Users obtain a domain name to establish a unique identity on the Internet. Domain names are not only used to serve names and addresses of computers and services but also to store security controls, such as SPF or CAA records. Many of the Internet protocols were designed at a time where built-in security was not a requirement. The IETF continues to standardize protocol extensions to address today’s security needs.
For some protocols security is added with controls stored in your domain names zone file. In order to have the desired effect, the pre-condition is of course that your domain name is secure. In other words, the security of your application that makes use of controls in DNS is only as secure as the security of your domain name.
Hijacking a domain name because of weak credentials at the registrar may get the job done but this is far from stealthy and will likely not last long. In many cases it is sufficient to hijack an abandoned subdomain. Taking over abandoned subdomains may be unnoticed by the owner for a very long period of time making it also very useful for targeted attacks.


The National Assessment Program – Literacy and Numeracy (NAPLAN) is an annual assessment for students in Year 3, Year 5, Year 7 and Year 9. It has been an everyday part of the school calendar since 2008. You can read, download and practice NAPLAN Past Papers 2016 with Answers Year 3, 5, 7 and 9 at the end of the article.
NAPLAN tests the sorts of skills that are essential for every child to progress through school and life, such as reading, writing, spelling and numeracy. The assessments are undertaken nationwide, every year, in the second full week in May.
NAPLAN is made up of tests in the four areas (or ‘domains’) of:
- language conventions (spelling, grammar and punctuation)
NAPLAN tests skills in literacy and numeracy that are developed over time through the school curriculum. [naplan]
You can read, download and practice with the NAPLAN Past Papers 2016 with Answers Year 3, 5, 7 and 9 below. If you have difficulties to download the files, you can read the guide at here How to / Guide to download the file with steps.


In a remarkably bold and landmark study, scientists in China have reportedly edited genes in human embryos to erase a fatal blood disorder.
Published in Protein & Cell, researchers led by Sun Yat-sen at University of Guangzhou are confirming the widespread rumours about human trails of CRISPR/Cas9 gene editing. The rumours sparked widespread debates about ethical implications and the unfair usage of the same.
According to their paper titled “CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes”, the researchers for now used ‘non-viable’ embryos which couldn’t have resulted in any form of live birth. The widely touted and popularized CRISPR/Cas9 gene editing technique was used to erase the genes causing β-thalassaemia in humans, a potentially fatal disorder of the blood. Thanks to fewer restrictions on human tests, the scientists became the first of many to conduct human trials.
Long Way Ahead for CRISPR/Cas9
The researchers are reported failure in their attempts to eradicate β-thalassaemia gene from the embryo. The system in which the enzyme complex of CRISPR/Cas9 binds to DNA and splices it has now been well studied in animal embryos and human cell lines. However, in human embryos the enzyme complex failed to repair the problematic gene. The researchers took precaution by creating ‘non-viable’ embryo following fertilisation of the embryo by two sperms. This prevents the chances of a live birth, however the embryo does reach the first stages of development.
Alarmingly Low Gene-Editing Success Rates
The team lead by Huang targeted the β-globin protein gene which is responsible for β-thalassaemia. Using 86 embryos, which the researchers injected with the CRISPR/Cas9 gene editing enzyme. Of the surviving embryos, 54 were tested for the spliced β-globin protein gene. Of these only 28 showed to be successfully spliced and just a fraction of these had the replacement β-globin gene. Not just that, a few off-target mutations were also found that were introduced by CRISPR/Cas9 technique.
The paper which was rejected by Nature and Science on ethical grounds, underlines the need to improve the technique before beginning experimentation in humans. Huang and his team will begin work on reducing the off-target mutations induced by CRISPR/Cas9 technique, using combination of other gene-editing techniques.
Source: Protein & Cell (Open Access)


Last updated on 15 August 2016
Red swamp crawfish, Crawfish, crayfish, Cangrejo americano, Cangrejo de las marismas
There is scarce information about the population structure of this species. According with Torres and Álvarez 2012, there is no significant differentiation between Red swamp crawfish in Louisiana.
Within FishSource, the term "fishery" is used to indicate each unique combination of a flag country with a fishing gear, operating within a particular management unit, upon a resource. That resource may have a known biological stock structure and/or may be assessed at another level for practical or jurisdictional reasons. A fishery is the finest scale of resolution captured in FishSource profiles, as it is generally the scale at which sustainability can most fairly and practically be evaluated.
No related FIPs
No related MSC certifications


The quest for fusion energy is more than 60 years old and the current great hope, the $18 billion ITER reactor, won't hit its stride until 2027 at the earliest. Surely there is a quicker and cheaper route. Behold the spherical tokamak, a plumped-up version of the mainstream tokamak reactor shaped more like a cored apple than the traditional doughnut. That simple shape change could open the way to a fusion power plant that would match ITER's promise, without the massive scale. The world's two front-rank machines—in the United States and the United Kingdom—are both being upgraded with stronger magnets and more powerful heating systems. Soon they will switch on and heat hydrogen fuel to temperatures much closer to those needed for generating fusion energy. If they perform well, spherical tokamaks could change the shape of fusion's future.
To read the full story, see the 22 May issue of Science.


By Jack Russillo/South Seattle Emerald
This story is contributed by The South Seattle Emerald, a husband or wife in InvestigateWest’s yearlong local climate reporting initiative.
When the time arrived for Gov. Jay Inslee to indication a much-reaching piece of environmental justice into regulation, the ceremony took place by the mouth of Seattle’s only river, the Duwamish, at the cultural heart of the people today who have referred to as on their own by the identical identify for generations.
“The Mend Act is a significant piece of legislation with the ambitious demand of generating it so that all people, specifically the most overburdened communities and individuals of colour, have a healthier surroundings, thoroughly clean air and drinking water, and can direct healthy lives,” said Cecile Hansen, chairwoman of the Duwamish Tribal Council.
The Balanced Environment for All Act was established to “reduce environmental and wellbeing disparities in Washington State and improve the wellbeing of all Washington Point out citizens,” according to the 2021 WFFA Legislative Report. It mandates that state organizations stick to environmental justice concepts and techniques when making decisions with the potential to generate environmental harm. The bill also creates a framework for the state to distribute funding and integrate neighborhood feed-back to support historically overburdened communities in recovering from previous damage and to protect against potential disparities.
To safeguard towards environmentally dangerous steps, the regulation establishes point out govt procedures, these types of as monitoring every single agency’s targets and its performance in adopting group engagement options.
The Recover Act does not, nevertheless, require all agencies to act on all recommendations from the Environmental Justice Activity Drive. Instead, legislators included language like “consider,” “seek,” and “where practical” when specifying when agencies need to stick to the endeavor force’s tips. Washington’s departments of Agriculture, Commerce, Ecology, Well being, Purely natural Sources, and Transportation are demanded to put into practice these environmental justice frameworks, but other businesses only “should strive to apply the laws” and the fairness concepts.
“With this bill in result, we now are starting up to make environmental justice a component of everything that we do in state government,” Inslee mentioned at the signing. “This is a considerably-achieving monthly bill for the reason that it’s likely to require condition organizations to think about this challenge in their budgeting and their legislative priorities. This is an order to bring environmental justice to the forefront of everything we do. It is about time that we do this. We have as well several spots in the state of Washington where overburdened communities are breathing diesel smoke from freeways and respiratory harmful fumes from industrial facilities. It’s time to do one thing about that.”
The Heal Act defines environmental justice dependent on the finding of the environmental task drive, which was formed in 2019 to develop tips for embedding environmental justice and strengthening the health of populations disproportionately impacted into just about every general public agency’s responsibilities.
The state’s new, lawful definition of environmental justice is: “the reasonable remedy and significant involvement of all persons, regardless of race, coloration, national origin, or money, with respect to the enhancement, implementation, and enforcement of environmental regulations, regulations, and insurance policies.” This features addressing disproportionate well being and environmental wellbeing impacts, prioritize hugely impacted populations, equitably distribute resources and advantages, and eliminate damage.”
“Today is a day of celebration and it is a day to recover,” explained point out Rep. Debra Lekanoff, who signifies the 40th district and was a sponsor of the bill. “Today we are bringing environmental well being to all. The Recover Act is a celebration for all Washingtonians.”
According to a report from the Environmental Justice Job Pressure in 2020, “People of shade and minimal-earnings people continue to be disproportionately exposed to environmental harms in their communities.” These frontline communities are normally Indigenous and other men and women of color, with lessen incomes and are linguistically isolated. They are typically hit first by the outcomes of pollution and extractive procedures and policies, building their current health and fitness and economic disparities even worse, and nevertheless these frontline communities are generally not prioritized in corrective plan that can guide to more healthy and more sustainable futures.
