1. Multiplexed single molecule immunoassays.

    Lab On a Chip 13(15):2902 (2013) PMID 23719780

    We have developed a method that enables the multiplexed detection of proteins based on counting single molecules. Paramagnetic beads were labeled with fluorescent dyes to create optically distinct subpopulations of beads, and antibodies to specific proteins were then immobilized to individual su...
  2. Multiplexed single molecule immunoassays.

    Lab On a Chip 13(15):2902 (2013) PMID 23719780

    We have developed a method that enables the multiplexed detection of proteins based on counting single molecules. Paramagnetic beads were labeled with fluorescent dyes to create optically distinct subpopulations of beads, and antibodies to specific proteins were then immobilized to individual su...
  3. Single molecule enzyme-linked immunosorbent assays: theoretical considerations.

    Journal of Immunological Methods 378(1-2):102 (2012) PMID 22370429 PMCID PMC3327511

    We have developed a highly sensitive immunoassay-called digital ELISA-that is based on the detection of single enzyme-linked immunocomplexes on beads that are sealed in arrays of femtoliter wells. Digital ELISA was designed to be highly efficient in the capturing of target proteins, labeling of ...
  4. Single molecule enzyme-linked immunosorbent assays: Theoretical considerations

    Journal of Immunological Methods 378(1-2):102 (2012)

    We have developed a highly sensitive immunoassay—called digital ELISA—that is based on the detection of single enzyme-linked immunocomplexes on beads that are sealed in arrays of femtoliter wells. Digital ELISA was designed to be highly efficient in the capturing of target proteins, la...
  5. Isolation and detection of single molecules on paramagnetic beads using sequential fluid flows in microfabricated polymer array assemblies.

    Lab On a Chip 12(5):977 (2012) PMID 22179487

    We report a method for isolating individual paramagnetic beads in arrays of femtolitre-sized wells and detecting single enzyme-labeled proteins on these beads using sequential fluid flows in microfabricated polymer array assemblies. Arrays of femtolitre-sized wells were fabricated in cyclic olef...
  6. Isolation and detection of single molecules on paramagnetic beads using sequential fluid flows in microfabricated polymer array assemblies.

    Lab On a Chip 12(5):977 (2012) PMID 22179487

    We report a method for isolating individual paramagnetic beads in arrays of femtolitre-sized wells and detecting single enzyme-labeled proteins on these beads using sequential fluid flows in microfabricated polymer array assemblies. Arrays of femtolitre-sized wells were fabricated in cyclic olef...
  7. Simultaneous detection of single molecules and singulated ensembles of molecules enables immunoassays with broad dynamic range.

    Analytical chemistry 83(6):2279 (2011) PMID 21344864 PMCID PMC3056883

    We report a method for combining the detection of single molecules (digital) and an ensemble of molecules (analog) that is capable of detecting enzyme label from 10(-19) M to 10(-13) M, for use in high sensitivity enzyme-linked immunosorbent assays (ELISA). The approach works by capturing protei...
  8. Simultaneous detection of single molecules and singulated ensembles of molecules enables immunoassays with broad dynamic range.

    Analytical chemistry 83(6):2279 (2011) PMID 21344864 PMCID PMC3056883

    We report a method for combining the detection of single molecules (digital) and an ensemble of molecules (analog) that is capable of detecting enzyme label from 10(-19) M to 10(-13) M, for use in high sensitivity enzyme-linked immunosorbent assays (ELISA). The approach works by capturing protei...
  9. Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid β levels in humans.

    PLoS ONE 6(12):e28263 (2011) PMID 22194817 PMCID PMC3237426

    Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brai...
  10. Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid β levels in humans.

    PLoS ONE 6(12):e28263 (2011) PMID 22194817 PMCID PMC3237426

    Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brai...
  11. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations.

