Microfluidic Lab-on-CMOS Packaging Using Wafer-Level Molding and 3D-Printed Interconnects.

Lab-on-a-chip (LoC) technologies continue to promise lower cost and more accessible platforms for performing biomedical testing in low-cost and disposable form factors. Lab-on-CMOS or lab-on-microchip methods extend this paradigm by merging passive LoC systems with active complementary metal-oxide semiconductor (CMOS) integrated circuits (IC) to enable front-end signal conditioning and digitization immediately next to sensors in fluid channels. However, integrating ICs with microfluidics remains a challenge due to size mismatch and geometric constraints, such as non-planar wirebonds or flip-chip approaches in conflict with planar microfluidics.

A 10 M Ω, 50 kHz-40 MHz Impedance Measurement Architecture for Source-Differential Flow Cytometry.

A low-power, impedance-based integrated circuit (IC) readout architecture is presented for cell analysis and cytometry applications. A three-electrode layout and source-differential excitation cancels baseline current prior to the sensor front-end, which enables the use of a high-gain readout circuit for the difference current. A lock-in architecture is employed with down-conversion and up-conversion in the feedback loop, enabling high closed-loop gain (up to 10 M Ω) and high bandwidth (up to 40 MHz).

DC-100 kHz Tunable Readout IC for Impedance Spectroscopy and Amperometric Measurement of Electrochemical Sensors.

This paper presents a low-noise, front-end sensor IC that includes both AC impedance spectroscopy and DC amperometric measurement capabilities for electrochemical and biosensor applications. A common-gate current buffer topology is proposed that supports both current-mode and voltage-mode sensor signals to allow an input frequency range from DC to 100 kHz. Low-noise operation is achieved across a wide input frequency range using tunable high-pass and low-pass frequency response.

A Batteryless Motion-Adaptive Heartbeat Detection System-on-Chip Powered by Human Body Heat.

This paper presents a batteryless heartbeat detection system-on-chip (SoC) powered by human body heat. An adaptive threshold generation architecture using pulse-width locked loop (PWLL) is developed to detect heartbeats from electrocardiogram (ECG) in the presence of motion artifacts. The sensing system is autonomously powered by harvesting thermal energy from human body heat using a thermoelectric generator (TEG) coupled to a low-voltage, self-starting boost converter and integrated power management system.

Insights into the Authentic Active Ingredients and Action Sites of Oral Exogenous Glutathione in the Treatment of Ischemic Brain Injury Based on Pharmacokinetic-Pharmacodynamic Studies.

Glutathione (GSH) has been reported to be closely related to various diseases of the central nervous system, yet its authentic active ingredients and action sites remain unclear. In the present study, oral exogenous GSH significantly alleviated ischemic brain injury, but this result was inconsistent with its low bioavailability and blood-brain barrier (BBB) permeability. To ascertain the exposure of GSH-derived ingredients, including GSH, cysteine (CYS), glutamate (Glu), glycine (GLY), CYS-GLY, and -glutamylcysteine (-GC) were systematically studied both in vitro and in vivo.

Systematically identifying the hepatoprotective ingredients of schisandra lignan extract from pharmacokinetic and pharmacodynamic perspectives.

Background: Herbal medicines (HMs) have been proven to be productive sources of leads for the development of drugs. To date approximately 150 lignans have been identified from Schisandra sphenanthera. Hepatoprotective activity is a well-known characteristic of schisandra lignans, yet the authentic types of active lignans are still not well known.

Activated charcoal significantly improved the reliability of methods for quantitative analysis of endogenous substances in biological specimens: Glutathione and cysteine as cases.

When developing a quantitative assay for exogenous or endogenous compounds, guidelines for method validation normally recommend that the biological specimens should be prepared in corresponding authentic matrices, yet "analyte-free authentic matrices" is in general not available. It is generally known that GSH and CYS are endogenous compounds and present in both prokaryotes and eukaryotes. Herein, an efficient approach for the quantitative analysis of endogenous substances in biological specimens was developed, and glutathione (GSH) & cysteine (CYS) were chosen as model endogenous substances.

Pharmacokinetic and pharmacodynamic evidence for developing an oral formulation of octreotide against gastric mucosal injury.

Among the somatostatin analogues, octreotide (OCT) is the most commonly used in clinic via intravenous or subcutaneous injection to treat various diseases caused by increased secretion of growth hormone, gastrin or insulin. In order to assesse the feasibility of developing oral formulations of OCT, we conducted systematical pharmacokinetic and pharmacodynamic analyses of OCT in several animal models. The pharmacokinetic studies in rats showed that intragastric administration of OCT had extremely low bioavailability (<0.

Low Cerebral Exposure Cannot Hinder the Neuroprotective Effects of Panax Notoginsenosides.

