Sensing nitriles with THz spectroscopy of urine vapours from cancers patients subject to chemotherapy

Abstract

A THz nonstationary high-resolution spectrometer based on semiconductor superlattice multipliers is applied to investigate the dynamics of urine composition for cancer patients treated with chemotherapy. The molecular urine composition of healthy volunteers and cancer patients was compared and contrasted. We have found a set of nitriles that either appeared after chemotherapy or increased in content, which are expected as a result of bio-chemical damage to the liver. While no damage can be detected at this stage by existing clinical methods, the identified nitriles are candidates for further large-scale systematic testing towards markers for nephrotoxicity of chemotherapy at an early stage of the treatment, when conventional diagnostics cannot identify substantial organ damage. Comparing the metabolite concentration dynamics with side effects during chemotherapy might then help individuate patients prone to severe complications and correct the treatment. Our devices are game-changers for THz spectroscopy of liquids: they allow spanning four different frequency ranges for a general evaluation of most substances found in the liquid and selecting a spectral interval that bypasses the strong absorption lines from substances such as water and ammonia, which may otherwise mask the detection of the target metabolites.

Figure 1

Experimental detection of the absorption spectral line of isobutyronitrile (i-C3H7CN) near the frequency f_c = 145.9481 GHz, measured in the sample of patient 2 before (solid, red) and after chemotherapy (solid, blue), together with the corresponding reference measurement for healthy volunteer 1 (dashed, green). There are two close lines near this frequency at f₋ = 145.9478961 GHz, characterized in the databases^, by Lg I = − 5.0754 and quantum numbers 38 5 33 ← 38 5 34 (v30 = 1) and f₊ = 145.9479272 GHz, with Lg I = − 5.0754 and quantum numbers 38 6 33 ← 38 4 34 (v30 = 1). These two lines overlap and are detected as one.

Figure 2

Experimental detection the absorption spectral lines of methyl butyronitrile (C₂H₅CHCNCH₃) near the frequency f_c1 = 145.6832 GHz and glycine conformer II (H₂NCH₂COOH) near the frequency f_c2 = 145.6864 GHz detected in the sample of patient 2 before (red) and after chemotherapy (blue), together with the corresponding reference measurement for healthy volunteer 1 (green). There are two close lines differing by less than tens of Hz for methyl butyronitrile, given in the databases^, at the frequency fc = 145.6833846 GHz, characterized by Lg I = − 4.9041 and quantum numbers (v = 0) 64 54 10 ← 64 53 11 and (v = 0) 64 54 11 ← 64 53 12. For glycine conformer II, there is only one line at the central frequency fc = 145.6860831 GHz, characterized by Lg I = − 3.1037 and quantum numbers 21 4 18 ← 20 4 17 in the databases^,.

Figure 3

Experimental detection of the absorption spectral line of ethanethiol (a-C2H5SH) measured in the sample of patient 2 before (solid, red) and after chemotherapy (solid, blue), compared with the corresponding reference measurement for healthy volunteer 1 (dashed, green). There are two quantum transitions near this frequency at f = 148.0132725 GHz, characterized in the databases^, by Lg I = − 5.5024 and quantum numbers 45 14 31 ← 46 13 34 and 45 14 32 ← 46 13 33.

Figure 4

Normalized output power $P_n/P_3$ for the 3rd, 6th, 9th, 12th and 15th harmonics. The input frequency is $\nu =$ 178 GHz and $\alpha =eEd/h\nu =$ 19.6. Using the vacuum impedance and frequencies in GHz the connection between the $\alpha$ parameter that leads to power control of the multiplication and the plane wave power in mW is $P_{\mathit{in}}\left(\mathrm{mW}\right)=29.6\times {10}^{-10}{\nu }^2{\alpha }^2.$ The experimental data are represented by (green) symbols, and the solid (blue) line is calculated using Refs.^–. Input parameters are obtained from NEGF calculations for the current–voltage using the nominal parameters for the sample, as provided by the sample grower.

Figure 5

Emitted harmonic powers as a function of plane wave power directly transmitted to the GaAs-AlAs SSLM and applied voltage. Each figure is independently normalized for easier visualization since, as shown in Fig. 4, there is a 3 order of magnitude drop in output from the 3rd to the 27th harmonic. From (a–d) the figures correspond to the 3rd, 6th, 9th and 12th harmonics of the input frequency at 178 GHz, i.e.: 534, 712, 890 and 1068 GHz. The power in the x-axis is calculated using the assumption of a plane wave. Using the vacuum impedance and frequencies in GHz the connection between the $\alpha$ parameter that leads to power control of the multiplication and the input plane wave power in mW is $P_{\mathit{in}}\left(\mathrm{mW}\right)=29.6\times {10}^{-10}{\nu }^2{\alpha }^2.$

Figure 6

Diagram describing the experimental setup where the radiation source and the receiving part (detection) are based on semiconductor superlattice multipliers and mixers (SSLMs).