“Today is a monumental day for our motion, for local climate and environmental justice,” reported condition Sen. Rebecca Saldaña, who signifies the 37th district and was a key sponsor of the invoice. “It is about how we approach all the do the job that we do and … all those procedures that resulted in devices and establishments that led to all those disparities that we now see on the map and exhibits that, by design and style, sure communities spend a a great deal greater price in health and in option than other people primarily based on exactly where they are living. And so, it is these guidelines that have introduced us in this article nowadays to undo those people harms and, as the governor said, to assure that environmental justice drives all that we do as we move ahead collectively for a Washington that is deserving of our small children and our grandchildren.”
The act also aims to deal with environmental overall health disparities that arise on tribal lands, especially ones “due to off-reservation pursuits inside the state,” and “on smaller reservations the place it is extremely hard to move away from a hazard.” The law will also support to “improve point out procedures to reduce contamination of standard foods anywhere they take place.”
Furthermore, the Recover Act claims that by July 2022, point out agencies “must produce and undertake a local community engagement strategy that describes how it will engage with overburdened communities and vulnerable populations,” and that their program “must explain how the company designs to aid equitable participation and guidance meaningful and immediate involvement of susceptible populations and overburdened communities.”
“You observed a coalescence of justice from all these communities and, definitely, acquiring this event at a tribal area is pretty essential,” mentioned Inslee. “We have reps of the Latinx group who had been talking about agricultural justice in the subject. We have local community members who treatment about bringing about law enforcement accountability. So, it is all about a coalescence of justice messages in multiple platforms: agriculture, police accountability, environmental, and cleanse air legal guidelines. It’s so fantastic to see that we’re advancing justice, not just in a single stream, but in multiple streams. Today was a major working day.”
On the exact day, on the other hand, Inslee issued a line-item-veto of the Climate Determination Act that could have presented tribes the possibility to halt carbon tax revenues from funding state jobs that they say would damage their cultural resources and sacred web-sites. In reaction to Inslee’s veto, the Washington BLM Alliance launched a statement that reported “vetoing the whole Tribal session portion of this monthly bill is a immediate and imminent menace to Tribal civil rights and protections” and that “the condition need to honor those people legal rights by demanding session with Tribes when their cultural resources are underneath risk.


News & Views
Nuclear plants in Russia and Ukraine keep breeding fish
January 5, 2022 By Vladislav Vorotnikov
Nuclear plants in post-Soviet space keep using fish in cooling ponds, expanding its number and range in order to maintain a sustainable operation.
Just recently, the management of the Khmelnytskyi nuclear plant in Ukraine announced plans to release 202,000 units of carp (Cyprinidae) fry in its cooling pond to reduce biological interference in the operation of circulation systems. The fish fights well against algae, phytoplankton, and mollusks, improving the water quality, the officials at the nuclear plant explained.
The cooling pond at nuclear plants is a technical reservoir designed for cooling water from the nuclear power plant. The pond’s heated water is used to cool the steam turbine equipment and pipelines of the nuclear plant’s secondary circuit.
As explained by Svetlana Averina, the head of the biomelioration department at the Khmelnytskyi nuclear plant, the presence of fish in the reservoir is a technological necessity. Water for cooling heat exchange equipment must meet certain chemical and physical characteristics. Its optimal state can be maintained, along with other factors, by natural biomeliorators.
The grass carp can eat various algae and prevents the overgrowth of vegetation on the water surface. Silver carp can filter water, passing phytoplankton through the gills, which is its main food. Crucian carp also have their own food base, part of which is small mollusks, crustaceans, and the like. All fish in the cooling pond work to improve water quality and, consequently, the safety of operating power units, Averina said.
In Russian, several nuclear plants also stock cooling ponds with fish. In 2020, the Balakovo plant released 1,238 carp fingerlings into its cooling pond.
Stocking of cooling ponds is a common practice for nuclear power plants in Russia. The pond’s warm water causes an intensive growth of algae and mollusks reproduction, which may disrupt the water intake pump operation, clogging the protective systems of the plant’s technical water supply. Most scientists believe the fish from nuclear plants are safe for consumption.
There is no clarity whether the fish from the cooling ponds is safe for human consumption. In general, it is believed that this is the case. However, some Russian environmentalists warned over possible fish contamination with tritium – the most dangerous radionuclide for humans today – with a half-life of 12.3 years.
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It was meant to be the safest place on Earth: when Cary Fowler started the Svalbard Global seed vaultSaatgutbankSeed Vault, thanks to financing from the Bill & Melinda Gates Foundation, he imagined a sleek modern building sunk into a frozen mountainside. Out there on the remoteentlegen, weit entferntremote Norwegian island of Spitsbergen, it would be completely secure and, of course, imperviousundurchdringlich, undurchlässigimpervious to the elements.
In 2008, that’s what the American agriculturalist got. But now the famous vault and its preciouswertvollprecious contents — nearly a million packets of seeds that represent the world’s food — are threatened by the effects of climate change.
The site of the vault in the Norwegian permafrost was initially considered to be stable, both tectonically and in terms of temperature. Recent water damage to its downward-slopingabschüssig, geneigtsloping access tunnel, however, has shown that the building’s architectural design ignored one key eventuality: what would happen if higher temperatures managed to weaken the permafrost? Unthinkable just nine years ago, this is now reality, especially since 2016 was the world’s hottest year on record.
Unthinkable just nine years ago, this is now reality: climate change has weakened the permafrost
“The solution is easy, and I give it for free,” Arne Kristoffersen, a former Svalbard coal miner, told The Guardian. “Make a new access tunnel going upwards so the water can run out of, not into, the seed bank. It is not very hard, but it will cost a lot of money.”
Norway is doing just that: it has recently promised to pay $4.4 million towards improving the structure by building an upward-sloping entry tunnel. Luckily, no seeds were damaged in the recent flooding.
Svalbard Global Seed Vault in 360°
This video by the New York Times lets you explore the Svalbard Global Seed Vault from all angles.


Developed by Maria Christina Prokou
Back in the 17th century Negotiation is related to a dialogue between two or more people where a compromise or an agreement is reached avoiding argument dispute, aiming to achieve a beneficial outcome. Negotiation is one of the most important factors for a business success and this is why it is one of the main qualities employers look for when recruiting staff nowadays. People negotiate everyday in their life even when they do not realize it and project management is no different, for that reason this article will focus on the importance of negotiation skills for a Project Manager to achieve the best deals in the demanding business world that is changing constantly.
Improved supplier relationships, sustainable competitive advantage and managing conflicts effectively are all advantages of successful negotiations. Being able to negotiate opens the door to more supportive stakeholders, better relationships with your clients and a more positive working environment where everyone feels they are getting something out of the engagements . Negotiation skills can be learned but in order to do that, it is essential that the Project Manager spends time, money and energy to learn about them and practice as much as possible to sharpen their skills and get more efficient in any situation.
Negotiation is not merely the first step of a new project; a project manager’s job will require that they continue negotiating throughout the entire process. Furthermore, negotiations do not solely occur between a project manager and an external party, like a vendor or client; they frequently occur within a project team or involve other project stakeholders . The process of negotiation eventuate at any time through a project, program or portfolio and can be formal of informal. A common example for formal negotiations is when providers need to agree on a contract. On the other hand informal negotiations arise when discussions are made in order to resolve conflicts or to obtain internal resources. Negotiation skills are used in many areas of P3 management such as conflict management, contract management, requirements management and stakeholder management .
- Project: negotiation skills should be applied from the project manager throughout the project life cycle. Even from the very first stages of a project, the project manager may need to balance the time, cost, quality and scope requirements of it and negotiate with the stakeholders. Following, the project manager will have to show again his negotiation skills to the potential recourse providers. When conflicts arise at the progress of the project, he will again show these skills in order to find appropriate solutions to them using formal or informal negotiations.
- Program: there is a big variety of negotiation scenarios within a program and this is why the program manager should know whether negotiations should take place in the project phase or in the program phase. A program includes project outputs that demand change on business-as-usual, this is when negotiation solutions are needed. Program managers and program sponsors are the visible leadership of the program and need to become personally involved to achieve a successful conclusion.
- Portfolio: this encompass the broadest range of negotiation scenarios.The only gradation from the portfolio is to the organisation’s managing board that must be fully committed to the portfolio’s strategic objectives and supportive in negotiations.
