NSF Directorate for Engineering | Division ofChemical, Bioengineering, Environmental, and Transport Systems (CBET)

Bioengineering and Engineering Healthcare Cluster

Biophotonics, Advanced Imaging, and Sensing for Human HealthProgram Director - Leon Esterowitz - lesterow @ nsf.gov

Biophotonics Defined

Examples of Biophotonics Topical Areas

Nuggets Illustrating Recent Achievements

Biophotonics

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Photonics is the technology of generating and harnessing light and other forms of radiant energy whose quantum unit is the photon

Biophotonics applies photonics to the fields of medicine, biology and biotechnology

Examples of Biophotonic Topical Areas

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CONTRAST AGENTS - New classes of photonic probes and contrast agents to label structures and push the envelope of optical sensing to the limits of detection, resolution, and identification

MOLECULAR IMAGING - Image and data fusion between optical imaging, spectroscopic techniques, and conventional imaging modalities for imaging diseases at the molecular and cellular level

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Examples of Biophotonic Topical Areas

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NEUROPHOTONICS - Development and application of photonic tools such as large scale parallel interfaces and interconnects for study and control of neural systems

MICRO- and NANO-PHOTONICS - Development and application of nanoparticle fluorescent quantum-dots; sensitive, multiplexed, high- throughput characterization of macromolecular properties of cells; nanomaterials and nanodevices for biomedicine

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SGER: Advances in Biophotonics to Enable Pancreatic Cancer Screening

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Of all major types of cancer, pancreatic cancer is the Of all major types of cancer, pancreatic cancer is the most lethal. The disease carries a dismal five-year most lethal. The disease carries a dismal five-year survival rate below 5%.  The major reason is that no survival rate below 5%.  The major reason is that no currently available techniques allow diagnosis of currently available techniques allow diagnosis of pancreatic cancer at a stage when a tumor is pancreatic cancer at a stage when a tumor is amenable to surgical resection.amenable to surgical resection.    Sponsored by NSF, this group invented and developed Sponsored by NSF, this group invented and developed a novel optical technology, low-coherence enhanced a novel optical technology, low-coherence enhanced backscattering (LEBS), which senses subtle changes backscattering (LEBS), which senses subtle changes in tissue nanoarchitecture otherwise undetectable by in tissue nanoarchitecture otherwise undetectable by histopathology.  LEBS can detect alterations in histopathology.  LEBS can detect alterations in histologically normal-appearing cells due to the histologically normal-appearing cells due to the presence of precancer in a different part of an organ.presence of precancer in a different part of an organ. This group showed that LEBS-derived optical markers This group showed that LEBS-derived optical markers from normal-appearing periampullary duodenal from normal-appearing periampullary duodenal mucosa can discriminate between pancreatic cancer mucosa can discriminate between pancreatic cancer patients and normal controls with 95% sensitivity and patients and normal controls with 95% sensitivity and 91% specificity.  Moreover, the diagnostic performance of these optical markers was 91% specificity.  Moreover, the diagnostic performance of these optical markers was not compromised by confounding factors such as tumor location and stage.  Thus, not compromised by confounding factors such as tumor location and stage.  Thus, these data provide the first evidence that optical analysis of histologically normal these data provide the first evidence that optical analysis of histologically normal duodenal mucosa can predict the presence of pancreatic cancer without direct duodenal mucosa can predict the presence of pancreatic cancer without direct visualization of the pancreas.visualization of the pancreas.

Low-coherence Enhanced Backscattering (LEBS) signal from duodenal mucosa.  It is signals like this one that contain information about tissue nano/microarchitecture and whose alterations in otherwise histologically normal-appearing tissue are diagnostic for the presence of pancreatic cancer.Credit: Vadim Backman & Young Kim, Northwestern University

Vadim Backman - Northwestern UniversityVadim Backman - Northwestern University

CBET-

0733868

An Ultrafast Micro-Scalpel with Vision

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The Ben-Yakar group has developed a unique The Ben-Yakar group has developed a unique miniaturized probe that combines femtosecond-laser miniaturized probe that combines femtosecond-laser microsurgery (FLMS) with two-photon microscopy (TPM).  microsurgery (FLMS) with two-photon microscopy (TPM).  The successful development of the probe has been The successful development of the probe has been achieved due to a novel optical design and photonics achieved due to a novel optical design and photonics devices such as photonic crystal fibers and MEMS devices such as photonic crystal fibers and MEMS scanning mirrors.  scanning mirrors. 

