A Virtual Symposium hosted by the Fitzpatrick Institute for Photonics | May 16-18, 2021

Special Topics: Advanced Interferometry • Light Technologies in The Brain •
Photonics and Pandemics

Duke Fitzpatrick Institute for Photonics


CELEBRATING 20 YEARS

Virtual Poster Session

Click a poster thumbnail image to enlarge.

Awardees of 2021 FIP Virtual Poster Session

1st Place
 #28 “Real-Time 3D Tracking and Imaging Microscopy” – Courtney Johnson et al


2nd Place
 #18 “Plasmonic Nanocavity for Chemical Sensing” Li-Lin Tay, et a

3rd Place TIE
 
#19 “Applications of Nonlinear Optical Spectra and Imaging in Cultural Artifacts Science” Yue Zhou, et al.
#26 “Microbubble Enhanced Photoacoustic and Ultrasound Tomography” Yuqi Tang, et al.

Honorable Mentions:
Poster #17 “Information-Efficient Localization Microscopy via Off-Center Illumination” Chen Zhang, et al.
Poster #27 “Deep Learning Reconstruction of Undersampled Photoacoustic Images” Anthony DiSpirito, et al.

1. Depth sensitive Raman spectroscopy for skin wounds in rodents

Joshua Weiming Su, Qiang Wang, Yao Tian, Leigh Madden, Erica Teo, David Becker and Quan Liu

School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore

Raman spectroscopy has demonstrated its great potential in skin wound assessment. Given that biochemical changes in wound healing is depth dependent as the skin is a layered structure, depth sensitive Raman spectroscopy could enhance the power of Raman spectroscopy in this application. Considering the critical importance of rodent studies in the field of skin wound assessment, it is necessary to develop and validate a system that can perform depth sensitive measurements in rat skin with a proper target depth range. We report the design, optimization and evaluation of a new snapshot depth-sensitive Raman instrument for rat skin measurements. The optical design and optimization process are presented first. The depth sensitive measurement performance is characterized on both ex vivo porcine skin with a gradient of layer thickness and ex vivo rat skin samples with wounds. The statistical analysis of the measured Raman spectra demonstrates the feasibility of differentiation between the wound edge and healthy skin. Moreover, the accuracy of classification improves monotonically as more data from new depths are used, which implies that each depth offers additional information useful for classification. This instrument demonstrates the ability to perform snapshot depth sensitive Raman measurements from rat skin, which paves the way towards in vivo preclinical studies of rat skin wounds.

 

Joshua Weiming

wsu004@e.ntu.edu.sg

2. Fiber-based planar antennas for biosensing and diagnostics

A. Giannetti1*, M. Agio2,3,
P. Cecchi4, F. Chiavaioli1,
A. Ferrini4, S. Howitz5,
P. Lombardi3, N. Soltani2,
F. Sonntag6, C. Toninelli3,
F. Baldini1

1. Istituto di Fisica Applicata “Nello Carrara”, CNR-IFAC, 50019 Sesto Fiorentino, Italy;
2. Laboratory of Nano-Optics and Cμ, University of Siegen, 57072 Siegen, Germany;
3. National Institute of Optics, CNR-INO, 50019 Sesto Fiorentino, Italy;
4. Cecchi Srl, 50142 Florence, Italy;
5. Gesellschaft für Silizium-Mikrosysteme (GeSiM) mbH, 01454 Radeberg, Germany;
6. Fraunhofer Institute for Material and Beam Technology IWS, 01277 Dresden, Germany

Sepsis, defined as the systemic inflammatory response to a confirmed or suspected source of infection, is the most severe infection-related condition and its identification can be particularly difficult in the initial stages. The importance of having a POCT platform capable of measuring sepsis biomarkers for a secure early-stage diagnosis is evident since traditional methods of pathogen determination delay treatment and also increase the recovery period for the patient. The biggest advantage of optical probes is the ability to detect low quantities of target molecules without direct contact to the sample. Nanophotonics-based sensing promises to build on the advantages of optical sensing, while overcoming its limitations by providing a high sensitivity, specificity, dynamic range, as well as the possibility for easy integration into simple and affordable devices. The project FASPEC (Fiber-based planar antennas for biosensing and diagnostics) aims at developing and prototyping a high-performance fluorescence-based molecular assay for invitro diagnostics that integrates lab-on-a-chip and optical readout functionalities within a single, fully automated platform. The key biophotonics innovation of the project is the replacement of the bulk optics used for collecting the fluorescence signal with a suitably designed optofluidic chip. The latter shall function as an optical antenna to direct fluorescence towards the sensor head, hence enhancing the sensitivity of the fluorescencebased assay by orders of magnitude. Application-specific lab-on-a-chip systems equipped with our high-throughput and ultrasensitive detection scheme have been envisioned.


