Dopamiinin hapettumisen lukija-anturirajapinta 65 nm CMOS teknologialla

Sensing and monitoring of neural activities within the central nervous system has become a fast-growing area of research due to the need to understand more about how neurons communicate. Several neurological disorders such as Parkinson’s disease, Schizophrenia, Alzeihmers and Epilepsy have been reported to be associated with imbalance in the concentration of neurotransmitters such as glutamate and dopamine [1] - [5]. Hence, this thesis proposes a solution for the measurement of dopamine concentration in the brain during neural communication. The proposed design of the dopamine oxidation readout sensor interface is based on a mixed-signal front-end architecture for minimizing noise and high resolution of detected current signals. The analog front-end is designed for acquisition and amplification of current signals resulting from oxidation and reduction at the biosensor electrodes in the brain. The digital signal processing (DSP) block is used for discretization of detected dopamine oxidation and reduction current signals that can be further processed by an external system. The results from the simulation of the proposed design show that the readout circuit has a current resolution of 100 pA and can detect minimum dopamine concentration of 10 μMol based on measured data from novel diamond-like carbon electrodes [6]. Higher dopamine concentration can be detected from the sensor interface due to its support for a wide current range of 1.2 μA(±600 nA). The digital code representation of the detected dopamine has a resolution of 14.3-bits with RMS conversion error of 0.18 LSB which results in an SNR of 88 dB at full current range input. However, the attained ENOB is 8-bits due to the effect of nonlinearity in the oscillator based ADC. Nonetheless, the achieved resolution of the readout circuit provides good sensitivity of released dopamine in the brain which is useful for further understanding of neurotransmitters and fostering research into improved treatments of related neurodegenerative diseases.Keskushermoston aktiivisuuden havainnointi ja tarkkailu on muodostunut tärkeäksi tutkimusalaksi, sillä tarve ymmärtää neuronien viestintää on kasvanut. Monien hermostollisten sairauksien kuten Parkinsonin taudin, skitsofrenian, Alzheimerin taudin ja epilepsian on huomattu aiheuttavan muutoksia välittäjäaineiden, kuten glutamaatin ja dopamiinin, pitoisuuksissa [1] - [5]. Aiheeseen liittyen tässä työssä esitetään ratkaisu dopamiinipitoisuuden mittaamiseksi aivoista. Esitetty dopamiinipitoisuuden lukijapiiri perustuu sekamuotoiseen etupäärakenteeseen, jolla saavutetaan matala kohinataso ja hyvä tarkkuus signaalien ilmaisemisessa. Suunniteltu analoginen etupää kykenee lukemaan ja vahvistamaan dopamiinipitoisuuden muutosten aiheuttamia virran muutoksia aivoihin asennetuista elektrodeista. Digitaalisen signaalinkäsittelyn avulla voidaan havaita dopamiinin hapettumis-ja pelkistymisvirtasignaalit, ja välittää ne edelleen ulkoisen järjestelmän muokattavaksi. Simulaatiotulokset osoittavat, että suunniteltu piiri saavuttaa 100 pA virran erottelukyvyn. Simuloinnin perustuessa hiilipohjaisiin dopamiinielektrodeihin piiri voi havaita 10 μMol dopamiinipitoisuuden [6]. Myös suurempia dopamiinipitoisuuksia voidaan havaita, sillä etupäärajapinta tukee 1.2 μA(±600 nA) virta-aluetta. Digitaalinen esitysmuoto tukee 14.3 bitin esitystarkkuutta 0.18 bitin RMS virheellä saavuttaen 88 dB dynaamisen virta-alueen. Saavutettu ENOB (tehollinen bittimäärä) on kuitenkin 8 bittiä oskillaattoripohjaisen ADC:n (analogia-digitaalimuuntimen) epälineaarisuuden takia. Saavutettu tarkkuus tuottaa hyvän herkkyyden dopamiinin havaitsemiseksi ja hyödyttää siten välittäjäainetutkimusta ja uusien hoitomuotojen kehittämistä hermostollisiin sairauksiin

Prevalence of Asymptomatic Bacteriuria in HIV Infected Patients in a Tertiary Hospital in Lagos, Nigeria

