Team:Imperial/Implementation

From 2014.igem.org

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                         <ul>
                         <ul>
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                            <li><a data-scroll href="#Introduction">Introduction</a>
 
-
                            </li>
 
                             <li><a data-scroll href="#Ultrafiltration">Ultrafiltration</a>
                             <li><a data-scroll href="#Ultrafiltration">Ultrafiltration</a>
                             </li>
                             </li>
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                             <li><a data-scroll href="#Phytochelatin-dCBD metal binding assay">Phytochelatin-dCBD metal binding assay</a>
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                             <li><a data-scroll href="#Aqualose">Aqualose</a>
 +
                            </li>
 +
                            <li><a data-scroll href="#Future Functionalisation">Future Functionalisation</a>
                             </li>
                             </li>
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                             <li><a data-scroll href="#Nickel filtration assay">Nickel filtration assay</a>
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                             <li><a data-scroll href="#Process Engineering">Process Engineering</a>
                             </li>
                             </li>
                             <li><a data-scroll href="#References">References</a>
                             <li><a data-scroll href="#References">References</a>
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                 <div class="pure-u-1-2">
                 <div class="pure-u-1-2">
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                     <h2>Overview</h2>
+
                     <h2> </h2>
-
                    <p>By attaching functional proteins to cellulose we can expand it's properties and selectivity capture specific contaminants in water. We used five different cellulose binding domains and fused them to different metal binding proteins, and sfGFP. We performed assays to test the binding of the CBD fusions to our cellulose.</p>
+
<p><em><strong>“To meet new environmental regulations, a step change is required in how we process water. Functionalised cellulose filtration could be a viable part of the solution.”</strong></em> - Dr. Michael Chipps, Principal Research Scientist at Thames Water
 +
</p>
                 </div>
                 </div>
                 <div class="pure-u-1-2">
                 <div class="pure-u-1-2">
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                     <h2>Key Achievements </h2>
+
                     <h2>At a Glance</h2>
                     <ul>
                     <ul>
-
                         <li>Made cellulose binding domains</li>
+
                         <li>Ultrafiltration has many advantages for <a href="https://2014.igem.org/Team:Imperial/Water_Report#wastewate"> wastewater recycling </a></li>
-
                        <li></li>
+
                         <li>Limitations in current ultrafiltration technologies can be addressed by functionalised membranes for specific contaminant binding</li>
-
                        <li></li>
+
                         <li>The modularity underlying membrane fuctionalisation allows future targeting of any current or emerging contaminant</li>
-
                        <li></li>
+
                         <li>Our aqualose water treatment process offers a cost effective alternative to traditional ultrafiltration</li>
-
                         <li></li>
+
                         <li>The process is adaptable functioning equally as a bolt on to existing treatment facilities or as a standalone purification solution</li>
-
                         <li></li>
+
-
                         <li></li>
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                         <li></li>
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     <div class="pure-u-1-1">
     <div class="pure-u-1-1">
         <section id="Introduction">
         <section id="Introduction">
-
             <h2>Introduction</h2>
+
             <h2>Ultrafiltration</h2>
-
             <p>
+
<figure class="content-image image-right">
 +
                <img class="image-full" src="https://static.igem.org/mediawiki/2014/4/47/IC-14_Water_Purification_Spectrum1.JPG">
 +
                <figcaption>Figure 1: Size exclusion for different grades of filter (from http://www.edstrom.com/)</figcaption>
 +
             </figure>           
 +
<p>
                 Ultrafiltration (UF) membranes have a pore size of 0.1 to 0.01um (10 to 100nm) and are capable of removing particulates, bacteria and viruses. Microbial cellulose sheets naturally have pore sizes in this range (Gatenholm, P., & Klemm, D. (2010), Mautner et al 2014). Current ultrafiltration cannot remove small molecule contaminants such as pesticides and heavy metals however. Whilst nanofiltration and reverse osmosis membranes can exclude these small molecules they are expensive and energy intensive to use. Flow rates are low, they require very high pressures and the input water must be already purified by primary and secondary processes to avoid damaging the membranes.</p>
                 Ultrafiltration (UF) membranes have a pore size of 0.1 to 0.01um (10 to 100nm) and are capable of removing particulates, bacteria and viruses. Microbial cellulose sheets naturally have pore sizes in this range (Gatenholm, P., & Klemm, D. (2010), Mautner et al 2014). Current ultrafiltration cannot remove small molecule contaminants such as pesticides and heavy metals however. Whilst nanofiltration and reverse osmosis membranes can exclude these small molecules they are expensive and energy intensive to use. Flow rates are low, they require very high pressures and the input water must be already purified by primary and secondary processes to avoid damaging the membranes.</p>
-
<p>
 