Ambra Giannetti

a.giannetti@ifac.cnr.it

3. Dual-modality gold nanostar bioimaging nanoprobe for sensitive brain cancer detection

Yang Liu, Austin B Carpenter, Christopher J Pirozzi, Hai Yan, Tuan Vo-Dinh

Department of Biomedical Engineering, Duke University; Department of Pathology, Duke University Medical Center

Glioblastoma (GBM) is the most aggressive brain cancer with a median survival of only 15 months and there is an urgent need for novel methods to improve GBM management. We have developed a dual-modality gold nanostar (GNS) bioimaging nanoprobe for sensitive brain cancer detection with positron emission tomography (PET) and subcellular tracking with two-photon photoluminescence (TPL). Experiment results demonstrated that the developed GNS nanoprobe can reach submillimeter intracranial brain tumor detection using PET scan, which is superior to any currently available non-invasive imaging modality. Microscopic examination using TPL and electron microscopy (EM) further confirmed that GNS nanoparticles permeated the brain tumor leaky vasculature and accumulated selectively in the brain tumor following systemic administration. Our sensitive GNS bioimaging nanoprobe has promise for future preclinical and translational applications aimed to improve GBM patients’ outcomes. 


Yang Liu

 yang.liu3@duke.edu

4. Bound States in the Continuum Modes for THz Biosensing

Natalie Rozman, Dr. Kebin Fan, and Dr. Willie Padilla

Department of Electrical and Computer Engineering,
Duke University

We numerically and experimentally demonstrate a high Q factor mode at terahertz (THz) frequencies for an all-dielectric metasurface comprised of a periodic array of free-standing asymmetric cylindrical resonators. This mode was used to detect a layer of a polymer analyte with an experimental sensitivity of S = 723 nm/RIU. 

Natalie Rozman
natalie.rozman@duke.edu

5. Miniaturized Optical BioSensor for Point-of-Care Total Protein Measurement

Fariah Mahzabeen, Ophir Vermesh, James S. Harris, Sanjiv S. Gambhir

Former: Dept. of Electrical Engineering,
Stanford University.
Current: Dept. of Aviation and Technology,
San Jose State University

The poster presents a point-of-care biosensor for measurement of total protein in human serum and urine, with applications to monitoring kidney health in diabetic nephropathy and other diseases. Most existing total protein assays are performed using large, expensive laboratory chemistry analyzers that are not amenable to point-of-care analysis or home monitoring and cannot provide real-time readouts. Our sensor is a miniaturized, handheld optoelectronic device comprising of a VCSEL, a PIN photodetector and emission filter bonded on the same chip. The sensor operates in the NIR (Near Infra-Red) region that is ideal for biomedical sensing. It induces and records a fluorescence signal from the biological sample, yielding photocurrent proportional to fluorescence intensity. In conjunction, a simplified assay preparation was developed using a bare fluorescent dye, Cy5.5 that exhibits increased fluorescence in the presence of protein, with signal change linearly proportional to protein concentration. We harnessed this ‘protein-induced fluorescence’ phenomenon to measure the concentration of total proteins present in biological fluid samples, such as human serum or urine. These samples were analyzed using our VCSEL sensor, which demonstrated a highly linear correlation between protein concentration and photocurrent (resulting from fluorescence emission) within a dynamic range much larger than the clinical standard. Comparison with gold standard clinical assays and standard fluorimetry tools showed that the sensor can accurately and reliably quantitate total protein in clinical urine samples from patients with diabetes with high sensitivity. Our VCSEL biosensor is amenable to integration with miniaturized electronics, which could afford a portable, low-cost, easy-to-use device for sensitive, accurate, and real-time total protein measurements from small biofluid volumes.

 

Fariah Mahzabeen

fariahmahzabeen@gmail.com

6. Shifted excitation Raman difference spectroscopy (SERDS) – From diode laser to portable sensor systems for outdoor experiments

Dr. Martin Maiwald, Dr. Bernd Sumpf

Ferdinand-Braun-Institut, Germany

Shifted excitation Raman difference spectroscopy (SERDS) has been successfully demonstrated in various in-situ application fields. Here, SERDS efficiently separates the wanted Raman signals from unwanted disturbing background interferences such as fluorescence and ambient light.  In this contribution, SERDS will be presented with respect to the development of tailor-made diode lasers as the excitation source, customized portable sensor systems and outdoor experiments for demonstration.

First, a brief overview of our developed diode laser based light sources for SERDS will be given. Hybrid devices such as micro-integrated external cavity diode laser at e.g. 671 nm and compact excitation sources at e.g. 488 nm based on nonlinear frequency conversion are realized. Single-chip dual-wavelength distributed Bragg-reflector (DBR) diode laser at 785 nm are presented which provide an optical power up to 200 mW at two emission lines with a spectral distance of 10 cm-1, as targeted for SERDS. This spectral distance can be adjusted from e.g., 0 cm-1 up to 30 cm-1 via on-chip resistor heater elements which are implemented close to the two DBR gratings of the device. A portable SERDS instrument including a compact handheld probe with an integrated dual-wavelength diode laser at 785 nm is realized for outdoor investigations. The instrument will be described and selected SERDS experiments in the apple orchard will be presented. Here, Raman spectra of green apple leaves show a huge background signal caused by laser induced fluorescence and daylight. SERDS successfully reveals the obscured Raman signals from chlorophyll and carotenoids. A further developed portable SERDS sensor system is realized and on-site soil investigations are performed very recently.

