Smartphone based biosensors

How has analytical chemistry and diagnosis evolved?

Traditionally, it relied on wet labs and skilled professionals using sophisticated instruments for sample handling/analysis, but it has shifted toward the use of standalone sensors with the development of new materials and sensing techniques

What have standalone sensors allowed?

It has allowed tests to be conducted on-site/in real time, leading to time and cost efficiency

Why are smartphones ideal platforms for standalone sensors?

Because they have extensive sensor capabilities, advanced processing power, and communication functionalities

How do smartphone-based assays use optical sensing?

By using built-in cameras, ambient light sensors, and other features

How do smartphone-based assays use electrochemical sensing?

Using micro-USB port, Bluetooth, and wireless connection, (this facilitates data transmission and analog voltage application)

What do analytical instruments in wet labs do?

Perform optical and electrochemical sensing

How is optical sensing carried out in a wet lab?

Using a spectrophotometer

How is electrochemical sensing carried out in a wet lab?

Using electrodes

What type of electrodes are used in electrochemical sensing?

pH, ion-selective, conductivity, and impedance analyzers

What is the disadvantage to optical and electrochemical sensing in a wet lab?

They use expensive, bulky instruments that aren’t widely available

What is the impact of the switch to standalone sensors?

Significant reductions in the cost and time required for the analysis and convenience to perform at the point of care or in patient’s home

What do sensors use to detect and measure analytes?

Receptor and transducer

What does the receptor do?

Specifically binds or reacts with the target analytes

What is necessary after the receptor has bonded or reacted with the target analyte?

To quantify the extent of the reaction

What does the transducer do?

Plays a crucial role in the quantification process of the target analyte reaction with the receptor

What are the most commonly used types of transducers?

Optical and electrochemical

What features do smartphones have?

Diverse arrays of sensors, integrated software features, processors, superior processing abilities, huge data storage capacities, ability to communicate raw/processed results to cloud storage or other devices

What features do smartphones have are useful for optical sensing?

Optical sensors like front/rear cameras, ambient light sensors(ALS), proximity sensors, IR sensors, white light-emitting diode flashes (LED)

What features does the smartphone use for electrochemical sensing?

Micro-USB port

What is the dual functionality of the micro-USB port?

1. Can serve as a means to charge the device’s battery using AC/DC converter

2. Transmits digital data and analog voltage to and from the device

What does electrochemical sensing need?

The application of analog voltage to the sensor and the gathering of voltage, current, and resistance signals

What function does an optical transducer have in a smartphone?

Serves as a light sensor

What are the key principles of optical sensing with an optical transducer?

Detecting light with the smartphone’s camera or ambient light sensor

Where can light come from during optical sensing with a smartphone?

The smartphone’s flash or an external source

How is the captured image processed during the optical sensing?

Using software algorithms to extract relevant information about the measured sample

What are smartphone flash lights composed of?

White light-emitting diodes (LEDs)

What do white LEDs mimic?

Daylight

How are LEDs and photodiodes created?

By combining p-type and n-type semiconductors

How is LED detecting light different from a photodiode?

In an LED, a forward-bias voltage is applied, whereas a reverse-bias voltage is used in photodiodes to detect light

What happens as additional electrons and holes flow into the LED?

They combine and generate photons

How many different LEDs do white LEDs consist of?

2 or 3 different LEDs, one emitting blue light, one emitting red and yellow light which combine to produce red, green, blue

How is the spectrum of white LEDs different from the spectrum of sunlight?

The spectrum of white LEDs isn’t flat, and the human eye cannot distinguish the difference

What do smartphone digital cameras contain?

An array of photodiodes

What are the photodiodes composed of?

Two distinct semiconductors, p-type and n-type

What is generated in the p-layer of photodiode in smartphone digital camera?

Holes

What is generated in the n-layer of photodiode in smartphone digital camera?

Electrons

What happens as holes and electrons move away from each other in the photodiode?

A small depletion region is formed at the p-n junction, making it less conductive

What happens when a reverse-bias is applied to the photodiode system?

The holes are drawn toward the negative voltage, and free electrons are attracted to the positive voltage. The separation of charges enhances the depletion region

What happens when light strikes the p-type semiconductor?

The light strips the electrons from the molecules, creating extra holes and free electrons

What happens to the additional charged species produced when light strikes the p-type semiconductor?

They are neutralized by incoming holes and free electrons from the voltage source, producing a current

What happens to the photodiode in the absence of light?

No current flows due to the presence of the depletion region

When can light stimulate electrons to a higher energy level?

When it strikes the semiconductor material in a photodiode

What happens when electrons are stimulated to a higher energy level by light striking semiconductor material in a photodiode?

Electrons move around and leave holes in their path

What moves toward the photodiode’s cathode terminal?

Electrons

What moves toward the photodiode’s anode terminal?

Holes

What happens as a result of the movement of charged species in a photodiode?

A voltage is produced between the two terminals

Is there voltage in a photodiode when there is no light?

Yes, it is dark current

What is dark current?

Small amount of current generated in the absence of visible light in a photodiode

What are zero-bias and photovoltaic mode?

Other names for dark current

What happens when a photodiode is operating in photoconductive mode?

The light that strikes the photodiode produces pairs of electrons and holes in the semiconductor material, and they move in opposite directions due to the applied bias voltage, creating a current passing through the photodiode

Does photovoltaic or photoconductive mode provide a quicker response?

Photoconductive mode provides a quicker response because the applied reverse-bias voltage causes the depletion layer to be wider and the capacitance to decrease

Which mode of the photodiode is more prevalent and sensitive

Photoconductive mode

How do photodiodes capture images?

One photodiode produces a singular signal, and a 2D array of photodiodes has the capacity to capture a whole image

How has the use of photodiodes to capture images evolved?