Background: People living with Human Immunodeficiency Virus (HIV) are more predisposed to urinary tract infections due to suppression of their immunity by the virus. Asymptomatic bacteriuria is associated with an increased risk of symptomatic urinary tract infection and the latter being an important contributor to development of chronic renal failure, hypertension and toxaemia of pregnancy. The aim of this study was to determine the prevalence of asymptomatic bacteriuria in HIV-infected patients and proffer a recommendation on the need or otherwise to screen. Methods: This was a cross sectional study of treatment-naive HIV-infected patients attending the HIV clinics of Lagos State University Teaching Hospital (LASUTH), Ikeja. A single voided aseptically collected mid-stream urine (MSU) was obtained from each patient and all samples processed immediately, were sent for urinalysis and culture. Isolates were considered significant if there were ≥105 colony forming unit/mL (CFU/mL) with 2 or less isolates, doubtful significance if <105 CFU/mL. Significant isolates were selected for identification. Data were analyzed using SPSS version 16.0 (Statistical Package for Social Sciences, Inc., Chicago, Ill). Results: A total of 156 consenting participants were recruited into the study. The mean age was 36.45 ± 8.65 years. There were 60 of 156 (38.4%) males and 96 of 156 (61.56%) females. Only 33 of 156 (21.2%) had significant bacteriuria, out of the 33 participants, 19 (57.8%) were asymptomatic, while 14 of 33 (42.4%) had significant growth but were symptomatic or on antibiotics. E. coli was isolated in 9 of 19 (47.3%), followed by Staph aureus 4 of 19 (21.05%). Conclusion: More than half of participants who had significant growth had asymptomatic bacteriuria, while one-fifth of all patients had significant growth. Considering this statistics, screening for or treatment of asymptomatic bacteriuria may be recommended in all HIV-infected patients

THE RELATIONSHIP BETWEEN THE ANTHROPOMETRIC MEASURES AND RESPIRATORY FUNCTIONS OF TOBACCO WORKERS

The aim of this research was to establish the relationship between some anthropometric measurements and peak expiratory flow rate of tobacco factory workers. Eighty permanent workers who had been employed for at least three years with no history of cardiovascular disease were involved with the study. The measured anthropometric data (chest width and depth, height and weight) were analyzed using SPSS (V 16.0) to develop predictive models for PEFR of tobacco factory workers. It was concluded that the developed models could determine the PEFR of workers in a tobacco manufacturing company

THE RELATIONSHIP BETWEEN THE ANTHROPOMETRIC MEASURES AND RESPIRATORY FUNCTIONS OF TOBACCO WORKERS

The aim of this research was to establish the relationship between some anthropometric measurements and peak expiratory flow rate of tobacco factory workers. Eighty permanent workers who had been employed for at least three years with no history of cardiovascular disease were involved with the study. The measured anthropometric data (chest width and depth, height and weight) were analyzed using SPSS (V 16.0) to develop predictive models for PEFR of tobacco factory workers. It was concluded that the developed models could determine the PEFR of workers in a tobacco manufacturing company

New-Onset Seizures in HIV Patients on Antiretroviral Therapy at a Tertiary Centre in South-West, Nigeria

Background: Seizures are associated with neurological manifestations of HIV. They may be the presenting symptom and can occur at any disease stage. Aim: To determine the frequency and clinical aspects of new-onset seizures in patients with human immunodeficiency virus (HIV) infection. Methods: A study of an HIV-infected patient cohort on highly active anti-retroviral therapy (HAART) in the out-patients clinic of the Lagos state university teaching hospital, Nigeria. In a cross-sectional design, 308 HIV infected patients were recruited over a period of 1 year. Cases with a first seizure during this period were further examined. Details of demographic data, the first seizure date, seizure characteristics, neurologic complications and CD4 count at the time of the seizure were documented. Results: A total of 20 (6.5%) had new-onset seizures during the study period. 6/20 (30%) were males and 14/20 (70%), females. Their ages ranged between 22 - 51 years with a mean of 34.2 ± 8.7 years. The seizure was focal in 2/20 (10%) of cases and generalised in 90% (18/20) of cases. A total of 13/20 (65%) had recurrence of their seizures. None of the cases had focal neurological deficit at the time of the first seizure. The mean CD4 count was 165.3 ± 145.7. The mean duration on HAART was 19.5 ± 12.7 months. Cases with CD4 counts ≤200 cells/mm3 constituted 70% (14/20) whilst those with CD4 counts >200 made up 30% (6/20) [p = 0.666]. Conclusions: Seizures remain a significant neurological manifestation of HIV infection and has a high recurrence rate. It occurs more commonly in the advanced stage with severe immune suppression and may be attributable to HIV encephalopathy. Early treatment would reduce the burden and improve patient’s quality of life