Types of negotiation
There are two main types of negotiation, the distributive negotiation and the integrative negotiation. The first one is also known as “win-lose” negotiations because each party's objective is to maximize its share of the resource being allocated. If the amount of resources is fixed, the only way one party can win is if the other party loses and it is not possible for both to “win” the distributive negotiation .
On the other hand, integrative negotiation is known as win-win negotiation because the expanded list of items being negotiated makes it possible for each side to claim items that have value. The expanded list of items that is being negotiated makes it possible for each side to claim items of value from that side's perspective. This type of negotiation is divided in two stages, beginning with the collaborative problem-solving activity where the people who are involved in the negotiation attempt to identify additional items that could be added to the overall mix of items that are being negotiated aiming to expand the total potential value of the negotiation. This step is vital because as the procedure continues, if the first step is successfully completed both sides will feel like winners also in the second stage. This final stage has some similarities to the distributive negotiations, as it is time for the allocation process where decisions need to be taken.
According to Lewicki, Barry, and Saunders there is also a third type of negotiation that is called accommodative negotiation. This is lose-win negotiations where the project manager has planed to lose on purpose, aiming to put the other party in a relationship to “win” in order to strengthen the long-term relationship and set the stage for future integrative negotiations.
Negotiation roles for a PM
A Project manager needs to fulfill the following three negotiation roles
- Negotiator: this is the first an obvious role for the project manager where he is one of the parties that are being involved in the negotiation process. All parties should be prepared on what attitude they will follow if a negotiation failure occurs and this should be done before the negotiation process begins. It is common for a negotiation to fail and there are two ways to deal with this deadlock process. The first option is that all negotiation parties walk off the negotiation and develop a contingency plan. Another alternative would be to ask for help from a third party to resolve the impasse. The are only two kinds of a third-party, the mediator and the arbitrator.
- Mediator: in this role the project manager pursues to accommodate the communication between the two parties so that they can conclude in a mutually agreed solution where communications is the most important factor that is being used for negotiation and as Fisher, Ury, and Patton (1991) declared “Without communication there is no negotiation”. Whenever a project manager is involved in a negotiation between two stakeholders he might become a mediator if the two parties ask for input or if he believes that he should attempt to resolve a conflict. In any case his goal is to facilitate the communication between the two parties and help them find common ground and a mutually acceptable solution. The mediator generates dialogue by making questions but if the negotiation still cannot be successful he is not responsible for making any decisions as he is just a facilitator for the two parties and in that case each negotiation party should fall back to the contingency plans identified prior to the negotiation.
- Arbitrator: is the role for a project manager who has to be a decision maker. At the beginning he listens both sides and asks questions similar to the ones that the mediator asks and after having received the needed information he acts like a judge who comes with a final decision which might be mandatory or optional. If the arbitrator's decision is optional, the parties may choose to accept the decision or return to their contingency plans for a failed negotiation. The project manager may also transition to an arbitrator role, after being asked, or because he feels that the conflict will not be resolved otherwise. The project manager may also use the threat of arbitration as a mediation toolbar threatening for example the two parties to find a solution otherwise he will find a solution that no-one would like.
Stages of negotiation
In order to achieve a successful negotiation, a structured approach is demanded. There are three main stages in this structure : planning ,engagement and closure. Each one of these stages also contains more steps that need to be done. All of the stages are clearly explained below:
- Preparation : before any negotiation starts, all parties should agree on when and where the meeting is going to take place and who is going to be present at it. It is also very important that the parties agree on a time-scale that they should follow to prevent the disagreement continuing. Undertaking preparation before discussing the disagreement will help to avoid further conflict and unnecessarily wasting time during the meeting.
- Discussion : at this early stage of engagement all parties should state their understanding of the situation through questioning, listening and clarification. At this point listening is very important as when disagreement takes place it is easy to make the mistake of saying too much and listening too little. Each side should have an equal opportunity to present their case.
- Clarification of goals: when the discussion comes to an end goals, interests and viewpoints of both sides should be understood and clarified in order to establish common ground and conclude in an agreement. Clarification is an essential part of the negotiation process, without it misunderstandings are likely to occur which may cause problems and barriers to reaching a beneficial outcome.
- Negotiate towards a Win-Win outcome: this final phase of the engagement focuses on a result that would be beneficial for both sides where everyone's perspective would have been taken into consideration. Although a win-win outcome may not always be possible through negotiation, it should be the ultimate goal as it is usually the best result. Suggestions of alternative strategies and compromises need to be considered at this point. Compromises are often positive alternatives which can often achieve greater benefit for all concerned compared to holding to the original positions.
- Agreement: it is essential to for everybody involved to keep an open mind in order to achieve an acceptable solution. Any agreement needs to be made perfectly clear so that both sides know what has been decided. Only after all parties have understood all aspects, the final agreement can be achieved
- Implementation of a course of action: is the process of turning your strategy and goals into action, while also taking your ideas and planning how to make them reality. From the agreement, a course of action has to be implemented to carry through the decision.
As it was mentioned above negotiation skills can be developed. The best negotiators are not born with these skills but they have evolved them through practice.
In order to become a successful negotiator, one manager should deploy several skills from distinct fields and use them in multiple contexts.
Project managers who want to perfect their skills should pursue the three following vital elements that are responsible for successful outcomes in any negotiation.
The negotiation process is extremely dependent on the underlying attitudes to the process itself. If one of the parties adopt an aggressive behavior, in a negotiation process, the other party will probably act defensively. A skilled negotiator espouses a plain behavior without letting his emotions affect this procedure. At the same time this person knows whether he needs to change his addressing and be more determinative or concessive.
Good preparation is essential for a successful negotiation as if one manager captures enough knowledge for an issue his participation in the negotiation process is going to be great. Preparation is responsible for the 90% of the negotiating success. The more prepared you are preceding a negotiation, the more likely it is that the result of the negotiation will be acceptable for all parties involved. The two most important things to do during preparation are: Firstly, make sure to have all the information that you can about the forthcoming negotiation. Secondly, think about the negotiation process from the beginning to the end and be fully prepared for any eventuality .
- Active Listening: instead of spending most of the time in negotiation defending his perspective, a skilled manager will spend most of the time listening to the other party to find areas for compromise during the meeting or to find clues for further debate. Active listening is the ability to listen carefully to the other party while at the same time it is the ability to read body language and verbal communication.
- Effective Verbal Communication: skilled negotiators must be able to communicate clearly and effectively to all the other parties through a negotiation. This can be achieved by choosing the appropriate words according to whom they are referring to. Shorter sentences and simple words are also easier to process and understand. In addition, the sound of someone's voice can reveal a lot about his personality and emotional state. For instance, if self-esteem is low, it may be reflected by hesitancy in the voice. A shy person may speak quietly, but someone who is confident in themselves will be more likely to have command of their voice and clarity of speech. It is worth for a negotiator taking time to improve his command over his voice, especially if he finds it hard to speak in public, while it can even help to boost his confidence. Eye contact, the way he uses his hands to emphasise his speech, facial expressions and posture are also very important as body language affects the overall communication a lot.
- Problem Solving: a good negotiator does not concentrate on his individual goals for the negotiation, but he is devoting himself to finding a variety of solutions to problems that will benefit both parties. A lot of the work in problem solving involves understanding what the underlying issues of the problem really are.
- Emotional Control: it is important that a negotiator has the ability to keep his emotions under control during the negotiation. Negotiating on sensitive issues can be frustrating and allowing emotions to take control can worsen the situation during the meeting and lead to negative results. The project manager should remember to stay calm during the negotiation process.
- Patience: good negotiators are often very patient and they mainly focus on getting agreement on all the parts of the contract that the two parties have in common. They should prepare good questions to ask to clarify and understand each point to avoid any confusion later.
- Decision Making: successful negotiators do not hesitate to make decisions on their own. They find it easy to choose between two or more possible solutions to a problem and they do not ask others for their opinion. Decisions can be made through either an intuitive or reasoned process, or a combination of the two.
- Dealing with difficult situations: instead of trying to avoid conflicts and stressful situations like most of the people, a skilled negotiator is ready face bravely any difficult situation.
- Ethics and Reliability: ethical standards and reliability in a skilled negotiator stimulate a trust for effective negotiation to take place. Both parties in a negotiation must trust that the other side will keep up with promises and agreements. A negotiator must have the skills to implement his promises after bargaining ends.
