Professor of Chemistry
Ph.D., University of Wyoming, 1987
darryl.bornhop@vanderbilt.edu
Bornhop Research Group

Analytical Chemistry

Our group interests center around multidisciplinary bioanalytical and biomedical research:

• the application of lasers to nanoscale chemical and biochemical analysis, and the use of micro-fluidics for onchip patterning, high throughput screening, proteomics and point of care analysis.
• the synthesis, characterization, and application of exogenous markers (particularly multi-modal signaling agents) for early disease detection, diagnosis, and in-vitro assays.

Back Scattering Interferometry (BSI)- Our group has developed a unique sensor, the Back Scattering Interferometor (BSI) and pioneered its use. This new Technology was reported in Science. For the first time, free-solution, label free detection of the interaction of molecules in a micro-chip format with zeptomole sensitivity is possible.  BSI is ideally suited for measuring molecular interaction kinetics and performing quantitative, end point assays.  The BSI platform  can be used to discover new biomarkers, rapidly develop assays, and run routine / quantitative molecular based assays in seconds, at picomolar concentrations in either free-solution or surface-bound, label free modes.  The BSI platform consists of a simple optical train employing a helium-neon laser like those used in grocery store scanners, a mirror, a CCD detector like those used in digital cameras and a special microfluidic chip.

Molecular Imaging/Chemical Synthesis - Multiple targets and various approaches to signaling and/or therapeutic intervention are under investigation. A main target of interest is the 18 kD protein, the Peripheral Benzodiazepine Receptor (PBR). PBR is found primarily in the mitochondria and is known to be associated with responsiveness to reactive oxygen species, apoptosis and steroidogenesis. PBR expression is upregulated in some cancers, and its density has been correlated with metabolic status of the cell. These observations make PBR an attractive target for the delivery of contrast agents and therapeutics to diseased tissue. Recently we prepared a PBR targeted imaging agent (1) {Eu-PK11195, Figure 1} based on our relatively unique lanthanide chelate chemistry (2). The lanthanides are brightly luminescent, show promise for early cancer detection (3) and can even be used as multi modal agents by simple exchange of the chelated lanthanide ion. In-vitro and in-vivo investigations along with new synthetic methodologies are being developed in our laboratory. Some of these new agents have also demonstrated promise as in-vitro diagnostic stains for use in histopathology. In addition, we are developing near-infrared fluorochromes (4), PET agents, and MR signaling agents that are smart, can precipitate selectively or can provide both a signature and a therapeutic effect. Also under intense investigation are the unique spectroscopic properties of the lanthanide chelates.

Selected Publications

Latham JC, Stein RA, Bornhop DJ, Mchaourab HS. Free-Solution Label-Free Detection of alpha-Crystallin Chaperone Interactions by Back-Scattering Interferometry. Analytical Chemistry. 2009, 81 (5): 1865-1871.

Hess BA, Kedziorski A, Smentek L, Bornhop DJ. Role of the antenna in tissue selective probes built of lanthanide-organic chelates. Journal of Physical Chemistry A. 2008, 112 (11): 2397-2407.

Manning HC, Merchant NB, Foutch AC, Virostko JM, Wyatt SK, Shah C, McKinley ET, Xie J, Mutic NJ, Washington MK , La Fleur B, Tantawy MN, Peterson TE, Ansari MS, Baldwin RM, Rothenberg ML, Bornhop DJ, Gore JC, Coffey RJ. Molecular Imaging of Therapeutic Response to Epidermal Growth Factor Receptor Blockade in Colorectal Cancer. Clinical Cancer Research. 2008, 14 (22): 7413-7422.

Bai M, Sexton M, Stella N, Bornhop D. MBC94, A Conjugable Ligand for Cannabinod CB2 Receptor Imaging. Bioconjugate Chemistry. 2008, 19 (5): 988-92.

Latham JC, Markov DA, Sorensen HS, Bornhop DJ. Photobiotin surface chemistry improves label-free interferometric sensing of biochemical interactions. Angewandte Chemie-International Edition. 2007, 45 (6): 955-958.

Bai M, Wyatt SK, Han Z, Papadopoulos V, Bornhop DJ. A novel conjugable translocator protein ligand labeled with a fluorescence dye for in vitro imaging. Bioconjugate Chemistry. 2007, 18 (4): 1118-1122.

Bornhop DJ, Latham JC, Kussrow A, Markov DA, Jones RD, Sorensen HS. Free-solution, label-free molecular interactions studied by back-scattering Interferometry. Science. 2007, 317 (5845): 1732-1736.

Deane NG, Manning HC, Foutch AC, Washington MK, Aronow BA, Bornhop DJ, Coffey RJ. Targeted imaging of colonic tumors in Smad3(-/-) mice discriminates cancer and inflammation. Molecular Cancer Research. 2007, 5 (4): 341-349.

