Describe the operating cycle and the cash cycle. What are the differences?
Solution
Operating Cycle:
An operating cycle is the amount of time a company spends between spending money operating
activities and collecting money from the same operating activity. Operating cycle often focus on
the purchase and sale of assets. For instance a retailer\'s operating cycle would be the time
between buying merchandise inventory and selling the same inventory. A manufacturer\'s
operating cycle might start when the company spends money on raw manufacturing materials to
make a product. The operating cycle wouldn\'t end until the products are produced and sold to
retailers or wholesalers.
Most companies try to keep their operating cycles at a year or less. This means that it would take
a retailer an entire year to sell its inventory. Depending on the industry, this kind of an inventory
turn might be unacceptable. Operating cycles are important because they determine cash flow. If
a company is able to keep a short operating cycle, its cash flow will consistent and the company
won\'t have problems paying current liabilities. Conversely, long operating cycle means that
current assets are not being turned into cash very quickly. In other words, cash is not being
collected from customer very quickly. Companies with longer operating cycles often have to
borrow from banks in order to pay short term liabilities. These companies are often less
profitable because of these extra loans.
Operating Cycle = Days\' Sales of Inventory + Days Sales Outstanding
Cash Conversion Cycle:
The cash conversion cycle is a cash flow calculation that attempts to measure the time it takes a
company to convert its investment in inventory and other resource inputs into cash. In other
words, the cash conversion cycle calculation measures how long cash is tied up in inventory
before the inventory is sold and cash is collected from customers.
The cash cycle has three distinct parts. The first part of the cycle represents the current inventory
level and how long it will take the company to sell this inventory. This stage is calculated by
using the days inventory outstanding calculation.
The second stage of the cash cycle represents the current sales and the amount of time it takes to
collect the cash from these sales. This is calculated by using the days sales outstanding
calculation.
The third stage represents the current outstanding payables. In other words, this represents how
much a company owes its current vendors for inventory and goods purchases and when the
company will have to pay off its vendors. This is calculated by using the days payables
outstanding calculation.
cash conversion cycle = Days inventory outstanding + Days Sales outstanding – Days payables
outstanding
DIFFERENCES OPERATING CYCLE CASH CONVERSION CYCLE
An operating cycle is the average time period between the acquisition of inventory and the
receipt of cash from the inventory\'s sale. A short operating cycle means a mo.
Describe the operating principle of the following FET sensor, and pr.pdf
1. Describe the operating principle of the following FET sensor, and provide a detailed diagram
(drawing), to illustrate how the sensor functions. Be sure to indicate the type of doping at the
source, drain and gate.
A field effect transistor (FET) for measuring glucose concentration. Hint: Consider using the
glucose oxidase enzyme and measure one of the by-products. As with (a), include a cross-section
drawing with proper labeling of doping at the source, drain, and gate, and any molecular
interactions at the gate.
Solution
Introduction
For several decades, much attention has been paid to silicon-based biosensors in the field of
bioanalytical applications due to their favorable characteristics, which include sensitivity,
speed,miniaturization, and low cost. This interest is evident in the numerous studies that have
monitored biological events such as nucleic acid hybridizations, protein-protein interactions,
antigen-antibody binding, and enzyme-substrate reactions using these silicon-based biosensors.
Among these, the ion-sensitive field-effect transistor (ISFET), is one of the most popular
electrical biosensors, and has been introduced as the first miniaturized silicon-based chemical
sensor. The ISFET, conventionally referred to as a pH sensor, has been used to measure ions
concentrations (H+ or OH) in a solution, causing an interface potential on the gate insulator. The
ISFET is a type of potentiometric device that operates in a way similar to the way the MOSFET
(Metal Oxide Semiconductor Field-Effect Transistor) works. Therefore, in order to evaluate the
performance of the ISFET, it makes sense to first understand the general principles behind the
operation of the potentiometric sensor.
After the introduction of the ISFET biosensor by Bergveld in 1970, and the first report by Caras
and Janata regarding the use of an enzymatically modified ISFET for the direct detection of
penicillin, numerous biosensors were established on the basis of theoretical development of
ISFET technology.
For example, there have recently been outstanding advances in the field of ISFET biosensors for
use in biosensing research, including the progress of the enzyme-immobilized FET which detects
H+ion concentration, the DNA (deoxyribonucleic acid)-modified FET based on DNA
hybridization detection, and the cell-based FET for cell metabolism sensing or the measurement
of extracellular potential.
Currently, the use of ISFET technology encompasses a wide range of applications in a variety of
areas,and those in the biomedical and environmental monitoring areas are particularly
2. noteworthy.
