Shunt peaking design summary.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2064",leadTitle:null,fullTitle:"Integrative Proteomics",title:"Integrative Proteomics",subtitle:null,reviewType:"peer-reviewed",abstract:"Proteomics was thought to be a natural extension after the field of genomics has deposited significant amount of data. However, simply taking a straight verbatim approach to catalog all proteins in all tissues of different organisms is not viable. Researchers may need to focus on the perspectives of proteomics that are essential to the functional outcome of the cells. In Integrative Proteomics, expert researchers contribute both historical perspectives, new developments in sample preparation, gel-based and non-gel-based protein separation and identification using mass spectrometry. Substantial chapters are describing studies of the sub-proteomes such as phosphoproteome or glycoproteomes which are directly related to functional outcomes of the cells. Structural proteomics related to pharmaceutics development is also a perspective of the essence. Bioinformatics tools that can mine proteomics data and lead to pathway analyses become an integral part of proteomics. Integrative proteomics covers both look-backs and look-outs of proteomics. It is an ideal reference for students, new researchers, and experienced scientists who want to get an overview or insights into new development of the proteomics field.",isbn:null,printIsbn:"978-953-51-0070-6",pdfIsbn:"978-953-51-4343-7",doi:"10.5772/2473",price:139,priceEur:155,priceUsd:179,slug:"integrative-proteomics",numberOfPages:454,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"82fe979a574466e287d597db196c0d67",bookSignature:"Hon-Chiu Eastwood Leung, Tsz-Kwong Man and Ricardo J. Flores",publishedDate:"February 24th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/2064.jpg",numberOfDownloads:118347,numberOfWosCitations:113,numberOfCrossrefCitations:25,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:113,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:251,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 1st 2011",dateEndSecondStepPublish:"March 29th 2011",dateEndThirdStepPublish:"August 3rd 2011",dateEndFourthStepPublish:"September 2nd 2011",dateEndFifthStepPublish:"December 31st 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8,9",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"105582",title:"Dr.",name:"Hon-Chiu",middleName:"Eastwood",surname:"Leung",slug:"hon-chiu-leung",fullName:"Hon-Chiu Leung",profilePictureURL:"https://mts.intechopen.com/storage/users/105582/images/5517_n.jpg",biography:"Dr Hon-Chiu Eastwood Leung finished his Ph.D. Degree in microbiology and molecular genetics from University of Texas, Houston in 1997. He did his post-doctoral training in Baylor College of Medicine studying genomics and proteomics profiles of pediatrics medulloblastoma and osteosarcoma. Dr. Leung was a research scientists in Ciphergen Biosystems Inc. Briefly, and then was recruited to Genome Institute of Singapore to lead the clinical proteomics section. In 2006 he returned to USA. He was the director of the genomics and proteomics core laboratory of the Texas Children´s Hospital and director of genomics profiling of Baylor College of Medicine. At present, he is the director of the mass spectrometry-proteomics core facility of Baylor College of Medicine.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Baylor College of Medicine",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"35047",title:"Prof.",name:"Tsz Kwong",middleName:null,surname:"Man",slug:"tsz-kwong-man",fullName:"Tsz Kwong Man",profilePictureURL:"https://mts.intechopen.com/storage/users/35047/images/system/35047.jpg",biography:"Dr. Chris Man is an Associate Professor of Pediatrics at Baylor College of Medicine where he participates in the Bone Tumor Program and the Cancer Genetics and Genomics Program at Texas Children’s Cancer Center. Dr. Chris Man’s laboratory is interested in applying computational and OMICS approaches to improve both the diagnosis and prognosis of pediatric cancer patients. The main focus of his research is to identify circulating and tumor biomarkers for early detection of chemoresistance and metastasis in pediatric osteosarcoma. Dr. Man and his lab are also interested in using bioinformatic and meta-analysis approaches to identify novel drug targets and pathways in pediatric cancers. The current projects include: 1) molecular classification of pediatric cancers based on genomic and proteomic profiling; 2) development of computational tools to integrate and analyze large-scale datasets; and 3) biomarker and target discovery in pediatric cancers using novel technologies.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Baylor College of Medicine",institutionURL:null,country:{name:"United States of America"}}},coeditorTwo:{id:"252252",title:"Dr.",name:"Ricardo",middleName:"J.",surname:"Flores",slug:"ricardo-flores",fullName:"Ricardo Flores",profilePictureURL:"https://mts.intechopen.com/storage/users/252252/images/system/252252.jpg",biography:"Dr. Ricardo J. Flores graduated from University of Puerto Rico School of Medicine with highest honors in 2004. He completed his training in Pediatrics at the University of Puerto Rico Pediatric Hospital in 2007, and his subspecialty training in pediatric hematology/oncology at Baylor College of Medicine and the Texas Children’s Cancer and Hematology Centers in 2010.\n\nWhile in medical school, Dr. Flores experienced the death of a very close family member who truly struggled against an aggressive type of leukemia. From this, he recognized that treating patients with cancer and blood diseases required an extremely concerted effort from family and health care providers, and decided to train in the field of hematology/oncology, which encompasses all aspects of the medical profession.\n\nDuring his initial year of hematology/oncology training, Dr. Flores became interested in pediatric bone tumors, especially in the patients who presented with aggressive disease and had limited treatment options. At that time, he resolved to focus his research efforts on the high-risk bone tumor pediatric patients.