Bioinstrumentation Interest Group

Members of the NIH Campus Bioinstrumentation Interest Group

MEMBERS: Please note that only a fraction of our members have chosen to be listed here, as many find their primary interest in another group.

Biomedical Optics: Noninvasive optical diagnosis, Laser Doppler Flowmetry, tissue optics, laser microsurgery, ocular phototoxicity, optical coherence microscopy, fluorescence imaging, IVUS and interventional cardiology devices.

Biomedical Optics (BEIP) and the Lasers and Modern Optics Research Facility (a shared intramural resource) have been principally concerned with developing new optical technologies with clinical applications. We have developed many interventional devices and methodologies such as ocular pulse laser microsurgery, laser angioplasty, 2-photon blood sterilization, controlled dosimetry photodynamic therapy. Noninvasive optical diagnostic techniques we have developed include optical coherence microscopy, diffuse optical imaging in tissues (both spectral absorption and fluorescence), quantitative intravascular ultrasound imaging, and optically-guided therapy. Our photon migration theories provide the necessary constructs for quantitative analysis, particularly of coherent light propagation. A recent focus has been the development of optical techniques to facilitate selection of pure cellular fractions from pathology for genetic analysis. Our Research Facility and ties to the broader optical community provide a range of laser sources and sophisticated instrumentation to facilitate feasibility studies of new biomedical technologies.

J.M. Schmitt, M.J. Yadlowsky and R.F. Bonner. Subsurface Imaging of living skin with optical coherence microscopy. Dermatology, 191:93-98.1995.

M.J. Yadlowsky, J.M. Schmitt, and R.F. Bonner. Multiple scattering in optical coherence microscopy. Applied Optics (Sept 1)34: 5699-5707.1995

Gandjbakhche AH, Nossal R, and Bonner RF. "Resolution limits for optical transillumination of abnormalities deeply imbedded in tissues." Medical Physics, 1994; 21:185-191.

Bonner RF, Cohen GE, Laue TM, and Priezzhev AV, Editors, Biochemical Diagnostic Instrumentation Proc SPIE 1994; 2136:1-354.

Date of this document: 11/28/95

Electrophysiology, Microscopy, Videomicroscopy, Fluorescence, Image analysis.

Studies of fusion of natural or artificial lipid vesicles with planar lipid bilayer membranes. Studies of ionic transport through protein channels in lipid bilayers and protein insertion into membranes.

L. Chernomordik, A.Chanturiya, J.Green and J.Zimmerberg. 1995. The hemifusion intermediate and its conversion into complete fusion: regulation by membrane composition. Biophysical J. 69:922-929.

L.Chernomordik, A.N.Chanturiya, E.Suiss-Toby, E.Nora and J.Zimmerberg. (1995) An amphipathic peptide from the C-terminal region of the human immunodeficiency virus envelope glycoprotein causes pore formation in membranes. J. of Virology 68:7115-7123.

A.N. Chanturiya, H.V. Nikoloshina. (1994) Correlations between changes in membrane capacitance induced by changes in ionic environment and the conductance of channels incorporated into bilayer lipid membranes. J.of Membrane Biology. 137:71-77.

Date of this document: 11/30/95

Mass spectrometry of peptides, proteins, nucleic acids, and oligosaccharides.

We are using Electrospray, Matrix assisted laser desorption, fast atom bombardment and electron impact mass spectrometers for the above analyses.

Davis et al. Inhibition of HIV-1 protease activity through cysteine modification, Biochemistry (in press);

Ijames et al. An iron centered triangle complex detected diuring use of propionic acid-isopropanol: a comment on the Finnigan TSQ-700 electrospray inlet system. J. Amer. Soc. Mass Spectrom. (in press, 1995);

Cao et al. Cellular sterol accumulation stimulated by cholesterol 5-beta, 6 beta-epoxide in J774 macrophages, Proc. Soc. Exp. Biol. Med. 209,195-204, 1995.

Date of this document:7 Dec. 1995

Membranes

Thermodynamics of membrane assembly and stability.