    Nature Biotechnology 28(6):595 (2010) PMID 20495550 PMCID PMC2919230

    The ability to detect single protein molecules in blood could accelerate the discovery and use of more sensitive diagnostic biomarkers. To detect low-abundance proteins in blood, we captured them on microscopic beads decorated with specific antibodies and then labeled the immunocomplexes (one or...
  12. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations.

    Nature Biotechnology 28(6):595 (2010) PMID 20495550 PMCID PMC2919230

    The ability to detect single protein molecules in blood could accelerate the discovery and use of more sensitive diagnostic biomarkers. To detect low-abundance proteins in blood, we captured them on microscopic beads decorated with specific antibodies and then labeled the immunocomplexes (one or...
  13. Use of colorimetric test strips for monitoring the effect of hemodialysis on salivary nitrite and uric acid in patients with end-stage renal disease: a proof of principle.

    Clinical Chemistry 54(9):1473 (2008) PMID 18676588 PMCID PMC2710817

    Initial screening of potential biomarkers for monitoring dialysis was performed with saliva samples collected from patients with end-stage renal disease (ESRD). A more thorough analysis of the most promising markers identified in the initial screening was conducted with saliva samples acquired a...
  14. Use of colorimetric test strips for monitoring the effect of hemodialysis on salivary nitrite and uric acid in patients with end-stage renal disease: a proof of principle.

    Clinical Chemistry 54(9):1473 (2008) PMID 18676588 PMCID PMC2710817

    Initial screening of potential biomarkers for monitoring dialysis was performed with saliva samples collected from patients with end-stage renal disease (ESRD). A more thorough analysis of the most promising markers identified in the initial screening was conducted with saliva samples acquired a...
  15. Distinct and long-lived activity states of single enzyme molecules.

    Journal of the American Chemical Society 130(15):5349 (2008) PMID 18318491

    Individual enzyme molecules have been observed to possess discrete and different turnover rates due to the presence of long-lived activity states. These stable activity states are thought to result from different molecular conformations or post-translational modifications. The distributions in k...
  16. Distinct and long-lived activity states of single enzyme molecules.

    Journal of the American Chemical Society 130(15):5349 (2008) PMID 18318491

    Individual enzyme molecules have been observed to possess discrete and different turnover rates due to the presence of long-lived activity states. These stable activity states are thought to result from different molecular conformations or post-translational modifications. The distributions in k...
  17. Stochastic inhibitor release and binding from single-enzyme molecules.

    PNAS 104(45):17680 (2007) PMID 17965235 PMCID PMC2077050

    Inhibition kinetics of single-beta-galactosidase molecules with the slow-binding inhibitor d-galactal have been characterized by segregating individual enzyme molecules in an array of 50,000 ultra small reaction containers and observing substrate turnover changes with fluorescence microscopy. In...
  18. Stochastic inhibitor release and binding from single-enzyme molecules.

    PNAS 104(45):17680 (2007) PMID 17965235 PMCID PMC2077050

    Inhibition kinetics of single-beta-galactosidase molecules with the slow-binding inhibitor d-galactal have been characterized by segregating individual enzyme molecules in an array of 50,000 ultra small reaction containers and observing substrate turnover changes with fluorescence microscopy. In...
  19. Microsensor arrays for saliva diagnostics.

    Annals of the New York Academy of Sciences 1098:389 (2007) PMID 17435144

    Optical fiber microarrays have been used to screen saliva from patients with end-stage renal disease (ESRD) to ascertain the efficacy of dialysis. We have successfully identified markers in saliva that correlate with kidney disease. Standard assay chemistries for these markers have been converte...
  20. Microsensor arrays for saliva diagnostics.

    Annals of the New York Academy of Sciences 1098:389 (2007) PMID 17435144

    Optical fiber microarrays have been used to screen saliva from patients with end-stage renal disease (ESRD) to ascertain the efficacy of dialysis. We have successfully identified markers in saliva that correlate with kidney disease. Standard assay chemistries for these markers have been converte...