Centralized Clinical Laboratories Research Articles

(Invited) Analytical Validation of Aptamer-Based Blood Drug Measurements Against Clinical Benchmark Methods

The practice of monitoring therapeutic drug concentrations in patient biofluids can significantly improve clinical outcomes while simultaneously minimizing adverse side effects. Although undeniably important to achieve effectiveness, therapeutic drug monitoring remains inconvenient in practice, due primarily to the lengthy process of sample collection, transport to a centralized facility, and analysis using costly instrumentation. Adding to this workflow is the possibility of backlogs at centralized clinical laboratories, which is not uncommon and may result in additional delays between biofluid sampling and concentration measurement, which can negatively affect clinical outcomes. In this talk I explore the possibility of using point-of-care, aptamer-based sensors to minimize the time delay between biofluid sampling and drug measurement. I will discuss analytical validations of aptamer-based blood measurements for two drugs, the antibiotic vancomycin and the antiretroviral drug emtricitabine. We conducted clinical agreement studies comparing the measurement outcomes of electrochemical and optical aptamer-based sensors to the benchmark (1) automated competitive immunoassays for vancomycin monitoring in serum, and (2) liquid chromatography coupled to mass spectrometry detection (LC-MS) for plasma emtricitabine. Our results demonstrate that aptamer-based sensors are selective for the free form of these drugs, and can achieve up to 95% positive correlation and 100% negative correlation with the benchmark assays. Given these results, aptamer sensors offer a promising path for point-of-care drug monitoring that is instantaneous and overcomes current barriers for broad implementation of drug monitoring in clinical settings.

Synovial Fluid Cutibacterium acnes Antigen Is Detected Among Shoulder Samples with High Inflammation and Early Culture Growth.

An emerging paradigm suggests that positive Cutibacterium acnes shoulder cultures can result from either true infection or contamination, with true infections demonstrating a host inflammatory response and early culture growth. This clinical retrospective study examines the relationship between C. acnes antigen, C. acnes culture results, and inflammation. From January 2021 to July 2023, 1,365 periprosthetic synovial fluid samples from 347 institutions were tested for shoulder infection at a centralized clinical laboratory. A biomarker scoring system based on the 2018 International Consensus Meeting (ICM) definition was utilized to assign each sample an inflammation score. Associations between inflammation, culture results, and C. acnes antigen results were assessed utilizing cluster and correlation analyses. Of 1,365 samples, 1,150 were culture-negative and 215 were culture-positive (94 C. acnes and 121 other organisms). Among the 94 C. acnes culture-positive samples, unsupervised clustering revealed 2 distinct sample clusters (silhouette coefficient, 0.83): a high-inflammation cluster (n = 67) and a low-inflammation cluster (n = 27). C. acnes antigen levels demonstrated moderate-strong positive correlation with inflammation (Spearman ρ, 0.60), with 166-fold higher levels of C. acnes antigen in high-inflammation samples (16.6 signal/cutoff [S/CO]) compared with low-inflammation samples (0.1 S/CO) (p < 0.0001). The days to C. acnes culture positivity demonstrated weak-inverse correlation with inflammation (Spearman ρ = -0.38), with 1.5-fold earlier growth among the 67 high-inflammation samples (6.7 compared with 10.4 days; p < 0.0001). Elevated C. acnes antigen was observed in only 4 (0.38%) of 1,050 low-inflammation culture-negative samples and in only 5 (4.9%) of 103 high-inflammation non- C. acnes -positive cultures. However, 19.0% of high-inflammation, culture-negative samples demonstrated elevated C. acnes antigen. Synovial fluid C. acnes antigen was detected among shoulder samples with high inflammation and early culture growth, supporting the emerging paradigm that these samples represent true infection. Future research should explore antigen testing to differentiate contamination from infection and to identify culture-negative C. acnes infections. Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Analytical Validation of Aptamer-Based Serum Vancomycin Monitoring Relative to Automated Immunoassays.

