Development of an Ultra-Small-Volume Detection and Sample Delivery System for Exploring Microscale Heterogeneity with NMR
EMSL Project ID
48587
Abstract
Microscale heterogeneity plays a key role in determining the outcome of attempts to decrease pollution, optimize industrial production for biotechnology, or understand cellular-level processes. Because of the unique capability of NMR to characterize biological and chemical systems in detail without significantly perturbing them, we seek to extend the reach of NMR spectroscopy to routine analysis of microscopic samples and enable it as a tool for studying the microscale variations that limit scientific, industrial, and medical capabilities. The current generation of commercial small-volume NMR detectors requires sample volumes of 5-10 microliters, and we intend to show that high-resolution NMR can be used for practical studies of volumes that are several orders of magnitude smaller, allowing for novel studies that address individual microsystems such as cells and aerosol particles. The methods and instrumentation that we are developing integrate high-resolution NMR spectroscopy with lab-on-a-chip technology for studying samples with volumes in the range of tens to hundreds of picoliters. Target applications will include cellular bioengineering, production of biofuels and biochemicals, analysis of metabolites, study of the structure and dynamics of aerosol particles, and characterization of batteries and battery materials. Objective: A longstanding limitation of high-resolution NMR spectroscopy is the need for samples with macroscopic dimensions (volume >= 5 microliter). We seek to overcome this limitation and perform the first high-resolution studies of microscopic samples (volume <= 0.5 nanoliter). We are developing an NMR probe that integrates a sensitive planar detector with a versatile microfluidic platform for sample delivery, and we intend to demonstrate that this probe can be used for a wide range of applications. A number of science drivers critical for BER programs will be addressed using this technology. In particular, programmatic priorities within the two divisions of BER (CESD and BSSD) focus on obtaining a predictive understanding of environmental systems and living organisms, as well as the coupling between energy production and the environment. EMSL science challenges have been set to “determine molecular-scale properties of organic aerosols (OA) that have greatest impact on atmospheric radiation and climate to improve accuracy of climate model predictions” and to “determine how the spatial organization and kinetics of biochemical pathways impact overall metabolism of a cell and model such processes”. These problems are among those directly driving our developments in small-volume NMR analysis Background: The inability to detect high-resolution NMR spectra of microscopic samples is a significant technical gap. As lab-on-a-chip technology assumes a more prominent role in a range of fields, the capability to integrate high-resolution NMR with microfluidic chips will become increasingly desirable. On a practical level, cost, waste, and risks to safety are typically minimized when microfluidic chips replace conventional tools for preparing and analyzing samples. On a fundamental level, the emerging capability to study individual microsystems such as biological cells or aerosol particles will yield understanding of microscopic heterogeneity and interaction dynamics. Such understanding is essential for in vitro cell culturing in biotechnology (El-Ali, Sorger et al. 2006), for example. The development of high-resolution NMR as a tool for studying microfluidic samples, including individual cells with micrometer dimensions, would be a notable technological and scientific advancement.
Project Details
Start Date
2014-10-01
End Date
2015-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members