Time-domain terahertz optoacoustics: manipulable water sensing and dampening Download: 848次
1 Introduction
Terahertz radiation, with wavelengths between 0.03 and 0.3 mm, can provide unique insights into the composition, structure, and dynamics of inorganic and biological materials unavailable with radiation of other frequencies.1
In this way, the strong absorption of terahertz radiation by water enables a range of analyses. On the other hand, it prevents other types of analysis, where the strong absorption drowns out absorption by the molecules of interest. To reduce this background, terahertz reflectance spectra or attenuated total reflectance spectra are obtained, or extremely thin samples are used.35
We wondered whether we could induce water itself to be a detector for interactions between terahertz radiation and water-rich samples, such as aqueous solutions and tissues. Relying on the water within the sample, rather than on external terahertz detectors to capture the terahertz radiation emitted from the surface of the sample, would avoid the limitation on measurement depth due to the strong absorption of water. Upon absorption of terahertz radiation, aqueous media heat up, inducing thermoelastic expansion that produces acoustic waves that can be detected, which is referred to as the opto- or photoacoustic effect.40
In this article, we present time-domain terahertz optoacoustics in analyzing water-rich samples, which enables water itself to be induced as a detector that directly detects the interactions between terahertz radiation and water in aqueous solutions and tissues. We demonstrate the significant potential of this method using agar-in-water phantoms,
2 Method
2.1 Experimental Setup and Data Acquisition
The THz-OA system presented here incorporates several unique characteristics that maximize the THz-OA signal from native tissues or aqueous solutions, while also allowing the dampening of signals from water to highlight signals from biomolecules of interest [
Fig. 1. Schematic for time-domain THz-OA measurement. (a) Schematic of the setup. MT, metal tape; , parabolic mirrors; PE, Peltier element; THz-OA, terahertz optoacoustic; TS, temperature sensor; UST, ultrasonic transducer. The light blue region represents the interaction area between the terahertz radiation and sample. (b) Amplitude of THz-OA signal from water measured by the UST as a function of the energy of the terahertz radiation measured by a terahertz pyroelectric detector. The best-fit line (dotted blue) is also shown.
The signals were detected using flat piezoelectric ultrasonic transducers (Olympus) with central frequencies of 1 to 2.5 MHz, according to the frequency range of simulated THz-OA signals of water (Fig. S4 in Supplementary Material). The signals were then amplified by a low-noise 50-dB amplifier (Usultratek), digitized at a sampling rate of
Microfluidic chips were custom-built to have a rear surface of polydimethylsiloxane (PDMS) (5 mm thick) and a front surface of PDMS (
Fig. 2. THz-OA responses from an agar-in-water phantom, water flowing through a microfluidic chip, and a fresh beef brisket slice. (a) Schematic of the production of THz-OA signal by an agar phantom of thickness after terahertz irradiation to a penetration depth l. I, II, and … denote the primary THz-OA signal and its echoes. (b) THz-OA signals in the time domain for three values. (c) First time-domain THz-OA signals from (b) were transformed to the frequency domain. (d) Schematic of the production of THz-OA signal by water circulating through a channel of depth on a microfluidic chip. A peristaltic pump drives water into the sample holder at the inlet, and the water exits at the outlet. (e) THz-OA signals in the time domain for three values. (f) THz-OA signals from (e) were transformed to the frequency domain. (g) Schematic of the production of THz-OA signal by ex vivo tissue, with the fatty and lean areas of interest marked. (h) Time-domain THz-OA signals from each area of interest. (i) THz-OA signals from (h) were transformed to the frequency domain.
The rear surface of the sample was covered with metal tape [
2.2 Samples
Cylindrical agar phantoms were prepared by mixing agar powder and distilled water in a mass ratio of 2.8:100. Phantom thickness
2.3 Basic Principles of Terahertz Optoacoustics
Illuminating an absorber with a short electromagnetic pulse leads to an initial optoacoustic pressure
In aqueous solutions, the parameters
The initial acoustic pressure is generated according to Eq. (1) and traverses the samples to the transducer.54 The detected signal will be affected by the spatial impulse response (SIR) and the electronic impulse response (EIR) of the transducer.48,55 The SIR is related to the shape and location of the transducer surface. The EIR is related to the properties of the piezoelectric crystal and the probe circuit. The final detected pressure can be expressed as
3 Results
First, we tested the detection of the time-domain THz-OA signals from water in different samples of agar-in-water phantoms, water in microfluidic chips, and
Next, we analyzed the variation in water’s THz-OA signal with varying sample thickness using a microfluidic chip, where we could accurately manipulate the penetration depth by altering the channel depth
To validate nondestructive THz-OA testing on biological samples, we applied this to slices
The experiments with agar-in-water phantoms, water in a microfluidic chip, and tissues
Fig. 3. Temperature dependence of the THz-OA signal of water. (a) Time-domain THz-OA signal of water at different temperatures. (b) The THz-OA signals from (a) were transformed to the frequency domain. (c) THz-OA amplitudes of water over the temperature range from 0°C to 5°C. The insets show the raw THz-OA signal at 0°C (dark blue) or 4°C (light blue).
This led us to ask whether the dampening of the water signal would allow isolation of the signal from biomolecular solutes of interest. To address this question, we measured NaCl aqueous solutions at light concentrations reaching the NaCl level in the human body.57 Time-domain analysis of signals from pure water and increasingly concentrated NaCl solutions showed that the transmitted amplitude measured by the commercially available THz-TDS system cannot be effectively distinguished with concentrations less than
Fig. 4. Concentration dependence of the time-domain THz-OA signal of NaCl solutions with light concentrations at 24°C and 5°C. (a) THz-TDS profiles of pure water and increasingly concentrated NaCl solutions. Measurements were taken at 24°C. (b) THz-OA response of pure water and increasingly concentrated NaCl solutions at 24°C. (c) The same measurements were performed as in (b) but at 5°C. (d) Normalized amplitudes obtained for different NaCl concentrations in aqueous solution using the proposed THz-OA effect at 24°C (purple) and 5°C (black) and a commercially available THz-TDS (brown).
