Visikol was featured this week at the NSF/NIH Innovation Zone at the BIO conference in San Diego. The Innovation Zone features biotech startup companies that have received SBIR grant funding.
Not all antibodies are made equal and not all will work for 3D tissue imaging with Visikol HISTO. Recently we have compiled a list of the best antibodies that our team and our collaborators have used so far with Visikol HISTO. Check it out here.
We have assembled all of our knowledge about using Visikol HISTO with various tissues into an easy-to-use tool that will generate a step-by-step protocol specifically for your tissue, label, and microscope. The Protocol Builder web app allows you to select parameters specific to your goals and delivers a printable and shareable protocol so you will be sure to get the best results from Visikol HISTO. Thanks so much to our beta testers for all the feedback we have incorporated into this tool.
To try out the protocol builder click below. Let us know what you think and if you have any feedback or questions.
Over the past six months, we have been compiling all the feedback, considerations, and advice about using Visikol HISTO into our comprehensive Visikol HISTO Guidebook. Our new and improved guidebook has detailed descriptions of every consideration that is important to labeling and tissue clearing. To read through our updated guidebook click below.
Seeing Deeper into 3D Tissue Cultures
Microtissues and organoids are too thick to be fully imaged using confocal microscopy. In PBS, only the outer layers of cells may be imaged. After treatment with Visikol HISTO-M, cells can be imaged on every plane through the center, allowing you to extract more information from your tissue models.
3D Tissue Culture in PBS
3D Tissue Culture with Visikol HISTO-M
Visikol was selected to exhibit at the NSF/NIH Innovation Zone at this years BIO2017 International Conference in San Diego. The company was awarded an NSF Phase I SBIR in 2016 and has submitted several other SBIR grants in the last year that are being considered for funding.
Visikol HISTO can be applied to a wide-range of applications from mapping the neurons within a mouse brain to characterizing a breast biopsy in its entirety. Here we show Visikol HISTO being used to visualize Ki67 expression within a 960 um thick piece of mouse mammary tumor tissue.
Over the last year we have developed the Visikol HISTO tool which can acquire huge quantities of 3D data from tissue - Michael chatted last week on a panel at the NJ Tech Council HealthTech Conference about the platform and big data in the healthcare space. We are working hard to turn our data into actionable insights for researchers and pharmaceutical companies.
As researchers optimize the Visikol HISTO process for their immunolabels of interest, it is important to use smaller tissues before proceeding to whole organs like the brain. This saves the researcher a lot of time and money through the optimization process and ensures that they achieve the best results possible. To help researchers with cutting their tissues into smaller pieces, we have added coronal and sagittal 2mm brain slicers to the Visikol store.
When we first launched Visikol HISTO in late 2016 we did not have a reliable protocol for use with fluorescent proteins and the technique would result in FP quenching. To address this problem we have developed two new protocols that allow for Visikol HISTO to be used with FP and immunolabeling at the same time.
See Visikol HISTO in action with a tdTomato mouse brain below that was imaged with a LaVision BioTec Ultramicroscope II
After launching Visikol HISTO we got a lot of questions from researchers on how best to image their tissues and to mount them. To address this problem we have introduced the ClearWell™ which is a silicon well that sticks to glass microscope slides and allows for Visikol HISTO to be used with a wide array of tissue thicknesses and objectives. We currently have three different ClearWell sizes to allow for imaging of all tissue thicknesses.
In a recent publication from Kyung Hee Univeristy in Korea, researchers used Visikol for Plant Biology to study seed shattering using GUS staining with tissue clearing.
Xena Flowers and Dr. Jeffrey Goodman from the Department of Developmental Neurobiology, NYS Institute for Basic Research and the College of Staten Island have been using Visikol HISTO to evaluate traumatic brain injury (TBI) in rat brains in 3D. Specifically, they have been characterizing the impact of TBI on the blood brain barrier. Stay tuned for a publication describing their work!
Visikol was recently selected by the National Council of Entrepreneurial Tech Transfer as one of the best Univeristy Startups in the country. The University Startups Conference and Demo Day brings together a diverse audience of university Startup Officers, university startups, entrepreneurs, Fortune 1000/Global 1000 corporations, VCs, angel investors, policy leaders, and federal government agencies. The event provides a venue to form and maintain robust transaction networks among the participants with the aim to align university IP and startups with investor and corporate needs.