Seroprevalence of human T lymphotropic virus antibodies among healthy blood donors at a tertiary centre in Lagos, Nigeria

Introduction: Transmission of human T-lymphotropic viruses (HTLV) occurs from mother to child, by sexual contact and blood transfusion. Presently, in most centres in Nigeria, there is no routine pre-transfusion screening for HTLV. The study aims to determine the prevalence of HTLV-1 and HTLV-2 among healthy blood donors at a tertiary centre in Lagos. Methods: A cross-sectional study was carried out at the blood donor clinic of the Lagos State University Teaching Hospital (LASUTH), Ikeja. About 5mls of venous blood was collected from each subject into a sterile plain bottle after obtaining subject's consent. The serum separated and stored at -200C. Sera were assayed for HTLV by an enzyme-linked immunoassay (ELISA) for the determination of antibodies to HTLV 1 and HTLV -2. Western blot confirmatory testing was done on reactive samples. All donors were also screened for HIV, HBsAg and HCV by rapid kits. Results: The seroprevalence of HTLV -1 by ELISA was 1.0% and 0.5% by Western Blot among blood donors. A total of 210 healthy blood donors were enrolled. Only 2 (1.0%) blood donors were repeatedly reactive with ELISA test. On confirmatory testing with Western Blot, 1 (0.5%) blood donor was positive for HTLV. All the healthy blood donors were negative for HIV, HbsAg and HCV. None of the 210 blood donors had been previously transfused; as such no association could be established between transfusion history and HTLV positivity among the blood donors. Conclusion: The seroprevalence of HTLV in this environment is low among healthy blood donors

Mean platelet volume and platelet counts in type 2 Diabetes: Mellitus on treatment and non-diabetic mellitus controls in Lagos, Nigeria

Introduction: The Mean platelet volume and platelet counts are indicators of thrombotic potentials, and risk factors for microvascular complications in diabetics. This study aimed to establish variations in platelet counts and mean platelet volume in type 2 diabetic patients on treatment and non-diabetic controls. Methods: This was an unmatched case-control study involving 200 participants consisting of 100 diabetics and 100 non-diabetic controls. Four and half milliliters of blood was collected from diabetics and non diabetic controls into EDTA anticoagulant tubes. Full blood count was performed using the Sysmex KN-21N, (manufactured by Sysmex corporation Kobe, Japan) a three- part auto analyzer able to run 19 parameters per sample including platelet counts and mean platelet volume. Results: The mean fasting blood sugar for the diabetics was 147.85±72.54 mg/dl and the controls 95.20±30.10 mg/dl. The mean platelet count for the diabetics was 235.29±76.81*109/L and controls, 211.32±66.44*109/L. The mean platelet volume, for the diabetics was 8.69±0.67 fl and the controls, 8.91±0.80 fl. There was a statistically significant difference in platelet counts of diabetics and healthy controls p =0.038 while none existed between the mean platelet volume in diabetics and healthy controls p=0.593. Conclusion: This study revealed a higher mean platelet count for diabetics on treatment than for non diabetic controls while mean platelet volume was lower in cases than controls. However, both parameters in diabetics on treatment were within the normal reference range for healthy individuals

