This PDF file contains the front matter associated with SPIE Proceedings Volume 12863, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

False positives from breast cancer screenings lead to billions of dollars of waste and suffering every year. X-ray diffraction of breast tissue for cancer detection is a promising technique that can potentially be used to reduce the significant number of unnecessary biopsies by first scanning suspicious areas, rather than performing a biopsy straightaway. Breast tissue diffraction patterns contain information about the structure and density of constituent fiber molecular structures, such as fatty acids and collagen. These structural biomarkers are known to change due to the presence of tumors. We ran a pilot study with biopsies from 38 cancer patients that were scanned using a low-cost diffractometer. Our diagnostic algorithm achieved an overall performance of 96.3% sensitivity, 91.6% specificity, and 93.4% positive predictive value based on a random train-test split. We believe X-ray diffraction technology is mature enough to be integrated into the clinical setting in the near future.

Quantum states of light allow for highly sensitive biosensing configurations, surpassing the limitations imposed by shot-noise. In this theoretical study, we focus on optical plasmonic sensors, which have extensive applications in disease diagnostics, including detection of diseases like HIV. Our investigation involves simulating the impact of quantum states of light, such as the NOON state and squeezed states, on enhancing the limit of detection in a plasmonic phase-sensing biosensor, surpassing coherent light states’ shot-noise limit. Specifically, we explore the use of quantum states to improve the limit of detection in phase-based biosensors for HIV detection, operating below the shot-noise limit. Through our analysis, we demonstrate that incorporating quantum states of light in surface plasmon resonance (SPR) biosensing leads to enhanced performance compared to classical states. Moreover, we take into account the impact of environmental losses in the biosensing setup, considering the real-world challenges in practical implementation. Our findings emphasize the potential of quantum SPR biosensors in the development of novel disease diagnostics devices.

Microtubules are self-assembling biological helical nanotubes made of the protein tubulin that are essential for cell motility, cell architecture, cell division, molecular signaling, and intracellular trafficking. It has been hypothesized that this hollow molecular nanostructure may support optical transitions in photoexcited tryptophan, tyrosine, or phenylalanine amino acid lattices to function as a light-harvester in similar fashion as photosynthetic units; this ability coupled with its shape is analogous to a quantum wire. In support of this, recent experimental work demonstrates that electronic energy can diffuse across microtubules in a manner that cannot be explained by conventional Förster theory making them effective light harvesters. Here we present theoretical work of energy transfer between amino acids in tubulin via dipole excitations in the presence and absence of a chemical perturbation. Results demonstrate the potential for chemical manipulation of the optical properties of aromatic amino acid lattices in microtubule protein structures.

Base stacking is fundamentally important to the stability of double-stranded DNA. However, few experiments can directly probe the local conformations and conformational fluctuations of the DNA bases. Here we report a new spectroscopic approach to study the local conformations of DNA bases using the UV-absorbing fluorescent guanine analogue, 6-methyl isoxanthopterin (6-MI), which can be used as a site-specific probe to label DNA. In these experiments, we apply a two-photon excitation (2PE) approach to two-dimensional fluorescence spectroscopy (2DFS), which is a fluorescence-detected nonlinear Fourier transform spectroscopy. In 2DFS, a repeating sequence of four collinear laser pulses (with center wavelength ~ 675 nm and relative phases swept at radio frequencies) is used to excite the lowest energy electronic-vibrational (vibronic) transitions of 6-MI (with center wavelength ~ 340 nm). The ensuing low flux fluorescence is phase-synchronously detected at the level of individual photons and as a function of inter-pulse delay. The 2PE transition pathways that give rise to electronically excited state populations include optical coherences between electronic ground and excited states and non-resonant (one-photon-excited) virtual states. Our results indicate that 2PE-2DFS experiments can provide information about the electronic-vibrational spectrum of the 6-MI monomer, in addition to the conformation-dependent exciton coupling between adjacent 6-MI monomers within a (6-MI)₂ dimer. In principle, this approach can be used to determine the local base-stacking conformations of (6-MI)₂ dimer-substituted DNA constructs.