Operating Principle of FET-Based Biosensors
In general, a field-effect transistor (FET) consists of three terminals; the source, drain, and gate.
The voltage between the source and drain of the FET regulates the current flow in the gate
voltage.Specifically, the current-control mechanism is based on an electric field generated by the
voltageapplied to the gate. The current is also conducted by only one type of carrier (electrons or
holes) depending on the type of FET (n-channel or p-channel). A positive voltage applied to the
gate causes positive charges (free holes) to be repelled from the region of the substrate under the
gate. These positive charges are pushed downward into the substrate, leaving behind a carrier-
depletion region.
The depletion region is populated by the bound negative charge associated with the acceptor
atoms.These charges are “uncovered” because the neutralizing holes have been pushed
downward into the substrate. The positive gate voltage also pulls negative charges (electrons)
from the substrate regions into the channel region. When sufficient electrons are induced under
the gate, an induced thin n-channel is in effect created, electrically bridging the source and drain
regions. The channel is formed by inverting the substrate surface from p-type to n-type
(inversion layer). When a voltage is applied between the drain and source with the created
channel, a current flows through this n-channel via the mobile electrons (n-type FET). In the case
of a p-type semiconductor, applying a positive gate voltage depletes carriers and reduces the
conductance, whereas applying a negative gate voltage leads to an accumulation of carriers and
an increase in conductance (the opposite effect occurs in n-type semiconductors). The applied
gate voltage generates an electric field which develops in the vertical direction. This field
controls the amount of charge in the channel, and thus it determines the conductivity of the
channel. The gate voltage applied to accumulate a sufficient number of electrons in the channel
for a conducting channel is called the threshold voltage (VTH). Note that VTH for an nchannel
(p-channel) FET is positive (negative).
With these properties, the FET can be configured as a biosensor by modifying the gate terminal
with molecular receptors or ion-selective membranes for the analyte of interest. The binding of a
charged biomolecule results in depletion or accumulation of carriers caused by change of electric
charges on the gate terminal. The dependence of the channel conductance on gate voltage makes
FETs good candidates for electrical biosensors because the electric field generating from the
binding of a charged biomolecule to the gate is analogous to applying a voltage to a gate. In
general, the drain current of the FET-type biosensor is defined as follows
3. Structure of ISFET. It consists of source, drain, gate insulator, and reference electrode.
Generally, there are two types of planar FET-based biosensors, according to their structure;
insulated-gate field-effect transistors (IGFET) and ISFET. In the case of IGFET, particularly
MOSFET (metal-oxide-semiconductor field-effect transistor), the gate terminal is electrically
isolated from the source and drain terminals. ISFET is similar to IGFET, but in the ISFET, the
metal gate is replaced by an ion-selective membrane, electrolyte and a reference electrode. In the
case of an ISFET biosensor, the amount of the current flow will be not only determined by the
charges of biomolecules interacting on the gate dielectric, but also sensitive to pH, different ions,
products of enzyme reactions, etc. An attractive feature of such FETs is that it is possible to
detect biomolecular interactions in a label-free manner through a direct change in conductance or
a related electrical property
BIOSENSOR BASICS
The field of biosensor technology originally developed in the 1960’s from
electrochemical sensors to detect glucose and urea. These sensors immobilized enzymes
(namely urease and glucose oxidase) onto an electrode and measured the concentration of the
analyte by the current produced through enzymatic reaction. A biosensor is defined by The
National Research Council (part of the U.S. National Academy of Sciences) as a detection device
that incorporates a) a living organism or product derived from living systems (e.g., an enzyme or
an antibody), b) a transducer to provide an indication, signal, or other form of recognition of the
presence of a specific substance in the environment, and c) an output for statistical processing of
the data generated. Ideally, biosensors must be designed to detect molecules of analytical
significance, pathogens, and toxic compounds to provide rapid, accurate, and reliable
information about the analyte of interrogation. A generalized schematic of a biosensor is in
Figure, highlighting the flow of how a biosensor works.
LABEL-FREE ELECTROCHEMICAL METHODS
In this section we will discuss the main types of electrochemical sensors, with emphasis on
amperometric and potentiometric based sensors. In particular, we will discuss the operating
principles of the amperometric sensor using the most widely accepted device (the glucose
sensor), as an example. For potentiometric sensors, we will focus mainly on the ones based upon
field-effect transistor (FET) technology, discussing ion selective field effect transistors
(ISFET’s) and the more recent nanoscale FET’s.