-
                https://static.igem.org/mediawiki/2014/4/47/IC-14_Water_Purification_Spectrum1.JPG
 
-
 
-
Size exclusion for different grades of filter (from http://www.edstrom.com/)
 
-
Depending on input water quality UF systems may replace or complement existing secondary (coagulation, flocculation, sedimentation) and tertiary filtration (sand filtration and chlorination) systems in water treatment plants. Pretreatment of feed water is usually required to prevent reduce damage to the membrane units though ultrafiltration may be used in standalone systems for isolated regions. UF processes have the following advantages over traditional treatment methods:
+
               
 +
<p>Depending on input water quality UF systems may replace or complement existing secondary (coagulation, flocculation, sedimentation) and tertiary filtration (sand filtration and chlorination) systems in water treatment plants. Pretreatment of feed water is usually required to prevent reduce damage to the membrane units though ultrafiltration may be used in standalone systems for isolated regions. UF processes have the following advantages over traditional treatment methods:
</p>
</p>
             <p>
             <p>
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                         Chemical free (aside from cleaning)</li>
                         Chemical free (aside from cleaning)</li>
                     <li>
                     <li>
-
                         Constant product quality regardless of feed quality (excluding small molecule contaminants, changes in input water quality affect only the life of the membrane, not the quality of the flow through)</li>
+
                         Constant output quality regardless of feed quality (excluding small molecule contaminants, changes in input water quality affect only the life of the membrane, not the quality of the flow through)</li>
                     <li>
                     <li>
                         Compact plant size, efficient for small scale, <a href="https://2014.igem.org/Team:Imperial/Water_Report#decentralisation"> decentralised</a> purification</li>
                         Compact plant size, efficient for small scale, <a href="https://2014.igem.org/Team:Imperial/Water_Report#decentralisation"> decentralised</a> purification</li>
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                 UF processes are currently limited by the high cost of membranes, inevitable membrane fouling means they must be regularly replaced. There use is also restricted by limitations in removal of small molecule contaminants. They can only be employed where feed water is free of these contaminants or in tandem with other (often slow or energy intensive) treatment methods for removing them. </p>
                 UF processes are currently limited by the high cost of membranes, inevitable membrane fouling means they must be regularly replaced. There use is also restricted by limitations in removal of small molecule contaminants. They can only be employed where feed water is free of these contaminants or in tandem with other (often slow or energy intensive) treatment methods for removing them. </p>
         </section>
         </section>
-
         <section id="Ultrafiltration">
+
         <section id="Aqualose">
-
             <h2>Ultrafiltration</h2>
+
             <h2>Aqualose</h2>
-
        </section>
+
                                                            <table class="tg image-full">
-
        <section id="Phytochelatin-dCBD metal binding assay">
+
  <tr>
-
            <h2>Phytochelatin-dCBD metal binding assay</h2>
+
    <th class="tg-e3zv">Component</th>
 +
    <th class="tg-e3zv">Quantity</th>
 +
    <th class="tg-e3zv">Source</th>
 +
    <th class="tg-e3zv">Cost breakdown (£)</th>
 +
    <th class="tg-e3zv">Cost (£)</th>
 +
  </tr>
 +
  <tr>
 +
    <td class="tg-031e">Water</td>
 +
    <td class="tg-031e">4l</td>
 +
    <td class="tg-031e">London South West Water</td>
 +
    <td class="tg-031e">4 liters of £5.5195 per m3</td>
 +
    <td class="tg-031e">0.02</td>
 +
  </tr>
 +
  <tr>
 +
    <td class="tg-031e">400 g granulated sugar</td>
 +
    <td class="tg-031e">400g</td>
 +
    <td class="tg-031e">Tesco's</td>
 +
    <td class="tg-031e">79p per 1 kg</td>
 +
    <td class="tg-031e">0.32</td>
 +
  </tr>
 +
  <tr>
 +
    <td class="tg-031e">Clipper green tea tea bags</td>
 +
    <td class="tg-031e">4</td>
 +
    <td class="tg-031e">Clipper tea</td>
 +
    <td class="tg-031e">300 teabags for £9.99</td>
 +
    <td class="tg-031e">0.13</td>
 +
  </tr>
 +
  <tr>
 +
    <td class="tg-031e">Aspall organic cider vinegar</td>
 +
    <td class="tg-031e">2</td>
 +
    <td class="tg-031e">Aspall Suffolk</td>
 +
    <td class="tg-031e">400 ml of a £2.25 500 ml bottle</td>
 +
    <td class="tg-031e">1.80</td>
 +
  </tr>
 +
  <tr>
 +
    <td class="tg-031e">Total</td>
 +
    <td class="tg-e3zv"></td>
 +
