue scattering and intrinsic autofluorescence. Here we develop wavelength-induced frequency filtering (WIFF) whereby the fluorescence excitation wavelength is modulated across the absorption peak of a nanosensor, allowing the emission signal to be separated from the autofluorescence background, increasing the desired signal relative to noise, and internally referencing it to protect against artefacts. Using highly scattering phantom tissues, an SKH1-E mouse model and other complex tissue types, we show that WIFF improves the nanosensor signal-to-noise ratio across the visible and near-infrared spectra up to 52-fold. This improvement enables the ability to track fluorescent carbon nanotube sensor responses to riboflavin, ascorbic acid, hydrogen peroxide and a chemotherapeutic drug metabolite for depths up to 5.5 ± 0.1 cm when excited at 730 nm and emitting between 1,100 and 1,300 nm, even allowing the monitoring of riboflavin diffusion in thick tissue. As an application, nanosensors aided by WIFF detect the chemotherapeutic activity of temozolomide transcranially at 2.4 ± 0.1 cm through the porcine brain without the use of fibre optic or cranial window insertion. The ability of nanosensors to monitor previously inaccessible in vivo environments will be important for life-sciences research, therapeutics and medical diagnostics. Weniger anzeigen

The majority of biomedical research is funded by public, governmental, and philanthropic grants. These initiatives often shape the avenues and scope of research across disease areas. However, the prioritization of disease-specific funding is not always reflective of the health and social burden of each disease. We identify a prioritization disparity between lung and breast cancers, whereby lung cancer contributes to a substantially higher socioeconomic cost on society yet receives significantly… Mehr zeigen

The majority of biomedical research is funded by public, governmental, and philanthropic grants. These initiatives often shape the avenues and scope of research across disease areas. However, the prioritization of disease-specific funding is not always reflective of the health and social burden of each disease. We identify a prioritization disparity between lung and breast cancers, whereby lung cancer contributes to a substantially higher socioeconomic cost on society yet receives significantly less funding than breast cancer. Using search engine results and natural language processing (NLP) of Twitter tweets, we show that this disparity correlates with enhanced public awareness and positive sentiment for breast cancer. Interestingly, disease-specific venture activity does not correlate with funding or public opinion. We use outcomes from recent early-stage innovation events focused on lung cancer to highlight the complementary mechanism by which bottom-up “grass-roots” initiatives can identify and tackle under-prioritized conditions. Weniger anzeigen

Label-free live cell imaging was performed using a custom-built high-speed confocal Raman microscopy system. For various cell types, cell-intrinsic Raman bands were monitored. The high-resolution temporal Raman images clearly delineated the intracellular distribution of biologically important molecules such as protein, lipid, and DNA. Furthermore, optical phase delay measured using quantitative phase microscopy shows similarity with the image reconstructed from the protein Raman peak. This… Mehr zeigen

Label-free live cell imaging was performed using a custom-built high-speed confocal Raman microscopy system. For various cell types, cell-intrinsic Raman bands were monitored. The high-resolution temporal Raman images clearly delineated the intracellular distribution of biologically important molecules such as protein, lipid, and DNA. Furthermore, optical phase delay measured using quantitative phase microscopy shows similarity with the image reconstructed from the protein Raman peak. This reported work demonstrates that Raman imaging is a powerful label-free technique for studying various biomedical problems in vitro with minimal sample preparation and external perturbation to the cellular system. Weniger anzeigen

Vitamins such as riboflavin and ascorbic acid are frequently utilized in a range of biomedical applications as drug delivery targets, fluidic tracers, and pharmaceutical excipients. Sensing these biochemicals in the human body has the potential to significantly advance medical research and clinical applications. In this work, a nanosensor platform consisting of single-walled carbon nanotubes (SWCNTs) with nanoparticle corona phases engineered to allow for the selective molecular recognition of… Mehr zeigen

Vitamins such as riboflavin and ascorbic acid are frequently utilized in a range of biomedical applications as drug delivery targets, fluidic tracers, and pharmaceutical excipients. Sensing these biochemicals in the human body has the potential to significantly advance medical research and clinical applications. In this work, a nanosensor platform consisting of single-walled carbon nanotubes (SWCNTs) with nanoparticle corona phases engineered to allow for the selective molecular recognition of ascorbic acid and riboflavin, is developed. The study provides a methodological framework for the implementation of colloidal SWCNT nanosensors in an intraperitoneal SKH1-E murine model by addressing complications arising from tissue absorption and scattering, mechanical perturbations, as well as sensor diffusion and interactions with the biological environment. Nanosensors are encapsulated in a polyethylene glycol diacrylate hydrogel and a diffusion model is utilized to validate analyte transport and sensor responses to local concentrations at the boundary. Results are found to be reproducible and stable after exposure to 10% mouse serum even after three days of in vivo implantation. A geometrical encoding scheme is used to reference sensor pairs, correcting for in vivo optical and mechanical artifacts, resulting in an order of magnitude improvement of p-value from 0.084 to 0.003 during analyte sensing. Weniger anzeigen

The COVID-19 pandemic has profoundly affected life worldwide. Governments have been faced with the formidable task of implementing public health measures, such as social distancing, quarantines, and lockdowns, while simultaneously supporting a sluggish economy and stimulating research and development (R&D) for the pandemic. Catalyzing bottom-up entrepreneurship is one method to achieve this. Home-grown efforts by citizens wishing to contribute their time and resources to help have sprouted… Mehr zeigen