The practice of monitoring therapeutic drug concentrations in patient biofluids can significantly improve clinical outcomes while simultaneously minimizing adverse side effects. A model example of this practice is vancomycin dosing in intensive care units. If dosed correctly, vancomycin can effectively treat methicillin-resistant streptococcus aureus (MRSA) infections. However, it can also induce nephrotoxicity or fail to kill the bacteria if dosed too high or too low, respectively. Although undeniably important to achieve effectiveness, therapeutic drug monitoring remains inconvenient in practice due primarily to the lengthy process of sample collection, transport to a centralized facility, and analysis using costly instrumentation. Adding to this workflow is the possibility of backlogs at centralized clinical laboratories, which is not uncommon and may result in additional delays between biofluid sampling and concentration measurement, which can negatively affect clinical outcomes. Here, we explore the possibility of using point-of-care electrochemical aptamer-based (E-AB) sensors to minimize the time delay between biofluid sampling and drug measurement. Specifically, we conducted a clinical agreement study comparing the measurement outcomes of E-AB sensors to the benchmark automated competitive immunoassays for vancomycin monitoring in serum. Our results demonstrate that E-ABs are selective for free vancomycin─the active form of the drug, over total vancomycin. In contrast, competitive immunoassays measure total vancomycin, including both protein-bound and free drug. Accounting for these differences in a pilot study consisting of 85 clinical samples, we demonstrate that the E-AB vancomycin measurement achieved a 95% positive correlation rate with the benchmark immunoassays. Therefore, we conclude that E-AB sensors could provide clinically useful stratification of patient samples at trough sampling to guide effective vancomycin dose recommendations.

Alanine aminotransferase assay biosensor platform using silicon nanowire field effect transistors

Frequent monitoring of serum alanine aminotransferase (ALT) activity is essential to prevent drug-induced liver injury (DILI). Current ALT assays are restricted to centralized clinical laboratories, making frequent patient monitoring logistically difficult. To address this, we demonstrated the capability of commercial foundry manufactured silicon nanowire field effect transistor (SiNW-FET) biosensors in a form factor that enables frequent near-patient monitoring. Here, we designed an ALT assay, by coupling the ALT-catalyzed production of pyruvate to the reduction of ferricyanide, enabling both spectrophotometric and electrical measurement of ALT activity. The two methods yield comparable ALT activity detection across a dynamic range wide enough to monitor patients at risk for DILI. This study demonstrates kinetic activity measurement of an endogenous enzyme using uncoupled SiNW-FETs, and commercial manufacturing of SiNW-FET sensor arrays for use in a portable biosensor platform.

Simplified Cas13-based assays for the fast identification of SARS-CoV-2 and its variants.

The widespread transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for rapid nucleic acid diagnostics that are easy to use outside of centralized clinical laboratories. Here we report the development and performance benchmarking of Cas13-based nucleic acid assays leveraging lyophilised reagents and fast sample inactivation at ambient temperature. The assays, which we named SHINEv.2 (for 'streamlined highlighting of infections to navigate epidemics, version 2'), simplify the previously reported RNA-extraction-free SHINEv.1 technology by eliminating heating steps and the need for cold storage of the reagents. SHINEv.2 detected SARS-CoV-2 in nasopharyngeal samples with 90.5% sensitivity and 100% specificity (benchmarked against the reverse transcription quantitative polymerase chain reaction) in less than 90 min, using lateral-flow technology and incubation in a heat block at 37 °C. SHINEv.2 also allows for the visual discrimination of the Alpha, Beta, Gamma, Delta and Omicron SARS-CoV-2 variants, and can be run without performance losses by using body heat. Accurate, easy-to-use and equipment-free nucleic acid assays could facilitate wider testing for SARS-CoV-2 and other pathogens in point-of-care and at-home settings.

Toward Decentralizing Antibiotic Susceptibility Testing via Ready-to-Use Microwell Array and Resazurin-Aided Colorimetric Readout.

In the face of the global threat from drug-resistant superbugs, there remains an unmet need for simple and accessible diagnostic tools that can perform important antibiotic susceptibility testing against pathogenic bacteria and guide antibiotic treatments outside of centralized clinical laboratories. As a potential solution to this important problem, we report herein the development of a microwell array-based resazurin-aided colorimetric antibiotic susceptibility test (marcAST). At the core of marcAST is a ready-to-use microwell array device that is preassembled with custom titers of various antibiotics and splits bacterial samples upon a simple syringe injection step to initiate AST against all antibiotics. We also employ resazurin, which changes from blue to pink in the presence of growing bacteria, to accelerate and enable colorimetric readout in our AST. Even with its simplicity, marcAST can accurately measure the minimum inhibitory concentrations of reference bacterial strains against common antibiotics and categorize the antibiotic susceptibilities of clinically isolated bacteria. With more characterization and refinement, we envision that marcAST can become a potentially useful tool for performing AST without trained personnel, laborious procedures, or bulky instruments, thereby decentralizing this important test for combating drug-resistant superbugs.