Using this probe, the Ben-Yakar group has demonstrated Using this probe, the Ben-Yakar group has demonstrated three-dimensional (3D) imaging of live cancer cells in three-dimensional (3D) imaging of live cancer cells in tissue phantoms, which are 3D cell cultures engineered tissue phantoms, which are 3D cell cultures engineered to mimic the optical properties of natural biological to mimic the optical properties of natural biological tissue.  In addition, selective ablation of individual cellstissue.  In addition, selective ablation of individual cellswas demonstrated with high precision.  was demonstrated with high precision. 

Such a device constitutes a novel all-optical Such a device constitutes a novel all-optical seek-and-treat tool, capable of diagnostics as well as seek-and-treat tool, capable of diagnostics as well as microsurgery with unrivaled precision.  This combined microsurgery with unrivaled precision.  This combined FLMS/TPM device would be valuable in a variety of medical applications, from early FLMS/TPM device would be valuable in a variety of medical applications, from early cancer detection and removal, to dermatology.cancer detection and removal, to dermatology.

An Ultrafast Micro-Scalpel with Vision.  A three-dimensional rendering of the combined femtosecond laser microsurgery and two-photon imaging probe designed by the Ben-Yakar Group. 

SEM micrographs (inset) of: (1) the air-core photonic crystal fiber and (2) the MEMS scanning mirror design are shown.

Credit: Adela Ben-Yakar, University of Texas at Austin

Adela BenYakarAdela BenYakar - Northwestern University- Northwestern University

A High Resolution, Lensless On-chip Microscope System

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The Yang group developed a high resolution on-chip The Yang group developed a high resolution on-chip microscope design that results in a microscope that microscope design that results in a microscope that is roughly the size of Washington’s nose on a quarter.  is roughly the size of Washington’s nose on a quarter.  This device abandons the conventional microscope This device abandons the conventional microscope design and instead uses a novel array in conjunction design and instead uses a novel array in conjunction with microfluidic flow to perform high resolution with microfluidic flow to perform high resolution imaging. imaging.  This design, termed Optofluidic Microscopy (OFM), This design, termed Optofluidic Microscopy (OFM), uniquely combines the strength of optics and uniquely combines the strength of optics and microfluidics.  The device does not contain any microfluidics.  The device does not contain any lenses or other optical elements and it can be lenses or other optical elements and it can be implemented using existing semiconductor and implemented using existing semiconductor and microfluidic technologies.microfluidic technologies. The Yang group employed this fully operational on-chip The Yang group employed this fully operational on-chip Optofluidic Microscope system and used it to image Optofluidic Microscope system and used it to image C. elegansC. elegans a popular animal model.  The team showed that, despite the a popular animal model.  The team showed that, despite the fact that it is ~ 108 times smaller than a conventional microscope, the fact that it is ~ 108 times smaller than a conventional microscope, the image quality of the device is comparable to a conventional 20x image quality of the device is comparable to a conventional 20x microscope.microscope.

The Optofluidic Microscope operates without optical elements that are generally associated with a conventional microscope. There are no eye pieces, no sample stages, and no microscope objectives. Instead the imaging principle is based on a novel aperture array arrangement that is emplaced directly onto a linear sensor array.

Credits: Xiquan Cui and Changhuei Yang, California Tech

ChanghueiChanghuei YangYang - California Institute of Technology- California Institute of Technology

On-chip microscope. The microscope itself is about the size of Washington's nose on a quarter.