    <td class="tg-e3zv"></td>
 +
    <td class="tg-e3zv"></td>
 +
    <td class="tg-e3zv">2.27</td>
 +
  </tr>
 +
  <tr>
 +
    <td class="tg-e3zv">Product</td>
 +
    <td class="tg-031e"></td>
 +
    <td class="tg-031e"></td>
 +
    <td class="tg-031e"></td>
 +
    <td class="tg-031e"></td>
 +
  </tr>
 +
  <tr>
 +
    <td class="tg-e3zv">Component</td>
 +
    <td class="tg-e3zv">Quantity</td>
 +
    <td class="tg-e3zv">Source</td>
 +
    <td class="tg-e3zv">Price breakdown (£)</td>
 +
    <td class="tg-e3zv">Price per g (£)</td>
 +
  </tr>
 +
  <tr>
 +
    <td class="tg-031e">Bacterial cellulose yield</td>
 +
    <td class="tg-031e">60 cm by 40 cm = 0.24 m2</td>
 +
    <td class="tg-031e">production from single tray</td>
 +
    <td class="tg-031e">110 g/m2 x 0.24 m2 = 26.4g</td>
 +
    <td class="tg-e3zv">0.09</td>
 +
  </tr>
 +
</table>
 +
<figcaption>Figure 2: Cost analysis of Aqualose </figcaption>
 +
            <p>Microbial cellulose membranes are considerably cheaper than competitors. Whilst Polyvinylidene fluoride (PVDF) ultrafiltration membranes typically sell to the wastewater industry at upwards of $100 /m<sup>2</sup> (Shenzhen Youber Technology Co., Ltd. no date). Current bacterial cellulose production for nata de coco costs around $1.6 /gram (Lee et al. 2014) and our cellulose with <em>G. xylinus</em> igem cost only £0.09 ($0.14) /g. Our thin cellulose membranes for filtration weighed around 20 g/m<sup>2</sup> so would cost just $2.80 /m<sup>2</sup>. Whilst <a href="https://2014.igem.org/Team:Imperial/Mechanical_Testing"> Our studies</a> and existing literature (Fifield 2012) suggest bacterial cellulose is a strong and durable material however we would expect a shorter membrane life than the highly durable PVDF. Being considerably cheaper and easier to dispose of however, cellulose membranes could be more regularly replaced and still provide a more cost effective solution. This would also save on chemical washes regularly required to sustain the extended life of PVDF membranes.
 +
                </p>
         </section>
         </section>
-
         <section id="Nickel filtration assay">
+
         <section id="Future Functionalisation">
-
             <h2>Nickel filtration assay</h2>
+
             <h2>Future Functionalisation</h2>
 +
<p>Our system for functionalising cellulose membranes is inherently modular. Proteins to bind or degrade a limitless range of contaminants can be bound to cellulose membranes. Filtration can then be adapted to the particular contaminants, altering seasonally, geographically and adapting over time to emerging threats. Metaldehyde contamination in the English home counties (Mathiesen 2013) could be addressed with specific degradation enzymes and microcystin could be removed from supplies in Ohio contaminated from algal blooms (Queally 2014).
 +
                </p>
 +
        </section>
 +
        <section id="Process Engineering">
 +
            <h2>Process Engineering</h2>
             <figure class="content-image image-right">
             <figure class="content-image image-right">
-
                 <img class="image-full" src="https://static.igem.org/mediawiki/2014/9/9d/IC14-Water_filtration_pictures.png">
+
                 <img class="image-full" src="https://static.igem.org/mediawiki/2014/3/3f/IC-14_Membrane_backwash.gif">
-
                 <figcaption>Figure X: The set up for the nickel filtration assay. A) The coffee press used for the mounting of the cellulose and for filtration process. B) Cellulose without attached phytochelatin-dCBD protein. C) Functionalised cellulose with attached phytochelatin-dCBD protein.</figcaption>
+
                 <figcaption>Figure 3: Schematic for dead end membrane filtration with backwash (from www.meco.com)</figcaption>
             </figure>
             </figure>
             <p>
             <p>
-
                The nickel ions are an example of heavy metals, poisonous even in relatively small concentrations in water and notoriously difficult to filter with current filtration methods. Therefore our filtration concept was tested against a concentration of nickel in water that far exceeds the safe limits. We have attempted to filter high amount of nickel (250 μM) through the cellulose filters grown by the <em>G. Xylinus</em> ATCC53582 strain (<a href=”http://parts.igem.org/Part:BBa_K1321305”>K1321305</a>). The phytochelatin-dCBD fusion (<a href=”http://parts.igem.org/Part:BBa_K1321110”>K1321110</a>) was coated on the surface of the cellulose to make a nickel specific functionalised ultra filtration membrane. To test the two membranes we have used coffee press. As a control measure we have also attempted to the filter the nickel solution through the cellulose that was not further functionalised.
+
              We envisage functionalised bacterial cellulose membranes utilised in a plate and frame, dead end filtration setup for easy backflush cleaning and replacement when fouled.
 +
 
