In the contemporary world, the need for quick, reliable, and easy-to-use diagnostic tests has become paramount due to the mounting challenges posed by fast-spreading viruses, chronic diseases, and drug-resistant bacteria. The prospect of conducting such tests anywhere, by anyone, using portable devices — akin to smartwatches — is becoming a reality. This vision hinges on developing microchips capable of detecting minuscule concentrations of viruses or bacteria in the air.
Recent advancements in this field have been demonstrated by a research team from NYU Tandon, consisting of Professor of Electrical and Computer Engineering Davood Shahrjerdi, Herman F. Mark Professor in Chemical and Biomolecular Engineering Elisa Riedo, and Industry Associate Professor in Chemical and Biomolecular Engineering Giuseppe de Peppo. Their breakthrough research shows the feasibility of developing and manufacturing microchips capable of identifying multiple diseases from a single cough or air sample and producing these chips at scale.
The Promise of Microchip-Based Diagnostics
Transforming Healthcare with Microchips
“This study opens new horizons in the field of biosensing,” states Riedo. The use of microchips, which have revolutionized communication, entertainment, and work, is now poised to transform healthcare. These microchips utilize field-effect transistors (FETs) — miniature electronic sensors that directly detect biological markers and convert them into digital signals. This approach offers a significant advantage over traditional color-based chemical diagnostic tests, such as home pregnancy tests.
Davood Shahrjerdi, who co-directs NYU’s NanoBioX initiative along with Riedo and serves as the Director of the NYU Nanofabrication Cleanroom, highlights that this advanced approach enables rapid results, the capability to test for multiple diseases simultaneously, and the immediate transmission of data to healthcare providers. This capability heralds a new era in which healthcare providers can swiftly and accurately diagnose and treat patients based on real-time data, reducing the time and resources required for traditional diagnostic methods.
The Role of Field-Effect Transistors (FETs)
FETs, integral components of modern electronics, are emerging as potent tools in the development of diagnostic instruments. These tiny devices are being adapted to function as biosensors, capable of detecting specific pathogens or biomarkers in real-time without the need for chemical labels or lengthy lab procedures. By converting biological interactions into measurable electrical signals, FET-based biosensors provide a rapid and versatile platform for diagnostics, offering critical advantages in speed, sensitivity, and specificity.
Advancements in the detection capabilities of FET biosensors have reached incredibly small levels — down to femtomolar concentrations, or one quadrillionth of a mole — by incorporating nanoscale materials such as nanowires, indium oxide, and graphene. These materials enhance the sensitivity of the sensors, enabling them to detect even the smallest quantities of biological markers. Despite their potential, FET-based sensors face challenges in detecting multiple pathogens or biomarkers simultaneously on a single chip. Current customization methods involving the drop-casting of bioreceptors like antibodies onto the FET’s surface lack the precision and scalability needed for more complex diagnostic tasks.
Overcoming Challenges in Multi-Disease Detection
Precision and Scalability in FET Customization
Current customization methods involving the drop-casting of bioreceptors like antibodies onto the FET’s surface lack the precision and scalability needed for more complex diagnostic tasks. To address these challenges, researchers are exploring new methods to modify FET surfaces, enabling each transistor on a chip to be tailored to detect a different biomarker, thereby allowing parallel detection of multiple pathogens.
One such promising technique is thermal scanning probe lithography (tSPL), which offers precise chemical patterning of a polymer-coated chip. This method enables the functionalization of individual FETs with different bioreceptors, such as antibodies or aptamers, at resolutions as fine as 20 nanometers. This is comparable to the tiny size of transistors in today’s advanced semiconductor chips. By allowing for the highly selective modification of each transistor, this technique paves the way for the development of FET-based sensors capable of detecting a wide variety of pathogens on a single chip with unmatched sensitivity.
The Impact of Thermal Scanning Probe Lithography (tSPL)
Riedo, who played a crucial role in the development and proliferation of tSPL technology, emphasizes its groundbreaking application, stating, “tSPL, now a commercially available lithographic technology, has been key to functionalize each FET with different bioreceptors to achieve multiplexing.” This innovative approach addresses the need for high specificity and sensitivity in detecting various biomarkers, crucial for effective disease diagnostics.
In experimental tests, FET sensors functionalized using tSPL exhibited remarkable performance, detecting concentrations as low as 3 attomolar (aM) of SARS-CoV-2 spike proteins and as few as 10 live virus particles per milliliter. These sensors also effectively distinguished between different types of viruses, including influenza A. The capacity to reliably detect such minuscule quantities of pathogens with high specificity is a critical milestone toward creating portable diagnostic devices that could be used in various settings, from hospitals to homes.
Industry Collaboration and Future Prospects
Support from Industry Partners
The study’s findings have been published by the Royal Society of Chemistry in Nanoscale. The research was supported by Mirimus, a biotechnology company based in Brooklyn, and LendLease, a multinational construction and real estate company from Australia. These industry partners are collaborating with the NYU Tandon team to develop illness-detecting wearables and home diagnostic devices, harnessing the power of these advanced microchip technologies.
“This research showcases the power of collaboration between industry and academia and its potential to reshape modern medicine,” remarks Prem Premsrirut, President and CEO of Mirimus. Alberto Sangiovanni Vincentelli of UC Berkeley, a collaborator on the project, notes, “Companies like Lendlease and other urban developers are seeking innovative solutions like this to detect biological threats in buildings. Biodefense measures like this will become a new infrastructural layer for the buildings of the future.”
The journey from laboratory research to real-world application requires the seamless integration of scientific discovery with practical implementation, underscoring the necessity for collaborative efforts. As semiconductor manufacturing continues to advance, the potential to integrate billions of nanoscale FETs onto microchips is becoming increasingly feasible, heralding the creation of sophisticated diagnostic tools capable of real-time, multi-disease detection with unprecedented speed and accuracy.
Advancing Towards a New Era of Diagnostics
In today’s world, the urgent need for quick, reliable, and easy-to-use diagnostic tests is crucial given the challenges posed by rapidly spreading viruses, chronic illnesses, and antibiotic-resistant bacteria. The idea of performing these tests anywhere, by anyone, with portable devices similar to smartwatches is becoming a reality. This vision relies on developing microchips that can detect tiny concentrations of viruses or bacteria in the air.
A recent example of advancements in this field comes from a team at NYU Tandon. This team includes Professor of Electrical and Computer Engineering Davood Shahrjerdi, Herman F. Mark Professor in Chemical and Biomolecular Engineering Elisa Riedo, and Industry Associate Professor in Chemical and Biomolecular Engineering Giuseppe de Peppo. Their groundbreaking research has demonstrated the potential to develop and mass-produce microchips that can diagnose multiple diseases from a single cough or air sample. This innovation underscores the feasibility and significant impact of these microchips on public health.