\n\nBeyond his clinical and research duties, Dr. Flores is actively involved in ongoing efforts to promote and advance underrepresented minorities in the fields of Science, Technology, Engineering, and Mathematics (STEM-fields). In 2010, the American STEM Association selected him as member of the Leadership Institute Training Program for the Advancement of Science. In 2011, he was invited to serve as Master of Ceremonies for the Society on the Advancement of Science Chicanos/Hispanics and Native Americans National Conference, with over 3,000 participants, including Nobel Prize and National Medal of Science recipients. As a result of his scientific and outreach work, he was selected as a 2012 distinguished young physician scientist and interviewed by the National Library of Medicine for their 'Career Pathways” video library. He has also been highly involved with mass media health education, and has participated on dozens of interviews on nationwide radio, newspapers, and TV networks, including Telemundo, Univision and PBS, among others.\n\nSince October 2016, Dr. Flores-Hernández has been the Clinical Director of Pediatric Hematology-Oncology at the Texas Children’s Hospital’s Woodlands location.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Baylor College of Medicine",institutionURL:null,country:{name:"United States of America"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"384",title:"Chemical Biology",slug:"chemical-biology"}],chapters:[{id:"29626",title:"Strategies for Protein Separation",doi:"10.5772/29363",slug:"strategies-for-protein-separation",totalDownloads:4027,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Fernanda Salvato, Mayra Costa da Cruz Gallo de Carvalho and Aline de Lima Leite",downloadPdfUrl:"/chapter/pdf-download/29626",previewPdfUrl:"/chapter/pdf-preview/29626",authors:[{id:"77472",title:"Dr.",name:"Fernanda",surname:"Salvato",slug:"fernanda-salvato",fullName:"Fernanda Salvato"},{id:"86792",title:"MSc.",name:"Aline",surname:"Leite",slug:"aline-leite",fullName:"Aline Leite"},{id:"86800",title:"Dr.",name:"Danielle Cristina Gregório Do Silva",surname:"Silva",slug:"danielle-cristina-gregorio-do-silva-silva",fullName:"Danielle Cristina Gregório Do Silva Silva"}],corrections:null},{id:"29627",title:"Evolution of Proteomic Methods for Analysis of Complex Biological Samples – Implications for Personalized Medicine",doi:"10.5772/29613",slug:"evolution-of-proteomic-methods-for-analysis-of-complex-biological-samples-implications-for-personali",totalDownloads:2331,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Amanda Nouwens and Stephen Mahler",downloadPdfUrl:"/chapter/pdf-download/29627",previewPdfUrl:"/chapter/pdf-preview/29627",authors:[{id:"78567",title:"Prof.",name:"Stephen",surname:"Mahler",slug:"stephen-mahler",fullName:"Stephen Mahler"},{id:"84197",title:"Dr.",name:"Amanda",surname:"Nouwens",slug:"amanda-nouwens",fullName:"Amanda Nouwens"}],corrections:null},{id:"29628",title:"Proteomic Analyses of Cells Isolated by Laser Microdissection",doi:"10.5772/30603",slug:"proteomic-analyses-of-cells-isolated-by-laser-microdissection",totalDownloads:2925,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Valentina Fiorilli, Vincent P. 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Therefore the goal of this chapter is to present an analysis overview of them as well as the main considerations of their design. Nevertheless, since their interconnections play an important role on performance and noise isolation, this chapter will also describe their AC and DC coupling.
Consider initially a simple common source amplifier stage, with the load impedance ZL, as given in Fig. 1. Consider also the simplified transistor model as shown in Fig. 2.
Simple common source stage.
Simplified circuit model of
The gain of this stage can be easily calculated as below.
Assume this common source stage drives the gate of the following circuit. This next stage needs proper biasing. Usually the DC bias of one stage does not interfere with the bias of another stage, thus the output of the common source stage and the input of the following stage are separated by a DC block capacitor as indicated in Fig. 3. Usually, the biasing resistor
AC coupling with DC block capacitor.
At high frequency, the effect of the DC block capacitor is negligible, since the DC block capacitor is virtually short. The effect of the large biasing is also negligible since it is connected in parallel with the drain resistor of the first stage. The simplified circuit model is presented in Fig. 4.
Common-source stage with RC-load.
When no inductor is used, the only available load is RC-load, thus the load amplifier becomes:
The circuit topology of Fig. 4 is well known and corresponds to a low pass filter configuration. The frequency response of this filter is shown in Fig. 5 and its gain is given by:
Frequency response of
Hence, the DC gain is -
Unfortunately, at low frequency, the effects of DC block capacitor and the bias resistor are more severe, since the equivalent circuit, at low frequency, is a high pass filter.
Therefore, one can expect huge loss of information at very low frequencies for some applications such as Direct-Conversion transceiver, which carries information around DC. Even for DC-free applications, the cutoff frequency should be considered for the high pass filter. Since the 3dB cutoff frequency is defined as 1/RC, one can increase resistance and capacitance. However the capacitor normally occupies more space in integrated circuit than a resistance. Therefore, only the resistance should be increased, only up to few Mega ohms, so that a smaller capacitance can be used.
As reviewed in previous section, the AC coupling is suitable for RF circuitry, but may present DC blocking problems for baseband analog circuitry. Thus, if information around DC is concerned, one should integrate blocks with DC coupling. The DC coupling consists of combining two blocks so that the DC output voltage level of the previous block is same as the DC input bias voltage of the following block, and thus there is no reason to insert a DC block capacitor between them. The DC coupling is certainly advantageous at low frequency, and since the common-source stage model of Fig. 4 is valid for both low and high frequency, it is also suitable for high frequencies; nevertheless it may restrict the freedom of biasing.
