Andrew Berlin

Single-molecule detection of biomolecules by surface-enhanced coherent anti-Stokes Raman scattering

We report on the applicability of combining surface-enhanced Raman scattering (SERS) with coherent anti-Stokes Raman scattering for high-sensitivity detection of biological molecules. We found that this combination of techniques provides more than 3 orders of signal enhancement compared with SERS and permits monitoring of biological molecules such as deoxyguanosine monophosphate (dGMP) and deoxyadenosine monophosphate at the single-molecule level. This combined technique also improved detection sensitivity for angiotensin peptide. As this is believed to be the first report of detection of dGMP at the single-molecule level, we suggest that this approach can serve as a new tool for biological studies.

Microfluidic operations using deformable polymer membranes fabricated by single layer soft lithography

We show that it is possible to use single layer soft lithography to create deformable polymer membranes within microfluidic chips for performing a variety of microfluidic operations. Single layer microfluidic chips were designed, fabricated, and characterized to demonstrate pumping, sorting, and mixing. Flow rates as high as 0.39 microl min(-1) were obtained by peristaltic pumping using pneumatically-actuated membrane devices. Sorting was attained via pneumatic actuation of membrane units placed alongside the branch channels. An active mixer was also demonstrated using single-layer deformable membrane units.

Specific Chemical Effects on Surface-Enhanced Raman Spectroscopy for Ultra-Sensitive Detection of Biological Molecules

Achieving high signal amplification in surface-enhanced Raman scattering (SERS) is important for reaching single molecule level sensitivity and has been the focus of intense research efforts. We introduce a novel chemical enhancer, lithium chloride, that provides an additional order of magnitude increase in SERS relative to previously reported enhancement results. We have duplicated single molecule detection of the DNA base adenine that has previously been reported, thereby providing independent validation of this important result. Building upon this work, we show that the chemical enhancer LiCl produces strong SERS signal under a wide range of experimental conditions, including multiple laser excitation wavelengths and target molecule concentrations, for nucleotides, nucleosides, bases, and dye molecules. This is significant because while selection of anions used in chemical enhancement is well known to affect the degree of amplification attained, cation selection has previously been reported to have no major effect on the magnitude of SERS enhancement. Our findings indicate that cation selection is quite important in ultra-sensitive SERS detection, opening the door to further discussion and theory development involving the role of cations in SERS.

Ultrasensitive detection and manipulation of biomolecules

Intels Precision Biology research effort is working to combine Intels expertise in nanotechnology with aspects of biology and medicine to create highly sensitive instrumentation for biomolecular analysis. The ability to manipulate, detect, and identify biological molecules at ultra-low concentrations is important for applications ranging from whole-genome DNA sequencing to protein-based early disease detection. In this paper we describe our work to develop a molecular labeling system based on Surface-Enhanced Raman Spectroscopy (SERS), to enable highly sensitive protein detection. We also present a variety of techniques our team has developed for microfluidic transport and identification of single molecules in solution.