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Risorse bibliografiche
Risorsa bibliografica obbligatoria
Risorsa bibliografica facoltativa
Scheda Riassuntiva
Anno Accademico 2018/2019
Scuola Scuola di Ingegneria Industriale e dell'Informazione
Insegnamento 095381 - BIOCHIP
Docente Carminati Marco
Cfu 5.00 Tipo insegnamento Monodisciplinare

Corso di Studi Codice Piano di Studio preventivamente approvato Da (compreso) A (escluso) Insegnamento
Ing Ind - Inf (Mag.)(ord. 270) - MI (471) BIOMEDICAL ENGINEERING - INGEGNERIA BIOMEDICA*AZZZZ095381 - BIOCHIP
Ing Ind - Inf (Mag.)(ord. 270) - MI (476) ELECTRONICS ENGINEERING - INGEGNERIA ELETTRONICA*AZZZZ095381 - BIOCHIP
Ing Ind - Inf (Mag.)(ord. 270) - MI (486) ENGINEERING PHYSICS - INGEGNERIA FISICA*AZZZZ095381 - BIOCHIP

Obiettivi dell'insegnamento

The objective of the course is to present to the students, approaching the end of their educational carrier, an overview of the field of biochips and analytical lab-on-chip microsystems (whose recent advances are relevant both from the scientific and industrial point of view) with specific insights on the technological aspects of the interface between (micro)electronics and electrochemistry and biology, both at cellular and molecular levels. The content of the course reflects the multidisciplinarity of the nano-bio-tech field and is mainly focused on the different manipulation and detection approaches of biochemical target analytes. The main goal is to provide the students with the fundamental theoretical tools for the design of active microfluidic systems (basics of fluid dynamics at the microscale), and of the engineering of the detection systems (optical and electrochemical transducers). At the same time, several practical examples are discussed in order to illustrate design choices and trade-offs.


Risultati di apprendimento attesi

Dublin Descriptor

Expected Learning Outcomes

1. Knowledge and understanding

At the end of the course the students are expected to:

·         possess a good understanding of lab-on-chip systems (needs, applications, advantages and limits) and bio-electronics convergence

·         possess a basic knowledge of hard and soft lithographic microfabrication approaches

·         possess a basic knowledge of the laws describing the flow of liquid in microchannels and the forces to actuate particles in liquid

·         presses a good knowledge of the electrochemical interface and instrumentation for biosensing

·         possess a good knowledge of the DNA macromolecule and the instrumentation for its analysis

·         understand the potentials and challenges of CMOS/biochips integration

2. Applying knowledge and understanding

At the end of the course the students are expected to:

·         be able to analyze and design a microfluidic system in laminar regime (fluidic sizing, choice of components such as pumps/valves), starting from the sample preparation and manipulation

·         be able to design an analytical assay (for instance for molecular recognition or DNA analysis)

·         be able to design integrated detectors (both optical and electrochemical)

·         be able to design current and impedance sensing circuits for biochips

3.Making judgements

Students will be able to:

·         evaluate the most appropriate approach (materials, fabrication) to address an analytical need

·         apply the knowledge to different application areas

·         apply the knowledge to design a novel micro-device

4. Communication

During the work in teams for the experimental laboratory, students will be able to communicate among each other (in the first phase at home, when the microfluidic channels are designed upon technological specifications set in the classroom). Then, during the lab. and the oral exam their communication skills are deployed to motivate their design choices and comment the experimental results.


Argomenti trattati

The course is articulated in theoretical lessons, combined with quantitative exercises and with case studies oriented to the analysis and design of microsystems. An experimental laboratory consisting of: a design phase at home in teams with a propor design software and two days of experimental activity in the lab. (fabrication and characterization of a PDMS microfluidic device). Experts in the biochip field are also invited during the course to lecture seminars on specific topics, such as micromagnetism and DNA analysis, or to present the point of view of companies carrying on R&D in the biochip field (STMicroelectronics, Flextronics, etc…). A visit to the renewed clean-room and microfabrication facility of Politecnico di Milano (PoliFab) concludes the course.

Topics:

1. Introduction to biochips: architecture of lab-a-chip micro-analytical systems, motivations and impact, design paradigms, market projections, basic biological macromolecules used for as receptors in affinity biosensors.