Since the modern integrated technology allows construction of inductors, the designer should know the advantages the inductor can add in the circuit design. This section shows how to enhance the bandwidth using the ‘shunt-peaking’ technique. It consists of adding an inductor in series with the resistor, as shown in Fig. 6.
Common-source stage with RLC-load.
The load impedance for this case becomes:
And, substituting this value in (2), one can find that:
Observe that the inductor added a zero, which always increases the bandwidth, and also two poles. These poles can be complex conjugate, and this also can increase bandwidth, yet they introduce peaking, hence the name of the method. On the other side, the difference between the number of finite poles and finite zeros is still one. This means that the asymptotic decrease of gain is the same as in the previous circuit, –20 dB/dec. Thus the inductor allows modifying the gain locally, in the vicinity of the frequency ω1, and the designer should use this possibility to his/her advantage.
Consider the amplitude of the frequency response for this circuit, given as
To facilitate subsequent derivations, it is introduced a factor
Here
The right side of (7) is considered the normalized gain.
First, the bandwidth will be maximized without any consideration regarding the behavior to the gain in the bandwidth. The frequency where the right side equals
From this equation one can find that:
And maximizing the right side of (10) by proper choice of
Differentiating and equating the derivative of (12) to zero, one can obtain:
Squaring both sides of this equation, then:
And from this equation one finally finds that the required value of
Substituting this value of
Hence the bandwidth is improved nearly two times as shown in Fig. 7. Consider as an example improving the bandwidth from 1 GHz to 1.85 GHz. This is tremendous improvement with the addition of just one inductor.
Unfortunately, however, this choice of
Where
The solution of this equation gives
And the normalized amplitude frequency response has the value of:
This corresponds to a peaking about 1.5dB, as shown in Fig. 7.
Frequency enhancement by
However, there are many applications where the frequency response should be completely free of peaking. Therefore, consider again:
Where
One of possible solutions of this equation is
One can see that two other solutions will be at
This gives:
Direct calculation using (10) shows that this value of
The corresponding amplitude frequency response is shown in Fig. 8.
Maximally flat frequency response.
For this choice of
In other situations, there may be a specification on the time response of the amplifier, rather than on frequency response. The amplifier must not only amplify uniformly the various spectral components of the signal over as large a bandwidth as practical, but the phase relationships among its Fourier components must be preserved as well. If all frequencies are delayed by an equal amount of time, then this fixed amount of time delay must represent a linearly increasing amount of phase shift as frequency increases. Phase distortion will be minimized if the deviation from this ideal linear phase shift is minimized. Evidently, then, the delay as the function of frequency must be examined. If this delay is the same for all frequencies, there will be no phase distortion. The delay is defined as
Where
Using (4), then:
And from this expression, one can find that:
It is impossible for this amplifier to provide a constant time delay over an infinite bandwidth. It is reasonable to provide, then, with an approximation to a constant delay over some finite bandwidth. A maximally flat time delay will result the number of derivatives of TD(ω), whose value is zero at DC, is maximized.
This derivation is rather complicated. Ultimately, however, on may derive the following cubic equation for
whose relevant root is:
which is corresponding to a bandwidth improvement factor a little bit less than 1.6.
Since the conditions for maximally flat amplitude frequency response and maximally flat time delay do not coincide, one can compromise. Depending on requirements, there is a range of useful inductance value. A larger
Condition | m=R2C/L | Normalized bandwidth | Normalized peak frequency response |
Maximum bandwidth | 1.414 | 1.85 | 1.19 |
Maximally flat bandwidth | 2.414 | 1.707 | 1 |
Maximally flat time delay | 3.104 | 1.6 | 1 |
No shunt peaking | ∞ | 1 | 1 |
Shunt peaking design summary.
Low noise amplifier – LNA is the most critical block in the receiver signal chain, since it determines the overall noise Fig. of the received signal, so that it determines the quality of communication system.
There are several issues on LNA design for UWB applications. First, it must provide wideband impedance matching for both optimal power transfer and noise characteristic. Second, it should be a low power implementation with high power gain. According to the 802.13a specification [1] [2], it is required a power gain of at least 15dB with less than 3dB noise Fig. Since, one of the biggest applications of UWB systems is low-power implementation, the LNA should be able to operate in low supply voltage. The third issue is gain flatness to avoid any signal distortion over such a wide bandwidth.
In terms of wideband impedance matching, the most popular methods are the feedback topology, the distributed impedance matching, the BPF configuration matching network, and the common-gate topology. Nevertheless, each method has advantages and disadvantages, so it is difficult to select one single method for UWB LNA design. For example, feedback topology has good noise and impedance matching performance, but degrades the achievable power gain. The other side, BPF configuration matching is able to achieve high power gain with spurious impedance matching performance in addition to great frequency selection characteristics, while increasing noise Fig. with more passive components used to implement the filter.
This section discussed a unique UWB CMOS LNA, which utilizes both feedback, and BPF configuration method, as presented in [3].
In general, it is very difficult to establish a systematic method for LNA design with satisfying simultaneously low noise factor, impedance matching, and high gain. The major difficulty comes from the fact that the optimal source impedance for optimal noise is different from the matching condition for maximum power delivery. So it is very important to confirm initial design decisions of circuit parameters because two matching conditions are highly related. Also, too simplified circuit model forces trial-and-error strategy for optimizing the circuit. Therefore, accurate circuit evaluation is required to avoid the tedious effort for circuit optimization. Thus, the accurate Miller effect of source degenerative topology with cascode topology, and a methodology to utilize the Miller effect for the input matching network implementation are presented in this section.
