Single-cell biology has opened up vast new frontiers of discovery, however, until now an entire dimension of space has been missing. While probing the genome and protein expression of the fundamental unit of life has revealed profound scientific insights, by and large we’ve been unable to study molecular and cell biology that reflects the actual conditions in which cells live and change. This is because we primarily conduct single-cell research outside of a precisely controlled environment. We separate cells from the contextual biology driving their function to isolate them in foreign buffers and then interrogate them, alone and adrift. The effect and relevance of nurturing or hostile native tissue is lost.
Mammalian cells naturally reside in an environment where they communicate, coordinate, activate pathways and secrete proteins other cells absorb and react to. Tissue contains a dizzyingly complex biological niche that’s essential to a cell’s function, state and fate. When we sequester cells prior to permeating or breaching their membranes to study genes and proteins, we lose that symphonic signaling and we lose the dance that results from that harmonic interplay. A 2014 Nature paper by Shalek et al. highlighted the importance of this cell interaction, showing that some immune cells are “precocious” in their response to putative bacterial invasions and that early response is vital to the signaling cascade mobilizing the immune response.
This is the dimension that had been missing. While single-cell genomics and proteomics are extremely powerful contributors to a growing wave of disruptive science, to date the tools haven’t allowed us to incorporate the critical biological influence of the cellular environment into our studies. As a result, we’ve been blind to the effects of the biological niche on cell fate and function.
Is this important? Absolutely. One look at induced pluripotent stem cells is enough to see how environmental changes affect cell function. Only four factors are required to turn a skin cell into a stem cell and completely rewrite its mission and possibilities. Imagine the changes in transcriptional profiles when immune cells recognize cytokines, when neurons respond to neurotransmitters or when a virus infects cells.
At Fluidigm, we became aware of this problem a few years ago. At first it was merely a vague, unsettling feeling that something important was missing. We worked hard to understand where the science of single-cell biology needed to go, through countless discussions with customers around the world. Gradually it became clear. For me, it came after staring at a picture of a tissue sample micrograph. I have seen hundreds, maybe thousands of these pictures yet I am continually struck by the amazing complexity of the cellular landscape. It is beautiful and strange, a world so small and infinite that it is to our bodies as the sun is to 100 Milky Way galaxies.
Something dawned on me that in retrospect is painfully obvious. This complexity and beauty is all-important: the ether soaking cells with stimulation and challenges provokes. Some cells will respond with heroics and others with mischief. We absolutely must understand this. Collectively, Fluidigmers racking our brains about the future of biology coalesced on the idea that a fresh dimension of single-cell analysis was needed, to incorporate the effects of the biological niche. And so we began to forge a star of our own.
Polaris is our new North Star. To date, it is our crowning technological achievement. We poured our ingenuity and our will and our passion for science into it. The result is an unprecedented span of single-cell biology capability. With Polaris, researchers will be able to actively select individual cells based on phenotype, precisely control the environment to which the cells are subjected and analyze the mRNA from each individual cell.
We believe the scientific ramifications of this aptitude are profound. Researchers will now be able to isolate promising individual stem cells and attempt to coax out their amazing potential to consistently make complete functional nerves, as well as heart and liver cells. Translational scientists can identify and select cancer cells, test a wide range of conditions that may weaken or kill and assess the underlying molecular biology resulting in vulnerability. Immunologists will be able to deliberately infect immune cells with HIV and study the underlying transcriptional signatures that signal an infected cell.
I could go on and on—and believe me, I’d love to. In short though, we are incredibly enthusiastic about the kinds of discoveries Polaris will enable, and we are thrilled to see how your research will benefit from its power. We at Fluidigm delight in investigating unexplored territory. The unmapped route pulls at us irresistibly, eliciting a nagging ache until we gear up and commit to the adventure, exhaustion and exhilaration of breaking trail.
Polaris embodies our love of discovery. It is built to enable bold exploration and, in combination with our customers’ universe of genius, to liberate knowledge and understanding that can change our understanding of life—and therefore, the world. For you: Polaris.