Lewis Edward MacKenzie

The concept of the “infinitesimal machine surgeon” was envisaged by Feynman in 1959 and 1983, describing a miniature, human-controllable machine capable of being directed to biological tissue to perform a physical intervention. This perspective explores the potential of combining Feringa-type rotary molecular motors (nanomachines) with upconversion nanoparticles (UCNPs) to realise the vision of the infinitesimal machine surgeon. In this approach, UCNPs convert near-infrared (NIR) excitation into ultraviolet/visible (UV/Vis) emission to activate molecular nanomachines within biological tissue. The fundamental operating principles are outlined, recent experimental advances in powering molecular motors and UCNPs in organic solvents are reviewed. Simple biophotonic calculations based on the Beer–Lambert law suggest that upconversion from 808 nm to 450–475 nm may offer a promising excitation strategy for activating molecular motors in biological tissues. Key challenges to biological implementation are identified, including permissible tissue light-exposure levels and the effects of tissue absorption and multiple scattering on the photon budget available to drive UCNPs and molecular motors. Finally, experimental strategies for evaluating these systems in biologically relevant environments are proposed, in accordance with the 3Rs principles of biomedical research.

The concept of the “infinitesimal machine surgeon” was envisaged by Feynman in 1959/1983, describing a miniature, human-controllable machine capable of being directed to biological tissue to perform a physical intervention. This perspective explores the potential of combining Feringa-type rotary molecular motors (nanomachines) with upconversion nanoparticles (UCNPs) to realize the vision of the infinitesimal machine surgeon. In this approach, UCNPs convert near-infrared (NIR) excitation into ultraviolet/visible (UV/Vis) emission to activate molecular nanomachines within biological tissue. The fundamental operating principles are outlined, recent experimental advances in powering molecular motors and UCNPs in organic solvents are reviewed. Simple biophotonic calculations based on the Beer–Lambert law suggest that upconversion from 808 nm to 450–475 nm may offer a promising excitation strategy for activating molecular motors in biological tissues. Key challenges to biological implementation are identified, including permissible tissue light-exposure levels and the effects of tissue absorption and multiple scattering on the photon budget available to drive UCNPs and molecular motors. Finally, experimental strategies for evaluating these systems in biologically relevant environments are proposed, in accordance with the 3Rs principles of biomedical research.

Mirror life presents a low-likelihood but high-severity global biosecurity threat that has attracted the attention of bioscientists, governments and international security organizations. However, current analytical techniques are not fit to identify mirror life biohazards. Herein, we propose the first assay method for screening against mirror life. This approach is based upon optical circularly polarized luminesce (CPL) signatures generated by fluorescent probes, which bind to subcellular targets (e.g. membranes, organelles, nucleic acids, etc.). Probes can either be achiral or be intrinsically chiral. We set out why a multi-probe reporter panel approach incorporating many CPL-generating probes is necessary to identify mirror life with a high degree of confidence (i.e. avoiding false positives). The distinct CPL signatures can be analysed via recent innovations in CPL detection, i.e. rapid CPL spectroscopy, CPL microscopy (enantioselective differential chiral contrast, EDCC, imaging) and CPL EDCC cameras. While these are advanced technologies, they share the same fundamental optical principles as three-dimensional cinema glasses and so are amenable to scaling and portable applications. The CPL assay approach to mirror life screening could be a useful tool for screening against mirror life biohazards and ensuring compliance with any potential future international legislation against mirror-life research.

The concept of the infinitesimal machine surgeon: a tiny nano-sized machine with moving parts “akin to a little knife”; which is guided to a biological target; and which is human controlled via an electromagnetic input; was loosely envisaged by Feynman two influential lectures in 1959 and 1983. In this perspective, we examine how chemistry – not physics - may be on the cusp on creating a true infinitesimal machine surgeon. We extract four key criteria for an infinitesimal machine surgeon. We set out how nanomachines – light activated molecular rotors – can trigger cell death via mechanical action, and highlight the recently demonstrated combination of nanomachines and photonic upconversion nanoparticles (UCNPs), which enable control of nanomachines with near-infrared (NIR) light. This advancement conceivably enables the ability to control nanomachines in deep tissue (> 1 cm) using diffuse NIR illumination, surpassing depth limits of conventional and two photon excitation (2PE) of nanomachines. We set out directions for future development of nanomachines and UCNPs, for deep-tissue applications, including opportunities for targeted delivery and multi-modal tracking. With sufficient development, we expect the conjunction of UCNPs and nanomachines can fulfil all four criteria to be considered an infinitesimal machine surgeon.