Once a year, the New Jersey Entrepreneurial Network provides the entrepreneurial community with an afternoon of posters and networking for startups in New Jersey. Poster presenters introduce their businesses to important contacts among New Jersey’s research universities, small and large business, potential funding sources and professional service providers.
The event was held at Princeton Univeristy and this year’s keynote speaker at the event was Jesse Treu, PhD of Domain Associates
Michael Johnson represented Visikol at the event and was awarded “Best in Class” amongst many other highly successful startups from New Jersey.
Each year, Visikol attends the Society of Toxicology (SOT) Annual Meeting with experts in toxicology from around the world. At SOT this year, the Visikol team discussed their Visikol TOX platform for DART studies as well as their Visikol HISTO platform for the 3D visualization of spheroids.
This year Michael Johnson presented a poster on the Visikol TOX process during the conference, comparing Visikol TOX skeletal processing for DART studies to traditional KOH-based processing. The Visikol TOX technology platform has the potential to accelerate DART studies by up to 30%, allowing contract research organizations to get studies back to pharmaceutical companies more quickly. For more, check out the poster here.
Over the last few months Visikol has launched the Visikol HISTO platform for the 3D histological visualization whole tissues. The team has applied this technology in the toxicology and drug development space to specifically improve the characterization of spheroids. Spheroids are 3D cell culture models that are starting to be used frequently for the drug development process as they more accurately mimic in vivo tissues than traditional 2D in vitro models. However, until Visikol HISTO, the characterization of spheroids was limited to 2D and 1D assays that limit the utility of spheroids and the information that can be obtained.
With Visikol HISTO, we are starting to move beyond traditional single end-point spheroid assays and towards whole spheroid characterization. Instead of just receiving a single data-point from a spheroid, Visikol HISTO allows researchers to better understand how drugs are interacting in 3D with spheroid models. We started offering Visikol HISTO kits and reagents in the fall of 2016 and are currently expanding our capacity for spheroid-specific characterization assays.
Visikol TOX for DART Studies
When we first devised the Visikol TOX platform in 2014, it was not entirely clear to us the value that it would have in the toxicology field. However, through the last three years of development we have transformed this technology into a robust skeletal visualization platform for developmental and reproductive toxicology studies that increases throughput by up to 30%, reducing costs and allowing therapeutics to get to market more quickly. We recently completed the development of this platform and are now offering it for use in developmental and reproductive toxicology (DART) studies, at a cost of $650 per study.
DART studies are one of the most expensive and time-consuming components of the regulatory data required to bring a new chemical entity into the marketplace. In these studies, pregnant animals (rats, rabbits, mice) are dosed with chemicals of interest and the impact of these chemicals on the development of fetuses is investigated. While these studies entail several concurrent processes, the biggest bottleneck in this process is the gross visualization of fetuses for skeletal abnormalities.
For over 90 years, scientists have visualized the gross skeletal morphology of animals using a process called diaphonization, where bones are stained with a red dye called Alizarin (sometimes with blue Alcian cartilage staining) and soft tissues are digested away with a strong base (potassium hydroxide) to reveal the stained bones. While this process is the gold standard for skeletal visualization in all DART studies, it can take up to two weeks for fetal rabbits, can destroy tissues, and requires consistent oversight.
With Visikol TOX we have replaced this destructive and slow process with a rapid and non-destructive process that leverages the Visikol tissue clearing technology. Instead of digesting the soft tissues to visualize bone, the tissue is rendered transparent, resulting in the same endpoint in 2-4 days instead of the traditional 7 to 14 days. We recently demonstrated in a 3rd party GLP equivalency study with Product Safety Labs (Dayton, NJ) that the Visikol TOX approach was equivalent in end-point to the traditional approach while drastically reducing tissue processing time.
We have designed Visikol TOX to be a drop in replacement to traditional KOH-based skeletal processing and are currently working with several CRO’s to integrate it into their DART workflow. All of the Visikol TOX reagents to conduct a 480 fetal rat study cost $650 and the technique can accelerate overall DART study time by up to 30%.
Building Visikol continues to be an amazingly fun, challenging, and rewarding endeavor. Every morning, I find myself checking my email right away to see what feedback we have gotten from our customers, and what complex research problems researchers are using our products to investigate. This feedback continually reminds me of why we launched Visikol in the first place – to accelerate innovation and to allow researchers to ask and answer new questions.