With sensitivity-enhanced time-domain terahertz optoacoustics, we also measure aqueous solutions of ions at high concentrations (see Fig. S2 in Supplementary Material) in order to study more characteristic parameters related to both terahertz absorption and ultrasonic propagation. The amplitudes of the THz-OA signals from pure water and increasingly concentrated
Fig. 5. Concentration dependence of THz-OA amplitude of and NaCl solutions with high concentrations at 24°C and 5°C. THz-OA amplitude of aqueous solutions of (a) and (b) NaCl before normalization (gray) and after normalization (blue). Measurements were taken at 24°C (solid bar and line) or 5°C (dotted bar and line).
4 Discussion and Conclusion
Using an ultrafast terahertz source and a conventional piezoelectric transducer, we detected time-domain THz-OA signals from agar-in-water phantoms,
We showed that terahertz optoacoustics can rely on water as a detector of terahertz radiation and that its detection sensitivity can be manipulated by altering temperature. By lowering the temperature of aqueous solutions of ions, we were able to mute the THz-OA contribution from water and enrich it for the contribution from solutes of interest. In fact, our system showed an order of magnitude greater sensitivity to changes in NaCl concentration than a commercially available THz-TDS system. Our method for the terahertz regime extends previous studies of optoacoustic spectroscopy of aqueous solutions in the near- and mid-infrared regimes, which established the potential of muting the water contribution.56,64 This water-manipulated THz-OA method can uniquely achieve sensitivity-enhanced label-free quantification of ion concentrations reaching the concentration level in the human body. More temperature- and concentration-related parameters related to both terahertz absorption and ultrasonic propagation can be acquired by THz-OA signals to potentially study the biological and chemical properties, such as the hydration number of ion solutions, through precise mathematical modeling. In addition, we have extended the proposed time-domain terahertz optoacoustics to characterize other biologically important solutes such as glucose and were able to reproduce these experimental results in simulations based on parameters in the literature (see Fig. S3 in Supplementary Material).51
The experimental setup in this work relies on a femtosecond laser amplifier and tilted-pulse-front excitation technology,43 which generates a more uniform terahertz pulse at safer energies than free-electron lasers.40,41 We used terahertz pulses lasting less than one picosecond in order to achieve stable and reproducible optoacoustic response without destructive shockwaves. Such short pulses with reasonable repetition rate and radiant exposure meet the laser limit needed for biological safety, which are unlike the terahertz pulses with excessively high repetition rate or high pulse energy that can influence protein structure or generate bubbles in liquid water.40,41
The experimental setup relies on a conventional piezoelectric ultrasonic transducer, which may perform more stably and at lower cost than an optical microring resonator.42 The universal ultrasonic transducers have been widely used in biomedical applications to detect both the transparent media and turbid samples, such as biotissues, while the shadowgraph imaging system in Refs. 40 and 41 can only obtain images of transparent samples. In addition, the conventional transducer can be upgraded with multiple channels, allowing simultaneous collection of THz-OA signals from multiple absorbers or even multidimensional THz-OA imaging. Our microfluidic chip was fabricated using PDMS, which allows efficient transmission of THz-OA signals to the detector.42 It is possible that derivatives of this polymer or even other materials may increase the intensity of acoustic waves arriving at the detector.
The proposed time-domain THz-OA method can directly reflect interactions between samples and multispectral terahertz radiation, rather than interactions between samples and optoacoustic waves in Refs. 40 and 41. To identify different target molecules based on their THz-OA fingerprints, it may be possible to use tunable, narrow-spectrum terahertz radiation sources or custom-designed contrast agents. Tunable terahertz sources would allow multispectral detection as well as functional imaging analogous to multispectral optoacoustic tomography,65
The ability of this time-domain THz-OA method to span such a large thickness range makes it well suited for optical- and acoustic-resolution microscopy as well as endoscopy. Terahertz optoacoustics offers far more potential than traditional terahertz imaging, in which information is obtained about a super thin layer on the surface of a sample based on reflection or transmission of terahertz radiation relative to a reference signal. In biomedical applications of traditional terahertz imaging, image contrast is strongly limited by the water content of the sample, and spatial resolution is limited by the terahertz diffraction limit.7,31,68 Indeed, terahertz optoacoustics offers the same imaging advantages as optoacoustics in other wavelength regimes. Regardless of wavelength, optoacoustics offers much deeper penetration than optical microscopy because acoustic waves are scattered orders of magnitude less than light waves as they pass through the sample.47 Another advantage is that optoacoustic signals can contain structural as well as functional information because the initial optoacoustic pressure is related to the functional parameters of samples such as absorption coefficient and thermal expansion coefficient (see Sec.
The time-domain THz-OA method described here may provide a foundation for innovations in spectroscopy and imaging. These include new terahertz-based platforms for biomedicine and chemistry, in particular, such as THz-OA spectroscopy, THz-OA imaging, THz-OA microscopy, THz-OA endoscopy, and multispectral THz-OA functional/molecular imaging.
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Article Outline
Jiao Li, Yixin Yao, Liwen Jiang, Shuai Li, Zhihao Yi, Xieyu Chen, Zhen Tian, Weili Zhang. Time-domain terahertz optoacoustics: manipulable water sensing and dampening[J]. Advanced Photonics, 2021, 3(2): 026003.