Fluorescence microscopy has become integral to biological studies for the technique’s ability to elucidate structures of biomolecules for in-situ studies with high selectivity and specificity. Imaging of intrinsic indicators, such as fluorescent amino acids in proteins, provides important information, but can be challenging to accomplish. Current microscopy techniques that measure native fluorescence without the use of exogenous labels involve either direct UV excitation which is commonly non-localized and can be detrimental to the system, or multiphoton absorption which must be conducted at high intensities, therefore posing high risks of photodamage. As such, we seek to investigate an efficient way to gently excite native fluorescence in biological systems in a way that overcomes these limitations. Quantum entangled photon pairs generated via spontaneous parametric downconversion (SPDC), may be an alternative to conducting two-photon absorption (TPA) to excite fluorescence in amino acids without the high fluences currently used. These photon pairs are highly correlated in time. Thus, the arrival of one photon is simultaneously followed by the arrival of its sister photon. As a result, a molecule interacting with the photon pair should simultaneously absorb both photons, leading to a linear two-photon absorption rate, and the linearity of the two-photon process should dramatically reduce the light intensity necessary for TPA. Therefore, quantum entangled photon pairs offer the possibility of performing low intensity UV excitation using photons in the visible wavelength range. With this work, we generated and characterized entangled photons generated via SPDC, and investigated whether fluorescent amino acids can be excited, and the subsequent fluorescence induced with entangled two-photon absorption. Results show that much higher entangled two-photon rates than what are currently available are needed to measure significant signals with entangled two-photon excitation.

Quantum ghost imaging can be an important tool in making optical measurements. One of the most useful aspects of ghost imaging is the unique ability to correlate two sets of independently collected information. We aim to use the principles of ghost imaging to build out a 3-dimensional microscope which utilizes detection from two imaging detectors that simultaneously capture entangled light. Further advancements and application of this relatively new imaging method depends on understanding the limits of the optical system. What quality should we expect? Can we image out-of-focus objects? How long do we need to expose? For ghost imaging, these answers are not so obvious. This is because entangled light sources are atypical: the light profile, frequency distribution, and intensity, for instance, all depend on an assortment of parameters associated with how the entangled light was generated. While we cannot practically explore the extent of this configuration space, we present here an exploration of a very accessible range. We show in which ways a commonly used bulk non-linear crystal can alter the imaging capabilities. In this study, we utilize a pair of state-of-the-art, single-photon avalanche diode (SPAD) array detectors. Thus, we also use this study as an opportunity to demonstrate the capabilities of these detectors in their use for ghost imaging applications.

Networks of interacting molecular optical dipoles play an important role in photosynthetic light harvesting, and also hold significant promise for future artificial technologies. This manuscript gives a brief overview of questions addressed by (our) recent theoretical work with a focus on taking inspiration from biological structures and processes to come up with designs for utilising bio-inspired collective quantum optical effects. These could, for instance, enable quantum-enhanced light harvesting, the charging of Dicke quantum batteries through superabsorption of light, and achieving efficient long-range energy transport. Particular attention is given to the role of inter-emitter quantum coherence as an enabler of these effects.

FCP, or Fucoxanthin Chlorophyll Protein, is a Light Harvesting Complex that can be found in diatoms and brown algae. One of its interesting features is its ability to efficiently capture blue-green light, which is due to the presence of specific chromophores such as fucoxanthin, chlorophyll a, and chlorophyll c. Recently, researchers were able to solve the crystallographic structure of FCP, providing insight into the arrangement of pigments within the protein scaffold. This information helps with interpreting the spectroscopic characteristics of FCP, but also raises questions about potential interactions between fucoxanthin and chlorophyll c, which have yet to be experimentally observed despite their spatial proximity. To investigate this possibility, two-dimensional electronic spectroscopy was used to study the rapid relaxation dynamics of FCP. The experiments showed an immediate spread of the excitation between fucoxanthin and chlorophyll c, indicating that there is a significant coupling between the chromophores.

There is a great promise in utilizing shallow paramagnetic luminescent defects such as NVcenters in conjunction with spin-labeled receptor proteins in biological and chemical sensing. One of the major challenges is the accurate and efficient placement of the receptor protein in the close vicinity of the luminescent center deposited within the host material. We analyze the FRET-driven functionalization of the surface, where the emission of the luminescent center serves as a donor of the excitation, and the photolabile group on the surface as the acceptor. The efficiency of biological detection with a combination of spin-labeled protein receptor and a shallow NV- center is considered.

