Design of a handheld and portable fluorescence imaging system for quantitative detection of pregnancy-specific biomarkers in cattle.

Reproductive management significantly impacts dairy farm productivity, necessitating accurate timely pregnancy detection in cattle. This paper presents a novel handheld and portable fluorescence imaging system designed for quantitative assessment of pregnancy-specific biomarkers, addressing the limitations of current detection methods. The objective was to develop a cost-effective, at-farm solution for detecting pregnancy-specific protein B (PSPB) in bovine plasma samples. The system integrates an imaging module and a custom software application, enabling image capture, data processing, and PSPB concentration determination. Calibration utilizing known PSPB concentrations achieved a 0.6 ng/mL limit of detection. Validation encompassed a comparison with a standard ELISA method using 100 bovine plasma samples; minimal bias and good agreement were observed within the linear range of the calibration curve for both methods. The system offers portability, user-friendliness, and potential for multiplex detection, promising real-time, at-farm reproductive management. This study demonstrates the successful development and validation of a portable fluorescence imaging system, offering an efficient and accurate approach to detecting pregnancy-specific biomarkers in cattle. Its implications extend to improving dairy farm productivity by enabling timely and reliable reproductive management practices.

Quantitative analysis of various targets based on aptamer and functionalized Fe3O4@graphene oxide in dairy products using pregnancy test strip and smartphone.

Pregnancy test strips are one of the most mature and widely used commercial lateral flow devices used to determine pregnancy. Being a simple and rapid detection method, human chorionic gonadotropin (hCG) was used with different aptamers (hCG-apt) as probes for the detection of metal ions, small organic molecules, and proteins. Quantitative detection of target analytes was achieved using a smartphone app and a portable device developed in our laboratory. The results showed detection ranges of 1 nM-1 µM, 0.1 nM-10 µM and 32 nM-500 nM for Pb2+, chloramphenicol, and ß-lactoglobulin, respectively, and the corresponding visual detection limits in dairy products were 5 nM, 1 nM and 50 nM, respectively. Based on these results, rapid detection of multiple analytes can be realized through aptamer modification, thereby broadening the application range of commercial lateral flow devices for analysis of food chemistry.

Diving deep to detect manta ray pregnancies.

Georgina Mills explains how researchers have used cutting-edge technology to learn more about reproduction in manta rays in the Maldives.

Characterizing urinary hCGßcf patterns during pregnancy.

OBJECTIVE: Elevated concentrations of hCG beta core fragment (hCGßcf) are known to cause false-negative results in qualitative urine pregnancy test devices, but the pattern of urinary hCGßcf during normal pregnancy has not been well characterized. Here, we evaluate the relationship between urine hCG, hCGßcf, and hCG free ß subunit (hCGß) during pregnancy. DESIGN AND METHODS: Banked second trimester urine specimens from 100 pregnant women were screened for high concentrations of hCGßcf using a qualitative point-of-care device known to demonstrate false-negative results in the presence of elevated hCGßcf concentrations. Additional first and third trimester specimens from the same pregnancy were obtained from 10 women who generated negative/faint positive results, 5 women who generated intermediate positive results, and 10 women who generated strong positive results on the point-of-care device. Intact hCG, hCGßcf, hCGß, and specific gravity were quantified in these 75 specimens. RESULTS: Urinary hCGßcf concentrations were greater than intact hCG concentrations at all times. A strong correlation (r(2)=0.70) was observed between urine intact hCG and hCGßcf concentrations. A poor correlation was observed between specific gravity and intact hCG (r(2)=0.32), hCGß (r(2)=0.32), and hCGßcf (r(2)=0.32). The highest hCGßcf concentrations were observed between 10 and 16weeks gestation but individual women demonstrated very different patterns of hCGßcf excretion. CONCLUSIONS: Urine specimens with elevated hCGßcf are frequently encountered during pregnancy but hCGßcf excretion patterns are unpredictable. Manufacturers and clinicians must appreciate that hCGßcf is the major immunoreactive component in urine during pregnancy and must design and interpret qualitative urine hCG test results accordingly.

Evaluation of a semi-quantitative pregnancy device for susceptibility to interference caused by hCGßcf.

