The Haes Research Group focuses on synthesizing standard gold and/or silver nanostructures and subsequently modifying their surfaces with novel, perm-selective surface chemistries for the direct and quantitative detection of small molecules and metabolites. Surface enhanced Raman scattering (SERS) is used to directly detect the small molecules while the novel surface layers facilitate molecular transport and recognition specificity. In comparison to traditional biological recognition elements, perm-selective and/or imprinted surface chemistries replace antibodies and/or nucleic acid functionality and should be relatively more stable in terms of temperature, matrix, shelf life, and pH. Finally, these materials and detection platforms are integrated with macroscale (cuvette and well-plate) to capillary electrophoresis platforms for the ultimate analysis of small sample volumes with fast analysis times. In the future, we will further exploit perm-selective surface chemistries on SERS substrates for the direct transport and detection of trace molecules in complex sample matrices to address biological/environmental detection challenges.

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As the composition, shape, size, stability, and local environment of noble metal nanostructures change; characteristic colors which arise from their localized surface plasmon resonance (LSPR) are observed. This occurs when incident electromagnetic energy (aka light) is selectively absorbed and scattered by the nanostructures.

Our research objectives focus on the applications, characterization, and synthesis of these optically-active nanomaterials. Our research investigations fall into at least one of the following four categories:

  • Understanding the synthesis and quality control parameters for improving nanomaterials with reproducible structure-function properties
  • Improving solution-phase nanomaterial design for fundamental studies and applications involving surface-enhanced spectroscopy
  • Integrating nanomaterials with capillary or microchip electrophoresis for reducing the required sample volumes per measurement
  • Designing novel methods to better detect biological and chemical species using nanoparticle-enhanced spectroscopy and/or capillary electrophoresis.

Current applications include: anti-cancer drug metabolism, hormone metabolism, Parkinson's disease biomarker detection, Vitamin D and metabolite detection for asthma, osteoporosis & cystic fibrosis, and small molecule, drug, and explosives detection.

Understanding Nanoparticle Synthesis & Quality Control Issues
An Example of Filtration vs. Centrifugation:
QC Issues

What you do to your nanomaterials during preparation impacts their properties and structures

Over the past 15-20 years, an effort to synthesize nanostructures with a high degree of monodispersity in shape and size was sought. Despite these efforts, most solution-phase nanoparticle preparations or storage conditions yield some degree of nanostructure heterogeneity which will cause variations in the resulting chemical and physical properties of the nanomaterials. This lack of "quality control" leads to poor prediction of nanoscale properties and as a result, limited application reproducibility. For instance, nanoparticle purification using high g x force centrifugation can yield linear chains or clusters while low g x force centrifugation or filtration yields <5% of clustered nanoparticles. In other words, nanoparticles are like finicky biomolecules - what you do to them during storage and handling can impact their properties and function. In an effort to use nanoparticles in a reproducible manner, we have learned that quality control measures must be taken and understood.


Some of our Publications on this Topic

Perm-Selective Surfaces on Nanomaterials for Enhanced Spectroscopy
An Example of the Synthesis of Novel Caged Nanoparticles:
perm-selective nanoparticles

Evaluation of perm-selective surface chemistries on gold nanospheres with surface-enhanced Raman scattering (SERS)

Plasmonic nanoparticles are excellent substrates for enhancing spectroscopic signatures of molecules. Surface chemistry and surface energy are two nanoparticle parameters that must be considered for reproducible use of these materials for fundamental studies and in various applications. This is both a challenge and an opportunity. To address this, we synthesize solution-phase noble metal nanoparticles with perm-selective surface chemistries (i.e. surface chemistries that promote the selective diffusion of analytes near the metal surface) for applications in SERS.

Some of our Publications on this Topic

Reducing Sample Volumes Required per Assay using Capillary Electrophoresis
An Example of Improving Parkinson's Disease Biomarker Detection Limits:
CE and Nanoparticles

Impacting the detection of Parkinson's disease biomarkers using gold nanoparticles and capillary electrophoresis

We investigated the impact of gold nanoparticle surface chemistry and morphology to capillary electrophoresis separations. Gold nanoparticles are modified with self assembled monolayers (SAMs) composed of thioctic acid, 6-mercaptohexanoic acid, or 11-mercaptoundecanoic acid. NMR, extinction spectroscopy, zeta potential, X-ray photoelectron spectroscopy, and flocculation provided information regarding the morphology, surface chemistry, optical properties, surface charge, SAM packing density, and stability of the nanoparticles, respectively. Using well-characterized nanostructures, gold nanoparticle pseudostationary phases were integrated with capillary electrophoresis, and nanoparticle surface chemistry proved to be the most important parameter in achieving reproducible detection of Parkinson’s disease biomarkers.

Some of our Publications on this Topic

Improving Environmental and Health Diagnostics
An Example of Anti-Cancer Drug Metabolism and Inhibition:
SERS applications

Using spectroscopic and separation techniques to facilitate the direct and quantitative detection of drugs and metabolites

Leukemia treatment typically includes chemotherapy to force the disease into remission and additional anti-cancer therapy using anti-cancer drugs to prevent subsequent relapses. The go-to drug for the anti-cancer treatment for acute lymphoblastic leukemia is 6-mercaptopurine. For most patients, this drug must be used in combination with other medications to promote its anti-cancer properties. Personalized treatment is important because as with most drugs, 6-mercaptopurine is metabolized into active, inactive, and toxic metabolites by multiple enzymes. Because everyone exhibits different enzyme levels, personalized treatment is warranted; however, this process take a long time and/or the patient serves as a guinea pig, and symptoms are observed after a prescribed drug dosage. To combat the negative impacts this can have on patients, we are developing a novel method in which drug metabolism is monitored using capillary electrophoresis and/or SERS.

Some of our Publications on this Topic