Real-time Colorimetric Quantitative Molecular Detection of Infectious Diseases on Smartphone-based Diagnostic Platform

Rapid diagnostics of infectious diseases and accurate identification of their causative pathogens play a crucial role in disease prevention, monitoring, and treatment. Conventional molecular detection of infectious pathogens requires expensive equipment and well-trained personnel, thus limiting its use in centralized clinical laboratories. To address this challenge, a portable smartphone-based quantitative molecular detection platform, termed “smart connected pathogen tracer” (SCPT), has been developed for pathogen monitoring and disease surveillance. The platform takes advantage of synergistically enhanced colorimetric loop-mediated isothermal amplification (LAMP) assay and smartphone-based color analysis, enabling simple, rapid and reliable nucleic acid quantification without need for expensive fluorescence detection equipment. The SCPT platform has been successfully applied to quantitatively detect: i) HPV DNA in saliva and clinical vaginal swab samples, and ii) HIV RNA in plasma samples with comparable sensitivity to state-of-art machine. It has also been demonstrated for disease spatiotemporal mapping and pathogen tracking by wireless connection and web-based surveillance. Such simple, cost-affordable, portable molecular detection platform has great potential for on-site early disease detection, remote healthcare monitoring, and epidemic surveillance.

An Automated, Quantitative, and Multiplexed Assay Suitable for Point-of-Care Hepatitis B Virus Diagnostics

Hepatitis B virus (HBV) infection has a global reach with high prevalence in resource-limited areas like China and Africa. HBV patients in these areas have limited access to the currently used, costly HBV assays, which are performed in centralized clinical laboratories using single-plexed assays with bulky and expensive instruments. We aim to overcome these limitations by developing a simple and affordable HBV diagnostic platform to allow for timelier diagnosis and intervention of HBV infection. Using giant magnetoresistive (GMR) biosensor chips, we developed an automated and multiplexed quantitative platform for the measurement of a panel of HBV serology markers, including HBV “e” antigen (HBeAg), HBV surface antigen (HBsAg), and the antibody against HBsAg (anti-HBs). Our assay platform was able to detect each HBV marker with high specificity and sensitivity (with three orders of magnitude in dynamic range for each marker). Blinded analysis of HBV patient sera showed excellent correlation between our multiplexed quantitative HBsAg results and the qualitative results obtained using FDA-approved immunoassays, as well as those obtained using quantitative, single-plexed, enzyme-linked immunosorbent assays (ELISAs). The portable, automated, multiplexed, quantitative HBV serology assay platform we designed shows great promise as a more accessible alternative for HBV screening, diagnosis, and treatment monitoring.

Clinical Impact of Rapid Point-of-Care PCR Influenza Testing in an Urgent Care Setting: a Single-Center Study.

Seasonal influenza virus causes significant morbidity and mortality each year. Point-of-care (POC) testing using rapid influenza diagnostic tests (RIDTs), immunoassays that detect viral antigens, are often used for diagnosis by physician offices and urgent care centers. These tests are rapid but lack sensitivity, which is estimated to be 50 to 70%. Testing by PCR is highly sensitive and specific, but historically these assays have been performed in centralized clinical laboratories necessitating specimen transport and increasing the time to result. Recently, Clinical Laboratory Improvement Amendments (CLIA)-waived, POC PCR influenza assays have been developed with >95% sensitivity and specificity compared to centralized PCR assays. To determine the clinical impact of a POC PCR test for influenza, we compared antimicrobial prescribing patterns of one urgent care location using the Cobas LIAT Influenza A/B assay (LIAT assay; Roche Diagnostics, Indianapolis, IN) to other urgent care centers in our health system using traditional RIDT, with negative specimens being reflexed to PCR. Antiviral prescribing was lower in patients with a negative LIAT PCR result (2.3%) than in patients with a negative RIDT result (25.3%; P < 0.005). Antivirals were prescribed more often in patients that tested positive by LIAT PCR (82.4%) than in those testing positive by either RIDT or reflex PCR (69.9%; P < 0.05). Antibacterial prescriptions for patients testing negative by LIAT PCR were higher (44.5%) than for those testing negative by RIDT (37.7%), although the difference was not statistically significant. In conclusion, having results from a PCR POC test during the clinic visit improved antiviral prescribing practices compared to having rapid results from an RIDT.

Control of Infectious Diseases in the Era of European Clinical Microbiology Laboratory Consolidation: New Challenges and Opportunities for the Patient and for Public Health Surveillance.