The COVID-19 pandemic has profoundly affected life worldwide. Governments have been faced with the formidable task of implementing public health measures, such as social distancing, quarantines, and lockdowns, while simultaneously supporting a sluggish economy and stimulating research and development (R&D) for the pandemic. Catalyzing bottom-up entrepreneurship is one method to achieve this. Home-grown efforts by citizens wishing to contribute their time and resources to help have sprouted organically, with ideas shared widely on the internet. We outline a framework for structured, crowdsourced innovation that facilitates collaboration to tackle real, contextualized problems. This is exemplified by a series of virtual hackathon events attracting over 9000 applicants from 142 countries and 49 states. A hackathon is an event that convenes diverse individuals to crowdsource solutions around a core set of predetermined challenges in a limited amount of time. A consortium of over 100 partners from across the healthcare spectrum and beyond defined challenges and supported teams after the event, resulting in the continuation of at least 25% of all teams post-event. Grassroots entrepreneurship can stimulate economic growth while contributing to broader R&D efforts to confront public health emergencies. Weniger anzeigen

Background
Convalescent plasma (CP) for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown preliminary signs of effectiveness in moderate to severely ill patients in reducing mortality. While studies have demonstrated a low risk of serious adverse events, the comprehensive incidence and nature of the spectrum of transfusion reactions to CP is unknown. We retrospectively examined 427 adult inpatient CP transfusions to determine incidence and types of… Mehr zeigen

Background
Convalescent plasma (CP) for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown preliminary signs of effectiveness in moderate to severely ill patients in reducing mortality. While studies have demonstrated a low risk of serious adverse events, the comprehensive incidence and nature of the spectrum of transfusion reactions to CP is unknown. We retrospectively examined 427 adult inpatient CP transfusions to determine incidence and types of reactions, as well as clinical parameters and risk factors associated with transfusion reactions.

Study Design and Methods
Retrospective analysis was performed for 427 transfusions to 215 adult patients with coronavirus 2019 (COVID-19) within the Mount Sinai Health System, through the US Food and Drug Administration emergency investigational new drug and the Mayo Clinic Expanded Access Protocol to Convalescent Plasma approval pathways. Transfusions were blindly evaluated by two reviewers and adjudicated by a third reviewer in discordant cases. Patient demographics and clinical and laboratory parameters were compared and analyzed.

Results
Fifty-five reactions from 427 transfusions were identified (12.9% incidence), and 13 were attributed to transfusion (3.1% incidence). Reactions were classified as underlying COVID-19 (76%), febrile nonhemolytic (10.9%), transfusion-associated circulatory overload (9.1%), and allergic (1.8%) and hypotensive (1.8%) reactions. Statistical analysis identified increased transfusion reaction risk for ABO blood group B or Sequential Organ Failure Assessment scores of 12 to 13, and decreased risk within the age group of 80 to 89 years.

Fazit
Our findings support the use of CP as a safe, therapeutic option from a transfusion reaction perspective, in the setting of COVID-19. Further studies are needed to confirm the clinical significance of ABO group B, age, and predisposing disease severity in the incidence of transfusion reaction events. Weniger anzeigen

Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency… Mehr zeigen

Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31–35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity. Weniger anzeigen

Dynamic measurements of steroid hormones in vivo are critical, but steroid sensing is currently limited by the availability of specific molecular recognition elements due to the chemical similarity of these hormones. In this work, a new, self-templating synthetic approach is applied using corona phase molecular recognition (CoPhMoRe) targeting the steroid family of molecules to produce near infrared fluorescent, implantable sensors. A key limitation of CoPhMoRe has been its reliance on library… Mehr zeigen

Dynamic measurements of steroid hormones in vivo are critical, but steroid sensing is currently limited by the availability of specific molecular recognition elements due to the chemical similarity of these hormones. In this work, a new, self-templating synthetic approach is applied using corona phase molecular recognition (CoPhMoRe) targeting the steroid family of molecules to produce near infrared fluorescent, implantable sensors. A key limitation of CoPhMoRe has been its reliance on library generation for sensor screening. This problem is addressed with a self-templating strategy of polymer design, using the examples of progesterone and cortisol sensing based on a styrene and acrylic acid copolymer library augmented with an acrylated steroid. The pendant steroid attached to the corona backbone is shown to self-template the phase, providing a unique CoPhMoRE design strategy with high efficacy. The resulting sensors exhibit excellent stability and reversibility upon repeated analyte cycling. It is shown that molecular recognition using such constructs is viable even in vivo after sensor implantation into a murine model by employing a poly (ethylene glycol) diacrylate (PEGDA) hydrogel and porous cellulose interface to limit nonspecific absorption. The results demonstrate that CoPhMoRe templating is sufficiently robust to enable a new class of continuous, in vivo biosensors. Weniger anzeigen

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments1. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus… Mehr zeigen

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments1. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses2,3. Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed1,2. This retrospective, propensity score–matched case–control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score–matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75–0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13–0.89; chi-square test P = 0.027). Convalescent plasma is potentially effective against COVID-19, but adequately powered, randomized controlled trials are needed. Weniger anzeigen

The COVID-19 virus is a formidable global threat, impacting all aspects of society and exacerbating the existing inequities of our current social systems.1 2 As we battle the virus across multiple fronts, data are critical for understanding this disease and for coordinating an effective global response. Given the current digitisation of so many aspects of life, we are amassing data that can be extrapolated and analysed for the effective forecasting, prevention and treatment of COVID-19. With… Mehr zeigen

The COVID-19 virus is a formidable global threat, impacting all aspects of society and exacerbating the existing inequities of our current social systems.1 2 As we battle the virus across multiple fronts, data are critical for understanding this disease and for coordinating an effective global response. Given the current digitisation of so many aspects of life, we are amassing data that can be extrapolated and analysed for the effective forecasting, prevention and treatment of COVID-19. With responsible stewardship, the tools and data-driven solutions currently in development for the COVID-19 pandemic will serve in the present while providing a much-needed foundation for a data-based response to future outbreaks and disasters.