(with L. Ginsberg) Rev. Neurosci. 6 : 1-13 (1995)

Date of this document: 11/28/95

Biomedical instrumentation, mechanical design, feedback control systems design, optics design

The following major projects have been completed:

a miniature probe employing multiple gas bearings to allow atraumatic electrical recording from single brain cells during human neurosurgery

a 1.5 ton magnet for MRI imaging with 1ppm field uniformity over a 20cm sphere

a miniature (1mm diameter) everting catheter for small tortuous blood vessels

a miniature fiber-optic pH probe for use in tissue (co-developer)

a computer-controlled laser-based scanner to automatically discriminate, locate and mark fluorescently labelled cell colonies growing on petri dishes

a laser-scanning video-rate confocal microscope using acousto-optics and an image dissector tube an electro-optic system to measure head motions inside PET and MRI scanners

Goldstein, S.R., Hubin, T., Smith, T. An Improved No-Moving-Parts Video-Rate Confocal Microscope. Micron and Microscopica Acta, Vol. 23/4, pp. 437-446, December 1992.

Goldstein, S.R., Hubin, T., Rosenthal, S., Washburn, C. A confocal video rate laser beam scanning reflected light microscope with no moving parts. J. Microscopy, Vol. 157, Pt. 1:29-38, 1990.

Goldstein, S.R., Guan-Xiong, Z., Siegel, R., Brownstein, M.: A system for Automatically Scanning Tissue Culture Dishes to Detect Fluorescently Labeled Cell Colonies. Review of Scientific Instruments 60(7) :1267-1274, July 1989.

Goldstein, S.R., Kidder, L.H.,Herne, T.M., Levin, I.W., Lewis, E.N. The Design and Implementation of a High Fidelity Raman Imaging Microscope - submitted to J. Microscopy 11/95

Date of this document: 11/29/95

Computer-controlled systems for potentiometric titrations, energy transduction in vesicular particles, and rapid enzyme kinetics. All unique systems developed in this laboratory.

Characterization of respiratory chains in terms of cytochromes present, their spectra, midpoint potentials, and numbers of electrons passed. Realtime measurements of conversions of respiratory or photoenergy by vesicles into membrane potentials, delta pH's, and proton fluxes. Rapid kinetics of electron transport and bacteriorhodopsin turnover. Deconvolutions of overlapping spectra, using singular value decomposition (SVD), the pseudoinverse, 2nd derivatives and Gaussians.

Combination of Potentiometry and Resonance Raman Spectroscopy for the Analysis of a Redox Protein. (1995) Anal. Chem. 224:309-314.

Influence of Excitation Energy on the Bacteriorhodopsin Photocycle. (1994) Biochem. 33:4604-4610.

Deconvolutions based on singular value decomposition and the pseudoinverse: a guide for beginners. (1994) J. Biochem. Biophys. Meth. 28:1-33.

Multiwavelength Analysis of the KInetics of Recuction of cytochrome aa3 by Cytochrome c. (1993) Biophys. J. 65:1307-1317.

Date of this document: November 28, 1995.

Analytical Electron Microscopy

1. Serial Block Face Imaging (SBFI), a new technique involving a miniature microtome within a scanning electron microscope for reconstruction of neural networks and other biological tissues.
   
2. Micromachined instruments for semi- automatic handling of single cells.
   
3. A prosthetic urethral valve.

US patent 5,301,671 Two-and Three-dimensional Autoradiographic Imaging Utilizing Charge-Coupled Devices.

US patent 5,262,128 Array Type Multiple Cell Injector
US patent 5,088,980 Prosthetic Urethral Valve with Integral Spring

Ryschon TW, Fowler MD, Wysong R, Leighton SB, Clem TR & Balaban RS. Dynamic Ergometer for Multinuclear Studies of Human Exercise. In: Proceedings of the 2nd Meeting of the Society for Magnetic Resonance. San Francisco, August 6-12, 1994, p.1261

Document date: 11/30/95

Raman and Infrared Spectroscopic imaging. Raman and infrared microscopy.

