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Noninvasive prenatal diagnosis (NIPD) aims to detect fetal-related genetic disorders before birth by detecting markers in the peripheral blood of pregnant women, holding the potential in reducing the risk of fetal birth defects. Fetal-nucleated red blood cells (fNRBCs) can be used as biomarkers for NIPD, given their remarkable nature of carrying the entire genetic information of the fetus. Here, we review recent advances in NIPD technologies based on the isolation and analysis of fNRBCs. Conventional cell separation methods rely primarily on physical properties and surface antigens of fNRBCs, such as density gradient centrifugation, fluorescence-activated cell sorting, and magnetic-activated cell sorting. Due to the limitations of sensitivity and purity in Conventional methods, separation techniques based on micro-/nanomaterials have been developed as novel methods for isolating and enriching fNRBCs. We also discuss emerging methods based on microfluidic chips and nanostructured substrates for static and dynamic isolation of fNRBCs. Additionally, we introduce the identification techniques of fNRBCs and address the potential clinical diagnostic values of fNRBCs. Finally, we highlight the challenges and the future directions of fNRBCs as treatment guidelines in NIPD. Graphical Abstract

Assays toward analysis of rare heterogeneous cells among identical specimen raise a significant challenge in many cell biological studies and clinical diagnosis applications. In this work, we report a disk-like hydrogel bead-based stratagem for rare cell researches at single cell level after a facile microfluidic-based particle synthesis approach. Cells of interested can be encapsulated into alginate droplets which are subsequently solidified into disk-like calcium alginate hydrogel beads and the bead size and cell number inside can be precisely controlled. Due to stability, permeability and disk-like shape of calcium alginate beads, cells immobilized in the disk-like beads can be treated with different chemicals with limited mechanical or fluidic operation influences and observed without distortion comparing with conventional methods or droplet microfluidic methods. Identification of circulating tumor cells, related to early-stage cancer diagnosis, is targeted to demonstrate the potential of our technique in rare cell analysis. This hydrogel bead-based stratagem is performed in immunofluorescence staining treatment and observation of cancer cells from normal hematological cells in blood sample. This method would have a great potential in single cell immobilization, manipulations and observation for biochemical cellular assays of rare cells.

In this work, we developed a shape-controllable nozzle inside a multilayer PDMS microchip. The nozzle was able to control the shape of the fluid channel in three dimensions. All the four walls of the fluid channel were comprised of pneumatic PDMS membrane valves, and their deformation was controlled by air pressure. As both the limitation of the fluid flux and the shape of the fluid channel were adjustable spatially in three dimensions, this valve-based nozzle generated droplets with less response time and in a more effectively controlled manner comparing to conventional droplet devices. It could also function as a microinjector to modulate the compositions of droplets precisely and continuously. In addition, the nozzle was able to form a specific shape to generate core–shell particles.

Results are presented on the influence of the size of diamond powders and the laser power on the main Raman line. These results show conclusively that there is a consistent and systematic, reversible, downshift with both decrease of powder size, and increase of power. The shift can be explained by local heating of about 500 °C in the extreme case. Its significance applies to interpretation of the alleged “downshifting” of the 1332 cm−1 line in all diamond research. In the future, the grain size, the thermal contact, and the beam power must be carefully monitored in reporting and interpreting any frequency shifts.

The first report of synthetic diamond involved a high-pressure high-temperature (HPHT) process in which diamond was the thermodynamically stable phase1. Subsequent attempts to make diamond at less extreme conditions culminated in the rapid growth of diamond films by chemical vapour deposition2,3. But the question of whether diamond might be grown in hydrothermal conditions mimicking those under which it is formed in the Earth has been long debated4–6. It seems reasonable to suppose that metals might play a catalytic or solubilizing role in this context, given their role in the HPHT method1, in a recent low-pressure solid-state synthetic approach7 and in the recrystallization of diamond in the Ni–NaOH–C system8. Hydrothermal synthesis of diamond has been explored at some length9–13, but with equivocal results. Here we report evidence from spectro-scopic, diffraction and microscopic techniques which suggest that aggregates, tens of micrometres in size, of small diamond crystals can be grown in a hydrothermal environment from a mixture of carbon, water and metal (usually pure nickel). Crucially, we have been able to distinguish new diamond from the diamond seeds added to nucleate new growth.