In response to COVID-19, and using data generated thus far, groups at the Massachusetts Institute of Technology (MIT) in partnership with the American Civil Liberties Union (ACLU) of Massachusetts, Google Cloud, Beth Israel Deaconess Medical Center (BIDMC) Innovations Group and Harvard Medical Faculty Physicians at BIDMC came together to host the MIT Challenge COVID-19 Datathon (COVID-19 Datathon) from 10–16 May 2020. A ‘datathon’ adopts the ‘hackathon’ model, with a focus on data and data science methodologies, which promotes collaboration, design thinking and problem solving.3 In a typical hackathon, participants with disparate but complementary backgrounds work together in small groups for a prescribed and intensive ‘sprint’, typically over the course of one weekend, to develop a new concept, product or business idea. Subject matter expert ‘mentors’' oversee and advise the teams. At the conclusion of the event, the teams present to a panel of judges. Winners are selected and are typically awarded seed funding. Weniger anzeigen

Fluorescent nanosensors hold promise to address analytical challenges in the biopharmaceutical industry. The monitoring of therapeutic protein critical quality attributes such as aggregation is a long-standing challenge requiring low detection limits and multiplexing of different product parameters. However, general approaches for interfacing nanosensors to the biopharmaceutical process remain minimally explored to date. Herein, we design and fabricate a integrated fiber optic nanosensor… Mehr zeigen

Fluorescent nanosensors hold promise to address analytical challenges in the biopharmaceutical industry. The monitoring of therapeutic protein critical quality attributes such as aggregation is a long-standing challenge requiring low detection limits and multiplexing of different product parameters. However, general approaches for interfacing nanosensors to the biopharmaceutical process remain minimally explored to date. Herein, we design and fabricate a integrated fiber optic nanosensor element, measuring sensitivity, response time, and stability for applications to the rapid process monitoring. The fiber optic–nanosensor interface, or optode, consists of label-free nIR fluorescent single-walled carbon nanotube transducers embedded within a protective yet porous hydrogel attached to the end of the fiber waveguide. The optode platform is shown to be capable of differentiating the aggregation status of human immunoglobulin G, reporting the relative fraction of monomers and dimer aggregates with sizes 5.6 and 9.6 nm, respectively, in under 5 min of analysis time. We introduce a lab-on-fiber design with potential for at-line monitoring with integration of 3D-printed miniaturized sensor tips having high mechanical flexibility. A parallel measurement of fluctuations in laser excitation allows for intensity normalization and significantly lower noise level (3.7 times improved) when using lower quality lasers, improving the cost effectiveness of the platform. As an application, we demonstrate the capability of the fully integrated lab-on-fiber system to rapidly monitor various bioanalytes including serotonin, norepinephrine, adrenaline, and hydrogen peroxide, in addition to proteins and their aggregation states. These results in total constitute an effective form factor for nanosensor-based transducers for applications in industrial process monitoring. Weniger anzeigen

New York City has been recognized as the world's epicenter of the novel Coronavirus pandemic. To identify the key inherent factors that are highly correlated to the Increase Rate of COVID-19 new cases in NYC, we propose an unsupervised machine learning framework. Based on the assumption that ZIP code areas with similar demographic, socioeconomic, and mobility patterns are likely to experience similar outbreaks, we select the most relevant features to perform a clustering that can best reflect… Mehr zeigen

New York City has been recognized as the world's epicenter of the novel Coronavirus pandemic. To identify the key inherent factors that are highly correlated to the Increase Rate of COVID-19 new cases in NYC, we propose an unsupervised machine learning framework. Based on the assumption that ZIP code areas with similar demographic, socioeconomic, and mobility patterns are likely to experience similar outbreaks, we select the most relevant features to perform a clustering that can best reflect the spread, and map them down to 9 interpretable categories. We believe that our findings can guide policy makers to promptly anticipate and prevent the spread of the virus by taking the right measures. Weniger anzeigen

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic cancer with limited treatment options. There is an urgent need for tools that monitor therapeutic responses in real-time. Drugs such as gemcitabine (GEM) and irinotecan elicit their therapeutic effect in cancer cells by producing hydrogen peroxide (H2O2). In this study, specific DNA- wrapped single-walled carbon nanotubes (SWCNTs), which precisely monitor H2O2, were used to determine the therapeutic response of PDAC cells in vitro… Mehr zeigen

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic cancer with limited treatment options. There is an urgent need for tools that monitor therapeutic responses in real-time. Drugs such as gemcitabine (GEM) and irinotecan elicit their therapeutic effect in cancer cells by producing hydrogen peroxide (H2O2). In this study, specific DNA- wrapped single-walled carbon nanotubes (SWCNTs), which precisely monitor H2O2, were used to determine the therapeutic response of PDAC cells in vitro and tumors in vivo. Drug therapeutic efficacy was evaluated in vitro by monitoring differences of H2O2 in situ using reversible alteration of Raman G-bands from the nanotubes. Implantation of the DNA-SWCNT probe inside the PDAC tumor resulted in ~50% reduction of Raman G-band intensity when treated with GEM versus the pre-treated tumor; the Raman G-band intensity reversed to its pretreatment level upon treatment withdrawal. In summary, we demonstrate using highly specific and sensitive DNA-SWCNT nanosensors that dynamic alteration of a key analyte can be used to evaluate the effectiveness of chemotherapeutics both in vitro and in vivo. Weniger anzeigen

