Visikol wins "Best in Class" at NJEN Posters, Pitches and Prize event at Princeton Univeristy

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. 

Michael Johnson - Visikol - NJEN Poster

Visikol at Society of Toxicology

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%. 

Visikol TOX - At SOT

Q1 Quarterly Review

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.

Grant Progress:

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.

-Michael

Visikol HISTO Spheroid Protocol

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.

Visikol HISTO Spheroid

First Visikol HISTO Publication!

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.

Virtual Reality and Visikol HISTO

At Visikol we are constantly thinking about new ways to image and analyze biological tissues. We have recently begun working with VR to interpret large 3D renderings and are very excited about the possibilities. If you are interested in learning more about applying VR to your 3D renderings reach out to us: info@visikol.com 

Dr. Graeme Gardner Joins the Visikol Team!

Visikol is happy to announce that Dr. Graeme Gardner recently joined the team as a research scientist! He obtained his PhD in chemistry from Rutgers University, New Brunswick, where he specialized in bioinorganic and materials chemistry. He is passionate about bridging the gaps between compatible disciplines in chemistry and biology that suffer from a lack of intercommunication, and is excited to work on solving problems in tissue clearing. Dr. Gardner will focus on the development of Visikol HISTO for 3D histology and working to improve the characertization of complex and heterogenous tissues. 

Michael met Dr. Gardner through their NSF IGERT Fellowships and worked together during their PhD work on the development of sustainable wastewater treatment systems. Dr. Gardner and Michael worked together on optimizing wastewater treatment systems in Argentina (below) and were finalists in the Agricultural Innovation Competition in 2014. 

Left to Right: Graeme Gardner, Michael Johnson, Sarah Wolfson

Left to Right: Graeme Gardner, Michael Johnson, Sarah Wolfson

2016 - Year in Review

2016 was an absolutely amazing year for Visikol in that we have far exceeded our initial expectations when we launched the company in March and are tracking well with our goals and milestones. I am incredibly proud of the work that our team has done in a very short period of time and I think we are well on our way to significantly disrupting the way that bio-imaging is conducted. Below I just wanted to focus on some of the highlights from the year and discuss our goals for 2017.

Launch of Visikol HISTO

This technology is the embodiment of years of work and was designed to replace traditional 2D histology with an easy-to-use and rapid 3D histological approach. We were very happy to receive positive feedback from our early beta-testers on this technology and have since launched a suite of Visikol HISTO products. We are continually improving these products and, to date, have had over 160 researchers use Visikol HISTO in their research. Check out some examples of Visikol HISTO being used below:

·       Visikol HISTO – Mouse Prostate

·       Visikol HISTO – Owl Brain

·       Visikol HISTO – Mouse Brain Vasculature

·       Visikol HISTO – Placenta Tissue

·       Visikol HISTO – Micro-tissue

NSF Phase I SBIR Grant

As young researchers with few publications and a short academic track record, we were thrilled to receive a $225,000 Phase I NSF SBIR grant. These grants are highly competitive, and receiving one was a major accomplishment for the team. This grant allowed us to finish the development of our Visikol TOX platform and to pursue the development of the Visikol HISTO technology for micro-tissues. Based upon this success, we have submitted several additional SBIR grants and will look to continue supporting our R&D efforts through SBIR grant funding in 2017.

Forbes 30 Under 30

A fitting cap to this year's accomplishments was being named to the Forbes 30 Under 30 list. I am really proud to have been selected among so many innovators and disruptors from across the country. Each and every person on this list is working to shape their respective industries and to create a lasting impact in the world. This accomplishment would not have been possible without a long list of people who have supported me and the Visikol team. My two-founders; Thomas Villani and Nick Crider have been instrumental to the success of Visikol and together we make a really great team. Over the last year, we have spent countless hours together in a 10 x 10-foot office and the experience has had an incredible impact on me.

