Background

Our senses are the basis of observing and interacting with our surroundings. Thus, one could argue that sensing is fundamental to life (i.e., the acquisition, conversion, and analysis of signals). As the phrase goes, “If you can’t sense it, you can’t control it.”

Useful Definitions

Sensing is defined as the process of detecting, monitoring, converting, and interpreting signals. A sensor is a measurement device that converts a quantity to be measured (the input) into a signal (the output). Often, the input is a physical quantity, such as concentration, and the output is an electrical signal.

Who Cares About Sensors & Sensing?

Not surprisingly, sensors are essential technology that enable monitoring and control of complex processes and systems. For example, sensors & sensing are ubiquitous in biology (e.g., cells and organisms have the ability to sense multiple quantities, including temperature and concentration). Sensors & sensing are also foundational to modern manufacturing and technology. For example, sensors are the basis of process monitoring and control. 

Thus, the ability to control a process (i.e., respond to a stimulus) is directly tied to sensor performance. 

For example, the quality (e.g., speed, impact) of decision-making (e.g., control actions) is directly dependent on sensor performance.   Therefore, high-performance sensing is foundational to future manufacturing and emerging technologies, such as sustainable biomanufacturing and wearable biosensors.

Property Sensing, Chemical Sensing & Biosensing - What Are They and Who Cares?

Among sensing applications, the measurement of molecular and material properties, such as binding affinity or rheological properties, and the detection, identification, characterization, and quantification of target chemical species or biologics (e.g., small molecules, macromolecules, viruses, and cells) are central to several critical industries and emerging technologies.  For example, sensing of rheological properties are useful in a significant number of applications including polymer processing, bioprocessing, and food science and engineering applications.  Rheological properties provide information on material composition, processability, and quality and can facilitate real-time bioprocess monitoring.

In particular, the selective detection of biologics is central to public health (e.g., pandemic management, medical diagnostics), advanced manufacturing (biomanufacturing), smart agriculture, environmental protection, and national security.   In these applications, it is critical to be able to answer the following questions about a target analyte that may be present in a sample or system: 1) is it there? (detection), 2) what is it? (identification), 3) what are its properties? (characterization), and 4) how much is there? (quantification). 

Sensors for the detection of molecules can be classified as “chemical sensors” or “biosensors.” Both types of sensors can detect ‘biomolecules,’ but biosensors utilize a ‘biorecognition element,’ such as an antibody or nucleic acid, in combination with a sensitive transducer to establish high selectivity for the target analyte. Thus, the biorecognition element is a distinguishing characteristic of a biosensor. The International Union of Pure and Applied Chemistry defines a biosensor as “a self-contained, integrated, analytical device, in which a biological recognition element (biochemical receptors, including enzymes, antibodies, antigens, peptides, DNA, aptamers or living cells) is retained in direct spatial contact with a transduction element (such as electrochemical, optical and mechanical transducers). 

The first biosensor dates back to the 1960s and was based on an electrochemical device for glucose detection. A lot of progress has been made in 60 years. For example, we now have biosensors with a range of form factors, size, and utility. However, not all biosensors were created equal. For example, the utility of biosensors in different applications, such as for process monitoring and control, is quite variable depending on the type of biosensors. Biosensing techniques can be broadly characterized as 1) mix-and-measure (e.g., nano-biosensors), 2) flow-and-measure (e.g., microfluidic-based biosensors), and 3) dip-and-measure (e.g., electrochemical biosensors).   Thus, some biosensing techniques are destructive (to the sample) while others are not. Some biosensing techniques are applicable in a manufacturing setting, while others have absolutely no applicability whatsoever. For example, there are several applications where it is not possible or undesirable to sample from the process or mix a nano-biosensor into the process as it may damage the process or affect the product quality. Alternatively, nano-biosensors have a unique ability to interrogate intracellular, extracellular, and intercellular processes. As they say, “The devil is in the details.”  Thus, our lab is focused on developing reliable device-based biosensors and nano-biosensors for practical applications.

Grand Challenges in Biosensing - What are the Limits of Current Practice?

Sensor performance is defined by many characteristics/attributes, including sensitivity, speed, and reliability. For example, sensitivity, detection limit, speed, selectivity, and accuracy are critical performance attributes of biosensors. 

While biosensors have enabled rapid detection of single molecules in controlled environments, such as laboratory conditions, biosensor measurement confidence/reliability and speed are critical technical challenges that must be overcome to create high-performance biosensors capable of continuously monitoring and controlling bioprocesses and associated biomanufacturing processes (e.g., bioreactors). In particular, false-positive and -negative results, time delay, and saturation are barriers to the widespread adoption of biosensors for industrial, healthcare, and military applications. For example, challenges of false results associated with rapid diagnostic tests were widely publicized during the COVID-19 pandemic. Likewise, biosensor saturation is also a significant technical challenge that limits biosensor reusability and continuous monitoring applications. And while various approaches have been established for biosensor regeneration, such methods often insult the biosensor with chemicals that may affect the biosensor quality and performance (e.g., stability of the biorecognition element).

What Do We Do and What’s New in Our Approach?

Our lab is focused on addressing these grand challenges in biosensing through interdisciplinary research in several engineering disciplines (primarily chemical, mechanical, and electrical), computer science, and applied mathematics. 

Broadly speaking, the Johnson Lab is dedicated to ushering in a new paradigm of high-performance and smart biosensing through innovations in biosensor design, methodology, surface chemistry, biorecognition, automation, and analytics. 

We are also dedicated to creating emerging technologies and advanced processes driven by smart sensing, including autonomous experimentation, such as for applications in high-throughput biosensing and accelerated materials discovery, and advanced biomanufacturing.

What are Biomanufacturing and the Bioeconomy and Who Needs Them?

What is the bioeconomy?  The bioeconomy is economic activity involving the use of biotechnology and biomass. Importantly, the 'bioeconomy' now represents ~5% of GDP.  Biomanufacturing refers to the production of products or services using biotechnology or biomass. Bioprocessing, a type of biomanufacturing process, refers to the generation of products using microbial technology (e.g., cells), in which the product is the cell itself or  products produced by the cell.  Thus, this is a unique field of manufacturing in which the product may be the process.  Biomanufacturing is a collective term that refers to making products using biotechnology, biomass, or cells (viable biomass).

Biomanufacturing is an essential industry responsible for the production of medicine, food, and energy.  Thus, biomanufacturing processes, and bioprocesses, in particular, are essential to public health, the economy, and national security. Biomanufacturing is also a critical component of solving grand challenges, such as associated with sustainability.  In fact, experts project that the bioeconomy may represent ~ 50% of GDP in the near future. 

Given biomanufacturing involves the production of biologics using microbial technology, chemical sensors and biosensors play a critical role in process monitoring, control, and characterization of product critical quality attributes.

Ideally, we would like to continuously monitor and control bioprocesses in real-time by detecting, identifying, characterizing, and quantifying the species involved in the process. Often, these species are process inputs, critical quality attributes, or the products (outputs) themselves. However, it remains a challenge to create device-based biosensors for practical biomanufacturing applications based on the aforementioned challenges.

Research on smart sensing and manufacturing, and applications thereof in the biosensing and biomanufacturing domains, is highly interdisciplinary and applies theory, principles, and methodology from various engineering disciplines as well as computer science, neuroscience, biology, chemistry, and physics. Students from all backgrounds are welcome to venture deeper into the fascinating world of advanced biosensing and biomanufacturing.