THE GLUCOSE SENSOR: AN AMPEROMETRIC EXAMPLE
The glucose enzyme electrode is probably the most studied biosensor method to date, with its
roots buried in the original patents by Clark and Lyons in 1962. Moreover, it is the ideal example
4. for a point-of-care device already in high demand. An excellent review of the history of
electrochemical glucose sensor was done by Joseph Wang in 2008, and goes into depth about all
the generations of glucose sensor up to the latest technologies. The basic mechanism of the
glucose sensor uses the enzyme glucose oxidase (GOx) and its reaction products to generate a
measurable current. the immobilized GOx catalyzes the oxidation of -D-glucose by molecular
oxygen producing gluconic acid and hydrogen peroxide. In order to perform this, GOx need a
redox catalyst–flavin adenine dinucleotide (FAD) to work as an electron acceptor, which then
gets reduced to FADH2 by the reaction below:
The first generation of glucose sensors was built upon this principle, but later it was realized
oxygen depletion was causing large drifts in the sensors responses which was hard to correct for
and interference with competing oxidizers such as ascorbic acid. The interference was in part due
to the large anodic potentials (+0.6V vs. Ag/AgCl electrode) that had to be applied in order to
oxidize the hydrogen peroxide. Thus, the second generation glucose sensors started using
artificial electron carriers to substitute for oxygen in shuttling electron from the enzyme redox
center to the electrode, as well as using the enzyme glucose dehydrogenase (GDH), which
removes the need for oxygen in the reaction.First, oxygen was replaced with an electron acceptor
called a redox mediator. The mediator was reduced instead of oxygen being converted to
hydrogen peroxide, which then was reoxidized at the platinum electrode to regenerate the
mediator.
An example of this is in Figure, whereby most glucose sensors operate on these principles today.
Several types of redox mediators are in play, with most of them derivatives of ferrocene,
ferricyanide, or quinines, with ferrocene derivatives being the most popular for current
devices.However, the Abbott Freestyle devices use an osmium based mediator, which has been
the stable for all three generations of the technology.GDH belongs to the class of quinoproteins,
which use pyrroloquinoline quinone (PQQ) as cofactor to convert glucose to gluconolactone.
GDH is also a dimeric enzyme composed of two identical protein monomers with each monomer
binding a PQQ molecule and three calcium ions. These calcium ions activate the PQQ cofactor,
and the reaction mechanism is similar to GOx with FAD, except PQQ is the cofactor and does
not require oxygen in the reduction.
An excellent review by Vashist et. al.highlights the latest type of electrochemical glucose
sensors in thorough detail. A table of the current technologies is in Table 2.1 below, along with
the largest manufacturers of glucose point-of-care sensors. The main one which I will discuss as
an example electrochemical platform is the Abbott Freestyle, which relies on an osmium redox
mediator and GDH-PQQ enzyme complex.
5. Each blood glucose meter (BGM) test strip has aimed to have high reproducibility, high
accuracy, low-cost, rapid results, and low sample volume amounts. These values for the most
widely used BGM’s are in Table 2.1 as well. The three main components of the BGM strip are
the working, counter, and reference electrodes. Additionally, fill electrodes are put on the device
to make sure a proper amount of sample has filled the chamber. A small capillary chamber is
located on the electrode substrate to work as reaction container and draw the blood into the
device through capillary action. A mixture of enzymes, mediators and other chemical
components is coated within the capillary chamber in dry form. This setup is discussed in Figure
, and is part of the Abbott Freestyle system. A working electrode, where the enzymes and
mediators are dried, is typically composed of carbon ink or vapor deposited gold or palladium,
and auxiliary and reference electrode are usually combined and made of the same material.
The auxiliary and reference electrode are usually composed of Ag/AgCl and are assembled
facing the working electrode at a distance of 50 microns in modern devices. Previously, a large
potential of 400-500mV must be applied to the working electrode vs. Ag/AgCl in coplanar
electrode devices, but this would cause “redox shuttling” from the mediator back and forth,
causing high background noise.
However, using osmium mediators, its oxidation potential is negative with respect to other
interfering agents, making the other reactions impossible. Moreover, it decrease the diffusion
time to the working electrode, and can give readouts within 5 seconds. Most electrochemical
devices for various analytes work off the principles of the glucose sensor, but with different
enzymes, electrodes, or redox mediators, to generate their signal.