In thee past, charge-coupled device (CCD) arrays were used, but now complementary metal oxide semiconductors (CMOS) arrays are used

Why must photodiode signals be amplified?

Because each individual photodiode has a very small quantity of charge

Why do CMOS arrays produce higher sensitivity and sharper images than CCD arrays?

Because CMOS arrays include amplifiers built into each photodiode, whereas CCD arrays amplify the signal after it is transferred from serial photodiodes to the collector register

What is used in a CMOS sensor to generate RBG?

Color filters

How do color filters work in CMOS sensors?

A color filter is placed on each photodiode, allowing only a specific wavelength of light to pass through. The filters are positioned in a Bayer pattern with a 2x2 grid of color filters comprising one red, one blue, two green filters, and each photodiode records the intensity of the filtered light. The intensity values for RBG are combined to create a complete color image

What do ambient light sensors consist of?

A small number of photodiodes with optical coating, each transmitting a different wavelength of light

What is a channel in ambient light sensors?

A pair of photodiode/coating

What channels are in a basic ambient light sensor?

Two channels, one for visible light and one for near-infrared light (NIR)

What does the visible light channel detect?

Ambient light levels

What does the NIR channel detect?

Proximity sensing (turning display off when close to user’s ear)

What channels are in more advanced sensors?

Multiple color channels (RGB)

What is the purpose of color (RGB) channels in ambient light sensors?

Provide more information about ambient lighting conditions

How does the smartphone operating system use the ambient light sensor

To control and optimize brightness of the smartphone display according to ambient conditions/surrounding light, thus reducing battery consumption

How is the front panel of smartphones structured?

It integrates a sensor module that combines ALS and proximity sensors

How is the sensor module of the smartphone’s front panel structured?

It includes two distinct photodiodes and a low-power infrared LED

Describe the sensitivity of the photodiodes in the smartphone sensor module

One photodiode is sensitive to visible and infrared light (for ambient light sensing), the other photodiode only detects IR light (for proximity sensing)

How can optical biochemical sensing be performed?

Using colorimetry or spectrometry for detection

Explain colorimetry

The concentration of the target is determined by measuring the light intensity at a specific wavelength. The target molecules selectively absorb certain wavelength ranges, causing a decrease in light intensity. The change in light intensity indicates the concentration of the target

Explain spectrometry

Light intensity is measured across a range of wavelengths, creating a spectrum which can indicate the presence of certain chemical groups

What does optical analytical equipment comprise?

A light source, monochromator, holder, and photodetector

How can smartphones be used to create simple colorimetry/spectrophotometry systems?

The smartphone’s flash, camera, or ALS can serve as the light excitation source and photodetector respectively

How can monochromatic light be separated from the smartphone flash’s polychromatic light?

By attaching optical filters or a diffraction grating

What will attaching a diffraction grating to the smartphone camera do?

It will enable the detection of specific wavelengths

What is a downside to optical biosensing using a smartphone?

Some target molecules may have a distinct color, separating them from other molecules in the sample, but distinguishing them based on absorption measurements at a specific wavelength can be hard, especially since the recorded image in a smartphone comprises an RGB matrix

What are the types of electrochemical sensors?

Conductometric, potentiometric, and amperometric sensors

What does the conductometric sensor measure?

Conductance

What does the potentiometric sensor measure?

Current

What does the amperometric sensor measure?

Voltage

What are the electrochemical sensors based on?

The principles of Ohm’s law (V=IR)

What does an electrochemical sensor’s basic electric circuit comprise?

Two resistors linked in series (resistance of a biochemical sensor Rs and a known resistor), connected with a constant bias

How is a conductive/conductometry sensor used?

To directly record alterations in the R_s

How do conductive sensors work?

They determine the concentration of ions or charged species in a sample solution by measuring the solution’s electrical conductivity

What do conductive sensors comprise?

Two electrodes submerged in the sample solution with a potential difference applied across them

What is the key relationship in conductive sensing?

The concentration of ions/charged species present in the solution is proportional to the conductivity of the solution

What specifically is a conductive/conductometry sensor meant to measure?

Changes caused by the introduction of a particular analyze or variations in ion concentration in the sample

What specifically is the potentiometric sensor meant to measure?

The change in voltage output (Vout) if the target variable being tested causes a change in Rs (resistance of biochemical sensor)

What is the most commonly used potentiometric sensor?

Ion-selective electrode (ISE)

What does the ISE do?

Measures the potential difference between two electrodes under no current flow

What is the key relationship in potentiometric sensors?

The measured potential is correlated to the concentration of the analyte of interest as given by Nernst equation (E = E^o-(RT/nF) * ln(Q))

What is the most common type of potentiometric sensor?

Membrane-based ion-selective electrode(ISE)

How are membrane-based ISEs mainly used?

In biosensing applications

How are ISEs made?

They are made of a glass tube containing a reference electrolyte solution and an ion-selective membrane at one end

How does the membrane-based ISE work?

The ion-specific membrane only allows the desired ions to pass through, resulting in a small change in the target ion concentration and an associated change in the potential difference

How specifically is an amperometric sensor used?

The current flowing through the circuit is varied while keeping Rs constant, and the resulting electric current is measured

How does an amperometric sensor work?

Constant potential is applied to the sensor electrodes and this measures the concentration of a target analyte in a sample by detecting the electrical current produced by an oxidation or reduction reaction

How are amperometric sensors composed?

They consist of a working electrode, a reference electrode, a counter electrode, and an electrolyte solution

How does the working electrode in the amperometric sensor work?

It is made of a material that facilitates the desired electrochemical reaction with the target analyte. As the target analyte is oxidized or reduced at this electrode, electrical current is generated, which is proportional to the concentration of the analyte