The overall LNA schematic, including input and output impedance matching network, is shown in Fig. 9. The LNA looks like a simple conventional narrowband LNA with one gate
Overall LNA architecture.
inductor. However, the LNA can achieve wideband input matching by using Miller effect as explained later. Also, the UWB LNA architecture does not make use of a source follower for output matching, but has passive output matching network, which consists of bandpass filter and impedance inverting scheme.
Since the size of transistors and their bias condition determine power dissipation, it is often recommended to establish them under a certain power budget. However, the size of transistor versus its bias condition should be evaluated carefully, because they are also related to impedance seen by input gate. Thus, the best choice is to determine the size and bias condition to satisfy both impedance matching and noise matching with limited bias current. In fact, there is no much freedom for this choice technically. According to the MOSFET noise analysis [4], the generator admittance for optimal noise performance is known as (31) and (32).
where
For the sake of simplicity, initially the correlation of noise can be ignored, so that c has to be 0. Therefore, (31) and (32) can be simplified as:
Furthermore, (35) can be modified to (36) in order to take account of the degenerative inductor at the source-end.
Note that expressions (34) and (35) represent real and imaginary terms of impedance, while (31) and (32) presents admittance expressions.
Observe from expression (36) that the imaginary term of the optimal noise generator impedance is inversely proportional to the gate-source capacitance. Since the gate-source capacitance is always positive, than noise matching can be achieved with inductive generator impedance. However, increasing L
However, it is not easy to make both
where Z
Since the reactance term of
As mentioned already, the bias condition should be achieved under a limited current, thus I
Note that considers minimum channel length L. Once V
where V
Assume, roughly, that
Finally, the minimum channel width W given in (44), is based on (38), (40)and (43) :
Again, minimum channel length is assumed and the results are roughly selected so that they must be optimized later. The obtained Z
Zopt, Zin_eq, and Zin_eq*.
The obtained condition so far should be applied to M1 in Fig. 9.
The Miller effect implies that the effective capacitance is increased by negative voltage gain between input and output. However, since the input impedance of the cascode device M2 is capacitive, the voltage gain is high in low frequency and low in high frequency, which implies the effective Miller capacitance will be high in low frequency and low in high frequency. Therefore, it explains that the Miller effect creates not only a single capacitor, but also an inductor in parallel with the Miller capacitor.
The input impedance ZLoad of the cascode device M2 seen at the source of M2 is described as
where ZL is the output load connected to drain of M2, and this is assumed as pure resistor over the frequency of interest, for simplicity.
The load impedance of the cascode device, therefore, can be expressed as R and C parallel circuit as shown in Fig 11, whose values are:
The resistance term of the cascode load is equal to 1/g
Input impedance of cascode device M2.
The effective transconductance for source degenerative topology can be obtained as:
Thus, the overall open voltage gain A
According to the non-flat open voltage gain between gate and drain of M1, the Miller capacitor is not a simple capacitor anymore, but an RLC combination circuit.
The Miller capacitance C
Finally, the overall Miller impedance caused by the non-flat voltage gain is:
Note that non dominant terms are eliminated for the sake of simplicity.
The equivalent impedance given by Miller effect is indicated in Fig. 12, whose values of individual components are:
where =1/R
Note that the resistive term R
Equivalent input circuit.
Now, the input impedance of the inductive degenerative topology including Miller effect must be re-evaluated.
The input impedance of the open circuit is well known as RLC series circuit, given as:
From the feedback system, the modified input impedance of the feedback system, as shown in Fig. 13, is given by:
Note that the close loop input impedance includes the Miller effect.
The feedback impedance Z
where Y
Thus, the actual RLC series circuit is changed by the feedback effect. The feedback effect effectively increases the inductive term L
Feedback system with effective transconductance.
For large R
Therefore, overall input impedance can be expressed as Fig. 12.
Note that the C
Mixers are non-linear devices used in systems to translate from one frequency to another. All mixer types work on the principle that a large Local Oscillator – LO drive will cause switching/modulating the incoming RF into an Intermediate Frequency – IF, or in opposite direction.
There are two types of mixer, passive and active. Generally the passive types have better IM3 performance, but present higher conversion losses and hence higher noise Fig.s than active mixers.
Additionally, mixers can also be classified as single balanced mixers and double balanced mixers. Single balanced mixers are much less complex, but have inferior performance in terms of RF to IF and LO to IF rejection, compared to double balanced mixers.
The advantages of double balanced mixers are:
Both LO and input signals are balanced, providing both LO and input rejection at the output.
All ports of the mixer are inherently isolated from each other.
Higher linearity, compared to singly balanced.
Improved suppression of spurious products (all even order products of the LO and/or the input are suppressed).
Higher intercept points.
Less susceptible to supply voltage noise due to differential topology.
The disadvantages are:
Require a higher LO drive level.
Require differential input and LO signal.
Ports are highly sensitive to reactive terminations.
The Gilbert double-balanced mixer configuration is widely used in RFIC applications because of its compact layout and moderately high performance. This section will walk through the design of a CMOS Gilbert mixer focusing on the parameters that influence the linearity of the signal path, the noise, and therefore the spurious-free dynamic range of the mixer. Finally, some techniques to enhance the bandwidth of the Gilbert mixer will be also presented, so to be suitable for UWB applications.
Depending on the application, the mixer may be designed with a low Single Side Band – SSB noise Fig., a particular gain or a high linearity. A good starting point is to use the differential LNA and add the switching transistors with the same W/L ratios.
