Optical tweezers have revolutionized the field of biological research with their unique advantages of non-contact and high-precision manipulation of various particles, including biomolecules. In 1986, Arthur Ashkin pioneered the development of optical tweezers by demonstrating their ability to capture microspheres in three dimensions, and his pioneering work had earned him a Nobel Prize in 2018. However, the optothermal effect and diffraction limit of lasers in traditional optical trapping techniques have restricted its wider applications. Nevertheless, in the past decade, researchers have turned the optothermal effect into a merit. With the synergy effect of optics and thermodynamics, one can perform high-precision nanoparticle manipulation in a large-scale range, which is called optical temperature field-driven tweezers (OTFT). This new type of tweezers can operate in rather low light density, which is two to three orders of magnitude lower than that of conventional optical tweezers. In addition, with the assistance of thermal energy, it greatly expands the categories of particles that can be manipulated, allowing for the large-scale manipulation of particles that limit the application of optical tweezers, such as opaque particles, metallic nanoparticles, and biomolecules. OTFT has become a useful research tool that enables researchers to study biological particles with high precision. Particularly in the detection of individual bio-nanoparticles, such as viruses, bacteria, proteins, and DNAs. The ability to detect single bio-nanoparticles enables observation of biological behavior on an individual level, which allows us to develop effective disease prevention strategies and expand our understanding of the biological world.

In this review, we systematically demonstrate the manipulation principles of OTFT and its applications in the biological field. In addition, the future development and challenges of OTFT are also discussed. Firstly, we provide a brief analysis of conventional optical tweezers (Fig. 1). Secondly, we demonstrate the basic principles of the common optothermal effects such as thermophoresis, thermoelectricity, electro-thermo-plasmonic flow, natural convection, thermal osmotic flow, depletion forces, and Marangoni convection (Figs. 2-6). Thirdly, we provide an in-depth analysis of OTFT's applications in biomedicine, such as manipulation of nanoparticles (Figs. 7-8), protein molecules (Figs. 9-10), nucleic acid molecules (Figs. 11-13), and sorting of other nano-bioparticles (Figs. 14-18), as well as the sensitizing effect of biosensing (Fig. 19). Notably, the study by Dieter Braun and Albert Libchaber regarding the capture of DNA through convection and thermophoresis in 2002 is often considered a pioneering study in using OTFT for biomolecule capture (Fig. 11). Lately, in 2015, Ho Pui Ho's group in The Chinese University of Hong Kong developed a series of optothermal manipulation schemes to capture nanoparticles or cells (Figs. 7, 15-17). In 2018, Zheng Yuebing's group in University of Texas at Austin utilized surfactants in OTFT to achieve precise manipulation and on-site spectroscopic detection of metal nanospheres (Fig. 8). In 2019, Cichos's group at Leipzig University developed a thermophoretic trapping and rotational diffusion measurement scheme for single amyloid fibrils, which may be useful for understanding neurodegenerative disorders (Fig. 9). In 2020, Ndukaife's group at Vanderbilt University combined OTFT with alternating electric fields to capture and manipulate individual protein molecules as small as 3.6 nm in diameter (Fig. 10). Furthermore, in 2021, Zheng Yuebing's group also accomplished the capture of nanoparticles via opto-refrigerative effect-induced temperature field, thereby avoiding the possible optothermal damage to the captured particles. In 2022, A method for biomolecule enrichment and interaction enhancement was developed by our team using flipped thermophoretic force (Fig. 19). This approach significantly boosted the sensitivity of conventional surface plasmon resonance imaging (SPRI) sensing methods by a factor of 23.6. These typical advances in OTFT technology mark a significant milestone, as they bring about notable enhancements in functionality and broaden the scope of potential applications for OTFT in areas such as nanotechnology and life sciences.

The implementation of OTFT relies heavily on various hydrodynamic effects generated by the temperature field and still faces several challenges. Firstly, the temperature gradient may cause some biologically active targets to lose their activity during manipulation. Secondly, various factors, such as ion concentration, temperature, pH value, and type, can easily affect the direction and size of particles driven by the temperature field. As a result, some optothermal tweezers require the addition of surfactants to modify the manipulated targets and achieve controlled particle capture. However, most surfactants are not compatible with biologically active particles and may lead to chemical toxicity or changes in the spatial structure of protein molecules. Additionally, the adsorption of surfactants may change the surface electrical properties of manipulated targets, thereby affecting their physicochemical properties. Thirdly, while OTFT currently utilizes two-dimensional potential wells to capture particles, the construction of spatial three-dimensional potential well capture remains a significant challenge.

In terms of future research directions for OTFT, efforts will be made on the development of biocompatible surfactants or the modulation of other environmental factors to achieve controlled and targeted particle trapping, especially in the field of biology. Furthermore, OTFT can be effectively integrated with other fields to address a broader range of issues. For instance, the combination of OTFT with dielectric microsphere-based super-resolution imaging enables large field-of-view imaging via microsphere scanning. OTFT can also be combined with surface Raman-enhanced scattering to enhance its chemical detection performance. In addition, OTFT is expected to be integrated with optical spanners to study the manipulation of the molecular orientation of liquid crystals. It can be anticipated that with the development of research on the light and matter interaction as well as surface chemistry, the optically-induced temperature field optical trapping technology will be further improved and will shine in the fields of biomedical and biochemical detection.