Negotiation skills are essential for successful agreements in the demanding business world that changes rapidly. In order for a project manager to succeed in negotiation, he must follow some steps throughout the whole lifecycle of the project. First, the negotiator should decide witch type of negotiation he is going to follow, while the distributive type of negotiation is recommended. Even if the negotiation begins with an integrative approach, ultimately the resources have to be allocated in a distributive manner. Following, the project manager should change his role according to the needs of each situation. Project management provides an excellent framework or approach for negotiation that consists of three phases which are planning, engagement, and closing. Finally, the success of the project depends on the manager's negotiation skills in distinct fields.
- 1.Skills You Need (no date) What is Negotiation? [online] available at https://www.skillsyouneed.com/ips/negotiation.html"
- Summary: This website explores the stages and types of negotiation.
- 2. Strategy Execution (2018) Negotiation Skills for Project Managers [online] available at https://www.strategyex.co.uk/blog/pmoperspectives/how-to-improve-your-negotiation-skills-project-managers/"
- Summary: This website explains the importance of the interpersonal negotiation skills for a project managers and describes each one of them.
- 3.Project Management (2018) 5 Negotiation Skills Project Managers Need to Master [online] available at https://project-management.com/5-negotiation-skills-project-managers-need-to-master/"
- Summary: This website offers a five step guide to managers succeed in negotiation.
- 4. Association for project management (no date) Negotiation [online] available at https://www.apm.org.uk/body-of-knowledge/people/interpersonal-skills/negotiation/"
- Summary:bThis website develops useful information about negotiation in project, program and portfolio management.
- 5.Craddock, W. T. (2010). Five things every project manager should know about negotiation. Paper presented at PMI® Global Congress 2010—North America, Washington, DC. Newtown Square, PA: Project Management Institute."
- Summary: This article describes negotiation and five main factors that every successful project manager should follow during this process.
- 6.Lewicki, R.J., Barry, B., & Saunders, D.M. (2010). Negotiation (6th ed.). New York: McGraw-Hill/Irwin"
- Summary: This book develops negotiation from many different perspectives in depth.
- Summary: This article emphasizes in seven interpersonal skills that all managers should perfect.
- ↑ 1.0 1.1 Skills You Need (no date) What is Negotiation? [online] available at https://www.skillsyouneed.com/ips/negotiation.html (Accessed February 2019)
- ↑ Strategy Execution (2018) Negotiation Skills for Project Managers [online] available at https://www.strategyex.co.uk/blog/pmoperspectives/how-to-improve-your-negotiation-skills-project-managers/ (Accessed February 2019)
- ↑ Project Management (2018) 5 Negotiation Skills Project Managers Need to Master [online] available at https://project-management.com/5-negotiation-skills-project-managers-need-to-master/ (Accessed February 2019)
- ↑ Association for project management (no date) Negotiation [online] available at https://www.apm.org.uk/body-of-knowledge/people/interpersonal-skills/negotiation/ (Accessed February 2019)
- ↑ 5.0 5.1 Craddock, W. T. (2010). Five things every project manager should know about negotiation. Paper presented at PMI® Global Congress 2010—North America, Washington, DC. Newtown Square, PA: Project Management Institute.
- ↑ Lewicki, R.J., Barry, B., & Saunders, D.M. (2010). Negotiation (6th ed.). New York: McGraw-Hill/Irwin
- ↑ Procurement Academy (2017) 7 Key Skills for successful negotiation [online] available at https://www.procurement-academy.com/7-key-skills-successful-negotiation/ (Accessed February 2019)


Biosensors for Health Applications
Cibele Marli Cação Paiva Gouvêa
Universidade Federal de Alfenas
The ability to assess health status, disease onset and progression, and monitor treatment
outcome through a non-invasive method is the main aim to be achieved in health care
promotion and delivery and research. There are three prerequisites to reach this goal:
specific biomarkers that indicates a healthy or diseased state; a non-invasive approach to
detect and monitor the biomarkers; and the technologies to discriminate the biomarkers.
The early disease diagnosis is crucial for patient survival and successful prognosis of the
disease, so that sensitive and specific methods are required for that. Among the numerous
mankind diseases, three of them are relevant because of their worldwide incidence,
prevalence, morbidity and mortality, namely diabetes, cardiovascular disease and cancer.
In recent years, the demand has grown in the field of medical diagnostics for simple and
disposable devices that also demonstrate fast response times, are user-friendly, cost-
efficient, and are suitable for mass production. Biosensor technologies offer the potential to
fulfill these criteria through an interdisciplinary combination of approaches from
nanotechnology, chemistry and medical science.
The emphasis of this chapter is on the recent advances on the biosensors for diabetes,
cardiovascular disease and cancer detection and monitoring. An overview at biorecognition
elements and transduction technology will be presented as well as the biomarkers and
biosensing systems currently used to detect the onset and monitor the progression of the
selected diseases. The last part will discuss some challenges and future directions on this
2. Biorecognition elements and transduction technology
2.1 Biorecognition elements
Clinical analyses are no longer carried out exclusively in the clinical chemistry laboratory.
Measurements of analytes in biological fluids are routinely performed in various locations,
including hospital, by caregivers in non-hospital settings and by patients at home.
Biosensors (bioanalytical sensors) for the measurement of analytes of interest in clinical
chemistry are ideally suited for these new applications. These factors make biosensors very
attractive compared to contemporary chromatographic and spectroscopic techniques.
A biosensor can be generally defined as a device that consists of a biological recognition
system and a transducer, for signal processing, to deduce and quantity a particular analyte
(Hall, 1990). Biosensors provide advanced platforms for biomarker analysis with the
advantages of being easy to use, rapid and robust as well as offering multianalyte testing
72 Biosensors for Health, Environment and Biosecurity
capability; however a specific biomarker is necessary. Biomarkers are molecules that can be
objectively measured and evaluated as indicators of normal or disease processes and
pharmacologic responses to therapeutic intervention (Rusling et al., 2010).
The first biosensor was reported by Clark and Lyons (1962) for glucose in blood
measurement. They coupled the enzyme glucose oxidase to an amperometric electrode for
PO2. The enzyme-catalyzed oxidation of glucose consumed O2 and lowered PO2 that was
sensed, proportionally to the glucose concentration in the sample. The enzyme-based sensor
was the first generation of biosensors and in the subsequent years a variety of biosensors for
other clinically important substances were developed. Therefore, biosensors can be
categorized according to the biological recognition element (enzymatic, immuno, DNA and
whole-cell biosensors; Spichiger-Keller, 1998) or the signal transduction method
(electrochemical, optical, thermal and mass-based biosensors; Wanekaya et al., 2008) (Fig 1).
Fig. 1. Schematic of a biosensor (Arya et al., 2008).
Substantial amounts of published work on the enzyme-based biosensors are found in the
literature due to their medical applicability, commercial availability or ease of enzyme
isolation and purification from different sources and also enzymes can be used in
combination for detection of a target analyte (D'Orazio, 2003). By acting as biocatalytic
elements, the enzymatic reaction is accompanied by the consumption or production of
species such as CO2, NH3, H2O2, H+, O2 or by the activation/inhibition activity that can be
detected easily by various transducers and correlate this species to the substrates. Amongst
various enzymes, glucose oxidase, horseradish peroxidase, and alkaline phosphatase have
been employed in most biosensor studies (Laschi et al., 2000; Wang, 2000). The detection
limit is satisfactory or exceeded but the enzyme stability is still a problem, especially
considering a long period of time. A major advantage of enzyme-based biosensors is the
ability, in some cases, to modify catalytic properties or substrate specificity by genetic
engineering. The major limitation is the lack of specificity in differentiating among
compounds of similar classes (Buerk, 1993; 2001; D'Orazio, 2003).
Affinity biosensors have received considerable attention in the last years, since they provide
information about binding of antibodies to antigens, cell receptors to their ligands,
DNA/RNA to complementary sequences of nucleic acids and functioning enzymatic
pathways that allow the screening of gene products for metabolic functions.
Immunosensors are based on the high selectivity of the antibody–antigen reaction. The
specific interaction is sensed by a transducer and measurements can be obtained directly,
in minutes, rather than the hours required for visualizing results of an ELISA test
Biosensors for Health Applications 73
(Spangler et al., 2001). Either an antigen or antibody can be immobilized onto a surface of
support in an array format (Huang et al., 2004) and participates in a biospecific interaction
with the other component, allowing detection and quantification of an analyte of interest
(Stefan et al., 2000). The sensors may operate either as direct or as indirect sensors often
referred to homogeneous and heterogeneous immunosensors, respectively. Antibodies are
the critical part of an immunosensor to provide sensitivity and specificity. As the
antibody–antigen complex is almost irreversible, only a single immunoassay can be
performed (Buerk, 1993) although intensive research effort has been directed toward the
regeneration of renewable antibody surfaces. Reproducibility is another concern, partly
due to the antibody orientation and immobilization onto the sensor surface.
