In recent years, we have developed several versatile analysis platforms for the manipulation and sensing of biomolecules, particularly for low-copy number molecule detection. In the first scenario, sub-30 nm insulating nanoconstriction, serving as molecular dam operating under the balance of negative dielectrophoresis (DEP), electrophoresis, and electroosmosis, enables protein enrichment of 10⁵-fold in 20 seconds [1], which can then be coupled with graphene-modified electrodes for sensitive electrochemical detection of peptides, cancer biomarkers, and cortisol [2-4] (Fig. 1). In the second scenario, an array of electrode nanogaps with sub-10 nm gap size function as templates for AC DEP-based molecular trapping, plasmonic hot spots for surface-enhanced Raman spectroscopy as well as electronic measurements, and fluorescence imaging (Fig. 2), demonstrated with R-phycoerythrin [5] and Alzheimer’s disease candidate biomarkers A-beta 40 and 42 peptides. In the third scenario, we implemented nanoslit as a cost-effective nanofluidic-based immunosensor for low-noise real-time kinetic measurement of fluorescently labeled protein binding (Fig. 3), with a limit of detection down to 1 pM, regardless of the analyte size [6]. Further, a 10 nm deep sub-nanoliter fluidic nanochannels is developed on germanium crystal for attenuated total reflection infrared (ATR-IR) spectroscopy for ultralow volume (~650 pL) molecular characterization [7] (Fig. 4). Our platforms open up simple ways for low-concentration or low-volume sample analysis.