The results demonstrate SERDS as a powerful and easy-to-use tool which enables rapid and undisturbed on-site Raman investigations in real-world scenarios e.g., for precision agriculture and soil nutrient management.

Dr. Martin Maiwald
martin.maiwald@fbh-berlin.de

7. Functional Outcomes Following Laser Interstitial Thermal Therapy (LITT) versus Resection in the Treatment of Lesions In or Near the Primary Motor Cortex

Emily C. Lerner, Ethan S. Srinivasan, Ryan M. Edwards, David Huie, Peter E. Fecci

Department of Neurosurgery, Duke School of Medicine

Laser interstitial thermal therapy (LITT) is an effective, minimally-invasive treatment option for radiographically-progressive (RP) brain metastases. This is the first study to compare functional outcomes of LITT vs resection for lesions in or near the primary motor cortex (PMC).

 

Methods

Retrospective review of pre- and post-operative courses was performed of patients treated for new or RP PMC lesions by LITT or resection. Functional outcomes were graded relative to pre-treatment symptoms and categorized as improved, stable, or worsened at 30, 90, and 180 days post-treatment.

 

Results

36 patients were identified with median follow-up of 194 days (IQR 72-503), age 64 years (57-72), and estimated baseline KPS 80 (80-90). 35 (98%) had pre-treatment weakness or motor seizure; 15 (42%) received LITT and 21 (58%) resection. All LITT patients were treated for RP lesions (radiation necrosis (RN) or disease progression) vs. 24% of resection patients. LITT patients trended towards smaller maximum diameters (1.9 cm vs 2.7 cm, p=0.03) and were more likely to show RN on pathology (67% vs 5%, p<0.01). At 30 days after treatment, 89% of surviving patients who underwent resection had stable or improved symptoms, compared to 46% of the LITT cohort (p=0.02), and at 180 days, 100% to 80% (p=0.2941). On Kaplan-Meier analysis there was no difference in overall survival between the two treatment groups, despite LITT being used predominantly for RP.

 

Conclusions

In the short term (30 days), resection patients had better functional outcomes compared to LITT, though those who survived to the 180-day timepoint had similar outcomes. These differences are likely due to transient, expected post-LITT edema that subsides with time. Taken together, prognosis and patient priorities are important considerations in the decision between LITT and resection, as those with better long-term prospects may benefit from the minimally invasive approach with similar longer-term functional recovery.

 

Emily Lerner

emily.sherber@duke.edu

 

8. Dry-state SERS for the “in-situ” identification of historical textile dyes

Margherita Longoni, Silvia Bruni

Department of Chemistry
Università degli Studi di Milano, Italy

Dry-state” SERS represents a promising tool for the non-destructive identification of chemical substances. If coupled with portable instrumentation, it would allow also in-the-field analyses and thus become a valuable technique for the non-invasive investigation of cultural heritage materials. The predominant electromagnetic component of the SERS enhancement in comparison with the chemical one makes dry-state SERS possible, in principle, as the proof of concept was already given1. To this aim, nano-structured silver substrates, yielding SERS spectra in the solid state with higher signal-to-noise ratio, were synthesised. Two different silver colloids (Lee-Meisel nanospheres2 and Garcia-Leis nanostars3), suitably pre-concentrated and pre-aggregated, were deposited on an optically transparent support, such as a microscope glass slide, previously functionalized to promote the adhesion of the nanoparticles. Finally, the obtained silver films were successfully tested for the non-invasive identification of the three red anthraquinonic dyes and of the blue dye indigo by a portable Raman micro-probe in mock-up samples of dyed textile fibres. The final aim of the work is the possibility of exploiting our SERS substrates for the in-situ identification of dyes used in ancient textiles.

[1] Zaffino C., Ngo H. T. , Register J., Bruni S. , Vo-Dinh T. Appl. Phys. A. 122 (2016), 707.

[2] P. C. Lee and D. Meisel, J. Phys. Chem. A 86 (17) (1982), 3391.

[3] A. Garcia-Leis, J. V. Garcia-Ramos, S. Sanchez-Cortes, J. Phys. Chem. C 117 (15) (2013), 7791.

Margherita Longoni
margherita.longoni@unimi.it

9. Mechanism and sensitivity of Fano resonance tuning in high-contrast gratings

Dr. Hsin Yu Yao, and Dr. Tsing-Hua Her 

Department of Physics and Optical Science, The University of North Carolina at Charlotte

We develop a theory for Fano resonance tuning in dual-mode high-contrast gratings (HCGs). Compact analytical formulas of tuning sensitivity are derived and verified numerically, and are in good agreement with reported experiments. We show that the resonance tuning in HCGs, containing cooperative contribution from two propagating modes, is fundamentally different from that in single-mode microresonators. Our theory reveals the important role of the higher-order mode, which can possess large modal dispersion, especially in the long-wavelength limit beyond the cutoff of slab waveguides, to enable large tuning sensitivity. Our findings will simplify the design and optimization of active and passive tuning in HCG resonators.

