Science and Research

The anti-pathogenic properties of copper

Copper is a metal that occurs naturally throughout the environment, in rocks, soil, water, and air.  It is an essential element in animals and plants, which means it is necessary for life; thus, humans  must absorb some copper from the environment.  

Copper is used to make many different kinds of products like wire, plumbing pipes, and sheet metal. It is combined with other metals to make brass and bronze pipes and faucets. Copper compounds are commonly used in agriculture to treat plant diseases like mildew, for water treatment and, as preservatives for wood, leather, and fabrics. 

Copper, however, is a malleable metal and for a variety of reasons would generally not be appropriate as biocidal protective shields for an outsole surface.  To harness the bactericidal benefits of copper on shoes, Armor29™ spent over four years of R&D, prototyping, testing and validating a process to create a successful, patented and viable product.   The advantages of copper as a safe and effective product in blocking person-to-person pathogenic transmission are numerous:

• Widespread use of copper as a bactericidal agent does not contribute to the widespread problem of antibiotic resistance.

• Copper is generally considered to be a bio-safe agent for use as a wearable.

• Copper does not break down like chemical or biochemical agents (antibiotics) that have a limited half life (can be as short as 30 min in biological systems). 

• Copper, as an inert solid surface, does not slough off to any appreciable extent and is clearly not a biohazard to the people (as noted, humans actually need small amounts of dietary copper).

• Copper works equally as well when oxidized or tarnished (green hue) versus shiny.

• Copper is especially effective at killing SARS-CoV-2 (etiologic agent for Covid-19) and this work has been recently published in a top medical journal.

• All bacterial pathogens tested to date are susceptible to copper mediated toxicity and it is reasonable to presume that most if not all  bacterial pathogens will respond similarly.

• Pathogenic yeast species are also growth inhibited by copper (such as candida species that are drug resistant). These pathogens have recently been shown to be a serious health threat in Hospital Acquired infections (or HAI).

• Enteric viruses are inactivated by copper as recently proposed using a bacteriophage MS2 as a model.12  

• Copper also has been proposed to be safe for use in preventing bacterial growth in drinking water.12  Copper inactivates MS2 under controlled conditions at doses between 0.3 and 3 mg/L. Although requiring longer contact times than conventional disinfectants, it is a candidate for improving the safety of stored drinking water.
  
  

• The mechanism of bactericidal action of copper is well understood. After exposure of the target pathogen to copper ions, membranes become damaged and ROS (Reactive Oxygen Species) form that cause further cell damage over time and ultimately induce DNA destruction, thereby inactivating the bacterium. It should be noted that copper ions can be transported to neighboring pathogens in the biofilm and can toxify bacterial ‘neighbors’ as well.

• Copper in low doses is harmless and as noted, small amounts of copper are essential in our diets.

• Copper is readily available and a cost-effective reagent for the applications proposed.
  
  
  
  

Armor29™ Science and Intellectual Property : Patent Number 11,617,411 
Elemental copper in sufficient doses and exposures, is a proven antibacterial, anti-yeast and antiviral agent, and this is very well documented in the scientific literature.3,4,13 Copper has been shown to exert its bactericidal effect in a broad array of environments, from hospitals, schools, pre-schools, office buildings, nursing home facilities and presumably any bio-hazardous environment. Pure copper is highly malleable and can be applied to surfaces to lower the incidence of transmission of infectious agents from inanimate surfaces in different everyday environments. Mechanistically, copper targets bacterial genomic DNA by generating an oxidative-rich environment leading to generalized DNA damage and loss of bacterial viability.5,6,11 Because copper is a ‘pleiotropic agent’ (meaning it targets multiple biochemical events), bacterial resistance is extremely unlikely.6 This is in stark contrast to conventional antibiotics, where resistant mutants appear with surprising efficiency. This means that widespread use of copper is not going to contribute to the antibiotic resistance problem in the way that overuse of antibiotics represents a global health threat. Most experts acknowledge that limiting the spread of Hospital Acquired Infections (HAI) is best achieved using multiple layers.9,10 No single layer of protection will be 100% effective; however, each layer creates additive protection, as seen with personal protective equipment (PPE). Pathogen spreading by contact is acutely difficult to address using ‘passive’ barriers, especially when dealing with potentially pathogen-rich spillage on floors (which may be infrequently sanitized). Armor29™ is a patented technology that uses an active layer to address this problem in a highly effective manner as another layer of protection or barrier.  Armor29™ has developed, prototyped and patented a visually appealing copper faced outer shoe-sole configured with inlay copper foil to engage with and inactivate contaminating bodily fluids or other contaminants picked up from flooring. Armor29™ outsoles have been made and wear tested by a cohort of healthcare professionals. The reviews were very favorable and the design was universally praised by all in the focus group. Armor29™ has an anti-bacterial/anti-viral outsole that has shown to be effective in mitigating pathogenic spread.  It is similar to PPE as it offers a layer of  protection that is unavailable in the market today. Importantly, there is no health risk associated with use of this product and because it is active and ongoing, user intervention (like routine cleaning, wiping or UV exposure) is not required for protection. 