Many new innovative diagnostic approaches have been made available during the last 10 years with major impact on patient care and public health surveillance. In parallel, to enhance the cost-effectiveness of the clinical microbiology laboratories (CMLs), European laboratory professionals have streamlined their organization leading to amalgamation of activities and restructuring of their professional relationships with clinicians and public health specialists. Through this consolidation process, an operational model has emerged that combines large centralized clinical laboratories performing most tests on one high-throughput analytical platform connected to several distal laboratories dealing locally with urgent analyses at near point of care. The centralization of diagnostic services over a large geographical region has given rise to the concept of regional-scale “microbiology laboratories network.” Although the volume-driven cost savings associated with such laboratory networks seem self-evident, the consequence(s) for the quality of patient care and infectious disease surveillance and control remain less obvious. In this article, we describe the range of opportunities that the changing landscape of CMLs in Europe can contribute toward improving the quality of patient care but also the early detection and enhanced surveillance of public health threats caused by infectious diseases. The success of this transformation of health services is reliant on the appropriate preparation in terms of staff, skills, and processes that would be inclusive of stakeholders. In addition, rigorous metrics are needed to set out more concrete laboratory service performance objectives and assess the expected benefits to society in terms of saving lives and preventing diseases.

Magnetic Levitation Coupled with Portable Imaging and Analysis for Disease Diagnostics.

Currently, many clinical diagnostic procedures are complex, costly, inefficient, and inaccessible to a large population in the world. The requirements for specialized equipment and trained personnel require that many diagnostic tests be performed at remote, centralized clinical laboratories. Magnetic levitation is a simple yet powerful technique and can be applied to levitate cells, which are suspended in a paramagnetic solution and placed in a magnetic field, at a position determined by equilibrium between a magnetic force and a buoyancy force. Here, we present a versatile platform technology designed for point-of-care diagnostics which uses magnetic levitation coupled to microscopic imaging and automated analysis to determine the density distribution of a patient's cells as a useful diagnostic indicator. We present two platforms operating on this principle: (i) a smartphone-compatible version of the technology, where the built-in smartphone camera is used to image cells in the magnetic field and a smartphone application processes the images and to measures the density distribution of the cells and (ii) a self-contained version where a camera board is used to capture images and an embedded processing unit with attached thin-film-transistor (TFT) screen measures and displays the results. Demonstrated applications include: (i) measuring the altered distribution of a cell population with a disease phenotype compared to a healthy phenotype, which is applied to sickle cell disease diagnosis, and (ii) separation of different cell types based on their characteristic densities, which is applied to separate white blood cells from red blood cells for white blood cell cytometry. These applications, as well as future extensions of the essential density-based measurements enabled by this portable, user-friendly platform technology, will significantly enhance disease diagnostic capabilities at the point of care.

Folate status of women in Toronto: Implications of folate fortification and supplementation.

To assess the percentage of women of childbearing age with suboptimal levels of folate for protecting against neural tube defects (&lt;906 nM), and assess folate status among the elderly. A total of 1,035 anonymous blood samples from a centralized clinical laboratory, with a catchment area across the Greater Toronto Area, were assessed for red blood cell (RBC) folate concentrations using a chemiluminescent immunoassay. Folate analysis was requested by physicians as part of clinical care. Available data included age, sex, and RBC folate concentration. Descriptive statistics were used to characterize the percent of women who had suboptimal blood folate concentrations, and a multiple regression was used to analyze determinants of folate status. Our data from 2013 show that 7% of women of childbearing age (15-45 years) had RBC folate concentrations below 906 nM, a substantially lower percentage than in our 2006 study (40%). Results from the multiple regression showed that age is a significant positive predictor of higher RBC folate status (p &lt; 0.001). Compared to our earlier data, we report a significant decrease in the suboptimal folate status among women of childbearing age. We also show that age is a predictor of higher RBC folate levels. Our data are limited due to a lack of information regarding patient or physician characteristics, and to the nature of our sample, yet our results are consistent with the continued increase in folate status observed among several population-level studies in the US and Canada post-fortification. Further research is needed to determine the reasons for and future implications of this continued increase in the elderly.