 

Dr. Tsing-Hua Her
ther@uncc.edu

 

10. Biosensing Of Tacrolimus In Blood Samples With A Drug Receptor Fused To A GFP

Bettina Glahn-Martínez,
Dr. Elena Benito-Peña,
Prof. María C. Moreno-Bondi

Department of Analytical Chemistry, Faculty of Chemistry, Universidad Complutense de Madrid, Spain

Tacrolimus (FK506) is an immunosuppressant drug used to prevent organ rejection after transplantation. It exhibits a narrow therapeutic window and wide inter- and intra-individual pharmacokinetics fluctuations, requiring therapeutic drug monitoring. The analysis of the drug is usually carried out using chromatographic techniques (HPLC-MS/MS) or immunoassays.

FKBP1A is a selective FK506 binding protein that can replace antibodies as a recognition element for the detection of the drug in biosensors. This protein and the immunosuppressant form a complex that inhibits the calcineurin affecting T-cell activation and proliferation.

This work describes the application of FKBP1A, for the development of bioassays with good specificity and affinity for the immunosuppressant, as a useful alternative to commonly applied antibodies. The target analyte is recognized by a recombinant FBP1A fused to the Emerald Green Fluorescent Protein (EmGFP). The sample is incubated with FKBP1A-EmGFP and magnetic beads (MB) functionalized with FK506 are used to capture the free FKBP1A-EmGFP responsible for the fluorescent signal. The method has an LOD of 3 ng/mL and is capable of analyzing up to 90 samples in 55 min.

Bettina Martinez
ab.glahn@ucm.es

11. THz Imaging with All Dielectric Metamaterial Absorbers and Super Resolution

Nicolas Lozada-Smith, Kebin Fan, Felix Jin, Sina Fairsu, Willie Padilla

Department of Electrical and Computer and Department of Biomedical Engineering,
Duke University

Imaging in the terahertz (THz) domain is difficult due to a lack of high-powered sources and limited devices.1 Here we use an all-dielectric metamaterial absorber (DMA) to image in the THz domain and apply Super Resolution (SR) to reconstruct high resolution THz images. We show that with SR, image features smaller than the Rayleigh diffraction limit of the system can be resolved.

 

Nicolas Lozada-Smith

nicolas.lozadasmith@duke.edu

12. Nanophotonic protein-metal complexes toward adaptive materials

Shunji Egusa

Department of Physics, University of North Carolina Charlotte

Proteins are inherently precise nano-materials. A challenge in the traditional inorganic nano-materials syntheses is the size distribution, which limits our ability to design nano-materials, or assemble them into ordered structures. Proteins may provide a more natural starting point for achieving precision, which is demonstrated in their precise functions in bio-organisms. Static structures are known for many proteins, but the dynamic characters are often overlooked. A combination of novel physical properties and dynamic nature of a protein building block may lead to adaptive functional materials.

J. M. Dixon and S. Egusa, J. Phys. Chem. Lett. 2021, 12, 2865.
J. M. Dixon, J. Tomida, and S. Egusa, J. Phys. Chem. Lett. 2020, 11, 3345.
J. M. Dixon and S. Egusa, J. Phys. Chem. C 2019, 123, 10094.
J. M. Dixon and S. Egusa, J. Am. Chem. Soc. 2018, 140, 2265.

Shunji Egusa
segusa@uncc.edu

13. Fiberoptics SERS Sensors using Plasmonic Gold Nanostar Probes for Detection of Molecular Biotargets

 Vanessa Cupil-Garcia, Pietro Strobbia, Bridget M. Crawford, Hsin-neng Wanga, Rodolfo Zentella, Tai-Ping Sun, and Tuan Vo-Dinh

Department of Chemistry,
Duke University

Our group has integrated surface-enhanced Raman scattering (SERS) silver coated gold nanostars on an optical fiber. Fiber-based sensors are an in situ technology that can simultaneously bring the sensor and light to the sample without disturbing the environment during the analysis. This technology is a multi-use method that does not require complex sample preparation and washing steps. Fiber sensors, also referred to as optrodes, enable the detection of analytes in samples that are difficult to access. Additionally, fiber-optrodes allow for specific detection while evading background signals from non-target regions. The fiber-optrode was used to detect miRNA and illegal food additives, such as Rhodamine B. Our group functionalized the tip of the fiber-optic with inverse molecular sentinel nanosensors. The fiber-optic biosensor was used to detect miR156 from leaf tissue of N. benthamiana. It is desirable to develop methods for field detection of miR156 since it is involved in the flowering of plants which is important in regulating plant growth and improving the production of biomass. The fiber-optic sensor was capable of only binding the target miRNA even in the presence of other miRNA. This optrode configuration is a promising candidate for remote and in-field analysis of trace chemicals and biotargets.