As in the case of LNA design, the linearity of the mixer source can be increased by adding degeneration resistors (or inductors). As an example consider Z
There are several parameters to be achieved during the design process, such as device width, biasing, linearity of transconductance amplifier (input circuit), stability, input matching network, gain compression, Inter Modulation Distortion – IMD, noise Fig. and spurious free dynamic range.
Though the design method introduced here emphasizes the distortion-limited (large-signal) performance over noise-limited (small-signal) performance, there are many design choices possible. In Fig. 14, one may have to decide proper bias current and device width W
The minimum current required to keep all devices in saturation must also be considered. Additionally, once the bias is determined, the linearity of signal path must be verified. The signal path from the transconductance amplifier through the source resistance and inductance is the dominant for the sake of linearization. As the resistance increases the linearity also increases, but the conversion gain also decreases to some degree. Source inductance is used mainly to guarantee stability by forcing a positive real component into the input impedance. This also helps to make the input impedance easier to match.
From Fig. 14, the voltage gain of the mixer with source degeneration is given by:
This equation implies lower conversion gain with larger impedance at the source of M
From the analysis of noise optimization, the optimal width can be found as [4]:
where R
For this width, I
Basic circuit of the Gilbert Cell Double Balanced (DB) Mixer.
In order to investigate the linearity of the signal path, a transfer characteristic can be simulated by sweeping the input DC voltage. Consider the example given in Fig. 15. Note that the DC input voltage V
It is expected that by increasing the resistance R
A popular technique in low voltage RFIC design is to substitute resistors by inductors. This has the advantages that the ideal inductor does not add noise to the circuit, and it reduces the supply voltage requirement for the circuit. The effectiveness of this approach is somewhat frequency dependent. At low frequency, the gain degeneration and linearity improvement for reasonable sized inductors is limited, but it becomes more effective at higher frequencies.
Setup for transfer characteristic simulation.
DC input voltage sweeping for linearity simulation.
Also, inductors on Si substrates have low Q, on the order of 2 to 3. For a Q of 2.5, for example, a 5 nH inductor at 4GHz would have a series resistance of about 50Ω, thus, in fact both resistance and inductance are being added to the circuit. Therefore, it is valuable to investigate the effect of both inductor and resistor as Z
As explained earlier, the input impedance seen at gate of source degenerative topology with impedance Z
where ω
Expression (67) was derived from a simple small-signal analysis; it neglected C
Similarly, a series inductance L produces a non-frequency dependent positive real part and a series LC resonant network. Only the capacitor produces a negative resistance, a condition desirable for oscillators, not mixers, and with unusual frequency dependence. Therefore, negative input resistance can be avoided eliminating the possibility of using a capacitor.
Zs | Re[Zin] + Im[Zin] |
R | |
L | |
C |
Summary of input impedance according to impedance at source.
Unfortunately, however, there is some parasitic capacitance between source and bulk of the transistors, as indicated in Fig. 17. Therefore, as R
Expression (68) describes the resistive input impedance by considering the presence of C
An extrapolation of i
So far, only inside of Gilbert cell mixer has been discussed. In fact, signal bandwidth at both input and output is another critical problem for UWB mixer. Therefore, input and output bandwidth enhancements are also necessary.
For integrated circuits, there is no restriction of intermediate impedance between blocks. In fact, the shunt-peaking method is widely used for bandwidth enhancement and interconnection between blocks. However, it is sometimes necessary to provide a specific impedance value for both input and output (in many cases 50 Ω), thus the wideband impedance matching methods can be applied. The applicable methods for bandwidth enhancement are:
Shunt-peaking: suitable for conjugate matching with non-standard intermediate impedance.
Wideband matching method: suitable for both conjugate matching and standard impedance matching, but requires more passive components.
Cascode topology: applicable for both previous methods, in addition by reducing RC constant time.
Since cascode topology reduces voltage gain between gate and drain of transconductance amplifier, it reduces the effect of the gate-drain capacitance, the so called Miller effect. However, if cascode topology is applied to reduce Miller effect, one have to consider reduced overhead voltage by voltage drop through drain to source of the cascode device.
Gilbert cell mixer with source to bulk capacitance.
This chapter provided the background foundations for the analysis and design of low noise amplifiers and mixers, along with their interconnections to other structures. Low noise amplifiers and mixers are among the most used structures in RF IC.
The performance of them may be compromised without proper interconnection. This chapter also presented the approaches to implement AC and DC coupling to interconnect structures, by taking into account performance and noise isolation.
The cornea and sclera are the two most external structures of the eye and the extracellular matrix (ECM) plays a crucial role in their activity. While the cornea is transparent and located in the front the eye, the sclera is the white part that forms the rest of the eye, giving it its spherical form, and providing hardness and structural protection to the internal part of the eye. Different types of collagen constitute the core of both structures, which is surrounded by the so-called “ground substance” that lies between the collagen fibers and around the few cells that are present in these elements. The viscoelastic properties of the cornea and sclera define the distensibility of the eye, which is related to the control these structures exert over intraocular pressure. Moreover, the cornea fulfils its main functions at the interface of the eye with air or water (depending on the habitat). Indeed, the cornea is the principal refracting surface of the dioptric system of the eye, which is why it is transparent, avascular, viscoelastic and quite resistant to deformation.