Background on risks of contamination and spread of pathogens via footwear 

Touch surfaces are effective vectors that foment the spread of pathogens from human to human. Pathogenic bacteria are hearty and highly evolved free living, single-cell organisms that have adapted to persist on surfaces for days, weeks and even months.1,2 It is no surprise that contaminated surfaces have been shown to promote pathogenic transmissions 1,2 in hospitals, where touch surfaces hold a higher risk for acquiring healthcare associated infections (HAIs). Other high-risk environments, such as crowded public areas (schools, offices, public transportation) are recognized as potential pathogenic or opportunistic transmission zones. Mitigating this kind of transmission is most effective using multiple layers of protection. The conventional layers are largely passive in nature and include proper hand hygiene, air filtration (HEPA filters), swabbing/cleaning practices, sterile attire, hairnets and proper aseptic protocols.  While these are all beneficial options, none of these barriers include an active bactericidal or viral-cidal step. We argue that passive barriers may still allow direct transmission of bacteria from contaminated inanimate surfaces to the human body. Footwear in particular, represents an ongoing source of pathogenic spread due to the rather large area on contact. In other words, there is continuing contact between outsoles and contaminated surfaces in pathogen-rich, high-risk environments as noted above. Creating a sterility barrier to disrupt the flooring to shoe-vector to self-inoculation cycle, is not always practical in an ongoing Emergency Department shift or clinical setting.  In some cases, sterile outer shoe covers (booties) may be used in high-risk areas (operating or trauma rooms); however, booties lose efficacy when exposed to aqueous contaminants, which is highly common in  clinical environments. For example, if a pathogen rich source solution soaks through a shoe cover, there is ongoing danger of contamination (self-inoculation of hands) when removing these outer covers, even with surgical gloves.
As noted, Copper is an effective antibacterial and antiviral material that has been thoroughly tested in lab studies with pathogens, including Staphylococcus aureus (MRSA),3,4,5  enteropathogenic E. coli, vancomycin resistant Enterococcus species (VRE), yeast (C. auris), K. pneumoniae, P. aeruginosa and A. baumannii. 4,5,6 In fact, studies in hospitals have shown reduced total microbial counts and a lower occurrence of pathogens in the presence of copper surfaces, specifically, VRE or MRSA.7,8,9,10 The antimicrobial efficacy of copper has been studied in a number of other environments. Different facilities (hospital, kindergarten, office, retirement home) and different touch surface types (floor drain lid, toilet flush button, door handle, light switch, closet touch surface, corridor handrail, front door handle, toilet support rail) were studied with varying cleaning practices and usage profiles.11 This recent study11 identified touch surface types that possess the highest bacterial loads in facilities in which individuals routinely work, recuperate or play. These authors also demonstrated the antibacterial efficacy of copper containing products as functional antimicrobial materials in these real-life scenarios.11 In summary, sheet-copper overlays on touch surface products are effective and functional antibacterial materials that reduce pathogenic loads on frequently contacted surfaces.


A Rational Approach to Create an outsole that Mitigates Pathogenic Spread.

