Remote, on site, and in situ analysis: Acquiring chemical information from analytes as they are, where they are
By and large, laboratory-based techniques and instrumentation are adequate for routine physicochemical analyses. At times, however, chemical analysis by traditional means becomes impractical due to limited sample access, lack of sample stability, the need for near-instantaneous data acquisition, or the sheer number of samples to be analyzed. In these cases, it is advantageous to supplement standard analytical techniques and tools with approaches that allow rapid remote, on-site, in situ and in vivo analysis—that is, examining samples “as they are, where they are”. The unique properties that many materials exhibit at the nanoscale provide unparalleled opportunities in these type of analyses. As a result, nanotechnology and nanomaterials will play a prominent role in our future research.
Our overall plans for remote, on-site, in situ, in vitro and in vivo analysis are far-reaching and will evolve as improved techniques, technology and materials become available. Three specific examples provide a good general summary of how we plan to enable remote, on-site, in situ, in vitro, and in vivo analysis:
1. We are designing fiber-optic nanoprobes for highly multiplexed in vitro biochemical analysis in single living cells;
2. We are developing techniques and instrumentation for non-contact remote, on-site and in situ analysis of biological and chemical hazards;
3. We are adapting and refining existing laboratory-based analytical methods to allow high-throughput on-site and in situ determination of the presence or absence of dangerous materials ranging from discrete chemicals to gene sequences.
Why Analyze Samples “As They Are, Where They Are?”
Chemical analysis can generally be split into three steps: Sample acquisition; sample preparation; and analyte quantitation. Sample acquisition often requires field work or hands-on chemical synthesis, but may be as simple as opening a package in the mail room. Sample preparation frequently involves stabilization, filtering, and/or extraction to separate analytes of interest from complex matrices or interferents. Analyte quantitation typically occurs days, months or occasionally years after samples are acquired. Potential pitfalls exist at every step of this process.
• Can samples be removed from their native environment?
• Can sufficient material be acquired to perform a traditional laboratory-based measurement?
• Are the samples safe to transport and store, or are the matrix or analytes be hazardous?
• Is the time required for analysis important? (i.e. is a building under lock-down, or is someone laying on an operating table awaiting the analytical results?)
• How many samples need to be examined? (i.e.. must contamination be mapped across square miles of brownfields, or does an entire neighborhood need to be profiled for the presence of lead-based paint or pipes?)
Alternative approaches are needed for the growing variety of measurements where little or no sample can be collected, the analyte is not sufficiently stable for delayed analysis, and when samples must be analyzed more rapidly than is allowed by traditional laboratory-based techniques and instrumentation. Optical spectroscopy is particularly well-suited to the real-time remote, on-site, in situ, in vitro and in vivo analyses which challenge traditional analytical techniques because it allows both elemental and molecular analysis within seconds for virtually any sample to which optical access exists. When coupled with the unique material properties encountered when moving from the macro to the micro to the nano scale, optical spectroscopy can provide sensitivity and selectivity which are currently unmatched by any existing field-portable analytical technique.
Left: A fiber optic nanosensor measuring the pH of a single living breast cancer cell acquired from a patient via RPFNA (a type of needle biopsy). We plan to develop similar nanosensors for a variety of biologically and biomedically-relevant analytes, such as reactive oxygen species, mRNA, and enxymes.
|Right: Sensing scheme for detection of enzymatic cleavage in vitro and ex vivo, meant to be used to test the effectiveness of anti-cancer drugs in patient cells. Similar sensing chemistry can be adapted for use in high-throughput "on-a-chip" type applications.|
|Left: Development of instrumentation to allow real-time cancer imaging in a doctor's office or the operating room. The goal is to improve diagnosis and tumor margin assessment, thereby decreasing the danger of metastasis and/or recurrence.|
|Right: Non-contact remote/stand-off detection of a potentially hazardous sample from a safe distance. Identification of hazards from a distance minimizes the danger of injury or death for first responders, technicians, etc. Potential analytes of interest include chemical or biological weapons, explosives, pesticides, and industrial hazards.|