The structural and chemical composition of the ECM of very large eyes like the whale’s eye has been little studied. The human eye measures approximately 2.3 cm in diameter and the two whale’s eyes that we have analyzed were 12 and 13 cm in diameter (Figure 1). In this chapter we compare the morphological and structural aspects of the human cornea and sclera with those structures in one of the largest eyes ever studied. We consider that at least some of the differences in the structure of these eyes is likely to help adapt the whale to its very extreme conditions of life. These animals live between two very different habitats, capable of rapidly shifting between the water surface and the very deep sea, experiencing huge changes in pressure that their eye can only support without deforming thanks to the strong structure of both the cornea and sclera.
(A) Scheme of the whale and human eye in proportional scale. In green the sclera and in blue the cornea (B) Picture of half of the whale’s eye. (C) cornea, (S) Sclera.
Here we will consider the two structures separately, the cornea and sclera, although there is a continuation between both in the eye. The composition of both structures is very similar, mainly comprised of an ECM that contains collagen, as mentioned above, although the organization of the collagen fibers in each differs underlies their distinct viscoelastic characteristics. Quick-freezing and the deep-etching methods have been used in ultrastructural studies of the collagen fibers in the cornea and sclera, demonstrating that corneal collagen fibers were separated by moderate interfibrillar spaces. By contrast, scleral collagen fibers were organized compactly, with fewer interconnecting filaments. In the sclera, the collagen fibers have a wider diameter (around 200 nm) than those in the cornea (around 40 nm), and the periodicity of the collagen striations was variable in each structure, although in the sclera these striations were difficult to detect because of the surrounding ground substance [1]. Here we used several techniques to study the whale’s cornea and sclera, from classical histochemical trichromic staining (Figure 2), fluorescent light microscopy (Figure 3) to scanning electron microscopy (SEM) (Figures 4 and 5), in addition to Raman spectroscopy (Figure 6). While microscopy will enable us to determine the structure and ultrastructure of the tissue, Raman spectroscopy is a technique that can be used to optically probe the molecular changes in the tissue. The result of this technique is a spectrum characterized by shifts in wave numbers, which in many cases can be associated with the vibration of particular chemical bond (or single functional group) in the molecule [2]. We will describe the two structures cornea and sclera, comparing human and whale main differences.
Trichrome staining of paraffin sections from cornea (A) and sclera (B) of whale’s eye. Note the linear and parallel organization of the fibres in cornea and the different orientation of the fibres in the sclera. Scale bar 50 μm.
Fluorescence microscopic picture of the nuclei of the keratocytes. Note their distribution and orientation in cornea (A) and sclera (B) stained with DAPI. In the cornea there are lower number of keratocytes and they are more organized than in the sclera. Scale bar 100 μm.
Scanning electron microscopy pictures of the whale’s (A) and human (B) corneas. Note the distribution of the fibers in laminar bundles. Scale in μm.
Scanning electron microscopic pictures of (A) and (B) are both sclera collagen fibers from whale’s sclera. (A) lower and (B) higher magnification. Scale in μm.
Raman spectrometry (A) overlapping the spectra from human bone (blue) and whale’s sclera.
Four methods were used to study the extracellular matrix. Two light microscopy methods, for that purpose the cornea and sclera were fixed for 12 h with paraformaldehyde (PAF) 4% and for the other two techniques of electron microscopy a post fixation with 2,5% glutaraldehyde for 2 h was performed after the previous fixation with PAF. The first histological technique used was Masson’s trichrome staining, performed in 5 micrometers paraffin sections to visualize the collagen fibers in blue/green from the extracellular matrix (Figure 2). The second technique used was fluorescence microscopic technique, to determine the organization of the keratocytes. For that purpose the nuclei of the keratocytes were stained with DAPI in cryostat sections (14 micrometers) (Figure 3). The third technique was the scanning electron microscopy (SEM) to visualize the ultrastructure of the matrix components, for that purpose, small portions (few mm2) of cornea and sclera were dehydrated in increasing gradation of alcohol followed by complete dehydration with hexamethyldisilazane (HDMS), then the pieces were oriented in the platform of the microscope and coated with gold (Figures 4 and 5). The last technique was RAMAN microscopy, for that purpose small portions of cornea and sclera were dehydrated as for the SEM, but the HDMS step was not carried out. Thus, the samples were analyzed with a confocal InVia Raman (Renishaw) connected to a spectrophotometer and an excitation laser of 785 nm was connected to a Leica microscope to register the spectro of the different tissues (Figure 6).
As indicated above, the cornea is a transparent organ that allows the light to enter into the eye. The features that contribute to its transparency are a thin epithelium, the absence of blood vessels and its chemical composition, mainly comprised of collagen and some important ground substance, with very few cells. The cornea has five main parts: (1) the epithelium; (2) Bowman’s layer; (3) the stroma; (4) Descement’s layer; and (5) the endothelium. In this chapter we will concentrate on the stroma, of which the ECM is the main component.
In humans the cornea is approximately 0.5 mm thick, while in the whale’s eye it measures 3 to 4 millimetres. In both cases it is composed almost entirely of collagenous lamellae. The collagen fibres are organized in lamellae approximately 6 mm in diameter but with certain variability in their width and thickness. The lamellae are arranged parallel to the corneal surface and sometimes they form loose fibrillar networks. The collagen fibres within the bundles lie parallel to each other, and they are uniform in size and spacing, a feature produced by the cementing ground substance that is distributed regularly between the fibres (Figure 2). In the most peripheral cornea, the lamellae gradually adopt a less regular orientation and little-by-little their structure approximates to the organization in the sclera [3]. The collagen fibres in the central cornea vary in diameter between 21–65 nm in humans [4], data that is consistent with that found in our human SEM preparations.