Serologic and Phenotypic Analysis of Blood Types Via Silicon Nanophotonics

Tens of millions of donor and patient samples are tested yearly to establish blood type compatibility between donor and recipient and to protect recipients from blood-borne infectious diseases. Blood type testing, particularly donor testing, is traditionally based in centralized clinical laboratories. However, current blood typing methods are encumbered by reagent availability, cost, technical training requirements, and time, placing a costly burden on the medical system. To address practical needs in blood typing, we have developed a multiplexed blood analysis platform using a low-cost and scalable silicon photonic biochip. This study investigates the use of silicon microring sensors to capture, detect, and quantify specific red blood cell (RBC) membrane antigens and anti-blood type antibodies from blood.To validate ABO blood phenotyping, microring resonators were streptavidin coated and functionalized with biotinylated anti-A IgM or biotinylated anti-B IgM antibodies. First, the response of anti-A/B functionalized microring resonators to characterized RBC membranes (RBC ghosts, 108 cells/ml) were measured in real-time (Figure 1). The biosensor arrays also exhibited minimal non-specific adsorption of RBC membrane fragments to the sensor surface. Microring resonators were shown to be suitable for identifying RBC ABO phenotype from donor blood samples.For ABO serologic analysis, silicon chips were functionalized with synthetic multivalent polymeric blood group antigens to serve as capture elements for circulating anti-ABO antibodies. Each chip also had sensors functionalized with biotinylated Protein A (btn-ProtA) and a biotinylated polyacrylamide polymer scaffold (btn-paa) to serve as on-chip positive and negative controls, respectively. The multiplexed biosensor chips were exposed to 100mL of plasma, followed by an anti-human-IgM antibody to enhance detection and quantification of antibodies bound to the surface. The resonance shift in each microring resonator was monitored over time, and the sensor response of the polymeric A and B blood group antigens was normalized to the control sensors. Figure 2 illustrates the levels of bound anti-A and anti-B for a panel of donor blood samples with varying ABO blood type, expressed as a relative shift in sensor resonance wavelength. These results demonstrate the detection of the 'naturally occurring’ anti-A/B IgM antibodies for each respective ABO blood type.We have demonstrated that microring resonator biosensor arrays can quantitatively determine the donor ABO phenotypic and serologic status while incorporating on-chip controls for process standardization. Our work serves as proof-of-concept that a multiplexed silicon nanophotonics platform can rapidly detect both RBC antigens and anti-RBC antibodies in biological samples. This method has the potential for broad applicability in hematology and transfusion medicine for blood typing, quantitative monitoring of specific antibodies, and pathogen screening. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A MicroRNA-Based Test Improves Endoscopic Ultrasound–Guided Cytologic Diagnosis of Pancreatic Cancer

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC. Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland. We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%-84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%-94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC (P < .001), with positive predictive values greater than 99% (95% confidence interval, 96%-100%). We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.

Cell-phone-based measurement of TSH using Mie scatter optimized lateral flow assays

Semi-quantitative thyroid stimulating hormone (TSH) lateral flow immunochromatographic assays (LFA) are used to screen for serum TSH concentration >5mIUL−1 (hypothyroidism). The LFA format, however, is unable to measure TSH in the normal range or detect suppressed levels of TSH (<0.4mIUL−1; hyperthyroidism). In fact, it does not provide quantitative TSH values at all. Obtaining quantitative TSH results, especially in the low concentration range, has until now required the use of centralized clinical laboratories which require specimen transport, specialized equipment and personnel, and result in increased cost and delays in the timely reporting of important clinical results. We have conducted a series of experiments to develop and validate an optical system and image analysis algorithm based upon a cell phone platform. It is able to provide point-of-care quantitative TSH results with a high level of sensitivity and reproducibility comparable to that of a clinical laboratory-based third-generation TSH immunoassay. Our research approach uses the methodology of the optimized Rayleigh/Mie scatter detection by taking into consideration the optical characteristics of a nitrocellulose membrane and gold nanoparticles on an LFA for quantifying TSH levels. Using a miniature spectrometer, LED light source, and optical fibers on a rotating benchtop apparatus, the light intensity from different angles of incident light and angles of detection to the LFA were measured. The optimum angles were found that the minimized Mie scattering from nitrocellulose membrane, consequently maximizes the Rayleigh scatter detection from the gold nanoparticles in the LFA bands. Using the results from the benchtop apparatus, a cell-phone-based apparatus was designed which utilized the embedded flash in the cell phone camera as the light source, piped the light with an optical fiber from the flash through a collimating lens to illuminate the LFA. Quantification of TSH was performed in an iOS application directly on the phone and verified using the code written in MATLAB. The limit of detection of the system was determined to be 0.31mIUL−1 (never achieved before on an LFA format), below the commonly accepted minimum concentration of 0.4mIUL−1 indicating clinical significance of hyperthyroidism. The system was further evaluated using human serum showing an accurate and reproducible platform for rapid and point-of-care quantification of TSH using a cell phone.