Over the last few months we have celebrated many firsts – On February 24th we celebrated our first anniversary as Visikol, Inc. and in January we brought on our first new team member: Dr. Graeme Gardner from Rutgers University. We are thrilled by the progress that we have made so far and are excited to continue to grow the company:
Visikol HISTO Progress:
To date, 300 research labs in 30 countries have used Visikol HISTO, and the feedback that we have received so far has been just fantastic. Bringing an enabling technology into the marketplace is a challenging process fraught with many roadblocks. Through beta-testing Visikol HISTO with researchers in new applications and soliciting feedback, we have been able to uncover these roadblocks and find strategies to mitigate them. To help our users get the most out of Visikol, we continually update and improve our product guidance with all the feedback received from researchers. If you are interested in learning more, please see our updated Visikol HISTO Guidebook.
Visikol TOX Progress:
Of all of the things that we have completed thus far, I am most proud of the Visikol TOX product for developmental and reproductive toxicology studies. Since inventing Visikol TOX in 2014, we have turned it into a valuable bio-imaging platform that not only accelerates the drug discovery process, but also reduces the number of animals required in toxicology studies. Visikol TOX represents to me the great synergies of our team as Tom, Nick, and I all worked on different components that came together to create a valuable and highly impactful platform.
Our team has absolutely no shortage of great ideas and we find ourselves continually submitting grants for new applications of the Visikol HISTO technology as well as other novel bio-imaging ideas. We are very fortunate that there are programs like the NIH and NSF small business innovation research grants (SBIR) that fund innovative and cutting edge technology development. In December and January we submitted for six Phase I SBIR grants with collaborators and expect to hear back on most of these grants in the near future. We are optimistic about these projects as we have teamed up with some great collaborators! We also submitted our Phase II NSF SBIR after the successful completion of our NSF Phase I project, and are very excited at the prospect of continuing our NSF funded research. Our goal for 2017 is to further expand our R&D efforts through the use of SBIR grants, and we have placed significant time and effort on these. Since launching Visikol we have submitted thirteen, been rejected from five, been awarded one, and are waiting to hear back on seven.
Things to come:
In the next few months you will see significant developments from our team around Visikol HISTO assays for spheroid visualization. Drug discovery is undergoing a paradigm shift where in-vitro work is moving from 2-D cell based assays to 3D cell based assays as they more accurately depict in-vivo tissues. However, researchers are still using 2D (histology) and 1D assays (total ATP) to evaluate these 3D spheroids, ignoring the spatial features that make them intrinsically more valuable than 2D cell cultures. We are developing 3D assays for spheroids that will allow researchers to move beyond traditional endpoints (IC50) and towards evaluating the spatial heterogeneity of spheroids. For example, we will enable companies to understand where their antibodies are targeting within tumors (necrotic core, periphery) and the type of cell these drugs target.
As we are now gaining traction in the marketplace with Visikol HISTO and Visikol TOX, our focus is shifting from pure research and development, to commercialization and the application of the Visikol HISTO platform to several areas including spheroids. We are excited to apply the Visikol HISTO technology to new problems and will be shifting to spending considerable resources on commercialization in the second half of the year.
I look forward to sharing more great news with you in Q2! Thanks for following our progress.
When we first launched Visikol HISTO back in August, it was a general purpose tool with general protocols and guidelines. While this platform worked very well for a wide range of tissue types and sizes, our initial beta testers asked us to optimize the protocols for speed and cost in a few of the most used tissues. Over the last six months we have been collaborating with several research partners to develop application specific protocols that are optimized for these specific usages. One of the first applications we will launch is a method for the 3D visualization of spheroids, a type of in-vitro model that is being rapidly adopted in the drug discovery process. And recently, we completed the development of a spheroid specific Visikol HISTO protocol that drastically cuts down processing time and steps compared to our original protocol. To check out this updated protocol and background on spheroids, click here.
Back in August of 2016 we started beta-testing our Visikol HISTO platform with researchers in the US and EU. The Visikol HISTO platform allows researchers to move beyond the 400-year-old practice of 2D histology and towards conducting what we call “3D histology.” To date, we have had over 300 researchers from around-the-world use this platform and are excited to announce the first publication using Visikol HISTO: Clarification and 3-D visualization of immunolabeled human placenta villi. This paper was authored by Dr. Carolyn Salafia, Dr. George Merz, Valerie Schwenk, Ruchit Shah and Phillip Necaise. The paper focused on applying the Visikol HISTO technology to visualize and characterize the complex vasculature of the human placenta.