In recent decades, biologists have sought to tag animals with various sensors to study aspects of their behavior otherwise inaccessible from controlled laboratory experiments. Despite this, chemical information, both environmental and physiological, remains challenging to collect despite its tremendous potential to elucidate a wide range of animal behaviors. In this work, we explore the design, feasibility, and data collection constraints of implantable, near-infrared fluorescent nanosensors… Mehr zeigen

In recent decades, biologists have sought to tag animals with various sensors to study aspects of their behavior otherwise inaccessible from controlled laboratory experiments. Despite this, chemical information, both environmental and physiological, remains challenging to collect despite its tremendous potential to elucidate a wide range of animal behaviors. In this work, we explore the design, feasibility, and data collection constraints of implantable, near-infrared fluorescent nanosensors based on DNA-wrapped single-wall carbon nanotubes (SWNT) embedded within a biocompatible poly(ethylene glycol) diacrylate (PEGDA) hydrogel. These sensors are enabled by Corona Phase Molecular Recognition (CoPhMoRe) to provide selective chemical detection for marine organism biologging. Weniger anzeigen

We describe a label-free approach based on Raman spectroscopy, to study drug-induced apoptosis in vivo. Spectral-shifts at wavenumbers associated with DNA, proteins, lipids, and collagen have been identified on breast and melanoma tumor tissues. These findings may enable a new analytical method for rapid readout of drug-therapy with miniaturized probes.

Magnetic iron-oxide nanoparticles have been developed as contrast agents in magnetic resonance imaging (MRI) and as therapeutic agents in magnetic hyperthermia. They have also recently been demonstrated as contrast and elastography agents in magnetomotive optical coherence tomography (MM-OCT) and elastography. Protein-shell microspheres containing suspensions of these magnetic nanoparticles in lipid cores, and with functionalized outer shells for specific targeting, have also been demonstrated… Mehr zeigen

Magnetic iron-oxide nanoparticles have been developed as contrast agents in magnetic resonance imaging (MRI) and as therapeutic agents in magnetic hyperthermia. They have also recently been demonstrated as contrast and elastography agents in magnetomotive optical coherence tomography (MM-OCT) and elastography. Protein-shell microspheres containing suspensions of these magnetic nanoparticles in lipid cores, and with functionalized outer shells for specific targeting, have also been demonstrated as efficient contrast agents for imaging modalities such as MM-OCT and MRI, and can be easily modified for other modalities such as ultrasound, fluorescence, and luminescence imaging. By leveraging the benefits of these various imaging modalities with the use of only a single agent, a magnetic microsphere, it becomes possible to use a wide-field imaging method (such as MRI or small animal fluorescence imaging) to initially locate the agent, and then use MM-OCT to obtain dynamic contrast images with cellular level morphological resolution. In addition to multimodal contrast-enhanced imaging, these microspheres could serve as drug carriers for targeted delivery under image guidance. Although the preparation and surface modifications of protein microspheres containing iron oxide nanoparticles have been previously described and feasibility studies conducted, many questions regarding their production and properties remain. Since the use of multifunctional microspheres could have high clinical relevance, here we report a detailed characterization of their properties and behavior in different environments to highlight their versatility. The work presented here is an effort for the development and optimization of nanoparticle-based microspheres as multimodal contrast agents that can bridge imaging modalities on different size scales, especially for their use in MM-OCT and MRI. Weniger anzeigen

Due to its label-free and non-destructive nature, applications of Raman spectroscopic imaging in monitoring therapeutic responses at the cellular level are growing. We have recently developed a high-speed confocal Raman microscopy system to image living biological specimens with high spatial resolution and sensitivity. In the present study, we have applied this system to monitor the effects of Bortezomib, a proteasome inhibitor drug, on multiple myeloma cells. Cluster imaging followed by… Mehr zeigen

Due to its label-free and non-destructive nature, applications of Raman spectroscopic imaging in monitoring therapeutic responses at the cellular level are growing. We have recently developed a high-speed confocal Raman microscopy system to image living biological specimens with high spatial resolution and sensitivity. In the present study, we have applied this system to monitor the effects of Bortezomib, a proteasome inhibitor drug, on multiple myeloma cells. Cluster imaging followed by spectral profiling suggest major differences in the nuclear and cytoplasmic contents of cells due to drug treatment that can be monitored with Raman spectroscopy. Spectra were also acquired from group of cells and feasibility of discrimination among treated and untreated cells using principal component analysis (PCA) was accessed. Findings support the feasibility of Raman technologies as an alternate, novel method for monitoring live cell dynamics with minimal external perturbation. Weniger anzeigen

The field of biomedical optics has grown quickly over the last two decades as various technological advances have helped increase the acquisition speeds and the sensitivity limits of the technology. During this time, optical coherence tomography (OCT) has been explored for a wide number of clinical applications ranging from cardiology to oncology to primary care. In this thesis, I describe the design and construction of an intraoperative clinical OCT system that can be used to image and… Mehr zeigen

The field of biomedical optics has grown quickly over the last two decades as various technological advances have helped increase the acquisition speeds and the sensitivity limits of the technology. During this time, optical coherence tomography (OCT) has been explored for a wide number of clinical applications ranging from cardiology to oncology to primary care. In this thesis, I describe the design and construction of an intraoperative clinical OCT system that can be used to image and classify breast cancer tumor margins as normal, close, or positive. I also demonstrate that normal lymph nodes can be distinguished from reactive or metastatic lymph nodes by looking at the difference in scattering intensity between the cortex and the capsule of the node. Despite the advances of OCT in the detection and diagnosis of breast cancer, this technology is still limited by its field of view and can only provide structural information about the tissue. Structural OCT would benefit from added contrast via sub-cellular or biochemical components via the use of contrast agents and functional OCT modalities. As with most other optical imaging techniques, there is a trade off between the imaging field of view and the high-resolution microscopic imaging. In this thesis, I demonstrate for the first time that MM-OCT can be used as a complimentary technique to wide field imaging modalities, such as magnetic resonance imaging (MRI) or fluorescence imaging, using targeted multi-modal protein microspheres. By using a single contrast agent to bridge the wide field and microscopic imaging modalities, a wide field imaging technique can be used to initially localize the contrast agent at the site of interest to guide the location of the MM-OCT imaging to provide a microscopic view. In addition to multi-modal contrast, the microspheres were functionalized with RGD peptides that can target various cancer cell lines. .... Weniger anzeigen