 +
 
 +
This process is particularly applicable for water recycling. Ultrafiltration combines well with activated sludge for purification when organic solids content is high and the additional membrane functionalisation can target removal of recalcitrant small molecules that can accumulate in recycled water. Current wastewater treatment plants could be easily retrofitted with the technology with dedicated facilities constructed in the longer term. </p>
 +
 
 +
<h3>Disposal of Contaminants</h3>
 +
<p>Heavy metal contaminants pose a serious problem for all water processing solutions as they ultimately cannot be destroyed. To prevent escape into the environment they must be recovered and disposed of into controlled landfill (European Commission 2002). Trapping contaminants on filtration membranes concentrates them for easy recovery. To prolong filter life, contaminants could be regularly eluted and collected. When membranes are spent they could either be disposed of directly into controlled landfill or to reduce volume - incinerated and the flue scrubbed. Incineration is the most effective solution to destroy recalcitrant organic pollutants and unlike for other materials, incineration of cellulose membranes produces no harmful by products.</p>
 +
 
             </p>
             </p>
</br>
</br>
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            <h3>Results</h3>
 
         </section>
         </section>
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         <section id="References">
         <section id="References">
             <h2>References</h2>
             <h2>References</h2>
 +
<p>European Commission (2002) “Heavy Metals in Waste - Final Report” Accessed 17th October 2014 http://ec.europa.eu/environment/waste/studies/pdf/heavy_metalsreport.pdf
 +
 +
Fifield, Leonard, “Bacterial Cellulose Composites Opportunities and Challenges” PNNL Applied Materials Science Group (2012). Accessed 17th October 2014
 +
http://www1.eere.energy.gov/manufacturing/rd/pdfs/sustainable_nanomaterials_workshop_pnnl.pdf
 +
 +
 +
Gatenholm, P., & Klemm, D. (2010). Bacterial nanocellulose as a renewable material for biomedical applications. MRS bulletin, 35(03), 208-213.
 +
 +
James Queally “Toledo's tap water undrinkable for a second day; test results delayed” The LA times 3 August 2014. Accessed 17th October 2014
 +
http://www.latimes.com/nation/nationnow/la-na-nn-toledo-ohio-toxins-water-20140802-story.html#page=1
 +
Karl Mathiesen “Slug poison found in one in eight of England's drinking water sources” the Guardian, Wednesday 10 July 2013. Accessed 17th October 2014
 +
http://www.theguardian.com/environment/2013/jul/10/slug-poison-drinking-water-metaldehyde
 +
 +
 +
Lee, Koon‐Yang, Gizem Buldum, Athanasios Mantalaris, and Alexander Bismarck. "More than meets the eye in bacterial cellulose: Biosynthesis, bioprocessing, and applications in advanced fiber composites." Macromolecular bioscience 14, no. 1 (2014): 10-32.
 +
 +
Mautner, A., Lee, K. Y., Lahtinen, P., Hakalahti, M., Tammelin, T., Li, K., & Bismarck, A. (2014). Nanopapers for organic solvent nanofiltration. Chemical Communications, 50(43), 5778-5781.
 +
 +
Shenzhen Youber Technology Co., Ltd. Accessed 17th October 2014 http://water-treatment.en.alibaba.com/
 +
 +
Figure references:
 +
http://www.edstrom.com/assets/1/7/Water_Purification_Spectrum1.JPG
 +
http://upload.wikimedia.org/wikipedia/en/c/c0/MBRvsASP_Schematic.jpg
 +
http://www.meco.com/meco-biopharmaceutical/products/membrane-filtration</p>
         </section>
         </section>