Immunosensors are inherently more versatile than enzyme-based biosensors because
antibodies are more selective and specific. Immunosensors are currently been used for
infectious diseases diagnosis (Huang et al., 2004).
DNA analysis is the most recent and most promising application of biosensors to clinical
chemistry. DNA is well suited for biosensing because the base pairing interactions between
complementary sequences are both specific and robust. DNA biosensors employ
immobilized relatively short synthetic single-stranded oligodeoxynucleotides that
hybridizes to a complementary target DNA in the sample (Palecek, 2002). Hybridization can
be performed either in solution or on solid supports. The system can be used for repeated
analysis since the nucleic acid ligands can be denatured to reverse binding and then
regenerated (Ivnitski et al., 1999). However, considerable research is still needed to develop
methods for directly targeting natural DNA present in organisms and in human blood with
high detection sensitivity (Palecek, 2002). Accurate tests for recognizing DNA sequences,
usually, need to multiply small amounts of DNA into readable quantities using the
polymerase chain reaction (PCR). Some of the new gene chips are sensitive enough to
eliminate the need for target amplification, a time-consuming process. This improvement
has stimulated the development of DNA biosensors with a view toward rapid analysis for
point-of-care diagnostics for infectious disease, testing cancer and genetic disease diagnosis
and measurement of drug resistance or susceptibility, and even a whole cancer circulating
cell can be identified (Liu et al., 2009).
Whole-cell biosensors are based in the general metabolic status of bacteria, fungi, yeasts,
animal or plant cells that are the recognition elements. Whole cells can easily be
manipulated and adapted to consume and degrade new substrates. Many enzymes and co-
factors that co-exist in the cells give them the ability to consume and hence detect a large
number of chemicals. However, this may compromise their selectivity (Ding et al., 2008).
The sensing molecule, in general, is hold on a solid support, the matrix. Chemical properties
of a desired support decide the method of immobilization and the operational stability of a
biosensor. In particular, it should be resistant to a wide range of physiological pHs,
temperature, ionic strength and chemical composition. The ability to co-immobilize more
than one biologically active component is desirable in some cases. Conducting polymers,
carbon nanotubes, nanoparticles, sol–gel/hydro-gels and self-assembled monolayer are
common used to immobilize a variety of sensing molecules (Arya et al., 2008).
2.2 Transduction technology
The interaction of the analyte with the bioreceptor is designed to produce an effect
measured by the transducer, which converts the information into a measurable signal. A
variety of transducer methods have been feasible toward the development of biosensor
74 Biosensors for Health, Environment and Biosecurity
technology; however the most common methods are electrochemical, optical and
piezoelectric (Buerk, 1993; Collings & Caruso 1997; Wang, 2000).
Electrochemical sensors measure the electrochemical changes that occur when analytes
interact with a sensing surface of the detecting electrode. The electrochemical assay is
simple, reliable, has a low detection limit and a wide dynamic range due to the fact that the
electrochemical reactions occur at the electrode–solution interfaces. Based on that and cost
competitiveness, more than half of the biosensors, reported in the literature, are based on
electrochemical transducers (Meadows, 1996). The electrical changes can be potentiometric
(a change in the measured voltage between the indicator and reference electrodes),
amperometric (a change in the measured current at a given applied voltage), or
conductometric (a change in the ability of the sensing material to transport charge).
Amperometry is the electrochemical technique usually applied in commercially available
biosensors for clinical analyses that detect redox reactions. The electrochemical platform is
suited for enzyme-based and DNA/RNA sensors, field monitoring applications (e.g. hand-
held) and miniaturization toward the fabrication of an implantable biosensor.
Optical transducers can be used to monitor affinity reactions and have been applied to
quantitate antigenic species of interest in clinical chemistry and to study the kinetics and
affinity of antigen–antibody and DNA interactions. Of particular interest have been direct
optical transducers based on methods such as internal reflectance spectroscopy, surface
plasmon resonance and evanescent wave sensing. Light entering an optical device is
directed through optical fibers or planar waveguides toward a sensing surface and reflected
back out again. The reflected light is monitored, using a detector such as a photodiode,
revealing information about the physical events occurring at the sensing surface. The
measured optical signals often include absorbance, fluorescence, chemiluminescence,
surface plasmon resonance (to probe refractive index), or changes in light reflectivity.
Optical biosensors are preferable for screening a large number of samples simultaneously;
however, they cannot be easily miniaturized for insertion into the bloodstream. Most optical
methods of transduction require a spectrophotometer to detect signal changes.
Mass sensors can produce a signal based on the mass of chemicals that interact with the
sensing film, usually a vibrating piezoelectric quartz crystal. Acoustic wave devices, made
of piezoelectric materials, are the most common sensors, which bend when a voltage is
applied to the crystal. Acoustic wave sensors are operated by applying an oscillating voltage
at the resonant frequency of the crystal, and measuring the change in resonant frequency
when the target analyte interacts with the sensing surface. Because a significant amount of
nonspecific adsorption occurs in solutions, piezoelectric sensors have received their widest
use in gas phase analyses. Extremely high sensitivities are possible with these devices
detecting femtogram levels of drug vapors. Similarly to optical detection, piezoelectric
detection requires large sophisticated instruments to monitor the signal.
Generation of heat during a reaction can be used in a calorimetric based biosensor. Changes
in solution temperature caused by the reaction are measured and compared to a sensor with
no reaction to determine the analyte concentration. This approach is well suited for
enzyme/substrate reactions that cause changes in solution temperature but not for receptor-
ligand reactions because there is no temperature change at steady-state and transient
measurements are very difficult to make. Calorimetric microsensors have been
manufactured for detection of cholesterol in blood serum based on the enzymatically
produced heat of oxidation and decomposition reactions (Caygill et al., 2010).
Biosensors for Health Applications 75
3. Biosensors for diabetes applications
3.1 Glucose as diabetes biomarker
About 3% of the population worldwide suffers from diabetes, a leading cause of death, and
its incidence is growing fast. Diabetes is a syndrome of disordered metabolism resulting in
abnormally high blood sugar levels. Diabetic individuals are at a greater heart disease,
stroke, high blood pressure, blindness, kidney failure, neurological disorders risk and other
health related complications without diligent monitoring blood glucose concentrations.
Through patient education, regular examinations and tighter blood glucose monitoring,
many of these complications can be reduced significantly (Turner & Pickup, 1985; Lasker,
1993). Optimal management of diabetes involves patients measuring and recording their
own blood glucose levels. Under normal physiological condition, the concentration of
fasting plasma glucose is in the range 6.1–6.9 mmolL−1, so the variation of the blood glucose
level can indicate diabetes mellitus, besides other conditions. Consequently, quantitation of
the glucose content is of extreme importance, as it is the main diabetes biomarker. The
American Diabetes Association recommends that insulin-dependent type 1 diabetics self-
monitor blood glucose 3–4 times daily, while insulin-dependent type 2 diabetics monitor
once-daily (American, 1997). However, frequent self-monitoring of glucose concentrations is
difficult, given the time, the inconvenience and the discomfort involved with the traditional
measurement technique. Several methods for glucose analysis have been reported.
However, most of these methods involve complex procedures or are expensive in terms of
costs. Therefore it is necessary to develop a simple, sensitive, accurate, micro-volume and
low-cost approach for glucose analysis which is appropriate for rapid field tests and is also
effective as an alternative to the existing methods.
3.2 Biosensors for glucose measuring
Glucose can be monitored by invasive and non-invasive technologies. Glucose biosensor
was the first reported biosensor (Clark & Lyons, 1962) and after that a great number of
different glucose biosensors were developed, including implantable sensors for measuring
glucose in blood or tissue. Glucose sensors are now widely available as small, minimally
invasive devices that measure interstitial glucose levels in subcutaneous fat (Cengiz &
Tamborlane, 2009). Requirements of a sensor for in vivo glucose monitoring include
miniaturization of the device, long-term stability, elimination of oxygen dependency,
convenience to the user and biocompatibility. Long-term biocompatibility has been the main
requirement and has limited the use of in vivo glucose sensors, both subcutaneously and
intravascular, to short periods of time. Diffusion of low-molecular-weight substances from
the sample across the polyurethane sensor outer membrane results in loss of sensor
sensitivity. In order to address the problem, microdialysis or ultrafiltration technology has
been coupled with glucose biosensors. The current invasive glucose monitors commercially
available use glucose oxidase-based electrochemical methods and the electrochemical
sensors are inserted into the interstitial fluid space. Most sensors are reasonably accurate
although sensor error including drift, calibration error, and delay of the interstitial sensor
value behind the blood value are still present (Castle & Ward, 2010). The glucose biosensor
is the most widely used example of an electrochemical biosensor which is based on a screen-
printed amperometric disposable electrode. This type of biosensor has been used widely
throughout the world for glucose testing in the home bringing diagnosis to on site analysis.