 

Vanessa Cupil-Garcia

vanessa.cupil.garcia@duke.edu

14. Quantitative lateral flow assays based on optical control of antibody kinetics for detection of high-molecular-weight antigens in complex samples

V.A. Bragina, V.R. Cherkasov, A.G. Burenin, A.V. Babenyshev, A.V. Orlov, N.V. Guteneva, D.O. Novichikhin 

Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, Russia 

Highly-sensitive lateral flow assays based on magnetic nanolabels and optically selected antibodies have been developed for detection of high-molecular-weight analytes. As models of antigens, the bacterial toxin of staphylococcal enterotoxin B and the biomarker of hepatitis B surface antigen were used. For optimization of assay parameters, selection of antibodies optimal in terms of kinetic characteristics and screening of immobilization interfaces, the advanced label-free optical biosensors were used. The developed rapid assays demonstrated very attractive limits of detections, wide dynamic range and at the same time they are simple, ease of handling and compatible with affordable consumables.

Vera Bragina
braginava@bk.ru

15. Imaging of vital organs such as kidney using microcapsules

Samia  Salem, Valery Tuchin,

Department of Optics and Biophotonics, Saratov State University, Russia

The work by Prikhozhdenko et al. [1] aims to injection 3-μm sized fluorescent capsules based on poly-L-arginine and dextran sulfate for targeting the kidney via a mice renal artery. Hemodynamic study of the target kidney in combination with the histological analysis reveals a safe dose of microcapsules (20 × 106), which has not lead to irreversible pathological changes in blood flow and kidney tissue.  Laser speckle contrast imaging system (for blood flow dynamic study) and histological analysis were used to determine a safe dosage of injected carriers. Blood flow changes in mice after left renal artery injection of microcapsule suspension in the same doses were performed on left kidneys. We are created a theoretical model by using COMSOL Multiphysics® Software to study the trajectory and capturing of particles transported in a branched blood vessel like kidney vessels. Also, a model has been developed to study the trajectory and capturing of particles transported in a branched blood vessel under the influence of cylindrical permanent magnet Ref. [2] that is located outside the vessel as shown in Fig.1. Magnetic nanoparticles, such as Superparamagnetic iron Oxide Nanoparticles (Fe3O4) are used in this theoretical study. The magnet is placed at one branched vessel to attract the magnetic particles towards targeted locations. The fluid (blood) is assumed being Newtonian; its flow is incompressible and laminar. The mechanisms of magnetic nanoparticles moving in Newtonian fluid (blood) in a static magnetic field are numerically studied in this work. The equations of motion for particles in the flow are governed by a combination of magnetic equations for the permanent magnet field and the Navier-Stokes equations for fluid. These equations were solved numerically using the OMSOL Multiphysics® Modeling Software. 

Keywords: Kidney, drug delivery, magnetic nanoparticles Fe3O4, magnetism, permanent magnet, targeted drug delivery, COMSOL Multiphysics® Software.

References

  1. E. S. Prikhozhdenko , O. I. Gusliakova, O. A. Kulikov, O. A. Mayorova, N. A. Shushunova, A. S. Abdurashitov, D. N. Bratashov, N. A. Pyataev, V. V. Tuchin, D. A. Gorin, G. B. Sukhorukov, O. A. Sindeeva. Target delivery of drug carriers in mice kidney glomeruli via renal artery. Balance between efficiency and safety. Journal of Controlled Release 329, p.175-190(2021). 
  2. O. A. Sindeeva, R. A. Verkhovskii, A. S. Abdurashitov, D. V. Voronin, O. I. Gusliakova, A. A. Kozlova, O. A. Mayorova, A. V. Ermakov, E.  V. Lengert, N. A. Navolokin, V. V. Tuchin, D. A. Gorin, G. B. Sukhorukov, D. N. Bratashov, “Effect of Systemic Polyelectrolyte Microcapsule Administration on the Blood Flow Dynamics of Vital Organs”, ACS Biomater. Sci. Eng. 6, 389−397 (2020).
     DOI:10.1021/acsbiomaterials.9b01669 .
Samia Salem
     s.salem_2010@yahoo.com

 

16. Time to Steroid Independence after LITT vs Medical Management for Treatment of Biopsy-Proven Radiation Necrosis Secondary to SRS for Brain Metastasis

Ryan M. Edwards, BA; Eric W. Sankey, MD; Matthew M. Grabowski, MD; Ethan S. Srinivasan, BS; Andrew S. Griffin, MD; Elizabeth P. Howell, MD; Balint Otvos, MD/PhD; Vadim Tsvankin, MD; Gene H. Barnett, MD; Alireza Mohammadi, MD/PhD; Peter E. Fecci, MD/PhD

Department of Neurosurgery, Duke University Medical Center

Introduction: Despite receiving substantial survival benefit, 9-14% of patients undergoing stereotactic radiosurgery (SRS) for brain metastasis (BM) will develop radiation necrosis (RN). RN can result in significant morbidity and impaired quality of life, which are often compounded by long courses of steroid therapy. In addition to direct side effects, steroids such as dexamethasone significantly impair the efficacy of commonly used immunotherapies. Laser interstitial thermal therapy (LITT) has evolved as a safe and effective minimally invasive procedure for RN that can offer an attractive early treatment, while also potentially obviating the need for prolonged steroid use.