Physician-scientists, with in-depth training in both medicine and research, are uniquely poised to address pressing challenges at the forefront of biomedicine. In recent years, a number of organizations have outlined obstacles to maintaining the pipeline of physician-scientists, classifying them as an endangered species. As in-training and early-career physician-scientists across the spectrum of the pipeline, we share here our perspective on the current challenges and available opportunities… Mehr zeigen

Physician-scientists, with in-depth training in both medicine and research, are uniquely poised to address pressing challenges at the forefront of biomedicine. In recent years, a number of organizations have outlined obstacles to maintaining the pipeline of physician-scientists, classifying them as an endangered species. As in-training and early-career physician-scientists across the spectrum of the pipeline, we share here our perspective on the current challenges and available opportunities that might aid our generation in becoming independent physician-scientists. These challenges revolve around the difficulties in recruitment and retention of trainees, the length of training and lack of support at key training transition points, and the rapidly and independently changing worlds of medical and scientific training. In an era of health care reform and an environment of increasingly sparse NIH funding, these challenges are likely to become more pronounced and complex. As stakeholders, we need to coalesce behind core strategic points and regularly assess the impact and progress of our efforts with appropriate metrics. Here, we expand on the challenges that we foresee and offer potential opportunities to ensure a more sustainable physician-scientist workforce. Weniger anzeigen

Carbon nanotube uptake was measured via high-speed confocal Raman imaging in live cells. Spatial and temporal tracking of two cell-intrinsic and nine nanotube-derived Raman bands was conducted simultaneously in RAW 264.7 macrophages. Movies resolved single (n, m) species, defects, and aggregation states of nanotubes transiently as well as the cell position, denoted by lipid and protein signals. This work portends the real-time molecular imaging of live cells and tissues using Raman… Mehr zeigen

Carbon nanotube uptake was measured via high-speed confocal Raman imaging in live cells. Spatial and temporal tracking of two cell-intrinsic and nine nanotube-derived Raman bands was conducted simultaneously in RAW 264.7 macrophages. Movies resolved single (n, m) species, defects, and aggregation states of nanotubes transiently as well as the cell position, denoted by lipid and protein signals. This work portends the real-time molecular imaging of live cells and tissues using Raman spectroscopy, affording multiplexing and complete photostability. Weniger anzeigen

In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications.

Fourier transform light scattering (FTLS) has been recently developed as a novel, ultrasensitive method for studying light scattering from inhomogeneous and dynamic structures. FTLS relies on quantifying the optical phase and amplitude associated with a coherent image field and propagating it numerically to the scattering plane. In this paper, we review the principle and applications of FTLS to static and dynamic light scattering from biological tissues and live cells. Compared with other… Mehr zeigen

Fourier transform light scattering (FTLS) has been recently developed as a novel, ultrasensitive method for studying light scattering from inhomogeneous and dynamic structures. FTLS relies on quantifying the optical phase and amplitude associated with a coherent image field and propagating it numerically to the scattering plane. In this paper, we review the principle and applications of FTLS to static and dynamic light scattering from biological tissues and live cells. Compared with other existing light scattering techniques, FTLS has significant benefits of high sensitivity, speed, and angular resolution. We anticipate that FTLS will set the basis for disease diagnosis based on intrinsic tissue optical properties and provide an efficient tool for quantifying cell structures and dynamics. Weniger anzeigen

During breast-conserving surgeries, axillary lymph nodes draining from the primary tumor site are removed for disease staging. Although a high number of lymph nodes are often resected during sentinel and lymph-node dissections, only a relatively small percentage of nodes are found to be metastatic, a fact that must be weighed against potential complications such as lymphedema. Without a real-time in vivo or in situ intraoperative imaging tool to provide a microscopic assessment of the nodes… Mehr zeigen

During breast-conserving surgeries, axillary lymph nodes draining from the primary tumor site are removed for disease staging. Although a high number of lymph nodes are often resected during sentinel and lymph-node dissections, only a relatively small percentage of nodes are found to be metastatic, a fact that must be weighed against potential complications such as lymphedema. Without a real-time in vivo or in situ intraoperative imaging tool to provide a microscopic assessment of the nodes, postoperative paraffin section histopathological analysis currently remains the gold standard in assessing the status of lymph nodes. This paper investigates the use of optical coherence tomography (OCT), a high-resolution real-time microscopic optical-imaging technique, for the intraoperative ex vivo imaging and assessment of axillary lymph nodes. Normal (13), reactive (1), and metastatic (3) lymph nodes from 17 human patients with breast cancer were imaged intraoperatively with OCT. These preliminary clinical studies have identified scattering changes in the cortex, relative to the capsule, which can be used to differentiate normal from reactive and metastatic nodes. These optical scattering changes are correlated with inflammatory and immunological changes observed in the follicles and germinal centers. These results suggest that intraoperative OCT has the potential to assess the real-time node status in situ, without having to physically resect and histologically process specimens to visualize microscopic features. Weniger anzeigen