A few specialized fibroblasts called keratocytes can be found between the collagen fibres, and they are responsible for the synthesis of the collagen and ground substance. Only a small proportion of the cornea is occupied by these cells, around 2–3% in humans, and as such, it is generally considered an almost acellular structure [5]. The small number of cells present in the corneal stroma, the avascular nature of this structure and the very well-organized collagen lamellae, all contributes to the characteristic transparency of the cornea (Figures 2 and 3).
The ground substance in the cornea consists of mucoproteins, glycoproteins and other substances exclusive to collagen, and it forms a cement like filling in the space between the corneal fibres. In 1969, using alkaline lead, citrate and uranyl acetate staining, 2 nm diameter filaments were seen to exist at right angles to the collagen fibres that they connected, postulating that these were the proteoglycans that bind to the corneal collagen D-period [6]. Using cationic dyes (alcian blue, cuprolinic blue, cupromeronic blue) in a critical electrolyte mode, the presence of proteoglycans was confirmed. Later studies described these proteoglycans to be keratan sulphate (lumincan) and dermatan sulphate (decorin) in the cornea [7], while only dermatan sulphate proteoglycan was found in the sclera, bound to the same sites as in cornea [8]. It was subsequently proposed that these molecules play a role in maintaining the relative positions of the fibrils, which is important for corneal transparency [9, 10]. So far, the most sophisticated and less invasive technique to study the ultrastructure of the cornea, without affecting the physiological state of hydration is the X-ray [11] and this will help in the future for a better understand the pathophysiology of the cornea.
The corneas of the whale studied are oval in shape, with axes of 5 x 3 cm, and they have a convex outer surface. The corneal thickness varies between the centre, where it is 2.5 mm thick, and the periphery where it is thicker, measuring 4 mm at the corneal-scleral boundary. The diameter of the corneal collagen fibres also differed significantly between the human and whale. Thus, while in humans the corneal fibres are around 60 nm in diameter, in whale they measure around 200 nm (Figure 4). The composition of the collagen is probably very similar in both species, not least because their histochemical staining is very similar, also resembling that of the pig, rat and mouse cornea. Moreover, and in addition to SEM and TEM, when the whale cornea and sclera was studied by Raman spectroscopy, the characteristics of the peaks for the collagen components were similar to those in humans [12].
The sclera is the white part of the eye and it is relative thin, ranging from 0.6 mm in the anterior part to 1 mm in the posterior part of human eyes. However, the sclera is very thick in large whales like the fin whales that we have studied, and it measures 3 to 4 cm at the back of the eye, although it is thinner (0,5 cm) in the anterior part (Figure 1). This thick and quite hard structure serves as a coffer in which the sensitive parts of the eye like the retina can be protected from the intense pressures these animals are exposed to when swimming in the deep seas.
The ECM of the human sclera is mainly composed of type I, III, V and VI collagen. The principal function of type I collagen is to resist tension, while type III collagen is considered essential in maintain the structure of expandable organs and type V collagen has been implicated in controlling fibril diameter. Type V collagen also fulfils a role in anchoring to the basement membrane and adjacent stromal matrix, a function it shares with type VI collagen [13]. In the sclera, the collagen fibrils have various diameters, ranging from 25 to 230 nm. Although these collagen fibrils form bundles, their arrangement is more heterogeneous in the sclera than in the cornea. These collagen bundles vary in width and thickness, often sprouting branches and intertwining with each other, at least in humans [14]. Moreover, in the sclera there is a narrower interfibrillar distance than in the cornea and the ground substance is more abundant, impairing the discrimination of the band periodicity of the collagen fibres. Indeed, it has been necessary to use special treatments and atomic force microscopy to describe the differences in the periodicity of the collagen bands between the cornea and sclera [15].
In transverse section of the eye the human sclera is thinner towards the corneo-scleral junction, while it thickens in the medial direction, posterior to the vitreous chamber, where it joins the bundle of the optic nerve. The dorsal part of the sclera is larger than the ventral domain, which means that the optic nerve can exit the eye with a ventral disposition. The collagen fibres that make up the sclera are mainly embedded in the ground substance and the characterization of the different types of collagen fibres has been achieved in humans by immunogold EM staining [16]. The fibres are tightly packed and arranged in different directions, which provides the eyeball with strength and shape (Figures 2B and 5). Close to the corneo-scleral limbus, large blood vessels circulate not far from the angle, forming a ring. In the sclero-corneal stroma of the limbus there is a large number of pigmented cells and numerous channels are present in this area that form the well-developed trabecular meshwork responsible for draining aqueous humour toward the veins.
The analysis of the whale’s sclera using Raman spectrometry showed us that even when the thick sclera is quite hard (with a texture like a spongiosum bone), hydroxyapatite does not appear to be present and thus, we concluded that the hard sclera is not ossified Indeed, when comparing the spectrometry fingerprint of human bone with that from the whale’s sclera, both structures share collagen peaks (Figure 6). The sclera is likely to be important in preserving the shape of the eyeball, shielding it from the effects of the deforming forces. Indeed, this large eye can be retracted or protruded thanks to a large muscle that surrounds the optic nerve and that is full of blood vessels, the ophthalmic rete [17]. It is possible that this large muscle also helps the eye and a thick sclera resist the pressure of the deep seas and avoid eye deformation.