Methods: A multicenter, retrospective study was performed of SRS-treated BM patients who developed biopsy-proven RN and were treated with LITT versus medical management (MM). Patients were stratified by modality. Radiographic progression was determined by modified Response Assessment in Neuro-oncology (RANO) criteria. Clinical outcome data including time to steroid cessation, overall survival (OS), and freedom from local progression (FFLP), were compared by treatment modality.

Results: Seventy-two patients met eligibility criteria, with a median follow up of 10.0 (4.2-25.1) months. Median age was 58 (53-66) years, with a median KPS of 80 (80-90) at biopsy. Primary pathologies included non-small cell lung cancer (NSCLC, 44%), melanoma (18%), breast (8%), and renal (6%) cancers, among others. Fifty-seven (79%) patients underwent LITT. Four medically managed patients (27%) and two LITT patients (5%) demonstrated radiographic progression (p=0.031) at a median of 5.3 and 4.0 months, respectively (p=0.40). On Kaplan-Meier analyses, there was no significant difference between the two groups in overall survival (LITT median of 15.2 months vs 11.6 months, p = 0.60) or FFLP (13.6 months vs. 7.06 months), though LITT trended to show a benefit in both metrics. Patients were able to stop steroid therapy earlier in the LITT cohort with median 37 days compared to 245 days after biopsy for MM (p < 0.001). LITT and follow-up duration were predictors of steroid cessation. When controlled for follow-up duration, patients treated with LITT were three times more likely to be weaned off steroids prior to the study endpoint compared to those who were medically managed (p=0.003).

Conclusion: These data suggest that LITT for treatment of biopsy-proven RN after SRS for BM significantly decreases time to steroid cessation, when controlling for other variables. Prospective trials should be designed to further validate the utility of LITT for RN and its impact on steroid-induced morbidity, as well as patient quality of life.

Ryan Edwards
ryan.m.edwards@duke.edu

17. Information-Efficient Localization Microscopy via Off-Center Illumination

Chen Zhang, Dr. Kevin Welsher

Department of Chemistry,
Duke University

In this work, we present a 3D single particle tracking system that can apply tailored sampling patterns to selectively extract photons that yield the most information for particle localization. Collecting more information from a fixed number of photons is very important as the total number of photons that can possibly be obtained from biological materials is often limited. After a thorough investigation of various sampling patterns in 1, 2 and 3 dimensions, we demonstrate that rather than directly sampling the particle, off-center sampling patterns overlapped with high Fisher information areas in the vicinity of the particle give highest precision. We show that precision can be doubled in 2D (XY-plane) or 1D (Z-axis) localization and a ~20% increase in precision was observed in 3D localization. 

 

Chen Zhang  

Chen.zhang2@duke.edu

18. Plasmonic Nanocavity for Chemical Sensing

Li-Lin Tay

National Research Council Canada

Plasmonic nanostructures confine incident light to dimensions much smaller than the wavelength of the light. Metallic nanostructures of gold or silver exhibit localized surface plasmon resonances (LSPR) at wavelengths determined by the material properties, shape and size. For tightly coupled nanostructures, the electromagnetic field is strongly localized in gap regions between the nanostructures or at sharp corners. Many advanced optical phenomena rely on strongly coupled nanostructures that sustain the strongest field enhancement and localization possible. One of the best known example is surface-enhanced Raman scattering (SERS). In this poster, we will highlight our research on the development of paper based plasmonic devices for chemical sensing, specifically for the detection of opioids. The second part of the poster explores the optical properties of plasmonic-particle-on-mirror system.

 

Li-Lin Tay

li-lin.tay@nrc-cnrc.gc.ca

19. Applications of Nonlinear Optical Spectra and Imaging in Cultural Artifacts Science

Yue Zhou, Jin Yu, Tana E. Villafana, Warren S. Warren, and Martin C. Fischer

Department of Chemistry,
Duke University

Pump-probe microscopy is a powerful technique to improve the diagnosis of artworks, such as the paint layers information, pigment properties and the degree of pigment degradation. Conventional research on historical artworks relied on the cross-sectional samples removed from the artworks, which could damage the paintings and limit the imaging areas. With the help of pump-probe microscopy, high-resolution, three-dimensional imaging of the paint layers can be potentially obtained. In this technology, two ultrafast laser pulses are focused at the same point to induce the nonlinear interactions between the laser pulses and the pigment samples . These nonlinear interactions can reveal the electronic and vibrational information with high chemical specificity and high spatial resolution. By scanning the focus, subsurface imaging can be achieved noninvasively with structural and molecular contrast. In previous studies, a 14th century painting was imaged and the nondestructive cross-sectioning capabilities of pump-probe was proved. In addition, the light-induced degradation of vermilion, a historical red pigment, was investigated and the distribution of the degradation product, β-HgS, was visualized on a microscopic scale. In the future, the degradation of cadmium sulfide (CdS), a popular yellow pigment produced since mid-19th century, will be studied under pump-probe microscopy in terms of the degradation products and potential degradation mechanisms.