76 Biosensors for Health, Environment and Biosecurity
Non-invasive glucose sensing is the ultimate goal of glucose monitoring and the main
approaches being pursued for glucose sensor development are: near infrared spectroscopy,
excreted physiological fluid (tears, sweat, urine, saliva) analysis, microcalorimetry, enzyme
electrodes, optical sensors, sonophoresis and iontophoresis, both of which extract glucose from
the skin (Koschwanez & Reichert, 2007; Beauharnois et al., 2006; Chu et al., 2011). Despite the
relative ease of use, speed and minimal risk of infection involved with infrared spectroscopy, this
technique is hindered by the low sensitivity, poor selectivity, frequently required calibrations,
and difficulties with miniaturization. Problems surrounding direct glucose analysis through
excreted physiological fluids include a weak correlation between excreted fluids and blood
glucose concentrations. Exercise and diet that alter glucose concentrations in the fluids also
produce inaccurate results (Pickup et al., 2005). The desire to create an artificial pancreas drives
for continued research efforts in the biosensor area. Nevertheless, the drawbacks of in vivo
biosensors must be solved before such an insulin modulating system can be achieved.
4. Biosensors for cardiovascular diseases applications
4.1 Cardiovascular disease biomarkers
Cardiovascular diseases are highly preventable, yet they are major cause of death of humans
over the world. One of the most important reasons of the increasing incidences of
cardiovascular diseases and cardiac arrest is hypercholesterolemia, i.e. increased
concentration of cholesterol in blood (Franco et al., 2011). Hence estimation of cholesterol
level in blood is important in clinical applications. The early evaluation of patients with
symptoms that indicates an acute coronary syndrome is of great clinical relevance.
Biomarkers have become increasingly important in this setting to supplement
electrocardiographic findings and patient history because one or both can be misleading.
Cardiac troponin is the only marker used routinely nowadays in this setting because it is
specific from the myocardial tissue, easily detected, and useful for therapeutic decision
making. Determination of the level of other non-myocardial tissue-specific markers might
also be helpful, such as myeloperoxidase, copeptin, growth differentiation factor 15 and C-
reactive protein (CRP). CRP, which reflects different aspects of the development of
atherosclerosis or acute ischemia, is one of the plasma proteins known as acute-phase
proteins and its levels rise dramatically during inflammatory processes occurring in the
body. This increment is due to a rise in the plasma concentration of IL-6, which is produced
predominantly by macrophages as well as adipocytes. CRP can rise as high as 1000-fold
with inflammation. CRP was found to be the only marker of inflammation that
independently predicts the risk of a heart attack.
4.2 Biosensors in cardiovascular disease
Biosensors for cholesterol measurement comprise the majority of the published articles in
the field of cardiovascular diseases. In the fabrication of cholesterol biosensor for the
estimation of free cholesterol and total cholesterol, mainly cholesterol oxidase (ChOx) and
cholesterol esterase (ChEt) have been employed as the sensing elements (Arya et al., 2008)
(Fig. 2). Electrochemical transducers have been effectively utilized for the estimation of
cholesterol in the system (Charpentier & Murr, 1995; Singh et al., 2006; Zhou et al., 2006;
Arya et al., 2007). Based on number and reliability of optical methods, a variety of optical
transducers have been employed for cholesterol sensing, namely monitoring: luminescence,
Biosensors for Health Applications 77
change in color of dye, fluorescence and others (Arya et al., 2008). Other cardiovascular
disease biomarkers are also quantified. CRP measurement rely mainly on immunosensing
technologies with optical, electrochemical and acoustic transducers besides approaches to
simultaneous analytes measurement (Albrecht et al., 2008; Heyduk et al., 2008; McBride &
Cooper, 2008; Niotis et al., 2010; Qureshi et al., 2010a,b; Sheu et al., 2010; Zhou et al., 2010).
Silva et al. (2010) incorporated streptavidin polystyrene microspheres to the electrode
surface of SPEs in order to increase the analytical response of the cardiac troponin T and
Park et al. (2009) used an assay based on virus nanoparticles for troponin I highly sensitive
and selective diagnostic, a protein marker for a higher risk of acute myocardial infarction.
Early and accurate diagnosis of cardiovascular disease is crucial to save many lives,
especially for the patients suffering the heart attack. Accurate and fast quantification of
cardiac muscle specific biomarkers in the blood enables accurate diagnosis and prognosis
and timely treatment of the patients. It is apparent that increasing incidences of
cardiovascular diseases and cardiac arrest in contemporary society denote the necessity of
the availability of cholesterol and other biomarkers biosensors. However, only a few have
been successfully launched in the market. One of the reasons lays in the optimization of
critical parameters, such as enzyme stabilization, quality control and instrumentation
design. The efforts directed toward the development of cardiovascular disease biosensors
have resulted in the commercialization of a few cholesterol biosensors. A better
comprehension of the bioreagents immobilization and technological advances in the
microelectronics are likely to speed up commercialization of the much needed biosensors for
Fig. 2. Pathway of cholesterol oxidase enzyme reaction (Arya et al., 2008).
78 Biosensors for Health, Environment and Biosecurity
5. Biosensors for cancer applications
5.1 Cancer biomarkers
Cancer is the leading cause of death in economically developed countries and the second
leading cause of death in developing countries. This disease continues to increase globally
largely because of the aging and growth of the world population alongside an increasing
adoption of cancer-causing behaviors, particularly smoking. Breast cancer is the most
frequently diagnosed cancer and the leading cause of cancer death among females and lung
cancer is the leading cancer site in males. Breast cancer is now also the leading cause of
cancer death among females in economically developing countries, a shift from the previous
decade during which the most common cause of cancer death was cervical cancer (Jemal et
al., 2011). Solid cancers are a leading cause of morbidity and mortality worldwide, primarily
due to the failure of effective clinical detection and treatment of metastatic disease in distant
sites (Chambers et al., 2002; Pantel & Brakenhoff, 2004). Cancer can be caused by a range of
factors, both genetic and environmental. Chemical, physical and biological factors such as
the exposure to carcinogenic chemicals, radiation, bacterial (e.g. stomach cancer), viral
infections (e.g. cervical cancer) and toxins (aflatoxin; e.g. liver cancer) can lead to cancer
development (Vineis et al., 2010). As the causes of cancer are so diverse, clinical testing is
also very complex. The multi-factorial changes (genetic and epigenetic) can cause the onset
of the disease and the formation of cancer cells. However, no single gene is universally
altered during this process, but a set of them that brings difficulties to the correct disease
diagnosis. All the changes which take place, in the tumors from different locations (organ),
as well within tumors from the same location, can be so variable and overlapping that it is
difficult to select a specific change or marker for the diagnosis of specific cancers. Therefore,
a range of biomarkers can potentially be analyzed for disease diagnosis. These biomarkers
or molecular signatures can be produced either by the tumor itself or by the body in
response to the presence of cancer (Robert, 2010). Several cancer biomarkers are listed in
The analysis of biomarkers in body fluids such as blood, urine and others is one of the
methods applied in the detection of the disease. Multi-marker profiles, both presence and
concentration level, can be essential for the diagnosis of early disease onset. These methods
should provide information to assist clinicians in making successful treatment decisions and
increasing patient survival rate (Tothill, 2009). A range of biomarkers have been identified
with different types of cancers. These include DNA modifications, RNA, proteins (enzymes
and glycoproteins), hormones and related molecules, molecules of the immune system,
oncogenes and other modified molecules. Several biomarkers are current being studied,
including genes and proteins; however few of them have routine cancer clinical testing
importance because of their complexity. The development of protein based biomarkers for
biosensors use in cancer diagnosis is more attractive than genetic markers due to protein
abundance, recovery and cost effective technique for the development of point-of-care
devices (Li et al., 2010).
5.2 Biosensors in cancer disease
Existing methods of screening for cancer are heavily based on cell morphology using
staining and microscopy which are invasive techniques. Furthermore, tissue removal can
miss cancer cells at the early onset of the disease. Biosensor-based detection becomes
practical and advantageous for cancer clinical testing, since it is faster, more user-friendly,
Biosensors for Health Applications 79
less expensive and less technically demanding than microarray or proteomic analyses.
