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Human Practices

Considerations

Paper-based sensors capable of detecting diseases and pollutants can directly benefit society in a myriad of ways. In order to facilitate the growth and utilization of our project, the 2015 Pitt iGEM team has made efforts to identify, investigate and address the human practice factors that will influence the success and utility of our paper-based sensors.

With our planned devices, one of the primary diseases we are investigating is cancer. In considering potential ethics questions raised by at-home disease tests especially for a serious disease such as cancer one might ask us, “is it ethical to produce a test that could give a consumer a false positive indication for a such a serious illness? Such a result could lead to significant anxiety, grief or depression—potentially damaging to the consumer—until the issue is resolved by a medical practitioner.” This concern is certainly a potential issue for our paper-based sensors. To resolve this issue we would use very clear disclaimers that inform our consumer that the tests are not 100% accurate and that a positive results should be followed up immediately by a visit to the doctor. However, there is a complementary question of ethics that we must pose in favor of our products: “is it ethical to value some peoples’ state of mind over the potential to save their lives or improve their prognoses?” The answer to this question—when posed in several studies (USA Today, Science 2.0, NPR)—is overwhelmingly ‘no.’ Especially of note the diseases we have chosen to study human adenocarcinomas, including breast, kidney, pancreatic, and colon cancer are diseases in which early intervention can lead to much better prognosis. Paper-based sensors provide an opportunity to help members of society in a significant and dynamic way, and brings benefits that dramatically outweigh the potential negatives of false-positive results.

Another important human factor aside from ethics is the safety of the paper-based sensors. Our product was designed with safety in mind; the tests for urine and water work by placing a sample from the source onto the paper test similar to at-home pregnancy tests already in widespread use. This ensures that the tests never make direct contact with the patient or water source, preventing any potential backwards contamination. For the tests based on blood we would include a sterile finger prick needle and ethanol wipe to carry out the test similar to tests for blood sugar already a process has been streamlined over decades for at home care to ensure a safe process. The conclusion based on our safety analysis is that paper-based sensors provide a safe and non-invasive method of disease and pollution detection.

In addition to ethical and safety concerns, we must determine whether our product is economically feasible for commercial production. An important question that an investor would likely pose to our team might be, “is your project scalable for mass-production?” The answer is yes. The seminal paper for our paper-based synthetic gene networks, Pardee et al. 2014 estimated that the cost of a paper based sensor would be a mere – $0.35-$0.65/ test. The systematic verification of product quality will also be performed continuously. The remaining processes will be easily carried out in large batch form; the main batch processes include centrifuging and lysing the bacterial cultures and freeze drying the paper-based sensors. Although these large scale processes will ensure a high throughput—and therefore a significant economy of scale—the important factor which will determine our magnitude of success would be the market price of the tests. This is an easily affordable test, which will help to ensure access to our product regardless of socioeconomic status.

The economic feasibility of our project is not only favorable for an entrepreneurial entrance into the healthcare market, but it is also conducive to social justice. Currently, low socioeconomic status prevents some people from seeking necessary healthcare—especially if they are unsure if they are afflicted with a given suspected disease. Since our paper-based sensors can be sold at a low market price, they will be available to be purchased by anyone. This availability ensures that most people are able to determine whether they are afflicted with their suspected ailment.

Clearly, there are a variety of interactions that paper-based sensors will have with the surrounding human environment; there are likely some outcomes that we cannot predict—the market inherently gives products their most thorough analysis—but we have certainly found the most profound human factors that will affect the way our product interacts with the surrounding society. Our identification and analysis of these factors combined with our complementary product design will allow for a sustainable and successful commercial launch of paper-based sensors.

Integrating Human Practice issues into our project design

The choice of paper-based sensors

When considering the many implications that releasing a paper-based sensor as a commercial product might have, the Pitt iGEM team selected two areas of focus. First and foremost, our goal was to create a very cheap sensor that is easily transportable. To this end, we designed our own protocol for generating such sensors, rather than purchasing expensive commercial cell-free extracts. With our protocol, we were able to create extracts in as little as three days in large quantity. With some simple automation of the process, we estimate that 100 paper strips can be created for less than a dollar, not including instrument time costs. With such cheap production available, this makes the final product affordable for many, especially considering the simple transport of the sensors.

Analogue-to-digital converter to transform mid-level signals to binary positive or negative results.

We have directly integrated the human practices issue of obtaining mid-level difficult to interpret signals into the design of our project attempting to minimize the possibility of false positives. With many cell extract-based assays, it is difficult to have a binary response, as a gradient of concentrations will produce an analog gradient of sensor outputs. We attempted to differentiate between a positive and negative response by building an analogue-to-digital converter bandpass circuit, where amplification would ensure a significantly positive result would be visible, and a low signal would be quenched by a set amount of decoy quencher DNA. The amplification loop consists of a T3 promoter driving the production of T3 RNA Polymerase. By having a second system sensing system output T3 RNA Polymerase, the amplification loop with create exponentially more of the polymerase, leading to a stronger signal from a reporter construct based on the T3 promoter. The quenching is based on simple competitive inhibition of T7 or T3 RNA polymerase by a DNA "dumbell" hairpin decoy. By varying the amount of decoy in the reaction, a user-defined amount of low level signal can effectively be quenched. For more information on this part of the project, click here.