Cerenkov radiation imaging as a method for quantitative measurements of beta particles in a microfluidic chip

Abstract

It has been observed that microfluidic chips used for synthesizing (18)F-labeled compounds demonstrate visible light emission without nearby scintillators or fluorescent materials. The origin of the light was investigated and found to be consistent with the emission characteristics from Cerenkov radiation. Since (18)F decays through the emission of high-energy positrons, the energy threshold for beta particles, i.e. electrons or positrons, to generate Cerenkov radiation was calculated for water and polydimethylsiloxane (PDMS), the most commonly used polymer-based material for microfluidic chips. Beta particles emitted from (18)F have a continuous energy spectrum, with a maximum energy that exceeds this energy threshold for both water and PDMS. In addition, the spectral characteristics of the emitted light from (18)F in distilled water were also measured, yielding a broad distribution from 300 nm to 700 nm, with higher intensity at shorter wavelengths. A photograph of the (18)F solution showed a bluish-white light emitted from the solution, further suggesting Cerenkov radiation. In this study, the feasibility of using this Cerenkov light emission as a method for quantitative measurements of the radioactivity within the microfluidic chip in situ was evaluated. A detector previously developed for imaging microfluidic platforms was used. The detector consisted of a charge-coupled device (CCD) optically coupled to a lens. The system spatial resolution, minimum detectable activity and dynamic range were evaluated. In addition, the calibration of a Cerenkov signal versus activity concentration in the microfluidic chip was determined. This novel method of Cerenkov radiation measurements will provide researchers with a simple yet robust quantitative imaging tool for microfluidic applications utilizing beta particles.

Figure 1

(a) Room light photograph of a microfluidic chip containing ¹⁸F-labeled compound residue in the microfluidic channels with a channel width of 200 μm. (b) Cerenkov signal image of the same microfluidic chip overlaid on the room light photograph (artificially colored).

Figure 2

A typical microfluidic chip cross section: (A) fluidic layer, (B) control layer and (C) substrate layer. The colored areas represent microchannels on the fluidic layer and the control layer, respectively. Fluids of interest are placed in a fluidic channel and their movement is controlled by pressure-actuated valves manipulated by microchannels on the control layer.

Figure 3

Schematic figure of the lens-coupled CCD system.

Figure 4

(a) Microfluidic chip geometry used for the signal calibration. (b) A room light photograph of the chip, used for signal calibration measurement, overlaid with artificially-colored Cerenkov signals.

Figure 5

Spectral characteristics of the emitted light from an aqueous ¹⁸F solution. The measured spectrum showed a broad and continuous distribution with higher intensity at shorter wavelengths. After the PMT quantum efficiency and the syringe transmittance corrections, the spectrum followed the theoretical Cerenkov emission spectrum from 300 nm to 580 nm, inversely proportional to the square of the wavelength.

Figure 6

Transmittance properties of PDMS from two manufacturers.

Figure 7

Cerenkov radiation imaging spatial resolution measurement. (a) A room light photographic image of a line pair microfluidic chip. The chip consisted of line channels with a thickness of 200 μm, and a spacing of 300 μm edge-to-edge. (b) A Cerenkov radiation image of the chip filled with [¹⁸F]FDG solution. The line pairs were clearly discernable.

Figure 8

Cerenkov radiation imaging spatial resolution measurement. (a) Artificially colored Cerenkov signal image overlaid on top of room light photograph of the line channel with a of 200 μm width. (b) A line profile of the microchannel. This resolution was dominated by the physical size of the channel.

Figure 9

The corresponding modulation transfer function (MTF) for the line profile of the channel from figure 8.

Figure 10

The system linearity and minimum detectable activity measurements.