Diabetic product design hits close to home for ASU students

January 25, 2011

In February 2010, Ben Skousen learned that his 2-year-old son had diabetes. The senior industrial design student in ASU’s InnovationSpace program said the diagnosis was life-changing.

Each night at 2 a.m., Skousen and his wife are roused from a deep sleep. Most often, the job of glucose monitoring falls to Skousen’s wife who grabs a bag of medical instruments and stumbles down the hall into their son’s room. After fumbling with the lights, she pulls out a lancet and pricks her son’s finger. A drop of blood is captured on a flimsy test strip that must carefully be inserted into the tiny slot of a glucometer. If his glucose reading is high, she reaches for a syringe and administers a dose of insulin. Download Full Image

By the time it’s all over, the Skousens are wide awake and struggling to get back to sleep. They are likely to repeat this ritual each night until their son reaches adulthood.

“I want to improve this process so that my wife and son can have a good night’s sleep again,” Skousen said. He plans to specialize in medical product design after graduation in May 2011.

Skousen may get a head start on his wish in the 2010-2011 InnovationSpace program, a transdiscipinary product-development lab in the ASU School of Architecture and Landscape Architecture. His Team Nexus is one of three student groups sponsored this academic year by Dow Corning, the Michigan-based company that specializes in silicone-based technology development. The teams are charged with utilizing the company’s materials in the design of a device or system that will help users better manage a chronic medical condition.

After crunching the numbers, Team Nexus chose to focus on diabetes. According to research published in the 2009 issue of the journal Diabetes Care, nearly 24 million people in the United States, alone, have been diagnosed with diabetes. By 2034, the number is expected to jump to more than 44 million people.

“When I learned about what a huge problem diabetes is and how it’s growing, that made focusing on diabetes worthwhile for me,” said Ana Field, a visual communication design senior on Team Nexus. “Our project could help so many people and do so much good.”

Business student Carolyn Stearns also is eager to improve the daily lives of people with the disease. She has struggled to manage her Type 1 diabetes since childhood. “The goal for me is in this project is to make something that I would buy,” she said.

Stearns points out that insulin-delivery technologies have improved exponentially. With careful monitoring, people with diabetes now live longer and enjoy a better quality of life. But strides in diabetes technologies have far outpaced design innovations in the user experience, Stearns said. In an optimum regimen, for example, diabetics test their blood sugar an average of 10 times daily. To conduct each test, Stearns must pull out a messy collection of implements. Many of them, such as test strips, are small and difficult to handle. Inevitably, some users drop their glucometers on the floor and tiny parts break off and scatter, forcing them to buy whole new monitors.

Sharps containers, used to store used needles, are bulky and unsightly. So when she’s at school or work, Stearns collects her used needles in a plastic pouch in her handbag, which often causes her to stick herself when retrieving a pen or her car keys. Most of her fellow diabetics simply discard their needles in public trashcans, a practice that poses hazards for everyone.

For their mid-year InnovationSpace assignment, Team Nexus has created three product concepts that help solve some of these problems. During the spring 2011 semester, students will choose one idea and develop a detailed product and engineering design, branding and communications strategy and business plan.

Their first concept Creo (from the Latin for “create”) features a modular and fully customizable carrying system for diabetic implements. The system can be stripped down to carry essentials for a night on the town, or expanded to store products on an extended European backpacking tour.

“By making it easier to carry your supplies, you’re better able to take care of your condition,” Field said.

Novo (the Latin word for “change”) is a portable device for disposing used syringe needles.

The third concept, the Wingman, rethinks the entire blood sugar-testing system. The device combines multiple functions in a single design that is so easy to use that it can be manipulated with one hand, says Albert Hsia, the team’s biomedical engineering student. According to Skousen, the Wingman includes at least one no-brainer design feature: built-in illumination so that parents like him don’t have to flick on their children’s bedroom lights in the middle of the night to carry out a simple blood test.

No matter which product concept they choose to develop for their final project, the members of Team Nexus plan to keep the spotlight squarely on making it easier for diabetics to manage their condition.

Skousen said that the problem with so many products currently on the market is that the user has to adapt to the medical device.

“We want to turn that around and make sure the device adapts to the user,” he said.

Written by Adelheid Fischer, manager, InnovationSpace

Britt Lewis

Communications Specialist, ASU Library

Research into synthetic antibodies offers hope for new diagnostics

January 25, 2011

Antibodies are watchdogs of human health, continuously prowling the body and registering minute changes associated with infection or disease with astonishing acuity. They also serve as biochemical memory banks, faithfully recording information about pathogens they encounter and efficiently storing this data for later use.