OBJECTIVE: Previous work has documented the ability of the Clearblue Advanced Test with Weeks Estimator, a new over-the-counter (OTC) urine hCG device, to accurately estimate weeks since ovulation in early pregnancy. In this study, the performance of this device in more advanced pregnancy was assessed. METHODS: The Clearblue Advanced Test with Weeks Estimator device was used to test solutions containing purified intact hCG and hCGßcf at concentrations consistent with early, middle and late pregnancy. Urine samples from three normal pregnant patients 9-13 weeks of gestation and from a patient 12 weeks of gestation known to generate false negative results on qualitative urine test devices due to excess hCGßcf were also evaluated. RESULTS: The Clearblue Weeks Estimator device gave expected results using solutions containing purified intact hCG and hCGßcf at concentrations observed throughout pregnancy. The device generated expected results using urine from three of four patients tested between 9 and 13 weeks of gestation. However, when urine from a patient with elevated concentrations of hCGßcf was used, the device correctly indicated pregnancy although the estimate for the date was incorrect. CONCLUSION: This device gave expected "pregnant" results using all samples tested. However, the "Weeks Estimator" should be interpreted with caution when used by patients after seven weeks of pregnancy.

Comparison of analytical sensitivity and women's interpretation of home pregnancy tests.

BACKGROUND: Internationally there are no defined standards for expressing the performance of home-based pregnancy tests, nor any pre-defined accuracy standard requirements. The aim of this study was to evaluate the accuracy of a selection of home-based pregnancy tests relative to their packaging/product insert claims. METHODS: Eight home-based pregnancy tests were evaluated using human chorionic gonadotrophin (hCG) urine standards (0, 15, 25 mlU/mL). Testing was performed by a technician and results were read by a technician and a panel of consumer volunteers (each blinded to the expected result) and compared with the expected result based on the manufacturer's claimed accuracy. Volunteers also completed questionnaires relating to various device attributes. RESULTS: The overall agreement between the technician reading and expected reading from the hCG concentration was >90% for the Clearblue® DIGITAL, Clearblue® PLUS, Confirme® Plus, David® and Haus™ tests, and approximately 80% for Predictor® Early; agreement was <50% for Femitest® Jet Ultra and Cyclotest® Early tests. RESULTS were available from 72 volunteers (aged 18-45 years). Overall the percentage agreement between volunteer result and expected result was >95% for Clearblue DIGITAL and Clearblue PLUS tests; agreement for all other tests was <75% (lowest were Cyclotest Early and Femitest Jet Ultra, 33.0% and 39.4%, respectively). The Clearblue DIGITAL test was scored most highly by volunteers in the questionnaires. CONCLUSIONS: Many home-based pregnancy tests commonly used by women are not as accurate as their packaging information claims. International test standards which define appropriate performance characteristics for home pregnancy tests are urgently required.

Screening method to evaluate point-of-care human chorionic gonadotropin (hCG) devices for susceptibility to the hook effect by hCG ß core fragment: evaluation of 11 devices.

BACKGROUND: The predominant hCG variant in urine, hCG ß core fragment (hCGßcf), has been demonstrated to cause false-negative results in qualitative point-of-care (POC) hCG devices. This is a major concern for healthcare professionals using POC pregnancy tests. We developed a screening method to evaluate qualitative POC hCG devices for their susceptibility to inhibition by hCGßcf. Using this method, we evaluated the performance of 11 commonly used devices. METHODS: A wide range of purified hCG and hCGßcf concentrations were mixed and tested on 2 POC devices. By use of those results, a screening method was defined and 9 additional POC devices were evaluated. Two solutions containing (a) 500 pmol/L (171 IU/L) intact hCG with 0 pmol/L hCGßcf and (b) 500 pmol/L intact hCG with 500 000 pmol/L hCGßcf were used to screen all POC devices. RESULTS: The OSOM and Cen-Med Elite devices were found to be most susceptible to false-negative results due to hCGßcf. The BC Icon 20 and the Alere were the least susceptible. The remaining 7 were moderately affected. Devices that gave the strongest signal with hCGßcf alone were those that were least likely to show a hook effect. CONCLUSIONS: The screening method put forth here can be used by device users and manufacturers to evaluate POC devices for inhibition by hCGßcf. Of 11 devices evaluated, only 2 have been identified that exhibit minimal to no susceptibility to hCGßcf.

Accuracy of a home-based device for giving an early estimate of pregnancy duration compared with reference methods.