Applications of infrared and Raman spectroscopy with emphasis placed on biomembranes and related macromolecular assemblies of biophysical interest. Recent attention has focused on the development of novel vibrational spectroscopic instrumentation, algorithms and computer software for collecting and analyzing spectroscopic data derived from complex biological systems. One such scheme has resulted in the development of a technique for performing spectroscopic imaging microscopy. The instrument simultaneously produces images and spectra faster and with significantly higher quality than that previously attainable.

Lewis, E.N. and Levin, I.W.: "Vibrational Spectroscopic Microscopy: Raman, Near-Infrared and Mid- Infrared Imaging Techniques": J. Mic. Soc. of America, 1, 1 (1995)

Lewis, E.N. and Levin, I.W.: "Real-Time, Mid-Infrared Spectroscopic Imaging Microscopy Using Indium Antimonide Focal-Plane Array Detection": Appl. Spectrosc., 49, 672. (1995)

Lewis, E.N., Treado, P.J., Reeder, R.C., Story, G.M., Dowrey, A.E., Marcott, C. and Levin, I.W.: "Fourier-Transform Spectroscopic Imaging Using an Infrared Focal-Plane Array Detector" : Anal. Chem., 67, 3377 (1995)

Document date: November 28th, 1995

Reversible complex formation and thermodynamically nonideal behavior in solutions of biological macromolecules.

Experimental work of our group focuses on the development and application of novel instrumentation and/or methodology for the characterization of reversible associations and nonideal behavior in solutions of biological macromolecules. Results obtained using these techniques are used to characterize the mechanism of reversible complex formation and the influence of "inert" additives on the rates and equilibria of complex-forming reactions.

A.P. Minton (1995). A molecular model for the dependence of the osmotic pressure of bovine serum albumin upon concentration and pH. Biophys. Chem. 57, 65-70.

S. Darawshe, N. Merezhinskaya, and A.P. Minton (1995). PhosphorImager enhancement of sedimentation equilibrium - quantitative polyacrylamide gel electrophoresis: a highly sensitive technique for quantitation of equilibrium gradients of individual components in mixtures. Anal. Biochem. 119, 8-14.

A.P. Minton (1995). Confinement as a determinant of macromolecular structure and reactivity. II. Effects of weakly attractive interactions between confined macrosolutes and confining structures. Biophys. J. 68, 1311-1322.

S. Darawshe and A.P. Minton (1994). Quantitative characterization of macromolecular associations in solution via real-time and postcentrifugation measurements of sedimentation equilibrium: a comparison. Anal. Biochem. 220, 1-4.

Date of this document: November 30, 1995

mass spectrometry, determination of structural features

http://sx102a.niddk.nih.gov/

Date of this document: 28 November 1995

Chemical and Optical Instrumentation, Fiber-Optics, Spectroscopy

Development of varied instrumentation for chemical measurements, recent work has been fiber-optic sensor development, dye indicator chemistry, computer-controlled instrumentation.

"A Fiber-Optic Broad-Range pH Sensor System For Gastric Measurements", E. J. Netto, J. I. Peterson, M. McShane, and V. A.Hampshire, Sensors & Actuators: B. Chemical, Vol. 29, No. 1-3, pp. 157-163.

Document date: November 8, 1995

Clinical and biomedical research systems which require the application of electronics and electrical engineering principles toward the design and development of custom instrumentation.

Broad technical experience in the design, development, and evaluation of advanced electronic circuits, communication equipment, and instrumentation. Hardware design experience includes: analog, digital, embedded microprocessor, radio-frequency, programmable logic, and digital signal processing. Software design experience includes: programming in assembly and C, and developing PC based (including "LabVIEW" type) instrumentation.

Pohida T., Fredrickson H., Tschudin R., Fessler J., Krishna M., Bourg J., Harrington F., and Subramanian S., Review of Scientific Instruments 65(8), 1994, "High Speed Digitizer/Averager Data Acquisition System for Fourier Transform Electron Paramagnetic Resonance Spectroscopy".