Stephen Albert Johnston, Neal Woodbury and their colleagues at the Biodesign Institute at ASU have been exploring mechanisms of antibody activity, particularly the ability of these sentries to bind – with high affinity and specificity – to their protein targets. A more thorough understanding of the antibody universe may lead to a new generation of rapid, low-cost diagnostic tools and speed the delivery of new vaccines and therapeutics. Download Full Image

Borrowing a script from nature, the group has been working to construct synthetic antibodies or synbodies, through a simple method developed in Johnston’s Center for Innovations in Medicine. They have also examined the broad portrait of antibody activity revealed in a sample of blood, harnessing this information for the presymptomatic diagnosis of disease. These immunosignatures, as Johnston has named them, provide a dynamic report card on human health.

In a pair of new papers, the group demonstrated a simple means of improving the binding affinity of synbodies, which are composed of 20 unit chains of amino acids, strung together in random order. They also used random peptide sequences spotted onto glass microarray slides to mine information concerning the active regions or epitopes of naturally occurring antibodies. These two projects recently appeared in the journals PloS ONE and Molecular and Cellular Proteomics, respectively.

While antibodies have been in use for biomedical research for a long time, conventional techniques for producing them have been time consuming and expensive. Normally, antibodies used for research are produced in animals, which respond to a given injected protein by producing a protein-specific antibody, which may then be extracted.

In earlier work, Johnston’s group showed that high-affinity antibody mimics can be produced synthetically by simple means. Their technique turns the traditional production approach on its head. Rather than beginning with a given protein and trying to generate a corresponding antibody, the new method involves building a synthetic antibody first, later determining the protein it effectively binds with, by screening it against a library of potential protein mates.

The first step in this process is to generate random strings of 20 amino acids. Roughly, 10,000 such random peptides are then spotted onto a glass microarray slide. The protein one is seeking an antibody to is screened against this random sequence array and peptides with high binding affinity are identified. Two such peptides can be linked together to form a synbody, whose binding affinity is the product of each separate peptide. In this way, two weakly binding peptides join forces to form a high affinity unit, useful for investigations into the proteome, the vast domain of proteins essential to virtually all biological processes.

In the PloS ONE study, lead author Matthew Greving and his collegues describe a strategy for further refinement of binding affinity in random sequence peptides. 

“The problem,” Johnston explains, is that the microarray contains about 10,000 peptides, but that is less than a quadrillionth of the possible peptides by sequence. So we’re sampling a very small part of the sequence space. ”A consequence of this is that the probability of generating a 20 amino acid sequence, that binds with optimal affinity, is pretty low."

To improve sequence affinity, a lead sequence is first selected. In the study, one such sequence was the 17 amino acid peptide TNF-1, a key regulator of immune cells. The lead sequence is then used as a template from which to generate additional peptide sequences in which a single amino acid at each subsequent position along the peptide chain is replaced with a different amino acid.

Using this method, 96 variant peptides are constructed on a microarray plate. These enhanced variants are screened against a desired protein for binding affinity and a map is produced  displaying this affinity from low to high. The most successful variants can then be assembled into a new high affinity peptide, whose binding strength is the sum of the components.

This simple, algorithmic process can rapidly optimize random sequence peptides, improving their binding affinity by 100 to 1000 times.  The method can also be used to improve the specificity of peptides, enabling the construction of binding agents able to attach to a given protein while excluding unwanted binding targets.

The MCP study asked whether a similar random peptide microarray could assist in the process of epitope mapping, in which the active binding regions of antibodies are identified. Epitope mapping is one method for determining if a given antibody is suitable for a particular application, and a faster, more cost-effective method would be of significant biomedical value.

For these experiments, antibodies of known epitope were screened against random sequence peptides on a microarray.  High affinity peptides were identified and bioinformatics techniques were used to see if the random peptides could help identify the antibody epitopes.

Two techniques were applied; one in which high affinity random sequence peptides were compared side by side with the antibody epitopes they bound with and similarities statistically analyzed. The other method searched the peptides for signature “motifs” – consisting of at least seven amino acids (or two shorter motifs in combination).  

Lead author Rebecca Halperin and colleagues were able to show that statistically useful information on epitopes could indeed be gleaned from such bioinformatic probing, bringing the prospect of high throughput, inexpensive exploration of natural antibodies a step closer.

Johnston stresses the importance of this research. “The paper asks if there are mechanisms to transfer from random sequence space to real sequence space based on antibody binding. No one has explored this as deeply as Rebecca has.”

Further refinement should allow diagnosis of the precise protein sequence causing a given illness, based purely on analysis of immune response.

Stephen Albert Johnston is the director of the Center for Innovations in Medicine at the Biodesign Institute at Arizona State University. For more info,visit: http://biodesign.asu.edu/" target="_blank">biodesign.asu.edu

Written by Richard Harth
Biodesign Institute
Science Writer

Britt Lewis

Communications Specialist, ASU Library