Latest revision as of 02:39, 18 October 2014

Imperial iGEM 2014

“To meet new environmental regulations, a step change is required in how we process water. Functionalised cellulose filtration could be a viable part of the solution.” - Dr. Michael Chipps, Principal Research Scientist at Thames Water

At a Glance

  • Ultrafiltration has many advantages for wastewater recycling
  • Limitations in current ultrafiltration technologies can be addressed by functionalised membranes for specific contaminant binding
  • The modularity underlying membrane fuctionalisation allows future targeting of any current or emerging contaminant
  • Our aqualose water treatment process offers a cost effective alternative to traditional ultrafiltration
  • The process is adaptable functioning equally as a bolt on to existing treatment facilities or as a standalone purification solution

Ultrafiltration

Figure 1: Size exclusion for different grades of filter (from http://www.edstrom.com/)

Ultrafiltration (UF) membranes have a pore size of 0.1 to 0.01um (10 to 100nm) and are capable of removing particulates, bacteria and viruses. Microbial cellulose sheets naturally have pore sizes in this range (Gatenholm, P., & Klemm, D. (2010), Mautner et al 2014). Current ultrafiltration cannot remove small molecule contaminants such as pesticides and heavy metals however. Whilst nanofiltration and reverse osmosis membranes can exclude these small molecules they are expensive and energy intensive to use. Flow rates are low, they require very high pressures and the input water must be already purified by primary and secondary processes to avoid damaging the membranes.

Depending on input water quality UF systems may replace or complement existing secondary (coagulation, flocculation, sedimentation) and tertiary filtration (sand filtration and chlorination) systems in water treatment plants. Pretreatment of feed water is usually required to prevent reduce damage to the membrane units though ultrafiltration may be used in standalone systems for isolated regions. UF processes have the following advantages over traditional treatment methods:

  • Chemical free (aside from cleaning)
  • Constant output quality regardless of feed quality (excluding small molecule contaminants, changes in input water quality affect only the life of the membrane, not the quality of the flow through)
  • Compact plant size, efficient for small scale, decentralised purification
  • High quality of output water particularly with regards to pathogen removal

UF processes are currently limited by the high cost of membranes, inevitable membrane fouling means they must be regularly replaced. There use is also restricted by limitations in removal of small molecule contaminants. They can only be employed where feed water is free of these contaminants or in tandem with other (often slow or energy intensive) treatment methods for removing them.

Aqualose

Component Quantity Source Cost breakdown (£) Cost (£)
Water 4l London South West Water 4 liters of £5.5195 per m3 0.02
400 g granulated sugar 400g Tesco's 79p per 1 kg 0.32
Clipper green tea tea bags 4 Clipper tea 300 teabags for £9.99 0.13
Aspall organic cider vinegar 2 Aspall Suffolk 400 ml of a £2.25 500 ml bottle 1.80
Total 2.27
Product
Component Quantity Source Price breakdown (£) Price per g (£)
Bacterial cellulose yield 60 cm by 40 cm = 0.24 m2 production from single tray 110 g/m2 x 0.24 m2 = 26.4g 0.09
Figure 2: Cost analysis of Aqualose

Microbial cellulose membranes are considerably cheaper than competitors. Whilst Polyvinylidene fluoride (PVDF) ultrafiltration membranes typically sell to the wastewater industry at upwards of $100 /m2 (Shenzhen Youber Technology Co., Ltd. no date). Current bacterial cellulose production for nata de coco costs around $1.6 /gram (Lee et al. 2014) and our cellulose with G. xylinus igem cost only £0.09 ($0.14) /g. Our thin cellulose membranes for filtration weighed around 20 g/m2 so would cost just $2.80 /m2. Whilst Our studies and existing literature (Fifield 2012) suggest bacterial cellulose is a strong and durable material however we would expect a shorter membrane life than the highly durable PVDF. Being considerably cheaper and easier to dispose of however, cellulose membranes could be more regularly replaced and still provide a more cost effective solution. This would also save on chemical washes regularly required to sustain the extended life of PVDF membranes.

