Search

The rapid and accurate analysis of micro-samples is a crucial foundation for precision medicine, particularly for early screening and monitoring of cancer, where it holds significant importance. Ultrasound-based multifunctional biocompatible manipulation techniques have been extensively applied in a variety of biomedical fields, providing insights for the development of rapid, cost-effective, and accurate biomarker detection strategies. In this chapter, we combine ultrasound-based gradient pressure fields with functionalized microsphere enrichment to develop a biosensing method for ultra-trace miRNA enrichment in nanoliter samples without PCR. This system relies on inexpensive capillaries, enabling simultaneous visual imaging and trace sample detection., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

[Display omitted] • First data from single early stage mammalian embryos having diameters of 130–190 μm. • CMOS-based microNMR device adapted for early stage embryos and 3D cell cultures. • Detection of lipids and observation of variation of spectra from sample to sample. The resolving power, chemical sensitivity and non-invasive nature of NMR have made it an established technique for in vivo studies of large organisms both for research and clinical applications. NMR would clearly be beneficial for analysis of entities at the microscopic scale of about 1 nL (the nanoliter scale), typical of early development of mammalian embryos, microtissues and organoids: the scale where the building blocks of complex organisms could be observed. However, the handling of such small samples (about 100 µm) and sensitivity issues have prevented a widespread adoption of NMR. In this article we show how these limitations can be overcome to obtain NMR spectra of a mammalian embryo in its early stage. To achieve this we employ ultra-compact micro-chip technologies in combination with 3D-printed micro-structures. Such device is packaged for use as plug & play sensor and it shows sufficient sensitivity to resolve NMR signals from individual bovine pre-implantation embryos. The embryos in this study are obtained through In Vitro Fertilization (IVF) techniques, transported cryopreserved to the NMR laboratory, and measured shortly after thawing. In less than 1 h these spherical samples of just 130–190 µm produce distinct spectral peaks, largely originating from lipids contained inside them. We further observe how the spectra vary from one sample to another despite their optical and morphological similarities, suggesting that the method can further develop into a non-invasive embryo assay for selection prior to embryo transfer. [ABSTRACT FROM AUTHOR]