However, significant technical development is still needed, particularly for protein based
biosensors. For cancer diagnosis multi-array sensors would be beneficial for multi-marker
analysis. A range of molecular recognition molecules have been used for biomarker
detection, being antibodies the most widely used. More recently, synthetic (artificial)
molecular recognition elements such as nanomaterials, aptamers, phage display peptides,
binding proteins and synthetic peptides as well as metal oxides materials have been
fabricated as affinity materials and used for analyte detection and analysis (Sadik et al.,
2009; Khati, 2010). Antibodies (monoclonal and polyclonal) have been applied in cancer
diagnostics tests targeting cancer cells and biomarkers. Polyclonal antibodies can be raised
against any biomarker or cells and with the introduction of high throughput techniques,
applying these molecules in sensors has been successful. The use of monoclonal antibodies
however, results in more specific tests. The drawbacks include that monoclonal antibodies
are more difficult to maintain and can be more expensive than polyclonal antibodies (Huang
et al., 2010). Replacing natural biomolecules with artificial receptors or biomimics has
therefore become an attractive area of research in recent years. The advantages of using
these molecules are that they are robust, more stable, less expensive to produce and can be
modified easily to aid immobilization on the sensor surface as well as adding labels as the
maker for detection (Liu et al., 2007). Those molecules can be synthesized after a selection
from combinatorial libraries with higher specificity and sensitivity when compared to the
ER,PR, HER2, CA15-3, CA125, CA27.29, CEA
Breast BRCA1, BRCA2, MUC-1, CEA, NY-BR-1, ING-
BAT, FDP, NMP22, HA-Hase, BLCA-4, CYFRA
P53, Bcl-2, Brn-3a, MCM, SCC-Ag, TPA,
CYFRA 21-1, VEGF, M-CSF
Colon HNPCC, FAP, CEA, CA19-9, CA24-2, p53
Leukemia Chromosomal aberrations
Liver AFP, CEA
NY-ESO-1, CEA, CA19-9, SCC, CYFRA21-1,
Melanoma Tyrosinase, NY-ESO-1
Ovarian CA125, AFP, hCG, p53, CEA
Pancreas CA19-9, CEA, MIC-1
Prostate PSA, PAP
Circulating tumour cells in biological fluids,
expression of targeted growth factor receptors
Stomach CA72-4, CEA, CA19-9
Table 1. Cancer biomaker
80 Biosensors for Health, Environment and Biosecurity
For cancer biomarkers analysis, bioaffinity based electrochemical biosensors are usually
applied to detect gene mutations of biomarkers and protein biomarkers. Electrochemical
affinity sensors based on antibodies offer great selectivity and sensitivity for early cancer
diagnosis and these include amperometric, potentiometric and impedimetric/conductivity
devices. Amperometric and potentiometric transducers have been the most commonly used,
but much attention in recent years has been devoted to impedance based transducers since
they are classified as label-free detection sensors. However, much of the technology is still at
the research stage (Lin & Ju, 2005; Wang, 2006). Besides based on antibodies, electrochemical
devices have been developed based on DNA hybridization and used for cancer gene
mutation detection. In this type of device a single stranded DNA sequence is immobilized
on the electrode surface where DNA hybridization takes place (Ahmed, 2008). ELISA based
assays conducted on the electrode surface are the most frequently used techniques for
cancer protein markers analysis, such as CEA. In this method the antibody (or antigen) is
labeled with an enzyme such as horseradish peroxidase (HRP), or alkaline phosphatase (AP)
and these will then catalyze an added substrate to produce an electroactive species which
can then be detected on an electrochemical transducer. Electrochemical detection of rare
circulating tumor cells has the potential to provide clinicians with a standalone system to
detect and monitor changes in cell numbers throughout therapy, conveniently and
frequently for efficient cancer treatment (Chung et al., 2011).
Many commercially available platforms use fluorescence labels as the detection system.
However, the instruments used for signal readout are usually expensive and are more
suitable for laboratory settings. As an example the Affymetrix gene chip (Affymetrix Inc.,
Santa Clara, USA) can be used for screening cancer and cancer gene identification. Other
biosensor platforms such as grating couplers, resonant mirrors and surface plasmon based
systems have also been used for cancer biomarkers diagnosis. These are classified as label-
free and real-time affinity reaction detection systems. Different SPR based biosensors have
been developed for cancer markers detection based on the above optical systems (Tothill,
2009). Recently, microcantilever based sensors have also been applied for early-stage
diagnosis of hepatocellular carcinoma (Liu et al., 2009b).
In spite of the achieved development in cancer biosensing, the point-of-care testing is not yet
available. In order to achieve this goal challenges must be overcome such as: development
of reproducible biomarker assays; improvement in recognition ligands; development of
multi-channel biosensors; advances in sample preparation; device miniaturization and
integration; development of more sensitive transducers; microfluidics integration; advanced
manufacturing techniques and cost reduction (Rasooly & Jacobson, 2006).
A precise diagnostic for a disease is essential for a successful treatment and recovery of
patients suffering from it. Diagnostics methods must be simple, sensitive and able to detect
multiple biomarkers that exist at low concentrations in biological fluids. Biosensors can
fulfill these requirements. However, biosensor devices need to be further developed and
improved to face these new challenges to allow, for example, multiplex analysis of several
biomarkers where arrays of sensors need to be developed on the same chip.
Biosensors are firmly established for application in clinical chemical analysis. Biosensors for
measurement of blood metabolites such as glucose, lactate, urea and creatinine, using both
electrochemical and optical modes of transduction, are commercially developed and used
Biosensors for Health Applications 81
routinely in the laboratory, in point-of-care settings and, in the case of glucose, for self-
testing. While immunosensors have difficulty competing with traditional immunoassay
based mainly on sensitivity requirements, they hold promise for testing where some
sensitivity can be sacrificed for improved ease of use and faster time to result, such as in
near-patient testing for cardiac and cancer markers. Although biosensors are used for
several clinical applications, few biosensors have been developed for cardiovascular and
cancer-related clinical testing. Development of molecular tools, both genomic and
proteomic, to profile tumors and produce molecular signatures, based on genetic and
epigenetic signatures, changes in gene expression and protein profiles and protein
posttranslational modifications has opened new opportunities for utilizing biosensors in
cancer testing. Harnessing the potential of biosensors is challenging because of cancer’s
complexity and diversity. Successful development of biosensor-based cancer testing will
require continued development and validation of biomarkers and development of ligands
for those biomarkers, as well as continued development of sample preparation methods and
multi-channel biosensors able to analyze many cancer markers simultaneously. The use of
biosensors for cancer clinical testing may increase assay speed and flexibility, enable multi-
target analyses and automation and reduced costs of diagnostic testing. Biosensors have the
potential to deliver molecular testing to the community health care setting and to
underserved populations. Cancer biomarkers identified from basic and clinical research, and
from genomic and proteomic analyses must be validated. Ligands and probes for these
markers can then be combined with detectors to produce biosensors for cancer-related
clinical testing. Point-of-care cancer testing requires integration and automation of the
technology as well as development of appropriate sample preparation methods (Rasooly &
A clear direction for future work in biosensor research is in molecular diagnostics.
Improving the sensitivity of DNA biosensors for a single-molecule detection in an
unamplified sample is an important goal to achieve. This goal will require enhancing the
signal-to-noise rate, improving the signal produced by the biochemical reaction or
increasing the sensitivity of the transducer while reducing background noise. Ultrasensitive
transducer technologies will be required. Some recent examples of transduction modes with
enhanced sensitivity include microcantilevers for the detection of mass changes upon
detection of a binding event and quartz crystal microbalances capable of monitoring
formation and rupturing of chemical bonds by sensing acoustic emissions. The latter has
demonstrated sensitivity to detect a single virus particle. Increasing the arrays amplitude for
more complete and rapid DNA sequencing information is another area of focus, and
improvements in this area may ultimately be limited by resolution of the detection
transducer. DNA chips are being incorporated into total analysis systems, including
microfluidics and the biosensor on a single structure. These systems should include, in the
future, no need for sample preparation, a user-friendly handling system, chemical analysis
and signal acquisition capabilities. Central to development of lab-on-a-chip analysis system
will be the homogeneous sensing formats and microfabrication technologies for DNA
analysis. One recent step towards a homogeneous assay has been the development of
synthetic polymeric probes that emit fluorescence only after the hybridization to native
DNA targets, allowing monitoring of hybridization in real time without the need for
separation steps. Further development and improvement of nanotechnologies will be
needed to produce nanoscale devices, with expanded sizes of arrays using reduced sample
volume. The future of such devices for rapid determination of a disease could be especially
82 Biosensors for Health, Environment and Biosecurity
used for point-of-care application. However, cost and quality control of these devices must
be strictly adjusted for the accurate devices to gain popular acceptance. Homogeneous assay
formats, removing the need for sample preparation and amplification steps and mass
fabrication will be important to lowering cost.
