Cells can be reprogrammed by humans to act as sensors or to complete more complex tasks.

Plasmids are small DNA messages that can be used by bacteria to alter their programming and behavior.

Bacterial biosensors are sensors that use genetically altered bacteria to detect the presence of chemicals.

There are multiple ways to solve an engineering (real world) problem.

Bacterial biosensor

Permeable membrane

GFP

RFP

Bacterial Biosensor Design Activity Presentation

Biosensor Design Challenge Virtual Worksheet

Groups of 3-4 students

2-3 hour

Students should have an understanding of what a biosensor is before starting this activity.  The lesson “Intro to Bacterial Biosensors” is a great introductory lesson. “Bacterial Transformation” is also a helpful pre-lesson, but not necessary.

• Reinforce DNA as the cell’s program/instructions. Develop student’s understanding that by altering the cell’s genes, the cells gain new functions and behaviors.
• Reinforce the concept of a biosensor, a cell that acts as a living sensor.
• Introduce to students the idea that cells can be engineered to solve problems.
• Encourage design thinking to solve real world problems.

Biosensors are living sensors that detect chemicals in the environment. A very simple example of a biosensor is a canary in a coal mine. The canary would die if certain toxic substances were in the air, but at significantly lower concentrations than would be deadly to humans. Many cellular biosensors are similar, used to detect toxic substances at concentrations far lower than humans can detect.  In this lesson, the sensor is made from e. coli bacteria. By altering and implanting plasmid DNA (a small loop of DNA commonly found in bacteria) into the e. coli bacteria, they can be converted into a biosensor that detects some chemical and responds by changing color (by turning on a gene that produce a pigment or a chemical compound that glows, like GFP).

Often the genes that are used to detect chemicals and change the color of the bacteria are genes already found in nature in some other species.  For example, there are bacteria that make their homes in toxic environments (like C. Metallidurans) that already have lead detecting genes.  And there are some organisms that glow (like A. Victoria, a fluorescent jellyfish).  When cellular engineers combine these two genes, they make sure that the glowing gene will only activate after the lead gene has activated (after the cell detects lead in the environment), thus ensuring that the new bacteria will only glow when lead is present. Thus, this biosensor would detect lead and glow as a result.

These bacterial biosensors can be used on their own (i.e. you can grow a bacterial biosensor in a petri dish or test tube, expose it to a water sample, wait, and use your eyes to detect any glow or change in color), but often cellular engineers will go a step beyond and create a device that surrounds the bacteria biosensor to make it easier, safer, and more accurate to use. For example, instead of growing the bacterial biosensor inside a petri dish, engineers have created small pill shaped containers for the biosensors so that they can be swallowed safely by patients, or small devices that attach directly to the water supply to be tested.  In either case, the bacteria are enclosed inside the device, but have access to the environment through a permeable membrane (that allows small chemical compounds through, but prevents the engineered bacteria from escaping the device).

Additionally, to automate the process, engineers might add a camera or other light sensor to automatically detect even small changes in bacteria color.  This camera could be connected to a wireless transmitter to allow collection of data even when the bacterial biosensor device is inaccessible (inside a patient or attached to plumbing).  But it’s important to remember that these technical additions are not the biosensor. The biosensor is the genetically altered bacteria. The container and/or cameras added around the bacterial biosensor just make the biosensor easier to use and read.

To help students start an engineering design challenge, it’s helpful to give them a few things to start: 1) what are the boundaries? What materials can the students use to build a solution? What must their design include? Who will be the end user of their design (an expert or a novice?), what safety factors or features must be included? 2) what are some examples? It’s often hard to start designing from scratch. Even though it might seem like you are influencing their designs and “giving them the answer”, offering other working designs as examples can help students get started on their own design and serve as points of inspiration. 3) Are there any tips or technical leaps that the students would be unlikely to guess on their own? For some design projects, there’s a technical component that would be hard for the student to guess. In the case of a device surrounding a biosensor, a permeable membrane would allow in toxins and nutrients for the bacteria, without letting the bacteria escape (pores too small to let bacteria through). This idea would be hard for the students to guess on their own, so presenting it up front will likely help them conceptualize their designs.

Introduction (10 mins):

Let students know that today they will designing a device that goes on the outside of the bacterial biosensor. This device should allow the students to test the tap water at their school for either lead or xylene. There are two bacterial biosensors to choose from (lead detecting and xylene detecting). The lead detecting bacteria glows green from GFP (green fluorescence protein) when they detect lead (although a UV light to activate the GFP). The xylene detecting bacteria turn red from RFP (red fluorescent protein), but no UV light is needed to see a color change. The device they design to contain the bacteria should isolate the bacteria from the tap water (no bacteria should be able to escape into the water supply) and should be easy to use for any high school student, even those that know nothing about biosensors or cellular engineering.

Criteria (share with students):

• Must use at least one bacterial biosensor in the design
• Must have bacterial biosensor a sealed compartment to allow transportation to other high schools. One way is to use a “permeable membrane” – a membrane that has pores that are smaller than the bacteria, that way bacteria can’t escape the device, but the lead or xylene they need to detect and still diffuse across the membrane to allow for detection.
  
• Must be relatively easy to use 
• Use of electronics (cameras, smartphone connection, etc.) optional. Manual color readout by users is fine
• This is a rough draft design, so no need to worry about specifics 
• Use articles and videos about biosensors to guide your design!

Activity (1 hr 20 mins):

In groups, students can use the “Biosensor Design Challenge” virtual worksheet to guide their design and collaborate virtually.  This worksheet includes:

• A description of the design challenge
• Table of contents
• Design criteria, including articles and videos describing other biosensor devices for inspiration
• A space for students to draw and write about their design
• An assignment description (with space to include a link to turn in their finished designs)
• Reference photos of what the bacteria look like when they do or do not detect something (either lead or xylene)

(30 mins)

Once all students have turned in their final designs you can either have the class participate in a gallery walk (Google “Jamboard” is useful for doing virutal gallery walks as students can place sticky notes on each other’s work (https://support.google.com/jamboard/answer/7424836?hl=en)) or you can have each group elect one representative that will give a short overview of their design to the class.

Many students get confused about what a bacterial biosensor is.  Because the articles and videos talk about the mechanical devices surrounding the bacteria, students often assume the sensor is the mechanical device around the bacteria and not the bacteria themselves.  Ask students if they know what part of the device is actually detecting the chemical for each example? (answer: the bacteria)  Is the device detecting bacteria (or chemicals made by a bacteria)? (answer: no) Would the devices work to detect the chemical without the bacteria? (answer: no)

The Bioethics (Portobello Colegio and the UCSF Biosensor) is a great extension after students have completed this activity.  While it doesn’t require extensive understanding of the science of a biosensor, student will benefit from having a firm foundational understanding of biosensors before engaging in the ethical case study that is the focus of the Bioethics lesson. 

ETS2 Links Among Engineering, Technology, Science, and Society

HS-LS1-1 From Molecules to Organisms: Structures and Processes

(The plasmid DNA determines the structure of the pigment or fluorescent protein, which allows bacteria to change color or glow.)

HS LS1.A Structure and Function

ETS2.A Interdependence of Science, Engineering, and Technology

(Science and engineering are linked and use similar tools to answer complex questions. In this example, the bacteria functions as a sensor to detect harmful chemicals. Engineers use the knowledge that scientists have generated about bacteria and how the function to create new bacteria that can be used as sensors.)

Practice 1. Asking Questions and Defining Problems

Practice 6. Constructing Explanations and Designing Solutions

Practice 8. Obtaining, Evaluating, and Communicating Information

Cause and Effect

Structure and Function