As breast cancer screening rates increase, smaller and more numerous lesions are being identified earlier, leading to more breast-conserving surgical procedures. Achieving a clean surgical margin represents a technical challenge with important clinical implications. Optical coherence tomography (OCT) is introduced as an intraoperative high-resolution imaging technique that assesses surgical breast tumor margins by providing real-time microscopic images up to 2 mm beneath the tissue surface. In… Mehr zeigen

As breast cancer screening rates increase, smaller and more numerous lesions are being identified earlier, leading to more breast-conserving surgical procedures. Achieving a clean surgical margin represents a technical challenge with important clinical implications. Optical coherence tomography (OCT) is introduced as an intraoperative high-resolution imaging technique that assesses surgical breast tumor margins by providing real-time microscopic images up to 2 mm beneath the tissue surface. In a study of 37 patients split between training and study groups, OCT images covering 1 cm(2) regions were acquired from surgical margins of lumpectomy specimens, registered with ink, and correlated with corresponding histologic sections. A 17-patient training set used to establish standard imaging protocols and OCT evaluation criteria showed that areas of higher scattering tissue with a heterogeneous pattern were indicative of tumor cells and tumor tissue in contrast to lower scattering adipocytes found in normal breast tissue. The remaining 20 patients were enrolled into the feasibility study. Of these lumpectomy specimens, 11 were identified with a positive or close surgical margin and 9 were identified with a negative margin under OCT. Based on histologic findings, 9 true positives, 9 true negatives, 2 false positives, and 0 false negatives were found, yielding a sensitivity of 100% and specificity of 82%. These results show the potential of OCT as a real-time method for intraoperative margin assessment in breast-conserving surgeries. Weniger anzeigen

Needle biopsy of small or nonpalpable breast lesions has a high nondiagnostic sampling rate even when needle position is guided by stereotaxis or ultrasound. We assess the feasibility of using a near-infrared fiber optic probe and computer-aided detection for the microscopic guidance of needle breast biopsy procedures. Specimens from nine consented patients undergoing breast-conserving surgery were assessed intraoperatively using a needle device with an integrated fiber-optic probe capable of… Mehr zeigen

Needle biopsy of small or nonpalpable breast lesions has a high nondiagnostic sampling rate even when needle position is guided by stereotaxis or ultrasound. We assess the feasibility of using a near-infrared fiber optic probe and computer-aided detection for the microscopic guidance of needle breast biopsy procedures. Specimens from nine consented patients undergoing breast-conserving surgery were assessed intraoperatively using a needle device with an integrated fiber-optic probe capable of assessing two physical tissue properties highly correlated to pathology. Immediately following surgical resection, specimens were probed by inserting the optical biopsy needle device into the tissue, simulating the procedure used to position standard biopsy needles. Needle positions were marked and correlated with histology, which verified measurements obtained from 58 needle positions, including 40 in adipose and 18 in tumor tissue. This study yielded tissue classifications based on measurement of optical refractive index and scattering. Confidence-rating schemes yielded combined sensitivity of 89% (16/18) and specificity of 78% (31/40). Refractive index tests alone identified tumor tissue with a sensitivity of 83% (15/18) and specificity of 75% (30/40). Scattering profiles independently identified tumor tissue with a sensitivity of 61% (11/18) and specificity of 60% (24/40). These results show that a biopsy needle with an integrated fiber optic probe can be used to identify breast tumor tissue for sampling. Integration of this probe into current practices offers the potential to reduce nondiagnostic sampling rates by directly evaluating in situ microscopic tissue properties in real-time, before removal. Weniger anzeigen

Powered by the computational muscle of bioinformatics and the broad perspective of systems biology, advances in biomedical science now have the capacity to transform medicine. Yet to fully realize the health benefits of new scientific insight, we must ensure a vibrant flow of information between the basic sciences and clinical medicine. This takes both systems and people. The U.S. government has made an unprecedented investment in the infrastructure required to support a new generation of… Mehr zeigen

Powered by the computational muscle of bioinformatics and the broad perspective of systems biology, advances in biomedical science now have the capacity to transform medicine. Yet to fully realize the health benefits of new scientific insight, we must ensure a vibrant flow of information between the basic sciences and clinical medicine. This takes both systems and people. The U.S. government has made an unprecedented investment in the infrastructure required to support a new generation of translational researchers. Through the Clinical and Translational Science Award program (CTSA), the National Institutes of Health has created a national consor- tium that already includes 39 centers in 23 states with an annual funding commitment of $500 million by 2012. Still in its infancy, this initiative seeks to shorten the time required to translate research results into therapies by many means, including training researchers and providing them with an academic home, developing tools for clinical research, streamlining regulatory processes, and fostering interdisciplinary and interinstitutional research. The potential is clear. But people are the prerequisite for success. We need an array of inno- vative investigators whose expertise spans all the disciplines of basic discovery and medical science. As a counterpoint to federal efforts, our private, nonprofit organizations have addressed the human capital need in robust ways, training and funding physicians and other clinical scientists, and piloting models for interdisciplinary graduate training involving biologists, physical and computational scientists and engineers, as well as a wide range of clinical and public health professionals. Weniger anzeigen

We employ Fourier-transform light scattering, a technique recently developed in our laboratory, to study the scattering properties of rat organ tissues. Using the knowledge of the complex field associated with high-resolution microscope images of tissue slices, we extracted the scattering mean-free path l(s) and anisotropy factor g, which characterize the bulk tissue for three different rat organs. This "bottom up" approach to measuring tissue scattering parameters allows for predicting the… Mehr zeigen

We employ Fourier-transform light scattering, a technique recently developed in our laboratory, to study the scattering properties of rat organ tissues. Using the knowledge of the complex field associated with high-resolution microscope images of tissue slices, we extracted the scattering mean-free path l(s) and anisotropy factor g, which characterize the bulk tissue for three different rat organs. This "bottom up" approach to measuring tissue scattering parameters allows for predicting the wave transport phenomena within the organ of interest at a multitude of scales-from organelle to organ level. Weniger anzeigen