Manning HC, Smith SM, Sexton M, Haviland S, Bai MF, Cederquist K, Stella N, Bornhop DJ. A peripheral benzodiazepine receptor targeted agent for in vitro imaging and screening. Bioconjugate Chemistry. 2006, 17 (3): 735-740.

Sexton M, Manning HC, Cudaback E, Bai M, Bornhop DJ, Stella N. Development of molecular imaging agents capable of assessing PBR expression in vivo. Journal of Neurochemistry. 2006, 96: 38-38.

Latham JC, Markov DA, Sorensen HS, Bornhop DJ. Photobiotin surface chemistry improves label-free interferometric sensing of biochemical interactions. Angewandte Chemie-International Edition. 2006, 45 (6): 955-958.

Manning HC, Bai MF, Anderson BM, Lisiak R, Samuelson LE, Bornhop DJ. Expeditious synthesis of 'P'-protected macrocycles en route to lanthanide chelate metal complexes. Tetrahedron Letters. 2005, 46 (28): 4707-4710.

Wang ZL, Bornhop DJ. Dual-capillary backscatter interferometry for high-sensitivity nanoliter-volume refractive index detection with density gradient compensation. Analytical Chemistry. 2005, 77 (24): 7872-7877.

Wang XD, Ku G, Wegiel MA, Bornhop DJ. Noninvasive Photoacoustic Angiography of Animal Brains in Vivo with Near-Infrared Light and an Optical Contrast Agent. Optics Letters. 2004, 29 (7): 730-732.

Bell, B. A.; Shilagard, T.; Goebel, T.; Bornhop, D. J. Spectroscopic Detection of Oral Cancer Using Lanthanide Chelate Complex as Topical Contrast Agent. Lasers in Surgery and Medicine. 2004, 160 Suppl. S16: 50.

Manning, H. C.; Goebel, T.; Thompson, R. C.; Bornhop, D. J. Targeted Molecular Imaging Agents for Cellular-Scale Bimodal Imaging. Bioconjugate Chemistry. 2004, 15 (6): 1488-1495.

Markov, D. A.; Dotson, S.; Wood, S.; Bornhop, D. J. Noninvasive Fluid Flow Measurements in Microfluidic Channels with Backscatter Interferometry. Electrophoresis. 2004, 25
(21-22): 3805-3809.

Markov, D. A.; Swinney, K.; Bornhop, D. J. Label-Free Molecular Interaction Determinations with Nanoscale Interferometry. Journal of the American Chemical Society. 2004, 126 (50): 16659-16664.

Z. Wang, Z.; Swinney, K.; and Bornhop, D. J. Attomole Sensitivity for Proteins and Polypeptides with On-chip CE and Universal Detection by Interferometric Backscatter. Electrophoresis. 2003, 24: 865-873.

Sorensen, H. S.; Pranov, H.; Larsen, N. B.; Bornhop, D. J. Absolute Refractive Index Determination by Microinterferometric Backscatter Detection. Analytical Chemistry. 2003, 75 (8): 1946-1953.

Bornhop, D. J.; Griffin, J. M. M.; Goebel, T. S.; Bornhop, D. J. Luminescent Lanthanide Chelate Contrast Agents and Detection of Lesions in the Hamster Oral Cancer Model. Applied Spectroscopy. 2003, 57 (10): 1216-1222.

H.C. Manning, H. C.; Goebel, T.; Marx, J. N.; and Bornhop, D. J. Facile, Efficient Conjugation of a Trifunctional Lanthanide Chelate to a Peripheral Benzodiazepine Ligand Analogue. Organic Letters. 2002, 4 (7): 1075-1078.

Griffin, J. M. M.; Skwierawska, A. M.; Manning, H. C.; Marx, J. N.; and Bornhop, D. J. Simple, High Yielding Synthesis of Trifunctional Fluorescent Lanthanide Chelates. Tetrahedron Letters. 2001, 42: 3823-3825.

Swinney, K.; Markov, D.; and Bornhop, D. J. Chip-Scale Universal Detection using Backscattering Interferometry. Analytical Chemistry. 2000, 72: 2690-2695. (This was an Accelerated Article.).

Bornhop, D. J.; Hubbard, D. S.; Houlne, M. P.; Adair, C.; Kiefer, G. E.; Pence, B. C.; and Morgan, D. L. Fluorescent Tissue Site-Selective Lanthanide Chelate, Tb-PTCMB for Enhanced Imaging of Cancer. Analytical Chemistry. 1999, 71: 2607-2615.

Specialties

• VICB
• Bioanalytical Chemistry

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