2. Introduction to microfluidics: fluid dynamics, Reynolds number, electrical equivalent of hydraulic circuits (fluidic capacitance) and electro-osmotic flow. Actuation forces for particle manipulation within biochips: diffusion, electrophoresis, dielectrophoresis, electrowetting and droplet-based digital microfluidics. Active and passive microfluidic components: valves, mixers and pumps.

3. Introduction to microfabrication: review of Silicon CMOS-MEMS processes, lithography, thin film deposition and patterning, as compared to elastomer (PDMS) and plastic based soft lithography (replica molding).

4. Optical detection: fluorescence (strengths and limitations, Atomic Force Microscopy), source-filter-detector architectures, integrated photonics for biosensing based on evanescent field (waveguides, Mach-Zehnder interferometers, ring resonators and contactless light monitors). Electrochemical detection: the electrochemical interface with physiological ionic solutions (charge transfer and induction).

5. Electrochemical instrumentation: analytical techniques (cyclic voltammetry, amperometry and impedance spectroscopy) and the potentiostatic workstations. Micro and nano-scale electrochemistry: effects of electrode scaling.

6. Low-noise current measurements: review of noise in electronic devices, the transimpedance amplifier (working principle, properties and limitations) and advanced circuit topologies (integrator-differentiator schemes with different CMOS-compatible bias resetting solutions).

7. Impedance measurements and instrumentation, comparison of sensing configurations: bridge, ratiometric, current sensing, lock-in detection, resonant circuits, FFT-based and time-domain approaches.

8. Detection of DNA: structure and properties, microarrays (spotting and probe synthesis), electrophoresis, amplification with Polymerase Chain Reaction and quantitative detection with real-time PCR and approaches for sequencing.

9. Biochips for molecular detection: resonating cantilevers for molecular weighing, amperometric detection of neurotransmitters, redox cycling, glucose sensors based on enzymatic mediators, and nanopores. Biochips for cellular detection: interface with electrogenic cells, equivalent model of passive cells, label-free impedance monitoring a cell colony dynamics and single cell counting and sizing with microfluidic impedance flow cytometry (design case study).

10. Sample preparation (cell lysis, sample mixing, concentration and purification). Microelectronics CMOS biochips: state of the art performance in CMOS detection, design criteria, advantages and limits, the critical role of the substrate, packaging and interfacing issues.


Prerequisiti

Basic prerequisites:

  • fundamentals of chemistry (ions, chemical bonds, redox reactions)
  • fundamental of physics (electric charge, electric and magnetic field, dielectrics)
  • fundamental of electronics (Ohm’s and Kickoff’s laws, operational amplifier, feedback circuit, impedance, Bode plots)

Modalità di valutazione

Exams are held at the end of the course (no intermediate tests). The exam consists of a written test (2 hours) followed by an oral exam. The oral discussion is mandatory for students achieving high marks (> 27/30) in the written test and optional and open for all students.

 

Type of assessment

Description

Dublin Descriptor

Written test

Solution of numerical exercises focusing on 2 types. The first type concerns the microfabrication and the fluidics (and components) of channels. The second focuses on electrochemical detection. The students will be asked to analyze circuits and systems, as well as to design them.

1,2

Oral discussion

Students will be asked discuss the ultimate limits of the different technologies, pros and cons, compare them, and to design complete systems to address novel design cases proposed during the oral exam.

1,2,3,4


Bibliografia
Risorsa bibliografica facoltativaPatrick Tabeling, Introduction to Microfluidics, Editore: Oxford University Press, Anno edizione: 2010, ISBN: 9780199588169

Forme didattiche
Tipo Forma Didattica Ore di attività svolte in aula
(hh:mm)
Ore di studio autonome
(hh:mm)
Lezione
30:00
45:00
Esercitazione
16:00
24:00
Laboratorio Informatico
0:00
0:00
Laboratorio Sperimentale
4:00
6:00
Laboratorio Di Progetto
0:00
0:00
Totale 50:00 75:00

Informazioni in lingua inglese a supporto dell'internazionalizzazione
Insegnamento erogato in lingua Inglese
Disponibilità di materiale didattico/slides in lingua inglese
Disponibilità di libri di testo/bibliografia in lingua inglese
Possibilità di sostenere l'esame in lingua inglese
Disponibilità di supporto didattico in lingua inglese
schedaincarico v. 1.6.1 / 1.6.1
Area Servizi ICT
08/12/2019