From Lenses to Semi-Permeable Capsules: How Scientists Keep Getting Closer to Life Itself 

Single-cell biology has moved from “seeing cells” to explaining how information becomes function. That shift exposed a practical bottleneck: we need platforms that keep single-cell resolution and let us run multi-step workflows at scale. Atrandi Biosciences’ patented Semi-Permeable Capsule (SPC) technology answers that need. SPCs isolate individual cells inside permeable hydrogel shells, so you can swap buffers, stage incompatible reactions, culture or lyse, then barcode and sequence, across tens of thousands of cells in parallel. In this paper, we trace the road to single-cell thinking, outline where current compartments fall short, and show how SPCs open up robust genomics and assay development, especially for eukaryotic systems. 

Seeing the Unseen 
The modern story starts with lenses. In 1665, Robert Hooke turned a compound microscope (now better known as Hooke's microscope), with only thirty-times magnification, on a thin slice of cork from the bark of an oak tree and named what he saw “cells” (Figure 1), giving language to a world we couldn’t otherwise access (Hooke, 1665). A few years later in 1673, Antonie van Leeuwenhoek, using exquisitely simple single-lens microscopes, reported “animalcules” in pond water – a living proof that the unseen was actually abundant (van Leeuwenhoek, 1676; Robertson, 2023). The early microscopy did more than delight: it reframed biological questions from surface to structure, and from appearance to process (Somssich, 2022).  By the nineteenth century, microscopy and careful observation converged into cell theory, that nucleated cells are the fundamental units of plants and animals. This concept was observed and published separately, first by the botanist, Matthias Schleiden, in 1838, and then by the zoologist, Theodor Schwann, in 1839. Rudolf Virchow in 1855 concluded that all living organisms are the sum of single cellular units and that cells multiply. This was the first durable model of a living organization and it still underpins how we teach biology (Ribatti, 2018). Over the next 300 years, improvements in optics, illumination, contrast, and sectioning took us from simple brightfield to phase contrast, fluorescence, confocal, live-cell imaging, and beyond (Zewail, 2010; Wollman et al., 2015). Each leap increased what we could resolve and track – from the way cells look, to how they change. 

From seeing to explaining  
The arc naturally set up the present: molecular biology. The rise of this field fused two threads. Structural methods revealed proteins and DNA at nanometer scales, while microbial genetics showed that DNA carries heredity and that genes specify enzymes. Those threads met in the double helix and the genetic code, moving biology from “seeing cells” to explaining how information is interpreted by cellular machinery into protein function (Ribatti, 2018; Klein and Treutlein, 2019).  Over the past two decades, single-cell analyses accelerated that logic. The field merged around two goals: map composition (what cell types/states are present) and track dynamics (how cells change) (Klein and Treutlein, 2019). Conceptual frameworks now integrate mor-phology, spatial context, and molecular readouts, pushing toward “holistic” cell states suitable for modeling and prediction (Rafelski and Theriot, 2024). In cancer and development biology alike, these tools have reframed heterogeneity as the signal, not the noise (Tirosh et al., 2024).  So what’s still missing? Resolution alone isn’t enough. To connect multi-step biochemistry with per-cell readouts we need throughput and modularity working reliably and at scale. 

Enter Semi-Permeable Capsules (SPCs)  
SPCs are microcapsules that have a liquid core surrounded by a thin, crosslinked hydrogel shell with size-selective permeability. Small molecules (e.g., salts, buffers, enzymes, primers, antibodies) diffuse freely; cells, genomic DNA and large complexes stay inside. Practically, that means you can wash, exchange, and stage any biochemical reaction all while preserving single-cell resolution. Thousands to tens of thousands of SPCs can be processed in the same tube at the same time. (Leonaviciene et al., 2020; Mullaney et al., 2025; Atrandi Biosciences, 2025).  SPCs are made by employing the principle of aqueous two-phase system (ATPS). Capsules are first formed as water-in-oil droplets prepared by co-flowing two immiscible aqueous polymers on a droplet microfluidic device (or chip). The polymers are chosen so, instead of mixing, they separate, with one polymer forming an outer shell, and the other – staying in the center (core). Visible-light crosslinking locks the shell, and droplets are broken to release capsules, yielding monodisperse SPCs whose diameters can range from 30 to 300 µm depending on flow and chip geometry (Atrandi Biosciences, 2025). 
...

Continue to the full piece here [ScienceSelect]