Integroidut aikapohjaiset tarkkailurajapintapiirit istutesovelluksiin

As the population ages, the prevalence of neurological and neurodegenerative disorders such as epilepsy, schizophrenia, dementia, as well as Parkinson's and Alzheimer's diseases, are expected to increase, which in turn increases the socio-economic burden on care-givers, global health care systems, and society at large. The progressive degeneration of neurons in patients suffering from neurological disorders affects the generation and release of key neurotransmitters such as serotonin, glutamate, histamine, and dopamine in the brain. Available treatment methods aim to alleviate the symptoms and alter the disease progression. However, there is still active research on understanding more about the causes and progression of these diseases. As a result, there is a need for real-time monitoring of neurotransmitter signalling in the brain that may lead to development of improved treatments for neurological and psychological disorders. The main research objective of this thesis is the design of integrated time-based sensor interface circuits for implant applications, targeted towards monitoring of neurochemical and neuroelectrical signals. The thesis and related publications (I - VI) describe the investigated and implemented circuits. First, a sensor interface circuit based on a current-controlled oscillator (CCO) for neurochemical sensing applications is presented. The acquired current from the neurochemical is converted to frequency, and then the frequency is quantized in the digital domain, for generating the digital code representation of changes in the current flowing as the neurochemical undergoes oxidation and reduction reactions. The proposed CCO-based sensor interface circuit is fabricated in 65 nm CMOS technology and results measured using novel diamond-like carbon electrodes, demonstrate the detection of a physiologically-relevant dopamine concentration of 500 nM. In addition, the use of an asynchronous ΣΔ modulator (ASDM) in the design of time-based analog-to-digital conversion is explored. ASDMs operate based on the principle of duty-cycle modulation, which results in a linear relationship between the duty-cycle of the generated pulse train and the input signal amplitude. As a result, the duty-cycle is quantized in the digital domain by a time-to-digital converter. The ASDM circuits are fabricated in 28 nm FDSOI technology and the results measured from the current-input ASDM show an effective resolution of 13.2 bits. The fully-differential, configurable, and noise-shaping features of the asynchronous ΣΔ modulator-based converter make the proposed circuit an attractive ADC for implantable and biomedical applications. In summary, this thesis provides an overview of the design of integrated biomedical sensor interfaces, an introduction to time-based analog-to-digital conversion, a description of the implemented time-based ADCs, as well as simulated and measured performance of the proposed circuits.Väestörakenteen vanhetessa oletetaan hermostollisten ja hermostoa rappeuttavien sairauksien, kuten epilepsian, skitsofrenian, dementian ja Parkinsonin taudin esiintyvyyden kasvavan väestössä. Tämä luonnollisesti lisää terveyden- ja sosiaalihuollon sosiaalistaloudellista kokonaiskuormaa. Etenevä hermosolujen rappeutuminen hermostollisista sairauksia sairastavissa potilaissa vaikuttaa hermostollisten välittäjäaineiden, kuten glutamaatin, histamiinin, ja dopamiinin pitoisuuksiin aivoissa. Käytössä olevilla hoitomenetelmillä pyritään lievittämään oireita ja vaikuttamaan sairauden etenemiseen. Lisäksi tutkimuksella pyritään lisäämään ymmärrystä taudin etenemiseen vaikuttavista tekijöistä. Viimeaikainen tutkimus on synnyttänyt tarpeen seurata välittäjäaineiden tiedonvälitystä aivoissa, sillä onnistuessaan se edistää uusien parempien hoitomuotojen kehittämistä hermostollisiin ja psykologisiin sairauksiin. Tämän työn tavoitteet ovat integroitujen istutteiden aikapohjaisten anturirajapintojen elektroniikan suunnittelussa aivokemiallisten ja aivosähköisten hermosignaalien seurantaan. Väitöskirja ja siihen liittyvät julkaisut (I-V) kuvaavat tehdyn tutkimuksen sekä toteutetut piirit. Työn alussa esitetään virtaohjattu anturirajapintapiiri aivokemiallisten ilmiöiden tarkkailuun. Piirin rakenne perustuu virtaohjattuun värähtelijäpiiriin (CCO). Aivokemiallisen välittäjäaineen tuottama virta muunnetaan taajuudeksi jonka jälkeen taajuus muunnetaan digitaaliseen esitysmuotoon. Näin saatu tulos seuraa virran muutoksia välittäjäaineessa tapahtuvien hapettumis- ja pelkistymisreaktioiden johdosta. Suunniteltu CCO:n pohjautuva piiri on toteutettu 65 nm CMOS piiteknologialla ja toiminta on mitattu käyttäen uutta timanttirakenteista hiilielektrodia. Saatu tulos todentaa fysiologisesti mielekkään 500nM dopamiinikonsentraation. Työssä on tutkittu myös asynkronisen ΣΔ-modulaattorin (ASDM) soveltamista digitaali-analogia muunnoksessa. ASDM:n toimintaperiaate on pulssisuhdemodulaatio, mikä tuottaa lineaariseen riippuvuuden värähtelijän pulssisuhteen ja tulosuureen välillä. Modulaation jälkeen pulssisuhde muunnetaan digitaaliseen muotoon ajasta-digitaaliseksi muuntimella. Työssä esitetty ASDM-piiri on toteutettu 28 nm FDSOI piiteknologialla. ASDM piirin saavuttaessa 13,2 bitin tehollisen erottelukyvyn, mittaustulokset ovat erittäin kilpailukykyisiä. Suunniteltu täysin eromuotoinen, uudelleenmääriteltävä, kohinaa muokkaava ASDM-pohjainen AD-muunnin on kirjoittajan tämänhetkisen tietämyksen mukaan ensimmäinen tämän tyyppinen julkaistu muunnin. Sen ominaisuudet tekevät asynkronisesta ΣΔ-modulaatttoripohjaisesta muuntimesta kiinnostavan muunninrakenteen biolääketieteellisiin istutesovelluksiin. Väitöskirjassa esitettään katsaus biolääketieteellisten anturirajapintojen suunnitteluun, johdanto aikapohjaisiin analogia-digitaali muunnokseen, kuvaus toteutetuista aikapohjaisista muunninpiireistä, sekä niiden simuloitu ja mitattu suorituskyky