Shown in Figure 1A, 1B is a bottom-up view of our copper sole concept and our rationale that underpins its design.  We reasoned that the placement of the copper is especially important in sub-regions (lineal distances that span a few inches) that represent a higher risk for retention of contaminated body fluids (saliva, sputum, feces, urine, blood, sera, etc.).  Such regions are retention gaps/valleys that physically trap and retain contaminants.  Once a contaminated fluid becomes entrapped in these areas, smaller volumes (<0.1mL) of aqueous material are most likely to dry out and desiccate forming crust that is difficult to physically remove. Moreover, these desiccated sites could be reactivated as potent sources of contamination when the sites become rehydrated upon subsequent exposure to moisture.  These high probability retention areas are less subject to frictional drag that comes with ambulation and movement.  In other words, once bio-organic deposits are in place, they are less likely to be scrubbed off.  By design, these areas of the outsole are packed with elemental copper sheeting, which offers maximal contact and micro-toxicity to problematic pathogens.

Experimental testing 
We are proposing that a copper-faced outer shoe sole will create an active, antibacterial surface barrier that mitigates transmission of pathogens in high-risk environments. The concept has scientific merit as discussed above; however, an important question still remains regarding the biophysical features of “copper-cide”: how far does copper diffuse into a small physical space (or 3D area) in order to exert its antimicrobial action?  To create a model to test diffusion and bacterial targeting, we used a disk-diffusion test (Fig 2).  The disk-diffusion method (aka “Kirby-Bauer”) tests the effectiveness of antibiotics on a specific microorganism. An agar plate is first spread with bacteria, then paper disks containing different antibiotics or test agents are placed in contact with the agar (Fig 2). The bacteria are allowed to grow on the agar media, and then growth is observed using a simple read-out:  a zone of clearing around the disk indicates no bacterial growth and conversely no clearing perimeter indicates bacterial resistance.  Control disks are important (i.e., no antibiotic or effector) to demonstrate that the test is reporting accurately.  The results are generally clear cut and sensitive. In some cases, the bacterial kill zone may be ‘hazy’ but still discernible as a clearing if the test drug (on the paper disk) is displaying weak bacterial killing. The Kirby-bauer test is used to evaluate antibiotic sensitivity in clinical labs.

For the first test, we used Pseudomonas aeruginosa (PAO) to examine copper sensitivity.  PAO is an opportunistic organism that is part of our normal flora (aka, our microbiome).  PAO is a good model of a commensal organism that is conditionally pathogenic (only in people who have debilitated immune systems, such as with AIDS or organ transplant patients whose immune system has been deliberately suppressed to prevent rejection of a donor organ).  In this experiment, we coated the plate a uniform layer of PAO at Time zero (T0, is the time of plating PAO before placing in the 37°C incubator), followed by placing two sterile paper disks (one with antibiotics and one with no antibiotics) and a sterile copper disk.  The culture was incubated for 24h and photographed (Fig 3).  The disks are marked in Fig. 3 and show the following.  The ‘paper disk negative control’ shows no zones of clearing.  The penicillin disk, in contrast, shows a clearing extending roughly 5-7mm from the edge of the 6mm disk.  This tells us that PAO is quite sensitive to the antibiotic and that sensitivity extends to roughly 6mm, due to diffusion of the antibiotic.  Penicillin is a rather large molecule with a molecular mass over 330 g/mol.  In general, larger molecules tend to be ‘diffusion limited’ in agarose. In contrast an inorganic atom like copper has an atomic mass of 63 g/mol and given its small mass and ionic charge (Cu++ in aqueous form) it will diffuse through the agar to a much greater extent. As shown in Fig. 3, the copper killing zone of PAO is significantly larger (25mm) than the higher molecular mass Penicillin (6mm).  This suggests that PAO is particularly sensitive to copper toxicity; even more so than Penicillin.  The shiny copper disk is oxidized on the plates (and appears black) yet still works well.  The pathogen MRSA (methicillin resistant Staphylococcus aureus) was also tested.  MRSA infections are caused by a type of staph bacteria that has become resistant to many of the antibiotics used to treat ordinary staph infections (cephalosporins, such as penicillin, oxacillin and amoxicillin).  Most MRSA infections occur in hospital care environments (nursing homes, ER, OR, dialysis centers).  This is called HA-MRSA (for health care-affiliated).  There is also a Community-affiliated (CA-MRSA) in the broader community. For this next experiment, we used MRSA to test Penicillin+Streptomycin (it should be streptomycin sensitive) compared to copper (as in Fig. 3) and cultures were left in the incubator for up to 6 days. 