Glaucoma is the main cause of blindness in the world. Although there are several types of glaucoma, the most common is characterized by an increase in the intraocular pressure (IOP) that induces neurodegeneration in the retina. Indeed, glaucoma leads to the death of the retinal ganglion cells that are the responsible for sending visual information from the eye to the brain, thus causing blindness [18]. The increasing of the intraocular pressure is due to the elevated secretion of aqueous humour or to a reduction in the evacuation of it, mainly through the trabecular meshwork. So far, in the human eye it has not been detected any sensor to detect and control the intraocular pressure. Interestingly, encapsulated sensory corpuscles are specialized nerve endings located in the corneo-scleral area that do not have a very clear function. These have been found in different cetaceans and in the whale
The thickness of the cornea is very important and has to be taken into consideration in order to measure IOP correctly. Since the way to measure the IOP is through the cornea, the instruments used must be adapted to the mean cornea thickness. However, in order to correct the defects, a refraction technique has been developed that involves correcting the curvature of the cornea by reshaping the stroma of the cornea with a laser, LASIK surgery. The thickness of the cornea is critical to be able to perform this surgery, particularly since the mean cornea thickness in humans is 500 um and it reaches a maximum of 600 um, and LASIK surgery should not be performed on thinner corneas. After LASIK surgery, the patient should retain a minimum of 250 μm corneal thickness. In this sense, IOP measurements can vary depending on the thickness of the cornea, being underestimated in patients with thinner corneas and overestimated in patients with thicker corneas. Another side effect of re-shaping a thin cornea is the deformation in the central part, which can alter corneal curvature, so-called keratoconus. This is a phenomenon that leads to a gradually bulging of the cornea outwards into a cone shape, which causes blurry, distorted vision. In order to correct this keratoconus crosslinking of the collagen fibers should be performed by applying UV light to the collagen fibers, thereby reinforcing the structure of the cornea. The UV light together with the application of riboflavin (vitamin B2) will enhance the bonds between collagen fibers in the stroma of the cornea [20]. It is also hypothesized that stiffening of ocular structures, including cornea and sclera may be related to the pathogenesis of glaucoma [21].
Another alteration to the cornea that can influence IOP measurement is the prolonged use of contact lenses. Initially, contact lenses can induce a flattening of the cornea during the first months of use, but prolonged use can cause a thinning of the cornea with some deformation. Thus, we can conclude that prolonged use of contact lenses negatively influences corneal physiology. Aging can also change central and peripheral corneal thickness. By using ultrasonic pachymetry in 250 patients aged 9 to 97 years, it was concluded that central corneal thickness increases significantly with age, whereas the degree of symmetry decreases [22]. Accordingly, there are different factors that can affect corneal thickness and thus, IOP measurements, which could influence the detection and treatment of glaucoma.
The sclera provides a tough fibrous support structure for the retina and optic nerve, fulfilling a biomechanical function that may be crucial in glaucoma. Several studies have assessed collagen fiber architecture in order to identify if uniaxial (one preferred direction) or biaxial (two directions) collagen organization of the sclera is related to glaucoma. So far, changes in fiber orientation have been detected between glaucomatous and non-glaucomatous eyes, although it could be an adaptation to the elevated pressure and it is not clear if there is a predisposition to glaucomatous axon damage [23]. However, the very hard, strong and thick sclera present in the whale’s eye means there is no capacity for distension or structural modification. As such, any elevation in IOP in whales would be sensed by the retina. The other structure in the eye that is sensitive to IOP is the lamina cribosa (LC) or cribiform plate that forms a scaffold for the passage of the optic nerve’s axon bundles, anchoring the bundles to each other and to the sides forming the optic nerve. It reinforces the posterior eye, protecting it from injury at the site of optic nerve exit. The LC is subject to mechanical strain as it lies at the border between two different compartments subject to pressure: the anterior compartment to IOP and the retrobulbar compartment to that of the cerebrospinal fluid [24]. Hence, the LC has been proposed as the main site controlling the pressure that represents the insult to retinal ganglion cell axons in glaucoma [25]. Moreover, the LC thickness and the posterior displacement of its components have been associated with the rate of progressive retinal fiber layer thinning and the severity of glaucoma. Changes in the structure of the LC have been found in patients with glaucoma, indicating that these structural changes could provide information regarding the evolution of glaucoma [26]. However, in our large exanimated animals, the LC of the whales is as hard as the sclera, which means it will be very difficult for it to deform. Thus, in these animals there is a very limited possibility for the eye to deform in response changes in the IOP.
In conclusion, we have evaluated the structure of the eye in the second largest mammalian on the planet, the long fin whale, considering the possible functional consequences of its features. These eyes are around 150 times larger than the human eye, although their structure is very similar and their ECM components are also comparable, albeit in different proportions. Thus, the cornea and sclera are thicker, adapting to the whale’s ecosystem and to the physiology of their body size. The very large structures and the rigid ECM lead us to consider the implication of the ECM in eye diseases like glaucoma and keratoconus, which in these animals will be very difficult to explain in the context of their very distinct dimensions and structure.
We would like to thank the support by: Grupos UPV/EHU GIU18/50; PIBA 2020-1-0026; Retos MINECO FEDER (PID2019-111139RB-I00); FECYT-19-14532 to EV. Basque Government Post-Doctoral Fellowship to XP.
The authors declare no conflict of interest.
We would like to thank AMBAR association for the help in getting the whale’s eye. In addition, we would like to thank all persons that unconditionally encouraged and supported us to carry out the research and to show the results in the art exhibition of scientific photography about the eye of the whale in the Bizkaia Aretoa in February 2020.
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Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. 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