A current controlled oscillator based readout front-end for neurochemical sensing in 65nm CMOS technology

This paper presents the design of an integrated current-controlled oscillator (CCO) based readout front-end for neurochemical sensing applications. The readout front-end chip is implemented in 65 nm CMOS technology and occupies an area of 0.059 mm2. The proposed design supports an input current range of 1.2 μA (±600 nA) and can also be configured to support wider current range. The CCO-based structure utilized in this design results in noise averaging of the detected neurochemical input signal due to its inherent ΔΣfirst-order noise shaping and anti-alias filtering characteristics. Thus, the prototype chip achieves a current resolution of 100 pA and can detect dopamine concentrations as small as 10 μMol based on measured data from novel diamond-like carbon electrodes. In addition, the digital codes obtained from the readout front-end attain a signal-to-noise (SNR) of 82 dB and linearity limited effective-number-of-bits (ENOB) of 8 at full current range input, without employing any calibration or linearizationtechniques. The proposed read-out front-end consumes 33.7 μW of power in continuous operation.Peer reviewe

Sub-1 V output-capacitor-less low-dropout regulator with two compensation amplifiers for enhanced power supply rejection

Funding Information: ACKNOWLEDGMENT This work has been funded by Academy of Finland, project number 269196. Publisher Copyright: © 2020 IEEEIn this paper we propose two methods to boost the power supply rejection (PSR) of an output-capacitor-less low-dropout regulator (LDO). Our LDO is targeted for low-power system-on-chip applications, such as medical electronics, RFIDs, and IoT devices, where applied energy harvesting techniques induce large voltage ripple to supply line, thus requiring high PSR out of the LDO. The regulator utilizes a feed-forward path through the amplifier power supply rail to pass-transistor gate. Furthermore it includes a feed-forward amplifier to improve the frequency response and a feedback amplifier to stabilize the LDO, eliminating the need for an area consuming compensation capacitor. The proposed LDO is implemented in 28-nm CMOS technology. It supplies 700-mV output level with a current range of 0-5 mA and a 100-mV dropout voltage. The three amplifiers within our LDO consume only a total of 13 μA, thus regardless of increased complexity, high current efficiency of 99.74% is maintained. At the nominal load of 1 mA, low-frequency PSR reaches a value of -97 dB and at the high-frequency range of 1-20 MHz PSR is boosted to remain below -20 dB and the region of 3-10 MHz below -30 dB.Peer reviewe