Life on Earth is predominately based upon a single chirality set, but so-called “mirror life” - speculated life of the opposite chirality, either of artificial or natural origin - presents a low-likelihood, but high severity global biosecurity threat. Such an existential risk necessitates that technologies for surveillance and containment of mirror life are developed as a contingency. In this perspective, we propose a method for screening against mirror life hazards via an optical chirality assay, based upon circularly polarized luminescence (CPL) generated either via achiral fluorophores (via supramolecular chirality effects) or intrinsically chiral molecular probes. When bound to biological molecules, CPL-generating probes enable Enantioselective Differential Chiral Contrast (EDCC) imaging to verify chirality of a biological specimen. We set out why a multi-reporter panel approach – incorporating many CPL generating fluorescent/luminescent complexes – in conjunction with testing on conventional life’s chirality set, would be necessary to avoid false positives, and thereby screen against mirror life with a high degree of confidence. The all-optical approach could be deployed via recently innovated optical technologies, i.e. rapid CPL spectroscopy, CPL EDCC microscopes, and CPL EDCC cameras. We envisage that this CPL-based approach to screening against mirror life could be a useful tool for safeguarding against mirror life biohazards in a complimentary manner to any future legislative controls.

Life on Earth is predominately based upon a single chirality set, but so-called “mirror life” - speculated life of the opposite chirality, either of artificial or natural origin - presents a low-likelihood, but high severity global biosecurity threat. Such an existential risk necessitates that technologies for surveillance and containment of mirror life are developed as a contingency. In this perspective, we propose a method for screening against mirror life hazards via an optical chirality assay, based upon circularly polarized luminescence (CPL) generated either via achiral fluorophores (via supramolecular chirality effects) or intrinsically chiral molecular probes. When bound to biological molecules, CPL-generating probes enable Enantioselective Differential Chiral Contrast (EDCC) imaging to verify chirality of a biological specimen. We set out why a multi-reporter panel approach – incorporating many CPL generating fluorescent/luminescent complexes – in conjunction with testing on conventional life’s chirality set, would be necessary to avoid false positives, and thereby screen against mirror life with a high degree of confidence. The all-optical approach could be deployed via recently innovated optical technologies, i.e. rapid CPL spectroscopy, CPL EDCC microscopes, and CPL EDCC cameras. We envisage that this CPL-based approach to screening against mirror life could be a useful tool for safeguarding against mirror life biohazards in a complimentary manner to any future legislative controls.

Life on Earth is predominately based upon a single chirality set, but so called "mirror life"-speculated life of the opposite chirality, either of artificial or natural origin-presents a low-likelihood, but high severity global biosecurity threat. Such an existential risk necessitates that technologies for surveillance and containment of mirror life are developed as a contingency. In this perspective, we propose screening against mirror life hazards via an optical-readout chirality assay, based upon circularly polarized luminescence (CPL) generated either via achiral fluorophores (via supramolecular chirality effects) or intrinsically chiral molecular probes. Such systems enable Enantioselective Differential Chiral Contrast (EDCC) imaging. We set out why a multi-reporter panel approach incorporating many CPL generating fluorescent/luminescent complexes-in conjunction with testing on conventional chirality life, would be necessary to avoid false positives, and thereby screen against mirror life with a high degree of confidence. The all-optical approach could be deployed via recently innovated CPL/EDCC optical technologies, i.e. CPL/EDCC rapid spectroscopy, microscopy, and cameras. CPL/EDCC microscopy could enable identification of even a single mirror life cell, whereas CPL/EDCC cameras could be used for in situ inspection. We envisage that this CPL-based approach to identifying mirror life would be complimentary to speculated future international legislation against mirror life research.

PEI molecular weight influences the morphology, upconversion luminescence and FRET response of NaYF ₄ :Yb,Er nanoparticles, highlighting the importance of polymer selection in UCNP design.

Ultra-fast upconverted room temperature quantum superfluorescence promises more photons per unit time. This article explores superfluorescence and how these particles can be considered as second-generation quantum technology materials.

Autoclave reactors are widely used across chemical and biological sciences, including for the synthesis of upconversion nanoparticles (UCNPs) and other nanomaterials. Yet, the details of how autoclave reactors are used in such synthesis are rarely reported in the literature, leaving several key synthesis variables widely unreported and thereby hampering experimental reproducibility. In this perspective, we discuss the safety considerations of autoclave reactors and note that autoclaves should only be used if they are (a) purchased from reputable suppliers/manufacturers and (b) have been certified compliant with relevant safety standards. Ultimately, using unsuitable autoclave equipment can pose a severe physical hazard and may breach legal safety requirements. In addition, we highlight several parameters in autoclave synthesis that should be reported as standard to maximise the reproducibility of autoclave synthesis experiments across materials and chemistry research. We encourage users of autoclave synthesis vessels to: (1) adopt high-safety autoclaves and (2) report the many experimental variables involved to enhance experimental reproducibility.