 

Yue Zhou

yue.zhou541@duke.edu

20. Silicon Nanowires for Low-Loss Plasmonics and Harmonic Generation

Corban Murphey, Seokhyoung Kim, Jin-Sung Park, Yusuke Fujii, Chentao Li, Prof. Hayk Harutyunyan, Prof. James F. Cahoon

Department of Chemistry, University of North Carolina at Chapel Hill

Silicon nanowires (SiNWs) provide an excellent template for a host of different materials applications. When a thin, conformal metallic shell is added to the surface of a SiNW, the surface plasmons from the metal are confined into a high-index, low loss silicon core, allowing the resonance to exist at a much lower energy and in a much smaller volume than it otherwise would. Additionally, characteristic SiNW Mie resonances are shifted and given Fano-character due to refractive index changes and coupling with the plasmon resonances, respectively. Here, we show the behavior and detection of the hybrid resonances. Furthermore, if geometric modifications are made to the SiNWs, novel optical properties emerge. Typically inaccessible optical modes, such as bound guided states and bound states in the continuum (BICs), become accessible due to the change in NW symmetry. Notably, when the geometry of the NW is at or near a BIC condition, the high field intensity within the wire corresponds with large enhancement in third harmonic generation. By combining different material classes and modulating NW geometries, we are able to manipulate light on a small scale, for applications in sensing, catalysis, or optical computing.

 

Corban Murphey

cmurphey@live.unc.edu

21. Expanding Access to Care for Population-Scale Disease Screening: Development of Low-Cost and Portable OCT Technologies

Ge Song, Evan T. Jelly, Adam Wax

Department of Biomedical Engineering, Duke University

Optical coherence tomography (OCT) has become the gold standard in ophthalmology due to its ability to acquire fast and highly sensitive in vivo, cross-sectional images of the retina . In order to increase its access for a wider range of applications and in low-resource settings, we developed a portable, low-cost OCT system that has comparable imaging performance to a commercial system. Here, we present the system design and evaluate its performance for population-scale disease screening.


Ge Song
gs172@duke.edu

22. Plasmonic Gold Nanostars: Synthesis and Application

Supriya Atta, Aidan Canning, Tuan Vo-Dinh

Department of Biomedical Engineering, Duke University

Among the various types of gold nanoparticle systems, gold nanostars have been widely recognized for their ability to create strong Localized Surface Plasmon Resonances (LSPRs), which is strongly depended on the size, shape, length, and number of the spikes of the nanostars. Unfortunately, traditional protocols for gold nanostars syntheses have failed to tune the size, shape, number and length of the spikes. Moreover, there is a lack of sufficient monodispersity and reproducibility of the traditional protocols. We will discuss here a facile seed-mediated synthesis of multibranched stars to control the spike length and spike number of the nanostars. This nanostars synthesis method produces a number of different spike length, and number which can be tuned by changing the on the concentrations of the seeds, AgNO3, ascorbic acid, and surfactant. The development of gold nanostars will lead to a wide variety of applications for in vitro and in vivo biomedical diagnostics.

 

Supriya Atta

supriya.atta@duke.edu

23. Plasmonic SERS Substrates for Diagnostic Applications

Aidan Canning1,2, Joy Li1,2, Hsin-Neng Wang1,2, Anuj Dhawan1,2, Hoan T. Ngo1,2, Tuan Vo-Dinh*1,2,3

1. Fitzpatrick Institute for Photonics
2. Department of Biomedical Engineering
3. Department of Chemistry Duke University, Durham, NC 27708, USA

Surface-enhanced Raman scattering (SERS)-based detection is sensitive and yields sample-specific, narrow, vibrational peaks, making the approach very suitable for chemical identification. Noble-medal, nanopatterned substrates are advantageous for SERS-based chemical detection techniques due to their stability and high plasmonic enhancement. We show the advancement of SERS substrates for chemical and biological sensing over the past decade, which can be attributed to advancements in both fabrication of higher enhancement SERS substrates as well as DNA probe technology. A nucleic acid biosensing probe, molecular sentinel (MS), was conjugated to triangular-shaped nanowire array substrate with sub 10nm gaps to detect the nucleic acid sequence of the breast cancer biomarker gene Ki-67. Next, the nanowave substrate, a noble metal coated monolayer of polystyrene beads, was conjugated with the second-generation nucleic acid biosensing probe, inverse molecular sentinel (iMS) to detect dengue virus DNA down to ~6 attomoles. Lastly, gold nanostars immobilized on a glass slide could detect 750 zemptomoles of Raman-active dyes: imidazole and pMBA. SERS substrates are a promising technology for nucleic acid and small molecule sensing.

 

Joy Li

joy.q.li@duke.edu

 

24. Detection of Plant miRNA using Plasmonic Biosensors with Shifted Excitation Raman Difference Spectroscopy

Ren A. Odion, Pietro Strobbia, Bridget Crawford, Rodolfo Zentella,  Martin Maiwald, Bernd Sumpf, Tai-ping Sun, Tuan Vo-Dinh

Department of Biomedical Engineering,
Duke University

The detection of micro-RNAs (miRNAs) is crucial in understanding the developmental process of key genes involved in the biomass production of plant biofuels. Current methods for understanding these pathways rely on slow methods such as polymerase chain reaction (PCR) to amplify a tediously purified sample of miRNA from plants. To this end, we have developed a combined plasmonic biosensing method based on a Surface Enhanced Raman Spectroscopy (SERS) platform called the inverse Molecular Sentinel (iMS) to directly detect miRNA such as miR858a to understand ligin production and increased biomass. This biosensor is then coupled with the Shifted Excitation Raman Difference Spectroscopy (SERDS) technique to detect these targets in the field, even in the presence of harsh background illumination. The application of such technology for monitoring plant gene expression in the field may potentially revolutionize agriculture technology through the use of nanotechnology-based monitoring for plant health, pollution, and pathogen detection.

