Optical ¹⁴C Tracing for Biological and Pharmaceutical Applications Using Two-Color Cavity Ringdown Spectroscopy

Area of Science:

• Analytical Chemistry
• Spectroscopy
• Isotope Tracing

Background:

• Accelerator Mass Spectrometry (AMS) is the standard for ¹⁴C quantitation but is costly and has low throughput.
• Laser-based methods offer a potentially more accessible and efficient alternative.
• Two-color cavity ringdown spectroscopy (2C-CRDS) has shown promise for sensitive optical measurements of ¹⁴CO₂.

Purpose of the Study:

• To demonstrate the feasibility of a mid-IR 2C-CRDS detector for low-level ¹⁴C isotope tracing in biological and pharmaceutical applications.
• To assess the sensitivity, accuracy, and throughput of the 2C-CRDS system for ¹⁴C quantitation.
• To evaluate the potential of 2C-CRDS as a cost-effective, high-throughput alternative to AMS.

Main Methods:

• Utilized a mid-IR 2C-CRDS system to measure ¹⁴CO₂ absorption signals from combusted samples.
• Applied the 2C-CRDS ¹⁴C sensor to biochemical analysis and pharmaceutical studies.
• Investigated a flow-through ¹⁴CO₂ sampling scheme to improve measurement throughput.

Main Results:

• Achieved detection sensitivity and quantitation accuracy competitive with AMS, at a few parts per quadrillion ¹⁴C/C mole fraction.
• Demonstrated sub-fCi level quantitation of sample ¹⁴C activity with a minimum sample size of 3 mg of carbon.
• Current throughput is ~25 min/sample, limited by sample processing, with potential for improvement to a few minutes per sample.

Conclusions:

• The 2C-CRDS ¹⁴C sensor is a feasible and competitive technology for low-level isotope tracing.
• The system offers high sensitivity and accuracy, making it suitable for biological, pharmaceutical, and clinical studies.
• Potential for revolutionizing ¹⁴C tracing due to improved efficiency, lower cost, and compact size.