OBJECTIVE: To assess a home pregnancy test's accuracy to concurrently detect pregnancy and determine pregnancy duration. DESIGN: Multicenter, prospective study. SETTING: Study sites in the United States. PATIENT(S): Women actively attempting to conceive who have menstrual bleeds (18-45 years). INTERVENTION(S): Volunteers collected early morning urine samples (three or fewer menstrual cycles). Pregnant volunteers underwent ultrasound dating scans. Ovulation day (LH surge +1 day) during pregnancy-resulting cycles was determined by quantitative measurement of LH. Random urine samples were tested with the hCG-measuring pregnancy test from 4 days before the expected period until 4 weeks later. MAIN OUTCOME MEASURE(S): A home pregnancy test's accuracy in determining pregnancy duration compared with ultrasound and ovulation day. RESULT(S): Agreement between pregnancy test results and time since ovulation was 93% (confidence interval [CI], 91.5-94.4). Agreement with ultrasound was dependent on the formula: there was 99% agreement when calculated with adjustment for Hadlock formula bias (Pexsters; CI, 98.2-99.4) or using a nonbias formula (Wu; CI, 98.6-99.6), when ultrasound error was accommodated. Agreement was lower when bias/measurement errors were not accounted for (Wu, 86%, CI, 83.9-88; Hadlock, 80.8, CI, 78.2-83.3). CONCLUSION(S): This home pregnancy test provides an accurate estimation of pregnancy duration in weeks categories, 1-2, 2-3, 3+ weeks since ovulation, thereby showing utility in dating pregnancy.

Health consumption as work: the home pregnancy test as a domesticated health tool.

A growing array of biomedical goods and services has become central to the North American experience of navigating illness and pursuing good health. Yet despite the utility of consumption as an analytical framework within the social sciences, the selection, purchase, and use of biomedical goods and services has been understudied. By using the home pregnancy test as a case study, we suggest new approaches to thinking about the consumption of these goods and services. We chose the home pregnancy test because it is the best-known example of a mass-produced diagnostic tool used by consumers. We draw on two sources of data for this qualitative analysis: a set of stories submitted between 2003 and 2005 by women and men to an online exhibit mounted by the National Institutes of Health called "A Thin Blue Line: The History of the Pregnancy Test Kit," which we analysed between 2006 and 2007; and web sampling conducted in 2009 and 2010 of personal web and video logs of women and men who have posted stories and opinions about their experiences with contemporary home pregnancy testing products. We adapt the term "domestication" from Science and Technology Studies scholarship to describe the movement of diagnostic devices into homes for use by consumers. Specifically, we propose that the consumption of domesticated biomedical devices, goods, and services should be theorized as work performed by consumers, in two senses: as a form of tool use that allows non-experts to produce diagnostic knowledge about their own bodies and health; and as the ongoing biopolitical work that is expected of citizens to produce healthy bodies. Our paper draws attention to these understudied phenomena, while suggesting new approaches to theorizing the social and cultural elements of goods and services for health.

Evaluation of Nischay scheme in improving antenatal care in a northern state of India.

OBJECTIVE: To evaluate Nischay scheme (provision of pregnancy detection kit) in improving antenatal care. METHODOLOGY: A natural experiment design was conducted during September 2011 to April 2012 in a randomly selected district of Haryana state of India. Community Health Center (CHC), Primary Health Center (PHC), sub-center and villages were selected using random sampling technique. The retrospective record analysis of antenatal data pertaining to 6 months before (April to September 2008) and after (October 2008 till March 2009) the launch of Nischay scheme was compared in the study. Only those centers were included in the study which have timely and adequate supply of the kits so that pregnant women would not have been missed (to be diagnosed as pregnant). The training status of ANMs and ASHA of selected sub-centers along with their knowledge about usage of kits was assessed. Besides this, beneficiaries were interviewed from selected sub-centers about their awareness and utilization of Nischay scheme. RESULTS: Before 6 months of a launch of Nischay scheme, the median of ANC registration per sub-center per month was in the range of 18-25.5, whereas after 6 months it was 16-22.5. The difference in key ANC parameters (ANC registration, ANC < 12 weeks and completed three ANC) before and after introduction of the scheme was not found to be statistically significant. Only 15.6 % of beneficiaries were aware about Nischay scheme. The primary source of the information is either ANM (60 %) or ASHA (40 %). Those who were aware of this scheme had utilized this kit from the nearby sub-center. All (100 %) ANMs and 93 % of ASHAs had been adequately trained about using Nischay kit and interpreting the result. CONCLUSIONS: There was no significant change in ANC registration in the period of 6 months after the launch of the scheme despite trainings to the frontline health workers. Further research is required to understand the bottlenecks so that corrective actions can be taken.

Pregnancy detection and monitoring in cattle via combined foetus electrocardiogram and phonocardiogram signal processing.