Fourier transform light scattering (FTLS) is a novel experimental approach that combines optical microscopy, holography, and light scattering for studying inhomogeneous and dynamic media. In FTLS the optical phase and amplitude of a coherent image field are quantified and propagated numerically to the scattering plane. Because it detects all the scattered angles (spatial frequencies) simultaneously in each point of the image, FTLS can be regarded as the spatial equivalent of Fourier transform… Mehr zeigen

Fourier transform light scattering (FTLS) is a novel experimental approach that combines optical microscopy, holography, and light scattering for studying inhomogeneous and dynamic media. In FTLS the optical phase and amplitude of a coherent image field are quantified and propagated numerically to the scattering plane. Because it detects all the scattered angles (spatial frequencies) simultaneously in each point of the image, FTLS can be regarded as the spatial equivalent of Fourier transform infrared spectroscopy, where all the temporal frequencies are detected at each moment in time. Weniger anzeigen

The American Society for Clinical Investigation (ASCI) was started a century ago to foster and to address the needs of the younger physician-scientists. A hundred years later, ASCI remains one of the premier organizations for physician-scientists and one of most well-respected organizations in the medical community. I have had the opportunity and pleasure to interact with the ASCI not only as an organization through my tenure as president of the American Physician Scientists Association, but… Mehr zeigen

The American Society for Clinical Investigation (ASCI) was started a century ago to foster and to address the needs of the younger physician-scientists. A hundred years later, ASCI remains one of the premier organizations for physician-scientists and one of most well-respected organizations in the medical community. I have had the opportunity and pleasure to interact with the ASCI not only as an organization through my tenure as president of the American Physician Scientists Association, but also with its members over the last four years. In my view, the same characteristics that permeate ASCI the organization also define ASCI the membership — mentorship, exemplary role models, advocacy, and leadership. Weniger anzeigen

Since its introduction, optical coherence tomography (OCT) technology has advanced from the laboratory bench to the clinic and back again. Arising from the fields of low coherence interferometry and optical time- and frequency-domain reflectometry, OCT was initially demonstrated for retinal imaging and followed a unique path to commercialization for clinical use. Concurrently, significant technological advances were brought about from within the research community, including improved laser… Mehr zeigen

Since its introduction, optical coherence tomography (OCT) technology has advanced from the laboratory bench to the clinic and back again. Arising from the fields of low coherence interferometry and optical time- and frequency-domain reflectometry, OCT was initially demonstrated for retinal imaging and followed a unique path to commercialization for clinical use. Concurrently, significant technological advances were brought about from within the research community, including improved laser sources, beam delivery instruments, and detection schemes. While many of these technologies improved retinal imaging, they also allowed for the application of OCT to many new clinical areas. As a result, OCT has been clinically demonstrated in a diverse set of medical and surgical specialties, including gastroenterology, dermatology, cardiology, and oncology, among others. The lessons learned in the clinic are currently spurring a new set of advances in the laboratory that will again expand the clinical use of OCT by adding molecular sensitivity, improving image quality, and increasing acquisition speeds. This continuous cycle of laboratory development and clinical application has allowed the OCT technology to grow at a rapid rate and represents a unique model for the translation of biomedical optics to the patient bedside. This work presents a brief history of OCT development, reviews current clinical applications, discusses some clinical translation challenges, and reviews laboratory developments poised for future clinical application. Weniger anzeigen

Magnetic iron oxide nanoparticles and near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWNT) form heterostructured complexes that can be utilized as multimodal bioimaging agents. Fe catalyst-grown SWNT were individually dispersed in aqueous solution via encapsulation by oligonucleotides with the sequence d(GT)15, and enriched using a 0.5 T magnetic array. The resulting nanotube complexes show distinct NIR fluorescence, Raman scattering, and visible/NIR absorbance features… Mehr zeigen

Magnetic iron oxide nanoparticles and near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWNT) form heterostructured complexes that can be utilized as multimodal bioimaging agents. Fe catalyst-grown SWNT were individually dispersed in aqueous solution via encapsulation by oligonucleotides with the sequence d(GT)15, and enriched using a 0.5 T magnetic array. The resulting nanotube complexes show distinct NIR fluorescence, Raman scattering, and visible/NIR absorbance features, corresponding to the various nanotube species. AFM and cryo-TEM images show DNA-encapsulated complexes composed of a approximately 3 nm particle attached to a carbon nanotube on one end. X-ray diffraction (XRD) and superconducting quantum interference device (SQUID) measurements reveal that the nanoparticles are primarily Fe2O3 and superparamagnetic. The Fe2O3 particle-enriched nanotube solution has a magnetic particle content of approximately 35 wt %, a magnetization saturation of approximately 56 emu/g, and a magnetic relaxation time scale ratio (T1/T2) of approximately 12. These complexes have a longer spin-spin relaxation time (T2 approximately 164 ms) than typical ferromagnetic particles due to the smaller size of their magnetic component while still retaining SWNT optical signatures. Macrophage cells that engulf the DNA-wrapped complexes were imaged using magnetic resonance imaging (MRI) and NIR mapping, demonstrating that these multifunctional nanostructures could potentially be useful in multimodal biomedical imaging. Weniger anzeigen

We present a novel needle-based device for the measurement of refractive index and scattering using low-coherence interferometry. Coupled to the sample arm of an optical coherence tomography system, the device detects the scattering response of, and optical path length through, a sample residing in a fixed-width channel. We report use of the device to make near-infrared measurements of tissues and materials with known optical properties. The device could be used to exploit the refractive index… Mehr zeigen