In addition to my fellow co-founders, this would not have been possible without the Foundation Venture Capital Group or Rutgers University who have supported us immensely along the way. Lastly, and most importantly, I would like to thank my wife Kassandra for her love and support and putting up with very early mornings and late nights of work. Building a company and creating new technologies is hard work that requires a great team and support from a myriad of people.

2017 Goals

One of the most important things for any team is to set goals. I find that committing goals to paper and sharing them with others makes you more accountable for your actions. Therefore, I wanted to share some of our goals for 2017 with all of you:

  1. Accelerate the commercialization of the Visikol HISTO technology for research applications and get it into the hands of 1,000 researchers
  2. Integrate the Visikol TOX technology into commercial developmental and reproductive toxicology studies
  3. Work with clinicians to evaluate high impact clinical applications for Visikol HISTO
  4. Raise $1,000,000 in SBIR award funding

Meeting these goals in 2017 will allow us to provide researchers with tools to answer complex scientific questions while building a successful commercial organization. Additionally, we will lay the groundwork for applying the Visikol HISTO technology directly to human health where 3D histology could potentially improve the diagnosis of heterogenous and complex diseases like breast cancer or Alzheimer's Disease.

Thank you all for your support of Visikol and best wishes for a happy and productive 2017!

-Michael

Michael Johnson - Visikol

Visikol for Plant Biology used in Cameroon for the Conservation of the African Manatee

We are always really excited to hear about what customers are using our products for and love to hear about their research. Aristide Takoukam Kamla, president of the African Marine Mammal Conservation Organization (AMMCO), recently told us about his work using Visikol for Plant Biology to study the diet of African Manatees.  AMMCO is a Cameroon-based NGO that is devoted to the conservation of African marine mammals. Learn more about AAMCO here

Visikol HISTO used for Barn Owl Connectome Project

Dr. William DeBello's group at UC Davis recently used Visikol HISTO as part of the Barn Owl Connectome Project. The goal of this project is to reconstruct the complete wiring diagram of local circuits in the barn owl auditory localization pathway. The barn owl is a classic model system for studying the neural bases of information processing, plasticity and learning. Dr. DeBello's group uses an integrative approach to studying this system that combines in vivo electrophysiology, auditory and visual receptive field mapping, tracer injection, immmunohistochemistry, confocal microscopy, automated transmission electron microscopy, 3D visualization, computer simulation and bootstrap analysis. To learn more about the DeBello group's work click here

To see the 3D characteristics of an owl brain click below. Video courtesy of Kelsey Lakowske (UC Davis, DeBello Lab).

Visikol HISTO used for 3D visualization of prostate tissue

Prostate cancer is a commonly misdiagnosed disease whereas indolent forms of the disease can be over-treated (radiation or radical prostatectomy) and aggressive forms of the disease can be incorrectly characterized and under-treated. Visikol HISTO represents a novel approach to visualizing prostate cancer in 3D and potentially improving disease characterization.

Over the last few weeks we have been very happy to see researchers starting to use Visikol HISTO for numerous disease-relevant applications like studying prostate cancer in mouse models. Check out some of the work from Ryan Trevena and Chad Vezina where they are adding a new dimension to their prostate tissue visualization with Visikol HISTO (The University of Wisconsin-Madison, School of Veterinary Medicine). 

 

Visikol HISTO Beta Test Feedback - Light Sheet Microscopy

First, you should reach out to your imaging core manager and find out what type of light sheet microscope you have access to and what type of objectives it uses. Many light sheet microscopes such as the ZEISS Z.1 and the OpenSPIM will have water immersion objectives that are matched to a refractive index of 1.33. These objectives have two disadvantages for imaging tissues that have been cleared with Visikol HISTO-2: 1) The mismatch in refractive index between the objective and Visikol HISTO-2 (1.51) will limit imaging depth to approx. 3 mm due to spherical aberrations and overall sample thickness to 6 mm if you image from both sides, 2) The sample will need to be mounted in a cuvette that is placed within the imaging chamber.