The deoxyribose moiety of a nucleotide in the DNA molecule can act as a quantum logic gate, in which the enantiomeric shift between the C2-endo and C3-endo conformations of each nucleotide, occurs within a logically and thermodynamically reversible situation of electron spin qubits, that are coherently held within the topologically insulating DNA crystalline nanostructure, and that are coherently conducted along the delocalized electrons of the pi-stacked nucleotide base pairs. The enantiomeric symmetry between the C2-endo and C3-endo conformations is logically and thermodynamically reversible because it functions as a symmetry-breaking Szilard engine that is effectively built out of the physicality of the information by which it functions, and therefore does not require information erasure to maintain function. Such a quantum logic gate is analogous to a Toffoli gate which operates across an energy barrier appropriate to the Landauer limit, to roll the DNA base pair and thereby break the pi-stacking coherence along a segment of the DNA molecule, thus effecting quantum-to-classical transition of information.

Local fluctuations of the sugar-phosphate backbones and bases of DNA (a form of DNA ‘breathing’) play a central role in the assembly of protein-DNA complexes. We present a single-molecule fluorescence method to sensitively measure the local conformational fluctuations of exciton-coupled cyanine [(iCy3)₂] dimer-labeled DNA fork constructs in which the dimer probes are placed at varying positions relative to the DNA fork junction. These systems exhibit spectroscopic signals that are sensitive to the local conformations adopted by the sugar-phosphate backbones and bases immediately surrounding the dimer probe label positions. The (iCy3)₂ dimer has one symmetric (+) and one anti-symmetric (–) exciton with respective transition dipole moments oriented perpendicular to one another. We excite single molecule samples using a continuous-wave, linearly polarized laser with its polarization direction rotated at a frequency of 1 MHz. The ensuing fluorescence signal is modulated as the laser polarization alternately excites the symmetric and anti-symmetric excitons of the (iCy3)₂ dimer probe. Phase-sensitive detection of the signal at the photon-counting level provides information about the distribution of local conformations and conformational dynamics. We analyze our data using a kinetic network model, which we use to parametrize the free energy surface of the system. In addition to observing DNA breathing at and near ss-dsDNA junctions, the approach can be used to study the effects of proteins that bind and function at these sites.

Fluorescence spectrum, intensity and decay measurements are powerful outputs to analyze molecular structure and energy transition in cellular biology and cytometry. Frequently, fluorescence measurements are made by photocurrent detection using Photomultiplier Tubes (PMTs) and recently using Avalanche Photo Diodes (APDs). To address the challenge of measuring nanosecond order fluorescence decay times on single cells, single photon detection technology has been developed using pixel-coupled Silicon Photo Multiplier (SiPM), GHz electronics and waveform analysis. As a result, photoelectron (PE) pulse widths of 500ps and saturation count of 1Gcps with 7 LOG dynamic range have been achieved. This capability enables detection of multiple fluorescence PE pulses during one START-STOP time interval measurement. Combined with high-speed pulsed excitation, it is possible to measure fluorescence intensity during the pulse excitation 10MHz repetition, 80ns ON time, and fluorescence decay during the 20ns OFF time. Statistically, measured decay time is different from currently defined decay time by impulse excitation. We named these techniques “time-correlated multiphoton counting (TCMPC)” and “successive molecular decay (SMD)” to distinguish from conventional definitions and methods. To confirm the techniques, the decay time of Rhodamine in polymer and other fluorescence materials was measured. To apply single photon detection to quantum flow cytometry, which involves several microseconds per event, full spectral detection with 42 channels from UV to IR wavelength and 10Gsps(100ps) data acquisition electronics is under development. SMD and TCMPC are innovative techniques to analyze single molecule behavior and structure and will be powerful tools to understand the quantum nature of biology.

The utilization of quantum resources can enhance the sensitivity of conventional measurement techniques beyond the standard quantum limit (SQL). The objective of quantum metrology is to enable such quantum enhancements in practical devices. To achieve this objective, it is essential to have devices that are compatible with existing quantum resources operating within the SQL. Plasmonic sensors are promising candidates among these devices since they are extensively employed in biochemical sensing applications. Plasmonic sensors exhibit a response to slight variations in the local refractive index, which manifests as a shift in their resonance response. This shift, in turn, induces changes in the amplitude and phase of the probing light. By utilizing quantum states of light, such as NOON states, squeezed states, or Fock states, to probe these sensors, the measurement noise floor can be lowered, enabling the detection of signals below the SQL. In this study, we compare two configurations of quantum plasmonic sensing: phase-based and amplitude-based. By considering the Quantum Cramér Rao bound for both configurations, we demonstrate that the phase-based configuration can more effectively exploit the available quantum resources than the amplitude-based configuration. A limitation of this work is that it did not consider loss.