The extended (6 day) incubation tests for the appearance of streptomycin + penicillin resistant strains (these appear as isolated colonies near the antibiotic loaded disk).   The data show that 1 day after growth of the cells on the petri-dish, killing or clearing zones form on the Pen-Strep disk (5mm wide) and to a greater extent around copper (>20mm).  As with PAO, the MRSA bacteria display a high sensitivity to copper; however, after 6 days, single clones appeared around the Pen-Strep disk showing that Strep resistant bacteria were selected.  In contrast, there were no colonies around the copper disk, suggesting that copper is an effective anti-bacterial with a low risk of developing resistance.  To be clear, it is possible for bacteria to acquire Copper resistance 11,13 but we did not see resistance in our short term (6 day) experiment.  We also can make some reasonable assumptions about the linear kill radius of copper based on the data in Figures 3 (and other data not shown).  Looking at the tread configuration and its micro-topography (see model outer-shoe sole in Fig 1A,B), it appears that copper will be effective in the recessed regions of high risk retention (defined in Fig 1).  This is because the disk sensitivity data show that copper can exert its bactericidal effect over a rather wide range (from 5-20mm), all other things being equal.  Copper, like many antimicrobial agents, requires a certain amount of time (3-5 minutes) to exert its influence. In a real-world situation, if small amounts of bodily fluid were to get entrapped in a retention area (Fig. 1), it is likely that small volumes (5-100 microliters) would dry and turn to a crusty material (depending on proteins present).  This would enhance exposure to the copper substrate which would naturally improve the bactericidal effect.



Seeing is believing
To demonstrate that our copper outsole works, you should rely on your eyes.  After all, humans are visual creatures.  Let’s do that using a genetically engineered fluorescent E. coli.  These cells glow as a fluorescent readout:  the brighter the fluorescence, the more bacteria there are. In the experiment shown (Fig 4), we prepared two outsoles:  without or with copper for direct comparison.  The outsoles were then exposed to a plate of bacteria and then imprinted on the fresh agar plates which were allowed to grow for 24 hours. Each colony represents Single bacterial cell. As shown, the GFP engineered bacteria make it easy to visualize bacterial loads on the outsole of a shoe and also clearly show copper toxicity effects.  We soaked the outsoles in the GFP bacteria and after a short exposure, we imprinted the outsoles onto sterile agar petri dishes.  Each fluorescent colony corresponds to a single bacterium, under these conditions.  It is obvious that the copper sole significantly reduced the number of bacterial colonies (>10,000 fold estimated reduction, Fig 5).  Other labs have demonstrated copper toxicity using this approach.

Copper effectively inhibits the outgrowth of bacteria that stick to shoes
Imagine you step in feces or clotted blood contaminated with MRSA in the hospital. There may be sufficient nutrients in organic matter on your shoe to promote growth and proliferation of a contaminating pathogen, even at room temperature. Bacteria grow really quickly (doubling every 30’ in some cases) and may replicate on your shoe after being deposited onto an outsole.  We wanted to test this.  We added a small piece of copper to a 1mL liquid culture of different bacteria and monitored growth with and without copper.  We tested three different bacterial species: Pseudomonas aeruginosa (an opportunistic pathogen), E. coli (a common bacterium in our gut microbiome) and Staphylococcus aureus (MRSA strain, drug resistant pathogen).

In this analysis we placed copper disks in broth cultures of 3 bacterial pathogens and we followed their growth over a 24h period. Data clearly show that ‘exponential’ or rapid growth of bacteria was strongly inhibited by copper ions. If a pathogen is trapped on a shoe along with nutrient rich organic matter, the copper will mitigate proliferation, thereby minimizing transmission. Shown is a representative growth curve for E. coli (other bacteria were identical).

