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Quantum-elevated Chiral Discrimination for Bio-molecules

Yiquan Yang, Xiaolong Hu, Wei Du, Shuhe Wu, Peiyu Yang, Guzhi Bao, Weiping Zhang

Abstract

Chiral discrimination of enantiomeric biomolecules is vital in chemistry, biology, and medicine. Conventional methods, relying on circularly polarized light, face weak chiroptical signals and potential photodamage. Despite extensive efforts to improve sensitivity under low-photon exposure, classical chiral probes remain fundamentally bounded by the shot-noise limit due to quantum fluctuations. To beat these limitations, we demonstrate quantum-elevated chiral discrimination using continuous-variable polarization-entangled states as moderate-photon-flux, high-sensitivity, quantum-noise-squeezed chiral probes. We achieve a 5 dB improvement beyond the SNL in distinguishing L- and D-amino acids in liquid phase. This non-destructive, biocompatible protocol enables high-sensitivity chiral analysis, with broad implications for drug development, biochemical research, environmental monitoring, and asymmetric synthesis.

Quantum-elevated Chiral Discrimination for Bio-molecules

Abstract

Chiral discrimination of enantiomeric biomolecules is vital in chemistry, biology, and medicine. Conventional methods, relying on circularly polarized light, face weak chiroptical signals and potential photodamage. Despite extensive efforts to improve sensitivity under low-photon exposure, classical chiral probes remain fundamentally bounded by the shot-noise limit due to quantum fluctuations. To beat these limitations, we demonstrate quantum-elevated chiral discrimination using continuous-variable polarization-entangled states as moderate-photon-flux, high-sensitivity, quantum-noise-squeezed chiral probes. We achieve a 5 dB improvement beyond the SNL in distinguishing L- and D-amino acids in liquid phase. This non-destructive, biocompatible protocol enables high-sensitivity chiral analysis, with broad implications for drug development, biochemical research, environmental monitoring, and asymmetric synthesis.

Paper Structure

This paper contains 10 sections, 5 equations, 5 figures.

Figures (5)

  • Figure 1: Schematic Diagram of Quantum-elevated Chiral Discrimination. The continuous-variable entangled state, created by superposing a pair of two-mode parametric amplifiers (PAs), functions as a quantum-elevated chiral probe to discriminate enantiomers. PAs are implemented using $^{85}$Rb atomic ensembles via four-wave mixing process. As illustrated in the inset, the polarization of light experiences either clockwise or counterclockwise rotation upon interaction with L-amino acids or D-amino acids. The positivity and magnitude of this rotation serve as reliable indicators of handedness and concentration of chiral molecules. The panels in the 'Data Processing' procedure indicate that the entangled probe suppresses quantum fluctuations compared to the coherent probe. $\delta\hat{X}_{-} = \delta \hat{X}_{a,H-V} - \delta \hat{X}_{b,H-V} = (\delta \hat{a}_{3,H-V}^{\dagger} + \delta \hat{a}_{3,H-V}) - (\delta \hat{b}_{3,H-V}^{\dagger} + \delta \hat{b}_{3,H-V})$ and $\delta\hat{X}_{+} = \delta \hat{X}_{a,H+V} + \delta \hat{X}_{b,H+V} = (\delta \hat{a}_{3,H+V}^{\dagger} + \delta \hat{a}_{3,H+V}) + (\delta \hat{b}_{3,H+V}^{\dagger} + \delta \hat{b}_{3,H+V})$. By measuring the polarization intensity difference operators in dual modes with photodetectors and a spectral analyzer, the polarization rotation angle is accurately determined with quantum-elevated sensitivity.
  • Figure 2: Noise and signal-to-noise ratio (SNR) comparison between coherent and entangled probe. (a) Noise power spectrum measured by spectral analyser. The resolution bandwidth (RBW) and video bandwidth (VBW) are 30 kHz and 300 Hz, respectively. The balanced photodetector's (PDB) transimpedance gain is $10^5$ V/A with a bandwidth of 4 MHz. The purple curve denotes the shot noise limit of coherent state. The red curve represents the intensity-difference squeezing of the entangled state, reaching $\thicksim$6 dB of squeezing at 0.7 MHz. The spike near 1 MHz is due to the inherent noise of pump laser. The cyan curve denotes the electronic noise level of PDB. (b) Measured signal and noise spectra of the classical probe (purple) and quantum probe (red) for a half-wave plate (HWP) with its optical axis oriented at $0.5^{\circ}$ relative to the horizontal direction. The entangled probe achieves a $\thicksim$5 dB enhancement in SNR compared to classical probes. (c) SNR comparison between the classical (purple) and quantum (red) probe for different optical axis angles of the HWP. The RBW and VBW are set to 100 Hz and 1 Hz, respectively, for data collection in (b) and (c).
  • Figure 3: Chiral discrimination of L/D-Amino Acids. Under liquid-phase conditions, we measure L- and D-arginine at varying concentrations using both coherent and quantum-entangled probes. The shot-noise level (SNL) defines the minimum resolvable polarization rotation angle for coherent light, while the quantum-squeezed noise level (QSNL) represents the rotation angle achievable with entangled light due to suppressed quantum fluctuations. (a) The coherent probe exhibits reduced sensitivity in detecting small rotation angles compared to the entangled case. (b) At equivalent photon flux, the entangled probe enables improved resolution of polarization rotations $\Delta\theta$ and $-\Delta\theta$, corresponding to left- and right-handed enantiomers, respectively. All data represent the average of five independent measurements. Shaded regions of the fitted linear curves represent 95% confidence intervals.
  • Figure 4: Enantiomeric excess determination of mixed L/D-Amino Acids. Under liquid-phase conditions, we measure the enantiomeric excess (e.e.) of L/D-arginine mixtures at varying concentrations using both coherent and quantum-entangled probes. The shot-noise level (SNL) and quantum-squeezed noise level (QSNL) determine the minimum resolvable e.e. achievable with coherent (a) and entangled (b) probes, respectively, as indicated by black and red star. At equal photon flux, the entangled probe exhibits enhanced sensitivity, enabling more precise discrimination of e.e., corresponding to the imbalance between left- and right-handed enantiomers. All data represent the average of five independent measurements. Shaded regions of the fitted linear curves represent 95% confidence intervals.
  • Figure 5: Experimental setup. Our experimental setup comprises three main modules: state preparation, phase stabilization, and quantum sensing. In the state preparation module, a continuous-variable (CV) polarization-entangled state is generated. An atomic ensemble of rubidium (Rb) atoms is employed to generate correlated signal-idler beams through a four-wave mixing (FWM) process based on Raman interactions. Two coherent FWM processes are superimposed to produce the entangled state. The phase stabilization module is designed to stabilize the phase of the CV entangled state. Error signals are generated by detectors D1 and D2 and are fed into a PID controller. The PID controller outputs modulation signals to maintain phase stability. The quantum sensing module is utilized for chiral discrimination. Differential measurements of the signal and idler beams are conducted by detectors D3 and D4, respectively. The electronic signals from these detectors are sent to a Diff circuit, which subtracts the two signals and outputs the result to an electrical spectrum analyzer (ESA) for spectral analysis. Digital storage oscilloscopes (DSOs) monitor the stability of the entire setup. GT: Glan lens. D1-D4: Balanced Amplified Photodetectors. ESA: Electronic Spectral Analyzer. DSO: Digital Signal Oscilloscope. PID: Proportional-Integral-Derivative control systems. Diff: difference channel.