Future Functionalisation

Our system for functionalising cellulose membranes is inherently modular. Proteins to bind or degrade a limitless range of contaminants can be bound to cellulose membranes. Filtration can then be adapted to the particular contaminants, altering seasonally, geographically and adapting over time to emerging threats. Metaldehyde contamination in the English home counties (Mathiesen 2013) could be addressed with specific degradation enzymes and microcystin could be removed from supplies in Ohio contaminated from algal blooms (Queally 2014).

Process Engineering

Figure 3: Schematic for dead end membrane filtration with backwash (from www.meco.com)

We envisage functionalised bacterial cellulose membranes utilised in a plate and frame, dead end filtration setup for easy backflush cleaning and replacement when fouled. This process is particularly applicable for water recycling. Ultrafiltration combines well with activated sludge for purification when organic solids content is high and the additional membrane functionalisation can target removal of recalcitrant small molecules that can accumulate in recycled water. Current wastewater treatment plants could be easily retrofitted with the technology with dedicated facilities constructed in the longer term.

Disposal of Contaminants

Heavy metal contaminants pose a serious problem for all water processing solutions as they ultimately cannot be destroyed. To prevent escape into the environment they must be recovered and disposed of into controlled landfill (European Commission 2002). Trapping contaminants on filtration membranes concentrates them for easy recovery. To prolong filter life, contaminants could be regularly eluted and collected. When membranes are spent they could either be disposed of directly into controlled landfill or to reduce volume - incinerated and the flue scrubbed. Incineration is the most effective solution to destroy recalcitrant organic pollutants and unlike for other materials, incineration of cellulose membranes produces no harmful by products.


References

European Commission (2002) “Heavy Metals in Waste - Final Report” Accessed 17th October 2014 http://ec.europa.eu/environment/waste/studies/pdf/heavy_metalsreport.pdf Fifield, Leonard, “Bacterial Cellulose Composites Opportunities and Challenges” PNNL Applied Materials Science Group (2012). Accessed 17th October 2014 http://www1.eere.energy.gov/manufacturing/rd/pdfs/sustainable_nanomaterials_workshop_pnnl.pdf Gatenholm, P., & Klemm, D. (2010). Bacterial nanocellulose as a renewable material for biomedical applications. MRS bulletin, 35(03), 208-213. James Queally “Toledo's tap water undrinkable for a second day; test results delayed” The LA times 3 August 2014. Accessed 17th October 2014 http://www.latimes.com/nation/nationnow/la-na-nn-toledo-ohio-toxins-water-20140802-story.html#page=1 Karl Mathiesen “Slug poison found in one in eight of England's drinking water sources” the Guardian, Wednesday 10 July 2013. Accessed 17th October 2014 http://www.theguardian.com/environment/2013/jul/10/slug-poison-drinking-water-metaldehyde Lee, Koon‐Yang, Gizem Buldum, Athanasios Mantalaris, and Alexander Bismarck. "More than meets the eye in bacterial cellulose: Biosynthesis, bioprocessing, and applications in advanced fiber composites." Macromolecular bioscience 14, no. 1 (2014): 10-32. Mautner, A., Lee, K. Y., Lahtinen, P., Hakalahti, M., Tammelin, T., Li, K., & Bismarck, A. (2014). Nanopapers for organic solvent nanofiltration. Chemical Communications, 50(43), 5778-5781. Shenzhen Youber Technology Co., Ltd. Accessed 17th October 2014 http://water-treatment.en.alibaba.com/ Figure references: http://www.edstrom.com/assets/1/7/Water_Purification_Spectrum1.JPG http://upload.wikimedia.org/wikipedia/en/c/c0/MBRvsASP_Schematic.jpg http://www.meco.com/meco-biopharmaceutical/products/membrane-filtration