Cells treated with copper disk had a significantly slower growing rate than the cells left untreated.  The “lag” phase of growth in copper treated cultures (which is the time period when cells are ‘adapting’ their growth environment) was significantly protracted by copper exposure. From this we infer that copper exposure will substantially reduce the yield of viable bacteria in any given micro-environment. 

Collectively the data strongly suggest that a copper overlay surface or a copper infused structure will negatively impact bacterial growth and substantially reduce the chances of cross contamination to other contact surfaces.

Does Copper kill Covid-19
The answer is yes, based on published data in a top medical journal (Fig 7).

New England Journal of Medicine  382;16 nejm.org April 16, 2020.

It is worth noting that the Covid-19 virus was SELECTIVELY destroyed by copper (a similar virus, SARS-CoV-1 that is a non-pathogenic strain was less sensitive to copper inactivation).

This shows that the Covid-19 virus ‘lives’ longer on cardboard, compared to a non-pathogenic virus. 

This also shows why Covid-19 spread between people is so effective, compared to other viruses.

Validation from our development partner CuVerro®
CuVerro® is a unique class of copper that continuously kills 99.9% (>1,000 FOLD reduction of harmful bacteria). It begins to kill bacteria on contact. It has been proven effective against bacteria by the Environmental Protection Agency (EPA.) All of our CuVerro copper is registered with the EPA; however under certain conditions, CuVerro copper will effectively kill most if not all bacteria. This was tested using a model that reflects our copper embedding system.

We asked a simple question:  if you have a very large population of bacteria on a surface (agar in this case) and add CuVerro copper grains to the surface for 30’, how many bacteria will survive to make new colonies?  The answer is essentially zero!  This means that CuVerro copper, under these conditions (aqueous exposure of actively growing bacteria for 30 min) the viable bacterial count is eliminated, as shown in Fig 8:

How do you measure the viability of bacteria?  

In Fig 10, the %viability is measured by what microbiologists call “Colony Counts”.  A live bacterium is capable of forming a single colony while a dead cell cannot.

References
1.  Boyce, J.M. (2007) Environmental contamination makes an important contribution to hospital infection. J Hosp Infect 65, 50–54. 

2.  Otter, J.A., Yezli, S., Salkeld, J.A.G. and French, G.L. (2013) Evidence that contaminated surfaces contribute to the transmission of hospital pathogens and an overview of strategies to address contaminated surfaces in hospital settings. Am J Infect Control 41, S6–S11 

3.  Noyce, J.O., Michels, H. and Keevil, C.W. (2006a) Potential use of copper surfaces to reduce survival of epidemic methicillin‐resistant Staphylococcus aureus in the healthcare environment. J Hosp Infect 63, 289–297. 

4.  Mehtar, S., Wiid, I. and Todorov, S.D. (2008) The antimicrobial activity of copper and copper alloys against nosocomial pathogens and Mycobacterium tuberculosis isolated from healthcare facilities in the Western Cape: an in‐vitro study. J Hosp Infect 68, 45–51.https://pubmed.ncbi.nlm.nih.gov/18069086/ 

5.  Gould, S.W.J., Fielder, M.D., Kelly, A.F., Morgan, M., Kenny, J. and Naughton, D.P. (2009) The antimicrobial properties of copper surfaces against a range of important nosocomial pathogens. Ann Microbiol 59, 151–156. 

6.  Koseoglu Eser, O., Ergin, A. and Hascelik, G. (2015) Antimicrobial activity of copper alloys against invasive multidrug‐resistant nosocomial pathogens. Curr Microbiol 71, 291–295. 

7.  Casey, A.L., Adams, D., Karpanen, T.J., Lambert, P.A., Cookson, B.D., Nightingale, P., Miruszenko, L., Shillam, R. et al. (2010) Role of copper in reducing hospital environment contamination. J Hosp Infect 74, 72–77. 

8.  Mikolay, A., Huggett, S., Tikana, L., Grass, G., Braun, J. and Nies, D.H. (2010) Survival of bacteria on metallic copper surfaces in a hospital trial. Appl Microbiol Biotechnol 87, 1875–1879. 