FIELD EFFECT TRANSISTOR BASED SENSORS
In this section I will discuss the most relevant literature and background into the operating
theory of FET’s and how they have been applied to biosensors. FET based devices operate on the
principle that changes in the electric field across a dielectric (the gate) cause changes in the
source-drain current of the underlying device. Since most biomolecules are charged, their
binding to the gate causes a change in the electric field due to their charge density, making FET
devices particularly enticing as a biosensor. A few of the benefits of using FET technology as a
biosensor include:
· High sensitivity due to the current gains inherent in FET devices based on
small surface potential changes
· Low cost due to the mass scaling and integration of FET devices in most
electronics
· Label-free since it is able to use the intrinsic charge of a molecule as it
6. detection principle
Each FET device is based upon a two-terminal device called a metal-oxidesemiconductor
capacitor, or MOSCAP. This structure typically contains a top metal gate, an insulating oxide as
the dielectric, and a p-type silicon body. A MOS structure, when a bias is applied to the gate, can
operate in three regimes, i) accumulation, ii) depletion, and iii) inversion. The three regimes are
outline in Figure . When a negative bias is applied to the gate, holes (the majority carrier) from
the p-type substrate collect at the silicon/oxide interface and the device is said to be in
accumulation. Depletion starts to occur when positive voltages are applied to the gate and holes
are repelled from the interface into the silicon, with the voltage between accumulation and
depletion modes called the flatband voltage (VFB). When negative charges (the minority) carrier
start to collect at the interface the device is said to be at inversion, and the voltage where this
occurs is called the threshold voltage. The equations which dictate the threshold voltage (VT)
are:
Ideally the flatband voltage should only rely on , but all devices contain some amount of the
charge densities above. As will be discussed, it has been the goal to minimize these charges as
much as possible in the CMOS industry, as they lead to non-ideal device characteristics and
degradation of device integrity. Fixed charge is important because it can cause large shifts in
threshold voltage, increasing the voltages needed to turn the device on. For transistors exposed to
fluids, it is especially important to keep this as low as possible because applying higher voltages
leads to higher possibilities of dielectric breakdown and gate leakage. Interface oxide trapped
charge can lead to degradation of device turn-on, and mobile charge to device hysteresis when
the voltage is swept.
Similarly, with fluid based devices these charges can lead to device drift and instability. The
most efficient way to study the effect of these defects is using a MOSCAP and looking at the
capacitance of the device vs. the gate voltage, most commonly referred to as C-V analysis. Using
high frequency C-V’s of a MOSCAP, the effect of these charges on the curve are overly
apparent. Interface traps will draw the curve out, leading to poorer sensitivity to applied voltages,
while fixed charges will shift the curve left or right from ideal, depending on the charge. A
demonstration of how these charges affect C-V characteristics is in Figure
A MOSFET is essentially a MOSCAP, but with a 3rd terminal added, known as the source and
drain, which forms a conducting channel underneath the MOSCAP. When the surface potential
of the oxide (s) reaches a critical value (threshold voltage), the underlying channel will conduct
and this is dependent on the gate voltage. The equation for the drain current of a MOSFET is
7. well known:
Ion Selective Field Effect Transistors, or ISFET’s, are a particular type of FET where the top
metal has been removed, and has been replaced by an electrolyte and an electrode, as shown in
Figure. The ISFET was originally developed by Bergveld in 1970 , and since then over 600
papers have been published in regards to the ISFET. The main difference between the MOSFET
and ISFET is the removal of the metal and replacing it with an electrolyte and an electrode. By
doing this, we expose the gate insulator to the solution, and remove the workfunction of the
metal, replacing it with a reference electrode potential. The new equation for the threshold
voltage of an ISFET is:
The pH and ion selective nature of the dielectric layer allows for to change due to the
interaction of the ions with the surface, this in turn changing the threshold voltage of the device
and providing the devices sensing mechanism.
The pH and ion sensitivity of ISFET’s can be described using a site-binding
model specific to the electrolyte/insulator interface. An in-depth description for ISFET’s using
this model was done by Van Hal et. [109]. In this model, the oxide surface sites are said to be
amphoteric, meaning the surface hydroxyl groups can be neutral, protonated, or deprotonated
depending on the pH of the bulk solution. Moreover, Van Hal and Eijkel showed how the
equation could be related to the equation for capacitors, Q=CV. Essentially, Q is the surface
charge in the form of protonated (OH2+) or deprotonated (O-)
OH groups of the oxide surface, C is the double-layer capacitance at the interface and V is the
resulting surface potential, denoted as the familiar . The capacity for the surface to take up or
release protons, in conjunction with the capacitance of the double layer, with a change in pH can
be accounted for in a sensitivity factor , , and its influence on the surface potential is given by the
following equation:
where BS symbolizes the surface buffer capacity, or the ability of the oxide surface to deliver or
take up protons, and CS is the differential double-layer capacitance, of which the value is mainly
determined by the ion concentration and the Debye length due to that concentration. It can be
seen that as approaches 1, near Nernstian sensitivity of the device can be achieved.