 

Ren Odion

ren.odion@duke.edu

25. Deep Image Prior for Undersampling High-speed Photoacoustic Microscopy

Tri Vu, Dr. Junjie Yao

Department of Biomedical Engineering,
Duke University

Photoacoustic microscopy (PAM) is an emerging imaging method combining light and sound. However, limited by the pulsed laser’s repetition rate, state-of-the-art high-speed PAM technology often sacrifices spatial sampling density (i.e., undersampling) for a increased imaging speed over a large field-of-view (FOV). Deep learning methods have recently been used to improve sparsely sampled PAM images; however, these methods often require time-consuming pre-training and a large training dataset with fully-sampled ground truth. In this paper, we propose the use of deep image prior (DIP) to improve the image quality of undersampled PAM images. Unlike other deep learning models, the DIP network does not require pre-training or fully-sampled ground truth, enabling its flexible and fast implementation on various imaging targets. Our results have demonstrated substantial improvement in PAM images with as few as 1.4% of the fully sampled pixels on high-speed PAM. Our DIP approach has outperformed interpolation methods and may be readily translated to other high-speed, undersampling imaging modalities.

 

Tri Vu

tri.vu@duke.edu

26. Microbubble Enhanced Photoacoustic and Ultrasound Tomography

Yuqi Tang, Shanshan Tang, Chengwu Huang, Shigao Chen, Junjie Yao

Department of Biomedical Engineering, Duke University

Photoacoustic tomography (PAT), a hybrid imaging modality that acoustically detects the optical contrast, is a promising candidate for imaging small vessel functions in deep tissue. PAT is physically compatible with and functionally complementary to ultrasound (US) imaging: while PAT can provide the vascular morphology and blood oxygenation, US imaging can provide blood flow. However, PAT’s application was partially hindered by the limited view problem due to the limited detection angle range. Current solutions either rely on exogenous contrast agent or use multiple imaging angles, neither are optimal. In this work, we use microbubble to overcome the limited view problem. Microbubbles can enhance detection sensitivity and image quality for both PA and US, providing more comprehensive functional information. The simulation, in vitro and in vivo results all demonstrate the method’s feasibility.

 

Yuqi Tang

yuqi.tang@duke.edu

27. Deep Learning Reconstruction of Undersampled Photoacoustic Images

Anthony DiSpirito, Daiwei Li, Tri Vu, Dong Zhang, Jianwen Luo, Roarke Horstmeyer, Maomao Chen, Junjie Yao

Department of Biomedical Engineering, Duke University

 

Current photoacoustic microscopy (PAM) systems are limited by an unavoidable compromise between spatial resolution and imaging speed. Traditional PAM systems form images by performing a point-by-point raster scan, with each acquired point adding a certain amount of time on average to the total image acquisition. To obtain a better resolution, typically more points must be acquired, inevitably resulting in a longer image acquisition time. One could acquire a low-resolution image, and upsample it using various interpolation methods, but this results in blurred images when imaging speed is prioritized. However, with the advent of deep learning comes a new avenue to transcend this resolution-imaging speed compromise, by training a data-driven upsampling method tailored to undersampled PAM images. We trained and tested various convolutional network (CNN) architectures and found a Fully-Dense U-net network to produce the best results. Our results and analysis show the ability of deep learning techniques to outperform interpolation and reconstruct PAM images with as few as 2% of the original pixels. With this approach, PAM image acquisitions can be shortened without substantially sacrificing image quality.

 

Anthony DiSpirito

anthony.dispirito@duke.edu

28. Real-Time 3D Tracking and Imaging Microscopy

Courtney Johnson, Dr. Jack Exell, Dr. Kevin Welsher

Department of Chemistry, Duke University

The interaction between a single virus and the cellular environment underlies many important biological questions, yet the spatial disparity and rapid diffusive motion of the virus relative to cells makes the study of these interactions an imaging challenge that no single microscope is optimally suited for. Here we introduce 3D Tracking and Imaging (3D-TrIm), a multimodal approach which combines real-time active feedback single particle tracking with rapid volumetric two-photon imaging to produce a synchronously acquired and co-registered single-virus trajectory and 3D map of the cellular environment. The tracking and imaging microscopes share an objective lens and piezoelectric stage, which acts as the master coordinate space for chromatically separated excitation and emission pathways. We demonstrate this approach using VSV-G pseudotyped virus particles, watching them diffuse near cells and capturing their dynamic transition from rapid diffusion to the membrane-bound state with high temporal resolution,

 

Courtney Johnson

courtney.c.johnson@duke.edu