BES-0547657

Functional Imaging with Functional Imaging with Diffuse Optical WavefieldsDiffuse Optical Wavefields

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Aims of Project:Aims of Project:

Develop reduced order non-linear inversion schemes that exploit MRI-Develop reduced order non-linear inversion schemes that exploit MRI-basedbased structural informationstructural information

Develop new methods for processing DOT data over timeDevelop new methods for processing DOT data over time

Develop fast forward model for DOT brain imagingDevelop fast forward model for DOT brain imaging

Diffuse optical tomography of brain Diffuse optical tomography of brain functionfunction

Passive movement of the right arm of a Passive movement of the right arm of a premature baby stimulated brain activation premature baby stimulated brain activation as indicated by increased blood flow as indicated by increased blood flow causing an increase in blood volume and causing an increase in blood volume and hemoglobin oxygen saturation.hemoglobin oxygen saturation.

Eric L. Miller - Northeastern UniversityEric L. Miller - Northeastern University

Large-Vertical-Displacement (LVD) Microactuator: MEMS- based Micromirrors and Microlenses for Biomedical Imaging

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1. Motivation High mortality of cancers is

due to lack of early detection modalities.

Commonly used biopsy is risky and has low early detection rate.

Optical coherence tomography (OCT) is a non-invasive high-resolution imaging technique, but conventional OCT is bulky and not suitable for in vivo internal organ imaging; and OCT has poor lateral resolution.

2. Objective Design MEMS actuators for

large vertical displacement of micromirrors and microlenses,

for phase-only scanning, and focusing, respectively

The micromirror can be used for

axial scanning in interferometry,

while the tunable microlens can

be used in confocal microscopy

Develop MEMS-based confocal microscopes

Huikai Xie - University of Florida- University of Florida

Anchor

Bimorph actuator z-

Frame

A

A’

Bimorph actuator z+

Frame

Silicon

AlPoly-Si

Oxide

Mirror

Polymer droplet

Frame

Single-crystal silicon

mirror

micro-lens (to be grown)

bimorph actuators

frame

4. Fabricated Devices3. Design Concept

5. Research Plan Integrate microlens on a LVD device using polymer droplets

Integrate capacitive vibration sensors for position control

Develop MEMS-based confocal imaging probes for in vivo imaging of internal organs

0.2mm vertical displacement at 6V DC, scan rate of ~ 2kHz

The basic idea is to use an oppositely tilted bimorph beam to compensate the tilted mirror, and thus the mirror surface will move vertically when a current is applied to both bimorph actuators.

Multimodal Miniature Microscope for Early Cancer Detection

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M. Descour - University of Arizona

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Multimodal Miniature Microscope for Early Cancer Detection

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M. Descour - University of Arizona

Ultra-compact microscope developed by M. Descour of the University of Arizona, together with the use of contrast agents, demonstrates the clear distinction between benign and early cancerous lesions.

A pen-sized, battery-powered multi-modal miniature microscope, designed to specifically image microscopic and molecular features of pre-cancer, is the goal of this research.

Benign EarlyCancer

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Genetic Optimization of Ultrabright Ag Nanodot Biolabels

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Robert Dickson - Georgia Tech & Yih-Ling Tzeng - Emory University

Dendrimer encapsulated Ag nanodots – Idealized single biolabels

Emission from sub-nm, 2-8 atom Ag nanocluster

Water soluble due to protective poly(amidoamine) dendrimer encapsulation

Greatly reduced blinking on single molecule level

Individual nanodots easily observed with weak Hg lamp excitation (>20x brighter than organic dyes)

Multicolored and incredibly photostable – outstanding single molecule labeling potential

Conjugatable to proteins

Investigate dendrimer as vehicle for nanodot transfer to peptides

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Photoactivated Coupling of Photoactivated Coupling of Nano-particle Multilayers and Nerve Nano-particle Multilayers and Nerve CellsCells

13

Nicholas Kotov - Oklahoma State University & Massoud Motamedi - University of Texas-Galveston

Artificial Retina ConceptArtificial Retina Concept

14

Mark Humayan – University of Southern California