Bourg J., Krishna M., Mitchell J., Tschudin R., Pohida T., Friauf W., Smith P., Metcalfe J., Harrington F., and Subramanian S., Journal of Magnetic Resonance B102, 1993, "Radiofrequency FT-EPR Spectroscopy and Imaging".

Date of this document: 12/5/95

3D ultrasound imaging using step motors and linear translation stages

This laboratory focuses on the application of ultrasound imaging to the oral and pharyngeal cavities. The use of ultrasound imaging to study speech and swallowing is a relatively new method that is not yet widely used clinically. Since it is non-invasive and can be used repeatedly, ultrasound has some inherent advantages over other more common diagnostic tools, such as x-ray videofluoroscopy. Some current projects of this laboratory include: 3D reconstruction of tongue surfaces using ultrasound, duplex-Doppler imaging of the hyoid bone during swallowing, and the detection and classification of head and neck tumors in ultrasound images.

Sapper DJ, Sonies BC, "Comparison of the Timing of Swallow Events Using Ultrasound and Videofluorography," Abstract from the Dysphagia Research Society Meeting, McLean, VA, October, 1995

Sonies BC, Wang C, Sapper DJ, "Ultrasound Duplex-Doppler Spectral Analysis of Hyoid Bone Movement During Swallowing," Summary from the Signal and Image Processing Meeting, Las Vegas, NV, November, 1995

Date of this document: 11/28/95

Measurement of binding kinetics with evanescent wave biosensors.

Analysis methods to extract chemical rate constants from biosensor data, with corrections for effects of mass transport limitations.

Multi-component analysis of reversible interactions in the analytical ultracentrifuge in sedimentation equilibrium. Methods to exploit differences in the absorption spectra of some interacting macromolecules.

Kinetics of ligand binding to receptor immobilized in a polymer matrix, as detected with an evanescent wave biosensor. I. A computer simulation of the influence of mass transport. (Biophys J 70:1230-1249)

Simultaneous radial and wavelength analysis with the Optima XL-A analytical ultracentrifuge. Progr. Colloid Polym. Sci. 94 (1994)1-13

Document date: Nov. 7, 1995

see: Mass Spectroscopy Discussion group

Biomedical application of lasers; optical, electro-optical, fluorescence and video technologies; fiber optics; and visible microscopies.

The Biomedical Optics resource through the design of unique instrumentation and the development of novel interventional methodologies continues to support and collaborate in both basic and clinical research. It has provided experimental design, instrumentation, analytical expertise, and clinical support in a long standing NCI collaboration advancing photodynamic therapy from tissue culture to current clinical (Phase II/III) trials. In other collaborations, Biomedical Optics developed instrumentation for microscopy, pioneering the concept of multiwavelength microscopy and lowering the limits of light level detection; designed and fabricated a state of the art optical multichannel analyzer; and provided an innovative communication system within MRI scanners. Currently the Biomedical Optics resource is using its expertise and capabilities to supply new approaches to the problems of molecular biology.

Summary of developments

1. Improvements and additions to High Resolution NMR Spectrometers to enable multinuclear experiments on commercial spectrometers.

2. Development of an experimental radio frequency EPR system with ultra high speed acquisition (in collaboration with NCI/DCS/RBB).

Measurement of homo- and heteronuclear J couplings fromquantitative J correlation. Ad Bax et al., Methods Enzymol. (1994), 239(Nuclear Magnetic Resonance, Pt. C), 79-105

High-speed digitizer/averager data-aquisition system for Fourier transform electron paramagnetic resonance spectroscopy. Tomas J. Pohida et al., Rev. Sci. Instrum. (1994), 65(8), 2500-2504

Radiofrequency FT EPR Spectroscopy and Imaging. John Bourg et al., J. Magn. Reson., Ser.B (1993), 102(1), 112-115

Document date: 11/28/95

Research interests:
Cardiovascular Bioengineering, Artificial Heart, Biomaterials and Imaging

Recent publications:
LVAS Study Group:Evaluation of an Implantable Ventricular Assist System for Humans with Chronic Refractory Heart Failure. ASAIO Journal 41,1:11-15, 1995.