The reason that the sample will need to be mounted in a separate cuvette is that the imaging chamber cannot be filled with Visikol HISTO-2 when using water immersion objectives as it is possible that the objective can be damaged by Visikol HISTO-2. Information on the preparation of samples cleared with solvent based techniques (Visikol HISTO-2, BABB, 3/i/uDISCO) for light sheet microscopy with water immersion objectives can be found here for the ZEISS Z.1

However, if you have a solvent compatible light sheet imaging system like the LaVision BioTec Ultramicroscope then you can image directly in Visikol HISTO-2. The LaVision BioTec Ultramicroscope has been designed to work with almost every clearing solution (1.33 to 1.56) and will not get damaged by solvents. 

For any additional questions on imaging please reach out to us at info@visikol.com 

Visikol HISTO Beta Test Feedback - Shallow Imaging Depth

If you image your samples without utilizing refractive index matched immersion lenses (e.g. glycerol immersion lens, CLARITY optimized objective), an objective with a refractive index adjusting collar, or without adapting your air-lens for use with Visikol HISTO to eliminate changes in refractive index in the system, the maximum depth of imaging is approximately 500 µm due to attenuation caused by spherical aberration. This will limit the thickness of the tissues you can image to 1 mm (imaging from both sides). Researchers commonly believe that they are seeing poor immunolabel penetration whereas they are actually experiencing the limitations of their imaging system. 

Using a multi-immersion objective or objectives with a refractive index correction collar can correct for this issue. Inverted microscopes are not recommended for use with Visikol HISTO (or other clearing techniques) because they cannot achieve a continuous path of matching refractive index, and will therefore limit the overall depth that can be achieved during imaging to approx. 500 µm. This concern is only for confocal instruments - light sheet microscopes should not have this issue, as most are built to deal with multiple clearing media (e.g. Ultramicroscope II). 

Visikol HISTO Beta Test Feedback - Visikol HISTO Products

One of the things we wanted to learn from our beta-test of our Visikol HISTO approach was how we should bring this tissue clearing technique to customers. What we realized through our beta-test of this technology is that there are three primary groups of researchers in regards to tissue clearing and 3D histology. The first group of researchers is a very small group and is comprised of researchers who currently use tissue clearing in their research and are experts in this field. The second much larger group are researchers who are interested in tissue clearing and 3D histology, but who do not have an expertise in this field. The last group of researchers are those who have research thrusts that cannot benefit from adding spatial information and thus are not interested in tissue clearing. 

Based upon this feedback about our customers, we have decided to launch a Visikol HISTO product portfolio that meets the needs of tissue clearing experts as well as researchers who do not have an expertise in tissue clearing. For researchers that are new to tissue clearing, we have developed a Visikol HISTO Starter Kit that comes with everything a researcher needs to drop tissue clearing right into their workflow, including all of the buffers for tissue processing. The purpose of this kit is to make tissue clearing and labeling so easy-to-use that any researcher can drop it right into their current bio-imaging workflow.

For researchers that are experts in tissue clearing, we have made our individual reagents available so that a researcher can purchase only the reagents that they need. Most of these researchers will already have all of the pre-treatment buffers on hand or would prefer to make them. We have provided the composition of these buffers in our protocols so that researchers can make them if they do not want to purchase them. 

 
Visikol HISTO Starter Kit Box
 
 

Visikol HISTO Beta Test Feedback - Publications and Grants

We are routinely asked by researchers whether or not we are interested in collaborating on publications and grants. The short answer is "YES!" We are very interested in new applications of the Visikol HISTO technology and enjoy working with researchers to apply it to new applications. We have recently teamed up with a few of our beta-testers to submit SBIR/STTR grants that focus on three-dimensional imaging with Visikol HISTO. If you are interested in working together on a publication or grant just reach out to us and let us know a little about what you are thinking and how we can help: info@visikol.com