Clinical application of anti-Müllerian hormone as a predictor of controlled ovarian hyperstimulation outcome

ObjectiveIn 2009 anti-Müllerian hormone (AMH) assay was approved for clinical use in Korea. This study was performed to determine the reference values of AMH for predicting ovarian response to controlled ovarian hyperstimulation (COH) using the clinical assay data.MethodsOne hundred sixty-two women who underwent COH cycles were included in this study. We collected data on age, basal AMH and FSH levels, total dose of gonadotropins, stimulation duration, and numbers of oocytes retrieved and fertilized. Blood samples were obtained on cycle day 3 before gonadotropin administration started. Serum AMH levels were measured at a centralized clinical laboratory center. The correlation between the AMH level and COH outcomes and cut-off values for poor and high response after COH was analyzed.ResultsConcentration of AMH was significantly correlated with the number of oocytes retrieved (OPU; r=0.700, p<0.001). The mean±SE serum AMH levels for poor (OPU≤3), normal (4≤OPU≤19), and high (OPU≥20) response were 0.94±0.15 ng/mL, 2.79±0.21 ng/mL, and 6.94±0.90 ng/mL, respectively. The cut-off level, sensitivity and specificity for poor and high response were 1.08 ng/mL, 85.8%, and 78.6%; and 3.57 ng/mL, 94.4%, and 83.3%, respectively.ConclusionOur data present clinical reference values of the serum AMH level for ovarian response in Korean women. The serum AMH level could be a clinically useful predictor of ovarian response to COH.

Saliva and the Clinical Pathology Laboratory

There have been increasing numbers of applications using oral fluids, saliva in particular, as the target substrate for performing clinical diagnostic tests. These have focused primarily on point-of-care (POC) testing. These POC testing approaches range from, for example, currently available, highly specialized screening tests for the presence of antibodies recognizing HIV to the potential development of "lab-on-a-chip" platforms. Broad claims have been made that the latter will revolutionize clinical laboratory testing. From the perspective of large centralized clinical laboratories, multiple issues must be considered before implementing individual tests using saliva as the target fluid in a POC format or using saliva as a universal test fluid for measuring multiple analytes in a centralized laboratory format. The current scope of laboratory testing is large and comprehensive, involving both POC and centralized testing. Current academic laboratory programs have the ability to qualitatively identify and/or quantitatively measure several thousand analytes in various target matrices including blood, plasma, serum, urine, joint fluid, pleural fluid, peritoneal fluid, cerebrospinal fluid, and tissue. These tests fall into multiple clinical pathology disciplines, including clinical chemistry, hematology, coagulation, transfusion medicine, microbiology, cytogenetics, molecular diagnosis, and immunology. In addition, before implementing a given test, multiple issues need to be evaluated to ensure the validity of the reported result; these include considerations involving the three major phases of testing: preanalytical (e.g., patient identification and specimen collection, stability, and transport), analytical (e.g., sensitivity, specificity, accuracy, and precision), and postanalytical (e.g., reporting results, quality improvement, and turn-around-time).

The Development of a Broad-Spectrum Toxicology Screening Program in Taiwan

Our institute serves as a centralized clinical laboratory for municipal and private hospitals in Taipei, a major international metropolis in the Asian region. Two key considerations leading to the development of our toxicology program are: a large number of foreign visitors and local residents returning from overseas trips may bring in chemicals which are less commonly seen in this region; and the lack of readily available assays for a large percentage of commonly used medicines, including prescription and over-the-counter drugs. Our toxicology screening program addresses the needs of both the Emergency Department Drug Screening and Drug of Abuse Screening. In Emergency Department Drug Screening, REMEDi HS is used as the general screening method. In Drug of Abuse Screening, the TDx is used for the initial screening of amphetamine-like substances and opiates, followed by REMEDi HS for the confirmation of positive samples. Emergency Department data collected at our institute over one year (September 1992 to August 1993) identified 57 different drugs in 713 samples. Opiates, narcotics and central stimulants accounted for 24% of the encountered drugs. Presently, there is no extensive reporting of misuse of benzodiazepines in this region. The detection of herbal ingredients like ephedrine and methylephedrine (from the Ma-Huang plant) in patient samples illustrates a large area often overlooked by western toxicology.