9.  Karpanen, T.J., Casey, A.I., Lambert, P.A., Cookson, B.D., Nightingale, P., Miruszenko, L. and Elliott, T.S.J. (2012) The antimicrobial efficacy of copper alloy furnishing in the clinical environment: a crossover study. Infect Control Hosp Epidemiol 33, 3–9https://pubmed.ncbi.nlm.nih.gov/22173515/. 

10.  Schmidt, M.G., Attaway, H.H., Sharpe, P.A., John, J., Sepkowitz, K.A., Morgan, A., Fairey, S.E., Singh, S. et al. (2012) Sustained reduction of microbial burden on common hospital surfaces through introduction of copper. J Clin Microbiol 50, 2217–2223. 

11. Inkinen, J. et al., (2016) Copper as an antibacterial material in different facilities.  Letters in Applied Microbiology 64, 19-26 

12.  Armstrong A. Sobsey M. and Casanova L.  2017.  Disinfection of bacteriophage MS2 by copper in water Appl Microbiol Biotechnol. 101:6891-6897https://pubmed.ncbi.nlm.nih.gov/28756591/. 

13.  Aillón-García P, Parga-Landa B, Guillén-Grima F. Effectiveness of copper as a preventive tool in health care facilities. A systematic review. Am J Infect Control. 2023 Feb 25:S0196-6553(23)00081-0. doi: 10.1016/j.ajic.2023.02.010. Epub ahead of print. PMID: 36842712. 

Acknowledgments

This progress report was carried out by TopoGEN, Inc. by technical staff who have no connection to Armor 29. Dr. Muller designed all experiments and provided oversight on the project while  lab work was carried out by TopoGEN employees. 
www.topogen.com
Dr. Muller’s LinkedIn information:
https://www.linkedin.com/in/mark-muller-a675902b/

TopoGEN has R&D facilities (documentation below**) consisting of 6000 sq ft of space that includes a business office, conference room, warehouse/loading dock, clean rooms and cell culture lab. This is a multi-million-dollar modern molecular biology and biochemistry laboratory as described below. We have a clinical lab director who is an MD and a technical team of others with advanced degrees. Dr. Muller’s Ph.D. thesis was in Molecular Virology (Murine Cytomegalovirus, a model herpes virus) and he has developed and taught numerous microbiology, virology, molecular genetics, biotechnology, biochemistry, cell biology and molecular biology courses. He established the first Department of Molecular Genetics in the US while a professor at The Ohio State University. He has held multiple leadership roles in academia and was responsible for establishing a new College of Medicine at the University of Central Florida (Orlando) in 2009. He has over 100 publications with >600 invited presentations around the globe. Dr. Muller founded TopoGEN in Central Colorado in 2015 with incentives from the State OEDIT program.

The report was compiled by Dr. Muller and reviewed independently  by TopoGEN’s  Scientific Advisory Board on June 12, 2023 and independently validated by a CLIA certified 3rd party Gnome Sciences, Powell, Ohio. Review available on request.


Facilities and Other Resources: TopoGEN Inc.

Laboratory:

The new laboratories for TopoGEN, Inc. are located in a 3000+ square foot commercial building owned by the Company. The R&D Building is located behind a security gate, monitored 24/7 with video, at a major municipal airport. There is no public access and the company facilities are located in a commercial building with a ground lease with the Federal Government (and approved by the FAA FSDO. There are outside security cameras that monitor access. A keycard system with biometric monitoring controls who comes and leaves the facilities. The main lab includes offices for staff, common equipment rooms, a clean room for cell culture, production lab, shipping benches for research diagnostic products, a QC lab and multiple benches/workstations for molecular biology and biochemistry. There are typical small equipment items (microfuges, waterbaths, various temperature blocks, nanodrop, uv-vis spec) and the usual assortment of large equipment items (Floor shakers, Sorvall centrifuge, Attune Flow Cytometer, sterilization/autoclave, RO polished water station) and ice machines that are standard for molecular and biochemical studies. Dishwashing facilities and glassware handling area is adjacent to the lab. There is a separate business office and a common office room with 5-6 desks. We just added a large conference room (300 sq ft) for board meetings and presentations by company staff and visiting consultants. Co-located with the R&D production lab for protein purification and column work (reach-in cold boxes with fraction collectors, integrated with UV monitors). This lab is designed to support the proposed studies as a complete biochemistry and molecular biology lab with the necessary equipment (analytical balance, pH meters, top balance, PC computers, low pressure columns, gel equipment, biohazard hoods, as noted). The overexpression and production facilities are located in this lab. A separate, climate controlled tissue culture room with isolated filtered air is located immediately contiguous to the main laboratory with CO2 incubators, waterbaths, BioGuard hoods, a Leica inverted phase contrast, a Cellometer and eye-wash stations. Liquid nitrogen (LN2) Cell line storage and handling facilities, computer tracking and QC services are in place for all aspects of the cell culture work on the project (our LN2 frozen storage is limited currently and we need to expand). Routine testing for contamination (mycoplasma, bacterial/yeast) are carried out in a separate facility. We also have backup LN2 storage and computer tracking of all cell lines is in place and will be duplicated at a distal location with our academic collaborator. Moreover, company resources will be used to assemble and produce research diagnostic reagents that will be needed for this project. The company products are highly controlled by a team of technicians who conduct rigorous quality control experiments per GLP. In addition, the Company is a CRO and maintains high standards in quality control and inventory tracking. The Company has made a significant investment in the developing cell-based diagnostic kits for researchers and is dedicated to providing all resources to ensure success of this project. The Company is expanding its operational footprint in 2020 by adding an additional 3000 sq. ft of R&D space, extra offices, seminar rooms and clean room facilities.

Computer:
State of the art PC workstations and company server and Apple computers are located in the main laboratory and in business offices along with a LAN and shared printing facilities. The company is connected to high speed internet (fiber) and the entire facility is firewalled wireless. The lab additionally has various state of the art peripherals (scanners, digital cameras, photo-documentation equipment). A group of IT professionals manage and maintain a new company web site and web based services, coordinate contact with distributors and perform routine maintenance on the company server. All data is stored on the cloud with server backup using FilePro to track lot numbers and QC data for products. Company data files are stored in the cloud with the latest cyber-security protections.

Offices/Conference Rooms:

There are desks for technicians and staff just off the main lab (see lab resources above). All offices have standard equipment and computers as noted above. A conference room is located onsite with space for 20 attendees. A projection screen and LCD camera, communication devices for video conferencing and computer are located in this room. Office equipment and resources (secretary, Xerox machine, fax, email services, supplies, etc.) is similar to that found in academic settings. The senior management for the company has separate corporate offices, with video conferencing capability, LCD projection with one screen. A new conference room has been added to accommodate 20 staff with audiovisual equipment for seminars & lab presentations as well as board meetings. One wall of the conference room is a painted-on ‘white board’ for lectures and presentations. The conference room serves as a lunch room to facilitate interaction between staff and ensure the ‘no food in lab’ policy is adhered to.

Scientific Corporate Environment:

The company is housed in a free-standing commercial building that houses the newly renovated wet- lab space. TopoGEN, as a for-profit Colorado-based Company, also has access to state of the art equipment at University of Colorado at Boulder BioFrontiers Institute. There are multiple cores in the new Biofrontiers Institute that we can use on a fee basis (same rates as CU Faculty are charged). The cores include: an imaging core, a NexGen sequencing core, a Bioinformatics core, a proteomics core and a cytometry core. The Scientific Advisory Board is composed of senior, research-oriented academics and is given strong oversight powers to all projects in the company pipeline. The company maintains ties with University of Colorado at Boulder and Colorado State University. The professional staff members are encouraged to attend seminars, engage in independent collaborations and utilize core services, at subsidized fee for service rates, and library facilities for access to on-line journals. The Company brings in undergraduate trainees from Colorado State University (Ft. Collins) and UC Boulder as interns and work-study hourly employees. In addition, we run an UG research program, funded by the State Office of Economic Development and International Trade for 3-5 students each summer. During the academic year, we attract local high school talent who undergo training (part time) and who will continue to work in summer months. Student training is considered a rather important contribution of TopoGEN to our local community, due to limited training/educational options for students.