Time-Evolved SERS Signatures of DEP-Trapped Aβ and ZnAβ Peptides Revealed by a Sub-10 nm Electrode Nanogap.

Alzheimer's disease (AD) has become highly relevant in aging societies, yet the fundamental molecular basis for AD is still poorly understood. New tools to study the undergoing structural conformation changes of amyloid beta (Aβ) peptides, the pathogenic hallmark of AD, could play a crucial role in the understanding of the underlying mechanisms of misfolding and cytotoxicity of this peptide. It has been recently reported that Zn interacts with Aβ and changes its aggregation pathway away from less harmful fibrillar forms to more toxic species.

Development of a focused high-energy macromolecular ion beam.

In this work, we report the development of a focused macromolecular ion beam with kinetic energy of up to 110 keV. The system consists of a quadrupole ion trap (QIT), einzel lens and linear accelerator (LINAC). Based on the combination of matrix-assisted laser desorption ionization (MALDI) and quadrupole ion trapping (QIT), ions were desorbed from the surface and trapped with an ion trap to form biomolecular ion packets.

A portable multiple ionization source biological mass spectrometer.

In the past, matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), used for large biomolecule detection, were usually installed in two separate mass spectrometers. In this study, they were equipped in the same mass spectrometer. This portable biological mass spectrometer has multiple ionization capabilities in the same mass spectrometer and shares the same mass analyzer and detector.

High Mass Ion Detection with Charge Detector Coupled to Rectilinear Ion Trap Mass Spectrometer.

Conventional linear ion trap mass analyzers (LIT-MS) provide high ion capacity and show their MS ability; however, the detection of high mass ions is still challenging because LIT-MS with secondary electron detectors (SED) cannot detect high mass ions. To detect high mass ions, we coupled a charge detector (CD) to a rectilinear ion trap mass spectrometer (RIT-MS). Immunoglobulin G ions (m/z ~150,000) are measured successfully with controlled ion kinetic energy.

Tandem array of nanoelectronic readers embedded coplanar to a fluidic nanochannel for correlated single biopolymer analysis.

We have developed a two-step electron-beam lithography process to fabricate a tandem array of three pairs of tip-like gold nanoelectronic detectors with electrode gap size as small as 9 nm, embedded in a coplanar fashion to 60 nm deep, 100 nm wide, and up to 150 μm long nanochannels coupled to a world-micro-nanofluidic interface for easy sample introduction. Experimental tests with a sealed device using DNA-protein complexes demonstrate the coplanarity of the nanoelectrodes to the nanochannel surface. Further, this device could improve transverse current detection by correlated time-of-flight measurements of translocating samples, and serve as an autocalibrated velocimeter and nanoscale tandem Coulter counters for single molecule analysis of heterogeneous samples.

Low-copy number protein detection by electrode nanogap-enabled dielectrophoretic trapping for surface-enhanced Raman spectroscopy and electronic measurements.

We report a versatile analysis platform, based on a set of nanogap electrodes, for the manipulation and sensing of biomolecules, as demonstrated here for low-copy number protein detection. An array of Ti nanogap electrode with sub-10 nm gap size function as templates for alternating current dielectrophoresis-based molecular trapping, hot spots for surface-enhanced Raman spectroscopy as well as electronic measurements, and fluorescence imaging. During molecular trapping, recorded Raman spectra, conductance measurements across the nanogaps, and fluorescence imaging show unambiguously the presence and characteristics of the trapped proteins.

Macromolecular ion accelerator mass spectrometer.

We present a newly developed macromolecular ion accelerator mass spectrometer that combines a dual-ion-trap device and a macromolecular ion accelerator (MIA) to achieve the capability of analyzing samples with a mixture of large biomolecules. MIA greatly increases detection efficiency. The dual ion trap includes a quadrupole ion trap (QIT) and a linear ion trap (LIT) in tandem.

Biomolecular dual-ion-trap mass analyzer.

We developed the first dual-ion-trap mass analyzer which can detect ions with a high mass-to-charge ratio (m/z > 6000). The first ion trap is a quadrupole ion trap (QIT), which was operated by step scanning of the trapping frequency for a sample containing mixtures of biomolecules. The second ion trap, linear ion trap (LIT), was utilized to capture selected ions ejected out of the QIT so that all ions from the QIT can be examined one by one.

Macromolecular ion accelerator.

Presented herein are the development of macromolecular ion accelerator (MIA) and the results obtained by MIA. This new instrument utilizes a consecutive series of planar electrodes for the purpose of facilitating stepwise acceleration. Matrix-assisted laser desorption/ionization (MALDI) is employed to generate singly charged macromolecular ions.

MALDI ion trap mass spectrometer with charge detector for large biomolecule detection.

Up to now, all commercial matrix-assisted laser desorption/ionization (MALDI) mass spectrometers still can not efficiently analyze very large biomolecules. In this work, we report the development of a novel MALDI ion trap mass spectrometer which can enrich biomolecular ions to enhance the detection sensitivity. A charge detector was installed to measure the large ions directly.

Charge monitoring cell mass spectrometry.

An instrument to directly measure the charge carried by a cell or a microparticle as well as mass-to-charge ratio of the cell/microparticle was developed for rapid mass distribution measurement. A successful mass spectrum with a record high mass has been demonstrated. In this article, the details of the construction and operation of the charge monitoring cell mass spectrometer are reported.