SENSOR INTEGRATION IN MICROFLUIDICS
Federico Paratore, IBM Research Europe, Switzerland
Federica Caselli, University of Rome Tor Vergata, Italy
Chii-Wann Lin, National Taiwan University, Taiwan
Workshop Description:
The coupling of sensors with microfluidics offers unprecedented opportunities for diagnostics and life science applications. In this workshop, after reviewing the basic principles of mass transport and reaction kinetics, we will focus on molecular and cell sensing using surface-based assays and impedance cytometry. We will present the most common approaches for molecular detection, with an in-depth focus on surface plasmon resonance (SPR); we will also discuss techniques for signal and specificity improvement, providing examples such as the use of functional aptamers for TB and SARS-COV-2 detection, and the use of electrokinetic focusing, e.g. ITP, ICP, for enhancing the reaction kinetics. Then, we will introduce microfluidic impedance cytometry and its use for characterizing biological cells, e.g. their morphological, electrical or mechanical properties, and we will discuss its integration with real-time processing approaches based on machine learning.
The workshop will be articulated in three lectures, as detailed in the following:
Lecture 1 (F. Paratore): TILL THE LAST MOLECULE: HOW TO MAKE THE BEST USE OF YOUR ANALYTE IN BIOSENSING
Lecture Description:
A biosensor can be roughly divided in four main elements: bioreceptor, transducer, electronics, and target analyte. In sensor design and miniaturization, while much emphasis is put on the first three elements, little attention is often given to the transport mechanism of the analyte to the sensor.
Because the binding reaction kinetic is inversely proportional to the analyte concentration, the spatio-temporal distribution of the analyte over the sensor determines the speed and the sensitivity of the assay. This represents a fundamental limit, particularly in detecting low-abundance targets, which is crucial for applications such as early disease diagnostic and analysis of single-cell contents.
Overview of Material to Be Covered and What Attendees Can Expect to Take Away From the Lecture:
In this lecture we will introduce the basic principles of mass transport, i.e. advection and diffusion, and reaction kinetics, and discuss their interplay to determine the sensor performance. We will analyze various transport regimes and discuss the key parameters that can be tuned to design and control the analyte distribution over the sensor. We will then present some advanced electrokinetic techniques for analyte focusing, such as isotachophoresis and ion concentration polarization, and their use for enhancing reaction kinetics.
Lecture 2 (C.W. Lin): RECENT ADVANCES IN SURFACE PLASMON RESONANCE BIOSENSING SYSTEMS
Lecture Description:
Surface plasmon resonance (SPR) has been accepted as the golden standard method for kinetic measurement of molecular interactions in biosensing applications. A typically SPR system consists four key components: optical (wavelength, phase), mechanical (scan and fluidic), electrical (signal processing and modeling), and biological parts (application specific). In this lecture, we will cover recent advances in these four aspects with both theoretical and practical examples. We will also provide a home-made automatic SPR system for on-site demonstration of the analytical processes.
Overview of Material to Be Covered and What Attendees Can Expect to Take Away From the Lecture:
How to avoid common pitfalls in SPR measurement!
Lecture 3 (F. Caselli): SINGLE-CELL MICROFLUIDIC IMPEDANCE CYTOMETRY: FROM RAW SIGNALS TO CELL PHENOTYPES
Lecture Description:
By integrating label-free sensing modalities into microfluidic platforms, the high-throughput biophysical characterization of single flowing cells has become possible. This lecture focuses on microfluidic impedance cytometry, whereby electrical sensing is used to characterize morphological, electrical or mechanical properties of biological cells.
Microfluidic impedance cytometry has already proved its potential in a number of applications. In recent years, novel concepts have been emerging, greatly enhancing the accuracy of the measurements as well as the information content embedded in the electrical fingerprints. Furthermore, hybrid platforms that combine microfluidic impedance cytometry with other sensing or manipulation modalities, and real-time processing approaches based on machine learning, are being developed. Overall, this opens up new opportunities for high-impact applications, with rapid phenotyping of complex samples being of central importance.
Overview of Material to Be Covered and What Attendees Can Expect to Take Away From the Lecture:
The lecture will answer these questions:
- Why is microfluidic impedance cytometry suitable for cell phenotyping?
- How can we design and use high-content single-cell electrical fingerprints?
- What are the emerging trends and opportunities?
Who Should Attend:
PhD students, post-docs, and researchers interested in designing surface-based reactions for biosensing as well as impedance-based devices for single-cell analysis. SPR users and system developers are also invited, and anyone interested in possible integration of sample handling for high throughput system.
Participants Will Need the Following:
No special requirements.