We present a novel needle-based device for the measurement of refractive index and scattering using low-coherence interferometry. Coupled to the sample arm of an optical coherence tomography system, the device detects the scattering response of, and optical path length through, a sample residing in a fixed-width channel. We report use of the device to make near-infrared measurements of tissues and materials with known optical properties. The device could be used to exploit the refractive index variations of tissue for medical and biological diagnostics accessible by needle insertion. Weniger anzeigen

Optical diagnostic imaging techniques are increasingly being used in the clinical environment, allowing for improved screening and diagnosis while minimizing the number of invasive procedures. Diffuse optical tomography, for example, is capable of whole-breast imaging and is being developed as an alternative to traditional X-ray mammography. While this may eventually be a very effective screening method, other optical techniques are better suited for imaging on the cellular and molecular scale.… Mehr zeigen

Optical diagnostic imaging techniques are increasingly being used in the clinical environment, allowing for improved screening and diagnosis while minimizing the number of invasive procedures. Diffuse optical tomography, for example, is capable of whole-breast imaging and is being developed as an alternative to traditional X-ray mammography. While this may eventually be a very effective screening method, other optical techniques are better suited for imaging on the cellular and molecular scale. Optical Coherence Tomography (OCT), for instance, is capable of high-resolution cross-sectional imaging of tissue morphology. In a manner analogous to ultrasound imaging except using optics, pulses of near-infrared light are sent into the tissue while coherence-gated reflections are measured interferometrically to form a cross-sectional image of tissue. In this paper we apply OCT techniques for the high-resolution three-dimensional visualization of lymph node morphology. We present the first reported OCT images showing detailed morphological structure and corresponding histological features of lymph nodes from a carcinogen-induced rat mammary tumor model, as well as from a human lymph node containing late stage metastatic disease. The results illustrate the potential for OCT to visualize detailed lymph node structures on the scale of micrometastases and the potential for the detection of metastatic nodal disease intraoperatively. Weniger anzeigen

We present an approach called pulsed multiline excitation (PME) for measurements of multicomponent, fluorescence species and demonstrate its application in capillary electrophoresis for DNA sequencing. To fully demonstrate the advantages of PME, a fluorescent dye set has been developed whose absorption maxima span virtually the entire visible spectrum. Unlike emission wavelength-dependent approaches for identifying fluorescent species, the removal of the spectral component in PME confers a… Mehr zeigen

We present an approach called pulsed multiline excitation (PME) for measurements of multicomponent, fluorescence species and demonstrate its application in capillary electrophoresis for DNA sequencing. To fully demonstrate the advantages of PME, a fluorescent dye set has been developed whose absorption maxima span virtually the entire visible spectrum. Unlike emission wavelength-dependent approaches for identifying fluorescent species, the removal of the spectral component in PME confers a number of advantages including higher and normalized signals from all dyes present in the assay, the elimination of spectral cross-talk between dyes, and higher signal collection efficiency. Base-calling is unambiguously determined once dye mobility corrections are made. These advantages translate into significantly enhanced signal quality as illustrated in the primary DNA sequencing data and provide a means for achieving accurate base-calling at lower reagent concentrations. Weniger anzeigen

We have previously proposed molecular circuits designed from polyaniline polymer strands, polyacetylene polymer strands and charge transfer salts acting as transistors. Due to unique properties that are demonstrated in this manuscript, we propose the use of carbon single wall nanotubes and transition metal endohedrally doped single wall carbon nanotubes (SWNTs) for utilization in molecular electronics. Different transition metals were used in a systematic fashion to manipulate the molecular… Mehr zeigen

We have previously proposed molecular circuits designed from polyaniline polymer strands, polyacetylene polymer strands and charge transfer salts acting as transistors. Due to unique properties that are demonstrated in this manuscript, we propose the use of carbon single wall nanotubes and transition metal endohedrally doped single wall carbon nanotubes (SWNTs) for utilization in molecular electronics. Different transition metals were used in a systematic fashion to manipulate the molecular orbital energy gap (HOMO-LUMO gap) of metallic (Ch = (n = m)) nanotubes. Gradient corrected, Density Functional Theory (DFT) Self Consistent Field (SCF) calculations were used to calculate molecular orbital energy levels, HOMO-LUMO gaps, electron affinities, ionization energies and other electronic properties for these molecules. The effect that a SWNT's length has on its HOMO-LUMO gap was investigated. DFT-SCF calculations were also used to demonstrate how multiple metal filled nanotubes could be used to construct a molecular nanotube based transistor. Weniger anzeigen

Reflectance and fluorescence spectroscopies have shown great promise for early detection of epithelial dysplasia. We have developed a clinical reflectance spectrofluorimeter for multimodal spectroscopic diagnosis of epithelial dysplasia. This clinical instrument, the FastEEM, collects white light reflectance and fluorescence excitation-emission matrices (EEM's) within a fraction of a second. In this paper we describe the FastEEM instrumentation, designed for collection of multi-modal… Mehr zeigen

Reflectance and fluorescence spectroscopies have shown great promise for early detection of epithelial dysplasia. We have developed a clinical reflectance spectrofluorimeter for multimodal spectroscopic diagnosis of epithelial dysplasia. This clinical instrument, the FastEEM, collects white light reflectance and fluorescence excitation-emission matrices (EEM's) within a fraction of a second. In this paper we describe the FastEEM instrumentation, designed for collection of multi-modal spectroscopic data. We illustrate its performance using tissue phantoms with well defined optical properties and biochemicals of known fluorescence properties. In addition, we discuss our plans to develop a system that combines a multi-spectral imaging device for wide area surveillance with this contact probe device. Weniger anzeigen