A bidirectional route of communication between the gastrointestinal tract and the central nervous system, termed the "gut-brain axis," is becoming increasingly relevant to treatment of cerebral damage. Panax Notoginsenoside extract (PNE) is popular for prevention and treatment of cardio-cerebrovascular ischemic diseases although plasma and cerebral exposure levels are extremely low. To date, the mechanisms underlying the neuroprotective effects of PNE remain largely unknown.

An integrated strategy for the quantitative analysis of endogenous proteins: A case of gender-dependent expression of P450 enzymes in rat liver microsome.

Liquid chromatography mass spectrometry based methods provide powerful tools for protein analysis. Cytochromes P450 (CYPs), the most important drug metabolic enzymes, always exhibit sex-dependent expression patterns and metabolic activities. To date, analysis of CYPs based on mass spectrometry is still facing critical technical challenges due to the complexity and diversity of CYP isoforms besides lack of corresponding standards.

Optimization and evaluation of MALDI TOF mass spectrometric imaging for quantification of orally dosed octreotide in mouse tissues.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) has received considerable attention in recent years since it allows molecular mapping of diverse bimolecular in animal/plant tissue sections, although some barriers still exist in absolute pixel-to-pixel quantification. Octreotide, a synthetic somatostatin analogue, has been widely used to prevent gastrointestine bleeding in the clinic. The aim of the present study is to develop a MALDI-TOF-MSI method for quantitatively visualizing spatial distribution of octreotide in mouse tissues.

Pharmacokinetic study based on a matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight imaging mass microscope combined with a novel relative exposure approach: A case of octreotide in mouse target tissues.

Application of imaging mass spectrometry in drug pharmacokinetics remains challenging due to its weak quantitative capability. Herein, an imaging mass microscope (iMScope), equipped with an optical microscope, an atmospheric pressure ion-source chamber for matrix-assisted laser desorption/ionization (AP-MALDI) and a hybrid quadrupole ion trap time-of-flight (QIT-TOF) analyzer, was first validated and applied to visualize drug disposition in vivo. The distribution and elimination rate of the therapeutic peptide octreotide, a long-acting analogue of the natural hormone somatostatin, was first calculated based on the data determined by iMScope system combining a novel relative exposure strategy.

Qualitatively and quantitatively investigating the regulation of intestinal microbiota on the metabolism of panax notoginseng saponins.

Ethnopharmacological Relevance: Intestinal microflora plays crucial roles in modulating pharmacokinetic characteristics and pharmacological actions of active ingredients in traditional Chinese medicines (TCMs). However, the exact impact of altered intestinal microflora affecting the biotransformation of TCMs remains poorly understood.

Aims Of The Study: This study aimed to reveal the specific enterobacteria which dominate the metabolism of panax notoginseng saponins (PNSs) via exploring the relationship between bacterial community structures and the metabolic profiles of PNSs.

Bioanalytical assay development and validation for simultaneous quantification of five schisandra lignans in rat primary hepatocytes based on LC-MS/MS: application to a real-time uptake study for Schisandra Lignan Extract.

Schisandra lignans, mainly including schizandrol A, schizandrol B, schisantherin A, schizandrin A, schizandrin B, etc., are the major active ingredients of Schisandra chinensis. In the present study, a robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous quantification of schisandra lignans in rat primary hepatocytes.

The metabolic and pharmacokinetic studies for HM-3 in rats based on LC-Q-TOF/MS and LC-MS/MS combing a convenient biological sample processing method.

In this contribution, the metabolic and pharmacokinetic characteristics for the therapeutic peptide HM-3 were investigated using LC-Q-TOF/MS and LC-MS/MS systems combing a fast biological sample processing method. According to the accurate MS(1) and MS(2) data generated by LC-Q-TOF/MS, a total of 6 metabolites in rats were detected and tentatively identified as the degradation products which formed by successive loss of amino acid from HM-3. The structures of the 2 main metabolites (M1 and M2) were confirmed by comparing the chromatographic and mass spectrographic characteristics with the corresponding synthetic standards.

Development of a novel sectional multiple filtering scheme for rapid screening and classifying metabolites of ziyuglycoside II in rat liver and excreta specimen based on high-resolution mass spectrometry.

Ziyuglycoside II, one of the major effective ingredients of Sanguisorba officinalis L., had various pharmacological activities including anticancer, anti-inflammation and anti-oxidation, etc. Better understanding of the pharmacology and toxicology of ziyuglycoside II requires the detailed elucidation of its biologic fates in vivo.

A robust LC-MS/MS method for the determination of pidotimod in different biological matrixes and its application to in vivo and in vitro pharmacokinetic studies.

Pidotimod, (R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, was frequently used to treat children with recurrent respiratory infections. Preclinical pharmacokinetics of pidotimod was still rarely reported to date. Herein, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine pidotimod in rat plasma, tissue homogenate and Caco-2 cells.