Molecular biology will play a central role in the future of biosensor development, for
example, to improve biocomponent stability, and for the development of aptamers. The
highly reproducible synthetic approach and ease of immobilization of aptamers hold great
promise for the custom design of future biosensors for molecular diagnostics (D’Orazio,
2003). Future innovation in biosensor technology to include biomarkers patterns, software
and microfluidics can make these devices of high potential for health applications. The
concept of using nanomaterials in the development of sensors for biomarkers diagnosis will
make these devices highly sensitive and more applicable for point-of-care early diagnosis.
Early diagnosis will aid in the increase in the survival rate of patients and successful
development of biosensors for disease diagnosis and monitoring will require appropriate
funding to move the technology from research through to the realization of commercial
Biosensor research and development over the past decades have demonstrated that it is still
a relatively young technology. The rationale behind the slow and limited technology
transfer could be attributed to cost considerations and some key technical barriers. Many of
the more recent major advances had to await miniaturization technologies that are just
becoming available through research in the electronic and optical solid state circuit
industries. Analytical chemistry has changed considerably, driven by automation,
miniaturization, and system integration with high throughput for multiple tasks. Such
requirements pose a great challenge in biosensor technology which is often designed to
detect one single or a few target analytes. Successful biosensors must be versatile to support
interchangeable biorecognition elements, and in addition miniaturization must be feasible to
allow automation for parallel sensing with ease of operation at a competitive cost. The
future is very bright for biosensors. These advancements will, however, require a concerted
multi-disciplinary approach for the sensor systems to successfully make the very big jump
from the research and development laboratory to the market place. Combination of several
new techniques, derived from physical chemistry, molecular biology, biochemistry, thick
and thin film physics, materials science and electronics with the necessary expertise has
revealed the promise for development of viable clinical useful biosensor.
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Biosensors for Health, Environment and Biosecurity
Edited by Prof. Pier Andrea Serra
Hard cover, 540 pages
Published online 19, July, 2011
Published in print edition July, 2011
A biosensor is a detecting device that combines a transducer with a biologically sensitive and selective
component. Biosensors can measure compounds present in the environment, chemical processes, food and
human body at low cost if compared with traditional analytical techniques. This book covers a wide range of
aspects and issues related to biosensor technology, bringing together researchers from 16 different countries.
The book consists of 24 chapters written by 76 authors and divided in three sections: Biosensors Technology
and Materials, Biosensors for Health and Biosensors for Environment and Biosecurity.
How to reference
In order to correctly reference this scholarly work, feel free to copy and paste the following:
Cibele Gouvea (2011). Biosensors for health applications, Biosensors for Health, Environment and Biosecurity,
Prof. Pier Andrea Serra (Ed.), ISBN: 978-953-307-443-6, InTech, Available from:
InTech Europe InTech China
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By 1500, the Empire had reclaimed most of its territory in Britannia.
The Western Mediterranean was fully in the Empire’s control, and Iberia was nearly fully reclaimed.
Persia and Arabia were stabilized and under the Empire’s control.
The Holy Roman Empire control central Europe, plus a few far flung provinces.
It was internally chaotic, as always.
Scandinavia was a mass of petty states, with the Golden Horde still attempting to hold on to a little of it.
The Golden Horde controlled much of northeastern Europe.
The Empire had begun stabilizing the steppes to the east.
Imperial traders had discovered much of the Indian Ocean, as well as the coast of eastern Africa.
Greeks dominated the Empire, though the were a few other cultures. And a few peoples still followed the Pope.
Imperial traders completely controlled trade within the Empire, but had little influence outside it.
Imperial diplomats did much to secure the Empire’s borders.
This was the world in 1500.
This was that portion of the world controlled by the Empire.


The emphasis is on fun, yet we inspire learning about concepts through dialogue and questioning.
Brand new programme for all weeks in summer.
***PLEASE NOTE THAT TOPICS AND/OR THE ORDER OF THE TOPICS ARE SUBJECT TO CHANGE WITHOUT PRIOR NOTICE***
Monday 30 July: Historical Mathematics
We commence our STEM Summer Camp by studying the contributions towards mathematics from different civilisations of the past. Your child will learn about the Babylonians, Ancient Romans, Ancient Egyptians and more.
Tuesday 31 July: Neurotic Neuroscience
Neuroscience is the study of the structure and function of the nervous system. Your child will have a unique opportunity to learn about the structure of the brain and perform a dissection. Children will learn about the reflex arc and more.
Wednesday 1 August: Biochemistry
Biochemistry is an interdisciplinary subject that incorporates elements of biology, chemistry and mathematics. Children will be learning and discovering the role of enzymes, DNA and more through a variety of hands-on activities.
Thursday 2 August: Sustainable Engineering
Sustainability is becoming an increasingly important area in STEM. Your child will be assigned the role of a sustainable engineer as they design, build and evaluate a pervious paving system, roof garden and more.
Friday 3 August: Rocket Science
In this science, engineering and mathematics-based day, children will be constructing and launching a variety of different rockets using different reaction masses. Children will perform calculations that estimate its velocity and will employ Newton’s laws of motion.
We offer 10% discount on siblings booking and multiple bookings.
Any days booked individually will be charged at £85.00 per child.


March 3, 2014 |
In addition to being a transportation fuel, methanol is an important ingredient in plastics, adhesives and solvents.
Now, researchers say they’ve found a clean and cheap way to convert the greenhouse gas carbon dioxide into methanol.
Scientists from the Technical University of Denmark, Stanford University and SLAC National Accelerator Laboratory found a new nickel-gallium catalyst that turns hydrogen and carbon dioxide into methanol with less side-products than the traditional catalyst.
“Methanol is processed in huge factories at very high pressures using hydrogen, carbon dioxide and carbon monoxide from natural gas,” said SLAC scientist Felix Studt. “We are looking for materials than can make methanol from clean sources under low-pressure conditions, while generating low amounts of carbon monoxide.”
Added Jens Nørskov, a chemical engineer at Stanford: “Imagine if you could synthesize methanol using hydrogen from renewable sources, such as water split by sunlight, and carbon dioxide captured from power plants and other industrial smokestacks…. Eventually we would also like to make higher alcohols, such as ethanol and propanol, which, unlike methanol, can be directly added to gasoline today.”
In a normal methanol plant, natural gas and water are turned into so-called synthesis gas, or syngas, which is mostly carbon monoxide, carbon dioxide and hydrogen. That, in turn, is turned into methanol via high-pressure and a catalyst made of copper, zinc and aluminum.
“We spent a lot of time studying methanol synthesis and the industrial process,” said Studt. “It took us about three years to figure out how the process works and to identify the active sites on the copper-zinc-aluminum catalyst that synthesize methanol.”
Once the team understood the molecular workings of methanol synthesis, they looked for a new catalyst to synthesize methanol at low pressures with just hydrogen and carbon dioxide. To help the hunt, they searched for promising candidates in a large database developed at SLAC.
“The technique is known as computational materials design,” said Nørskov. “You get ideas for new functional materials based entirely on computer calculations. There is no trial-and-error in the lab first. You use your insight and enormous computer power to identify new and interesting materials, which can then be tested experimentally.”
The researchers compared the copper-zinc-aluminum catalyst with thousands of other materials in the database. The most promising candidate turned out to be a little-known compound called nickel-gallium. “Once we got the name of the compound out of the computer, someone still had to test it,” Nørskov said. “We don’t do lab experiments here, so we have to have a good experimental partner.”
Lab tests confirmed it was the right choice. Nickel-gallium made more methanol than the conventional copper-zinc-aluminum catalyst, and less of the carbon monoxide byproduct. “You want to make methanol, not carbon monoxide,” Chorkendorff said. “You also want a catalyst that’s stable and doesn’t decompose. The lab tests showed that nickel-gallium is, in fact, a very stable solid.” Nickel is fairly abundant, and gallium is already is widely used in the electronics industry. Because of this, the new catalyst could eventually be scaled up for industrial use, the authors say.