BACKGROUND: Pregnancy testing in cattle is commonly invasive requiring manual rectal palpation of the reproductive tract that presents risks to the operator and pregnancy. Alternative non-invasive tests have been developed but have not gained popularity due to poor specificity, sensitivity and the inconvenience of sample handling. Our aim is to present the pilot study and proof of concept of a new non invasive technique to sense the presence and age (limited to the closest trimester of pregnancy) of the foetus by recording the electrical and audio signals produced by the foetus heartbeat using an array of specialized sensors embedded in a stand alone handheld prototype device. The device was applied to the right flank (approximately at the intercept of a horizontal line drawn through the right mid femur region of the cow and a vertical line drawn anywhere between lumbar vertebrae 3 to 5) of more than 2000 cattle from 13 different farms, including pregnant and not pregnant, a diversity of breeds, and both dairy and beef herds. Pregnancy status response is given "on the spot" from an optimized machine learning algorithm running on the device within seconds after data collection. RESULTS: Using combined electrical and audio foetal signals we detected pregnancy with a sensitivity of 87.6% and a specificity of 74.6% for all recorded data. Those values increase to 91% and 81% respectively by removing files with excessive noise (19%).Foetus ageing was achieved by comparing the detected foetus heart-rate with published tables. However, given the challenging farm environment of a restless cow, correct foetus ageing was achieved for only 21% of the correctly diagnosed pregnant cows. CONCLUSIONS: In conclusion we have found that combining ECG and PCG measurements on the right flank of cattle provides a reliable and rapid method of pregnancy testing. The device has potential to be applied by unskilled operators. This will generate more efficient and productive management of farms. There is potential for the device to be applied to large endangered quadrupeds in captive breeding programs where early, safe and reliable pregnancy diagnosis can be imperative but currently difficult to achieve.

The utility of six over-the-counter (home) pregnancy tests.

BACKGROUND: The home pregnancy market is rapidly evolving. It has moved from detection of pregnancy on the day of missed menstrual bleeding, to detection claims 4 days prior. It is moving from all manual tests to digital tests, with a monitor reading the bands and informing women they are pregnant. A thorough study is needed to investigate the validity of claims and evolving usefulness of devices. METHODS: Studies were proposed to examine the sensitivity and specificity of home tests and their abilities to detect pregnancy. Methods examined the abilities of tests to detect human chorionic gonadotropin (hCG), hyperglycosylated hCG, free ß-subunit, a mixture of these antigens in 40 individual early pregnancy urines. RESULTS: Using a mixture of hCG, hyperglycosylated hCG and free ß-subunit typical for early pregnancy, the sensitivity of the First Response manual and digital tests was 5.5 mIU/mL, while the sensitivities of the EPT and ClearBlue brand manual and digital tests was 22 mIU/mL. On further evaluation, the First Response manual and digital tests both detected 97% of 120 pregnancies on the day of missed menstrual bleeding. The EPT manual and digital devices detected 54% and 67% of pregnancies, respectively, and the ClearBlue manual and digital devices detected 64% and 54% of pregnancies, respectively. CONCLUSIONS: First Response manual and digital claim >99% detection on the day of missed menses. The results here suggest similar sensitivity for these two tests. The EPT and ClearBlue manual and digital test make similar >99% claims, the data presented here disputes their elevated claim.

Home pregnancy test compared to standard-of-care ultrasound dating in the assessment of pregnancy duration.

OBJECTIVE: To determine the level of agreement between the Clearblue Digital Pregnancy Test with Conception Indicator home pregnancy test and standard-of-care ultrasound in assessing pregnancy duration in a real-life, observational setting encompassing routine, clinical care. RESEARCH DESIGN AND METHODS: This was a prospective observational study of non-pregnant women seeking conception. Women collected daily urine samples from day 1 of their next menstrual cycle. If any volunteer became pregnant, daily urine samples continued to be collected for 43 days after the LH surge. Samples from day -7 to day +28 relative to the expected period (LH surge + 15 days) were tested using the home pregnancy test. This categorised any resulting pregnancies into one of three groups: 1-2 weeks, 2-3 weeks, and 3+ weeks since conception. Information from the standard UK ultrasound dating scan was also recorded by the midwife, including the expected delivery date according to ultrasound and the expected delivery date according to LMP. MAIN OUTCOME MEASURES: Full data were available from 52 pregnant women who had conceived naturally. During the study analysis, 4786 urine samples were cross-compared with 52 routine 12-week NHS ultrasound assessments and the level of agreement between home pregnancy testing and standard-of-care ultrasound in determining pregnancy duration was calculated. RESULTS: The agreement between the gestational age as calculated by the home pregnancy test result and the exact midwife-recorded gestational age using ultrasound was 82.3%. However, when a ± 5-day range was applied to the ultrasound reading (as per routine UK clinical practice), the level of agreement was 98%. CONCLUSIONS: The home pregnancy test provides a significantly high (98%) level of agreement with standard-of-care ultrasound when assessing pregnancy duration in a real-life, observational setting which closely mirrors daily clinical practice.